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Sample records for antiretroviral drugs arvs

  1. Effect of antiretroviral drug (arved) on hepatic enzymes in albino rats ...

    African Journals Online (AJOL)

    In the rush to put as many patients as possible on a potent ART, with very little or no laboratory monitory, limited attention has been given to side effects. This study was therefore designed to evaluate the effects of antiretroviral drugs arved® , on aspartate amino transferase (AST), alanine amino transferase (ALT) and ...

  2. Abuse of antiretroviral drugs combined with addictive drugs by ...

    African Journals Online (AJOL)

    Reports of the use of antiretroviral drugs (ARVs) to produce a highly addictive drug called nyaope or whoonga are of major concern as ARVs are easily accessible in sub-Saharan Africa, including to pregnant women. Use of illicit drugs by pregnant women may result in serious adverse effects in their infants. We have ...

  3. Anaesthesia and ARV

    African Journals Online (AJOL)

    Adele

    As more and more HIV infected patients gain access to antiretroviral medication, this drug class and its patients have gained particular significance for anaesthetists. This paper offers an overview of antiretrovirals (ARV) with a specific focus on the implications for anaesthetic management. The four main classes of ARV's are ...

  4. Antiretroviral drug resistance: A guide for the southern African clinician

    African Journals Online (AJOL)

    Both private and public sector see a bewildering clinical array of patients taking failing antiretroviral (ARV) regimens. We intend this article to provide a practical guide to help clinicians understand and manage ARV drug resistance in an African context. ARV resistance is a rapidly evolving field, requiring expertise in dealing ...

  5. Pharmaceutical Equivalence of Distributed Generic Antiretroviral (ARV) in Asian Settings: The Cross-Sectional Surveillance Study - PEDA Study.

    Science.gov (United States)

    Sapsirisavat, Vorapot; Vongsutilers, Vorasit; Thammajaruk, Narukjaporn; Pussadee, Kanitta; Riyaten, Prakit; Kerr, Stephen; Avihingsanon, Anchalee; Phanuphak, Praphan; Ruxrungtham, Kiat

    2016-01-01

    Ensuring that medicines meet quality standards is mandatory for ensuring safety and efficacy. There have been occasional reports of substandard generic medicines, especially in resource-limiting settings where policies to control quality may be less rigorous. As HIV treatment in Thailand depends mostly on affordable generic antiretrovirals (ARV), we performed quality assurance testing of several generic ARV available from different sources in Thailand and a source from Vietnam. We sampled Tenofovir 300mg, Efavirenz 600mg and Lopinavir/ritonavir 200/50mg from 10 primary hospitals randomly selected from those participating in the National AIDS Program, 2 non-government organization ARV clinics, and 3 private drug stores. Quality of ARV was analyzed by blinded investigators at the Faculty of Pharmaceutical Science, Chulalongkorn University. The analysis included an identification test for drug molecules, a chemical composition assay to quantitate the active ingredients, a uniformity of mass test and a dissolution test to assess in-vitro drug release. Comparisons were made against the standards described in the WHO international pharmacopeia. A total of 42 batches of ARV from 15 sources were sampled from January-March 2015. Among those generics, 23, 17, 1, and 1 were Thai-made, Indian-made, Vietnamese-made and Chinese-made, respectively. All sampled products, regardless of manufacturers or sources, met the International Pharmacopeia standards for composition assay, mass uniformity and dissolution. Although local regulations restrict ARV supply to hospitals and clinics, samples of ARV could be bought from private drug stores even without formal prescription. Sampled generic ARVs distributed within Thailand and 1 Vietnamese pharmacy showed consistent quality. However some products were illegally supplied without prescription, highlighting the importance of dispensing ARV for treatment or prevention in facilities where continuity along the HIV treatment and care cascade

  6. Problems associated with substandard and counterfeit drugs in developing countries: a review article on global implications of counterfeit drugs in the era of antiretroviral (ARVs) drugs in a free market economy.

    Science.gov (United States)

    Nsimba, Stephen E D

    2008-12-01

    To review the global implications associated with the use of substandard and or counterfeit drugs in developing and may be developed countries. The focus of this review is particularly on antiretroviral (ARVs), antimalarials and other drugs. Review of various literatures through Pub-Med, Medline, Google and Internet search to retrieve and download published materials was done by the author of this review paper. When patients receive a counterfeit medicines, they are subjected to multiple risks. They often suffer more than just an inconvenience; as they become victims of fraud medicines and are all put at risk of adverse effects from unprescribed medicines or substandard ingredients. Additionally, patients may lose confidence in health care professionals including their physician and pharmacist, and potentially modern medicine or the pharmaceutical industry in general. Counterfeit or substandard (poor quality) drugs pose threats to society; not only to the individual in terms of the health side effects experienced, but also to the public in terms of trade relations, economic implications, and the effects on global pandemics. It is vital for suppliers, providers, and patients to be aware of current trends in counterfeiting in order to best prepare for encounters with suspicious products. Furthermore, this is an issue that needs to be continually dealt with on national and international policy levels. Developing countries should try their level best to establish good laboratories for monitoring and checking quality of all pharmaceuticals manufactured locally and those imported or donated to these countries. The Ministries of Health and all stakeholders involved in this issue must ensure that all drugs meet the set or established international standards and national standards. Failure to do so will be to misuse the hard earned forex that is normally borrowed from banks for the procurement and distribution of drugs to its people. Indeed sub-standard medications do more

  7. Supply chain solutions to improve the distribution of antiretroviral drugs (ARVs to clinics in rural areas: A case study of the QwaQwa district

    Directory of Open Access Journals (Sweden)

    Mamolise Mokheseng

    2017-10-01

    Full Text Available This article serves as a case study based on research that was performed in the QwaQwa district in the Free State Province where the distribution of ARVs to the regional Manapo hospital, as well as between the hospital and its peripheral clinics, was interrupted and inconsistent due to problems in the supply chain. An unreliable and interrupted ARV supply chain creates the risk of virus reactivation and eventual patient mortality. The objectives of the study were to explore the problems experienced with the ARV distribution practices at the Manapo hospital, and to recommend ways in which the distribution of ARVs can be improved so that patients can receive an uninterrupted supply. The nature of the topic researched dictated the use of mainly the quantitative research method. The main problems identified include: Wrong and no uniform practice of ordering stock by the hospital and the clinics; lack of reliable, structured transportation from the depot to the hospital; as well as poor inventory management and poor overall communication. Recommendations to address the problems include: Implementing a supply chain planning and design process; improving inventory management and warehousing practices; implementing more effective and reliable distribution and transportation processes; as well as improving supply chain coordination and overall communication.

  8. The Role of ARV Associated Adverse Drug Reactions in Influencing Adherence Among HIV-Infected Individuals: A Systematic Review and Qualitative Meta-Synthesis.

    Science.gov (United States)

    Li, Haochu; Marley, Gifty; Ma, Wei; Wei, Chongyi; Lackey, Mellanye; Ma, Qingyan; Renaud, Françoise; Vitoria, Marco; Beanland, Rachel; Doherty, Meg; Tucker, Joseph D

    2017-02-01

    Poor adherence remains a major barrier to achieving the clinical and public health benefits of antiretroviral drugs (ARVs). A systematic review and qualitative meta-synthesis was conduct to evaluate how ARV adverse drug reactions may influence ARV adherence. Thirty-nine articles were identified, and 33 reported that ARV adverse drug reactions decreased adherence and six studies found no influence. Visually noticeable adverse drug reactions and psychological adverse reactions were reported as more likely to cause non-adherence compared to other adverse drug reactions. Six studies reported a range of adverse reactions associated with EFV-containing regimens contributing to decreased adherence. Informing HIV-infected individuals about ARV adverse drug reactions prior to initiation, counselling about coping mechanisms, and experiencing the effectiveness of ARVs on wellbeing may improve ARV adherence.

  9. Do national drug policies influence antiretroviral drug prices? Evidence from the Southern African Development community.

    Science.gov (United States)

    Liu, Yao; Galárraga, Omar

    2017-03-01

    The efficacy of low- and middle-income countries’ (LMIC) national drug policies in managing antiretroviral (ARV) pharmaceutical prices is not well understood. Though ARV drug prices have been declining in LMIC over the past decade, little research has been done on the role of their national drug policies. This study aims to (i) analyse global ARV prices from 2004 to 2013 and (ii) examine the relationship of national drug policies to ARV prices. Analysis of ARV drug prices utilized data from the Global Price Reporting Mechanism from the World Health Organization (WHO). Ten of the most common ARV drugs (first-line and second-line) were selected. National drug policies were also assessed for 12 countries in the South African Development Community (SADC), which self-reported their policies through WHO surveys. The best predictor of ARV drug price was generic status—the generic versions of 8 out of 10 ARV drugs were priced lower than branded versions. However, other factors such as transaction volume, HIV prevalence, national drug policies and PEPFAR/CHAI involvement were either not associated with ARV drug price or were not consistent predictors of price across different ARV drugs. In the context of emerging international trade agreements, which aim to strengthen patent protections internationally and potentially delay the sale of generic drugs in LMIC, this study shines a spotlight on the importance of generic drugs in controlling ARV prices. Further research is needed to understand the impact of national drug policies on ARV prices.

  10. Quality of antiretroviral drugs, stavudine and indinavir capsules ...

    African Journals Online (AJOL)

    Background: The number of antiretroviral drugs (ARVs) available to HIV/AIDS patients in Tanzania is increasing due to a number of intervention programs such as PEPFAR and the Clinton Foundation. These ARVs are imported from a number of countries. However, currently there are no reports on the quality of these ...

  11. Preventing and managing antiretroviral drug resistance.

    Science.gov (United States)

    Kuritzkes, Daniel R

    2004-05-01

    Development of resistance to antiretroviral drugs (ARVs) is a major impediment to optimum treatment of HIV-1 infection. Although resistance testing can help to select subsequent regimens when virologic failure occurs, cross-resistance, which affects all classes of ARVs, may make it more difficult to achieve optimum control of HIV. We have known for some time that our first choice of antiretroviral therapy offers the best chance to control HIV replication and that initial therapy should be selected with an eye on future options. Potency is the first line of defense against the development of resistance. Other factors that affect resistance development include: tolerability, potential for optimum adherence, and genetic and pharmacologic barriers to development of resistance. If resistance emerges, only a single drug may be affected initially, and a rapid change in ARVs may preserve the efficacy of other components. One cautionary note is that we can no longer assume that a patient's HIV is fully susceptible to all ARVs even in the initial regimen. Transmission of drug-resistant HIV means that the genetic composition may be that of an "experienced" virus with reduced susceptibility to ARVs. Resistance testing at the time of transmission is most likely to reveal this resistance, but over time the dominant genetic pattern may revert to wild-type, and be missed by resistance testing. Because "archived" resistant HIV may emerge quickly once treatment is initiated, we need to keep this in mind when selecting initial therapy.

  12. Antiretroviral therapeutic drug monitoring

    African Journals Online (AJOL)

    Winnie

    A narrow therapeutic window. □ Good correlation between drug ... Antiretroviral therapeutic drug monitoring (TDM) is an additional monitoring tool to assist in the management of HIV-infected patients. Antiretroviral TDM is ... Antiretroviral TDM could play an important adjunctive role in our area. Clearly this will be a limited ...

  13. Adverse drug reactions associated with antiretroviral therapy during pregnancy.

    Science.gov (United States)

    Santini-Oliveira, Marilia; Grinsztejn, Beatriz

    2014-12-01

    Antiretroviral (ARV) drug use during pregnancy significantly reduces mother-to-child HIV transmission, delays disease progression in the women and reduces the risk of HIV transmission to HIV-serodiscordant partners. Pregnant women are susceptible to the same adverse reactions to ARVs as nonpregnant adults as well as to specific pregnancy-related reactions. In addition, we should consider adverse pregnancy outcomes and adverse reactions in children exposed to ARVs during intrauterine life. However, studies designed to assess the safety of ARV in pregnant women are rare, usually with few participants and short follow-up periods. In this review, we discuss studies reporting adverse reactions to ARV drugs, including maternal toxicity, adverse pregnancy outcomes and the consequences of exposure to ARV in infants. We included results of observational studies, both prospective and retrospective, as well as randomized clinical trials, systematic reviews and meta-analyses. The benefits of ARV use during pregnancy outweigh the risks of adverse reactions identified to date. More studies are needed to assess the adverse effects in the medium- and long term in children exposed to ARVs during pregnancy, as well as pregnant women using lifelong antiretroviral therapy and more recently available drugs.

  14. Technology Development Through Pooling ARV Drug Patents: A Vision from China

    Science.gov (United States)

    Liu, Li; Lu, Hongzhou

    2010-01-01

    Unaffordable prices still bar the end-users in China from accessing ARV drugs. Patent protection of ARV drugs has dramatically limited the availability of these lifesaving drugs to AIDS patients in China. The way Chinese government can go to breakthrough the ARV drug patents are suggested as: Make more generic drugs available through compulsory licensing, impartment from other countries or building ARVs plants by partnerships between governments or generic drug companies.Do a thorough and detailed research on the patent application of ARV drugs to find out the loophole.Try patent pool to make AIDS medicines more affordable and appropriate for patients. PMID:20224635

  15. Prevalence and predictors of traditional medicine utilization among persons living with AIDS (PLWA) on antiretroviral (ARV) and prophylaxis treatment in both rural and urban areas in South Africa.

    Science.gov (United States)

    Hughes, G D; Puoane, T R; Clark, B L; Wondwossen, T L; Johnson, Q; Folk, W

    2012-01-01

    Previous studies have reported that majority of antiretroviral (ARV) treatment-naïve patients use traditional medicine (TM). Given that TM use is ubiquitous in South Africa especially for chronic conditions, there is a potential for ARV non-adherence and serious drug interactions among patients with HIV/AIDs who use TM. The motivating factors for TM use in HIV/AIDS patients on ARV and prophylaxis treatment have not been well defined in South Africa. This study aimed to investigate the prevalence, facilitators, predictors, and types of TM used among persons living with HIV/AIDS on antiretroviral treatment. The study was a cross-sectional survey which involved 100 participants enrolled at ARV clinics in two South African provinces. Univariate and bivariate analyses were performed to assess the relationships between variables and potential predictors of TM. Sixteen percent of participants on ARV reported TM use. Seventy-nine percent used TM prior to a diagnosis of HIV. Participants were more likely to use TM if they were from a rural province, female, older, unmarried, employed, had limited education, or were HIV-positive for less than five years. TM users reported utilizing herbal or medicinal mixtures that were claimed to heal all conditions. This study provides insights into the treatment modalities selected by patients with HIV/AIDS in South Africa who are receiving ARV. This study revealed that less than 20% of participants co-used TM and ARV. However, close to 80% of participants utilize TM before contracting HIV, which is in keeping with approximate estimates by the WHO.

  16. Anti-retroviral (ARV) rationing schemes in developing countries: a ...

    African Journals Online (AJOL)

    Indeed counterfeit drugs pose many threats to society; not only to the individual in terms of the health side effects experienced, but also to the public in terms of trade relations, economic implications, and the effects on global pandemics. Apart from the pharmaceutical aspect in producing substandard drugs, there area also ...

  17. The Demand for Antiretroviral Drugs in the Illicit Marketplace: Implications for HIV Disease Management Among Vulnerable Populations.

    Science.gov (United States)

    Tsuyuki, Kiyomi; Surratt, Hilary L; Levi-Minzi, Maria A; O'Grady, Catherine L; Kurtz, Steven P

    2015-05-01

    The diversion of antiretroviral medications (ARVs) has implications for the integrity and success of HIV care, however little is known about the ARV illicit market. This paper aimed to identify the motivations for buying illicit ARVs and to describe market dynamics. Semi-structured interviews (n = 44) were conducted with substance-involved individuals living with HIV who have a history of purchasing ARVs on the street. Grounded theory was used to code and analyze interviews. Motivations for buying ARVs on the illicit market were: to repurchase ARVs after having diverted them for money or drugs; having limited access or low quality health care; to replace lost or ruined ARVs; and to buy a back-up stock of ARVs. This study identified various structural barriers to HIV treatment and ARV adherence that incentivized ARV diversion. Findings highlight the need to improve patient-provider relationships, ensure continuity of care, and integrate services to engage and retain high-needs populations.

  18. Prevalence of drug-drug interactions of antiretroviral agents in the ...

    African Journals Online (AJOL)

    drug-drug interactions (DDIs). This study aimed to determine the prevalence of possible DDIs between antiretrovirals (ARVs) themselves and other drugs. Design. Retrospective drug utilisation study using data from a national medicine claims database for the period 1 January to 31 December 2004. Setting. A section of the ...

  19. Adverse drug reactions associated with antiretroviral therapy in ...

    African Journals Online (AJOL)

    South Africa has one of the highest prevalences of HIV and AIDS in the world. HIV/AIDS patients face countless challenges, one of which is the risk of adverse drug reactions (ADRs). This study aimed to describe the ADRs reported in South Africa with reference to the type of ADRs, antiretrovirals (ARVs) implicated, ...

  20. [Characteristics of antiretroviral drugs].

    Science.gov (United States)

    Ribera, Esteban; Tuset, Montse; Martín, Maite; del Cacho, Elena

    2011-05-01

    As of November 2010, a total of 22 antiretroviral agents are marketed in Spain. These agents are divided into 6 classes according to their mechanism of action: 1) nucleos(t)ide reverse transcriptase inhibitors (NRTI) (abacavir, didanosine, emtricitabine, stavudine, lamivudine, zidovudine, and tenofovir), 2) non-nucleoside reverse transcriptase inhibitors (NNRTI) (efavirenz, etravirine, and nevirapine), 3) protease inhibitors (PI) (atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir), 4) entry inhibitors (enfuvirtide), 5) coreceptor CCR5 inhibitors (maraviroc), and 6) integrase inhibitors (raltegravir). All 22 agents are indicated for the treatment of HIV-1 infection in combination with other antiretroviral drugs. Most have also proven to be active against HIV-2 (except the NNRTIs, enfuvirtide, and maraviroc) and some are active against hepatitis B virus (lamivudine, emtricitabine, and tenofovir). The present article reviews the main characteristics of the different antiretroviral agents and classes, namely, commercial presentations, paediatric and adult dosages, dose adjustments in renal and hepatic insufficiency, pharmacokinetics and interactions, mechanism of action, treatment indications, resistance, adverse effects, and safety during pregnancy and breastfeeding. Some of the characteristics of antiretrovirals are class-specific and common to other agents of the same class, and others are individual and different from those of other drugs in the same class. Knowledge of these characteristics enables us to prepare efficacious therapeutic regimens according to the specific requirements of the patient (tolerability, simplicity, adaptability to lifestyle) and clinical setting (naive, simplification, rescue, resistance). Copyright © 2010 Elsevier España, S.L. All rights reserved.

  1. Antiretroviral Drug Use in a Cross-Sectional Population Survey in Africa: NIMH Project Accept (HPTN 043).

    Science.gov (United States)

    Fogel, Jessica M; Clarke, William; Kulich, Michal; Piwowar-Manning, Estelle; Breaud, Autumn; Olson, Matthew T; Marzinke, Mark A; Laeyendecker, Oliver; Fiamma, Agnès; Donnell, Deborah; Mbwambo, Jessie K K; Richter, Linda; Gray, Glenda; Sweat, Michael; Coates, Thomas J; Eshleman, Susan H

    2017-02-01

    Antiretroviral (ARV) drug treatment benefits the treated individual and can prevent HIV transmission. We assessed ARV drug use in a community-randomized trial that evaluated the impact of behavioral interventions on HIV incidence. Samples were collected in a cross-sectional survey after a 3-year intervention period. ARV drug testing was performed using samples from HIV-infected adults at 4 study sites (Zimbabwe; Tanzania; KwaZulu-Natal and Soweto, South Africa; survey period 2009-2011) using an assay that detects 20 ARV drugs (6 nucleoside/nucleotide reverse transcriptase inhibitors, 3 nonnucleoside reverse transcriptase inhibitors, and 9 protease inhibitors; maraviroc; raltegravir). ARV drugs were detected in 2011 (27.4%) of 7347 samples; 88.1% had 1 nonnucleoside reverse transcriptase inhibitors ± 1-2 nucleoside/nucleotide reverse transcriptase inhibitors. ARV drug detection was associated with sex (women>men), pregnancy, older age (>24 years), and study site (P < 0.0001 for all 4 variables). ARV drugs were also more frequently detected in adults who were widowed (P = 0.006) or unemployed (P = 0.02). ARV drug use was more frequent in intervention versus control communities early in the survey (P = 0.01), with a significant increase in control (P = 0.004) but not in intervention communities during the survey period. In KwaZulu-Natal, a 1% increase in ARV drug use was associated with a 0.14% absolute decrease in HIV incidence (P = 0.018). This study used an objective, biomedical approach to assess ARV drug use on a population level. This analysis identified factors associated with ARV drug use and provided information on ARV drug use over time. ARV drug use was associated with lower HIV incidence at 1 study site.

  2. Equity in access to ARV drugs in Malawi

    African Journals Online (AJOL)

    2007-05-01

    May 1, 2007 ... Based on data collected through a qualitative research methodology, it was found that achieving equity in provision ... RÉSUMÉ. Cette communication aborde le sujet de l'équité vis-à-vis la distribution des drogues ARV au sein du système de .... exhaustive because it was in large measure determined.

  3. Vietnamese Women's Struggle to Access Antiretroviral Drugs in a Context of Free Treatment

    DEFF Research Database (Denmark)

    Nguyen, Nam Thi Thu; Rasch, Vibeke; Bygbjerg, Ib Christian

    2013-01-01

    This qualitative study aims to explore how HIV positive women living in a northern province of Vietnam experience seeking antiretroviral (ARV) treatment in the public health system, and how they address obstacles encountered along the way. Despite the fact that antiretroviral drugs were freely...... provided, they were not always accessible for women in need. A variety of factors at the population and health system level interacted in ways that often made access to ARV drugs a complicated and time-consuming process. We have suggested changes that could be made at the health system level that may help...

  4. Trends in Decline of Antiretroviral Resistance among ARV-Experienced Patients in the HIV Outpatient Study: 1999–2008

    Directory of Open Access Journals (Sweden)

    Kate Buchacz

    2012-01-01

    Full Text Available Background. Little is known about temporal trends in frequencies of clinically relevant ARV resistance mutations in HIV strains from U.S. patients undergoing genotypic testing (GT in routine HIV care. Methods. We analyzed cumulative frequency of HIV resistance among patients in the HIV Outpatient Study (HOPS who, during 1999–2008 and while prescribed antiretrovirals, underwent GT with plasma HIV RNA >1,000 copies/mL. Exposure ≥4 months to each of three major antiretroviral classes (NRTI, NNRTI and PI was defined as triple-class exposure (TCE. Results. 906 patients contributed 1,570 GT results. The annual frequency of any major resistance mutations decreased during 1999–2008 (88% to 79%, P=0.05. Resistance to PIs decreased among PI-exposed patients (71% to 46%, P=0.010 as exposure to ritonavir-boosted PIs increased (6% to 81%, P<0.001. Non-significant declines were observed in resistance to NRTIs among NRTI-exposed (82% to 67%, and triple-class-resistance among TCE patients (66% to 41%, but not to NNRTIs among NNRTI-exposed. Conclusions. HIV resistance was common but declined in HIV isolates from subgroups of ARV-experienced HOPS patients during 1999–2008. Resistance to PIs among PI-exposed patients decreased, possibly due to increased representation of patients whose only PI exposures were to boosted PIs.

  5. Antiretroviral drug supply challenges in the era of scaling up ART in Malawi.

    Science.gov (United States)

    Schouten, Erik J; Jahn, Andreas; Ben-Smith, Anne; Makombe, Simon D; Harries, Anthony D; Aboagye-Nyame, Francis; Chimbwandira, Frank

    2011-07-06

    The number of people receiving antiretroviral treatment (ART) has increased considerably in recent years and is expected to continue to grow in the coming years. A major challenge is to maintain uninterrupted supplies of antiretroviral (ARV) drugs and prevent stock outs. This article discusses issues around the management of ARVs and prevention of stock outs in Malawi, a low-income country with a high HIV/AIDS burden, and a weak procurement and supply chain management system. This system for ARVs, paid for by the Global Fund to Fight AIDS, Tuberculosis and Malaria, and bypassing the government Central Medical Stores, is in place, using the United Nations Children's Fund's (UNICEF's) procurement services. The system, managed by a handful of people who spend limited time on supply management, is characterized by a centrally coordinated quantification based on verified data from all national ART clinics, parallel procurement through UNICEF, and direct distribution to ART clinics. The model worked well in the first years of the ART programme with a single first-line ARV regimen, but with more regimens becoming available (e.g., alternative first-line, second-line and paediatric regimens), it has become more difficult to administer. Managing supplies through a parallel system has the advantage that weaknesses in the national system have limited influence on the ARV procurement and supply chain management system. However, as the current system operates without a central warehouse and national buffer stock capacity, it diminishes the ability to prevent ARV stock outs. The process of ordering ARVs, from the time that estimates are made to the arrival of supplies in health facilities, takes approximately one year. Addressing the challenges involved in maintaining ARVs through an efficient procurement and supply chain management system that prevents ARV stock outs through the establishment of a dedicated procurement team, a central warehouse and/or national buffer stock is a

  6. Bioanalysis, metabolism & clinical pharmacology of antiretroviral drugs

    NARCIS (Netherlands)

    Heine, R. ter

    2009-01-01

    The aims of all studies described in this thesis were to develop new bioanalytical and more patient friendly methods for studying the clinical pharmacology of antiretroviral drugs and to ultimately improve antiretroviral treatment.

  7. Antiretroviral therapeutic drug monitoring

    African Journals Online (AJOL)

    Winnie

    GENERAL PRINCIPLES OF TDM. The vast majority of drugs used in clinical practice do not require TDM. It is far easier for clinicians to adopt a 'one size fits all' approach to dosing. Alternatively doses may be modified according to response. However, with some drugs this will result in high rates of toxicity, or suboptimal ...

  8. Price Reversal Pattern of ARV Drugs: A Transaction-Cost Approach Digression

    Directory of Open Access Journals (Sweden)

    Frank LORNE

    2015-05-01

    Full Text Available A price reversal pattern of ARV drugs was noted across lower and middle income countries in that the lower-income countries have higher prices relative to higher-income countries based on a 2008-2009 Summary Report by World Health Organization. The transaction costs affecting AVR drug pricing can be broadly classified into two kinds: One between the final users and the opinion/knowledge experts, and the other between the opinion/knowledge experts and the manufacturers. Economist’s version of price discrimination needs to be modified by including transaction costs. Transaction costs also point to institution creditability factors that will affect NGO procurement.

  9. Of Remedies and Poisons: Recreational Use of Antiretroviral Drugs ...

    African Journals Online (AJOL)

    Abstract. During an ethnographic study of barriers to, and compliance with, antiretroviral (ARv ) treat- ment in the South Africa's West Coast region, our team came across a general sense amongst heath care providers that there was a lively illicit trade in antiretroviral medications. in itself, this is seen to be a barrier to ...

  10. In-vitro photo-translocation of antiretroviral drug delivery into TZMbl cells

    Science.gov (United States)

    Malabi, Rudzani; Manoto, Sello; Ombinda-Lemboumba, Saturnin; Maaza, Malik; Mthunzi-Kufa, Patience

    2017-02-01

    The current human immunodeficiency virus (HIV) treatment regime possesses the ability to diminish the viral capacity to unnoticeable levels; however complete eradication of the virus cannot be achieved while latent HIV-1 reservoirs go unchallenged. Therapeutic targeting of HIV therefore requires further investigation and current therapies need modification in order to address HIV eradication. This deflects research towards investigating potential novel antiretroviral drug delivery systems. The use of femtosecond (fs) laser pulses in promoting targeted optical drug delivery of antiretroviral drugs (ARVs) into TZMbl cells revolves around using ultrafast laser pulses that have high peak powers, which precisely disrupt the cell plasma membrane in order to allow immediate transportation and expression of exogenous material into the live mammalian cells. A photo-translocation optical setup was built and validated by characterisation of the accurate parameters such as wavelength (800 nm) and pulse duration (115 fs). Optimisation of drug translocation parameters were done by performing trypan blue translocation studies. Cellular responses were determined via cell viability (Adenosine Triphosphate activity) and cell cytotoxicity (Lactate Dehydrogenase) assays which were done to study the influence of the drugs and laser exposure on the cells. After laser irradiation, high cell viability was observed and low toxicity levels were observed after exposure of the cells to both the ARVs and the laser. Our results confirmed that, with minimal damage and high therapeutic levels of ARVs, the fs laser assisted drug delivery system is efficient with benefits of non-invasive and non-toxic treatment to the cells.

  11. HIV Drug Resistance-Associated Mutations in Antiretroviral Naïve HIV-1-Infected Latin American Children

    Directory of Open Access Journals (Sweden)

    Luis E. Soto-Ramirez

    2010-01-01

    Full Text Available Our goal was to describe the presence of HIV drug resistance among HIV-1-infected, antiretroviral (ARV naïve children and adolescents in Latin America and to examine resistance in these children in relation to drug exposure in the mother. Genotyping was performed on plasma samples obtained at baseline from HIV-1-infected participants in a prospective cohort study in Brazil, Argentina, and Mexico (NISDI Pediatric Study. Of 713 HIV-infected children enrolled, 69 were ARV naïve and eligible for the analysis. At enrollment, mean age was 7.3 years; 81.2% were infected with HIV perinatally. Drug resistance mutations (DRMs were detected in 6 (8.7%; 95% confidence interval 3.1–18.2% ARV-naïve subjects; none of the mothers of these 6 received ARVs during their pregnancies and none of the children received ARV prophylaxis. Reverse transcriptase mutations K70R and K70E were detected in 3 and 2 subjects, respectively; protease mutation I50 V was detected in 1 subject. Three of the 6 children with DRMs initiated ARV therapy during followup, with a good response in 2. The overall rate of primary drug resistance in this pediatric HIV-infected population was low, and no subjects had more than 1 DRM. Mutations associated with resistance to nucleoside reverse transcriptase inhibitors were the most prevalent.

  12. Behavioral Economics Matters for HIV Research: The Impact of Behavioral Biases on Adherence to Antiretrovirals (ARVs).

    Science.gov (United States)

    Linnemayr, Sebastian; Stecher, Chad

    2015-11-01

    Behavioral economics (BE) has been used to study a number of health behaviors such as smoking and drug use, but there is little knowledge of how these insights relate to HIV prevention and care. We present novel evidence on the prevalence of the common behavioral decision-making errors of present-bias, overoptimism, and information salience among 155 Ugandan HIV patients, and analyze their association with subsequent medication adherence. 36 % of study participants are classified as present-biased, 21 % as overoptimistic, and 34 % as having salient HIV information. Patients displaying present-bias were 13 % points (p = 0.006) less likely to have adherence rates above 90 %, overoptimistic clients were 9 % points (p = 0.04) less likely, and those not having salient HIV information were 17 % points (p behavioral biases and the associated suboptimal adherence.

  13. Behavioral Economics Matters for HIV Research: The Impact of Behavioral Biases on Adherence to Antiretrovirals (ARVs)

    Science.gov (United States)

    Stecher, Chad

    2016-01-01

    Behavioral economics (BE) has been used to study a number of health behaviors such as smoking and drug use, but there is little knowledge of how these insights relate to HIV prevention and care. We present novel evidence on the prevalence of the common behavioral decision-making errors of present-bias, overoptimism, and information salience among 155 Ugandan HIV patients, and analyze their association with subsequent medication adherence. 36 % of study participants are classified as present-biased, 21 % as overoptimistic, and 34 % as having salient HIV information. Patients displaying present-bias were 13 % points (p = 0.006) less likely to have adherence rates above 90 %, overoptimistic clients were 9 % points (p = 0.04) less likely, and those not having salient HIV information were 17 % points (p < 0.001) less likely. These findings indicate that BE may be used to screen for future adherence problems and to better design and target interventions addressing these behavioral biases and the associated suboptimal adherence. PMID:25987190

  14. Combined antiretroviral and anti- tuberculosis drug resistance ...

    African Journals Online (AJOL)

    these epidemics, many challenges remain.[3] Antiretroviral and anti-TB drug resistance pose considerable threats to the control of these epidemics.[4,5]. The breakdown in HIV/TB control within prisons is another emerging threat.[6,7] We describe one of the first reports of combined antiretroviral and anti-TB drug resistance ...

  15. Confocal fluorescence microscopy: An ultra-sensitive tool used to evaluate intracellular antiretroviral nano-drug delivery in HeLa cells

    Science.gov (United States)

    Mandal, Subhra; Zhou, You; Shibata, Annemarie; Destache, Christopher J.

    2015-08-01

    In the last decade, confocal fluorescence microscopy has emerged as an ultra-sensitive tool for real-time study of nanoparticles (NPs) fate at the cellular-level. According to WHO 2007 report, Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the world's major health threats by claiming approximately 7,000 new infections daily worldwide. Although combination antiretroviral drugs (cARV) therapy has improved the life-expectancy of HIV-infected patients, routine use of high doses of cARV has serious health consequences and requires complete adherence to the regimen for success. Thus, our research goal is to fabricate long-acting novel cARV loaded poly(lactide-co-glycolic acid) (PLGA) nanoparticles (cARV-NPs) as drug delivery system. However, important aspects of cARV-NPs that require special emphasis are their cellular-uptake, potency, and sustained drug release efficiency over-time. In this article, ultra-sensitive confocal microscopy is been used to evaluate the uptake and sustained drug release kinetics of cARV-NPs in HeLa cells. To evaluate with the above goal, instead of cARV-drug, Rhodamine6G dye (fluorescent dye) loaded NPs (Rho6G NPs) have been formulated. To correlate the Rhodamin6G release kinetics with the ARV release from NPs, a parallel HPLC study was also performed. The results obtained indicate that Rho6G NPs were efficiently taken up at low concentration (treatment. Therefore, high drug assimilation and sustained release properties of PLGA-NPs make them an attractive vehicle for cARV nano-drug delivery with the potential to reduce drug dosage as well as the number of drug administrations per month.

  16. Drug-transporter mediated interactions between anthelminthic and antiretroviral drugs across the Caco-2 cell monolayers.

    Science.gov (United States)

    Kigen, Gabriel; Edwards, Geoffrey

    2017-05-04

    Drug interactions between antiretroviral drugs (ARVs) and anthelminthic drugs, ivermectin (IVM) and praziquantel (PZQ) were assessed by investigating their permeation through the Caco-2 cell monolayers in a transwell. The impact of anthelminthics on the transport of ARVs was determined by assessing the apical to basolateral (AP → BL) [passive] and basolateral to apical (BL → AP) [efflux] directions alone, and in presence of an anthelminthic. The reverse was conducted for the assessment of the influence of ARVs on anthelminthics. Samples from the AP and BL compartments were taken at 60, 120, 180 and 240 min and quantified either by HPLC or radiolabeled assay using a liquid scintillating counter for the respective drugs. Transepithelial resistance (TEER) was used to assess the integrity of the monolayers. The amount of compound transported per second (apparent permeability, Papp) was calculated for both AP to BL (Papp AtoB ), and BL to AP (Papp BtoA ) movements. Samples collected after 60 min were used to determine the efflux ratio (ER), quotient of secretory permeability and absorptive permeability (PappBL-AP/PappAP-BL). The reverse, (PappAP-BL/PappBL-AP) constituted the uptake ratio. The impact of SQV, EFV and NVP on the transport of both IVM and PZQ were investigated. The effect of LPV on the transport of IVM was also determined. The influence of IVM on the transport of SQV, NVP, LPV and EFV; as well as the effect PZQ on the transport of SQV of was also investigated, and a two-tailed p value of <0.05 was considered significant. IVM significantly inhibited the efflux transport (BL → AP movement) of LPV (ER; 6.7 vs. 0.8, p = 0.0038) and SQV (ER; 3.1 vs. 1.2 p = 0.00328); and increased the efflux transport of EFV (ER; 0.7 vs. 0.9, p = 0.031) suggesting the possibility of drug transporter mediated interactions between the two drugs. NVP increased the efflux transport of IVM (ER; 0.8 vs. 1.8, p = 0.0094). The study provides in vitro

  17. Expanding community through ARV provision in Thailand.

    Science.gov (United States)

    Lyttleton, C; Beesey, A; Sitthikriengkrai, M

    2007-01-01

    Anti-retrovirals (ARVs) have altered the complexion of HIV/AIDS management in Thailand. In 2005, ARVs were included within a subsidised health scheme making provision widespread. Increased access has been brought about through the legal and political advocacy of the Thai Network for People Living with HIV/AIDS (TNP+) who now play a central role in expanded ARV provision. HIV-infected volunteers help the state deliver comprehensive services and assist with follow-up and adherence programs. Alongside improvements in drug provision, a focus on pharmaceutical treatment has left other issues, such as community support of orphans and the social responses to living with HIV, less central within community responses. As they take on new responsibilities, people living with HIV/AIDS (PLHA) groups move from activities focused on reversing local stigma to constitute a new social movement that is increasingly prominent in Thai civil society. Networks of PLHA confront new social and political challenges as they also seek to broaden access to marginalised groups who remain excluded from these services. Many ethnic minority groups without full Thai citizenship have been denied access to subsidised health services including ARVs. As part of a broadening advocacy profile, the PLHA movement is now engaging in a politics of difference defined not simply by presence or absence of HIV but also by wider issues of national identity and belonging.

  18. New antiretroviral drugs: What\\'s on the horizon in 2005? | Wood ...

    African Journals Online (AJOL)

    Despite the present number of available antiretrovirals (ARVs), there continues to be a need for new medications with improved tolerability, and activity against resistant virus. This article will review three groups of ARVs: those available in North America and. Europe but not yet registered in South Africa; new formulations of ...

  19. Analysis of clinical drug-drug interaction data to predict uncharacterized interaction magnitudes between antiretroviral drugs and co-medications.

    Science.gov (United States)

    Stader, Felix; Kinvig, Hannah; Battegay, Manuel; Khoo, Saye; Owen, Andrew; Siccardi, Marco; Marzolini, Catia

    2018-04-23

    Despite their high potential for drug-drug-interactions (DDI), clinical DDI studies of antiretroviral drugs (ARVs) are often lacking, because the full range of potential interactions cannot feasibly or pragmatically be studied, with some high-risk DDI studies also ethically difficult to undertake. Thus, a robust method to screen and to predict the likelihood of DDIs is required.We developed a method to predict DDIs based on two parameters: the degree of metabolism by specific enzymes such as CYP3A and the strength of an inhibitor or inducer. These parameters were derived from existing studies utilizing paradigm substrates, inducers and inhibitors of CYP3A, to assess the predictive performance of this method by verifying predicted magnitudes of changes in drug exposure against clinical DDI studies involving ARVs.The derived parameters were consistent with the FDA classification of sensitive CYP3A substrates and the strength of CYP3A inhibitors and inducers. Characterized DDI magnitudes (n = 68) between ARVs and co-medications were successfully quantified meaning 53%, 85% and 98% of the predictions were within 1.25-fold (0.80 - 1.25), 1.5-fold (0.66 - 1.48) and 2-fold (0.66 - 1.94) of the observed clinical data. In addition, the method identifies CYP3A substrates likely to be highly or conversely minimally impacted by CYP3A inhibitors or inducers, thus categorizing the magnitude of DDIs.The developed effective and robust method has the potential to support a more rational identification of dose adjustment to overcome DDIs being particularly relevant in a HIV-setting giving the treatments complexity, high DDI risk and limited guidance on the management of DDIs. Copyright © 2018 American Society for Microbiology.

  20. Expression of Genes for Drug Transporters in the Human Female Genital Tract and Modulatory Effect of Antiretroviral Drugs.

    Directory of Open Access Journals (Sweden)

    Karolin Hijazi

    Full Text Available Anti-retroviral (ARV -based microbicides are one of the strategies pursued to prevent HIV-1 transmission. Delivery of ARV drugs to subepithelial CD4+ T cells at concentrations for protection is likely determined by drug transporters expressed in the cervicovaginal epithelium. To define the role of drug transporters in mucosal disposition of topically applied ARV-based microbicides, these must be tested in epithelial cell line-based biopharmaceutical assays factoring the effect of relevant drug transporters. We have characterised gene expression of influx and efflux drug transporters in a panel of cervicovaginal cell lines and compared this to expression in cervicovaginal tissue. We also investigated the effect of dapivirine, darunavir and tenofovir, currently at advanced stages of microbicides development, on expression of drug transporters in cell lines. Expression of efflux ABC transporters in cervical tissue was best represented in HeLa, Ect1/E6E7 and End1/E6E7 cell lines. Expression of influx OCT and ENT transporters in ectocervix matched expression in Hela while expression of influx SLCO transporters in vagina was best reflected in VK2/E6E7 cell line. Stimulation with darunavir and dapivirine upregulated MRP transporters, including MRP5 involved in transport of tenofovir. Dapivirine also significantly downregulated tenofovir substrate MRP4 in cervical cell lines. Treatment with darunavir and dapivirine showed no significant effect on expression of BCRP, MRP2 and P-glycoprotein implicated in efflux of different ARV drugs. Darunavir strongly induced expression in most cell lines of CNT3 involved in cell uptake of nucleotide/nucleoside analogue reverse transcriptase inhibitors and SLCO drug transporters involved in cell uptake of protease inhibitors. This study provides insight into the suitability of cervicovaginal cell lines for assessment of ARV drugs in transport kinetics studies. The modulatory effect of darunavir and dapivirine on

  1. Perceptions of the benefits and affordability of antiretrovirals among ...

    African Journals Online (AJOL)

    To assess the affordability of antiretroviral drugs (ARVs) and accessibility to treatment for opportunistic infections (OIs) among HIV-1 seropositive persons, we used semi-structured interviewer-administered questionnaires to interview 154 individuals seeking ARV treatment at the Daughter of Charity German Leprosy and ...

  2. The Decline in HIV-1 Drug Resistance in Heavily Antiretroviral-Experienced Patients Is Associated with Optimized Prescriptions in a Treatment Roll-Out Program in Mexico.

    Science.gov (United States)

    Calva, Juan J; Larrea, Silvana; Tapia-Maltos, Marco A; Ostrosky-Frid, Mauricio; Lara, Carolina; Aguilar-Salinas, Pedro; Rivera, Héctor; Ramírez, Juan P

    2017-07-01

    A decrease in the rate of acquired antiretroviral (ARV) drug resistance (ADR) over time has been documented in high-income settings, but data on the determinants of this phenomenon are lacking. We tested the hypothesis that in heavily ARV-experienced patients in the Mexican ARV therapy (ART) roll-out program, the drop in ADR would be associated with changes in ARV drug usage. Genotypic resistance tests obtained from 974 HIV-infected patients with virological failure and at least 2 previously failed ARV regimens from throughout the country were analyzed for the presence of nucleos(t)ide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitor (PI) resistance-associated mutations (RAMs). Patients were divided into two groups according to their first ART start date: 488 patients initiated ART before mid-2003 (group 1) and 486 after mid-2003 (group 2). The rate of RAMs, median resistance score of several sentinel ARVs, and composition of ART drugs in patient's entire treatment history were compared between both groups. Patients in group 2 were less likely to have >3 thymidine analogue-associated mutations (TAMs) and >3 PI-mRAMs [adjusted odds ratio (aOR) = 0.37; 95% confidence interval (95% CI) = 0.25-0.54; p mRAM has significantly declined over time. This can be explained by treatment optimization in the national ART roll-out program in recent years.

  3. Factors contributing to antiretroviral drug adherence among adults living with HIV or AIDS in a Kenyan rural community

    Directory of Open Access Journals (Sweden)

    Mary T. Kioko

    2017-01-01

    Full Text Available Background: Antiretroviral (ARV adherence of ≥ 95% is recommended for suppressing HIV. However, studies have shown that the ≥ 95% recommended level is rarely achieved.Objective: This cross-sectional community-based study sought to assess factors contributing to ARV drug adherence among adults living with HIV or AIDS.Setting: The study was conducted in a rural community in Machakos County, Kenya.Methods: The questions used for the study were adapted from the Patient Medicine Adherence Questionnaire (PMAQ, a tool grounded in the Health Belief Model. Adherence to ARV was measured using self-reports and pill counts. The perception social support was measured with a 5-point Likert scale, whereas the type and the number of side effects experienced were recorded using ‘yes’ and ‘no’ questions. We used the chi-square test to test associations and binary logistic regression to assess factors explaining dose adherence to ARV.Results: The levels of adherence of 86% using self-reports were significantly higher (p < 0.001 than the pill count of 58.6%. The immediate family was rated high in providing social support (3.7 ± 0.6 followed by social support groups (3.1 ± 0.8. A binary logistic regression analysis was conducted to predict ARV adherence (adherent, non-adherent using social support, side effects and marital status as explanatory variables. The Wald criterion demonstrated that marital status (p = 0.019 and burden of side effects (p ≤ 0.001 made a significant contribution to the prediction of ARV adherence.Conclusion: The burden of side effects and being a divorcee are primary predictors of ARV adherence.

  4. Social arv

    DEFF Research Database (Denmark)

    Jensen, Bente

    Denne publikation er det første arbejdspapir/rapport i serien om forskningsprojektet "Handlekompetence i pædagogisk arbejde med socialt udsatte børn og unge - indsats og effekt (HPA-projektet). Social arv og det deraf afledte begreb om 'udsatte børn', som er det samfundsproblem, der danner rammen...... om HPA-projektets intervenstionsdel og -analyser er ikke et entydigt begreb. Formålet med papiret er derfor at indkredse diskussionen om social arv set som reproduktion af ulighed og på den baggrund belyse relevante indikatorer som kan tjene som baggrundvariable i studiet af effekter i relation til...... samfundets institutionelle mulighder for at skabe fornyelse på det sociale område gennem social intervention...

  5. Interaction between pharmaceutical companies and physicians who prescribe antiretroviral drugs for treating AIDS.

    Science.gov (United States)

    Scheffer, Mário César

    2014-01-01

    Given that Brazil has a universal public policy for supplying medications to treat HIV and AIDS, the aim here was to describe the forms of relationship between physicians and the pharmaceutical companies that produce antiretrovirals (ARVs). Cross-sectional epidemiological study conducted in the state of São Paulo. Secondary database linkage was used, with structured interviews conducted by telephone among a sample group of 300 physicians representing 2,361 professionals who care for patients with HIV and AIDS. Around two thirds (64%) of the physicians prescribing ARVs for HIV and AIDS treatment in the state of São Paulo who were interviewed declared that they had some form of relationship with pharmaceutical companies, of which the most frequent were receipt of publications (54%), visits by sales promoters (51%) and receipt of small-value objects (47%). Two forms of relationship between the pharmaceutical industry and physicians who deal with HIV and AIDS can be highlighted: facilitation of professionals' access to continuing education; and antiretroviral drug brand name promotion.

  6. Interaction between pharmaceutical companies and physicians who prescribe antiretroviral drugs for treating AIDS

    Directory of Open Access Journals (Sweden)

    Mario Cesar Scheffer

    Full Text Available CONTEXT AND OBJECTIVE: Given that Brazil has a universal public policy for supplying medications to treat HIV and AIDS, the aim here was to describe the forms of relationship between physicians and the pharmaceutical companies that produce antiretrovirals (ARVs. DESIGN AND SETTING: Cross-sectional epidemiological study conducted in the state of São Paulo. METHODS : Secondary database linkage was used, with structured interviews conducted by telephone among a sample group of 300 physicians representing 2,361 professionals who care for patients with HIV and AIDS. RESULTS : Around two thirds (64% of the physicians prescribing ARVs for HIV and AIDS treatment in the state of São Paulo who were interviewed declared that they had some form of relationship with pharmaceutical companies, of which the most frequent were receipt of publications (54%, visits by sales promoters (51% and receipt of small-value objects (47%. CONCLUSIONS: Two forms of relationship between the pharmaceutical industry and physicians who deal with HIV and AIDS can be highlighted: facilitation of professionals' access to continuing education; and antiretroviral drug brand name promotion.

  7. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

    Science.gov (United States)

    Günthard, Huldrych F.; Saag, Michael S.; Benson, Constance A.; del Rio, Carlos; Eron, Joseph J.; Gallant, Joel E.; Hoy, Jennifer F.; Mugavero, Michael J.; Sax, Paul E.; Thompson, Melanie A.; Gandhi, Rajesh T.; Landovitz, Raphael J.; Smith, Davey M.; Jacobsen, Donna M.; Volberding, Paul A.

    2016-01-01

    IMPORTANCE New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory

  8. Problems Associated With Substandard And Counterfeit Drugs In ...

    African Journals Online (AJOL)

    Problems Associated With Substandard And Counterfeit Drugs In Developing Countries: A Review Article On Global Implications Of Counterfeit Drugs In The Era Of Anti-Retroviral (ARVS) Drugs In A Free Market Economy.

  9. Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance.

    Science.gov (United States)

    Sagna, Tani; Bisseye, Cyrille; Compaore, Tegewende R; Kagone, Therese S; Djigma, Florencia W; Ouermi, Djeneba; Pirkle, Catherine M; Zeba, Moctar T A; Bazie, Valerie J T; Douamba, Zoenabo; Moret, Remy; Pietra, Virginio; Koama, Adjirita; Gnoula, Charlemagne; Sia, Joseph D; Nikiema, Jean-Baptiste; Simpore, Jacques

    2015-01-01

    Vertical human immunodeficiency virus (HIV) transmission is a public health problem in Burkina Faso. The main objective of this study on the prevention of mother-to-child HIV-1 transmission was to determine the residual risk of HIV transmission in infants born to mothers receiving highly active antiretroviral therapy (HAART). Moreover, we detect HIV antiretroviral (ARV) drug resistance among mother-infant pairs and identify subtypes and circulating recombinant forms (CRF) in Burkina Faso. In this study, 3,215 samples of pregnant women were analyzed for HIV using rapid tests. Vertical transmission was estimated by polymerase chain reaction in 6-month-old infants born to women who tested HIV positive. HIV-1 resistance to ARV, subtypes, and CRFs was determined through ViroSeq kit using the ABI PRISM 3,130 sequencer. In this study, 12.26% (394/3,215) of the pregnant women were diagnosed HIV positive. There was 0.52% (2/388) overall vertical transmission of HIV, with rates of 1.75% (2/114) among mothers under prophylaxis and 0.00% (0/274) for those under HAART. Genetic mutations were also isolated that induce resistance to ARV such as M184V, Y115F, K103N, Y181C, V179E, and G190A. There were subtypes and CRF of HIV-1 present, the most common being: CRF06_CPX (58.8%), CRF02_AG (35.3%), and subtype G (5.9%). ARV drugs reduce the residual rate of HIV vertical transmission. However, the virus has developed resistance to ARV, which could limit future therapeutic options when treatment is needed. Resistance to ARV therefore requires a permanent interaction between researchers, physicians, and pharmacists, to strengthen the network of monitoring and surveillance of drug resistance in Burkina Faso.

  10. Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

    Directory of Open Access Journals (Sweden)

    Jacinta Nwamaka Nwogu

    2016-01-01

    Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.

  11. Of Remedies and Poisons: Recreational Use of Antiretroviral Drugs ...

    African Journals Online (AJOL)

    In itself, this is seen to be a barrier to adherence for many of their patients whose medication is traded to, or stolen by, drug dealers. Independent anecdotal evidence is emerging about this trade, though there has been little hard data verifying the existence of a recreational market for ARVs. While there are rumours that ...

  12. [High activity antiretroviral therapy change associated to adverse drug reactions in a specialized center in Venezuela].

    Science.gov (United States)

    Subiela, José D; Dapena, Elida

    2016-03-01

    Adverse drug reactions (ADRs) represent the first cause of change of the first-line highly active antiretroviral therapy (HAART) regimen, therefore, they constitute the main limiting factor in the long-term follow up of HIV patients in treatment. A retrospective study was carried out in a specialized center in Lara State, Venezuela, including 99 patients over 18 years of age who had change of first-line HAART regimen due to ADRs, between 2010 and 2013. The aims of this research were to describe the sociodemographic and clinical variables, frequency of ADRs related to change of HAART, duration of the first-line HAART regimen, to determine the drugs associated with ARVs and to identify the risk factors. The ADRs constituted 47.5% of all causes of change of first-line HAART regimen, the median duration was 1.08±0.28 years. The most frequent ADRs were anemia (34.3%), hypersensitivity reactions (20.2%) and gastrointestinal intolerance (13.1%). The most frequent ARV regimen type was the protease inhibitors-based regimen (59.6%), but zidovudine was the ARV most linked to ADRs (41.4%). The regression analysis showed increased risk of ADRs in singles and students in the univariate analysis and heterosexuals and homosexuals in multivariate analysis; and decreased risk in active workers. The present work shows the high prevalence of ADRs in the studied population and represents the first case-based study that describes the pharmacoepidemiology of a cohort of HIV-positive patients treated in Venezuela.

  13. Maternal and infant health is protected by antiretroviral drug ...

    African Journals Online (AJOL)

    Maternal and infant health is protected by antiretroviral drug strategies that preserve breastfeeding by HIV-Positive women. L Kuhn ... By so doing, it recognises that any intervention that might detract from breast feeding poses a serious threat to infant survival. Since evidence is now strong that antiretroviral drugs used ...

  14. Antiretroviral Drugs Used in the Treatment of HIV Infection

    Science.gov (United States)

    ... HIV/AIDS Treatment Antiretroviral drugs used in the treatment of HIV infection Share Tweet Linkedin Pin it More sharing ... Pin it Email Print Drugs Used in the Treatment of HIV Infection All FDA-approved medicines used in the ...

  15. The discovery and development of antiretroviral agents

    NARCIS (Netherlands)

    Lange, Joep M. A.; Ananworanich, Jintanat

    2014-01-01

    Since the discovery of HIV as the causative agent of AIDS in 1983/1984, remarkable progress has been made in finding antiretroviral drugs (ARVs) that are effective against it. A major breakthrough occurred in 1996 when it was found that triple drug therapy (HAART) could durably suppress viral

  16. Effect of Antiretroviral Drug (arved) on the Kidney in Albino Rat ...

    African Journals Online (AJOL)

    A total of fifty two (52) albino rats were randomly divided into four groups labeled A, B, C and D and kept in a well ventilated room. All experimental groups shared the same environmental conditions. Group A served as the control and rats were treated with distil water. Rats in groups B, C and D were, respectively treated ...

  17. Can voluntary pooled procurement reduce the price of antiretroviral drugs? a case study of Efavirenz.

    Science.gov (United States)

    Kim, Sung Wook; Skordis-Worrall, Jolene

    2017-05-01

    : A number of strategies have aimed to assist countries in procuring antiretroviral therapy (ARV) at lower prices. In 2009, as the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) commenced a voluntary pooled procurement scheme, however, the impact of the scheme on ARV prices remains uncertain. This study aims to estimate the effect of VPP on drug prices using Efavirenz as a case study. This analysis uses WHO Global price report mechanism (GPRM) data from 2004 to 2013. Due to the highly skewed distribution of drug Prices, a generalized linear model (GLM) was used to conduct a difference-in-difference estimation of drug price changes over time. These analyses found that voluntary pooled procurement reduced both the ex-works price of generic Efavirenz and the incoterms price by 16.2 and 19.1%, respectively ( P <  0.001) in both cases). The year dummies were also statistically significant from 2006 to 2013 ( P <  0.001), indicating a strong decreasing trend in the price of Efavirenz over that period. Voluntary pooled procurement significantly reduced the price of 600 mg generic Efavirenz between 2009 and 2013. Voluntary pooled procurement therefore offers a potentially effective strategy for the reduction in HIV drug prices and the improvement of technical efficiency in HIV programming. Further work is required to establish if these findings hold also for other drugs. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  18. Quality of Life and Adherence to Antiretroviral Drugs

    African Journals Online (AJOL)

    Sitwala

    Quality of Life and Adherence to Antiretroviral Drugs. Medical Journal of Zambia, Volume 37 Number 1 (2010). *P. Mweemba, M.K. Makukula, P.K. Mukwato, M.M. Makoleka. Department of Nursing Sciences, School of Medicine, University of Zambia, Lusaka, Zambia. ABSTRACT. Introduction: Antiretroviral therapy has led to ...

  19. Class of Antiretroviral Drugs and the Risk of Myocardial Infarction

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Reiss, P; Sabin, CA

    2007-01-01

    BACKGROUND: We have previously demonstrated an association between combination antiretroviral therapy and the risk of myocardial infarction. It is not clear whether this association differs according to the class of antiretroviral drugs. We conducted a study to investigate the association of cumu...

  20. A MultiFactorial Risk Score to weigh toxicities and co-morbidities relative to costs of antiretrovirals in a cohort of HIV-infected patients

    OpenAIRE

    M Tontodonati; F Sozio; F Vadini; E Polilli; T Ursini; G Calella; P Di Stefano; E Mazzotta; A Costantini; C D'Amario; G Parruti

    2012-01-01

    Purpose of the study: Considering costs of antiretrovirals (ARVs) for HIV patients is increasingly needed. A simple and comprehensive tool weighing comorbidities and ARV-related toxicities could be useful to judge the appropriateness of use of more expensive drugs. We conceived a MultiFactorial Risk Score (MFRS) to evaluate the appropriateness of ARVs prescription relative to their costs. Methods: HIV patients were consecutively enrolled in 2010-2011. We considered socio-demographic character...

  1. The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs

    Directory of Open Access Journals (Sweden)

    Russell Barrett Van Dyke

    2016-05-01

    Full Text Available The Surveillance Monitoring for ART Toxicities (SMARTT cohort of the Pediatric HIV/AIDS Cohort Study (PHACS includes over 3500 HIV-exposed but uninfected (HEU infants and children at 22 sites in the U.S. including Puerto Rico. The goal of the study is to determine the safety of in utero exposure to antiretrovirals (ARV and to estimate the incidence of adverse events. Domains being assessed include metabolic, growth and development, cardiac, neurological, neurodevelopmental, behavior, language, and hearing. SMARTT employs an innovative trigger-based design as an efficient means to identify and evaluate adverse events. Participants who met a predefined clinical or laboratory threshold (trigger undergo additional evaluations to define their case status. After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain with exposure to combination ARVs (cARV, any ARV class, or any specific ARV. However, several individual ARVs were significantly associated with case status in individual domains, including zidovudine for a metabolic case, first trimester stavudine for a language case, and didanosine plus stavudine for a neurodevelopmental case. We found an increased rate of preterm birth with first trimester exposure to protease inhibitor-based cARV. Although there was no overall increase in congenital anomalies with first trimester cARV, a significant increase was seen with exposure to atazanavir, ritonavir, and didanosine plus stavudine. Tenofovir exposure was associated with significantly lower mean whole-body bone mineral content in the newborn period and a lower length and head circumference at 1 year of age. With neurodevelopmental testing at 1 year of age, specific ARVs (atazanavir, ritonavir-boosted lopinavir, nelfinavir, and tenofovir were associated with lower performance, although all groups were within the normal range. No ARVs or classes were

  2. Potential drug–drug interactions in HIV-infected children on antiretroviral therapy in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Oshikoya KA

    2014-04-01

    Full Text Available Kazeem A Oshikoya,1 Ibrahim A Oreagba,2 Saheed Lawal,2 Olufunsho Awodele,2 Olayinka O Ogunleye,1 Idowu O Senbanjo,3 Sunday O Olayemi,2 Veronica C Ezeaka,4,5 Edamisan O Temiye,4,5 Titilope A Adeyemo,4,6 Oluranti Opanuga,4,7 Olufunmilayo A Lesi,4,8 Sulaimon A Akanmu4,6 1Department of Pharmacology, Lagos State University College of Medicine, Ikeja, Lagos, Nigeria; 2Department of Pharmacology, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria; 3Department of Paediatrics, Lagos State University College of Medicine, Ikeja, Lagos, Nigeria; 4APIN Clinic, Lagos University Teaching Hospital, Lagos, Nigeria; 5Department of Paediatrics, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria; 6Department of Haematology and Blood Transfusion, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria; 7Department of Pharmacy, Lagos University Teaching Hospital, Idi-Araba Lagos, Nigeria; 8Department of Medicine, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria Background: Multi-therapy is common in HIV-infected children, and the risk for clinically significant drug interactions (CSDIs is high. We investigated the prevalence of CSDIs between antiretroviral (ARV and co-prescribed drugs for children attending a large HIV clinic in Lagos, Nigeria. Methods: The case files of pediatric patients receiving treatment at the HIV clinic of the Lagos University Teaching Hospital (LUTH, Idi-Araba, between January 2005 and December 2010 were reviewed. The ARV and co-prescribed drug pairs were evaluated for potential interactions using the Liverpool HIV Pharmacology Group website. The potential interactions were rated as A (no known interaction, B (minor/no action needed, C (moderate/monitor therapy, D (major/therapy modification, and X (contraindicated/avoid combination. Results: Of the 310 cases reviewed, 208 (67.1% patients were at risk of CSDIs. Artemisinin-based combination therapy was prescribed for over one

  3. Designing ARVs Patent Pool Up to Trade & Policy Evolutionary Dynamics.

    Science.gov (United States)

    Dionisio, Daniele; Racalbuto, Vincenzo; Messeri, Daniela

    2010-01-19

    Patent pools for second and third-line Fixed Dose Combination (FDC) antiretroviral drugs (ARVs) should not be delayed as they are instrumental to urgent public health needs in the under-served markets.Nonetheless, multinational originator companies still seem to perceive patent pooling for ARVs as a minefield that would offer the generic competitors lots of deeply exploitable opportunities, to the detriment of patent owner's rights.This paper analyses the brand industry concerns, while looking for a strategy up to a really equitable and free world market, without any discrimination between end-users in wealthy and resource-limited countries.This strategy would urge partnerships between originator companies first to make newer FDC ARVs quickly available and allow patent pool agreements with generic counterparts to be negotiated straight afterwards.The patent pool strategy highlighted in this paper would assert the primacy of health over for-profit policies, while aligning with the 61(st) WHO's Assembly recommendations and G7, G8 and World Trade Organisation's warnings and pledges against trade protectionism.

  4. Antiretroviral adverse drug reactions and their management

    African Journals Online (AJOL)

    2011-06-02

    Jun 2, 2011 ... This article discusses the common and serious adverse effects (AEs) related to the above antiretrovirals ... transaminases to more than 5 times the upper limit of normal. This is more frequent in ..... The prime suspect for causing the tumours is aloin A, which together with other aloe extracts was removed from ...

  5. Insulin resistance induced by antiretroviral drugs: Current ...

    African Journals Online (AJOL)

    Treatment with highly active antiretroviral therapy (HAART) has improved the prognosis of patients with AIDS, but it has also increased the incidence of various metabolic disorders, in particular insulin resistance accompanied by dyslipidaemia, hyperglycaemia and lipodystrophy. This is often accompanied by frank type 2 ...

  6. [Prevalence of primary antiretroviral resistance among HIV infected patients in Chile].

    Science.gov (United States)

    Afani, Alejandro; Beltrán, Carlos; María Gallardo, Ana; Roessler, Patricia; Acevedo, William; Vásquez, Patricia

    2010-06-01

    The main cause of virological failure during AIDS treatment is the resistance to antiretroviral medications (ARV). To search for mutations associated with ARV resistance in recently HIV-1 infected patients naïve to treatment, in Chile. Patients over 18 years old with HIV-1 infection, naïve to anti-retroviral drugs before the study were included. Patients with CD4 cell counts less than 200 cells/mm3, viral load below 2000 copies/mL or any condition indicative of advanced AIDS were excluded. Criteria for diagnosis of recent infection (Chile. Therefore, a genotyping test before starting antiretroviral therapy is not necessary.

  7. Antiretroviral procurement and supply chain management.

    Science.gov (United States)

    Ripin, David J; Jamieson, David; Meyers, Amy; Warty, Umesh; Dain, Mary; Khamsi, Cyril

    2014-01-01

    Procurement, the country-level process of ordering antiretrovirals (ARVs), and supply chain management, the mechanism by which they are delivered to health-care facilities, are critical processes required to move ARVs from manufacturers to patients. To provide a glimpse into the ARV procurement and supply chain, the following pages provide an overview of the primary stakeholders, principal operating models, and policies and regulations involved in ARV procurement. Also presented are key challenges that need to be addressed to ensure that the supply chain is not a barrier to the goal of universal coverage. This article will cover the steps necessary to order and distribute ARVs, including different models of delivery, key stakeholders involved, strategic considerations that vary depending on context and policies affecting them. The single drug examples given illustrate the complications inherent in fragmented supply and demand-driven models of procurement and supply chain management, and suggest tools for navigating these hurdles that will ultimately result in more secure and reliable ARV provision. Understanding the dynamics of ARV supply chain is important for the global health community, both to ensure full and efficient treatment of persons living with HIV as well as to inform the supply chain decisions for other public health products.

  8. Safety and effectiveness of antiretroviral drugs during pregnancy, delivery and breastfeeding for prevention of mother-to-child transmission of HIV-1: the Kesho Bora Multicentre Collaborative Study rationale, design, and implementation challenges.

    Science.gov (United States)

    2011-01-01

    To evaluate strategies to reduce HIV-1 transmission through breastfeeding, a multicentre study including a nested randomized controlled trial was implemented in five research sites in West, East and South Africa (The Kesho Bora Study). The aim was to optimize the use of antiretroviral (ARV) drugs during pregnancy, delivery and breastfeeding to prevent mother-to-child transmission of HIV-1 (PMTCT) and to preserve the health of the HIV-1-infected mother. The study included long-term ARV treatment for women with advanced disease, and short-course ARV prophylaxis stopped at delivery for women with early disease. Women with intermediate disease participated in a randomized controlled trial to compare safety and efficacy of triple-ARV prophylaxis prolonged during breastfeeding with short-course ARV prophylaxis stopped at delivery. Between January 2005 and August 2008 a total of 1140 women were enrolled. This paper describes the study design, interventions and protocol amendments introduced to adapt to evolving scientific knowledge, international guidelines and availability of ARV treatment. The paper highlights the successes and challenges during the conduct of the trial. The Kesho Bora Study included one of the few randomized controlled trials to assess safety and efficacy of ARV prophylaxis continued during breastfeeding and the only randomized trial to assess maternal prophylaxis started during pregnancy. The findings have been important for informing international and national guidelines on MTCT prevention in developing countries where, due to poverty, lack of reliable and affordable supply of replacement feed and stigma associated with HIV/AIDS, HIV-infected women have little or no option other than to breastfeed their infants. (ISRCTN71468401). Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.

    Science.gov (United States)

    Tittle, Victoria; Bull, Lauren; Boffito, Marta; Nwokolo, Nneka

    2015-01-01

    More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women

  10. Pharmacoepidemiology of antiretroviral drugs in a teaching hospital ...

    African Journals Online (AJOL)

    Objective: Prescribing, adherence, and adverse drug events to HAART in a large antiretroviral programme in Lagos was evaluated. Design: A retrospective 5 year open cohort study. Setting: The AIDS Prevention Initiative in Nigeria (APIN) clinic at LUTH is one of the United States Presidential Emergency Plan for AIDS ...

  11. Spirituality and adherence to antiretroviral drugs among HIV positive ...

    African Journals Online (AJOL)

    Poor drug adherence is a major problem in the care of HIV patients on antiretroviral treatment. Spirituality is one of the several factors that affects ... The Functional Assessment of Chronic Illness Therapy- Spirituality (FACIT-Sp) tool was used to determine their level of spirituality. Participants were classified as having high or ...

  12. Safety of in utero and neonatal antiretroviral exposure: cognitive and academic outcomes in HIV-exposed, uninfected children 5-13 years of age.

    Science.gov (United States)

    Nozyce, Molly L; Huo, Yanling; Williams, Paige L; Kapetanovic, Suad; Hazra, Rohan; Nichols, Sharon; Hunter, Scott; Smith, Renee; Seage, George R; Sirois, Patricia A

    2014-11-01

    Long-term effects of in utero and neonatal antiretroviral (ARV) exposure on cognitive and academic development in HIV-exposed, uninfected school-age children are unknown. HIV-exposed, uninfected children, ages 5-13 years, in Pediatric HIV/AIDS Cohort Study Surveillance Monitoring for Antiretroviral Treatment Toxicities, a US-based multisite cohort study, completed age-appropriate Wechsler intelligence and academic scales (WPPSI-III, WASI, WIAT-II-A). Associations between cognitive and academic outcomes and in utero ARV exposure by regimen, class and individual ARVs were evaluated, adjusting for potential confounders. Children completing WPPSI-IIIs (n = 350) were 49% male, 74% Black, 25% Hispanic; WASI (n = 337) and WIAT-II-A (n = 415) cohorts were similar. The percentage exposed to combination ARV (cARV) was 84% (WPPSI-III), 64% (WASI) and 67% (WIAT-II-A). Among ARV-exposed children, there were no significant associations between any ARV regimen or class and any cognitive or academic outcome. In addition, in both unadjusted models and after adjustment for caregiver IQ, sociodemographic factors and maternal health and substance use during pregnancy, no individual ARV drug was associated with significantly lower cognitive or academic scores. Factors typically associated with lower cognitive and academic scores in the general population, such as prematurity, small for gestational age, maternal alcohol use and lower maternal cognitive status, were also associated with lower scores in this study. Overall, the safety of prenatal and neonatal ARV use was supported.

  13. Pharmacological interactions between rifampicin and antiretroviral drugs: challenges and research priorities for resource-limited settings

    NARCIS (Netherlands)

    Semvua, H.H.; Kibiki, G.S.; Kisanga, E.R.; Boeree, M.J.; Burger, D.M.; Aarnoutse, R.

    2015-01-01

    Coadministration of antituberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis (TB) is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and many antiretroviral drugs is complicated by pharmacokinetic

  14. Potential drug interactions in patients given antiretroviral therapy.

    Science.gov (United States)

    Santos, Wendel Mombaque Dos; Secoli, Silvia Regina; Padoin, Stela Maris de Mello

    2016-11-21

    to investigate potential drug-drug interactions (PDDI) in patients with HIV infection on antiretroviral therapy. a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r). Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000) and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p sistema nervoso central e cardiovascular, mas também podem interferir em testes utilizados para a detecção da resistência do HIV aos medicamentos antirretrovirais. investigar las posibles interacciones fármaco-fármaco (PDDI en inglés) en pacientes con infección por VIH que reciben terapia antirretroviral. un estudio transversal se llevó a cabo en 161 adultos con infección por VIH. Se recogieron datos clínicos, socio demográficos, y de tratamiento antirretroviral. Para analizar las posibles interacciones entre medicamentos, se utilizó el software Micromedex(r). El análisis estadístico se realizó mediante regresión logística binaria, considerando estadísticamente significativo un valor de p de ≤0.05. de todos los participantes, el 52,2% fueron expuestos a posibles interacciones entre fármacos. En total, aparecieron 218 interacciones entre fármacos potenciales, de las que el 79,8% se produjo entre los fármacos utilizados para el tratamiento antirretroviral. Se observó una asociación entre el uso de cinco o más medicamentos y posibles

  15. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel.

    Science.gov (United States)

    Günthard, Huldrych F; Saag, Michael S; Benson, Constance A; del Rio, Carlos; Eron, Joseph J; Gallant, Joel E; Hoy, Jennifer F; Mugavero, Michael J; Sax, Paul E; Thompson, Melanie A; Gandhi, Rajesh T; Landovitz, Raphael J; Smith, Davey M; Jacobsen, Donna M; Volberding, Paul A

    2016-07-12

    New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and

  16. Social opdrift - social arv

    DEFF Research Database (Denmark)

    Ejrnæs, Morten; Gabrielsen, G.; Nørrung, Per

    "Social opdrift - social arv" stiller på flere måder spørgsmål ved begrebet social arv. Bogen konkluderer blandt andet, at langt de fleste børn, der opvokser i en socialt belastet familie, bliver velfungerende voksne. Professionelle, der møder socialt belastede familier, har derfor et stort ansvar....... Naturligvis skal der tages hånd om udsatte børn, men det kræver samtidig stor opmærksomhed at sørge for, at fokuseringen på den sociale arv ikke tager overhånd, så det bliver en selvopfyldende profeti."Social opdrift - social" arv viser, hvordan forskningsresultater er blevet fremlagt på en måde, som har...... medvirket til at skabe en skæv opfattelse af, at forældrenes problemer er hovedårsag til børns sociale problemer. I selvstændige analyser vises, hvordan data, der normalt bruges som "bevis" for den sociale arvs betydning, tydeligt illustrerer, at det er en undtagelse, at børn får sociale problemer af samme...

  17. Antiretroviral Drug Interactions: Overview of Interactions Involving New and Investigational Agents and the Role of Therapeutic Drug Monitoring for Management

    Directory of Open Access Journals (Sweden)

    R. Chris Rathbun

    2011-10-01

    Full Text Available Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450 and uridine diphosphate glucuronosyltransferase (UGT enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide. The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed.

  18. Adherence to anti-retroviral drugs in pregnant and lactating HIV ...

    African Journals Online (AJOL)

    Background: Anti-retroviral drugs reduce morbidity and mortality due to HIV and prevent transmission from mother to child. But compliance on anti-retroviral treatment is an essential element for the success of therapeutic goals. Objective: To assess the level of compliance of anti-retroviral treatment in pregnant and lactating ...

  19. HIV status disclosure and ARV adherence among patients attending ...

    African Journals Online (AJOL)

    HIV status disclosure and ARV adherence among patients attending Jomo Kenyatta University comprehensive care clinic. ... Failure to daily intake of Anti Retrovirals (ARV) not only prevents treatment failure but may also lead to viral development of resistance to the drugs. The fact that HIV is mainly sexually transmitted ...

  20. (ARV) treatment training programme

    African Journals Online (AJOL)

    A successful ARV programme requires that all components of a functional management system be put in place for effective and efficient functioning. This would include logistics, human resources, financial planning, and monitoring and evaluation systems, as well as sustainable institutional capacities. The Nigerian national ...

  1. (ARV) treatment training programme

    African Journals Online (AJOL)

    Winnie

    successful ARV programme requires that all components of a functional management system be put in place for ... It examines knowledge and skills gained, ... Oluwole Odutolu is a public health physician and consultant monitoring and evaluation specialist to the World Bank/UNAIDS Global HIV/AIDS Monitoring and.

  2. Thyroid function among HIV/AIDS patients on highly active anti-retroviral therapy.

    Science.gov (United States)

    Thaimuta, Z L; Sekadde-Kigondu, C; Makawiti, D W

    2010-12-01

    To assess the thyroid function among Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) patients on anti-retroviral drugs: stavudine, lamivudine and nevirapine and to establish the prevalence of non-thyroid illness. Laboratory based comparative cross-sectional study. Comprehensive care clinics at KNH and Mbagathi District Hospital. Eighty four HIV-infected patients on treatment with ARVs (ARV +ve) and an ARV naive (ARV naive) group of 26 HIV-infected patients. Thyroid stimulating hormone levels were not altered following treatment whereas the levels of FT4 decreased. The frequency of those with low FT4 were increasing with continued ARV use. The prevalence of non-thyroidal illness state defined by TSH within reference ranges and low FT4 was comparable among the ARV +ve and ARV naive groups (44 and 46% respectively). Progressive use of HAART causes decline in FT4 hormone levels. It is debatable whether interventions for low FT4 is necessary in ARV treatment but a longitudinal study would explain the progressive trend of thyroid hormones and implications with HAART treatment. The prevalence of NTI is comparable to both HAART users and non-users. Low levels of thyroid hormone (FT 4) may be an adaptive response by thyroid gland to minimize calorie utilisation as in chronic diseases.

  3. Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems.

    Science.gov (United States)

    Kumar, Santosh; Rao, P S S; Earla, Ravindra; Kumar, Anil

    2015-03-01

    Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse.

  4. A clinical assessment of antiretroviral-treated patients Referred from ...

    African Journals Online (AJOL)

    HAART) on the immunological, virological and clinical status of two groups of patients in the South African government antiretroviral (ARV) programme in KwaZulu-Natal, viz. patients previously treated with ARVs in the private sector and then ...

  5. Guidelines for antiretroviral therapy in adults

    Directory of Open Access Journals (Sweden)

    G Meintjes

    2012-08-01

    Full Text Available These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in January 2008. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART in Southern Africa has continued to grow. Cohort studies from the region show excellent clinical outcomes; however, ART is still being started late (in advanced disease, resulting in relatively high early mortality rates. New data on antiretroviral (ARV tolerability in the region and several new ARV drugs have become available. Although currently few in number, some patients in the region are failing protease inhibitor (PI-based second-line regimens. To address this, guidelines on third-line (or ‘salvage’ therapy have been expanded.

  6. Heideggers sorte arv

    DEFF Research Database (Denmark)

    Olesen, Søren Gosvig

    2015-01-01

    Martin Heidegger var antisemit, men er hans tænkning og intellektuelle arv det også? Søren Gosvig Olesen opsøger den store tyske tænkers arvinger og bindene fra 1938-48 i Heideggers efterladte ’Sorte hæfter’, hvor den lille mands meninger blander sig med en stor tænkers tanker......Martin Heidegger var antisemit, men er hans tænkning og intellektuelle arv det også? Søren Gosvig Olesen opsøger den store tyske tænkers arvinger og bindene fra 1938-48 i Heideggers efterladte ’Sorte hæfter’, hvor den lille mands meninger blander sig med en stor tænkers tanker...

  7. Possible drug-metabolism interactions of medicinal herbs with antiretroviral agents.

    NARCIS (Netherlands)

    Beukel, C.J.P. van den; Koopmans †, P.P.; Ven, A.J.A.M. van der; Smet, P.A.G.M. de; Burger, D.M.

    2006-01-01

    Herbal medicines are widely used by HIV patients. Several herbal medicines have been shown to interact with antiretroviral drugs, which might lead to drug failure. We have aimed to provide an overview of the modulating effects of Western and African herbal medicines on antiretroviral

  8. Social arv og ulighed

    DEFF Research Database (Denmark)

    Jensen, Bente

    2017-01-01

    Artiklen søger at komme tættere på spørgsmål om hvordan dagtilbud kan gøre en forskel for social udsatte børn ved for det første at indkredse forskning om dagtilbuds betydning set i relation til en social arv- og ulighedsproblematik. For det andet belyses eksempler fra dansk interventionsforskning...

  9. Therapeutic drug monitoring: an aid to optimising response to antiretroviral drugs?

    NARCIS (Netherlands)

    Aarnoutse, R.E.; Schapiro, J.M.; Boucher, C.A.B.; Hekster, Y.A.; Burger, D.M.

    2003-01-01

    Therapeutic drug monitoring (TDM) has been proposed as a means to optimise response to highly active antiretroviral therapy (HAART) in HIV infection. Protease inhibitors (PIs) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine satisfy many criteria for TDM.

  10. MORBILI PADA ANAK DALAM PENGOBATAN ANTI RETRO VIRAL (ARV

    Directory of Open Access Journals (Sweden)

    Surya Dipta Nugraha

    2016-03-01

    Full Text Available MEASLES IN CHILDREN WITH ANTI RETRO VIRAL (ARV ON TREATMENT ABSTRACT Introduction: Morbili is an acute viral infectious disease caused by a virus transmitted morbili. Morbili is a contagious acute viral infectious disease that is characterized by three stages: catarrhal stage, eruption stage and convalence stage. Another name morbili is measles, measles, or rubeola. Morbili caused by a virus that is classified as Family paramyxovirus, the virus genus morbili contained in nasopharyngeal secretions and blood during the prodromal period until 24 hours after the onset of spots. Case: Patient male, 6 years old, Hindu, Balinese tribe, came with complaints of febris since 5 days ago. Febris is not measured with a thermometer. The heat is felt up and down, getting better with medicine. Complaints red spots felt since 1 day ago. Originally discovered red spots appear in the neck area and then to the face and chest. The incidence of rash accompanied by itching and heat. This complaint is accompanied with nosebleeds 1 day ago, cough with sputum since 5 days ago and the red eye from one day ago. Patients feel the first time such complaints. Having a history of antiretroviral use regularly since 1.5 years old. Keywords: rash, morbili, HIV, antiretroviral drugs.

  11. Modifying Antiretroviral Therapy in Virologically Suppressed HIV-1-Infected Patients.

    Science.gov (United States)

    Collins, Sean E; Grant, Philip M; Shafer, Robert W

    2016-01-01

    HIV-1-infected patients with suppressed plasma viral loads often require changes to their antiretroviral (ARV) therapy to manage drug toxicity and intolerance, to improve adherence, and to avoid drug interactions. In patients who have never experienced virologic failure while receiving ARV therapy and who have no evidence of drug resistance, switching to any of the acceptable US Department of Health and Human Services first-line therapies is expected to maintain virologic suppression. However, in virologically suppressed patients with a history of virologic failure or drug resistance, it can be more challenging to change therapy while still maintaining virologic suppression. In these patients, it may be difficult to know whether the discontinuation of one of the ARVs in a suppressive regimen constitutes the removal of a key regimen component that will not be adequately supplanted by one or more substituted ARVs. In this article, we review many of the clinical scenarios requiring ARV therapy modification in patients with stable virologic suppression and outline the strategies for modifying therapy while maintaining long-term virologic suppression.

  12. Rates of inappropriate antiretroviral prescription among injection drug users

    Directory of Open Access Journals (Sweden)

    Bonner Simon

    2007-01-01

    Full Text Available Abstract Background Although the survival benefits of antiretroviral therapy (ART for the treatment of HIV infection are well established, the clinical management of HIV disease continues to present major challenges. There are particular concerns regarding access to appropriate HIV treatment among HIV-infected injection drug users (IDU. Methods In a prospective cohort study of HIV-infected IDU in Vancouver, Canada, we examined initial ART regimens vis-à-vis the provincial government's therapeutic guidelines at the time ART was initiated. Briefly, there have been four sets of guidelines: Era 1 (1992 to November 1995; double-drug (dual NRTIs ART for patients with a CD4 cell count of 350 or less; Era 2 (December 1995 to May 1996; double-drug therapy for patients with a CD4+ cell count of 500 or less; Era 3 (June 1996 to June 1997; triple-drug therapy (dual NRTIs with a PI or NNRTI for patients who had a plasma viral load of > 100,000 HIV-1 RNA copies/mL; dual therapy with two NRTIs for those with a plasma viral load of 5,000 to 100,000 HIV-1 RNA copies/mL; Era 4 (since July 1997; universal use of triple drug therapy as first-line treatment. Results Between May 1996 and May 2003, 431 HIV-infected individuals were enrolled into the cohort. By May 31, 2003, 291 (67.5% individuals had initiated ART. We noted instances of inappropriate antiretroviral prescription in each guideline era, with 9 (53% in Era 1, 3 (12% in Era 2, 22 (28% in Era 3, and 23 (15% in Era 4. Of the 57 subjects who received an inappropriate ART regimen initially, 14 never received the appropriate therapy; among the remaining 43, the median time to the initiation of a guideline-appropriate ART regimen was 12 months (inter-quartile range 5 – 20. Conclusion The present study identified measurable rates of guideline-inappropriate ART prescription for patients who were injection drug users. Rates were highest in the era of dual therapy, although high rates persisted into the triple

  13. opinion maternal and infant health is protected by antiretroviral drug

    African Journals Online (AJOL)

    2012-03-01

    Mar 1, 2012 ... clinicians, health professionals and civil society groups has been enthusiastic support. Moreover, the .... conjunction with research findings demonstrating the efficacy of ARVs to significantly reduce the risk .... to reduce inequities and provide highly effective interventions to everyone and not just a number of.

  14. HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam

    NARCIS (Netherlands)

    Thao, Vu P.; Le, Thuy; Török, Estee M.; Yen, Nguyen T. B.; Chau, Tran T. H.; Jurriaans, Suzanne; van Doorn, Rogier H.; de Jong, Menno D.; Farrar, Jeremy J.; Dunstan, Sarah J.

    2012-01-01

    Background: Access to antiretroviral therapy (ART) for HIV-infected individuals in Vietnam is rapidly expanding, but there are limited data on HIV drug resistance (HIVDR) to guide ART strategies. Methods: We retrospectively conducted HIVDR testing in 220 ART-naive individuals recruited to a

  15. The status of HIV-1 resistance to antiretroviral drugs in sub-Saharan Africa

    NARCIS (Netherlands)

    Hamers, Raph L.; Derdelinckx, Inge; van Vugt, Michèle; Stevens, Wendy; Rinke de Wit, Tobias F.; Schuurman, Rob

    2008-01-01

    Access to highly active antiretroviral therapy (HAART) for persons infected with HIV in sub-Saharan Africa has greatly improved over the past few years. However, data on long-term clinical outcomes of Africans receiving HAART, patterns of HIV resistance to antiretroviral drugs and implications of

  16. Affordable HIV drug-resistance testing for monitoring of antiretroviral therapy in sub-Saharan Africa

    NARCIS (Netherlands)

    Inzaule, Seth C.; Ondoa, Pascale; Peter, Trevor; Mugyenyi, Peter N.; Stevens, Wendy S.; Rinke de Wit, Tobias F.; Hamers, Raph L.

    2016-01-01

    Increased provision of antiretroviral therapy in sub-Saharan Africa has led to a growing number of patients with therapy failure and acquired drug-resistant HIV, driving the demand for more costly further lines of antiretroviral therapy. In conjunction with accelerated access to viral load

  17. Improving access to antiretrovirals in rural South Africa – a call to ...

    African Journals Online (AJOL)

    Improving access to antiretrovirals in rural South Africa – a call to action. South Africa (SA) already has the world's biggest antiretroviral (ARV) programme. With the introduction of extended criteria for initiating ARVs, the National Department of Health (NDoH) wishes to increase the number of people on ARVs by around.

  18. Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya.

    Directory of Open Access Journals (Sweden)

    Harris Onywera

    Full Text Available HIV-1 transmitted drug resistance (TDR is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15-59 years with acute HIV-1 infections (AHI and recent HIV-1 infections (RHI as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5% of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7-17.1. No TDR was observed among persons with AHI (n = 7. TDR prevalence was 4.6% (95% CI 1.8-11.2 for nucleoside reverse transcriptase inhibitors (NRTIs, 6.9% (95% CI 3.2-14.2 for non- nucleoside reverse transcriptase inhibitors (NNRTIs, and 1.2% (95% CI 0.2-6.2 for protease inhibitors. Three (3.4% 95% CI 0.8-10.1 persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6% and M184V (2.3%; only M46I/L (1.1% occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%, C (6.9%, D (21.8%, G (2.3%, and circulating recombinant forms (11.5%. Only low CD4 count was associated with TDR (p = 0.0145. Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines

  19. In-vitro photo-translocation of antiretroviral drug delivery into TZMbl cells

    CSIR Research Space (South Africa)

    Malabi, Rudzani

    2017-01-01

    Full Text Available . Therapeutic targeting of HIV therefore requires further investigation and current therapies need modification in order to address HIV eradication. This deflects research towards investigating potential novel antiretroviral drug delivery systems. The use...

  20. Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda

    Directory of Open Access Journals (Sweden)

    Ahoua Laurence

    2009-06-01

    Full Text Available Abstract Background Little is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice. Methods Cross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/ml and subtherapeutic antiretroviral (ARV concentrations were investigated with multiple logistic regression. Results At 12 and 24 months of ART, 72% (n = 701 and 70% (n = 369 of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (1,000 copies/ml were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations. Conclusion Efforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy.

  1. Quality of Life and Adherence to Antiretroviral Drugs | Mweemba ...

    African Journals Online (AJOL)

    Quality of life is a complex broad ranging multidimensional concept defined in terms of individual's subjective experiences. The definition by the ... Antiretroviral regimens are demanding and difficult, with numerous possible side effects and patients need to take the pills for indefinite periods of time. Efficacy of antiretroviral ...

  2. Global patient safety and antiretroviral drug-drug interactions in the resource-limited setting.

    Science.gov (United States)

    Seden, Kay; Khoo, Saye H; Back, David; Byakika-Kibwika, Pauline; Lamorde, Mohammed; Ryan, Mairin; Merry, Concepta

    2013-01-01

    Scale-up of HIV treatment services may have contributed to an increase in functional health facilities available in resource-limited settings and an increase in patient use of facilities and retention in care. As more patients are reached with medicines, monitoring patient safety is increasingly important. Limited data from resource-limited settings suggest that medication error and antiretroviral drug-drug interactions may pose a significant risk to patient safety. Commonly cited causes of medication error in the developed world include the speed and complexity of the medication use cycle combined with inadequate systems and processes. In resource-limited settings, specific factors may contribute, such as inadequate human resources and high disease burden. Management of drug-drug interactions may be complicated by limited access to alternative medicines or laboratory monitoring. Improving patient safety by addressing the issue of antiretroviral drug-drug interactions has the potential not just to improve healthcare for individuals, but also to strengthen health systems and improve vital communication among healthcare providers and with regulatory agencies.

  3. Pregnancy-related changes of antiretroviral pharmacokinetics: an argument for therapeutic drug monitoring.

    Science.gov (United States)

    Simonetti, Francesco R; Cattaneo, Dario; Zanchetta, Nadia; Giacomet, Vania; Micheli, Valeria; Ciminera, Nadia; Gervasoni, Cristina

    2017-01-01

    Here we describe a case of an HIV-infected young woman with extensive drug-resistant virus, who was successfully switched from a raltegravir-based regimen to a dolutegravir-based intensified antiretroviral regimen a few days before scheduled caesarean section because of the still detectable viral load. The trough concentrations of all antiretroviral drugs before and after delivery are also described. Our case underlines both the difficult management of young women, HIV-infected at young age with very limited treatment options and the great variability in the pregnancy-related physiological changes affecting the pharmacokinetics of antiretrovirals.

  4. Modeling HIV/AIDS Drug Price Determinants in Brazil: Is Generic Competition a Myth?

    OpenAIRE

    Meiners, Constance; Sagaon-Teyssier, Luis; Hasenclever, Lia; Moatti, Jean-Paul

    2011-01-01

    BACKGROUND: Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs) being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of internat...

  5. Antiretroviral purchasing and prescription practices in Mexico: constraints, challenges and opportunities.

    Science.gov (United States)

    Chaumont, Claire; Bautista-Arredondo, Sergio; Calva, Juan José; Bahena-González, Roberto Isaac; Sánchez-Juárez, Gerda Hitz; González de Araujo-Muriel, Arturo; Magis-Rodríguez, Carlos; Hernández-Ávila, Mauricio

    2015-01-01

    This study examines the antiretroviral (ARV) market characteristics for drugs procured and prescribed to Mexico's Social Protection System in Health beneficiaries between 2008 and 2013, and compares them with international data. Procurement information from the National Center for the Prevention and the Control of HIV/AIDS was analyzed to estimate volumes and prices of key ARV. Annual costs were compared with data from the World Health Organization's Global Price Reporting Mechanism for similar countries. Finally, regimens reported in the ARV Drug Management, Logistics and Surveillance System database were reviewed to identify prescription trends and model ARV expenditures until 2018. Results show that the first-line ARV market is concentrated among a small number of patented treatments, in which prescription is clinically adequate, but which prices are higher than those paid by similar countries. The current set of legal and structural options available to policy makers to bring prices down is extremely limited. Different negotiation policies were not successful to decrease ARV high prices in the public health market. The closed list approach had a good impact on prescription quality but was ineffective in reducing prices. The Coordinating Commission for Negotiating the Price of Medicines and other Health Supplies also failed to obtain adequate prices. To maximize purchase efficiency, policy makers should focus on finding long-term legal and political safeguards to counter the high prices imposed by pharmaceutical companies.

  6. LC-MS/MS determination of antiretroviral drugs in influents and effluents from wastewater treatment plants in KwaZulu-Natal, South Africa.

    Science.gov (United States)

    Abafe, Ovokeroye A; Späth, Jana; Fick, Jerker; Jansson, Stina; Buckley, Chris; Stark, Annegret; Pietruschka, Bjoern; Martincigh, Bice S

    2018-06-01

    South Africa has the largest occurrence of the human immune deficiency virus (HIV) in the world but has also implemented the largest antiretroviral (ARV) treatment programme. It was therefore of interest to determine the presence and concentrations of commonly used antiretroviral drugs (ARVDs) and, also, to determine the capabilities of wastewater treatment plants (WWTPs) for removing ARVDs. To this end, a surrogate standard based LC-MS/MS method was optimized and applied for the detection of thirteen ARVDs used in the treatment and management of HIV/acquired immune deficiency syndrome (HIV/AIDS) in two major and one modular WWTP in the eThekwini Municipality in KwaZulu-Natal, South Africa. The method was validated and the detection limits fell within the range of 2-20 ng L -1 . The analytical recoveries for the ARVDs were mainly greater than 50% with acceptable relative standard deviations. The concentration values ranged from effluent) in a decentralized wastewater treatment facility (DEWATS); effluent) in Northern WWTP and 61-34000 ng L -1 (influent), effluent) in Phoenix WWTP. Whilst abacavir, lamivudine and zidovudine were almost completely removed from the effluents, atazanavir, efavirenz, lopinavir and nevirapine persisted in the effluents from all three WWTPs. To estimate the ecotoxicological risks associated with the discharge of ARVDs, a countrywide survey focussing on the occurrence of ARVDs in WWTPs, surface and fresh water bodies, and aquatic organisms, is necessary. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Antiretroviral Drug Resistance- implications for HIV/AIDS reduction ...

    African Journals Online (AJOL)

    Saharan Africa and other developing countries. ... Abstract: Background: The introduction of the highly active antiretroviral therapy in the mid-1990s has significantly reduced morbidities and prolonged the lifespan of people living with HIV. However ...

  8. Antiretroviral Resistance and Pregnancy Characteristics of Women with Perinatal and Nonperinatal HIV Infection

    Directory of Open Access Journals (Sweden)

    Gweneth B. Lazenby

    2016-01-01

    Full Text Available Objective. To compare HIV drug resistance in pregnant women with perinatal HIV (PHIV and those with nonperinatal HIV (NPHIV infection. Methods. We conducted a multisite cohort study of PHIV and NPHIV women from 2000 to 2014. Sample size was calculated to identify a fourfold increase in antiretroviral (ARV drug resistance in PHIV women. Continuous variables were compared using Student’s t-test and Wilcoxon rank-sum tests. Categorical variables were compared using χ2 and Fisher’s exact tests. Univariate analysis was used to determine factors associated with antiretroviral drug resistance. Results. Forty-one PHIV and 41 NPHIV participants were included. Women with PHIV were more likely to have drug resistance than those with NPHIV ((55% versus 17%, p=0.03, OR 6.0 (95% CI 1.0–34.8, p=0.05, including multiclass resistance (15% versus 0, p=0.03, and they were more likely to receive nonstandard ARVs during pregnancy (27% versus 5%, p=0.01. PHIV and NPHIV women had similar rates of preterm birth (11% versus 28%, p=0.08 and cesarean delivery (47% versus 46%, p=0.9. Two infants born to a single NPHIV woman acquired HIV infection. Conclusions. PHIV women have a high frequency of HIV drug resistance mutations, leading to nonstandard ARVs use during pregnancy. Despite nonstandard ARV use during pregnancy, PHIV women did not experience increased rates of adverse pregnancy outcomes.

  9. Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

    Science.gov (United States)

    Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

    2017-06-28

    Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

  10. Pharmacogenetic & pharmacokinetic biomarker for efavirenz based ARV and rifampicin based anti-TB drug induced liver injury in TB-HIV infected patients.

    Directory of Open Access Journals (Sweden)

    Getnet Yimer

    Full Text Available BACKGROUND: Implication of pharmacogenetic variations and efavirenz pharmacokinetics in concomitant efavirenz based antiviral therapy and anti-tubercular drug induced liver injury (DILI has not been yet studied. We performed a prospective case-control association study to identify the incidence, pharmacogenetic, pharmacokinetic and biochemical predictors for anti-tubercular and antiretroviral drugs induced liver injury (DILI in HIV and tuberculosis (TB co-infected patients. METHODS AND FINDINGS: Newly diagnosed treatment naïve TB-HIV co-infected patients (n = 353 were enrolled to receive efavirenz based ART and rifampicin based anti-TB therapy, and assessed clinically and biochemically for DILI up to 56 weeks. Quantification of plasma efavirenz and 8-hydroxyefaviernz levels and genotyping for NAT2, CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 genes were done. The incidence of DILI and identification of predictors was evaluated using survival analysis and the Cox Proportional Hazards Model. The incidence of DILI was 30.0%, or 14.5 per 1000 person-week, and that of severe was 18.4%, or 7.49 per 1000 person-week. A statistically significant association of DILI with being of the female sex (p = 0.001, higher plasma efavirenz level (p = 0.009, efavirenz/8-hydroxyefavirenz ratio (p = 0.036, baseline AST (p = 0.022, ALT (p = 0.014, lower hemoglobin (p = 0.008, and serum albumin (p = 0.007, NAT2 slow-acetylator genotype (p = 0.039 and ABCB1 3435TT genotype (p = 0.001. CONCLUSION: We report high incidence of anti-tubercular and antiretroviral DILI in Ethiopian patients. Between patient variability in systemic efavirenz exposure and pharmacogenetic variations in NAT2, CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co-infected patients. Close monitoring of plasma efavirenz level and liver enzymes during early therapy and/or genotyping practice in HIV clinics is recommended for early identification

  11. Mobile phone use for a social strategy to improve antiretroviral refill experience at a low-resource HIV clinic: patient responses from Nigeria.

    Science.gov (United States)

    Adetunji, Adedotun A; Muyibi, Sufiyan A; Imhansoloeva, Martins; Ibraheem, Olusola M; Sunmola, Adegbenga; Kolawole, Olubunmi O; Akinrinsola, Oluwasina O; Ojo-Osagie, James O; Mosuro, Olusola A; Abiolu, Josephine O; Irabor, Achiaka E; Okonkwo, Prosper; Adewole, Isaac F; Taiwo, Babafemi O

    2017-05-01

    In sub-Saharan African areas where antiretroviral (ARV) drugs are not available through community pharmacies, clinic-based pharmacies are often the primary source of ARV drug refills. Social pressure is mounting on treatment providers to adjust ARV refill services towards user-friendly approaches which prioritize patients' convenience and engage their resourcefulness. By this demand, patients may be signalling dissatisfaction with the current provider-led model of monthly visits to facility-based pharmacies for ARV refill. Mobile phones are increasingly popular in sub-Saharan Africa, and have been used to support ARV treatment goals in this setting. A patient-centred response to on-going social pressure requires treatment providers to view ARV refill activities through the eyes of patients who are negotiating the challenges of day-to-day life while contemplating their next refill appointment. Using focus groups of five categories of adult patients receiving combination ARV therapy, we conducted this cross-sectional qualitative study to provide insight into modifiable gaps between patients' expectations and experiences of the use of mobile phones in facility-based ARV refill service at a public HIV clinic in Nigeria. A notable finding was patients' preference for harnessing informal social support (through intermediaries with mobile phones) to maintain adherence to ARV refill appointments when they could not present in person. This evolving social support strategy also has the potential to enhance defaulter tracking. Our study findings may inform the development of ARV refill strategies and the design of future qualitative studies on client-provider communication by mobile phones in under-resourced HIV treatment programmes.

  12. Evolving Human Rights and the Science of Antiretroviral Medicine

    OpenAIRE

    Kavanagh, Matthew; Cohn, Jennifer; Mabote, Lynette; Meier, Benjamin Mason; Williams, Brian; Russell, Asia; Sikwese, Kenly; Baker, Brook

    2015-01-01

    Recent years have seen significant advances in the science of using antiretroviral medicines (ARVs) to fight HIV. Where not long ago ARVs were used late in disease to prevent sick people from dying, today people living with HIV can use ARVs to achieve viral suppression early in the course of disease. This article reviews the mounting new scientific evidence of major clinical and prevention ARV benefits. This has changed the logic of the AIDS response, eliminating competition between "treatmen...

  13. Fate of the antiretroviral drug tenofovir in agricultural soil

    Energy Technology Data Exchange (ETDEWEB)

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne; Chapman, Ralph; Lapen, David R.; Topp, Edward, E-mail: ed.topp@agr.gc.ca [Agriculture and Agri-Food Canada, London, ON, N5V 4T3 (Canada)

    2010-10-15

    Tenofovir (9-(R)-(2-phosphonylmethoxypropyl)-adenine) is an antiretroviral drug widely used for the treatment of human immunodeficiency virus (HIV-1) and Hepatitis B virus (HBV) infections. Tenofovir is extensively and rapidly excreted unchanged in the urine. In the expectation that tenofovir could potentially reach agricultural lands through the application of municipal biosolids or wastewater, and in the absence of any environmental fate data, we evaluated its persistence in selected agricultural soils. Less than 10% of [adenine-8-{sup 14}C]-tenofovir added to soils varying widely in texture (sand, loam, clay loam) was mineralized in a 2-month incubation under laboratory conditions. Tenofovir was less readily extractable from clay soils than from a loam or a sandy loam soil. Radioactive residues of tenofovir were removed from the soil extractable fraction with DT{sub 50}s ranging from 24 {+-} 2 to 67 + 22 days (first order kinetic model) or 44 + 9 to 127 + 55 days (zero order model). No extractable transformation products were detectable by HPLC. Tenofovir mineralization in the loam soil increased with temperature (range 4 {sup o}C to 30 {sup o}C), and did not occur in autoclaved soil, suggesting a microbial basis. Mineralization rates increased with soil moisture content, ranging from air-dried to saturated. In summary, tenofovir was relatively persistent in soils, there were no extractable transformation products detected, and the response of [adenine-8-{sup 14}C]-tenofovir mineralization to soil temperature and heat sterilization indicated that the molecule was biodegraded by aerobic microorganisms. Sorption isotherms with dewatered biosolids suggested that tenofovir residues could potentially partition into the particulate fraction during sewage treatment.

  14. Barriers and facilitating factors to the uptake of antiretroviral drugs for prevention of mother-to-child transmission of HIV in sub-Saharan Africa: a systematic review

    Science.gov (United States)

    Gourlay, Annabelle; Birdthistle, Isolde; Mburu, Gitau; Iorpenda, Kate; Wringe, Alison

    2013-01-01

    Objectives To investigate and synthesize reasons for low access, initiation and adherence to antiretroviral drugs by mothers and exposed babies for prevention of mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa. Methods A systematic literature review was conducted. Four databases were searched (Medline, Embase, Global Health and Web of Science) for studies conducted in sub-Saharan Africa from January 2000 to September 2012. Quantitative and qualitative studies were included that met pre-defined criteria. Antiretroviral (ARV) prophylaxis (maternal/infant) and combination antiretroviral therapy (ART) usage/registration at HIV care and treatment during pregnancy were included as outcomes. Results Of 574 references identified, 40 met the inclusion criteria. Four references were added after searching reference lists of included articles. Twenty studies were quantitative, 16 were qualitative and eight were mixed methods. Forty-one studies were conducted in Southern and East Africa, two in West Africa, none in Central Africa and one was multi-regional. The majority (n=25) were conducted before combination ART for PMTCT was emphasized in 2006. At the individual-level, poor knowledge of HIV/ART/vertical transmission, lower maternal educational level and psychological issues following HIV diagnosis were the key barriers identified. Stigma and fear of status disclosure to partners, family or community members (community-level factors) were the most frequently cited barriers overall and across time. The extent of partner/community support was another major factor impeding or facilitating the uptake of PMTCT ARVs, while cultural traditions including preferences for traditional healers and birth attendants were also common. Key health-systems issues included poor staff-client interactions, staff shortages, service accessibility and non-facility deliveries. Conclusions Long-standing health-systems issues (such as staffing and service accessibility) and community

  15. Correlation of Adherence by Pill Count, Self-report, MEMS and Plasma Drug Levels to Treatment Response Among Women Receiving ARV Therapy for PMTCT in Kenya.

    Science.gov (United States)

    Mudhune, Victor; Gvetadze, Roman; Girde, Sonali; Ndivo, Richard; Angira, Frank; Zeh, Clement; Thomas, Timothy; Lecher, Shirley Lee

    2018-03-01

    Success of antiretroviral therapy depends on adherence to effective treatment. We evaluated four adherence methods and their correlation with immunological and virologic response among women receiving PMTCT. Univariable and multivariable analyses were used to assess how adherence by pill count (n = 463), self-report (n = 463), MEMS (n = 129) and plasma drug level (n = 89) was associated with viral load suppression within a 6 months period. Longitudinal analysis was performed to determine the correlation of CD4 cell count with each measure of adherence. For all measures of adherence, sustained viral suppression was less likely for participants in the lowest category of adherence. Although CD4 cell count increased substantially over time, there was no significant association with adherence by the methods. Multiple strategies can be used successfully to monitor treatment adherence. Persons with ≥95% adherence by any method used in this study were more likely to have a favorable treatment outcome.

  16. Primary antiretroviral drug resistance among HIV type 1-infected individuals in Brazil.

    Science.gov (United States)

    Sprinz, Eduardo; Netto, Eduardo M; Patelli, Maria; Lima, J S; Lima, Maria Patelli J S; Furtado, Juvênao J D; da Eira, Margareth; Zajdenverg, Roberto; Madruga, José V; Lewi, David S; Machado, Alcyone A; Pedro, Rogério J; Soares, Marcelo A

    2009-09-01

    Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) has been documented in all countries that have surveyed for it and may result in an unfavorable response to therapy. The prevalence and characteristics of individuals with transmitted resistance to antiretroviral drugs have been scarcely described in Brazil. We performed antiretroviral resistance testing prior to initiation of therapy in 400 subjects enrolled from 20 centers in 13 Brazilian cities between March and September 2007. Genotyping was conducted using PCR-amplified HIV pol products by automated sequencing, and genotype interpretation was done according to the IAS-USA consensus. Of 400 eligible participants, 387 (95.8%) were successfully tested. Seven percent of antiretroviral-naive patients carried viruses with one or more major mutation associated with drug resistance. The prevalence of these mutations was 1.0% for protease inhibitors, 4.4% for nonnucleoside reverse transcriptase inhibitors, and 1.3% for nucleoside reverse transcriptase inhibitors. The frequency of multidrug resistance among the resistant strains was 13.6%. Among subjects infected with drug-resistant virus, the majority were infected with subtype B viruses (91%). Subjects from the city of São Paulo had higher transmitted resistance mutations compared to the rest of the country. Reporting a partner taking antiretroviral medications was associated with a higher chance of harboring HIV variants with major drug resistance mutations [odds ratio = 2.57 (95% confidence interval, 1.07-6.16); p = 0.014]. Resistance testing in drug-naive individuals identified 7% of subjects with mutations associated with reduced susceptibility to antiretroviral drugs. Continued surveillance of drug-resistant HIV-1 in Brazil is warranted when guidelines for HIV prophylaxis and treatment are updated. Resistance testing among drug-naive patients prior to treatment initiation should be considered, mainly directed at subjects whose partners are

  17. Activity of antiretroviral drugs in human infections by opportunistic agents

    Directory of Open Access Journals (Sweden)

    Izabel Galhardo Demarchi

    2012-03-01

    Full Text Available Highly active antiretroviral therapy (HAART is used in patients infected with HIV. This treatment has been shown to significantly decrease opportunist infections such as those caused by viruses, fungi and particularly, protozoa. The use of HAART in HIV-positive persons is associated with immune reconstitution as well as decreased prevalence of oral candidiasis and candidal carriage. Antiretroviral therapy benefits patients who are co-infected by the human immunodeficiency virus (HIV, human herpes virus 8 (HHV-8, Epstein-Barr virus, hepatitis B virus (HBV, parvovirus B19 and cytomegalovirus (CMV. HAART has also led to a significant reduction in the incidence, and the modification of characteristics, of bacteremia by etiological agents such as Staphylococcus aureus, coagulase negative staphylococcus, non-typhoid species of Salmonella, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. HAART can modify the natural history of cryptosporidiosis and microsporidiosis, and restore mucosal immunity, leading to the eradication of Cryptosporidium parvum. A similar restoration of immune response occurs in infections by Toxoplasma gondii. The decline in the incidence of visceral leishmaniasis/HIV co-infection can be observed after the introduction of protease inhibitor therapy. Current findings are highly relevant for clinical medicine and may serve to reduce the number of prescribed drugs thereby improving the quality of life of patients with opportunistic diseases.A terapia HAART (terapia antirretroviral altamente ativa é usada em pacientes infectados pelo vírus da imunodeficiência humana (HIV e demonstrou diminuição significativa de infecções oportunistas, tais como as causadas por vírus, fungos, protozoários e bactérias. O uso da HAART está associado com a reconstituição imunológica e diminuição na prevalência de candidíase oral. A terapia antirretroviral beneficia pacientes co-infectados pelo HIV, v

  18. Reasons for Change of Anti-Retroviral Therapy (ART) Drugs: Local ...

    African Journals Online (AJOL)

    Background: Highly active anti-retroviral therapy (HAART) reduces morbidity and mortality in HIV/AIDS infected patients. HAART is used indefinitely and the regimens are changed over the course of treatment due to resistance, adverse drug reactions or access to drugs. Few studies have been done in resource constrained ...

  19. Adherence to antiretroviral drugs in North-Central zone of Nigeria ...

    African Journals Online (AJOL)

    A cross-sectional study of 110 patients attending State House Clinic, Abuja were assessed for compliance in time and dose of anti-retroviral drugs for one month. One hundred and five of the patients complied to taking the drugs (taking complience >95%) and compliance to the dosage was also good (98.1%). However, the ...

  20. Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients.

    Science.gov (United States)

    Baril, Jean-Guy; Angel, Jonathan B; Gill, M John; Gathe, Joseph; Cahn, Pedro; van Wyk, Jean; Walmsley, Sharon

    2016-01-01

    We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the

  1. Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging

    Science.gov (United States)

    Andreu-Crespo, Àngels; Llibre, Josep M; Cardona-Peitx, Glòria; Sala-Piñol, Ferran; Clotet, Bonaventura; Bonafont-Pujol, Xavier

    2015-01-01

    While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) – with a cost of 47,139.91€ – would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets. PMID:26273190

  2. Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging.

    Science.gov (United States)

    Andreu-Crespo, Àngels; Llibre, Josep M; Cardona-Peitx, Glòria; Sala-Piñol, Ferran; Clotet, Bonaventura; Bonafont-Pujol, Xavier

    2015-01-01

    While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) - with a cost of 47,139.91 € - would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets.

  3. Determinants of non-adherence to subsidized anti-retroviral treatment in southeast Nigeria.

    Science.gov (United States)

    Uzochukwu, B S C; Onwujekwe, O E; Onoka, A C; Okoli, C; Uguru, N P; Chukwuogo, O I

    2009-05-01

    The anti-retroviral (ARV) treatment programme in Nigeria is delivered through selected teaching and mission hospitals at a free/subsidized rate. The government aims to scale up ARV treatment in the country. However, non-adherence to ARV medication can lead to viral resistance, treatment failure, toxicities and waste of financial resources. This study examined the factors responsible for non-adherence to free/subsidized ARV treatment in south-east Nigeria. The study was cross-sectional and descriptive. Information was collected from 174 patients selected by simple random sampling from the register of all patients who had been on anti-retroviral therapy (ART) for at least 12 months at the beginning of the study period. Patients were identified during their clinic visits. Information on their socio-demographic profile, ARV treatment and determinants of non-adherence to ARV treatment was obtained from those who gave consent, using pre-tested interviewer-administered questionnaires. All patients clearly understood the need to take ARV drugs throughout their lives, and what the costs entailed. They understood the need for periodic testing, the probability that complications would develop, cost of transportation to treatment site and the daily treatment regimen. Seventy-five per cent of respondents were not adhering fully to their drug regimen; the mean number of days that respondents had been off drugs was 3.57 days the preceding month. Reasons for non-adherence included: physical discomfort (side effects); non-availability of drugs at treatment site; forgetting to carry drugs during the day; fear of social rejection; treatment being a reminder of HIV status; and selling of own drugs to those unable to enrol in the projects. Being female, under 35 years, single, and having higher educational status were significantly associated with non-adherence. It is important that policy makers and programme managers address the factors responsible for non-adherence when scaling up

  4. HIV antiretroviral medication stock-outs in Ghana: contributors and consequences.

    Science.gov (United States)

    Poku, Rebecca A; Owusu, Adobea Yaa; Mullen, Patricia Dolan; Markham, Christine; McCurdy, Sheryl A

    2017-09-01

    Drug stock-outs are an unfortunate yet common reality for patients living in low and middle income countries, particularly in sub-Saharan Africa where trouble with consistent stock of antiretroviral medications (ARVs) continues. Our study takes a snapshot of this problem in Ghana. Although the country launched its antiretroviral therapy (ART) programme in 2003, progress toward realising the full benefit of ART for treated individuals has been limited, in part, because of stock-outs. In Ghana's Greater Accra region, we conducted semi-structured interviews with 40 women living with HIV (WLHIV) and 15 individuals with a history of HIV-related work in government or non-governmental organisations, or healthcare facilities. We used repeated review with coding and mapping techniques to analyse the transcripts and identify common themes. Stock-outs of ARVs result in inconsistent administration of therapy, increased indirect medical costs for WLHIV, and negative labelling of patients. Inefficiencies in drug supply, poor coordination with port authorities, inadequate government funding and dependence on international aid contribute to the stock-outs experienced in Ghana. Although using ARVs produced in-country could reduce supply problems, the domestically-manufactured product currently does not meet World Health Organization (WHO) standards. We recommend focused efforts to produce WHO standard ARVs in Ghana, and a review of current supply chain management to identify and mend pitfalls in the system.

  5. An analysis of volumes, prices and pricing trends of the pediatric antiretroviral market in developing countries from 2004 to 2012.

    Science.gov (United States)

    Lee, Janice Soo Fern; Sagaon Teyssier, Luis; Dongmo Nguimfack, Boniface; Collins, Intira Jeannie; Lallemant, Marc; Perriens, Joseph; Moatti, Jean-Paul

    2016-03-15

    The pediatric antiretroviral (ARV) market is poorly described in the literature, resulting in gaps in understanding treatment access. We analyzed the pediatric ARV market from 2004 to 2012 and assessed pricing trends and associated factors. Data on donor funded procurements of pediatric ARV formulations reported to the Global Price Reporting Mechanism database from 2004 to 2012 were analyzed. Outcomes of interest were the volume and mean price per patient-year ARV formulation based on WHO ARV dosing recommendations for a 10 kg child. Factors associated with the price of formulations were assessed using linear regression; potential predictors included: country income classification, geographical region, market segment (originator versus generic ARVs), and number of manufacturers per formulation. All analyses were adjusted for type of formulations (single, dual or triple fixed-dose combinations (FDCs)) Data from 111 countries from 2004 to 2012 were included, with procurement of 33 formulations at a total value of USD 204 million. Use of dual and triple FDC formulations increased substantially over time, but with limited changes in price. Upon multivariate analysis, prices of originator formulations were found to be on average 72 % higher than generics (p market as represented by the GPRM database is small, and lacks price competition. It is dominated by generic drugs due to the lower prices offered and the practicality of FDC formulations. This market requires continued donor support and the current initiatives to protect it are important to ensure market viability, especially if new formulations are to be introduced in the future.

  6. Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging

    Directory of Open Access Journals (Sweden)

    Andreu-Crespo À

    2015-08-01

    Full Text Available Àngels Andreu-Crespo,1,* Josep M Llibre,2,3,* Glòria Cardona-Peitx,1 Ferran Sala-Piñol,1 Bonaventura Clotet,2,4 Xavier Bonafont-Pujol1 1Pharmacy Department, 2HIV Unit and “Lluita contra la SIDA” Foundation, University Hospital Germans Trias i Pujol, Badalona, 3Universitat Autònoma de Barcelona, 4Universitat de Vic-Universitat Central de Catalunya (UVIC-UCC, Vic, Barcelona, Spain *These authors contributed equally to the work Abstract: While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals – with a cost of 47,139.91€ – would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar, should minimize the treatment expenditures paid by national health budgets. Keywords: antiretroviral treatment, cost efficacy, drug packaging, treatment change

  7. Estimating prevalence of accumulated HIV-1 drug resistance in a cohort of patients on antiretroviral therapy

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Cozzi-Lepri, Alessandro; Kjær, Jesper

    2011-01-01

    Estimating the prevalence of accumulated HIV drug resistance in patients receiving antiretroviral therapy (ART) is difficult due to lack of resistance testing at all occasions of virological failure and in patients with undetectable viral load. A method to estimate this for 6498 EuroSIDA patients...

  8. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Kirk, Ole; Reiss, Peter

    2010-01-01

    OBJECTIVES:: Chronic kidney disease (CKD) in HIV-positive persons might be caused by both HIV and traditional or non-HIV-related factors. Our objective was to investigate long-term exposure to specific antiretroviral drugs and CKD. DESIGN:: A cohort study including 6843 HIV-positive persons...

  9. Mass Spectrometry to Determine Intracellular Concentrations of Antiretroviral Drugs: From chemistry to clinical application

    NARCIS (Netherlands)

    J.J.A. van Kampen (Jeroen)

    2009-01-01

    textabstractAround 1995 – 1996, treatment options for patients infected with the human immunodefiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS) 1, 2, improved dramatically. Therapy with a combination of several classes of antiretroviral drugs resulted in a

  10. Comparison of adherence to generic multi-tablet regimens vs. brand multi-tablet and brand single-tablet regimens likely to incorporate generic antiretroviral drugs by breaking or not fixed-dose combinations in HIV-infected patients.

    Science.gov (United States)

    Rwagitinywa, Joseph; Lapeyre-Mestre, Maryse; Bourrel, Robert; Montastruc, Jean-Louis; Sommet, Agnès

    2018-03-05

    Adherence to antiretroviral (ARV) is crucial to achieve viral load suppression in HIV-infected patients. This study aimed to compare adherence to generic multi-tablet regimens (MTR) vs. brand MTR likely to incorporate ARV drugs without breaking fixed-dose combinations (FDC) and brand single-tablet regimens (STR) likely to incorporate generics by breaking the FDC. Patients aged of 18 years or over exposed to one of the generic or the brand of lamivudine (3TC), zidovudine/lamivudine (AZT/TC), nevirapine (NVP), or efavirenz (EFV), or the brand STR of efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF). Adherence was measured by medication possession ratio (MPR) using both defined daily dose (DDD) and daily number of tablet recommended for adults (DNT). Adherence to generic MTR vs. brand MTR and brand STR was compared using Kruskal-Wallis. The overall median adherence was 0.97 (IQR 0.13) by DNT method and 0.97 (0.14) by DDD method. Adherence in patients exposed to generic MTR (n = 165) vs. brand MTR (n = 481) and brand STR (n = 470) was comparable by DNT and DDD methods. In conclusion, adherence to generic MTR was high and comparable with adherence to brand MTR and to STR. Utilization of DDD instead DNT to measure the MPR led to small but nonsignificant difference that has no clinical impact. © 2018 Société Française de Pharmacologie et de Thérapeutique.

  11. [Non-antiretroviral drugs uses among HIV-infected persons receiving antiretroviral therapy in Senegal: Costs and factors associated with prescription].

    Science.gov (United States)

    Diouf, A; Youbong, T J; Maynart, M; Ndoye, M; Diéye, F L; Ndiaye, N A; Koita-Fall, M B; Ndiaye, B; Seydi, M

    2017-08-01

    In addition to antiretroviral therapy, non-antiretroviral drugs are necessary for the appropriate care of people living with HIV. The costs of such drugs are totally or partially supported by the people living with HIV. We aimed to evaluate the overall costs, the costs supported by the people living with HIV and factors associated with the prescription of non-antiretroviral drugs in people living with HIV on antiretroviral therapy in Senegal. We conducted a retrospective cohort study on 331 people living with HIV who initiated antiretroviral therapy between 2009 and 2011 and followed until March 2012. The costs of non-antiretroviral drugs were those of the national pharmacy for essential drugs; otherwise they were the lowest costs in the private pharmacies. Associated factors were identified through a logistic regression model. The study population was 61 % female. At baseline, 39 % of patients were classified at WHO clinical stage 3 and 40 % at WHO clinical stage 4. Median age, body mass index and CD4 cells count were 41 years, 18kg/m 2  and 93 cells/μL, respectively. After a mean duration of 11.4 months of antiretroviral therapy, 85 % of patients received at least one prescription for a non-antiretroviral drug. Over the entire study period, the most frequently prescribed non-antiretroviral drugs were cotrimoxazole (78.9 % of patients), iron (33.2 %), vitamins (21.1 %) and antibiotics (19.6 %). The mean cost per patient was 34 Euros and the mean cost supported per patient was 14 Euros. The most expensive drugs per treated patient were antihypertensives (168 Euros), anti-ulcer agents (12 Euros), vitamins (8.5 Euros) and antihistamines (7 Euros). The prescription for a non-antiretroviral drug was associated with advanced clinical stage (WHO clinical stage 3/4 versus stage 1/2): OR=2.25; 95 % CI=1.11-4.57 and viral type (HIV-2 versus HIV-1/HIV-1+HIV-2): OR=0.36; 95 % CI=0.14-0.89. Non-antiretroviral drugs are frequently prescribed to

  12. knowledge and attitudes towards the use of arvs among adults

    African Journals Online (AJOL)

    To assess knowledge and attitudes towards the use of ARV drugs among adults in Dodoma urban district. Study design ... (75.6%) reported to be getting information through the media such as television, radio and magazine. About 84.9% of males and ... social empowerment and implementation of a programme on ARV ...

  13. Modeling HIV/AIDS drug price determinants in Brazil: is generic competition a myth?

    Science.gov (United States)

    Meiners, Constance; Sagaon-Teyssier, Luis; Hasenclever, Lia; Moatti, Jean-Paul

    2011-01-01

    Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs) being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care. Our analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition. In order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies.

  14. Modeling HIV/AIDS drug price determinants in Brazil: is generic competition a myth?

    Directory of Open Access Journals (Sweden)

    Constance Meiners

    Full Text Available BACKGROUND: Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care. METHODS AND FINDINGS: Our analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition. SIGNIFICANCE: In order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies.

  15. Suministro de antirretrovirales en Argentina: Programa Nacional de Lucha contra los Retrovirus del Humano, SIDA y ETS Antiretroviral drug supply in Argentina: National Program to Combat Human Retroviruses, AIDS, and STDs

    Directory of Open Access Journals (Sweden)

    Marisel Colautti

    2009-01-01

    Full Text Available OBJETIVOS: Evaluar el circuito de suministro de antirretrovirales (ARV dentro del Programa Nacional de Lucha contra los Retrovirus del Humano, SIDA y ETS, mediante indicadores de desempeño, y recuperar la perspectiva de actores involucrados en el circuito de provisión. Se busca mejorar las acciones programáticas satisfaciendo las necesidades de los pacientes. MÉTODOS: En el servicio de farmacia de dos hospitales de Rosario, Argentina, de abril a septiembre de 2005 se llevó a cabo una investigación evaluativa con un abordaje cuantitativo, mediante indicadores y basado en fuentes secundarias, y otro cualitativo, con entrevistas semiestructuradas. RESULTADOS: Los indicadores revelan el impacto de las interrupciones en la provisión de ARV desde el Programa (nivel central y la acumulación de stock en el nivel local para paliar esas faltas. Los cambios de tratamiento con ARV representan más de 50% de las prescripciones. El cumplimiento en el retiro de ARV se aleja del valor de referencia. Los entrevistados describieron estrategias alternativas para superar dificultades de comunicación entre niveles, acumular stock, garantizar disponibilidad y acortar tiempos de espera; se establecieron acuerdos informales ante la falta de normativas y la escasez de recursos humanos; las instancias jurisdiccionales (central, intermedia y local o municipal suman dificultades, y se reconocen esfuerzos del nivel local para mejorar la gestión. CONCLUSIONES: Estos hallazgos pueden ser el punto de partida para la construcción de propuestas que involucren equipos de trabajo afectados en el circuito de provisión en su totalidad, a fin de lograr una descentralización efectiva, en congruencia con el papel rector que le corresponde necesariamente al Programa.OBJECTIVES: To evaluate the supply cycle of antiretroviral (ARV drugs, overseen by the National Program to Combat Human Retroviruses, AIDS, and STDs, through its order fulfillment indicators, and to obtain input

  16. Use of non-antiretroviral drugs among individuals with and without HIV-infection

    DEFF Research Database (Denmark)

    Rasmussen, Line D; Kronborg, Gitte; Larsen, Carsten S

    2017-01-01

    no injection drug abuse or hepatitis C infection. Population controls were identified from The Danish Civil Registration System and matched on age and gender (5:1). We analyzed the proportion of individuals who redeemed 0-1, 2-4, 5-9, or 10 or more non-antiretroviral drugs. Data were analyzed according...... considerably. Thus, use in the HIV-infected population only differed marginally from that of the background population in recent years. This difference was most pronounced in men who have sex with men (MSM). CONCLUSION: Compared to the background population, HIV infected individuals have increased use of non......-antiretroviral drugs. The excess use is mainly observed in MSM and has decreased with calendar time, why it in recent years only differs marginally from that observed in the background population....

  17. Impact of the trade-related aspects of intellectual property rights (TRIPS) agreement on India as a supplier of generic antiretrovirals.

    Science.gov (United States)

    Babovic, Sonja; Wasan, Kishor M

    2011-03-01

    This is a commentary on how the trade-related aspects of intellectual property rights (TRIPS) agreement has impacted India as a supplier of generic antiretrovirals (ARVs). We provide a systematic review of the issues related to the TRIPS agreement that affects India. This includes discussion around (a) the legal landscape underpinning India as a supplier of generic ARVs; (b) supply of second-line ARVs; and (c) the future of generic drug production in India. The proclamation into force of TRIPS-compliant intellectual property law in India is likely to affect its position as a supplier of affordable ARVs, especially drugs brought to market after 2005. Currently, mechanisms exist for the generic production of almost all ARVs in India, including second-line drugs; however, the manufacture of these drugs by generic pharmaceutical companies may require additional market incentives. Compulsory licensing may emerge as an additional mechanism by which India can provide affordable versions of patented drugs to Least Developed Countries (LDCs). Copyright © 2010 Wiley-Liss, Inc.

  18. Pharmacokinetics of antiretroviral drugs in infancy | McIlleron ...

    African Journals Online (AJOL)

    Dosing in infancy is complicated by inadequate characterisation of pharmacokinetics, unpredictable drug concentrations and a lack of suitable dosage forms. Additional challenges are presented by the concomitant administration of interacting drugs (e.g. rifampicin in antituberculosis treatment) and disease conditions that ...

  19. Pros and cons of therapeutic drug monitoring of antiretroviral agents.

    NARCIS (Netherlands)

    Burger, D.M.; Aarnoutse, R.E.; Hugen, P.W.H.

    2002-01-01

    Therapeutic drug monitoring has the promise to become a part of routine patient care in the treatment of HIV infection. It is known that plasma drug concentrations of protease inhibitors and non-nucleoside reverse transcriptase inhibitors are better predictors of antiviral response or toxicity than

  20. The discovery and development of antiretroviral agents.

    Science.gov (United States)

    Lange, Joep M A; Ananworanich, Jintanat

    2014-01-01

    Since the discovery of HIV as the causative agent of AIDS in 1983/1984, remarkable progress has been made in finding antiretroviral drugs (ARVs) that are effective against it. A major breakthrough occurred in 1996 when it was found that triple drug therapy (HAART) could durably suppress viral replication to minimal levels. It was then widely felt, however, that HAART was too expensive and complex for low- and middle-income countries, and so, with the exception of a few of these countries, such as Brazil, a massive scale-up did not begin until the WHO launched its '3 by 5' initiative and sizeable funding mechanisms, such as the Global Fund to Fight AIDS, TB and Malaria and the US President's Emergency Plan for AIDS Relief (PEPFAR), came into existence. A pivotal enabler of the scale-up was a steady lowering of drug prices through entry of generic antiretrovirals, competition between generic manufacturers and the making of volume commitments. The WHO Prequalification of Medicines Programme and the Expedited Review Provision of the US Food and Drug Administration have been important for the assurance of quality standards. Antiretroviral drug development by research-based pharmaceutical companies continues, with several important innovative products, such as long-acting agents, in the pipeline.

  1. Development and assessment of an innovative culturally sensitive educational videotape to improve adherence to highly active antiretroviral therapy in Soweto, South Africa.

    Science.gov (United States)

    Wong, Ilene Y; Lawrence, Nicholas V; Struthers, Helen; McIntyre, James; Friedland, Gerald H

    2006-12-01

    The increasing availability of antiretroviral medication (ARV) therapy in the face of limited chronic medication-taking experience among resource-poor South Africans has raised concerns about adequate adherence to these medications. We hypothesized that a culturally sensitive audiovisual patient education program would be of substantial and measurable benefit in increasing patient understanding of the concepts of ARV resistance risk and medication-taking skills. To identify potential barriers to adherence and successful strategies to promote adherence, 6 focus groups with health care providers and HIV-positive adherence counselors were held, resulting in the production of a 17-minute culturally sensitive educational videotape. Basic drug-taking concepts and practical advice on how to improve adherence were presented in the videotape. Thirty-four HIV-positive patients (including 11 ARV-naive patients and 23 ARV-experienced patients) were shown the educational videotape, and their knowledge about medication taking was evaluated by a 24-point pre- and postvideotape questionnaire. On average, the 34 patients gained 2.2 knowledge points (P = 0.021). ARV-naive patients had an average improvement of 3.0 points (P = 0.0028), with most significant gains in the areas of understanding medication-taking strategies and side effects. These preliminary findings indicate that a culturally sensitive educational videotape can improve medication-taking knowledge in South Africa and that further study of the potential efficacy of using media technology to improve individuals' adherence to ARV therapy is warranted.

  2. In-vitro photo-translocation of antiretroviral drug delivery into TZMbl cells

    CSIR Research Space (South Africa)

    Malabi, Rudzani

    2017-01-01

    Full Text Available The objectives of this study are to use femtosecond laser pulses in a photo-translocation system to deliver ARVs into HIV infected TZMbl cells, and to investigate the influence of ARVs and laser on cellular processes using different molecular...

  3. Combined antiretroviral and antituberculosis drug resistance following incarceration

    Directory of Open Access Journals (Sweden)

    Katharine Elizabeth Stott

    2013-09-01

    Full Text Available We describe a case of HIV/tuberculosis (TB co-infection from KwaZulu-Natal, South Africa, characterised by drug resistance in both pathogens. The development of drug resistance was linked temporally to two periods of incarceration. This highlights the urgent need for improved integration of HIV/TB control strategies within prison health systems and within the broader public health framework.

  4. Affordable HIV drug-resistance testing for monitoring of antiretroviral therapy in sub-Saharan Africa.

    Science.gov (United States)

    Inzaule, Seth C; Ondoa, Pascale; Peter, Trevor; Mugyenyi, Peter N; Stevens, Wendy S; de Wit, Tobias F Rinke; Hamers, Raph L

    2016-11-01

    Increased provision of antiretroviral therapy in sub-Saharan Africa has led to a growing number of patients with therapy failure and acquired drug-resistant HIV, driving the demand for more costly further lines of antiretroviral therapy. In conjunction with accelerated access to viral load monitoring, feasible and affordable technologies to detect drug-resistant HIV could help maximise the durability and rational use of available drug regimens. Potential low-cost technologies include in-house Sanger and next-generation sequencing in centralised laboratories, and point mutation assays and genotype-free systems that predict response to antiretroviral therapy at point-of-care. Strengthening of centralised high-throughput laboratories, including efficient systems for sample referral and results delivery, will increase economies-of-scale while reducing costs. Access barriers can be mitigated by standardisation of in-house assays into commercial kits, use of polyvalent instruments, and adopting price-reducing strategies. A stepwise rollout approach should improve feasibility, prioritising WHO-recommended population-based surveillance and management of complex patient categories, such as patients failing protease inhibitor-based antiretroviral therapy. Implementation research, adaptations of existing WHO guidance, and political commitment, will be key to support the appropriate investments and policy changes. In this Personal View, we discuss the potential role of HIV drug resistance testing for population-based surveillance and individual patient management in sub-Saharan Africa. We review the strengths and challenges of promising low-cost technologies and how they can be implemented. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Jørgensen, Louise B; Kronborg, Gitte

    2007-01-01

    . The median number of resistance mutations was eight (interquartile range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy...... of death according to the number of mutations and individual mutations was estimated by Cox regression analysis and adjusted for potential confounders. RESULTS: Resistance tests were done for 133 of the 179 patients who experienced TCF. The median number of resistance mutations was eight (interquartile...... range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus

  6. Clinically relevant pharmacokinetic herb-drug interactions in antiretroviral therapy

    Science.gov (United States)

    For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In t...

  7. Antiretroviral therapy supply chain quality control and assurance in improving people living with HIV therapeutic outcomes in Cameroon.

    Science.gov (United States)

    Djobet, M P Ngogang; Singhe, David; Lohoue, Julienne; Kuaban, Christopher; Ngogang, Jeanne; Tambo, Ernest

    2017-04-04

    Evaluation of medication efficacy and safety is an essential guarantee to successful therapeutic outcome in public health practices. However, larger distribution chain supply in developing countries such as Cameroon is often challenged by counterfeit drugs, poor manufacturing, storage and degradation leading to health and patient adverse consequences. Yet, access to supply chain management in strengthening ARVs quality assurance and outcomes remains poorly documented. More than 53,000 patients have been enrolled on free ARVs medications, but little is documented on quality assurance and validity of safety for affected populations along the supply chain management since 2008. The cross sectional study was conducted in ARVs distribution units and centers in central, littoral and south west regions of Cameroon. ARVs drugs samples included Nevirapine, Efavirenz, and fixed dose combinations of Zidovudine + Lamivudine, Lamivudine + Stavudine and Zidovudine + Lamivudine + Nevirapine. Drugs packaging and labeling was assessed and galenic assays were performed at National Laboratory of quality Control of Medications and Expertise (LANACOME), Yaoundé, Cameroon. The study covered 16 structures located in eight different towns including the central ARVs store, two regional pharmaceutical procurement centers and thirteen HIV approved treatment centers and management units. A total of 35 ARVs products were collected. Only eight ARVs drugs containing Lamivudine and Stavudine presented with white stains on tablets, however these drugs were standard for all other tests performed. The others 28 ARVs products were standards to all assays performed. We concluded that ARVs drugs freely accessible and distributed to PLWHA are of good quality in Cameroon. However, with the increase number of patients under HAART since 2013, adoption of "Test and Treat" approach to reach the 90-90-90 goals and with the implementation of new national antiretroviral regimen guidelines and molecules

  8. Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and Sequence-Level Meta-Analysis

    NARCIS (Netherlands)

    S.Y. Rhee (Soo Yoon); J.L. Blanco (Jose Luis); M.R. Jordan (Michael); J. Taylor (Jonathan); P. Lemey (Philippe); V. Varghese (Vici); R.L. Hamers (Raph); S. Bertagnolio (Silvia); M. De Wit (Meike); A.F. Aghokeng (Avelin); J. Albert (Jan); R. Avi (Radko); S. Avila-Rios (Santiago); P.O. Bessong (Pascal O.); J.I. Brooks (James I.); C.A.B. Boucher (Charles); Z.L. Brumme (Zabrina L.); M.P. Busch (Michael P.); H. Bussmann (Hermann); M.L. Chaix (Marie Laure); B.S. Chin (Bum Sik); T.T. D’Aquin (Toni T.); C. de Gascun (Cillian); A. Derache (Anne); D. Descamps (Diane); A.K. Deshpande (Alaka K.); C.F. Djoko (Cyrille F.); S.H. Eshleman (Susan H.); H. Fleury (Hervé); P. Frange (Pierre); S. Fujisaki (Seiichiro); P. Harrigan (Pr); J. Hattori (Junko); A. Holguin (Africa); G.M. Hunt (Gillian M.); H. Ichimura (Hiroshi); P. Kaleebu (Pontiano); D. Katzenstein (David); S. Kiertiburanakul (Sasisopin); J.H. Kim (Jerome H.); S.S. Kim (Sung Soon); Y. Li (Yanpeng); I. Lutsar (Irja); L. Morris (L.); N. Ndembi (Nicaise); K.P. NG (Kee Peng); R.S. Paranjape (Ramesh S.); M.C. Peeters (Marian); M. Poljak (Mario); M.A. Price (Matt A.); M.L. Ragonnet-Cronin (Manon L.); G. Reyes-Terán (Gustavo); M. Rolland (Morgane); S. Sirivichayakul (Sunee); D.M. Smith (Davey M.); M.A. Soares (Marcelo A.); V. Soriano (Virtudes); D. Ssemwanga (Deogratius); M. Stanojevic (Maja); M.A. Stefani (Mariane A.); W. Sugiura (Wataru); S. Sungkanuparph (Somnuek); A. Tanuri (Amilcar); K.K. Tee (Kok Keng); H.-H.M. Truong (Hong-Ha M.); D.A.M.C. van de Vijver (David); N. Vidal (Nicole); C. Yang (Chunfu); R. Yang (Rongge); G. Yebra (Gonzalo); J.P.A. Ioannidis (John); A.M. Vandamme (Anne Mieke); R.W. Shafer (Robert)

    2015-01-01

    textabstractRegional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We

  9. Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis

    NARCIS (Netherlands)

    Rhee, Soo-Yon; Blanco, Jose Luis; Jordan, Michael R.; Taylor, Jonathan; Lemey, Philippe; Varghese, Vici; Hamers, Raph L.; Bertagnolio, Silvia; Rinke de Wit, Tobias F.; Aghokeng, Avelin F.; Albert, Jan; Avi, Radko; Avila-Rios, Santiago; Bessong, Pascal O.; Brooks, James I.; Boucher, Charles A. B.; Brumme, Zabrina L.; Busch, Michael P.; Bussmann, Hermann; Chaix, Marie-Laure; Chin, Bum Sik; D'Aquin, Toni T.; de Gascun, Cillian F.; Derache, Anne; Descamps, Diane; Deshpande, Alaka K.; Djoko, Cyrille F.; Eshleman, Susan H.; Fleury, Herve; Frange, Pierre; Fujisaki, Seiichiro; Harrigan, P. Richard; Hattori, Junko; Holguin, Africa; Hunt, Gillian M.; Ichimura, Hiroshi; Kaleebu, Pontiano; Katzenstein, David; Kiertiburanakul, Sasisopin; Kim, Jerome H.; Kim, Sung Soon; Li, Yanpeng; Lutsar, Irja; Morris, Lynn; Ndembi, Nicaise; Ng, Kee Peng; Paranjape, Ramesh S.; Peeters, Martine; Poljak, Mario; Price, Matt A.; Ragonnet-Cronin, Manon L.; Reyes-Terán, Gustavo; Rolland, Morgane; Sirivichayakul, Sunee; Smith, Davey M.; Soares, Marcelo A.; Soriano, Vincent V.; Ssemwanga, Deogratius; Stanojevic, Maja; Stefani, Mariane A.; Sugiura, Wataru; Sungkanuparph, Somnuek; Tanuri, Amilcar; tee, Kok Keng; Truong, Hong-Ha M.; van de Vijver, David A. M. C.; Vidal, Nicole; Yang, Chunfu; Yang, Rongge; Yebra, Gonzalo; Ioannidis, John P. A.; Vandamme, Anne-Mieke; Shafer, Robert W.

    2015-01-01

    Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to

  10. The financial and service implications of splitting fixed-dose antiretroviral drugs - a case study.

    Science.gov (United States)

    Taylor, R; Carlin, E; Sadique, Z; Ahmed, I; Adams, E J

    2015-02-01

    In 2010/2011, regional commissioners withdrew payment for the fixed-dose combination Combivir, forcing a switch to component drugs. This was deemed clinically acceptable and annual savings of £44 k expected. We estimated the true costs of switching and examined patient outcomes. Information for 46 patients using Combivir was extracted from case notes for each clinical contact in the 12 months pre- and post-switch (clinician seen, tests, antiretrovirals). Post-switch care costs £93/patient more annually versus pre-switch (95% CI £424 to £609), yielding £4278/year more post-switch for all patients. Drug and pathology costs were more expensive post-switch and extra clinical visits required. None of these results were statistically significant. Forty-two per cent of patients switched directly or in the subsequent year to an alternative fixed-dose combination rather than generics. Costs in this group were significantly higher post-switch driven by drug cost. Six patients (13%) reported problems with the switch including confusion around dosing and new side effects. As less-expensive generic antiretroviral drugs become available, it may appear cheaper to switch from fixed-dose combinations to component drugs. However, the additional clinical costs involved may outweigh the initial cost savings of the drugs and switching may cause confusion for some patients, risking loss of adherence. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  11. Directly administered antiretroviral therapy for HIV-infected drug users does not have an impact on antiretroviral resistance: results from a randomized controlled trial.

    Science.gov (United States)

    Maru, Duncan Smith-Rohrberg; Kozal, Michael J; Bruce, R Douglas; Springer, Sandra A; Altice, Frederick L

    2007-12-15

    Directly administered antiretroviral therapy (DAART) is an effective intervention that improves clinical outcomes among HIV-infected drug users. Its effects on antiretroviral drug resistance, however, are unknown. We conducted a community-based, prospective, randomized controlled trial of DAART compared with self-administered therapy (SAT). We performed a modified intention-to-treat analysis among 115 subjects who provided serum samples for HIV genotypic resistance testing at baseline and at follow-up. The main outcomes measures included total genotypic sensitivity score, future drug options, number of new drug resistance mutations (DRMs), and number of new major International AIDS Society (IAS) mutations. The adjusted probability of developing at least 1 new DRM did not differ between the 2 arms (SAT: 0.41 per person-year [PPY], DAART: 0.49 PPY; adjusted relative risk [RR] = 1.04; P = 0.90), nor did the number of new mutations (SAT: 0.76 PPY, DAART: 0.83 PPY; adjusted RR = 0.99; P = 0.99) or the probability of developing new major IAS new drug mutations (SAT: 0.30 PPY, DAART: 0.33 PPY; adjusted RR = 1.12; P = 0.78). On measures of GSS and FDO, the 2 arms also did not differ. In this trial, DAART provided on-treatment virologic benefit for HIV-infected drug users without affecting the rate of development of antiretroviral medication resistance.

  12. Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort

    DEFF Research Database (Denmark)

    Borges, Álvaro H; Hoy, Jennifer; Florence, Eric

    2017-01-01

    Background: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes. Methods: EuroSIDA participants were followed to assess...

  13. HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy.

    Science.gov (United States)

    Avila-Ríos, Santiago; García-Morales, Claudia; Tapia-Trejo, Daniela; Meza, Rita I; Nuñez, Sandra M; Parham, Leda; Flores, Norma A; Valladares, Diana; Pineda, Luisa M; Flores, Dixiana; Motiño, Roxana; Umanzor, Víctor; Carbajal, Candy; Murillo, Wendy; Lorenzana, Ivette; Palou, Elsa Y; Reyes-Terán, Gustavo

    2015-01-01

    We assessed HIV drug resistance (DR) in individuals failing ART (acquired DR, ADR) and in ART-naïve individuals (pre-ART DR, PDR) in Honduras, after 10 years of widespread availability of ART. 365 HIV-infected, ART-naïve, and 381 ART-experienced Honduran individuals were enrolled in 5 reference centres in Tegucigalpa, San Pedro Sula, La Ceiba, and Choluteca between April 2013 and April 2015. Plasma HIV protease-RT sequences were obtained. HIVDR was assessed using the WHO HIVDR mutation list and the Stanford algorithm. Recently infected (RI) individuals were identified using a multi-assay algorithm. PDR to any ARV drug was 11.5% (95% CI 8.4-15.2%). NNRTI PDR prevalence (8.2%) was higher than NRTI (2.2%) and PI (1.9%, p500 vs. Honduras remains at the intermediate level, after 10 years of widespread availability of ART. Evidence of ADR influencing the presence of PDR was observed by phylogenetic analyses and ADR/PDR mutation frequency correlations.

  14. Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.

    Directory of Open Access Journals (Sweden)

    Thuy Le

    Full Text Available BACKGROUND: It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL were obtained from a specimen bank (from 2004-2007. The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36% detected by deep sequencing; the majority of these (95% were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53. The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%. When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016. CONCLUSIONS/SIGNIFICANCE: Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional

  15. A comparison of self-report and antiretroviral detection to inform estimates of antiretroviral therapy coverage, viral load suppression and HIV incidence in Kwazulu-Natal, South Africa.

    Science.gov (United States)

    Huerga, Helena; Shiferie, Fisseha; Grebe, Eduard; Giuliani, Ruggero; Farhat, Jihane Ben; Van-Cutsem, Gilles; Cohen, Karen

    2017-09-29

    Accurately identifying individuals who are on antiretroviral therapy (ART) is important to determine ART coverage and proportion on ART who are virally suppressed. ART is also included in recent infection testing algorithms used to estimate incidence. We compared estimates of ART coverage, viral load suppression rates and HIV incidence using ART self-report and detection of antiretroviral (ARV) drugs and we identified factors associated with discordance between the methods. Cross-sectional population-based survey in KwaZulu-Natal, South Africa. Individuals 15-59 years were eligible. Interviews included questions about ARV use. Rapid HIV testing was performed at the participants' home. Blood specimens were collected for ARV detection, LAg-Avidity HIV incidence testing and viral load quantification in HIV-positive individuals. Multivariate logistic regression models were used to identify socio-demographic covariates associated with discordance between self-reported ART and ARV detection. Of the 5649 individuals surveyed, 1423 were HIV-positive. Median age was 34 years and 76.3% were women. ART coverage was estimated at 51.4% (95%CI:48.5-54.3), 53.1% (95%CI:50.2-55.9) and 56.1% (95%CI:53.5-58.8) using self-reported ART, ARV detection and both methods combined (classified as ART exposed if ARV detected and/or ART reported) respectively. ART coverage estimates using the 3 methods were fairly similar within sex and age categories except in individuals aged 15-19 years: 33.3% (95%CI:23.3-45.2), 33.8% (95%CI:23.9-45.4%) and 44.3% (95%CI:39.3-46.7) using self-reported ART, ARV detection and both methods combined. Viral suppression below 1000cp/mL in individuals on ART was estimated at 89.8% (95%CI:87.3-91.9), 93.1% (95%CI:91.0-94.8) and 88.7% (95%CI:86.2-90.7) using self-reported ART, ARV detection and both methods combined respectively. HIV incidence was estimated at 1.4 (95%CI:0.8-2.0) new cases/100 person-years when employing no measure of ARV use, 1.1/100PY (95%CI:0

  16. Increased incidence of antiretroviral drug discontinuation among patients with viremic hepatitis C virus coinfection and high hyaluronic acid, a marker of liver fibrosis

    DEFF Research Database (Denmark)

    Grint, Daniel; Peters, Lars; Rockstroh, Juergen K

    2014-01-01

    Most antiretroviral drugs are metabolized by the liver; hepatic disease or liver damage as a result of hepatitis C virus (HCV) could impair this metabolism leading to an increased risk of drug toxicity. This study aimed to determine the risk of antiretroviral drug discontinuation among HCV/HIV co...

  17. Different origin of adipogenic stem cells influences the response to antiretroviral drugs

    Energy Technology Data Exchange (ETDEWEB)

    Gibellini, Lara; De Biasi, Sara; Nasi, Milena; Carnevale, Gianluca; Pisciotta, Alessandra; Bianchini, Elena; Bartolomeo, Regina [Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia School of Medicine, Via Campi 287, 41125 Modena (Italy); Polo, Miriam [Department of Pharmacology, University of Valencia, Av.da Blasco Ibáñez 15, Valencia (Spain); FISABIO–Hospital Universitario Dr. Peset, Av.da Gaspar Aguilar 90, Valencia (Spain); De Pol, Anto [Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia School of Medicine, Via Campi 287, 41125 Modena (Italy); Dipartimento Sperimentale Interaziendale, Campus San Lazzaro, University of Modena and Reggio Emilia, 42122 Reggio Emilia (Italy); Pinti, Marcello [Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena (Italy); Cossarizza, Andrea, E-mail: andrea.cossarizza@unimore.it [Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia School of Medicine, Via Campi 287, 41125 Modena (Italy); Dipartimento Sperimentale Interaziendale, Campus San Lazzaro, University of Modena and Reggio Emilia, 42122 Reggio Emilia (Italy)

    2015-10-01

    Lipodystrophy (LD) is a main side effect of antiretroviral therapy for HIV infection, and can be provoked by nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs). LD exists in different forms, characterized by fat loss, accumulation, or both, but its pathogenesis is still unclear. In particular, few data exist concerning the effects of antiretroviral drugs on adipocyte differentiation. Adipose tissue can arise either from mesenchymal stem cells (MSCs), that include bone marrow-derived MSCs (hBM-MSCs), or from ectodermal stem cells, that include dental pulp stem cells (hDPSCs). To analyze whether the embryonal origin of adipocytes might impact the occurrence of different phenotypes in LD, we quantified the effects of several antiretroviral drugs on the adipogenic differentiation of hBM-MSCs and hDPSCs. hBM-MSCs and hDPSCs were isolated from healthy donors. Cells were treated with 10 and 50 μM stavudine (d4T), efavirenz (EFV), atazanavir (ATV), ritonavir (RTV), and ATV-boosted RTV. Viability and adipogenesis were evaluated by staining with propidium iodide, oil red, and adipoRed; mRNA levels of genes involved in adipocyte differentiation, i.e. CCAAT/enhancer-binding protein alpha (CEBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), and in adipocyte functions, i.e. fatty acid synthase (FASN), fatty acid binding protein-4 (FABP4), perilipin-1 (PLIN1) and 1-acylglycerol-3-phosphate O-acyltransferase-2 (AGPAT2), were quantified by real time PCR. We found that ATV, RTV, EFV, and ATV-boosted RTV, but not d4T, caused massive cell death in both cell types. EFV and d4T affected the accumulation of lipid droplets and induced changes in mRNA levels of genes involved in adipocyte functions in hBM-MSCs, while RTV and ATV had little effects. All drugs stimulated the accumulation of lipid droplets in hDPSCs. Thus, the adipogenic differentiation of human stem cells can be influenced by antiretroviral drugs, and depends, at least in

  18. Different origin of adipogenic stem cells influences the response to antiretroviral drugs

    International Nuclear Information System (INIS)

    Gibellini, Lara; De Biasi, Sara; Nasi, Milena; Carnevale, Gianluca; Pisciotta, Alessandra; Bianchini, Elena; Bartolomeo, Regina; Polo, Miriam; De Pol, Anto; Pinti, Marcello; Cossarizza, Andrea

    2015-01-01

    Lipodystrophy (LD) is a main side effect of antiretroviral therapy for HIV infection, and can be provoked by nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs). LD exists in different forms, characterized by fat loss, accumulation, or both, but its pathogenesis is still unclear. In particular, few data exist concerning the effects of antiretroviral drugs on adipocyte differentiation. Adipose tissue can arise either from mesenchymal stem cells (MSCs), that include bone marrow-derived MSCs (hBM-MSCs), or from ectodermal stem cells, that include dental pulp stem cells (hDPSCs). To analyze whether the embryonal origin of adipocytes might impact the occurrence of different phenotypes in LD, we quantified the effects of several antiretroviral drugs on the adipogenic differentiation of hBM-MSCs and hDPSCs. hBM-MSCs and hDPSCs were isolated from healthy donors. Cells were treated with 10 and 50 μM stavudine (d4T), efavirenz (EFV), atazanavir (ATV), ritonavir (RTV), and ATV-boosted RTV. Viability and adipogenesis were evaluated by staining with propidium iodide, oil red, and adipoRed; mRNA levels of genes involved in adipocyte differentiation, i.e. CCAAT/enhancer-binding protein alpha (CEBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), and in adipocyte functions, i.e. fatty acid synthase (FASN), fatty acid binding protein-4 (FABP4), perilipin-1 (PLIN1) and 1-acylglycerol-3-phosphate O-acyltransferase-2 (AGPAT2), were quantified by real time PCR. We found that ATV, RTV, EFV, and ATV-boosted RTV, but not d4T, caused massive cell death in both cell types. EFV and d4T affected the accumulation of lipid droplets and induced changes in mRNA levels of genes involved in adipocyte functions in hBM-MSCs, while RTV and ATV had little effects. All drugs stimulated the accumulation of lipid droplets in hDPSCs. Thus, the adipogenic differentiation of human stem cells can be influenced by antiretroviral drugs, and depends, at least in

  19. HIV-1 genetic diversity, geographical linkages and antiretroviral drug resistance among individuals from Pakistan.

    Science.gov (United States)

    Khan, Saeed; Zahid, Maria; Qureshi, Muhammad Asif; Mughal, Muhammad Nouman; Ujjan, Ikram Din

    2018-01-01

    Worldwide antiretroviral therapy (ART) has reduced the mortality and morbidity rates in individuals with HIV infection. However, the increasing occurrence of drug resistance is limiting treatment options. In recent years, Pakistan has witnessed a concentrated epidemic of HIV. It is very important to identify geographical linkages and mutations that generate selective pressure and drive resistance of HIV in our population. The aim of this work was to identify genetic diversity and drug resistance patterns of HIV in Pakistan, using available sequences and bioinformatics tools, which may help in selecting effective combination of available drugs. A total of 755 Pakistani HIV gag, pol and env sequences were retrieved from the Los Alamos HIV database. Sequences were aligned with reference sequences of different subtypes. For geographical linkages, sequences of predominant subtypes were aligned with sequences of the same subtypes from different countries. Phylogenetic trees were constructed using the maximum-likelihood method in MEGA 7 software. For drug resistance analysis, sequences were entered into the Stanford University HIV Drug Resistance Database. Phylogenetic trees for studying genetic diversity showed that 82% of the sequences were of subtype A, while the rest of the sequences were of subtypes B (9.5%), K (2%), D (2%) and AE (1%). Moreover, trees that were constructed to examine geographical linkages showed close clustering of strains with those of the neighboring countries Afghanistan and India, as well as some African countries. A search for drug resistance mutations showed that 93% of the sequences had no major or minor mutations. The remaining 7% of the sequences contained a major mutation, Y115F, which causes the virus to exhibit low to intermediate resistance against lamivudine and emtricitabine. Our data indicate that HIV subtype A is the major subtype, while subtypes K, D and AE are also present in our country, suggesting gradual viral evolution and

  20. Cutting the cost of South African antiretroviral therapy using newer, safer drugs

    Directory of Open Access Journals (Sweden)

    W F Venter

    2017-01-01

    Full Text Available Antiretrovirals are a significant cost driver for HIV programmes. Current first-line regimens have performed well in real-life programmes, but have a low barrier to virological resistance and still carry toxicity that limits adherence. New drug developments may mean that we have access to safer, more robust and cheaper regimens, but only if the appropriate clinical trials are conducted. We briefly discuss these trials, and demonstrate the large cost savings to the South African HIV programme if these are successful.

  1. Astrocyte Senescence and Metabolic Changes in Response to HIV Antiretroviral Therapy Drugs

    Directory of Open Access Journals (Sweden)

    Justin Cohen

    2017-08-01

    Full Text Available With the advent of highly active antiretroviral therapy (HAART survival rates among patients infected by HIV have increased. However, even though survival has increased HIV-associated neurocognitive disorders (HAND still persist, suggesting that HAART-drugs may play a role in the neurocognitive impairment observed in HIV-infected patients. Given previous data demonstrating that astrocyte senescence plays a role in neurocognitive disorders such as Alzheimer’s disease (AD, we examined the role of HAART on markers of senescence in primary cultures of human astrocytes (HAs. Our results indicate HAART treatment induces cell cycle arrest, senescence-associated beta-galactosidase, and the cell cycle inhibitor p21. Highly active antiretroviral therapy treatment is also associated with the induction of reactive oxygen species and upregulation of mitochondrial oxygen consumption. These changes in mitochondria correlate with increased glycolysis in HAART drug treated astrocytes. Taken together these results indicate that HAART drugs induce the senescence program in HAs, which is associated with oxidative and metabolic changes that could play a role in the development of HAND.

  2. Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

    Science.gov (United States)

    Giraldo, N A; Amariles, P; Monsalve, M; Faus, M J

    Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV ® ) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Access to highly active antiretroviral therapy for injection drug users: adherence, resistance, and death

    Directory of Open Access Journals (Sweden)

    David Vlahov

    Full Text Available Injection drug users (IDUs continue to comprise a major risk group for HIV infection throughout the world and represent the focal population for HIV epidemics in Asia and Eastern Europe/Russia. HIV prevention programs have ranged from HIV testing and counseling, education, behavioral and network interventions, drug abuse treatment, bleach disinfection of needles, needle exchange and expanded syringe access, as well as reducing transition to injection and primary substance abuse prevention. With the advent of highly active antiretroviral therapy (HAART in 1996, dramatic clinical improvements have been seen. In addition, the treatment's impact on reducing HIV viral load (and therefore transmission by all routes provides a stronger rationale for an expansion of the focus on prevention to emphasize early identification and treatment of HIV infected individuals. However, treatment of IDUs has many challenges including adherence, resistance and relapse to high risk behaviors, all of which impact issues of access and ultimately effectiveness of potent antiretroviral treatment. A major current challenge in addressing the HIV epidemic revolves around an appropriate approach to HIV treatment for IDUs.

  4. Access to highly active antiretroviral therapy for injection drug users: adherence, resistance, and death

    Directory of Open Access Journals (Sweden)

    Vlahov David

    2006-01-01

    Full Text Available Injection drug users (IDUs continue to comprise a major risk group for HIV infection throughout the world and represent the focal population for HIV epidemics in Asia and Eastern Europe/Russia. HIV prevention programs have ranged from HIV testing and counseling, education, behavioral and network interventions, drug abuse treatment, bleach disinfection of needles, needle exchange and expanded syringe access, as well as reducing transition to injection and primary substance abuse prevention. With the advent of highly active antiretroviral therapy (HAART in 1996, dramatic clinical improvements have been seen. In addition, the treatment's impact on reducing HIV viral load (and therefore transmission by all routes provides a stronger rationale for an expansion of the focus on prevention to emphasize early identification and treatment of HIV infected individuals. However, treatment of IDUs has many challenges including adherence, resistance and relapse to high risk behaviors, all of which impact issues of access and ultimately effectiveness of potent antiretroviral treatment. A major current challenge in addressing the HIV epidemic revolves around an appropriate approach to HIV treatment for IDUs.

  5. Existing capacity to manage pharmaceuticals and related commodities in East Africa: an assessment with specific reference to antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Anokbonggo Willy W

    2009-03-01

    Full Text Available Abstract Background East African countries have in the recent past experienced a tremendous increase in the volume of antiretroviral drugs. Capacity to manage these medicines in the region remains limited. Makerere University, with technical assistance from the USAID supported Rational Pharmaceutical Management Plus (RPM Plus Program of Management Sciences for Health (MSH established a network of academic institutions to build capacity for pharmaceutical management in the East African region. The initiative includes institutions from Uganda, Tanzania, Kenya and Rwanda and aims to improve access to safe, effective and quality-assured medicines for the treatment of HIV/AIDS, TB and Malaria through spearheading in-country capacity. The initiative conducted a regional assessment to determine the existing capacity for the management of antiretroviral drugs and related commodities. Methods Heads and implementing workers of fifty HIV/AIDS programs and institutions accredited to offer antiretroviral services in Uganda, Kenya, Tanzania and Rwanda were key informants in face-to-face interviews guided by structured questionnaires. The assessment explored categories of health workers involved in the management of ARVs, their knowledge and practices in selection, quantification, distribution and use of ARVs, nature of existing training programs, training preferences and resources for capacity building. Results Inadequate human resource capacity including, inability to select, quantify and distribute ARVs and related commodities, and irrational prescribing and dispensing were some of the problems identified. A competence gap existed in all the four countries with a variety of healthcare professionals involved in the supply and distribution of ARVs. Training opportunities and resources for capacity development were limited particularly for workers in remote facilities. On-the-job training and short courses were the preferred modes of training. Conclusion There

  6. Existing capacity to manage pharmaceuticals and related commodities in East Africa: an assessment with specific reference to antiretroviral therapy.

    Science.gov (United States)

    Waako, Paul J; Odoi-adome, Richard; Obua, Celestino; Owino, Erisa; Tumwikirize, Winnie; Ogwal-Okeng, Jasper; Anokbonggo, Willy W; Matowe, Lloyd; Aupont, Onesky

    2009-03-09

    East African countries have in the recent past experienced a tremendous increase in the volume of antiretroviral drugs. Capacity to manage these medicines in the region remains limited. Makerere University, with technical assistance from the USAID supported Rational Pharmaceutical Management Plus (RPM Plus) Program of Management Sciences for Health (MSH) established a network of academic institutions to build capacity for pharmaceutical management in the East African region. The initiative includes institutions from Uganda, Tanzania, Kenya and Rwanda and aims to improve access to safe, effective and quality-assured medicines for the treatment of HIV/AIDS, TB and Malaria through spearheading in-country capacity. The initiative conducted a regional assessment to determine the existing capacity for the management of antiretroviral drugs and related commodities. Heads and implementing workers of fifty HIV/AIDS programs and institutions accredited to offer antiretroviral services in Uganda, Kenya, Tanzania and Rwanda were key informants in face-to-face interviews guided by structured questionnaires. The assessment explored categories of health workers involved in the management of ARVs, their knowledge and practices in selection, quantification, distribution and use of ARVs, nature of existing training programs, training preferences and resources for capacity building. Inadequate human resource capacity including, inability to select, quantify and distribute ARVs and related commodities, and irrational prescribing and dispensing were some of the problems identified. A competence gap existed in all the four countries with a variety of healthcare professionals involved in the supply and distribution of ARVs. Training opportunities and resources for capacity development were limited particularly for workers in remote facilities. On-the-job training and short courses were the preferred modes of training. There is inadequate capacity for managing medicines and related

  7. Factors affecting adherence to short-course ARV prophylaxis for preventing mother-to-child transmission of HIV in sub-Saharan Africa: a review and lessons for future elimination.

    Science.gov (United States)

    Colombini, Manuela; Stöckl, Heidi; Watts, Charlotte; Zimmerman, Cathy; Agamasu, Enyonam; Mayhew, Susannah H

    2014-01-01

    Despite the biomedical potential to eliminate vertical HIV transmission, drug adherence to short regimens is often sub-optimal. To inform future programmes, we reviewed evidence on the factors influencing maternal and infant drug adherence to preventing MTCT drug regimens at delivery in sub-Saharan Africa. A literature review yielding 14 studies on adherence to drug regimes among HIV-positive pregnant women and mothers in sub-Saharan Africa was conducted. Rates of maternal adherence to preventive drug regimens at time of delivery varied widely across sites between 35 and 93.5%. Factors most commonly associated with low adherence to antiretroviral therapy (ARV) prophylaxis for preventing MTCT at the health system level include giving birth at home, quality and timing of HIV testing and counselling, and late distribution of nevirapine (NVP). Socio-demographic and demand-side factors include fear of stigma, lack of male involvement, fear of partner's reaction to disclosure, few antenatal (ANC) visits, young age and lack of education. With the implementation of the newly published WHO guidelines recommending triple-drug ARV regimen during pregnancy and breastfeeding for all women with HIV, it is important that women are able to adhere to recommended drug regimens. Service improvements should include clear and timely communication with women about the benefits of combined regimens and greater emphasis on patient confidentiality. Efforts must be made to help women overcome barriers that reduce adherence, such as financial logistical challenges, social stigma and women's fear of violence.

  8. Hidden costs of HIV treatment in Spain: inefficiency of the antiretroviral drug packaging.

    Science.gov (United States)

    Llibre-Codina, Josep M; Andreu-Crespo, Angels; Cardona-Peitx, Gloria; Sala-Piñol, Ferran; Clotet-Sala, Bonaventura; Bonafont-Pujol, Xavier

    2014-01-01

    Antiretroviral drugs in Spain are delivered by law only in hospital pharmacies. Commercial packages meet variable quality standards when dispensed drugs are returned due to treatment changes or adherence problems Nearly 20-25% of the initial regimens will be changed at 48 weeks for different reasons. We evaluated the economic impact on public health system of the inability of using returned drugs due to inefficient packaging. We defined socially efficient packaging as the best adapted one to being delivered in unit dose to outpatients and classified: Class A - Drug packed in unit doses with complete info (name of drug, dosage in mg, lot, and expiring date) in each unit, maintaining complete information of the drug if returned when the external package is opened. Class B - packed in blisters with complete info in the blister, but not in unit doses, without special conservation conditions (should be re-packed in unit doses in the pharmacy before its dispensation to assure a class A excellence). Class C - packed in plastic containers with complete info written only on a label over the container, would allow repackaging only before its initial delivery, but not when returned. Class D - drug packed in plastic containers with manufacturer's warning that the product cannot be placed outside of the original package due to special conditions of conservation (fridge, humidity) that doesn't allow a unit dose repackaging or reusing an opened container. We analysed a 12-month period (July 2011-June 2012) in a hospital-based HIV outpatient pharmacy that serves 2413 treated individuals. Patients generated 23,574 visits to pharmacy, and received 48,325 drug packages, with 2.529.137 pills delivered. The patients suffered 1051 treatment changes for any reason. A total amount of 122.945€ in treatment were returned to pharmacy in opened packages during the study period. 47.139.91€ would be totally lost, mainly due to being packaged in class C and D boxes, the equivalent of

  9. FACTORS INFLUENCING ADHERENCE TO ARVS AMONG PATIENTS ATTENDING COMPREHENSIVE CARE CLINIC WITHIN JOMO KENYATTA UNIVERSITY OF AGRICULTURE AND TECHNOLOGY, KIAMBU COUNTY, KENYA.

    Science.gov (United States)

    Mwangi, A N; Ng'ang'a, Z; Wanzala, P; Karanja, S M

    2014-04-01

    The efficacy of anti-retroviral Therapy (ART) depends on adherence to the prescribed regimen. However, lack of adherence leads to treatment failure and drug resistance among other negative outcomes. To determine factors influencing adherence to ARVS among patients attending the Comprehensive Care Clinic (CCC) within Jomo Kenyatta University of Agriculture and Technology (JKUAT). A descriptive cross sectional study. Comprehensive Care Clinic within JKUAT. Three hundred HIV positive patients, undergoing ART treatment and follow up at the JKUAT clinic for a minimum duration of one month before the study, were recruited. Of the 300 patients enrolled for the study (70% females and 30% males), 81% were adhering to ARV treatment. The factors that were significantly associated with adherence included; Support (encouragement and reminder to take drugs) (P = 0.025); the number of meals respondents took in a day (P = 0.001); pill burden (P = 0.002) and forgetfulness (P = 0.001). However, there was no significant relationship between adherence and age, marital status, education, employment status or time taken to travel to the clinic. This study concluded that, the observed level of sub-optimal adherence to ART (19%) is of public health concern. These patients are vulnerable to treatment failure and development of resistant viral strains. Consequently the modifiable factors (Support, Number of meals taken, pill burden, and forgetfulness, should be addressed to change the current tread.

  10. In vitro assessment of the adverse effects of antiretroviral drugs on the human male gamete.

    Science.gov (United States)

    Ahmad, G; Moinard, N; Jouanolou, V; Daudin, M; Gandia, P; Bujan, L

    2011-03-01

    This study was designed to investigate the in vitro effects of didanosine, zidovudine, saquinavir and indinavir, commonly used in highly active antiretroviral therapy, on human sperm fertility parameters. Thirty semen samples from healthy men were collected and prepared by gradient density method. Aliquots of 90% fractions with >80% motile spermatozoa were incubated for 1, 3, and 6h with different concentrations of the antiretroviral drugs (20, 40, and 80 μg/ml). Sperm motility was evaluated by computer assisted sperm analysis system. Sperm mitochondrial potential was evaluated using 3,3'-dihexyloxacarbocyanine iodide (DIOC(6)) and the acrosome reaction was examined using pisum sativum agglutinin method. A dose-dependent decrease in sperm motility was observed with saquinavir. Saquinavir also induced a significant time and dose-dependent decrease in mitochondrial potential and an increase in spontaneous acrosome reaction. These findings indicate that, in vitro, higher doses of saquinavir have adverse effects on sperm motility, mitochondrial potential and acrosome reaction. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Coumarins as Potential Inhibitors of DNA Polymerases and Reverse Transcriptases. Searching New Antiretroviral and Antitumoral Drugs.

    Science.gov (United States)

    Garro, Hugo A; Pungitore, Carlos R

    2015-01-01

    Human Immunodeficiency Virus (HIV) is the viral agent of Acquired Immunodeficiency Syndrome (AIDS), and at present, there is no effective vaccine against HIV. Reverse Transcriptase (RT) is an essential enzyme for retroviral replication, such as HIV as well as for other RNA infectious viruses like Human T lymphocyte virus. Polymerases act in DNA metabolism, modulating different processes like mitosis, damage repair, transcription and replication. It has been widely documented that DNA Polymerases and Reverse Transcriptases serve as molecular targets for antiviral and antitumoral chemotherapy. Coumarins are oxygen heterocycles that are widely distributed throughout the plant kingdom. Natural coumarins have attraction due to their bioactive properties such as tumor promotion inhibitory effects, and anti-HIV activity. Coumarins and derivates exhibit potent inhibitory effects on HIV-1 replication in lymphocytes and compounds isolated from Calophyllum inophyllum or DCK derivates showed inhibitory activity against human RT. Furthermore, natural isocoumarins isolated from cultures of fungi or hydroxycoumarins were able to inhibit human DNA polymerase. In view of their importance as drugs and biologically active natural products, and their medicinally useful properties, extensive studies have been carried out on the synthesis of coumarin compounds in recent years. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), a class of antiretroviral chemotherapeutic agents, act by binding to an allosteric pocket showing, generally, low toxicity. This work tries to summarize the investigation about natural and synthetic coumarins with the ability to inhibit key enzymes that play a crucial role in DNA metabolism and their possible application as antiretroviral and antitumoral agents.

  12. Pattern of drug therapy problems and interventions in ambulatory patients receiving antiretroviral therapy in Nigeria

    Directory of Open Access Journals (Sweden)

    Ojeh VB

    2015-06-01

    Full Text Available Objectives: We describe the frequency and types of drug therapy problems (DTPs, and interventions carried out to resolve them, among a cohort of HIV- infected patients on ART in Jos, Nigeria. Methods: A prospective pharmacists’ intervention study was conducted between January and August 2012 at the outpatient HIV clinic of the Jos University Teaching Hospital (JUTH. Pharmacists identified DTPs and made recommendations to resolve them. The main outcome measures were number of DTPs encountered, interventions proposed and acceptance rate of recommendations. Results: A total of 42,416 prescriptions were dispensed to 9339 patients during the eight months study. A total of 420 interventions (Intervention rate of 1 per 100 prescriptions were made to resolve DTPs in 401 (4.3% patients with a mean age of 41 (SD=10 years, and made up of 73% females. DTPs encountered were drug omission (n=89, 21.2%, unnecessary drug (n=55, 13.1% and wrong drug indication (n=55, 13.1%. Recommendations offered included; Addition of another drug to the therapy (n=87, 20.7%, rectification of incomplete prescriptions (n=85, 20.2%, change of drug or dosage (n=67, 16.0%, and discontinuation of the offending drug (n=59, 14.0%. A total of 389 (93% out of 420 of the recommendations were accepted. In all, 50.4% (212 of the problematic prescriptions were changed and dispensed, 22.2% (89 were clarified and dispensed, while wrong identities were corrected in 11.7% (49. However, 7.5% (30 prescriptions were dispensed as prescribed, 5.2% (21 were not dispensed, and 3% (12 were unresolved. Conclusion: Our findings suggest that pharmacists-initiated interventions can ameliorate DTPs in patients receiving ART given the high intervention acceptance rate recorded. The implication of this finding is that pharmacists with requisite training in HIV pharmacotherapy are an excellent resource in detecting and minimizing the effect of antiretroviral drug-related errors.

  13. The National Access to Antiretroviral Program for PHA (NAPHA) in Thailand.

    Science.gov (United States)

    Chasombat, Sanchai; Lertpiriyasuwat, Cheewanan; Thanprasertsuk, Sombat; Suebsaeng, Laksami; Lo, Ying Ru

    2006-07-01

    To describe the development, components, initial results and lessons learned from Thailand's National Access to Antiretroviral Program for People living with HIV/AIDS (NAPHA), a historical review was conducted and program monitoring was analyzed. The national antiretroviral therapy program at different levels of the public health system was implemented with all major program components; ARV protocol development, health care professional training, drug supply chain management, laboratory network formation, monitoring and evaluation, and multi-sector and PHA involvement since 2001, which was based on elements of research, pilot projects, training, national guideline development, experiences and policy making. A national monitoring system was developed to monitor the progress of the program. From February 2001 to December 2004, the monitoring reports received from implementing hospitals showed that 58,133 cases had received antiretroviral therapy (ART), and 85% (49,477) of them were continuing to take ARV drugs. In conclusion, the NAPHA was implemented nationwide with comprehensive systems. The reports indicate achievement of expansion of the ART program. Lessons learned from the program initiation and scaling up show local leadership, comprehensive training, adherence, and coordination are essential to program effectiveness and sustainability.

  14. HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy

    Science.gov (United States)

    Tapia-Trejo, Daniela; Meza, Rita I.; Nuñez, Sandra M.; Parham, Leda; Flores, Norma A.; Valladares, Diana; Pineda, Luisa M.; Flores, Dixiana; Motiño, Roxana; Umanzor, Víctor; Carbajal, Candy; Murillo, Wendy; Lorenzana, Ivette; Palou, Elsa Y.; Reyes-Terán, Gustavo

    2015-01-01

    Introduction We assessed HIV drug resistance (DR) in individuals failing ART (acquired DR, ADR) and in ART-naïve individuals (pre-ART DR, PDR) in Honduras, after 10 years of widespread availability of ART. Methods 365 HIV-infected, ART-naïve, and 381 ART-experienced Honduran individuals were enrolled in 5 reference centres in Tegucigalpa, San Pedro Sula, La Ceiba, and Choluteca between April 2013 and April 2015. Plasma HIV protease-RT sequences were obtained. HIVDR was assessed using the WHO HIVDR mutation list and the Stanford algorithm. Recently infected (RI) individuals were identified using a multi-assay algorithm. Results PDR to any ARV drug was 11.5% (95% CI 8.4–15.2%). NNRTI PDR prevalence (8.2%) was higher than NRTI (2.2%) and PI (1.9%, p500 vs. <350 CD4+ T cells/μL. PDR in recently infected individuals was 13.6%, showing no significant difference with PDR in individuals with longstanding infection (10.7%). The most prevalent PDR mutations were M46IL (1.4%), T215 revertants (0.5%), and K103NS (5.5%). The overall ADR prevalence in individuals with <48 months on ART was 87.8% and for the ≥48 months on ART group 81.3%. ADR to three drug families increased in individuals with longer time on ART (p = 0.0343). M184V and K103N were the most frequent ADR mutations. PDR mutation frequency correlated with ADR mutation frequency for PI and NNRTI (p<0.01), but not for NRTI. Clusters of viruses were observed suggesting transmission of HIVDR both from ART-experienced to ART-naïve individuals and between ART-naïve individuals. Conclusions The global PDR prevalence in Honduras remains at the intermediate level, after 10 years of widespread availability of ART. Evidence of ADR influencing the presence of PDR was observed by phylogenetic analyses and ADR/PDR mutation frequency correlations. PMID:26558396

  15. HIV-1 Drug Resistance Mutations Are Present in Six Percent of Persons Initiating Antiretroviral Therapy in Lusaka, Zambia

    NARCIS (Netherlands)

    Hamers, Raph L.; Siwale, Margaret; Wallis, Carole L.; Labib, Moheb; van Hasselt, Robbert; Stevens, Wendy S.; Schuurman, Rob; Wensing, Annemarie M. J.; van Vugt, Michèle; Rinke de Wit, Tobias F.

    2010-01-01

    Objective: To assess the mutational patterns and factors associated with baseline drug-resistant HIV-1 present at initiation of first-line antiretroviral therapy (ART) at 3 sites in Lusaka, Zambia, in 2007-2008. Methods: Population sequencing of the HIV-1 pol gene was performed in the PharmAccess

  16. Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study

    DEFF Research Database (Denmark)

    Cozzi-Lepri, Alessandro; Phillips, Andrew N; Clotet, Bonaventura

    2008-01-01

    OBJECTIVE(S): To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death. DESIGN: Virological failure was defined as experiencing two consecutive viral loads of more than 400...

  17. Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba.

    Science.gov (United States)

    Pérez, Lissette; Kourí, Vivian; Alemán, Yoan; Abrahantes, Yeisel; Correa, Consuelo; Aragonés, Carlos; Martínez, Orlando; Pérez, Jorge; Fonseca, Carlos; Campos, Jorge; Álvarez, Delmis; Schrooten, Yoeri; Dekeersmaeker, Nathalie; Imbrechts, Stijn; Beheydt, Gertjan; Vinken, Lore; Soto, Yudira; Álvarez, Alina; Vandamme, Anne-Mieke; Van Laethem, Kristel

    2013-06-01

    In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24_BG (19.5%), CRF19_cpx (18.0%) and CRF18_cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the

  18. Intellectual property rights, market competition and access to affordable antiretrovirals.

    Science.gov (United States)

    Pascual, Fernando

    2014-01-01

    The number of patients receiving antiretroviral therapy (ART) has increased from around half a million in 2003 to almost 10 million in only 10 years, and will continue to increase in the coming years. Over 16 million more are eligible to start ART according to the last World Health Organization (WHO) guidelines. The demand is also switching from the less expensive antiretrovirals (ARVs) that allowed such scale-up to newer more expensive ones with fewer side effects or those that can be used by people who have developed resistance to first-line treatment. However, patents on these new drugs can delay robust generic competition and, consequently, price reduction made possible by economies of scale. Various ways to address this issue have been envisaged or implemented, including the use of the flexibilities available under the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), systematic widespread voluntary licensing, of which the Medicines Patent Pool (MPP) is an example, and the application of different prices in different countries, called tiered pricing. This paper helps explain the impact of patents on market competition for ARVs and analyses various approaches available today to minimize this impact.

  19. Factorial design studies of antiretroviral drug-loaded stealth liposomal injectable: PEGylation, lyophilization and pharmacokinetic studies

    Science.gov (United States)

    Sudhakar, Beeravelli; Krishna, Mylangam Chaitanya; Murthy, Kolapalli Venkata Ramana

    2016-01-01

    The aim of the present study was to formulate and evaluate the ritonavir-loaded stealth liposomes by using 32 factorial design and intended to delivered by parenteral delivery. Liposomes were prepared by ethanol injection method using 32 factorial designs and characterized for various physicochemical parameters such as drug content, size, zeta potential, entrapment efficiency and in vitro drug release. The optimization process was carried out using desirability and overlay plots. The selected formulation was subjected to PEGylation using 10 % PEG-10000 solution. Stealth liposomes were characterized for the above-mentioned parameters along with surface morphology, Fourier transform infrared spectrophotometer, differential scanning calorimeter, stability and in vivo pharmacokinetic studies in rats. Stealth liposomes showed better result compared to conventional liposomes due to effect of PEG-10000. The in vivo studies revealed that stealth liposomes showed better residence time compared to conventional liposomes and pure drug solution. The conventional liposomes and pure drug showed dose-dependent pharmacokinetics, whereas stealth liposomes showed long circulation half-life compared to conventional liposomes and pure ritonavir solution. The results of statistical analysis showed significance difference as the p value is (<0.05) by one-way ANOVA. The result of the present study revealed that stealth liposomes are promising tool in antiretroviral therapy.

  20. Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system

    Science.gov (United States)

    Gomes, Maria João; Neves, José das; Sarmento, Bruno

    2014-01-01

    Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS) is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood–brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretroviral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood–brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS. PMID:24741312

  1. Patients' recommendations for a patient-centred public antiretroviral ...

    African Journals Online (AJOL)

    Background: The South African antiretroviral therapy (ART) programme, which is in its second decade of existence, includes many successes and challenges. This study provides patients' recommendations to address the challenges they currently experience at four antiretroviral (ARV) clinics based in urban public hospitals ...

  2. Surveillance of transmitted HIV drug resistance in antiretroviral-naive patients aged less than 25 years, in Bangkok, Thailand.

    Science.gov (United States)

    Sungkanuparph, Somnuek; Pasomsub, Ekawat; Chantratita, Wasun

    2014-01-01

    Emergence of transmitted HIV drug resistance (TDR) is a concern after global scale-up of antiretroviral therapy (ART). World Health Organization had developed threshold survey method for surveillance of TDR in resource-limited countries. ART in Thailand has been scaling up for >10 years. To evaluate the current TDR in Thailand, a cross-sectional study was conducted among antiretroviral-naive HIV-infected patients aged Thailand after a decade of rapid scale-up of ART. Interventions to prevent TDR at the population level are essentially needed in Thailand. Surveillance for TDR in Thailand has to be regularly performed.

  3. Mind the gap: access to ARV medication, rights and the politics of scale in South Africa.

    Science.gov (United States)

    Jones, Peris Sean

    2012-01-01

    Global access to anti-retroviral medication (ARVs) has increased exponentially in recent years. As a relatively recent phenomenon for the global South, much knowledge is being added, but analysis of 'access' to ARVs remains partial. The main research objective of this article is to gain a fuller picture of the range of forces constituting 'access' to ARVs by providing a local community case study from Hammanskraal, South Africa. A qualitative and relational approach situates specific points of 'local' access to ARVs within relations stretched over space. Spatial awareness enables us to consider the reinforcing effects of local geographies upon access to health care but also simultaneously sees this in relation to non-local geographies. The concept of scale is pivotal to creating linkages across space and reveals a number of 'gaps' in access that otherwise might not be shown. Elaborating on the meaning of "access" to treatment produces a more rounded picture of the context that people-living-with-AIDS encounter. A multi-scale and multi-disciplinary analysis of 'access' is therefore also highly informative in a related sense, namely, for closing the gap between human rights standards and actual implementation. A geographical imagination is useful not only to 'mind' but also to close the 'gap' in both senses. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure

    OpenAIRE

    Kyeyune, Fred; Gibson, Richard M.; Nankya, Immaculate; Venner, Colin; Metha, Samar; Akao, Juliet; Ndashimye, Emmanuel; Kityo, Cissy M.; Salata, Robert A.; Mugyenyi, Peter; Arts, Eric J.; Quiñones-Mateu, Miguel E.

    2016-01-01

    Most patients failing antiretroviral treatment in Uganda continue to fail their treatment regimen even if a dominant drug-resistant HIV-1 genotype is not detected. In a recent retrospective study, we observed that approximately 30% of HIV-infected individuals in the Joint Clinical Research Centre (Kampala, Uganda) experienced virologic failure with a susceptible HIV-1 genotype based on standard Sanger sequencing. Selection of minority drug-resistant HIV-1 variants (not detectable by Sanger se...

  5. HIV drug resistance following a decade of the free antiretroviral therapy programme in India: A review.

    Science.gov (United States)

    Karade, Santosh; Chaturbhuj, Devidas N; Sen, Sourav; Joshi, Rajneesh K; Kulkarni, Smita S; Shankar, Subramanian; Gangakhedkar, Raman R

    2018-01-01

    The objective of this review was to assess the burden of HIV drug resistance mutations (DRM) in Indian adults exposed to first-line antiretroviral therapy (ART) as per national guidelines. An advanced search of the published literature on HIV drug resistance in India was performed in the PubMed and Scopus databases. Data pertaining to age, sex, CD4 count, viral load, and prevalence of nucleoside reverse transcriptase inhibitor (NRTI)/non-nucleoside reverse transcriptase inhibitor (NNRTI) DRM were extracted from each publication. Year-wise Indian HIV-1 reverse transcriptase (RT) sequences were retrieved from the Los Alamos HIV database and mutation analyses were performed. A time trend analysis of the proportion of sequences showing NRTI resistance mutations among individuals exposed to first-line ART was conducted. Overall, 23 studies (1046 unique RT sequences) were identified indicating a prevalence of drug resistance to NRTI and NNRTI. The proportion of RT sequences with any DRM, any NRTI DRM, and any NNRTI DRM was 78.39%, 68.83%, and 73.13%, respectively. The temporal trend analysis of individual DRM from sequences retrieved during 2004-2014 indicated a rising trend in K65R mutations (p=0.013). Although the overall burden of resistance against first-line ART agents remained steady over the study decade, periodic monitoring is essential. There is the need to develop an HIV-1 subtype C-specific resistance database in India. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Christian theology of life, death and healing in an era of antiretroviral ...

    African Journals Online (AJOL)

    This article discusses Christian understandings of life, death and healing in context of antiretroviral (ARV) therapy. The discussion is a response to the reactions of some Botswana Pentecostal and African Independent Churches to the availability of ARV therapy, as reflected in several media reports of churches discouraging ...

  7. The incidence rate of HIV type-1 drug resistance in patients on antiretroviral therapy: a nationwide population-based Danish cohort study 1999-2005

    DEFF Research Database (Denmark)

    Audelin, A.M.; Lohse, N.; Obel, N.

    2009-01-01

    BACKGROUND: Newer antiretroviral treatment regimens for HIV carry a lower risk of inducing drug resistance mutations. We estimated changes in incidence rates (IRs) of new mutations in HIV-infected individuals receiving highly active antiretroviral therapy (HAART). METHODS: Population-based data...

  8. Antiretroviral agents and acid-base balance at delivery of the neonate

    Directory of Open Access Journals (Sweden)

    P. El-Beitune

    2007-07-01

    Full Text Available Limited evidence is available regarding antiretroviral (ARV safety for uninfected infants exposed to these drugs in utero. Our objective was to determine if ARV administered to pregnant women is associated with decreasing umbilical arterial pH and base excess in uninfected infants. A prospective study was conducted on 57 neonates divided into three groups: ZDV group, born to mothers taking zidovudine (N = 20, triple therapy (TT group, born to mothers taking zidovudine + lamivudine + nelfinavir (N = 25, and control group (N = 12, born to uninfected mothers. Umbilical cord blood was used to determine umbilical artery gases. A test was performed to calculate the sample by comparing means by the unpaired one-tailed t-test, with a = 0.05 and ß = 20%, indicating the need for a sample of 18 newborn infants for the study groups to detect differences higher than 20%. The control and ARV groups were similar in gestational age, birth weight, and Apgar scores. Values of pH, pCO2, bicarbonate, and base excess in cord arterial blood obtained at delivery from the newborns exposed to TT were 7.23, 43.2 mmHg, 19.5 mEq/L, and -8.5 nmol/L, respectively, with no significant difference compared to the control and ZDV groups. We conclude that intrauterine exposure to ARV is not associated with a pathological decrease in umbilical arterial pH or base excess. While our data are reassuring, follow-up is still limited and needs to be continued into adulthood because of the possible potential for adverse effects of triple antiretroviral agents.

  9. Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons

    DEFF Research Database (Denmark)

    Kovari, Helen; Sabin, Caroline A; Ledergerber, Bruno

    2016-01-01

    Background.  Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods.  Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without ...... a consistent association between tenofovir and cLEE emerging within the first 2 years after drug initiation. This novel tenofovir-cLEE signal should be further investigated.......Background.  Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods.  Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without...

  10. Gag drug resistance mutations in HIV-1 subtype C patients, failing a protease inhibitor inclusive treatment regimen, with detectable lopinavir levels

    OpenAIRE

    Kelly Pillay, Sameshnee; Singh, Urisha; Singh, Avashna; Gordon, Michelle; Ndungu, Thumbi

    2014-01-01

    The development of antiretroviral (ARV) drugs and their use in human immunodeficiency virus type 1 (HIV-1) has led to the effective control of HIV replication in infected patients. However the emergence of resistant HIV-1 strains still remains a problem. Literature has shown that mutations may accumulate in the protease (PR) and gag regions of HIV-1 patients who fail therapy with protease inhibitor (PI) drugs (1, 2). Gag mutations have also been found to play an important role in the evolutio...

  11. Antiretroviral Drug Resistance Among Children and Youth in the United States With Perinatal HIV.

    Science.gov (United States)

    Van Dyke, Russell B; Patel, Kunjal; Kagan, Ron M; Karalius, Brad; Traite, Shirley; Meyer, William A; Tassiopoulos, Katherine K; Seage, George R; Seybolt, Lorna M; Burchett, Sandra; Hazra, Rohan; Lurie, Robert H; Yogev, Ram; Sanders, Margaret Ann; Malee, Kathleen; Hunter, Scott; Shearer, William; Paul, Mary; Cooper, Norma; Harris, Lynnette; Purswani, Murli; Baig, Mahboobullah; Cintron, Anna; Puga, Ana; Navarro, Sandra; Garvie, Patricia; Blood, James; Burchett, Sandra; Karthas, Nancy; Kammerer, Betsy; Wiznia, Andrew; Burey, Marlene; Nozyce, Molly; Dieudonne, Arry; Bettica, Linda; Adubato, Susan; Chen, Janet; Bulkley, Maria Garcia; Ivey, Latreaca; Grant, Mitzie; Knapp, Katherine; Allison, Kim; Wilkins, Megan; Acevedo-Flores, Midnela; Rios, Heida; Olivera, Vivian; Silio, Margarita; Jones, Medea; Sirois, Patricia; Spector, Stephen; Norris, Kim; Nichols, Sharon; McFarland, Elizabeth; Katai, Alisa; Dunn, Jennifer; Paul, Suzanne; Scott, Gwendolyn; Bryan, Patricia; Willen, Elizabeth

    2016-07-01

    Among 234 US youths with perinatal human immunodeficiency virus, 75% had antiretroviral resistance, substantially higher than that of the reference laboratory overall (36%-44%). Resistance to newer antiretrovirals and to all antiretrovirals in a class was uncommon. The only factor independently associated with future resistance was a higher peak viral load. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  12. Pattern and Determinants of Antiretroviral Drug Adherence among Nigerian Pregnant Women

    Directory of Open Access Journals (Sweden)

    S. O. Ekama

    2012-01-01

    Full Text Available Background. The need for a high level of adherence to antiretroviral drugs has remained a major hurdle to achieving maximal benefit from its use in pregnancy. This study was designed to determine the level of adherence and identify factors that influence adherence during pregnancy. Method. This is a cross-sectional study utilizing a semistructured questionnaire. Bivariate and multiple logistic regression models were used to determine factors independently associated with good drug adherence during pregnancy. Result. 137 (80.6% of the interviewed 170 women achieved adherence level of ≥95% using 3 day recall. The desire to protect the unborn child was the greatest motivation (51.8% for good adherence. Fear of being identified as HIV positive (63.6% was the most common reason for nonadherence. Marital status, disclosure of HIV status, good knowledge of ART, and having a treatment supporter were found to be significantly associated with good adherence at bivariate analysis. However, after controlling for confounders, only HIV status disclosure and having a treatment partner retained their association with good adherence. Conclusion. Disclosure of HIV status and having treatment support are associated with good adherence. Maternal desire to protect the child was the greatest motivator for adherence.

  13. Towards universal ARV access: Achievements and challenges in ...

    African Journals Online (AJOL)

    Information on staff training, vacancy rates and funding allocations for the ARV roll-out was obtained from official government reports. Projections were made of expected new ARV enrolments for 2008 and 2009 and compared with goals set by the National Strategic Plan (NSP) to achieve universal access to ARVs by 2011.

  14. Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Cambiano, Valentina; Miners, Alec

    2014-01-01

    BACKGROUND: With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial......-effectiveness threshold. Results from our model will help inform WHO recommendations on monitoring of HIV drug resistance in people starting ART. FUNDING: WHO (with funds provided by the Bill & Melinda Gates Foundation), CHAIN (European Commission)....

  15. A pharmacovigilance study of adults on highly active antiretroviral therapy, South Africa: 2007 – 2011

    Science.gov (United States)

    Dube, Nomathemba Michell; Summers, Robert; Tint, Khin-San; Mayayise, Guistee

    2012-01-01

    Background Of the 1.6 million South African people infected with human immunodeficiency virus (HIV), approximately 970,000 (55%) have been initiated on HAART. Despite these numbers, very little has been published about the safety profile of antiretroviral (ARV) medicines in the country. This study was performed at the Medunsa National Pharmacovigilance Centre and aimed to describe the demographic characteristics of patients enrolled in the pharmacovigilance surveillance study; highly active antiretroviral therapy (HAART) initiation regimen patterns; reasons for regimen changes; and adverse effects of ARV medicines. Methods A cohort study of HIV-infected individuals aged 15 years or older who were on ARV medicines was conducted at four sentinel sites. Results After HAART initiation, with an average lapse of 17.8 months (range: 0 – 83.8 months), 2,815 patients were enrolled into the study. Results show that patients were observed for 1,606.2 person-years for pharmacy visits (collection of ARV medicines) and 817.1 person-years for clinical visits (consultation with the doctor). Females constituted 69.6% (1,958/2,815) of the study population. Almost all patients initiated HAART on first-line regimens (2,801/2,815). Some patients (6.7%, 190/2,815) dropped out of the study after HAART initiation. Reasons for regimen changes were not recorded for 2.5% (22/891) of the patients who changed regimens. The primary reason for regimen changes was drug-related toxicity (76.1%, 678/891), mostly evident in patients taking first-line regimens. Adverse effects experienced by patients were polyneuropathy (24.0%, 163/678); lipodystrophy (23.9%, 162/678); neuropathy (10.6%, 72/678); and suspected lactic acidosis (3.8%, 26/678). Conclusion The majority of prescribers complied with the HAART guidelines and initiated most patients on first-line regimens. However, adverse effects are evident in patients taking first-line regimens. We recommend that the Department of Health should

  16. Poly(lactic-co-glycolic Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations

    Directory of Open Access Journals (Sweden)

    Faithful Makita-Chingombe

    2016-01-01

    Full Text Available Poly(lactic-co-glycolic acid (PLGA chitosan (CS coated nanoparticles (NPs were loaded with two antiretrovirals (ARVs either lamivudine (LMV which is hydrophilic or nevirapine (NVP which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1 treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI, and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and −20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC. Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1.

  17. Global strategies to reduce the price of antiretroviral medicines: evidence from transactional databases.

    Science.gov (United States)

    Waning, Brenda; Kaplan, Warren; King, Alexis C; Lawrence, Danielle A; Leufkens, Hubert G; Fox, Matthew P

    2009-07-01

    To estimate the impact of global strategies, such as pooled procurement arrangements, third-party price negotiation and differential pricing, on reducing the price of antiretrovirals (ARVs), which currently hinders universal access to HIV/AIDS treatment. We estimated the impact of global strategies to reduce ARV prices using data on 7253 procurement transactions (July 2002-October 2007) from databases hosted by WHO and the Global Fund to Fight AIDS, Tuberculosis and Malaria. For 19 of 24 ARV dosage forms, we detected no association between price and volume purchased. For the other five ARVs, high-volume purchases were 4-21% less expensive than medium- or low-volume purchases. Nine of 13 generic ARVs were priced 6-36% lower when purchased under the Clinton Foundation HIV/AIDS Initiative (CHAI). Fifteen of 18 branded ARVs were priced 23-498% higher for differentially priced purchases compared with non-CHAI generic purchases. However, two branded, differentially priced ARVs were priced 63% and 73% lower, respectively, than generic non-CHAI equivalents. Large purchase volumes did not necessarily result in lower ARV prices. Although current plans for pooled procurement will further increase purchase volumes, savings are uncertain and should be balanced against programmatic costs. Third-party negotiation by CHAI resulted in lower generic ARV prices. Generics were less expensive than differentially priced branded ARVs, except where little generic competition exists. Alternative strategies for reducing ARV prices, such as streamlining financial management systems, improving demand forecasting and removing barriers to generics, should be explored.

  18. Drug resistance in antiretroviral-naive children newly diagnosed with HIV-1 in Manaus, Amazonas.

    Science.gov (United States)

    Andrade, Solange Dourado de; Sabidó, Meritxell; Monteiro, Wuelton Marcelo; Benzaken, Adele Schwartz; Tanuri, Amilcar

    2017-06-01

    To determine the prevalence of drug resistance mutations (DRM), the prevalence of drug susceptibility [transmitted drug resistance (TDR)] and the prevalence of HIV-1 variants among treatment-naive HIV-infected children in Manaus, Amazonas state, Brazil. Children born to HIV-infected mothers and diagnosed with HIV in an HIV reference service centre and with available pol sequence between 2010 and 2015 prior to antiretroviral initiation were included. TDR was identified using the Calibrated Population Resistance Tool. HIV-1 subtypes were defined by Rega and phylogenetic analyses. One hundred and seventeen HIV-infected children with a median age of 3.7 years were included. Among them, 28.2% had been exposed to some form of prevention of mother-to-child transmission (PMTCT). HIV DRM were present in 21.4% of all children. Among PMTCT-exposed children, 3% had NRTI mutations, 15.2% had NNRTI mutations and 3% had PI mutations. Among PMTCT-unexposed children, 1.2% had NRTI mutations, 21.4% had non-NNRTI mutations and 1.2% had PI mutations. The most common DRM was E138A (8.5%). The prevalence of TDR was 16.2%; 21.1% among PMTCT-exposed children and 14.3% among PMTC-unexposed children. The analysis of HIV-1 subtypes revealed that 80.2% were subtype B, 6.0% were subtype C, 3.4% were subtype F1 and 10.3% were possible unique recombinant forms (BF1, 4.3%; DB, 4.3%; BC, 0.9%; KC, 0.9%). We report a high prevalence of DRM in this population, including in almost a quarter of children with no reported PMTCT. The high prevalence of TDR observed might compromise ART effectiveness. Results show extensive HIV-1 diversity and expansion of subtype C, which highlights the need for surveillance of HIV-1 subtypes in Amazonas state.

  19. Sustainability of ARV provision in developing countries: challenging a framework based on program history

    Directory of Open Access Journals (Sweden)

    Thiago Botelho Azeredo

    Full Text Available Abstract The provision of ARVs is central to HIV/AIDS programs, because of its impact on the course of the disease and on quality of life. Although first-line treatments costs have declined, treatment-associated expenses are steeper each year. Sustainability is therefore an important variable for the success of treatment programs. A conceptual framework on sustainability of ARV provision was developed, followed by data collection instruments. The pilot study was undertaken in Brazil. Bolivia, Peru and Mozambique, were visited. Key informants were identified and interviewed. Investigation of sustainability related to ARV provision involved implementation and routinization events of provision schemes. Evidence of greater sustainability potential was observed in Peru, where provision is implemented and routinized by the National HIV/AIDS program and expenditures met by the government. In Mozambique, provision is dependent on donations and external aid, but the country displays a great effort to incorporate ARV provision and care in routine healthcare activities. Bolivia, in addition to external dependence on financing and management of drug supply, presents problems regarding implementation and routinization. The conceptual framework was useful in recognizing events that influence sustainable ARV provision in these countries.

  20. The global pediatric antiretroviral market: analyses of product availability and utilization reveal challenges for development of pediatric formulations and HIV/AIDS treatment in children

    Directory of Open Access Journals (Sweden)

    Jambert Elodie

    2010-10-01

    Full Text Available Abstract Background Important advances in the development and production of quality-certified pediatric antiretroviral (ARV formulations have recently been made despite significant market disincentives for manufacturers. This progress resulted from lobbying and innovative interventions from HIV/AIDS activists, civil society organizations, and international organizations. Research on uptake and dispersion of these improved products across countries and international organizations has not been conducted but is needed to inform next steps towards improving child health. Methods We used information from the World Health Organization Prequalification Programme and the United States Food and Drug Administration to describe trends in quality-certification of pediatric formulations and used 7,989 donor-funded, pediatric ARV purchase transactions from 2002-2009 to measure uptake and dispersion of new pediatric ARV formulations across countries and programs. Prices for new pediatric ARV formulations were compared to alternative dosage forms. Results Fewer ARV options exist for HIV/AIDS treatment in children than adults. Before 2005, most pediatric ARVs were produced by innovator companies in single-component solid and liquid forms. Five 2-in1 and four 3-in-1 generic pediatric fixed-dose combinations (FDCs in solid and dispersible forms have been quality-certified since 2005. Most (67% of these were produced by one quality-certified manufacturer. Uptake of new pediatric FDCs outside of UNITAID is low. UNITAID accounted for 97-100% of 2008-2009 market volume. In total, 33 and 34 countries reported solid or dispersible FDC purchases in 2008 and 2009, respectively, but most purchases were made through UNITAID. Only three Global Fund country recipients reported purchase of these FDCs in 2008. Prices for pediatric FDCs were considerably lower than liquids but typically higher than half of an adult FDC. Conclusion Pediatric ARV markets are more fragile than

  1. The global pediatric antiretroviral market: analyses of product availability and utilization reveal challenges for development of pediatric formulations and HIV/AIDS treatment in children.

    Science.gov (United States)

    Waning, Brenda; Diedrichsen, Ellen; Jambert, Elodie; Bärnighausen, Till; Li, Yun; Pouw, Mieke; Moon, Suerie

    2010-10-17

    Important advances in the development and production of quality-certified pediatric antiretroviral (ARV) formulations have recently been made despite significant market disincentives for manufacturers. This progress resulted from lobbying and innovative interventions from HIV/AIDS activists, civil society organizations, and international organizations. Research on uptake and dispersion of these improved products across countries and international organizations has not been conducted but is needed to inform next steps towards improving child health. We used information from the World Health Organization Prequalification Programme and the United States Food and Drug Administration to describe trends in quality-certification of pediatric formulations and used 7,989 donor-funded, pediatric ARV purchase transactions from 2002-2009 to measure uptake and dispersion of new pediatric ARV formulations across countries and programs. Prices for new pediatric ARV formulations were compared to alternative dosage forms. Fewer ARV options exist for HIV/AIDS treatment in children than adults. Before 2005, most pediatric ARVs were produced by innovator companies in single-component solid and liquid forms. Five 2-in1 and four 3-in-1 generic pediatric fixed-dose combinations (FDCs) in solid and dispersible forms have been quality-certified since 2005. Most (67%) of these were produced by one quality-certified manufacturer. Uptake of new pediatric FDCs outside of UNITAID is low. UNITAID accounted for 97-100% of 2008-2009 market volume. In total, 33 and 34 countries reported solid or dispersible FDC purchases in 2008 and 2009, respectively, but most purchases were made through UNITAID. Only three Global Fund country recipients reported purchase of these FDCs in 2008. Prices for pediatric FDCs were considerably lower than liquids but typically higher than half of an adult FDC. Pediatric ARV markets are more fragile than adult markets. Ensuring a long-term supply of quality, well

  2. Maternal and infant health is protected by antiretroviral drug strategies that preserve breastfeeding by HIV-positive women

    Directory of Open Access Journals (Sweden)

    Louise Kuhn

    2012-03-01

    Full Text Available The South African Department of Health is justified in withdrawing support for free infant formula. By so doing, it recognises that any intervention that might detract from breast feeding poses a serious threat to infant survival. Since evidence is now strong that antiretroviral drugs used during lactation prevent transmission of infection from a seropositive mother, strategies that promote breastfeeding can now be recommended for enhancing the health of mothers and infants.

  3. Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance.

    Directory of Open Access Journals (Sweden)

    Nadia Bakkour

    2007-10-01

    Full Text Available The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16 that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.

  4. Effectiveness of second-line antiretroviral therapy: the impact of drug switches.

    Science.gov (United States)

    Braga, Letícia Penna; Mendicino, Cássia Cristina Pinto; Reis, Edna Afonso; Carmo, Ricardo Andrade; Menezes de Pádua, Cristiane Aparecida

    2017-12-01

    Including antiretroviral drug switches as a measure of ART failure could be more suitable than conventional measures to evaluate health outcomes in "real-world" settings. This is part of a historical cohort of HIV-infected adults who initiated ART from 2001-2005, and were followed up for a maximum of five years in three HIV/AIDS centers in Belo Horizonte, Brazil. Follow-up information included data from 2001-2010. All patients switched from first-line ART were included. Second-line ART effectiveness was measured as the time-to-ART failure. Failure was defined simulating two scenarios: (1) Clinical, immunological and virological failure (scenario 1); and scenario 1 plus ART switches (scenario 2). Descriptive analysis, Kaplan-Meier curves, log-rank test, and Cox proportional hazards model were performed. We identified 119 eligible patients; most had protease inhibitor (PI)-based regimens prescribed as second-line. The incidence of failure was different for the two scenarios (29.4% vs. 54.6% for scenario 1 and 2, respectively; p impact of ART switches in representing lack of ART effectiveness.

  5. Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs.

    Science.gov (United States)

    Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin Cs; Peter, Aniekan I; Azu, Onyemaechi O

    2016-10-01

    Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A-D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility ( P coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter ( P coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

  6. Perinatal genotoxicity and carcinogenicity of anti-retroviral nucleoside analog drugs

    International Nuclear Information System (INIS)

    Poirier, Miriam C.; Olivero, Ofelia A.; Walker, Dale M.; Walker, Vernon E.

    2004-01-01

    The current worldwide spread of the human immunodeficiency virus-1 (HIV-1) to the heterosexual population has resulted in approximately 800 000 children born yearly to HIV-1-infected mothers. In the absence of anti-retroviral intervention, about 25% of the approximately 7000 children born yearly to HIV-1-infected women in the United States are HIV-1 infected. Administration of zidovudine (AZT) prophylaxis during pregnancy reduces the rate of infant HIV-1 infection to approximately 7%, and further reductions are achieved with the addition of lamivudine (3TC) in the clinical formulation Combivir. Whereas clinically this is a remarkable achievement, AZT and 3TC are DNA replication chain terminators known to induce various types of genotoxicity. Studies in rodents have demonstrated AZT-DNA incorporation, HPRT mutagenesis, telomere shortening, and tumorigenicity in organs of fetal mice exposed transplacentally to AZT. In monkeys, both AZT and 3TC become incorporated into the DNA from multiple fetal organs taken at birth after administration of human-equivalent protocols to pregnant dams during gestation, and telomere shortening has been found in monkey fetuses exposed to both drugs. In human infants, AZT-DNA and 3TC-DNA incorporation as well as HPRT and GPA mutagenesis have been documented in cord blood from infants exposed in utero to Combivir. In infants of mice, monkeys, and humans, levels of AZT-DNA incorporation were remarkably similar, and in newborn mice and humans, mutation frequencies were also very similar. Given the risk-benefit ratio, these highly successful drugs will continue to be used for prevention of vertical viral transmission, however evidence of genotoxicity in mouse and monkey models and in the infants themselves would suggest that exposed children should be followed well past adolescence for early detection of potential cancer hazard

  7. Clinical implications of antiretroviral drug interactions with warfarin: a case-control study.

    Science.gov (United States)

    Esterly, John S; Darin, Kristin M; Gerzenshtein, Lana; Othman, Fidah; Postelnick, Michael J; Scarsi, Kimberly K

    2013-06-01

    Warfarin, a frequently prescribed anticoagulant with a narrow therapeutic index, is susceptible to drug-drug interactions with antiretroviral therapy (ART). This study compared the warfarin maintenance dose (WMD) between patients receiving and not receiving ART and evaluated predictors of warfarin dosage among those on ART. This was a case-control (1:2) study. Cases were HIV-infected patients receiving warfarin and protease inhibitor (PI)- and/or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Controls were randomly selected HIV-uninfected patients receiving warfarin. The WMD was compared between cases and controls and between cases on varying ART regimens. Bivariate comparisons were performed and a linear regression model was developed to identify predictors of WMD. We identified 18 case and 36 control patients eligible for inclusion. Cases were younger than controls (mean age: 45.8 versus 63.1 years, P African American (50.0% versus 22.2%, P=0.04). ART was classified as PI-based (n=9), NNRTI-based (n=7) and PI + NNRTI-based (n=2). The WMD (mean ± SD) differed between cases and controls (8.6  ±  3.4 mg versus 5.1 ± 1.5 mg, P ART regimens (PI: 8.8  ±  4.5 mg; NNRTI: 8.6   ± 1.8 mg; PI + NNRTI: 7.3  ±  3.3 mg; P = 0.86). Race and ritonavir dose were independent predictors of WMD, predicting an increase of 3.9 mg (95% CI: 0.88-6.98, P = 0.02) if a patient was African American or 3.7 mg (95% CI: 0.53-6.89, P = 0.03) if the total daily ritonavir dose was 200 mg. The required WMD was significantly higher in patients receiving ART. Prompt dose titration to achieve a higher WMD with vigilant monitoring may be required due to these drug-drug interactions.

  8. Solubility and Dissolution Rate Determination of Different Antiretroviral Drugs in Different pH Media Using UV Visible Spectrophotometer

    OpenAIRE

    Prakash, K.; Narayana Raju, P.; Shanta Kumari, K.; Lakshmi Narasu, M.

    2008-01-01

    Solubility and dissolution rate of three antiretroviral drugs such as lamivudine, zidovudine and stavudine was studied in four media having different pH. The samples were analyzed by using UV Visible spectrophotometer. lamivudine shows more solubility that is 276.08 mg/mL in 0.01 N HCl. Stavudine showing highest solubility that is 101.23 mg/mL in pH 4.5 acetate buffer. Zidovudine showing highest solubility that is 28.90 mg/mL in both water and 0.01 N HCl. All three drugs showing lower solubi...

  9. Prevalence of transmitted HIV drug resistance among newly diagnosed antiretroviral therapy-naive pregnant women in Lilongwe and Blantyre, Malawi.

    Science.gov (United States)

    Wadonda-Kabondo, Nellie; Banda, Richard; Moyo, Kundai; M'bang'ombe, Maurice; Chiwaula, Mabvuto; Porter, Carol; Jordan, Michael R

    2012-05-01

    In 2006, a survey of transmitted human immunodeficiency virus (HIV) drug resistance (TDR) was conducted in Lilongwe, Malawi. The survey followed the World Health Organization method to classify TDR to nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) among primigravid women aged Blantyre. Findings show that in Lilongwe TDR to NRTIs and PIs was Blantyre, TDR was <5% to all drug classes. Observed moderate TDR in Lilongwe is cause for concern and signals the need for closer monitoring of Malawi's antiretroviral therapy program.

  10. Access to highly active antiretroviral therapy (HAART) for injecting drug users in the WHO European Region 2002-2004

    DEFF Research Database (Denmark)

    Donoghoe, Martin C; Bollerup, Annemarie R; Lazarus, Jeff

    2007-01-01

    Providing equitable access to highly active antiretroviral treatment (HAART) to injecting drug users (IDUs) is both feasible and desirable. Given the evidence that IDUs can adhere to HAART as well as non-IDUs and the imperative to provide universal and equitable access to HIV/AIDS treatment for all...... the injecting status of those initiating HAART and the use of opioid substitution therapy among HAART patients, and discuss how HAART might be better delivered to injecting drug users. Our data adds to the evidence that IDUs in Europe have poor and inequitable access to HAART, with only a relatively small...

  11. Metabolic and renal adverse effects of antiretroviral therapy in HIV-infected children and adolescents.

    Science.gov (United States)

    Fortuny, Clàudia; Deyà-Martínez, Ángela; Chiappini, Elena; Galli, Luisa; de Martino, Maurizio; Noguera-Julian, Antoni

    2015-05-01

    Worldwide, the benefits of combined antiretroviral (ARV) therapy in morbidity and mortality due to perinatally acquired human immunodeficiency virus infection are beyond question and outweigh the toxicity these drugs have been associated with in HIV-infected children and adolescents to date. In puberty, abnormal body fat distribution is stigmatizating and leads to low adherence to ARV treatment. The other metabolic comorbidities (mitochondrial toxicity, dyslipidemias, insulin resistance and low bone mineral density) and renal toxicity, albeit nonsymptomatic in most children, are increasingly being reported and potentially put this population at risk for early cardiovascular or cerebrovascular atherosclerotic disease, diabetes, pathologic fractures or premature renal failure in the third and fourth decades of life. Evidence from available studies is limited because of methodological limitations and also because of several HIV-unrelated factors influencing, to some degree, the development of these conditions. Current recommendations for the prevention, diagnosis, monitoring and treatment of metabolic and renal adverse effects in HIV-children and adolescents are based on adult studies, observational pediatric studies and experts' consensus. Healthy lifestyle habits (regarding diet, exercise and refraining from toxic substances) and wise use of ARV options are the only preventive tools for the majority of patients. Should abnormal findings arise, switches in one or more ARV drugs have proved useful. Specific therapies are also available for some of these comorbidities, although the experience in the pediatric age is still very scarce. We aim to summarize the epidemiological, clinical and therapeutic aspects of metabolic and renal adverse effects in vertically HIV-infected children and adolescents.

  12. Intervening in global markets to improve access to HIV/AIDS treatment: an analysis of international policies and the dynamics of global antiretroviral medicines markets.

    Science.gov (United States)

    Waning, Brenda; Kyle, Margaret; Diedrichsen, Ellen; Soucy, Lyne; Hochstadt, Jenny; Bärnighausen, Till; Moon, Suerie

    2010-05-25

    Universal access to antiretroviral therapy (ART) in low- and middle-income countries faces numerous challenges: increasing numbers of people needing ART, new guidelines recommending more expensive antiretroviral (ARV) medicines, limited financing, and few fixed-dose combination (FDC) products. Global initiatives aim to promote efficient global ARV markets, yet little is known about market dynamics and the impact of global policy interventions. We utilize several data sources, including 12,958 donor-funded, adult first-line ARV purchase transactions, to describe the market from 2002-2008. We examine relationships between market trends and: World Health Organization (WHO) HIV/AIDS treatment guidelines; WHO Prequalification Programme (WHO Prequal) and United States (US) Food and Drug Administration (FDA) approvals; and procurement policies of the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM), US President's Emergency Plan for AIDS Relief (PEPFAR) and UNITAID. WHO recommended 7, 4, 24, and 6 first-line regimens in 2002, 2003, 2006 and 2009 guidelines, respectively. 2009 guidelines replaced a stavudine-based regimen ($88/person/year) with more expensive zidovudine- ($154-260/person/year) or tenofovir-based ($244-465/person/year) regimens. Purchase volumes for ARVs newly-recommended in 2006 (emtricitabine, tenofovir) increased >15-fold from 2006 to 2008. Twenty-four generic FDCs were quality-approved for older regimens but only four for newer regimens. Generic FDCs were available to GFATM recipients in 2004 but to PEPFAR recipients only after FDA approval in 2006. Price trends for single-component generic medicines mirrored generic FDC prices. Two large-scale purchasers, PEPFAR and UNITAID, together accounted for 53%, 84%, and 77% of market volume for abacavir, emtricitabine, and tenofovir, respectively, in 2008. PEPFAR and UNITAID purchases were often split across two manufacturers. Global initiatives facilitated the creation of fairly efficient markets

  13. Intervening in global markets to improve access to HIV/AIDS treatment: an analysis of international policies and the dynamics of global antiretroviral medicines markets

    Directory of Open Access Journals (Sweden)

    Hochstadt Jenny

    2010-05-01

    Full Text Available Abstract Background Universal access to antiretroviral therapy (ART in low- and middle-income countries faces numerous challenges: increasing numbers of people needing ART, new guidelines recommending more expensive antiretroviral (ARV medicines, limited financing, and few fixed-dose combination (FDC products. Global initiatives aim to promote efficient global ARV markets, yet little is known about market dynamics and the impact of global policy interventions. Methods We utilize several data sources, including 12,958 donor-funded, adult first-line ARV purchase transactions, to describe the market from 2002-2008. We examine relationships between market trends and: World Health Organization (WHO HIV/AIDS treatment guidelines; WHO Prequalification Programme (WHO Prequal and United States (US Food and Drug Administration (FDA approvals; and procurement policies of the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM, US President's Emergency Plan for AIDS Relief (PEPFAR and UNITAID. Results WHO recommended 7, 4, 24, and 6 first-line regimens in 2002, 2003, 2006 and 2009 guidelines, respectively. 2009 guidelines replaced a stavudine-based regimen ($88/person/year with more expensive zidovudine- ($154-260/person/year or tenofovir-based ($244-465/person/year regimens. Purchase volumes for ARVs newly-recommended in 2006 (emtricitabine, tenofovir increased >15-fold from 2006 to 2008. Twenty-four generic FDCs were quality-approved for older regimens but only four for newer regimens. Generic FDCs were available to GFATM recipients in 2004 but to PEPFAR recipients only after FDA approval in 2006. Price trends for single-component generic medicines mirrored generic FDC prices. Two large-scale purchasers, PEPFAR and UNITAID, together accounted for 53%, 84%, and 77% of market volume for abacavir, emtricitabine, and tenofovir, respectively, in 2008. PEPFAR and UNITAID purchases were often split across two manufacturers. Conclusions Global initiatives

  14. An interdisciplinary HIV-adherence program combining motivational interviewing and electronic antiretroviral drug monitoring.

    Science.gov (United States)

    Krummenacher, Isabelle; Cavassini, Matthias; Bugnon, Olivier; Schneider, Marie P

    2011-05-01

    To ensure successful treatment, HIV patients must maintain a high degree of medication adherence over time. Since August 2004, patients who are (or are at risk of) experiencing problems with their HIV antiretroviral therapy (ART) have been referred by their physicians to an interdisciplinary HIV-adherence program. The program consists of a multifactorial intervention along with electronic drug monitoring (MEMS(TM)). The pharmacists organize individualized semi-structured motivational interviews based on cognitive, emotional, behavioral, and social issues. At the end of each session, the patient brings an adherence report to the physician. This enables the physician to use the adherence results to evaluate the treatment plan. The aim of this study was to retrospectively analyze this on-going interdisciplinary HIV-adherence program. All patients who were included between August 2004 and the end of April 2008 were analyzed. One hundred and four patients were included (59% women, median age 39 (31.0, 46.0) years, 42% black ethnicity). Eighty (77%) patients were ART-experienced patients and 59% had a protease inhibitor-based treatment. The retention rate was high (92%) in the program. Patient inclusion in this HIV-adherence program was determined by patient issues for naive patients and by nonadherence or suboptimal clinical outcomes for ART-experienced patients. The median time spent by a subject at the pharmacy was 35 (25.0, 48.0) minutes, half for the medication handling and half for the interview. The adherence results showed a persistence of 87% and an execution of 88%. Proportion of undetectable subjects increased during study. In conclusion, retention and persistence rates were high in this highly selected problematic population.

  15. Effect of misclassification of antiretroviral treatment status on the prevalence of transmitted HIV-1 drug resistance

    Directory of Open Access Journals (Sweden)

    Castro Hannah

    2012-03-01

    Full Text Available Abstract Background Estimates of the prevalence of transmitted HIV drug resistance (TDR in a population are derived from resistance tests performed on samples from patients thought to be naïve to antiretroviral treatment (ART. Much of the debate over reliability of estimates of the prevalence of TDR has focused on whether the sample population is representative. However estimates of the prevalence of TDR will also be distorted if some ART-experienced patients are misclassified as ART-naïve. Methods The impact of misclassification bias on the rate of TDR was examined. We developed methods to obtain adjusted estimates of the prevalence of TDR for different misclassification rates, and conducted sensitivity analyses of trends in the prevalence of TDR over time using data from the UK HIV Drug Resistance Database. Logistic regression was used to examine trends in the prevalence of TDR over time. Results The observed rate of TDR was higher than true TDR when misclassification was present and increased as the proportion of misclassification increased. As the number of naïve patients with a resistance test relative to the number of experienced patients with a test increased, the difference between true and observed TDR decreased. The observed prevalence of TDR in the UK reached a peak of 11.3% in 2002 (odds of TDR increased by 1.10 (95% CI 1.02, 1.19, p(linear trend = 0.02 per year 1997-2002 before decreasing to 7.0% in 2007 (odds of TDR decreased by 0.90 (95% CI 0.87, 0.94, p(linear trend Conclusion The effect of misclassification of ART on estimates of the prevalence of TDR may be appreciable, and depends on the number of naïve tests relative to the number of experienced tests. Researchers can examine the effect of ART misclassification on their estimates of the prevalence of TDR if such a bias is suspected.

  16. Utilization Patterns and Projected Demand of Antiretroviral Drugs in Low- and Middle-Income Countries

    Directory of Open Access Journals (Sweden)

    Françoise Renaud-Théry

    2011-01-01

    Full Text Available Background. The rapid scale-up of antiretroviral therapy in resource-limited settings has greatly increased demand for antiretroviral medicines and raised the importance of good forward planning, especially in the context of the new 2010 WHO treatment guidelines. Methods. Forecasting of the number of people receiving antiretroviral therapy from 2010 to 2012 was produced using three approaches: linear projection, country-set targets, and a restricted scenario. Two additional scenarios were then used to project the demand for various antiretroviral medicines under a fast and slower phase-out of stavudine. Results. We projected that between 7.1 million and 8.4 million people would be receiving ART by the end of 2012. Of these, 6.6% will be on second-line therapy. High variation in forecast includes reductions in the demand for d4T and d4T increases in the demand for tenofovir, emtricitabine followed by efavirenz, ritonavir, zidovudine and lopinavir; lamivudine, atazanavir, and nevirapine. Conclusion. Despite the global economic crisis and in response to the revised treatment guidelines, our model forecasts an increasing and shifting demand for antiretrovirals in resource-limited settings not only to provide treatment to new patients, but also to those switching to less toxic regimens.

  17. Prevalence of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatment.

    Science.gov (United States)

    Murillo, Wendy; de Rivera, I L; Parham, L; Jovel, E; Palou, E; Karlsson, A C; Albert, J

    2010-02-01

    The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals. We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the ANRS algorithm. Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR) = 1) vs. immunological failure (OR = 0.11; 95% confidence interval (CI) 0.030-0.43) vs. clinical failure (OR = 0.037; 95% CI 0.0063-0.22)], route of transmission (OR = 42.8; 95% CI 3.73-491), and years on therapy (OR = 1.81; 95% CI 1.11-2.93). The prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.

  18. Adverse Drug Reactions to Antiretroviral Therapy in HIV-Infected Patients at the Largest Public Hospital in Nicaragua.

    Science.gov (United States)

    Lorío, Marco; Colasanti, Jonathan; Moreira, Sumaya; Gutierrez, Gamaliel; Quant, Carlos

    2014-01-01

    Adverse drug reactions (ADRs) to antiretroviral therapy (ART) are an important cause of hospitalization, treatment discontinuation, and regimen changes in both developed and developing countries. This study is the first to examine and understand ADRs in HIV-infected patients in Nicaragua. A retrospective descriptive study was conducted from May 2010 to March 2011, in a cohort of HIV-infected patients receiving ART at the largest public hospital in Managua, Nicaragua. Patients were identified based on ADRs reporting on a standardized antiretroviral pharmacotherapy form. Subsequently, chart reviews of these patients were performed in order to document the specific ADRs. Six hundred ninety-two patients on ART were included. The incidence of ADRs was 6.4% (95% confidence interval [CI] 4.5-8.2). Females demonstrated a higher incidence, that is, 10.2% (95% CI 5.3-15.1, P = .020). Patients treated with combinations of zidovudine (ZDV)/lamivudine (3TC) and emtricitabine (FTC)/tenofovir (TDF) had fewer ADRs (P reactions. Adverse drug reactions were classified as "likely ADRs" (25 of 44) and "possible ADRs" (19 of 44). No ADRs were preventable. Adverse drug reactions most frequently affected the central nervous system. No ADR was life threatening. The frequency of ADRs in this Nicaraguan patient population was less than that reported from other studies in resource-limited settings. © The Author(s) 2014.

  19. Serious treatment related adverse drug reactions amongst anti-retroviral naïve MDR-TB patients.

    Directory of Open Access Journals (Sweden)

    Martha Van der Walt

    Full Text Available BACKGROUND: Globally treatment outcomes for multidrug-resistant Mycobacterium tuberculosis (MDR-TB remain poor and this is compounded by high drug toxicity. Little is known about the influence of adverse drug reactions (ADRs on treatment outcomes in South Africa. METHODS: We evaluated the impact of severe ADRs among a prospective cohort of MDR-TB patients in South Africa (2000-2004. The HIV-infected study participants were anti-retroviral naïve. RESULTS: Of 2,079 patients enrolled, 1,390 (66.8% were included in this analysis based on known HIV test results (39.1% HIV-infected. At least one severe ADR was reported in 83 (6.9% patients with ototoxicity being the most frequent ADR experienced (38.9%. CONCLUSIONS: We found that being HIV-infected but antiretroviral naïve did not increase occurrence of SADRs in patients on second-line anti-tuberculosis drugs. Early screening and proactive management of ADRs in this patient population is essential, especially given the rollout of decentralized care and the potential for overlapping toxicity of concomitant MDR-TB and HIV treatment.

  20. Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

    DEFF Research Database (Denmark)

    Wittkop, Linda; Günthard, Huldrych F; de Wolf, Frank

    2011-01-01

    The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration....

  1. Patterns of HIV-1 Drug Resistance After First-Line Antiretroviral Therapy (ART) Failure in 6 Sub-Saharan African Countries: Implications for Second-Line ART Strategies

    NARCIS (Netherlands)

    Hamers, Raph L.; Sigaloff, Kim C. E.; Wensing, Annemarie M.; Wallis, Carole L.; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E.; Wellington, Maureen; Osibogun, Akin; Stevens, Wendy S.; Rinke de Wit, Tobias F.; Schuurman, Rob; Siwale, M.; Njovu, C.; Labib, M.; Menke, J.; Botes, M. E.; Conradie, F.; Ive, P.; Sanne, I.; Wallis, C. L.; Letsoalo, E.; Stevens, W. S.; Hardman, M.; Wellington, M.; Luthy, R.; Mandaliya, K.; Abdallah, S.; Jao, I.; Dolan, M.; Namayanja, G.; Nakatudde, L.; Nankya, I.; Kiconco, M.; Abwola, M.; Mugyenyi, P.; Osibogun, A.; Akanmu, S.; Schuurman, R.; Wensing, A. M.; Straatsma, E.; Wit, F. W.; Dekker, J.; van Vugt, M.; Lange, J. M.

    2012-01-01

    Background. Human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy (ART). This cohort study examined patterns of drug-resistance mutations (DRMs) in individuals with virological failure on first-line ART at 13 clinical sites in 6 African

  2. Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, Alessandro; Phillips, Andrew N; Ruiz, Lidia

    2007-01-01

    (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1...... to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1...

  3. Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia

    DEFF Research Database (Denmark)

    Abdissa, Alemseged; Yilma, Daniel; Fonager, Jannik

    2014-01-01

    BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub......-Saharan Africa is sparse. METHODS: HIV viral load (VL) and resistance mutations pre-ART and after 6 months were determined in a prospective cohort study of ART-naïve HIV patients initiating first-line therapy in Jimma, Ethiopia. VL measurements were done at baseline and after 3 and 6 months. Genotypic HIV drug...... was observed among 14 (5.3%) participants out of 265 patients. Twelve samples were genotyped and six had HIV drug resistance (HIVDR) mutations at baseline. Among virological failures, 9/11 (81.8%) harbored one or more HIVDR mutations at 6 months. The most frequent mutations were K103N and M184VI. CONCLUSIONS...

  4. Standardized representation, visualization and searchable repository of antiretroviral treatment-change episodes

    Directory of Open Access Journals (Sweden)

    Rhee Soo-Yon

    2012-05-01

    Full Text Available Abstract Background To identify the determinants of successful antiretroviral (ARV therapy, researchers study the virological responses to treatment-change episodes (TCEs accompanied by baseline plasma HIV-1 RNA levels, CD4+ T lymphocyte counts, and genotypic resistance data. Such studies, however, often differ in their inclusion and virological response criteria making direct comparisons of study results problematic. Moreover, the absence of a standard method for representing the data comprising a TCE makes it difficult to apply uniform criteria in the analysis of published studies of TCEs. Results To facilitate data sharing for TCE analyses, we developed an XML (Extensible Markup Language Schema that represents the temporal relationship between plasma HIV-1 RNA levels, CD4 counts and genotypic drug resistance data surrounding an ARV treatment change. To demonstrate the adaptability of the TCE XML Schema to different clinical environments, we collaborate with four clinics to create a public repository of about 1,500 TCEs. Despite the nascent state of this TCE XML Repository, we were able to perform an analysis that generated a novel hypothesis pertaining to the optimal use of second-line therapies in resource-limited settings. We also developed an online program (TCE Finder for searching the TCE XML Repository and another program (TCE Viewer for generating a graphical depiction of a TCE from a TCE XML Schema document. Conclusions The TCE Suite of applications – the XML Schema, Viewer, Finder, and Repository – addresses several major needs in the analysis of the predictors of virological response to ARV therapy. The TCE XML Schema and Viewer facilitate sharing data comprising a TCE. The TCE Repository, the only publicly available collection of TCEs, and the TCE Finder can be used for testing the predictive value of genotypic resistance interpretation systems and potentially for generating and testing novel hypotheses pertaining to the

  5. Food insecurity as a barrier to sustained antiretroviral therapy adherence in Uganda.

    Directory of Open Access Journals (Sweden)

    Sheri D Weiser

    2010-04-01

    Full Text Available Food insecurity is emerging as an important barrier to antiretroviral (ARV adherence in sub-Saharan Africa and elsewhere, but little is known about the mechanisms through which food insecurity leads to ARV non-adherence and treatment interruptions.We conducted in-depth, open-ended interviews with 47 individuals (30 women, 17 men living with HIV/AIDS recruited from AIDS treatment programs in Mbarara and Kampala, Uganda to understand how food insecurity interferes with ARV therapy regimens. Interviews were transcribed, coded for key themes, and analyzed using grounded theory.Food insecurity was common and an important barrier to accessing medical care and ARV adherence. Five mechanisms emerged for how food insecurity can contribute to ARV non-adherence and treatment interruptions or to postponing ARV initiation: 1 ARVs increased appetite and led to intolerable hunger in the absence of food; 2 Side effects of ARVs were exacerbated in the absence of food; 3 Participants believed they should skip doses or not start on ARVs at all if they could not afford the added nutritional burden; 4 Competing demands between costs of food and medical expenses led people either to default from treatment, or to give up food and wages to get medications; 5 While working for food for long days in the fields, participants sometimes forgot medication doses. Despite these obstacles, many participants still reported high ARV adherence and exceptional motivation to continue therapy.While reports from sub-Saharan Africa show excellent adherence to ARVs, concerns remain that these successes are not sustainable in the presence of widespread poverty and food insecurity. We provide further evidence on how food insecurity can compromise sustained ARV therapy in a resource-limited setting. Addressing food insecurity as part of emerging ARV treatment programs is critical for their long-term success.

  6. New antiretrovirals: What\\'s in it for southern Africa | Venter ...

    African Journals Online (AJOL)

    The rise of novel antiretrovirals (ARVs) has introduced a new evolutionary phase in HIV care. In developed countries, the 1980s and early 1990s were characterised by palliative care and opportunistic infection prophylaxis; the late 1990s by an attempt to use a limited and toxic antiretroviral arsenal effectively while cycling ...

  7. Regional differences in use of antiretroviral agents and primary prophylaxis in 3122 European HIV-infected patients. EuroSIDA Study Group

    DEFF Research Database (Denmark)

    Lundgren, Jens Dilling; Phillips, A N; Vella, S

    1997-01-01

    Little is known about how widely HIV-related drugs are used outside controlled clinical trials. We therefore assessed factors associated with use of antiretroviral (ARV) therapy and primary prophylactic regimens to prevent HIV-associated opportunistic infections. Baseline data from a prospective...... was higher in central Europe compared with other regions (27%, 50%, and 31% for southern, central, and northern Europe, respectively, p pneumonia (PCP) was used by 85% of patients with a CD4 count ... count risk patients. U.S. recommendations on the use...

  8. Treatment Adherence and Outcomes of Antiretroviral Agents in HIV Positive Patients

    International Nuclear Information System (INIS)

    Tahir, N. B.; Uddin, Q. T.

    2014-01-01

    Objective: To describe the treatment outcomes in terms of adherence, outcomes and side effects of antiretroviral (ARV) agents. Study Design: An observational study. Place and Duration of Study: Teaching Hospital of Khyber Medical University, Institute of Medical Sciences, Kohat, from February 2007 to December 2012. Methodology: Human Immunodeficiency Virus (HIV) positive patients, taking 1st line ARV agents for at least 6 months were included. Adherence was calculated by self report on asking the number of doses missed in last 30 days. ARVs were provided on monthly basis. Adherence data was noted over a period of 6 months. ARVs outcomes were recorded in the form of adherence, CD4 count, functional status of the patient, change in weight, further transmission of the disease, number of hospital admissions and deaths. Adverse Drug Reactions (ARDs) to ARVs were assessed clinically and by laboratory markers. Mean and standard deviation were calculated for numerical variables while frequencies and percentages were calculated for categorical variables. Results: Total number of patients included in this study were 107. Out of them, 66.4% were males and 33.6% were females. The mean age was 39.9 +- 13.80 years. Patients taking AZT/3TC/NVP, AZT/3TC/EFZ, D4T/3TC/NVP, D4T/3TC/EFZ, TNF/3TC/NVP or EFZ were 49.5%, 22.4%, 10.3%, 4.7% and 13% respectively. Most adverse affects were observed in 10 days to 90 days of initiation of therapy. Rash was observed in 71 (66.4%) patients, anaemia in 4 (3.7%) patients while only one patient (0.93%) had nausea / vomiting. Thirty (28%) patients reported no side effects. Out of 107 patients, 98 (91.5%) were alive whereas 9 (8.4%) died at the end of the study period. Twelve patients had one hospital admission (11.21%) whereas 9 (8.4%) patients had two admissions during the study period. The first mean CD4 was 325.27 cells /mcL whereas mean last CD4 count was 389.86 cells/mcL. Conclusion: ARVs have very satisfactory outcomes in HIV/AIDS patients

  9. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study

    DEFF Research Database (Denmark)

    Worm, Signe Westring; Sabin, Caroline; Weber, Rainer

    2010-01-01

    BACKGROUND. The risk of myocardial infarction (MI) in patients with human immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. METHODS. Poisson regression models were adjusted for cardiovascular risk...... factors, cohort, calendar year, and use of other antiretroviral drugs and assessed the association between MI risk and cumulative (per year) or recent (current or in the past 6 months) use of antiretroviral drugs, with >30,000 person-years of exposure. RESULTS. Over 178,835 person-years, 580 patients......% CI, 1.01-1.17], respectively) after adjustment for lipids but were not altered further after adjustment for other metabolic parameters. CONCLUSIONS. Of the drugs considered, only indinavir, lopinavir-ritonavir, didanosine, and abacavir were associated with a significantly increased risk of MI...

  10. Antiretroviral Drug as a Cause of Bilateral Avascular Necrosis of the ...

    African Journals Online (AJOL)

    Background: Avascular necrosis (AVN) is one of the most dreadful disease conditions of the hip which may be very difficult to treat if not detected early. Protease inhibitor is useful in combined antiretroviral therapy but now being reported as one of the causes of AVN. In this case report, we present a case of bilateral ...

  11. An appeal for large scale production of antiretroviral drugs in Africa ...

    African Journals Online (AJOL)

    activities, including the supply of Antiretroviral Treatment (ART), highlights the concern of sustainability. So far, solutions that have been proposed are mainly symptomatic, claiming more budget commitment from government. Without rejecting this view, we call for the implementation of sustainable solutions to deal with the ...

  12. Islamic perspectives on HIV/AIDS and antiretroviral treatment: the case of Nigeria.

    Science.gov (United States)

    Balogun, Amusa Saheed

    2010-12-01

    Some religious reactions to the HIV epidemic in Africa unwittingly contributed to the expansion of the epidemic in its early years. This was because many religious people regarded the emergence of HIV and AIDS as divine punishment for man's sins as a result of people's sexual promiscuity. Some also opposed public promotion of the use of condoms for HIV prevention. However, religious bodies have made positive contributions to HIV/AIDS responses in many African countries in recent times. Though Christian bodies are taking the lead in faith-based responses to HIV and AIDS in Africa, Islamic bodies have also been major partners in HIV/AIDS interventions in several countries. Against this background, this article examines some Islamic perceptions of HIV and AIDS, and especially the impact of antiretroviral treatment (ART) for people living with HIV in Africa, with particular emphasis on Nigeria. In spite of the emergence of antiretroviral (ARV) drugs in Africa, Islam still emphasises the prevention of new infections and care for people living with HIV or AIDS. The article discusses basic issues associated with ARVs, such as health, sickness, life-prolongation and death, from an Islamic viewpoint, as well as some Islamic measures to prevent HIV-risk-taking behaviours in an era of ARVs. It also looks at the nature and extent of Islamic involvement in the national HIV/AIDS response in Nigeria. The paper concludes that while Islam sees HIV and AIDS and other diseases as 'tests' from Allah, the religion is not opposed to ART. Thus, efforts need to be intensified by Islamic bodies and Muslim leaders in Nigeria for an improved response to HIV and AIDS in the country.

  13. RISK FACTORS OF HIV-1 VERTICAL TRANSMISSION (VT AND THE INFLUENCE OF ANTIRETROVIRAL THERAPY (ART IN PREGNANCY OUTCOME

    Directory of Open Access Journals (Sweden)

    Maria F.M. Barral

    2014-04-01

    Full Text Available In the absence of intervention, the rate of vertical transmission of HIV can range from 15-45%. With the inclusion of antiretroviral drugs during pregnancy and the choice of delivery route this amounts to less than 2%. However ARV use during pregnancy has generated several questions regarding the adverse effects of the gestational and neonatal outcome. This study aims to analyze the risk factors for vertical transmission of HIV-1 seropositive pregnant women living in Rio Grande and the influence of the use of ARVs in pregnancy outcome. Among the 262 pregnant women studied the rate of vertical transmission of HIV was found to be 3.8%. Regarding the VT, there was a lower risk of transmission when antiretroviral drugs were used and prenatal care was conducted at the referral service. However, the use of ART did not influence the outcome of pregnancy. However, initiation of prenatal care after the first trimester had an influence on low birth weight, as well as performance of less than six visits increased the risk of prematurity. Therefore, the risk factors analyzed in this study appear to be related to the realization of inadequate pre-natal and maternal behavior.

  14. Risk factors of HIV-1 vertical transmission (VT) and the influence of antiretroviral therapy (ART) in pregnancy outcome.

    Science.gov (United States)

    Barral, Maria F M; de Oliveira, Gisele R; Lobato, Rubens C; Mendoza-Sassi, Raul A; Martínez, Ana M B; Gonçalves, Carla V

    2014-01-01

    In the absence of intervention, the rate of vertical transmission of HIV can range from 15-45%. With the inclusion of antiretroviral drugs during pregnancy and the choice of delivery route this amounts to less than 2%. However ARV use during pregnancy has generated several questions regarding the adverse effects of the gestational and neonatal outcome. This study aims to analyze the risk factors for vertical transmission of HIV-1 seropositive pregnant women living in Rio Grande and the influence of the use of ARVs in pregnancy outcome. Among the 262 pregnant women studied the rate of vertical transmission of HIV was found to be 3.8%. Regarding the VT, there was a lower risk of transmission when antiretroviral drugs were used and prenatal care was conducted at the referral service. However, the use of ART did not influence the outcome of pregnancy. However, initiation of prenatal care after the first trimester had an influence on low birth weight, as well as performance of less than six visits increased the risk of prematurity. Therefore, the risk factors analyzed in this study appear to be related to the realization of inadequate pre-natal and maternal behavior.

  15. Clinic Attendance for Medication Refills and Medication Adherence amongst an Antiretroviral Treatment Cohort in Uganda: A Prospective Study

    Directory of Open Access Journals (Sweden)

    Setor Kunutsor

    2010-01-01

    Full Text Available Background. Regular clinic attendance for antiretroviral (ARV drug refills is important for successful clinical outcomes in HIV management. Methods. Clinic attendance for ARV drug refills and medication adherence using a clinic-based pill count in 392 adult patients receiving antiretroviral therapy (ART in a district hospital in Uganda were prospectively monitored over a 28-week period. Results. Of the 2267 total scheduled clinic visits, 40 (1.8% were missed visits. Among the 392 clients, 361 (92% attended all appointments for their refills (regular attendance. Clinic attendance for refills was statistically significantly associated with medication adherence with regular attendant clients having about fourfold greater odds of achieving optimal (≥95% medication adherence [odds ratio (OR=3.89, 95% CI: 1.48 to 10.25, exact P=.013]. In multivariate analysis, clients in age category 35 years and below were less likely to achieve regular clinic attendance. Conclusion. Monitoring of clinic attendance may be an objective and effective measure and could be a useful adjunct to an adherence measure such as pill counting in resource-constrained settings. Where human resource constraints do not allow pill counts or other time-consuming measures, then monitoring clinic attendance and acting on missed appointments may be an effective proxy measure.

  16. hiv management rural arv provision – policy implications for ...

    African Journals Online (AJOL)

    2006-12-02

    Dec 2, 2006 ... high level of horizontal integration of the ARV programme into existing PHC services from the start. ... different approaches, the integration of ARV services into PHC level of care is key in the success of many ... be linked to TB tracing teams, home-based care systems, community health worker programmes ...

  17. Towards universal ARV access: Achievements and challenges in ...

    African Journals Online (AJOL)

    New ARV enrolments increased annually to 25% of the estimated need by the end of 2007. Average waiting times to enrolment decreased from 5.82 months to 3.24 months. Median CD4 counts at enrolment increased from 89 to 124 cells/μl. There is a staff vacancy rate of 38% in the ARV programme and an inadequate ...

  18. Simultaneous determination of antiretroviral drugs in human hair with liquid chromatography-electrospray ionization-tandem mass spectrometry.

    Science.gov (United States)

    Wu, Yan; Yang, Jin; Duan, Cailing; Chu, Liuxi; Chen, Shenghuo; Qiao, Shan; Li, Xiaoming; Deng, Huihua

    2018-04-15

    The determination of the concentrations of antiretroviral drugs in hair is believed to be an important means for the assessment of the long-term adherence to highly active antiretroviral therapy. At present, the combination of tenofovir, lamivudine and nevirapine is widely used in China. However, there was no research reporting simultaneous determination of the three drugs in hair. The present study aimed to develop a sensitive method for simultaneous determination of the three drugs in 2-mg and 10-mg natural hair (Method 1 and Method 2). Hair samples were incubated in methanol at 37 °C for 16 h after being rinsed with methanol twice. The analysis was performed on high performance liquid chromatography tandem mass spectrometry with electronic spray ionization in positive mode and multiple reactions monitoring. Method 1 and Method 2 showed the limits of detection at 160 and 30 pg/mg for tenofovir, at 5 and 6 pg/mg for lamivudine and at 15 and 3 pg/mg for nevirapine. The two methods showed good linearity with the square of correlation coefficient >0.99 at the ranges of 416-5000 and 77-5000 pg/mg for tenofovir, 12-5000 and 15-5000 pg/mg for lamivudine and 39-50,000 and 6-50,000 pg/mg for nevirapine. They gave intra-day and inter-day coefficient of variation <15% and the recoveries ranging from 80.6 to 122.3% and from 83.1 to 114.4%. Method 2 showed LOD and LOQ better than Method 1 for tenofovir and nevirapine and matched Method 1 for lamivudine, but there was high consistency between them in the determination of the three drugs in hair. The population analysis with Method 2 revealed that the concentrations in hair were decreased with the distance of hair segment away from the scalp for the three antiretroviral drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Risks of cardiovascular or central nervous system adverse events and immune reconstitution inflammatory syndrome, for dolutegravir versus other antiretrovirals: meta-analysis of randomized trials.

    Science.gov (United States)

    Hill, Andrew M; Mitchell, Nikkita; Hughes, Sophie; Pozniak, Anton L

    2018-03-01

    Results from nonrandomized cohort studies suggest higher risks of CNS adverse events for dolutegravir, versus other ARVs. There have been two case reports of myocarditis on dolutegravir. Integrase inhibitors have been associated with IRIS in two cohort studies. Meta-analysis of randomized trials can be used to cross-check potential safety signals. This systematic review of drug safety used an EMBASE and MEDLINE search combined with serious adverse event (SAE) reports on the website www.clinicaltrials.gov. Cardiovascular, CNS or IRIS-associated adverse events were analysed for dolutegravir versus other ARVs. Relative risks for the comparison between dolutegravir and other antiretrovirals were calculated for each adverse event. Meta-analyses applied Mantel-Haenszel random-effects models. There was a higher risk of Grade 1-4 insomnia adverse events for DTG (6.1%) versus other ARVs (4.5%; P = 0.02). There was no significant difference between DTG and other ARVs in the risk of cardiovascular serious adverse events. In the SINGLE and SPRING-1 trials comparing DTG with efavirenz, there were 5/465 patients with reported suicidality SAEs on DTG (1.1%) versus 6/469 (1.3%) on EFV. In other studies, serious adverse events of suicidality were reported for 15/2250 patients on DTG (0.7%) versus 9/2257 patients on other ARVs (0.4%). Risks of IRIS were low, but event rates were low and the main trials excluded CDC stage C disease. In this meta-analysis, there was no significant effect of dolutegravir on the risk of cardiac, IRIS or suicide-related serious adverse events. There was a higher risk of insomnia for DTG. Other completed randomized trials should be included in new evaluations of DTG safety. Continued pharmacovigilance, with regular meta-analyses, should be used to monitor safety.

  20. Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

    Science.gov (United States)

    Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

    2016-07-01

    Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

  1. Evaluation of 4 weeks' neonatal antiretroviral prophylaxis as a component of a prevention of mother-to-child transmission program in a resource-rich setting.

    LENUS (Irish Health Repository)

    Ferguson, Wendy

    2011-05-01

    In resource-rich settings, universal adoption of a 4- rather than 6-week neonatal antiretroviral (ARV) prophylaxis regimen could reduce toxicity and results in cost savings, provided prevention of mother-to-child transmission program effectiveness is not compromised.

  2. The First Characterization of HIV-1 Subtypes and Drug Resistance Mutations among Antiretrovirally Treated Patients in Kermanshah, Iran.

    Science.gov (United States)

    Golmohammadi, Reza; Baesi, Kazem; Moradi, Abdolvahab; Farrokhi, Molood; McFarland, Willi; Parsamajd, Shahryar

    2017-01-01

    Insufficient therapy during HIV-1 replication can promote the emergence of drug-resistant strains, reduce the effectiveness of antiretroviral treatment (ART), and increase the likelihood of the onward transmission of drug-resistant viruses. We characterized, for the first time, the prevalence of HIV-1 subtypes and drug resistance mutations in a western region of Iran. This study was conducted among 122 patients on ART at a major referral center in Kermanshah, Iran. Nested PCR was performed using RT gene-specific primers from the pol gene. Sequencing was followed by amplification and purification of the desired sequence. Subtypes and mutations were determined using the Stanford HIV Drug Resistance Database. Most patients (92.6%) had subtype CRF 35-AD; 7.4% had subtype B. In total, 36.1% of the patients had at least 1 mutation associated with resistance RT inhibitors. The greatest rates of high-level resistance were observed for nevirapine (21.3%) and efavirenz (19.7%). Our results showed a high prevalence of drug resistance mutations in strains isolated from patients on treatment. At our center, we therefore recommend that genotyping be performed. This would allow the physician to prescribe appropriate drugs, reduce treatment costs, and increase the longevity and quality of life of patients. © 2017 S. Karger AG, Basel.

  3. Is infant exposure to antiretroviral drugs during breastfeeding quantitatively important? A systematic review and meta-analysis of pharmacokinetic studies

    Science.gov (United States)

    Waitt, Catriona John; Garner, Paul; Bonnett, Laura Jayne; Khoo, Saye Hock; Else, Laura Jayne

    2015-01-01

    Objectives The objectives of this study were to summarize antiretroviral drug concentrations in breast milk (BM) and exposure of breast-fed infants. Methods This was a systematic review of pharmacokinetic studies of HIV-positive women taking antiretrovirals that measured drugs in BM. The quality of pharmacokinetic and laboratory methods was assessed using pre-defined criteria. Pooled ratios and 95% CIs were calculated using the generalized inverse variance method and heterogeneity was estimated by the I2 statistic. PubMed Central, SCOPUS and LactMed databases were searched. No date or language restrictions were applied. Searches were conducted up to 10 November 2014. Clinical relevance was estimated by comparing ingested dose with the recommended therapeutic dose for each drug. Results Twenty-four studies were included. There was substantial variability in the clinical and laboratory methods used and in reported results. Relative to maternal plasma (MP), NRTIs accumulate in BM, with BM : MP ratios (95% CI estimates) from 0.89 to 1.21 (14 studies, 1159 paired BM and MP samples). NNRTI estimates were from 0.71 to 0.94 (17 studies, 965 paired samples) and PI estimates were from 0.17 to 0.21 (8 studies, 477 paired samples). Relative to the recommended paediatric doses, a breast-fed infant may ingest 8.4% (95% CI 1.9–15.0), 12.5% (95% CI 2.6–22.3) and 1.1% (95% CI 0–3.6) of lamivudine, nevirapine and efavirenz, respectively, via BM. Conclusions Transfer to untreated infants appears quantitatively important for some NRTIs and NNRTIs. The pharmacokinetic methods varied widely and we propose standards for the design, analysis and reporting of future pharmacokinetic studies of drug transfer during breastfeeding. PMID:25858354

  4. HIV-related symptoms and management in HIV and antiretroviral ...

    African Journals Online (AJOL)

    Karl Peltzer

    2014-01-03

    Jan 3, 2014 ... To cite this article: Karl Peltzer (2013) HIV-related symptoms and management in HIV and antiretroviral therapy patients in KwaZulu-Natal ..... ARV-related symptoms they had experienced, list the strategies. (medications .... over weight loss, headaches, dry mouth, memory loss, and weakness; at Time 2,.

  5. HIV-related symptoms and management in HIV and antiretroviral ...

    African Journals Online (AJOL)

    reportedmanagement of HIV- or ARV-related symptoms among HIVpatients prior to antiretroviral therapy (ART) and over three time points while receivingARTinKwaZulu-Natal, SouthAfrica. Method: A total of 735 consecutive patients (29.8% male and ...

  6. Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Cozzi-Lepri, Alessandro; Clotet, Bonaventura

    2008-01-01

    OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients...... with detection of TDR, with virological (viral loadresponse (>or=50% increase) to combination antiretroviral therapy at months 6-12. RESULTS: The overall prevalence of TDR was 11.4%, which was stable over 1996-2004. There were no significant differences in virological suppression...... (those resistant to at least one drug prescribed versus susceptible), adjusted odds ratio: 0.68 (95% confidence interval: 0.27 to 1.71; P=0.408) or CD4 count response, adjusted odds ratio: 1.65 (95% confidence interval: 0.73 to 3.73; P=0.231). CONCLUSIONS: Prevalence of TDR in antiretroviral...

  7. HIV drug resistance early warning indicators in cohorts of individuals starting antiretroviral therapy between 2004 and 2009: World Health Organization global report from 50 countries.

    Science.gov (United States)

    Bennett, Diane E; Jordan, Michael R; Bertagnolio, Silvia; Hong, Steven Y; Ravasi, Giovanni; McMahon, James H; Saadani, Ahmed; Kelley, Karen F

    2012-05-01

    The World Health Organization developed a set of human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) to assess antiretroviral therapy clinic and program factors associated with HIVDR. EWIs are monitored by abstracting data routinely recorded in clinical records, and the results enable clinics and program managers to identify problems that should be addressed to minimize preventable emergence of HIVDR in clinic populations. As of June 2011, 50 countries monitored EWIs, covering 131 686 patients initiating antiretroviral treatment between 2004 and 2009 at 2107 clinics. HIVDR prevention is associated with patient care (appropriate prescribing and patient monitoring), patient behavior (adherence), and clinic/program management efforts to reduce treatment interruptions (follow up, retention on first-line ART, procurement and supply management of antiretroviral drugs). EWIs measure these factors and the results have been used to optimize patient and population treatment outcomes.

  8. Prediction of phenotypic susceptibility to antiretroviral drugs using physiochemical properties of the primary enzymatic structure combined with artificial neural networks

    DEFF Research Database (Denmark)

    Kjaer, J; Høj, L; Fox, Z

    2008-01-01

    of physiochemical properties for mutations in HIV-1 protease (PR) and reverse transcriptase (RT) to predict phenotypic susceptibility to all currently approved ARVs. METHOD: We extracted pairs of PR and RT gene sequences (n=1507; 98.5% sub-type B) and their corresponding exact phenotype values (PhenoSense only, n...... coefficient was 0.89. CONCLUSIONS: ANNs, based on the physiochemical properties of the PR and RT amino-acid sequences, predict phenotypic susceptibility to ARVs inhibiting these enzymes to an extent that is comparable to routine phenotypic susceptibility testing. These ANNs can also be used to predict...

  9. Depo-medroxyprogesterone in women on antiretroviral therapy: effective contraception and lack of clinically significant interactions.

    Science.gov (United States)

    Cohn, S E; Park, J-G; Watts, D H; Stek, A; Hitti, J; Clax, P A; Yu, S; Lertora, J J L

    2007-02-01

    We conducted an open-label, steady-state pharmacokinetic (PK) study of drug interactions among HIV-infected women treated with depo-medroxyprogesterone acetate (DMPA) while on nucleoside analogues plus nelfinavir (N=21), efavirenz (N=17), or nevirapine (N=16); or nucleosides only or no antiretroviral therapy as a control group (N=16). PK parameters were estimated using non-compartmental analysis, with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of ARV PKs before and 4 weeks after DMPA dosing. Plasma progesterone levels were measured at baseline and at 2, 4, 6, 8, 10, and 12 weeks after DMPA dosing. There were no significant changes in MPA area under the concentration curve, peak or trough concentrations, or apparent clearance in the nelfinavir, efavirenz, or nevirapine groups compared to the control group. Minor changes in nelfinavir and nevirapine drug exposure were seen after DMPA, but were not considered clinically significant. Suppression of ovulation was maintained.

  10. Highly active antiretroviral therapy (HAART) among HIV-infected drug users: a prospective cohort study of sexual risk and injecting behaviour

    NARCIS (Netherlands)

    Smit, Colette; Lindenburg, Karen; Geskus, Ronald B.; Brinkman, Kees; Coutinho, Roel A.; Prins, Maria

    2006-01-01

    AIMS: To study sexual risk and injecting behaviour among HIV-infected drug users (DU) receiving highly active antiretroviral therapy (HAART). DESIGN AND SETTING: As part of an ongoing prospective cohort study, HIV-infected DU who commenced HAART (n=67) were matched with those not starting HAART

  11. Long-term effectiveness of combination antiretroviral therapy and prevalence of HIV drug resistance in HIV-1-infected children and adolescents in Rwanda

    NARCIS (Netherlands)

    Mutwa, Philippe R.; Boer, Kimberly R.; Rusine, John; Muganga, Narcisse; Tuyishimire, Diane; Schuurman, Rob; Reiss, Peter; Lange, Joep M. A.; Geelen, Sibyl P. M.

    2014-01-01

    To determine the long-term outcomes of treatment and prevalence of genotypic drug resistance in children and adolescents on combination antiretroviral therapy. A cross-sectional study (September 2009 to October 2010) in which clinical, immunologic and virologic outcomes were assessed at a

  12. Payment for antiretroviral drugs is associated with a higher rate of patients lost to follow-up than those offered free-of-charge therapy in Nairobi, Kenya

    NARCIS (Netherlands)

    Zachariah, R.; van Engelgem, I.; Massaquoi, M.; Kocholla, L.; Manzi, M.; Suleh, A.; Phillips, M.; Borgdorff, M.

    2008-01-01

    This retrospective analysis of routine programme data from Mbagathi District Hospital, Nairobi, Kenya shows the difference in rates of loss to follow-up between a cohort that paid 500 shillings/month (approximately US$7) for antiretroviral drugs (ART) and one that received medication free of charge.

  13. Genital tract, cord blood, and amniotic fluid exposures of seven antiretroviral drugs during and after pregnancy in human immunodeficiency virus type 1-infected women.

    Science.gov (United States)

    Yeh, Rosa F; Rezk, Naser L; Kashuba, Angela D M; Dumond, Julie B; Tappouni, Hiba L; Tien, Hsiao-Chuan; Chen, Ya-Chi; Vourvahis, Manoli; Horton, Amanda L; Fiscus, Susan A; Patterson, Kristine B

    2009-06-01

    The objective of the study was to measure antiretroviral exposures in four physiological compartments during pregnancy, delivery, and postpartum. This prospective, open-label, longitudinal study collected paired blood plasma (BP) and genital tract (GT) aspirates antepartum, at delivery, and up to 12 weeks postpartum. Antiretroviral cord BP and amniotic fluid concentrations were also measured. Drug concentrations were analyzed by validated high-performance liquid chromatography/UV and liquid chromatography/tandem mass spectrometry methods, with secondary compartment concentrations presented as the percentage of BP. Fourteen women taking lamivudine plus zidovudine and either lopinavir-ritonavir (n = 7), nelfinavir (n = 6), or nevirapine (n = 1) were enrolled; four also received tenofovir. GT penetration relative to BP was highest for the nucleoside reverse transcriptase inhibitors compared to the protease inhibitors and nevirapine. Only antepartum nelfinavir GT penetration was significantly higher than in the second trimester (geometric mean ratio [GMR], 179.3) or third trimester (GMR, 41.9). Compared to nonpregnant historical controls, antepartum GT penetration was significantly lower (P or = 100%), with cord BP levels of the remaining drugs ranging from 49 to 86% of that of the respective BP level. Amniotic exposures for lamivudine, zidovudine, tenofovir, and nelfinavir were > or = 100%, nevirapine exposure was 53%, and lopinavir and ritonavir exposures were amniotic fluid exposures vary within and between antiretroviral drug classes and biologic sites. Measurement of antiretroviral exposure in maternal genital secretions, cord BP, and amniotic fluid may be needed to identify signals of subtherapeutic or supratherapeutic drug exposure.

  14. Prevalence and Factors Associated with Fixed-Dose Combination Antiretroviral Drugs Adherence among HIV-Positive Pregnant Women on Option B Treatment in Mpumalanga Province, South Africa

    Directory of Open Access Journals (Sweden)

    Shandir Ramlagan

    2018-01-01

    Full Text Available The possibility for all babies to be born and remain HIV-negative for the first year of life is achievable in South Africa. HIV-positive mothers’ adherence to their antiretroviral medication is one of the crucial factors to achieve this target. Cross-sectional data were collected at 12 community health centres, over 12 months (2014–2015, from 673 HIV-positive women, less than 6 months pregnant, attending antenatal care, and on Option B treatment. Adherence measures included the Adults AIDS Clinical Trials Group (AACTG four-day measure, as well as the Visual Analog Scale (VAS seven-day measure. Bivariate analyses and multivariate logistic regressions are presented. 78.8% of respondents were adherent on AACTG, while 68.8% reported VAS adherence. Bivariate analyses for increased adherence show significant associations with older age, less/no alcohol usage, disclosure of HIV status, higher HIV knowledge, no desire to avoid ARV side effects, low stigma, and low depression. AACTG showed a negative association with intimate partner violence. Multivariable logistic regression on AACTG and VAS adherence rates resulted in unique contributions to increased adherence of older age, less/no alcohol usage, higher HIV knowledge, lack of depression, and non-disclosure. Programs targeting closer side effect monitoring, HIV disclosure, pre-natal depression, alcohol intake, and HIV knowledge need consideration.

  15. Antiretroviral therapy adherence and self-efficacy among people living with HIV and a history of drug use in Vietnam.

    Science.gov (United States)

    Li, Li; Lin, Chunqing; Lee, Sung-Jae; Tuan, Le Anh; Feng, Nan; Tuan, Nguyen Anh

    2017-10-01

    People living with HIV with a history of drug use face additional psychosocial challenges that could compromise their adherence to antiretroviral therapy (ART). This study examined ART treatment adherence and adherence self-efficacy among people living with HIV with a history of drug use in Vietnam. We used cross-sectional baseline data collected between October 2014 and February 2015 from a randomized controlled trial in Vietnam. Of the 900 persons with a history of drug use in the trial, a sample of 109 people living with HIV currently on ART were included in the study. The vast majority (92%) of the participants reported not missing any medications in the past 30 days. Multiple regression results indicated that social support was positively associated with adherence self-efficacy (β = 0.420, P social challenges facing people living with HIV with a history of drug use to promote ART treatment adherence. Clinical management of HIV should identify and address concurrent substance use behaviors to maximize adherence and treatment outcomes.

  16. Antiretroviral therapy for prevention of HIV transmission: potential role for people who inject drugs in Central Asia.

    Science.gov (United States)

    McNairy, Margaret L; Deryabina, Anna; Hoos, David; El-Sadr, Wafaa M

    2013-11-01

    Interest in the use of antiretroviral therapy (ART) for prevention stems from mounting evidence from research studies demonstrating that ART is associated with a decrease in sexual HIV transmission among serodiscordant couples and, perhaps, in other populations at risk. There is paucity of data on the efficacy of ART for prevention in key populations, including persons who inject drugs (PWID). In this paper, we examine the current status of HIV services for PWID in Central Asia, the use of ART by this population and explore ART for prevention for PWID in this context. We also discuss research and implementation questions with relevance to such a strategy in the region. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Significant interaction between activated charcoal and antiretroviral therapy leading to subtherapeutic drug concentrations, virological breakthrough and development of resistance.

    Science.gov (United States)

    Tseng, Alice L; la Porte, Charles; Salit, Irving E

    2013-01-01

    A 42-year-old, treatment-experienced woman, virologically suppressed on tenofovir/emtricitabine and boosted atazanavir, experienced virological breakthrough, drop in CD4(+) T-cell count and undetectable drug concentrations. Adherence to treatment was confirmed, but repeat testing yielded similar results. After 2 months, the patient stated that she had been taking activated charcoal to manage gastrointestinal symptoms associated with her combination antiretroviral therapy, but she had recently discontinued the charcoal. Atazanavir concentrations were therapeutic but the patient's viral load rebounded and genotype testing revealed new reverse transcriptase mutations. The patient was changed to zidovudine, lamivudine, and boosted darunavir and achieved viral suppression. At 1 year follow-up, her viral load remained activated charcoal and atazanavir/ritonavir leading to virological breakthrough and development of resistance.

  18. Low Non-structured Antiretroviral Therapy Interruptions in HIV-Infected Persons Who Inject Drugs Receiving Multidisciplinary Comprehensive HIV Care at an Outpatient Drug Abuse Treatment Center.

    Science.gov (United States)

    Vallecillo, Gabriel; Mojal, Sergio; Roquer, Albert; Samos, Pilar; Luque, Sonia; Martinez, Diana; Martires, Paula Karen; Torrens, Marta

    2016-05-01

    Continuous HIV treatment is necessary to ensure successful combined antiretroviral therapy (cART). The aim of this study was to evaluate the incidence of patient-initiated non-structured treatment interruptions in HIV-infected persons who inject drugs and who received a multidisciplinary comprehensive program, including medical HIV care, drug-dependence treatment and psychosocial support, at a drug outpatient addiction center. Non-structured treatment interruptions were defined as ≥30 consecutive days off cART without medical indication. During a median follow-up of 53.8 months, 37/132 (28 %) patients experienced the first non-structured treatment interruptions. The cumulative probability of cART interruption at 5 years was 31.2 % (95 % CI 22.4-40.0). Current drug use injection ≥1/day (HR 14.77; 95 % CI 5.90-36.96) and cART naive patients (HR 0.35, 95 % CI 0.14-0.93) were predictive factors for non-structured treatment interruptions. HIV care provided at a drug addiction center is a useful strategy to sustain continuous cART, however, drug abstinence is essential for the long-term maintenance of cART.

  19. Antiretroviral neuropenetration scores better correlate with cognitive performance of HIV-infected patients after accounting for drug susceptibility.

    Science.gov (United States)

    Fabbiani, Massimiliano; Grima, Pierfrancesco; Milanini, Benedetta; Mondi, Annalisa; Baldonero, Eleonora; Ciccarelli, Nicoletta; Cauda, Roberto; Silveri, Maria C; De Luca, Andrea; Di Giambenedetto, Simona

    2015-01-01

    The aim of the study was to explore how viral resistance and antiretroviral central nervous system (CNS) penetration could impact on cognitive performance of HIV-infected patients. We performed a multicentre cross-sectional study enrolling HIV-infected patients undergoing neuropsychological testing, with a previous genotypic resistance test on plasma samples. CNS penetration-effectiveness (CPE) scores and genotypic susceptibility scores (GSS) were calculated for each regimen. A composite score (CPE-GSS) was then constructed. Factors associated with cognitive impairment were investigated by logistic regression analysis. A total of 215 patients were included. Mean CPE was 7.1 (95% CI 6.9, 7.3) with 206 (95.8%) patients showing a CPE≥6. GSS correction decreased the CPE value in 21.4% (mean 6.5, 95% CI 6.3, 6.7), 26.5% (mean 6.4, 95% CI 6.1, 6.6) and 24.2% (mean 6.4, 95% CI 6.2, 6.6) of subjects using ANRS, HIVDB and REGA rules, respectively. Overall, 66 (30.7%) patients were considered cognitively impaired. No significant association could be demonstrated between CPE and cognitive impairment. However, higher GSS-CPE was associated with a lower risk of cognitive impairment (CPE-GSSANRS odds ratio 0.75, P=0.022; CPE-GSSHIVDB odds ratio 0.77, P=0.038; CPE-GSSREGA odds ratio 0.78, P=0.038). Overall, a cutoff of CPE-GSS≥5 seemed the most discriminatory according to each different interpretation system. GSS-corrected CPE score showed a better correlation with neurocognitive performance than the standard CPE score. These results suggest that antiretroviral drug susceptibility, besides drug CNS penetration, can play a role in the control of HIV-associated neurocognitive disorders.

  20. Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa.

    Directory of Open Access Journals (Sweden)

    Theresa M Rossouw

    Full Text Available Limited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors.Data from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis.The study included 65 young children (median age 16.8 months [IQR 7.8; 23.3] with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease, severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;-2.4], high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47 and frequent tuberculosis co-infection (66% at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05; longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005; unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001; tuberculosis treatment at antiretroviral therapy initiation (p = 0.048 and use of ritonavir as single protease inhibitor (p = 0.038. On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033.Major protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy

  1. HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya.

    Science.gov (United States)

    Koigi, Peter; Ngayo, Musa Otieno; Khamadi, Samoel; Ngugi, Caroline; Nyamache, Anthony Kebira

    2014-12-09

    The ever-expanding rollout of antiretroviral therapy in poor resource settings without routine virological monitoring has been accompanied with development of drug resistance that has resulted in limited treatment success. A cross-sectional study with one time viral load was conducted during the period between 2012 and 2013 to determine treatment failure and drug resistance mutations among adults receiving first-line (44) (3TC_d4T/AZT_NVP/EFV) and second-line (20) (3TC/AZT/LPV/r) in Nairobi, Kenya. HIV-1 pol-RT genotyping for drug resistance was performed using an in-house protocol. A total of 64 patients were recruited (mean age 36.9 yrs.) during the period between 2012 and 2013 of the 44 adult patients failing first-line 24 (40.9%) had drug resistance mutations. Eight (8) patients had NRTI resistance mutations with NAMS M184V (54.2%) and K65R (8.4%) mutations being the highest followed by TAMs T215Y and K70R (12.5%). In addition, among patients failing second-line (20), six patients (30%) had NNRTI resistance; two patients on K103N and G190A mutations while V106A, Y184V, A98G, Y181C mutations per patient were also detected. However, for NRTI two patients had TAM T215Y. M184V mutation occurred in one patient. The study findings showed that HIV-1 drug resistance was significantly high in the study population. The detected accumulated resistance strains show that emergence of HIV drug resistance will continue to be a big challenge and should be given more attention as the scale up of treatment in the country continues.

  2. Influence of ARVs on Some Biochemical Changes in Liver Non ...

    African Journals Online (AJOL)

    Influence of ARVs on Some Biochemical Changes in Liver Non Enzymatic Markers of HIV Positive Patients Attending Specialist Hospital Sokoto, Nigeria. MG Abubakar, MM Abduljalil, G Bola-Alaka, YI Nasiru ...

  3. Hybrid Underwater Vehicle: ARV Design and Development

    Directory of Open Access Journals (Sweden)

    Zhigang DENG

    2014-02-01

    Full Text Available The development of SMU-I, a new autonomous & remotely-operated vehicle (ARV is described. Since it has both the characteristics of autonomous underwater vehicle (AUV and remote operated underwater vehicle (ROV, it is able to achieve precision fix station operation and manual timely intervention. In the paper the initial design of basic components, such as vehicle, propulsion, batteries etc. and the control design of motion are introduced and analyzed. ROV’s conventional cable is replaced by a fiber optic cable, which makes it available for high-bandwidth real-time video, data telemetry and high-quality teleoperation. Furthermore, with the aid of the manual real-time remote operation and ranging sonar, it also resolves the AUV’s conflicting issue, which can absolutely adapt the actual complex sea environment and satisfy the unknown mission need. The whole battery system is designed as two-battery banks, whose voltages and temperatures are monitored through CAN (controller area network bus to avoid battery fire and explosion. A fuzzy-PID controller is designed for its motion control, including depth control and direction control. The controller synthesizes the advantage of fuzzy control and PID control, utilizes the fuzzy rules to on-line tune the parameters of PID controller, and achieves a better control effect. Experiment results demonstrate to show the effectiveness of the test-bed.

  4. Incidence and associated factors of HIV drug resistance in Chinese HIV-infected patients receiving antiretroviral treatment.

    Directory of Open Access Journals (Sweden)

    Hui Xing

    Full Text Available BACKGROUND: A critical indicator of the future success of highly active antiretroviral therapy (HAART is the incidence of HIV drug resistance, which has not been studied in China on the national scale. METHODS: HIV drug resistance baseline survey was conducted in the eight provinces with the largest numbers of patients on HAART in 2009, and a prospective cohort study with 12-month follow-up was completed in 2010. Patients completed an interviewer-administrated questionnaire and provided blood for CD4+ T-lymphocyte count (CD4 count, HIV viral load (VL, and HIV drug resistance genotyping. Factors associated with incidence of HIVDR were identified by Cox regression analysis. RESULTS: The overall prevalence of HIV RNA ≥ 1000 copies/ml and HIVDR at baseline was 12.4% and 5.6%, respectively. Incidence of HIVDR in the one year follow-up was 3.5 per 100 person years. Independently associated factors were started treatment with a didanosine-based regimen, received care at township hospital or village clinic, low baseline CD4 counts, and high baseline VL. CONCLUSIONS: The incidence of HIVDR in China was higher than that of some developed countries. China urgently needs to provide comprehensive education and training to doctors at village clinics and township hospitals to improve quality community-based care and treatment.

  5. Incidence and associated factors of HIV drug resistance in Chinese HIV-infected patients receiving antiretroviral treatment.

    Science.gov (United States)

    Xing, Hui; Wang, Xia; Liao, Lingjie; Ma, Yanling; Su, Bin; Fu, Jihua; He, Jianmei; Chen, Lin; Pan, Xiaohong; Dong, Yonghui; Liu, Wei; Hsi, Jenny H; Yang, Liting; Ruan, Yuhua; Shao, Yiming

    2013-01-01

    A critical indicator of the future success of highly active antiretroviral therapy (HAART) is the incidence of HIV drug resistance, which has not been studied in China on the national scale. HIV drug resistance baseline survey was conducted in the eight provinces with the largest numbers of patients on HAART in 2009, and a prospective cohort study with 12-month follow-up was completed in 2010. Patients completed an interviewer-administrated questionnaire and provided blood for CD4+ T-lymphocyte count (CD4 count), HIV viral load (VL), and HIV drug resistance genotyping. Factors associated with incidence of HIVDR were identified by Cox regression analysis. The overall prevalence of HIV RNA ≥ 1000 copies/ml and HIVDR at baseline was 12.4% and 5.6%, respectively. Incidence of HIVDR in the one year follow-up was 3.5 per 100 person years. Independently associated factors were started treatment with a didanosine-based regimen, received care at township hospital or village clinic, low baseline CD4 counts, and high baseline VL. The incidence of HIVDR in China was higher than that of some developed countries. China urgently needs to provide comprehensive education and training to doctors at village clinics and township hospitals to improve quality community-based care and treatment.

  6. Effect of an Empowerment Intervention on Antiretroviral Drug Adherence in Thai Youth.

    Science.gov (United States)

    Kaihin, Ratchaneekorn; Kasatpibal, Nongyao; Chitreechuer, Jittaporn; Grimes, Richard M

    2015-01-01

    A pilot study was conducted to determine effects of an empowerment intervention on antiretroviral therapy (ART) adherence among Thai youth living with HIV/AIDS. It compared two groups of 23 young persons (15-24 years) who receive ART from AIDS clinics at two community hospitals. One hospital's patients served as the experimental group, and the other as a control group. The experimental groups attended five sessions that empowered them to take control of their own health. The control group received the standard of care. The data were analyzed using descriptive statistics and Chi-square statistics. Before the empowerment, no one from the experimental group or the control group had ART adherence ≥ 95%. After the intervention, the 82.6% of the experimental group had ≥ 95% adherence compared to the control group, which had 21.7% adherence (p < .0001). The empowerment intervention resulted in a significant increase in ART adherence among Thai youth.

  7. Antiretroviral therapy provided to HIV-infected Malawian women in a randomized trial diminishes the posiitive effect of lipid-based nutrient supplements on breast milk B-vitamins

    Science.gov (United States)

    Background: There is little information on B-vitamin concentrations in human milk or how they are affected by maternal B-vitamin deficiencies, antiretroviral (ARV) therapy or maternal supplementation. Objective: To evaluate effects of ARV therapy and/or lipid-based nutrient supplements (LNS) on B-v...

  8. Analyses of nanoformulated antiretroviral drug charge, size, shape and content for uptake, drug release and antiviral activities in human monocyte-derived macrophages.

    Science.gov (United States)

    Nowacek, Ari S; Balkundi, Shantanu; McMillan, JoEllyn; Roy, Upal; Martinez-Skinner, Andrea; Mosley, R Lee; Kanmogne, Georgette; Kabanov, Alexander V; Bronich, Tatiana; Gendelman, Howard E

    2011-03-10

    Long-term antiretroviral therapy (ART) for human immunodeficiency virus type one (HIV-1) infection shows limitations in pharmacokinetics and biodistribution while inducing metabolic and cytotoxic aberrations. In turn, ART commonly requires complex dosing schedules and leads to the emergence of viral resistance and treatment failures. We posit that the development of nanoformulated ART could preclude such limitations and affect improved clinical outcomes. To this end, we wet-milled 20 nanoparticle formulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz, collectively referred to as "nanoART," then assessed their performance using a range of physicochemical and biological tests. These tests were based on cell-nanoparticle interactions using monocyte-derived macrophages and their abilities to uptake and release nanoformulated drugs and affect viral replication. We demonstrate that physical characteristics such as particle size, surfactant coating, surface charge, and most importantly shape are predictors of cell uptake and antiretroviral efficacy. These studies bring this line of research a step closer to developing nanoART that can be used in the clinic to affect the course of HIV-1 infection. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Low primary and secondary HIV drug-resistance after 12 months of antiretroviral therapy in human immune-deficiency virus type 1 (HIV-1)-infected individuals from Kigali, Rwanda

    NARCIS (Netherlands)

    Rusine, John; Asiimwe-Kateera, Brenda; van de Wijgert, Janneke; Boer, Kimberly Rachel; Mukantwali, Enatha; Karita, Etienne; Gasengayire, Agnes; Jurriaans, Suzanne; de Jong, Menno; Ondoa, Pascale

    2013-01-01

    Treatment outcomes of HIV patients receiving antiretroviral therapy (ART) in Rwanda are scarcely documented. HIV viral load (VL) and HIV drug-resistance (HIVDR) outcomes at month 12 were determined in a prospective cohort study of antiretroviral-naïve HIV patients initiating first-line therapy in

  10. Alternation of antiretroviral drug regimens for HIV infection. Efficacy, safety and tolerability at week 96 of the Swatch Study.

    Science.gov (United States)

    Negredo, Eugenia; Paredes, Roger; Peraire, Joaquim; Pedrol, Enric; Côté, Helene; Gel, Silvia; Fumoz, Carmina R; Ruiz, Lidia; Abril, Vicente; Rodriguez de Castro, Eduardo; Ochoa, Claudia; Martinez-Picado, Javier; Montaner, Julio; Rey-Joly, Celestino; Clotet, Bonaventura

    2004-12-01

    Alternation of antiretroviral drug regimens has been proposed as a novel treatment strategy for HIV infection. However, some concerns persist regarding antiviral efficacy, adherence, toxicity and resistance evolution in the long term. A total of 161 antiretroviral-naive HIV-1-infected patients were randomized to receive stavudine/didanosine/efavirenz (group A) or zidovudine/lamivudine/ nelfinavir (group B) or to alternate between the two regimens every 3 months starting with regimen A (group C). Antiviral efficacy, adherence, safety and tolerability were analysed every 12 weeks. After 96 weeks, time to virological failure was significantly delayed in the alternating regimen compared with the standards of care regimens. Virological suppression was seen in 46%, 48% and 58% of patients in groups A, B and C, respectively, in the intention-to-treat analysis and in 75%, 76% and 97% in the on-treatment analysis (A vs C: P=0.014; B vs C: P=0.016; A vs B: P=0.849). At the end of the study, 94% of patients in group A and 92% in groups B and C reported an adherence greater than 95%. Alternating therapy was associated with a similar impact on CD4+ counts in comparison with the standards of care regimens, as well as a lower mitochondrial DNA/nuclear DNA (mtDNA/nDNA) ratio decrease in the mitochondrial substudy performed on 37 patients. The frequency and intensity of adverse events in the alternating group decreased during subsequent cycles. Our results favour the hypothesis that proactive therapy switching may delay the accumulation of resistance mutations. Moreover, the alternating regimen was well tolerated and adherence remained comparably high in all treatment groups. The lower mtDNA/nDNA ratio decrease observed in this group may imply a lower impact on mitochondrial toxicity than in standard regimens.

  11. An appeal for large scale production of antiretroviral drugs in Africa.

    Science.gov (United States)

    Martial, Nkamedjie Pete Patrick; Sieleunou, Isidore

    2016-01-01

    The Acquired Immuno Deficiency Syndrome (AIDS) remains a major global public health challenge especially in Africa. The deadline set for the Millennium Development Goals (MDGs) has elapsed, meanwhile most low and middle income countries did not reach the targets. With regards to the fight against HIV / AIDS, many African countries show slow progress in implementing efficient and effective strategies to counter this pandemic. The fact that most HIV/AIDS programs in Sub-Saharan African countries are still very dependent on external funding to carry out their activities, including the supply of Antiretroviral Treatment (ART), highlights the concern of sustainability. So far, solutions that have been proposed are mainly symptomatic, claiming more budget commitment from government. Without rejecting this view, we call for the implementation of sustainable solutions to deal with the long term ART challenges. A way forward is to promote the establishment of an effective machinery for the manufacturing and large scale distribution of ART. In addition to the health gains, we argue that such an initiative would have a three-dimensional impact: (i) political, (ii) economic and (iii) social.

  12. Ergotism in Thailand caused by increased access to antiretroviral drugs: a global warning

    NARCIS (Netherlands)

    Avihingsanon, A.; Ramautarsing, R.A.; Suwanpimolkul, G.; Chetchotisakd, P.; Bowonwatanuwong, C.; Jirajariyavej, S.; Kantipong, P.; Tantipong, H.; Ohata, J.P.; Suankratay, C.; Ruxrungtham, K.; Burger, D.M.

    2014-01-01

    Ergotism is a toxic condition resulting from overexposure to the ergot compounds produced by various fungi of the genus Claviceps. Traditionally, such exposure was due to ingestion of infected grains, but long-term or excessive use of medications containing ergot derivatives or drug-drug

  13. Sources of motivation and frustration among healthcare workers administering antiretroviral treatment for HIV in rural Zimbabwe.

    Science.gov (United States)

    Campbell, C; Scott, K; Madenhire, C; Nyamukapa, C; Gregson, S

    2011-07-01

    The roll-out of accessible and affordable antiretroviral (ARV) drugs for people living with HIV in low-income countries is drastically changing the nature of HIV-related healthcare. The Zimbabwean Ministry of Health has renewed efforts to make antiretroviral treatment (ART) for HIV free and publically available across the country. This paper describes the findings from a multi-method qualitative study including interviews and a focus group with healthcare workers (mostly nurses), totalling 25 participants, and field notes from over 100 hours of ethnographic observation in three rural Zimbabwean health centres. These health centres began providing free ARV drugs to HIV-positive people over one year prior to the research period. We examined sources of motivation and frustration among nurses administering ART in these resource-poor health centres. The findings suggest that healthcare workers administering ART in challenging circumstances are adept at drawing strength from the dramatic physical and emotional recoveries made possible by ART and from their personal memories of the suffering caused by HIV/AIDS among close friends or family. However, healthcare staff grappled with extreme resource shortages, which led to exhaustion and frustration. Surprisingly, only one year into ART provision, healthcare workers did not reference the professional challenges of their HIV work before ART became available, suggesting that medical breakthroughs such as ART rapidly come to be seen as a standard element of nursing. Our findings provide a basis for optimism that medical breakthroughs such as ART can reinvigorate healthcare workers in the short term. However, we caution that the daily challenges of nursing in poor environments, especially administering an ongoing and resource-intensive regime such as ART, must be addressed to enable nurses to continue delivering high-quality ART in sub-Saharan Africa.

  14. Impact of injecting drug use on response to highly active antiretroviral treatment in HIV-1-infected patients: a nationwide population-based cohort study

    DEFF Research Database (Denmark)

    Larsen, Mette Vang; Omland, Lars Haukali Hvass; Gerstoft, Jan

    2010-01-01

    The objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients infected through injecting drug use (injecting drug users, IDUs) compared to patients infected via other routes (non-IDUs). We conducted...... for non-IDUs, and IDUs initiated HAART later than non-IDUs. In conclusion, more than half of the HIV-infected patients in Denmark infected through injecting drug use gained full viral suppression after initiating HAART. Absolute CD4(+) cell count was lower and mortality higher among IDUs than non-IDUs....

  15. Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting

    Science.gov (United States)

    Maiga, Almoustapha Issiaka; Fofana, Djeneba Bocar; Cisse, Mamadou; Diallo, Fodié; Maiga, Moussa Youssoufa; Traore, Hamar Alassane; Maiga, Issouf Alassane; Sylla, Aliou; Fofana, Dionke; Taiwo, Babafemi; Murphy, Robert; Katlama, Christine; Tounkara, Anatole; Calvez, Vincent; Marcelin, Anne-Geneviève

    2012-01-01

    Objectives We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. Methods We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. Results Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm3. Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). Conclusion Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings. PMID:22888273

  16. Drug resistance mutations after the first 12 months on antiretroviral therapy and determinants of virological failure in Rwanda.

    Science.gov (United States)

    Ndahimana, Jean d'Amour; Riedel, David J; Mwumvaneza, Mutagoma; Sebuhoro, Dieudone; Uwimbabazi, Jean Claude; Kubwimana, Marthe; Mugabo, Jules; Mulindabigwi, Augustin; Kirk, Catherine; Kanters, Steve; Forrest, Jamie I; Jagodzinski, Linda L; Peel, Sheila A; Ribakare, Muhayimpundu; Redfield, Robert R; Nsanzimana, Sabin

    2016-07-01

    To evaluate HIV drug resistance (HIVDR) and determinants of virological failure in a large cohort of patients receiving first-line tenofovir-based antiretroviral therapy (ART) regimens. A nationwide retrospective cohort from 42 health facilities was assessed for virological failure and development of HIVDR mutations. Data were collected at ART initiation and at 12 months of ART on patients with available HIV-1 viral load (VL) and ART adherence measurements. HIV resistance genotyping was performed on patients with VL ≥1000 copies/ml. Multiple logistic regression was used to determine factors associated with treatment failure. Of 828 patients, 66% were women, and the median age was 37 years. Of the 597 patients from whom blood samples were collected, 86.9% were virologically suppressed, while 11.9% were not. Virological failure was strongly associated with age CD4 counts <200 cells/μl (aOR 3.4; 95% CI: 1.9-6.2). Overall, 9.1% of all patients on ART had drug resistance mutations after 1 year of ART; 27% of the patients who failed treatment had no evidence of HIVDR mutations. HIVDR mutations were not observed in patients on the recommended second-line ART regimen in Rwanda. The last step of the UNAIDS 90-90-90 target appears within grasp, with some viral failures still due to non-adherence. Nonetheless, youth and late initiators are at higher risk of virological failure. Youth-focused programmes could help prevent further drug HIVDR development. © 2016 John Wiley & Sons Ltd.

  17. Formulation and characterization of solid lipid nanoparticles for an anti-retroviral drug darunavir

    Science.gov (United States)

    Bhalekar, Mangesh; Upadhaya, Prashant; Madgulkar, Ashwini

    2017-02-01

    Darunavir, an anti-HIV drug having poor solubility in aqueous and lipid medium, illustrates degradation above its melting point, i.e. 74 °C, thus, posing a challenge to dosage formulation. Despite, the drug suffers from poor oral bioavailability (37%) owing to less permeability and being poly-glycoprotein and cyp3A metabolism substrate. The study aimed formulating a SLN system to overcome the formulation and bioavailability associated problems of the drug. Based on the drug solubility and stable dispersion findings, lipid and surfactant were chosen and nanoparticles were prepared using hot-homogenization technique. Optimization of variables such as lipid concentration, oil-surfactant and homogenization cycle was carried and their effect on particle size and entrapment efficiency was studied. Freeze-dried SLN further characterized using SEM, DSC and PXRD analysis revealed complete entrapment of the drug and amorphous nature of the SLN. In vitro pH release studies in 0.1 N HCl and 6.8 pH buffer demonstrated 84 and 80% release at the end of 12th h. The apparent permeability of the SLN across rat intestine was found to be 24 × 10-6 at 37 °C at the end of 30 min while at 4 °C the same was found to be 5.6 × 10-6 prompting involvement of endocytic processes in the uptake of SLN. Accelerated stability studies revealed no prominent changes upon storage.

  18. Combination of anti-retroviral drugs and radioimmunotherapy specifically kills infected cells from HIV infected individuals

    Directory of Open Access Journals (Sweden)

    Dina Tsukrov

    2016-09-01

    Full Text Available Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT, a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infect-ed cells. Since gp41 expression by infected cells is likely down-regulated in patients on an-tiretroviral therapy (ART, we evaluated the ability of RIT to kill ART-treated infected cells us-ing both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal anti-body to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. conjugated to the human monoclonal antibody 2556, which binds to HIV gp41. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: ten on ART and five ART-naive. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART, and supports continued development of 213Bi

  19. HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis

    International Nuclear Information System (INIS)

    Jiang Bo; Hebert, Valeria Y.; Li, Yuchi; Mathis, J. Michael; Alexander, J. Steven; Dugas, Tammy R.

    2007-01-01

    Numerous reports now indicate that HIV patients administered long-term antiretroviral therapy (ART) are at a greater risk for developing cardiovascular diseases. Endothelial dysfunction is an initiating event in atherogenesis and may contribute to HIV-associated atherosclerosis. We previously reported that ART induces direct endothelial dysfunction in rodents. In vitro treatment of human umbilical vein endothelial cells (HUVEC) with ART indicated endothelial mitochondrial dysfunction and a significant increase in the production of reactive oxygen species (ROS). In this study, we determined whether ART-induced endothelial dysfunction is mediated via mitochondria-derived ROS and whether this mitochondrial injury culminates in endothelial cell apoptosis. Two major components of ART combination therapy, a nucleoside reverse transcriptase inhibitor and a protease inhibitor, were tested, using AZT and indinavir as representatives for each. Microscopy utilizing fluorescent indicators of ROS and mitochondria demonstrated the mitochondrial localization of ART-induced ROS. MnTBAP, a cell-permeable metalloporphyrin antioxidant, abolished ART-induced ROS production. As a final step in confirming the mitochondrial origin of the ART-induced ROS, HUVEC were transduced with a cytosolic- compared to a mitochondria-targeted catalase. Transduction with the mitochondria-targeted catalase was more effective than cytoplasmic catalase in inhibiting the ROS and 8-isoprostane (8-iso-PGF 2α ) produced after treatment with either AZT or indinavir. However, both mitochondrial and cytoplasmic catalase attenuated ROS and 8-iso-PGF 2α production induced by the combination treatment, suggesting that in this case, the formation of cytoplasmic ROS may also occur, and thus, that the mechanism of toxicity in the combination treatment group may be different compared to treatment with AZT or indinavir alone. Finally, to determine whether ART-induced mitochondrial dysfunction and ROS production

  20. Impact of opioid substitution therapy on the HIV prevention benefit of antiretroviral therapy for people who inject drugs.

    Science.gov (United States)

    Mukandavire, Christinah; Low, Andrea; Mburu, Gitau; Trickey, Adam; May, Margaret T; Davies, Charlotte F; French, Clare E; Looker, Katharine J; Rhodes, Tim; Platt, Lucy; Guise, Andy; Hickman, Matthew; Vickerman, Peter

    2017-05-15

    A recent meta-analysis suggested that opioid substitution therapy (OST) increased uptake of antiretroviral treatment (ART) and HIV viral suppression. We modelled whether OST could improve the HIV prevention benefit achieved by ART among people who inject drugs (PWID). We modelled how introducing OST could improve the coverage of ART across a PWID population for different baseline ART coverage levels. Using existing data on how yearly HIV-transmission risk is related to HIV plasma viral load, changes in the level of viral suppression across the population were used to project the relative reduction in yearly HIV-transmission risk achieved by ART, with or without OST, compared with if there was no ART - defined here as the prevention effectiveness of ART. Owing to OST use increasing the chance of being on ART and achieving viral suppression if on ART, the prevention effectiveness of ART for PWID on OST (compared with PWID not on OST) increases by 44, 31, or 20% for a low (20%), moderate (40%), or high (60%) baseline ART coverage, respectively. Improvements in the population-level prevention effectiveness of ART are also achieved across all PWID, compared with if OST was not introduced. For instance, if OST is introduced at 40% coverage, the population-level prevention effectiveness of ART could increase by 27, 20, or 13% for a low (20%), moderate (40%), or high (60%) baseline ART coverage, respectively. OST could improve the HIV prevention benefit of ART; supporting strategies that aim to concurrently scale-up OST with ART.

  1. The constraints of antiretroviral uptake in rural areas: the case of Thamaga and surrounding villages, Botswana.

    Science.gov (United States)

    Bene, Matlhogonolo; Darkoh, Michael B K

    2014-01-01

    This article examines the constraints of antiretroviral (ARV) uptake in the villages of Thamaga, Kumakwane, Mankgodi and Gakgatla which are in the Kweneng District of Botswana. The social interactionist approach and theories of health behaviour provided the theoretical basis of the study. Data were obtained by using interviewer-administered questionnaires which were applied to a sample of 145 respondents and 61 people living with HIV/AIDS in the four villages. The results of the study showed that people aged 30-39 years represented the highest proportion of the persons on ARV treatment in the villages. Some of the people living with HIV believed that ARV therapy could better their lives during the initial stages of introduction, but with time, they lost hope and gave up the treatment. Culturally, parents and children in the villages do not discuss sexual matters at home and it was found in the study that there was little communication between parents and children on AIDS and ARV issues. Some churches in the area discouraged the use of ARV. There were also traditional doctors who made their patients mix traditional herbs treatment with ARV treatment. Distance, travel costs, cultural beliefs, stigma and discrimination among others were found to be important socio-economic factors inhibiting ARV uptake. Even though there were constraints on ARV uptake in the villages, efforts were being made by Government and non-governmental organizations to overcome them. The Ministry of Health provided information and education to the public using its strategy known as Information, Education and Communication. Nurses, doctors and chiefs taught people at kgotlas (traditional courts) in the villages about the dangers of the epidemic. Free HIV testing, ARVs and condoms were provided to the villagers. The outlook for ARV uptake looks generally promising for the future. However, if HIV/AIDS is to be contained, sexual behaviour of people in the villages needs to change.

  2. Transmitted antiretroviral drug resistance in New York State, 2006-2008: results from a new surveillance system.

    Directory of Open Access Journals (Sweden)

    Adam C Readhead

    Full Text Available HIV transmitted drug resistance (TDR is a public health concern because it has the potential to compromise antiretroviral therapy (ART at the population level. In New York State, high prevalence of TDR in a local cohort and a multiclass resistant case cluster led to the development and implementation of a statewide resistance surveillance system.We conducted a cross-sectional analysis of the 13,109 cases of HIV infection that were newly diagnosed and reported in New York State between 2006 and 2008, including 4,155 with HIV genotypes drawn within 3 months of initial diagnosis and electronically reported to the new resistance surveillance system. We assessed compliance with DHHS recommendations for genotypic resistance testing and estimated TDR among new HIV diagnoses.Of 13,109 new HIV diagnoses, 9,785 (75% had laboratory evidence of utilization of HIV-related medical care, and 4,155 (43% had a genotype performed within 3 months of initial diagnosis. Of these, 11.2% (95% confidence interval [CI], 10.2%-12.1% had any evidence of TDR. The proportion with mutations associated with any antiretroviral agent in the NNRTI, NRTI or PI class was 6.3% (5.5%-7.0%, 4.3% (3.6%-4.9% and 2.9% (2.4%-3.4%, respectively. Multiclass resistance was observed in <1%. TDR did not increase significantly over time (p for trend = 0.204. Men who have sex with men were not more likely to have TDR than persons with heterosexual risk factor (OR 1.0 (0.77-1.30. TDR to EFV+TDF+FTC and LPV/r+TDF+FTC regimens was 7.1% (6.3%-7.9% and 1.4% (1.0%-1.8%, respectively.TDR appears to be evenly distributed and stable among new HIV diagnoses in New York State; multiclass TDR is rare. Less than half of new diagnoses initiating care received a genotype per DHHS guidelines.

  3. Patients' adherence to antiretroviral therapy at Antiretroviral Therapy ...

    African Journals Online (AJOL)

    Adherence is the most important factor influencing successful antiretroviral therapy. Long term success with antiretroviral therapy (ART) requires taking 95% of medication. Less than 95% adherence can result in less than optimal therapeutic response and drug resistance. The aim of this study was to determine the ...

  4. Incidence of adverse drug reactions in human immune deficiency virus-positive patients using highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    B Akshaya Srikanth

    2012-01-01

    Full Text Available To estimate the incidence of adverse drug reactions (ADRs in Human immune deficiency virus (HIV patients on highly active antiretroviral therapy (HAART. To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%. The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52% was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/μl were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ≤250 cells/mm 3 with comorbid conditions.

  5. Sub-therapeutic nevirapine concentration during antiretroviral treatment initiation among children living with HIV: Implications for therapeutic drug monitoring.

    Directory of Open Access Journals (Sweden)

    Bindu Parachalil Gopalan

    Full Text Available Nevirapine, a component of antiretroviral therapy (ART in resource-limited settings, known for auto-induction of metabolism, is initiated at half therapeutic dose until day 14 ('lead-in period', and subsequently escalated to full dose. However, studies have shown that this dosing strategy based on adult studies may not be appropriate in children, given that younger children have higher drug clearance rates. In this prospective cohort study, we studied trough plasma nevirapine levels by high performance liquid chromatography (HPLC at days 7, 14 (lead-in period and 28 (full dose period after ART initiation amongst HIV-1 infected children initiating nevirapine-based ART in southern India. Among the 20 children (50% male, median age 9 years included in the study, sub-therapeutic trough plasma nevirapine concentration (<4μg/ml was seen in 65% (13/20 of children during the lead-in period within two weeks of ART initiation and among 10% of children at 4 weeks during full-dose nevirapine. Adherence was documented as ≥95% in all children by both caregiver self-report and pill count. Median nevirapine concentrations achieved at week 1 was 4.8 μg/ml, significantly lower than 8 μg/ml, the concentration achieved at week 4 (p = 0.034. Virological failure at one year of ART was observed in six children, and was not associated with median nevirapine concentration achieved during week 1, 2 or 4. We conclude that the dose escalation strategy currently practiced among young children living with HIV-1 resulted in significant subtherapeutic nevirapine concentration (≤4μg/ml during the lead-in period. We call for a closer look at pediatric-focused dosing strategies for nevirapine initiation in young children. Further studies to establish age-appropriate threshold nevirapine concentration are warranted in young children to corroborate the role of therapeutic drug monitoring in predicting virological outcome.

  6. HIV/AIDS drugs for Sub-Saharan Africa: how do brand and generic supply compare?

    Directory of Open Access Journals (Sweden)

    Colleen V Chien

    Full Text Available BACKGROUND: Significant quantities of antiretroviral drugs (ARVs to treat HIV/AIDS have been procured for Sub-Saharan Africa for the first time in their 20-year history. This presents a novel opportunity to empirically study the roles of brand and generic suppliers in providing access to ARVs. METHODOLOGY/PRINCIPAL FINDINGS: An observational study of brand and generic supply based on a dataset of 2,162 orders of AIDS drugs for Sub-Saharan Africa reported to the Global Price Reporting Mechanism at the World Health Organization from January 2004-March 2006 was performed. Generic companies supplied 63% of the drugs studied, at prices that were on average about a third of the prices charged by brand companies. 96% of the procurement was of first line drugs, which were provided mostly by generic firms, while the remaining 4%, of second line drugs, was sourced primarily from brand companies. 85% of the generic drugs in the sample were manufactured in India, where the majority of the drugs procured were ineligible for patent protection. The remaining 15% was manufactured in South Africa, mostly under voluntary licenses provided by brand companies to a single generic company. In Sub-Saharan African countries, four first line drugs in the dataset were widely patented, however no general deterrent to generic purchasing based on a patent was detected. CONCLUSIONS/SIGNIFICANCE: Generic and brand companies have played distinct roles in increasing the availability of ARVs in Sub-Saharan Africa. Generic companies provided most of the drugs studied, at prices below those charged by brand companies, and until now, almost exclusively supplied several fixed-dose combination drugs. Brand companies have supplied almost all second line drugs, signed voluntary licenses with generic companies, and are not strictly enforcing patents in certain countries. Further investigation into how price reductions in second line drugs can be achieved and the cheapest drugs can

  7. Stock-outs of antiretroviral drugs and coping strategies used to prevent changes in treatment regimens in Kinondoni District, Tanzania: a cross-sectional study.

    Science.gov (United States)

    Mori, Amani Thomas; Owenya, Joyce

    2014-01-01

    Since 2004, the government of Tanzania has been rolling out antiretroviral treatment programs all over the country. However, the capacity of the health system to cope with the rapid scale-up of these programs is a major concern, and problems may result in drug stock-outs that force changes in treatment regimens. This study aims to explore stock-outs of antiretroviral drugs and further determine the coping strategies employed to prevent changes in treatment regimens in HIV/AIDS care and treatment clinics in Kinondoni District, Dar es Salaam, Tanzania. A cross-sectional study was conducted in 20 HIV/AIDS care and treatment clinics. Interviews were conducted with the person in charge and a member of the pharmacy staff from each clinic using a pre-tested semi-structured interview guide. Verbal responses were transcribed, coded and analysed by thematic approach. Quantitative data were analysed using Excel spreadsheet (Microsoft Excel®, Microsoft Corporation). The total number of clients enrolled in the visited clinics was 32,147, of whom 20,831 (64.8%) had already been initiated onto antiretroviral therapies (ART). Stock-out of antiretroviral drugs was reported in 16 out of the 20 clinics, causing 210 patients to change their ART regimens, during the 12 months preceding the survey. Inefficient supply systems, quantification problems and short expiry duration were cited as the main causes of stock-outs. The coping strategies utilised to prevent changes in ART regimens were: shortening of the refill period, borrowing and moving patients to other clinics. Changes in ART regimens due to stock-outs of antiretroviral drugs occurred in a small but significant number of patients. This increases the risk of the emergence of drug-resistant HIV strains. Healthcare workers use various coping strategies to prevent changes in ART regimens but, unfortunately, some of these strategies are likely to increase patient-borne costs, which may discourage them from attending their routine

  8. Ergotism in Thailand caused by increased access to antiretroviral drugs: a global warning.

    Science.gov (United States)

    Avihingsanon, Anchalee; Ramautarsing, Reshmie A; Suwanpimolkul, Gompol; Chetchotisakd, Ploenchan; Bowonwatanuwong, Chureeratana; Jirajariyavej, Supunnee; Kantipong, Patcharee; Tantipong, Hutsaya; Ohata, June Pirapon; Suankratay, Chusana; Ruxrungtham, Kiat; Burger, David M

    2014-01-01

    Ergotism is a toxic condition resulting from overexposure to the ergot compounds produced by various fungi of the genus Claviceps. Traditionally, such exposure was due to ingestion of infected grains, but long-term or excessive use of medications containing ergot derivatives or drug-drug interactions between these medications can result in ergotism. Ergotamine, typically used to treat migraine, has less than 5% bioavailability due to extensive first-pass metabolism by cytochrome P450 3A4 (CYP3A4). Concurrent intake of ergotamine and strong CYP3A4 inhibitors, such as the HIV protease inhibitors (PIs), can lead to clinical ergotism. A total of 13 cases of clinical ergotism in HIV-infected patients has been published since 1997 (most recently reviewed by Frohlich et al).

  9. Concurrent use of Antiretroviral and African traditional medicines amongst people living with HIV/AIDS (PLWA) in the eThekwini Metropolitan area of KwaZulu Natal.

    Science.gov (United States)

    Mncengeli, Sibanda; Manimbulu, Nlooto M; Panjasaram, Naidoo

    2016-12-01

    People living with HIV/AIDS (PLWA) often use African Traditional Medicines (ATM) either alone or in combination with Western medicines including Antiretrovirals (ARV). To explore the prevalence of concurrent Antiretrovirals (ARV) and African Traditional medicines (ATM) use and determine the effects of any concurrent use on the CD4+ Lymphocyte count and Viral Load (VL) of PLWA in the eThekwini Metropolitan area. A descriptive and exploratory study was carried out on 360 patients. Information was gathered on patients socioeconomic characteristics, ATM usage, outcome measures of HIV disease progression (CD4+ Count, VL). The data was analysed using descriptive statistics, univariate and multivariate analyses. 4.98% (14/281) of the patients used ATM and ARV concurrently during the study period. Over 65% (185/281) reported ATM use before diagnosis with HIV whilst 77.6% (218/281) reported previous ATM use after their HIV diagnosis but before initiation with ARV. Place of residence (p=0.004), age (p<0.001) and education level (P=0.041) were found to be significantly and positively correlated with ATM use. There were no statistically significant changes in mean plasma CD4+ Count and inconclusive effects on VL during the period of the study in the group taking ARV alone when compared with the group using ARV and ATM concomitantly. Concurrent ARV and ATM use is quite low (4.98%) when compared to ATM use before HIV diagnosis and after HIV diagnosis but before initiation with ARV. This may point to efficient pre-counselling efforts before ARV initiation by health care professionals. This study also demonstrated that there were no significant differences in the CD4+ and inconclusive effects on VL, between patients taking both ARV and ATM concomitantly and those using ARV alone.

  10. Impact of low-level-viremia on HIV-1 drug-resistance evolution among antiretroviral treated-patients.

    Directory of Open Access Journals (Sweden)

    Constance Delaugerre

    Full Text Available BACKGROUND: Drug-resistance mutations (DRAM are frequently selected in patients with virological failure defined as viral load (pVL above 500 copies/ml (c/mL, but few resistance data are available at low-level viremia (LLV. Our objective was to determine the emergence and evolution of DRAM during LLV in HIV-1-infected patients while receiving antiretroviral therapy (ART. METHODS: Retrospective analysis of patients presenting a LLV episode defined as pVL between 40 and 500 c/mL on at least 3 occasions during a 6-month period or longer while on the same ART. Resistance genotypic testing was performed at the onset and at the end of LLV period. Emerging DRAM was defined during LLV if never detected on baseline genotype or before. RESULTS: 48 patients including 4 naive and 44 pretreated (median 9 years presented a LLV episode with a median duration of 11 months. Current ART included 2NRTI (94%, ritonavir-boosted PI (94%, NNRTI (23%, and/or raltegravir (19%. Median pVL during LLV was 134 c/mL. Successful resistance testing at both onset and end of the LLV episode were obtained for 37 patients (77%, among who 11 (30% acquired at least 1 DRAM during the LLV period: for NRTI in 6, for NNRTI in 1, for PI in 4, and for raltegravir in 2. During the LLV period, number of drugs with genotypic resistance increased from a median of 4.5 to 6 drugs. Duration and pVL level of LLV episode, duration of previous ART, current and nadir CD4 count, number of baseline DRAM and GSS were not identified as predictive factors of resistance acquisition during LLV, probably due to limited number of patients. CONCLUSION: Persistent LLV episodes below 500 c/ml while receiving ART is associated with emerging DRAM for all drug classes and a decreasing in further therapeutic options, suggesting to earlier consider resistance monitoring and ART optimization in this setting.

  11. Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission.

    Directory of Open Access Journals (Sweden)

    Andrea Hauser

    Full Text Available BACKGROUND: WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT, nevirapine single-dose (NVP-SD at labor onset and AZT/lamivudine (3TC during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis. METHOD: 1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1-2, 4-6 and 12-16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F, NVP (K103N/Y181C and 3TC (M184V at detection limits of <1%. RESULTS: 50/87 HIV-infected women having started complex prophylaxis were eligible for the study. All women took AZT with a median duration of 53 days (IQR 39-64; all women ingested NVP-SD, 86% took 3TC. HIV-1 resistance mutations were detected in 20/50 (40% women, of which 70% displayed minority species. Variants with AZT-resistance mutations were found in 11/50 (22%, NVP-resistant variants in 9/50 (18% and 3TC-resistant variants in 4/50 women (8%. Three women harbored resistant HIV-1 against more than one drug. 49/50 infants, including the seven vertically HIV-infected were breastfed, 3/7 infants exhibited drug-resistant virus. CONCLUSION: Complex prophylaxis resulted in lower levels of NVP-selected resistance as compared to NVP-SD, but AZT-resistant HIV-1 emerged in a substantial proportion of women. Starting AZT in pregnancy week 14 instead of 28 as recommended by the current WHO-guidelines may further increase

  12. Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission.

    Science.gov (United States)

    Hauser, Andrea; Sewangi, Julius; Mbezi, Paulina; Dugange, Festo; Lau, Inga; Ziske, Judith; Theuring, Stefanie; Kuecherer, Claudia; Harms, Gundel; Kunz, Andrea

    2012-01-01

    WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP-SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis. 1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1-2, 4-6 and 12-16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of HIV-infected women having started complex prophylaxis were eligible for the study. All women took AZT with a median duration of 53 days (IQR 39-64); all women ingested NVP-SD, 86% took 3TC. HIV-1 resistance mutations were detected in 20/50 (40%) women, of which 70% displayed minority species. Variants with AZT-resistance mutations were found in 11/50 (22%), NVP-resistant variants in 9/50 (18%) and 3TC-resistant variants in 4/50 women (8%). Three women harbored resistant HIV-1 against more than one drug. 49/50 infants, including the seven vertically HIV-infected were breastfed, 3/7 infants exhibited drug-resistant virus. Complex prophylaxis resulted in lower levels of NVP-selected resistance as compared to NVP-SD, but AZT-resistant HIV-1 emerged in a substantial proportion of women. Starting AZT in pregnancy week 14 instead of 28 as recommended by the current WHO-guidelines may further increase the frequency of AZT-resistance mutations. Given its impact on

  13. Maternal HIV-1 disease progression 18-24 months postdelivery according to antiretroviral prophylaxis regimen (triple-antiretroviral prophylaxis during pregnancy and breastfeeding vs zidovudine/single-dose nevirapine prophylaxis): The Kesho Bora randomized controlled trial.

    Science.gov (United States)

    2012-08-01

    Antiretroviral (ARV) prophylaxis effectively reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV). However, it is unclear whether stopping ARVs after breastfeeding cessation affects maternal HIV disease progression. We assessed 18-24-month postpartum disease progression risk among women in a randomized trial assessing efficacy and safety of prophylactic maternal ARVs. From 2005 to 2008, HIV-infected pregnant women with CD4(+) counts of 200-500/mm(3) were randomized to receive either triple ARV (zidovudine, lamivudine, and lopinavir/ritonavir during pregnancy and breastfeeding) or AZT/sdNVP (zidovudine until delivery with single-dose nevirapine without postpartum prophylaxis). Maternal disease progression was defined as the combined endpoint of death, World Health Organization clinical stage 4 disease, or CD4(+) counts of prolonged triple ARV prophylaxis had no effect on HIV progression following cessation (compared with AZT/sdNVP). However, women on triple ARV prophylaxis had lower progression risk during the time on triple ARV. Given the high rate of progression among women with CD4(+) cells of <350/mm(3), ARVs should not be discontinued in this group. ISRCTN71468410.

  14. Compulsory drug detention exposure is associated with not receiving antiretroviral treatment among people who inject drugs in Bangkok, Thailand: a cross-sectional study.

    Science.gov (United States)

    Hayashi, Kanna; Ti, Lianping; Avihingsanon, Anchalee; Kaplan, Karyn; Suwannawong, Paisan; Wood, Evan; Montaner, Julio S G; Kerr, Thomas

    2015-05-06

    Thailand has experienced a longstanding epidemic of HIV among people who inject drugs (PWID). However, antiretroviral treatment (ART) coverage among HIV-positive PWID has historically remained low. While ongoing drug law enforcement involving periodic police crackdowns is known to increase the risk of HIV transmission among Thai PWID, the impact of such drug policy approaches on the ART uptake has been understudied. Therefore, we sought to identify factors associated with not receiving ART among HIV-positive PWID in Bangkok, Thailand, with a focus on factors pertaining to drug law enforcement. Data were collected from a community-recruited sample of HIV-positive PWID in Bangkok who participated in the Mitsampan Community Research Project between June 2009 and October 2011. We identified factors associated with not receiving ART at the time of interview using multivariate logistic regression. In total, 128 HIV-positive PWID participated in this study, with 58 (45.3%) reporting not receiving ART at the time of interview. In multivariate analyses, completing less than secondary education (adjusted odds ratio [AOR]: 3.32 ; 95% confidence interval [CI]: 1.48 - 7.45), daily midazolam injection (AOR: 3.22, 95% CI: 1.45 - 7.15) and exposure to compulsory drug detention (AOR: 3.36, 95% CI: 1.01 - 11.21) were independently and positively associated with not receiving ART. Accessing peer-based healthcare information or support services was independently and positively associated with receiving ART (AOR: 0.21, 95% CI: 0.05 - 0.84). Approximately half of our study group of HIV-positive PWID reported not receiving ART at the time of interview. Daily midazolam injectors, those with lower education attainment, and individuals who had been in compulsory drug detention were more likely to be non-recipients of ART whereas those who accessed peer-based healthcare-related services were more likely to receive ART. These findings suggest a potentially adverse impact of compulsory drug

  15. Early warning indicators for HIV drug resistance in Cameroon during the year 2010.

    Science.gov (United States)

    Billong, Serge C; Fokam, Joseph; Nkwescheu, Armand S; Kembou, Etienne; Milenge, Pascal; Tsomo, Zephirin; Dion, Grace Ngute; Aghokeng, Avelin F; Mpoudi, Eitel N; Ndumbe, Peter M; Colizzi, Vittorio; Elat Nfetam, Jean B

    2012-01-01

    Rapid scale-up of antiretroviral therapy (ART) in resource-limited settings is accompanied with an increasing risk of HIV drug resistance (HIVDR), which in turn could compromise the performance of national ART rollout programme. In order to sustain the effectiveness of ART in a resource-limited country like Cameroon, HIVDR early warning indicators (EWI) may provide relevant corrective measures to support the control and therapeutic management of AIDS. A retrospective study was conducted in 2010 among 40 ART sites (12 Approved Treatment Centers and 28 Management Units) distributed over the 10 regions of Cameroon. Five standardized EWIs were selected for the evaluation using data from January through December, among which: (1) Good ARV prescribing practices: target = 100%; (2) Patient lost to follow-up: target ≤ 20%; (3) Patient retention on first line ART: target ≥ 70%; (4) On-time drug pick-up: target ≥ 90%; (5) ARV drug supply continuity: target = 100%. Analysis was performed using a Data Quality Assessment tool, following WHO protocol. THE NUMBER OF SITES ATTAINING THE REQUIRED PERFORMANCE ARE: 90% (36/40) for EWI(1), 20% (8/40) for EWI(2); 20% (8/40) for EWI(3); 0% (0/37) for EWI(4); and 45% (17/38) for EWI 5. ARV prescribing practices were in conformity with the national guidelines in almost all the sites, whereas patient adherence to ART (EWI(2), EWI(3), and EWI(4)) was very low. A high rate of patients was lost-to-follow-up and others failing first line ART before 12 months of initiation. Discontinuity in drug supply observed in about half of the sites may negatively impact ARV prescription and patient adherence. These poor ART performances may also be due to low number of trained staff and community disengagement. The poor performance of the national ART programme, due to patient non-adherence and drug stock outs, requires corrective measures to limit risks of HIVDR emergence in Cameroon.

  16. Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093.

    Science.gov (United States)

    Watts, D Heather; Park, Jeong-Gun; Cohn, Susan E; Yu, Song; Hitti, Jane; Stek, Alice; Clax, Pamela A; Muderspach, Laila; Lertora, Juan J L

    2008-02-01

    Concomitant use of antiretroviral (ARV) and hormonal contraceptives may change the metabolism of each and the resulting safety profiles. We evaluated the safety and tolerability of depot medroxyprogesterone acetate (DMPA) among women on ARV. HIV-infected women on selected ARV regimens or no ARV were administered DMPA 150 mg intramuscularly and evaluated for 12 weeks for adverse events, changes in CD4+ count and HIV RNA levels, and ovulation. Seventy evaluable subjects were included, 16 on nucleoside only or no ARV, 21 on nelfinavir-containing regimens, 17 on efavirenz-containing regimens and 16 on nevirapine-containing regimens. Nine Grade 3 or 4 adverse events occurred in seven subjects; none were judged related to DMPA. The most common findings possibly related to DMPA were abnormal vaginal bleeding (nine, 12.7%), headache (three, 4.2%), abdominal pain, mood changes, insomnia, anorexia and fatigue, each occurring in two (2.9%) subjects. No significant changes in CD4+ count or HIV RNA levels occurred with DMPA. No evidence of ovulation was detected, and no pregnancies occurred. The clinical profile associated with DMPA administration in HIV-infected women, most on ARV, appears similar to that seen in HIV-uninfected women. DMPA prevented ovulation and did not affect CD4+ counts or HIV RNA levels. In concert with previously published DMPA/ARV interaction data, these data suggest that DMPA can be used safely by HIV-infected women on the ARV studied.

  17. ORIGINAL ARTICLES Prevalence of drug-drug interactions of ...

    African Journals Online (AJOL)

    2008-02-02

    Feb 2, 2008 ... Table II. Frequency of level 2 interactions between ARVs and the other drugs. Interacting ARVs and other drugs. N. %*. Didanosine + ketoconazole. 1. 0.91. Didanosine + ofloxacin. 1. 0.91. Didanosine + ciprofloxacin. 2. 1.82. Didanosine + iraconazole. 3. 2.73. Didanosine + ketoconazole. 2. 1.82. Efavirenz ...

  18. Arved Viirlaid teises kaanonis / Jüri Talvet

    Index Scriptorium Estoniae

    Talvet, Jüri, 1945-

    2002-01-01

    Arved Viirlaid 80. Ka tema juubeliks ilmunud ingliskeelsest luulekogust "Selected poems" (tlk. Taimi Ene Moks ja R. W. Stedingh). Ilmunud ka kogumikus: Talvet, Jüri. Tõrjumatu äär. Tartu : Ilmamaa, 2005, lk. 417-420, pealk.: Teises Kaanonis: Viirlaiu luule inglise keeles

  19. factors influencing adherence to arvs among patients attending

    African Journals Online (AJOL)

    2014-04-01

    Apr 1, 2014 ... FACTORS INFLUENCING ADHERENCE TO ARVS AMONG PATIENTS ATTENDING COMPREHENSIVE CARE CLINIC. WITHIN JOMO KENYATTA ... AIDS-related mortality is increasing among 20 to 49 year olds (Adults in their ..... Impact of HIV/AIDS on Labor Markets, Productivity and Welfare in Southern ...

  20. Challenges confronting health care workers in government's ARV ...

    African Journals Online (AJOL)

    Challenges confronting health care workers in government's ARV rollout: rights and responsibilities. ... Potchefstroom Electronic Law Journal/Potchefstroomse Elektroniese Regsblad ... Unless the rights of HCWs are recognised and their needs adequately addressed, the best laid plans of government will be at risk.

  1. Abortide arv kahaneb Eestis iga aastaga / Rebekka Lotman

    Index Scriptorium Estoniae

    Lotman, Rebekka, 1978-

    2005-01-01

    Vt. ka Zdorovje dlja Vsehh 2005 märts, lk. 6. Kuigi abortide arv väheneb Eestis iga aastaga, tuleb naistearstide hinnangul oodata veel kümmekond aastat, et see langeks sama madalale tasemele nagu Põhjamaades. Lisaks diagramm abortide arvu kohta 1991-2004

  2. Electrochemical evaluation and determination of antiretroviral drug fosamprenavir using boron-doped diamond and glassy carbon electrodes.

    Science.gov (United States)

    Gumustas, Mehmet; Ozkan, Sibel A

    2010-05-01

    Fosamprenavir is a pro-drug of the antiretroviral protease inhibitor amprenavir and is oxidizable at solid electrodes. The anodic oxidation behavior of fosamprenavir was investigated using cyclic and linear sweep voltammetry at boron-doped diamond and glassy carbon electrodes. In cyclic voltammetry, depending on pH values, fosamprenavir showed one sharp irreversible oxidation peak or wave depending on the working electrode. The mechanism of the oxidation process was discussed. The voltammetric study of some model compounds allowed elucidation of the possible oxidation mechanism of fosamprenavir. The aim of this study was to determine fosamprenavir levels in pharmaceutical formulations and biological samples by means of electrochemical methods. Using the sharp oxidation response, two voltammetric methods were described for the determination of fosamprenavir by differential pulse and square-wave voltammetry at the boron-doped diamond and glassy carbon electrodes. These two voltammetric techniques are 0.1 M H(2)SO(4) and phosphate buffer at pH 2.0 which allow quantitation over a 4 x 10(-6) to 8 x 10(-5) M range using boron-doped diamond and a 1 x 10(-5) to 1 x 10(-4) M range using glassy carbon electrodes, respectively, in supporting electrolyte. All necessary validation parameters were investigated and calculated. These methods were successfully applied for the analysis of fosamprenavir pharmaceutical dosage forms, human serum and urine samples. The standard addition method was used in biological media using boron-doped diamond electrode. No electroactive interferences from the tablet excipients or endogenous substances from biological material were found. The results were statistically compared with those obtained through an established HPLC-UV technique; no significant differences were found between the voltammetric and HPLC methods.

  3. Occurrence of intestinal parasites amongst persons on highly active antiretroviral drug therapy in Calabar, Cross River State, Nigeria

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    Paul C. Inyang-Etoh

    2015-02-01

    Full Text Available Opportunistic and intestinal parasite infections are common health problem among HIV/AIDS patients. Early detection and treatment of these parasites are important to improve the quality of life of this category of patients. The occurrence of intestinal parasites among 400 patients on highly active anti-retroviral drug therapy (HAART aged 11-60 years was investigated. Standard parasitological techniques like direct microscopy, formol ether concentration and modified Ziehl- Neelsen staining techniques were used to analyze the stool samples. Intestinal parasite infections were positive in 116 (29% of the subjects on HAART while control subjects had 12 (12% and the difference was statistically significant (P<0.05. Subjects in the age group 21-30 years had the highest infection rate 54 (35.1%. There was no statistically significant difference in infection according to age (P>0.05. Females 76 (32.5% had a higher prevalence rate than males 40 (24.1%. But there was no statistically significant difference in infection according to gender (P<0.05. Patients with CD4 count of less than 200 cells/mm3 were observed to be more infected than those with CD4 count of more than 200 cells/mm3. There was a strong positive correlation (r=0.94 between CD4 count and the occurrence of intestinal parasite infection. Protozoan parasites 84 (21.0% accounted for a higher prevalence rate than helminthic parasites 32 (8.0%. These findings has revealed a high prevalence of intestinal parasite infection among patients on HAART thus the routine screening of stool samples from these category of patients for intestinal parasites is advocated for effective management of the disease.

  4. Information-Motivation-Behavioral Skills Barriers Associated with Intentional versus Unintentional ARV Non-adherence Behavior among HIV-Positive Patients in Clinical Care

    Science.gov (United States)

    Norton, Wynne E.; Amico, K. Rivet; Fisher, William A.; Shuper, Paul A.; Ferrer, Rebecca A.; Cornman, Deborah H.; Trayling, Cynthia; Redding, Caroline; Fisher, Jeffrey D.

    2014-01-01

    Since the arrival of antiretroviral (ARV) therapy, HIV has become better characterized as a chronic disease rather than a terminal illness, depending in part on one’s ability to maintain relatively high levels of adherence. Despite research concerning barriers and facilitators of ARV adherence behavior, relatively little is known about specific challenges faced by HIV-positive persons who report “taking a break” from their ARV medications. The present study employed the Information-Motivation-Behavioral Skills Model of ARV Adherence as a framework for understanding adherence-related barriers that may differentiate between non-adherent patients who report “taking a break” versus those who do not report “taking a break” from their ARV medications. A sample of 327 HIV-positive patients who reported less than 100% adherence at study baseline provided data for this research. Participants who reported “taking a break” from their HIV medications without first talking to their healthcare provider were classified as intentionally non-adherent, while those who did not report “taking a break” without first talking with their healthcare provider were classified as unintentionally non-adherent. Analyses examined differences between intentionally versus unintentionally non-adherent patients with respect to demographic characteristics and responses to the adherence-related information, motivation, and behavioral skills questionnaire items. Few differences were observed between the groups on demographics, adherence-related information or adherence-related motivation; however, significant differences were observed on about half of the adherence-related behavioral skills items. Implications for future research, as well as the design of specific intervention components to reduce intentionally non-adherent behavior, are discussed. PMID:20552469

  5. EVALUATION OF THE ADVERSE REACTIONS OF ANTIRETROVIRAL DRUG REGIMENS IN A TERTIARY CARE HOSPITAL IN KOLKATA: A PROSPECTIVE OBSERVATIONAL STUDY

    Directory of Open Access Journals (Sweden)

    Avishek Banerjea

    2016-09-01

    Full Text Available BACKGROUND The introduction of Highly Active Antiretroviral Therapy (HAART has led to a significant decrease in AIDS-related mortality and morbidity. However, adverse reactions to these drugs, being inevitable, have led to major obstacles in its success, especially in developing nations like India. Moreover, the latest changes made by W.H.O. in the treatment guidelines of ART naive patients would expectedly lead to changes in the Adverse Drug Reaction (ADR patterns as well. Hence, this study aimed at evaluating the ADRs of currently prescribed ART regimens in a tertiary care hospital in Kolkata (WB. METHODOLOGY 168 ART naive patients enrolled initially were studied prospectively over a period of 1 year; each patient being followed up individually for 6 months. All patients were asked to visit the ART centre once a month or whenever they developed any symptom. They were screened clinically and investigated suitably by the physician according to the latest NACO guidelines. RESULTS Majority were males (56% with an M:F ratio of 1:0.774; 93.3% patients belonging to the 15-49 yrs. age group. TDF+3TC+EFV (56% was the commonest 1st line regimen prescribed. 76.6% patients experienced ADRs. Total 184 ADRs were noted, of which, GIT contributed the most (27.17%. Majority (66.67% of neurological ADRs was contributed by neuropsychiatric manifestations. Rash (10.3% was the commonest cutaneous ADR. Anaemia (13.6% was the commonest haematological ADR with a statistically significant female preponderance. Most ADRs were grade 1 (63.04%. Majority ADRs were “possible” (65.76% while 34.24% were “probable” by Naranjo scale. Maximal ADRs (48.37% were noted from patients under AZT+3TC+NVP regime. IRIS was observed as a paradoxical reaction to ART in 10% cases. CONCLUSION It should not be forgotten that ADRs are the inevitable consequence of pharmacotherapy. Hence, proper implementation of current protocols designed for screening of patients especially during

  6. Association between U.S. State AIDS Drug Assistance Program (ADAP) Features and HIV Antiretroviral Therapy Initiation, 2001–2009

    Science.gov (United States)

    Hanna, David B.; Buchacz, Kate; Gebo, Kelly A.; Hessol, Nancy A.; Horberg, Michael A.; Jacobson, Lisa P.; Kirk, Gregory D.; Kitahata, Mari M.; Korthuis, P. Todd; Moore, Richard D.; Napravnik, Sonia; Patel, Pragna; Silverberg, Michael J.; Sterling, Timothy R.; Willig, James H.; Collier, Ann; Samji, Hasina; Thorne, Jennifer E.; Althoff, Keri N.; Martin, Jeffrey N.; Rodriguez, Benigno; Stuart, Elizabeth A.; Gange, Stephen J.

    2013-01-01

    Background U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes. Methods We analyzed data from HIV-infected individuals who were clinically-eligible for ART between 2001 and 2009 (i.e., a first reported CD4+ <350 cells/uL or AIDS-defining illness) from 14 U.S. cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Using propensity score matching and Cox regression, we assessed ART initiation (within 6 months following eligibility) and virologic suppression (within 1 year) based on differences in two state ADAP features: the amount of state funding in annual ADAP budgets and the implementation of waiting lists. We performed an a priori subgroup analysis in persons with a history of injection drug use (IDU). Results Among 8,874 persons, 56% initiated ART within six months following eligibility. Persons living in states with no additional state contribution to the ADAP budget initiated ART on a less timely basis (hazard ratio [HR] 0.73, 95% CI 0.60–0.88). Living in a state with an ADAP waiting list was not associated with less timely initiation (HR 1.12, 95% CI 0.87–1.45). Neither additional state contributions nor waiting lists were significantly associated with virologic suppression. Persons with an IDU history initiated ART on a less timely basis (HR 0.67, 95% CI 0.47–0.95). Conclusions We found that living in states that did not contribute additionally to the ADAP budget was associated with delayed ART initiation when treatment was clinically indicated. Given the changing healthcare environment, continued assessment of the role of ADAPs and their features that facilitate prompt treatment is needed. PMID:24260137

  7. Optical delivery of ARV drugs into HIV-1 permissive cells

    CSIR Research Space (South Africa)

    Khanyile, T

    2013-10-01

    Full Text Available into HIV-1 permissive cells Thulile Khanyile1,2, Maria Papathanasopoulos2, Andrew Forbes1 and Patience Mthunzi1* 1. National Laser Centre, Council for Scientific and Industrial Research, PO Box 395, Pretoria, 0001, South Africa 2. HIV Pathogenesis... perspectives Dr Patience Mthunzi (NLC-CSIR) Prof Maria Papathanasopoulos (Wits) Prof Andrew Forbes (NLC-CSIR) Dr Hazel Mufhandu (Biosciences – CSIR) Dr Dalu Ncama (Biosciences – CSIR) Acknowledgements Thank you ...

  8. Trends in antiretroviral therapy prescription, durability and modification: new drugs, more changes, but less failure.

    Science.gov (United States)

    Eaton, Ellen F; Tamhane, Ashutosh; Davy-Mendez, Thibaut; Mathews, William C; Moore, Richard D; Saag, Michael S; Mugavero, Michael J

    2018-01-28

    To evaluate the real world durability of contemporary ART for treatment-naïve people living with HIV (PLWH). A retrospective follow-up study in a multisite cohort. This study of the CNICS (CFAR Network of Integrated Clinical Systems) cohort integrates data from eight Center for AIDS Research (CFARs). PLWH initiating ART between 2007 and 2014 were included. Durability was defined as time from the initiation until discontinuation/modification using Kaplan-Meier survival curves. Cox Proportional Hazards measured associations with various sociodemographic and clinical characteristics. Among 5373 PLWH, the initial regimen was modified in 2285 (43%) patients. Efavirenz/emtricitabine/tenofovir (n = 2173, 40%) was the most commonly prescribed initial ART regimen; elvitegravir/cobicistat/emtricitabine/tenofovir became more common after 2012. Median durability for all regimens was 48.6 months. There were statistically significant differences in median durability for NNRTI, InSTI, and protease inhibitor-based regimens, which lasted 61, 44, and 32 months, respectively. Female sex (aHR = 1.4; 95% CI 1.2-1.6), intravenous drug use (aHR = 1.6; 95% CI 1.3-1.9), and CD4 cell count less than 200 cells/μl (aHR = 1.2; 95% CI 1.1-1.3) were significantly associated with regimen modification. Compared with InSTI, those receiving an InSTI/protease inhibitor (aHR = 2.7; 95% CI 2.0-3.7) or protease inhibitor-based ART (aHR = 1.9; 95% CI 1.6-2.2) were significantly more likely to be modified; but those receiving NNRTI (aHR = 1.1; 95% CI 0.9-1.3) were not. In treatment-naive PLWH, NNRTI and InSTI-based ART were most durable, relative to protease inhibitor and InSTI/protease inhibitor-based ART, and were least likely to be modified/discontinued. A greater understanding of reasons for regimen modification/discontinuation is needed to analyze contemporary regimen durability.

  9. Clinical manifestations and treatment outcomes in HIV-1-infected children receiving antiretroviral therapy in Karachi, Pakistan.

    Science.gov (United States)

    Mir, Fatima; Qamar, Farah Naz; Baig-Ansari, Naila; Abro, Azra Ghayas; Abbas, Syed Qamar; Kazi, Mohammed Ahmed; Rizvi, Arjumand; Zaidi, Anita Kaniz Mehdi

    2014-04-15

    The impact of antiretroviral (ARV) therapy on immunological and growth parameters in HIV-positive children in Pakistan has not been reported to date. A retrospective chart review of children diagnosed with HIV at the Sindh AIDS Control Proigramme (SACP) and registered at the Aga Khan University, Karachi, between January 2005 and 2013 was conducted, evaluating clinical and laboratory profiles of HIV+ ARV+ children for ARV impact (serial height and weight CD4 and viral counts). Twenty-four children were diagnosed and registered as HIV positive over five years, and 20 were started on ARV. Six were excluded from analysis (ARV duration treatment failure at a median duration of 25 weeks (IQR 18-32) on ARV and underwent resistance genotyping. All nine had NNRTI resistance, two had high-grade NRTI resistance (≥ 4 thymidine analog mutations). Median age at start of ARV was 71.5 weeks (IQR 37.5-119). Median baseline weight for age (WAZ) and height for age (HAZ) z-scores changed from -1.94 to 1.69 and -1.99 to -1.59, respectively, after six months of therapy. Median CD4 percentage and viral load at baseline changed from 13.8 to 17.8, while viral load changed from 285 × 104 copies to zero at six months. ARV improved absolute CD4 and viral counts. Weight and height did not  improve significantly, highlighting the need for aggressive nutritional rehabilitation. Early development of ARV resistance in these children requires formal assessment.

  10. Antiretrovirals and safer conception for HIV-serodiscordant couples

    Science.gov (United States)

    Matthews, Lynn T.; Smit, Jennifer A.; Cu-Uvin, Susan; Cohan, Deborah

    2013-01-01

    Purpose of review Many men and women living with HIV and their uninfected partners attempt to conceive children. HIV-prevention science can be applied to reduce sexual transmission risk while respecting couples’ reproductive goals. Here we discuss antiretrovirals as prevention in the context of safer conception for HIV-serodiscordant couples. Recent findings Antiretroviral therapy (ART) for the infected partner and pre-exposure prophylaxis (PrEP) for the uninfected partner reduce the risk of heterosexual HIV transmission. Several demonstration projects suggest the feasibility and acceptability of antiretroviral (ARV)s as periconception HIV-prevention for HIV-serodiscordant couples. The application of ARVs to periconception risk reduction may be limited by adherence. Summary For male-infected (M+F−) couples who cannot access sperm processing and female-infected (F+M−) couples unwilling to carry out insemination without intercourse, ART for the infected partner, PrEP for the uninfected partner, combined with treatment for sexually transmitted infections, sex limited to peak fertility, and medical male circumcision (for F+M couples) provide excellent, well tolerated options for reducing the risk of periconception HIV sexual transmission. PMID:23032734

  11. Diversidade e prevalência das mutações de resistência genotípica aos antirretrovirais entre crianças infectadas pelo HIV-1 Diversity and prevalence of antiretroviral genotypic resistance mutations among HIV-1-infected children

    Directory of Open Access Journals (Sweden)

    Flávia J. Almeida

    2009-04-01

    que é compatível com o uso ARV nesses pacientes.OBJECTIVE: To evaluate genotyping and subtyping in antiretroviral (ARV naïve and experienced children, as well as drug resistance profiles through genotyping in these children. METHODS: This retrospective study assessed ARV-naïve HIV children and HIV children failing highly active antiretroviral treatment (HAART followed up at Santa Casa de São Paulo. Genotyping was performed using purified polymerase chain reaction (PCR products from retrotranscribed RNA using Kit Viroseq HIV-1 Genotyping System 2.0 or nested PCR in-house. Sequencing was performed using automatic equipment (ABI 3100. ARV resistance mutations were analyzed in the Stanford HIV Drug Resistance Database and subtyping was performed at the National Center for Biotechnology Information (NCBI, using SimPlot analysis, together with phylogenetic analysis. RESULTS: No primary ARV resistance mutation was detected in the 24 ARV-naïve children, although there were mutations that may contribute to resistance to nucleoside analogue reverse transcriptase inhibitors (NRTI (12.5% and to protease inhibitors (PI (95.8%. For the 23 children failing HAART, we found ARV resistance mutations to NRTI in 95.6% and to non-nucleoside analogue reverse transcriptase inhibitors (NNRTI in 60.8%. For PI, we found ARV resistance mutations in 95.7%, 47.8% of which had only polymorfisms. In the subtyping analyses, 78.3% of the sequences clustered in HIV-1 subtype B, 4.3% in C, 13% in F and 4.4% in recombinant forms. CONCLUSION: Our results show low rates of primary resistance in ARV-naïve children and high rates of resistance in children failing ARV treatment, which is compatible with ARV use in these patients.

  12. In Silico and in Vitro Screening for P-Glycoprotein Interaction with Tenofovir, Darunavir, and Dapivirine: An Antiretroviral Drug Combination for Topical Prevention of Colorectal HIV Transmission.

    Science.gov (United States)

    Swedrowska, Magda; Jamshidi, Shirin; Kumar, Abhinav; Kelly, Charles; Rahman, Khondaker Miraz; Forbes, Ben

    2017-08-07

    The aim of the study was to use in silico and in vitro techniques to evaluate whether a triple formulation of antiretroviral drugs (tenofovir, darunavir, and dapivirine) interacted with P-glycoprotein (P-gp) or exhibited any other permeability-altering drug-drug interactions in the colorectal mucosa. Potential drug interactions with P-gp were screened initially using molecular docking, followed by molecular dynamics simulations to analyze the identified drug-transporter interaction more mechanistically. The transport of tenofovir, darunavir, and dapivirine was investigated in the Caco-2 cell models and colorectal tissue, and their apparent permeability coefficient (P app ), efflux ratio (ER), and the effect of transporter inhibitors were evaluated. In silico, dapivirine and darunavir showed strong affinity for P-gp with similar free energy of binding; dapivirine exhibiting a ΔG PB value -38.24 kcal/mol, darunavir a ΔG PB value -36.84 kcal/mol. The rank order of permeability of the compounds in vitro was tenofovir silico findings. Neither tenofovir nor dapivirine transport was influenced by P-gp inhibitors. The absorptive permeability of darunavir (P app = 6.4 ± 0.9 × 10 -6 cm/s) was concentration dependent with ER = 6.3, which was reduced by verapamil to 1.2. Administration of the drugs in combination did not alter their permeability compared to administration as single agents. In conclusion, in silico modeling, cell culture, and tissue-based assays showed that tenofovir does not interact with P-gp and is poorly permeable, consistent with a paracellular transport mechanism. In silico modeling predicted that darunavir and dapivirine were P-gp substrates, but only darunavir showed P-gp-dependent permeability in the biological models, illustrating that in silico modeling requires experimental validation. When administered in combination, the disposition of the proposed triple-therapy antiretroviral drugs in the colorectal mucosa will depend on their distinctly

  13. Initial Virologic Response and HIV Drug Resistance Among HIV-Infected Individuals Initiating First-line Antiretroviral Therapy at 2 Clinics in Chennai and Mumbai, India

    Science.gov (United States)

    Hingankar, Nitin K.; Thorat, Smita R.; Deshpande, Alaka; Rajasekaran, S.; Chandrasekar, C.; Kumar, Suria; Srikantiah, Padmini; Chaturbhuj, Devidas N.; Datkar, Sharda R.; Deshmukh, Pravin S.; Kulkarni, Smita S.; Sane, Suvarna; Reddy, D. C. S.; Garg, Renu; Jordan, Michael R.; Kabra, Sandhya; Paranjape, Ramesh S.

    2012-01-01

    Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of Mumbai due to high rates of loss to follow-up. Findings highlight the need for defaulter tracing and scale-up of routine viral load testing to identify patients failing first-line ART. PMID:22544202

  14. Confirmation of factors that influence antiretroviral regimen change and the subsequent patient outcomes at a Regional Hospital in rural KwaZulu-Natal

    Directory of Open Access Journals (Sweden)

    Vereesha Soorju

    2016-03-01

    Full Text Available Background: Treatment failure (TF and adverse drug reactions (ADRs are the main indications for antiretroviral therapy (ART regimen change. Identification of factors influencing regimen change and subsequent health outcomes of patients after regimen change is essential in providing a sustainable and effective antiretroviral roll-out campaign.Aim: To confirm the factors that influence antiretroviral regimen change and to evaluate patient outcomes post regimen change.Methods: A retrospective chart analysis of 269 HIV-infected non-pregnant patients (age >18 years, who underwent an antiretroviral (ARV regimen change and were followed up for approximately one year since initiation, was undertaken at a Provincial Hospital ARV Clinic in KwaZulu-Natal, from January 2008 to December 2012.Results: Of the 269 patients, there were 200 females (75%. Most patients were between the ages 30 and 44 (57.6%. Only five patients had coexisting tuberculosis (TB infection (2%. The most common first-line ART regimen to be changed was stavudine (D4T/lamivudine(3TC/ efavirenz(EFV n = 111(41%. The most common regimen patients were changed to was tenofovir (TDF/3TC/EFV n = 89(33%. Stavudine was the most commonly substituted drug (35.5%. Lipodystrophy was the most common ADR (56.8%. ADR was the indication for ART regimen change in 175 patients (65%, whilst TF accounted for ART regimen change in 94 patients (35%. Immunological success (CD4 counts was shown after regimen change (374.21 ± 243.16 vs. 456.09 ± 250.07, CI: 0.95, p < 0.001. Undetectable viral loads were measured in 172/205 (83.9% patients post regimen change.Conclusion: ADRs were the main cause for antiretroviral regimen change. Stavudine was the most substituted drug with lipodystrophy being the most common side effect. Coexisting TB infection did not influence regimen change. Immunological and virological success was shown after regimen modification.

  15. HIV drug resistance and hepatitis co-infections in HIV-infected adults and children initiating antiretroviral therapy in Rwanda

    NARCIS (Netherlands)

    Rusine-Bahunde, J.

    2015-01-01

    Since the roll-out of antiretroviral therapy (ART), few data have been generated on outcomes and outcome predictors of ART in adults and children in Rwanda. Equally, the extent of chronic hepatitis virus infections and their impact on the ART outcomes in the country are not known. This information

  16. Lapsetoetuse saajate arv tõuseb / Eli Lilles

    Index Scriptorium Estoniae

    Lilles, Eli

    2007-01-01

    1. septembrist saavad lapsetoetust ja teisi peretoetusi ka 16-19-aastased noored, kes õpivad õhtuses õppevormis või kaugõppes. Ilmunud ka Türi Rahvaleht 7. september 2007, lk. 4, pealkiri kujul : lapsetoetuse saajate arv suurenes; Vooremaa 11. september 2007, lk. 5, pealkiri kujul: lapsetoetust saavad ka õhtukoolis õppijad; Lõuna-Mulgimaa 8. september 2007, lk. 6, pealkiri kujul: lapse- ja peretoetused

  17. Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study.

    Science.gov (United States)

    Flax, Valerie L; Bentley, Margaret E; Combs, Gerald F; Chasela, Charles S; Kayira, Dumbani; Tegha, Gerald; Kamwendo, Debbie; Daza, Eric J; Fokar, Ali; Kourtis, Athena P; Jamieson, Denise J; van der Horst, Charles M; Adair, Linda S

    2014-04-01

    Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants. We tested the effects of lipid-based nutrient supplements (LNS) that contained 1.3 times the Recommended Dietary Allowance of sodium selenite and antiretroviral drugs (ARV) on maternal plasma and breast-milk selenium concentrations. HIV-infected Malawian mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomly assigned at delivery to receive: LNS, ARV, LNS and ARV, or a control. In a subsample of 526 mothers and their uninfected infants, we measured plasma and breast-milk selenium concentrations at 2 or 6 (depending on the availability of infant samples) and 24 wk postpartum. Overall, mean (± SD) maternal (range: 81.2 ± 20.4 to 86.2 ± 19.9 μg/L) and infant (55.6 ± 16.3 to 61.0 ± 15.4 μg/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 ± 11.5 to 9.8 ± 7.3 μg/L) from 2 or 6 to 24 wk postpartum (all P maternal plasma or breast-milk selenium from 2 or 6 to 24 wk postpartum (both P maternal plasma and breast-milk selenium, but maternal selenium concentrations were positively associated with infant plasma selenium at 2 or 6 and 24 wk postpartum (P breastfeeding women.

  18. Mother-to-child transmission (MTCT) of HIV and drugs of abuse in post-highly active antiretroviral therapy (HAART) era.

    Science.gov (United States)

    Purohit, Vishnudutt; Rapaka, Rao S; Shurtleff, David

    2010-12-01

    In the pre-highly active antiretroviral therapy (HAART) era, prenatal "vertical" mother-to-child transmission (MTCT) of HIV was about 25% and exposure of pregnant mothers to drugs of abuse (illicit drugs and tobacco smoking) was a significant contributory factor of MTCT. However, with the introduction of HAART, the rate of MTCT of HIV has decreased to less that 2%. But, it is estimated that currently about 5.1% of pregnant women use illicit drugs and 16.4% smoke tobacco. The residual prevalence of MTCT is of concern and may be related to this continued prevalence of substance use among pregnant mothers. In this report, we review and present evidence that supports the hypothesis that drugs of abuse do have the potential to increase MTCT of HIV in the presence of HAART. Exposure to drugs of abuse during pregnancy may increase MTCT of HIV through a variety of mechanisms that are addressed in detail including possible damage to the placenta, induction of preterm birth, and increasing maternal plasma viral load though a variety of putative mechanisms such as: (a) promoting HIV replication in monocyte/macrophages; (b) increasing the expression of CCR5 receptors; (c) decreasing the expression of CCR5 receptor ligands; (d) increasing the expression of CXCR4 receptors; (e) increasing the expression of DC-SIGN; (f) impairing the efficacy of HAART through drug-drug interaction; and (g) promoting HIV mutation and replication through non-adherence to HAART.

  19. Factors associated with clinical, immunological and virological responses in protease-inhibitor-experienced brazilian children receiving highly active antiretroviral therapy containing Lopinavir-Ritonavir

    Directory of Open Access Journals (Sweden)

    Daisy Maria Machado

    Full Text Available This study evaluates clinical, virological and immunological responses to antiretroviral (ARV therapy based on Lopinavir/ritonovir (LPV/r in previously protease -inhibitor-experienced children. The study included 29 Brazilian children (median age = 5.91 years who had failed previous ARV therapy and had begun a regimen based on LPV/r. At 12 months follow-up, a good virological response to LPV/r therapy was defined as achieving an undetectable viral load or as a decrease in plasma HIV RNA levels to > 1 log. A good immunological response was defined as an increase in CD4+ cell count from baseline sufficient to attain a better CDC immune stage classification. The number of infectious episodes 12 months before and 12 months after beginning LPV/r was assessed. Sixteen (55.2% and 19 (65.5% of 29 patients exhibited good virological and immunological responses, respectively. Baseline CD4+ values (>500 predicted both virological and immunological responses (p<0.05. Older children were less likely to develop an immunological response (p<0.001 than younger children. Nine children receiving 3 ARV drugs plus LPV/r showed an immunological response (100% compared to 10/20 (50% children receiving 2 drugs plus LPV/r (p=0.01. A lower number (n<5 of infectious episodes was noted after 12 months follow-up in children using the LPV/r regimen (p=0.006. There was a positive correlation between children whose baseline CD4+ values were greater than 500 cells/mm³ and virological responses. Although virological responses to therapy were seen in about half the children (55.2%, the use of HAART containing LPV/r provided clinical and immmunological benefits.

  20. "Every drug goes to treat its own disease…" - a qualitative study of perceptions and experiences of taking anti-retrovirals concomitantly with anti-malarials among those affected by HIV and malaria in Tanzania

    DEFF Research Database (Denmark)

    Mangesho, Peter E; Reynolds, Joanna; Lemnge, Martha

    2014-01-01

    and supporting the clinical management and treatment for co-infected individuals. METHODS: A qualitative study was conducted in Tanzania alongside a clinical trial of concomitant treatment for HIV and malaria co-infection. Focus group discussions were held with people receiving treatment for HIV and/or malaria...... to their compromised immune status but saw the disease as unavoidable. For those enrolled in the clinical controlled study, taking anti-malarials together with ARVs was largely seen as unproblematic, with health workers' advice and endorsement of concomitant drug taking influential in reported adherence. However......, perceptions of drug strength appeared to compel some people not enrolled in the clinical study to take the drugs at separate times to avoid anticipated harm to the body. CONCLUSIONS: Management of HIV and malaria concurrently often requires individuals to cross the domains of different disease programmes...

  1. Low Prevalence of Antiretroviral Resistance Among HIV Type 1-Positive Prisoners in the Southeast United States

    Science.gov (United States)

    Rosen, David; Wohl, David A.; Kiziah, Nichole; Sebastian, Joseph; Eron, Joseph J.; White, Becky

    2013-01-01

    Abstract Drug-resistant HIV complicates management of HIV infection. Although an estimated 14% of all HIV-positive persons pass through a prison or jail in the United States each year, little is known about the overall prevalence of antiretroviral (ARV) resistance in incarcerated persons. All genotypic sequence data on HIV-positive prisoners in the North Carolina (NC) Department of Corrections (DOC) were obtained from LabCorp. Screening for major resistance mutations in protease (PI) and reverse transcriptase (NRTI and NNRTI) was done using Genosure and the Stanford HIV Database. For subjects with multiple genotype reports, each mutation was counted only once and considered present on all subsequent genotypes. Between October 2006 and February 2010, the NC DOC incarcerated 1,911 HIV+ individuals of whom 19.2% (n=367) had at least one genotype performed. The overall prevalence of a major resistance mutation was 28.3% (95% CI 23.7, 33.0). Among prisoners ever exposed to an ARV during incarceration (n=329) prevalence of a major resistance mutation was 29.8% (95% CI 24.9, 34.7); resistance by class was 20.4% (95% CI 16.0, 24.7) for NRTIs, 19.8% (95% CI 15.5, 24.1) for NNRTIs, and 8.8% (95% CI 5.8,11.9) for PIs. Single class drug resistance was most prevalent at 14.2% (10.2,17.7) followed by dual 12.5% (I8.9,16.0) and triple class 3.3% (1.4,5.3) resistance. The three most prevalent mutations were K103N 15.8% (12.0, 20.2), M184V 14.3% (10.7,18.5), and M41L 4.9% (2.8,7.8). In the NC DOC ARV resistance prevalence, dual and triple class drug resistance was moderate over the study period. Resistance to PIs was lower than NNRTIs and NRTIs, likely reflecting higher usage of these two classes or a lower barrier to resistance. PMID:22966822

  2. Relations of pursuance taking drug of HIV patients with the success of Antiretroviral Therapy (ART in Poli Serunai Hospital Dr. Achmad Muchtar Bukittinggi Year 2014

    Directory of Open Access Journals (Sweden)

    YELMI RENI PUTRI

    2016-06-01

    Full Text Available Relations of pursuance taking drug of HIV patients with the success of Antiretroviral Therapy (ART in Poli Serunai Hospital Dr. Achmad Muchtar Bukittinggi Year 2014 Yelmi Reni Putri, AdrianiProgram Studi Ilmu Keperawatan STIKes Fort De Kock BukittinggiEmail : Yelmi.reni@gmail.com ABSTRACT1st of of December is the day each year is celebrated as a day of HIV / AIDS this year themed "prevent HIV / AIDS, protect workers, families and the nation", this is when the right moment for us health workers give a good contribution to overcome or provide suggestions for improving services to patients with HIV / AIDS. The increasing number of patients with HIV / AIDS today is not only to make our health care workers need to be vigilant, even patients and families also need to work together to overcome this proble.The purpose of this study was to identify the level of compliance of patients taking antiretroviral drugs and HIV-positive people do with the success of antiretroviral therapy, the study sample taken in accident sampling with the number of respondents 40 patients idODHA of the month from May to October 2014. The study design using qualitative and quantitative method Mix , measuring instrument used in this research is a questionnaire that contains the characteristics of patients living with HIV, guided interviews to assess the role of the KPA, manager of HIV RSAM, and people living with HIV patients themselves.The result showed 57.5% of patients did not obey, and as much as 52.5% of patients successfully in HIV treatment, but there is no relationship between adherence with therapy success with value value 0.583 and 0.677 OR it is associated with the patient's anxiety and fear to know the results of which he repeated CD4 CD4 is one measure of the success of therapy. The conclusion of this study is important to know the patients' adherence PLWHA still low this will impact on the occurrence of resistance will even increase mortality, it is recommended

  3. Impact of injecting drug use on response to highly active antiretroviral treatment in HIV-1-infected patients: a nationwide population-based cohort study

    DEFF Research Database (Denmark)

    Larsen, Mette Vang; Omland, Lars; Gerstoft, Jan

    2010-01-01

    The objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients infected through injecting drug use (injecting drug users, IDUs) compared to patients infected via other routes (non-IDUs). We conducted...... a nationwide population-based cohort study of all HIV-infected patients who initiated HAART during the study period of 1 January 1995 to 31 December 2007. We compared changes in CD4(+) cell counts, percentage of full viral suppression (....0002). Absolute CD4(+) cell count and survival were lower for IDUs compared to non-IDUs (adjusted mortality rate ratio 3.6 (95% CI 2.9-4.3)). IDUs were more likely to receive a first regimen based on protease inhibitors (PIs) compared to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens...

  4. Quality of antiretroviral and opportunistic infection medications dispensed from developing countries and Internet pharmacies.

    Science.gov (United States)

    Wang, Ting; Hoag, Stephen W; Eng, Maria L; Polli, James; Pandit, Neha Sheth

    2015-02-01

    Generic manufacturers help decrease the cost of antiretroviral (ARV) and antimicrobial medications which are used to treat opportunistic infections (OIs) in developing countries. Concerns have been expressed about potential quality issues with such medications as a result of the identification of numerous counterfeit medications in developing countries. However, few studies have assessed the quality of these medications using the United States Pharmacopeia (USP) compendial standards. The goal of this study was to assess the quality of ARV and OI medications obtained from various sources, including South Africa, United States, China, Ethiopia, Thailand, Laos, Mexico, Nigeria and five Internet pharmacies. Zidovudine, lamivudine, efavirenz, nevirapine, isoniazid and sulfamethoxazole/trimethoprim tablets/capsules were obtained from eight countries and five Internet pharmacies. The tablets/capsules were separated into distinct samples, based on the drug's active ingredient, manufacturer and drug control number. Each distinct sample was analysed for drug content, dissolution, content uniformity and breaking force using USP 32-National Formulary 27 (USP 32-NF 27) compendial methods and compared to the USP standards. A total of 2027 tablets/capsules were obtained with 88 distinct samples identified. All samples met the USP 32-NF 27 standards for drug content with a range of 92.7-108.6%. Six of the 88 samples failed the dissolution test by 1.5-8.3% below the standard range. Ninety-eight per cent of all 88 samples met the USP criteria for content uniformity based on weight variation. One sample of isoniazid was found to have a low breaking force of 2.8 kiloponds. The results of this study show that there were no problems with the samples of ARV and OI medications tested for drug quality from the specified locations. As there are many studies and reports that discuss the poor quality of generic medications with only a few assessing drug quality, the implications of this study

  5. Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Ying Zhou

    2016-01-01

    Full Text Available Antiretroviral therapy (ART has been shown to improve survival of patients with Human Immunodeficiency Virus (HIV infection and to reduce HIV-1 transmission. Therefore, the Chinese central government initiated a national program to provide ART free of charge to HIV-1 patients. We conducted a cross-sectional survey in Jiangsu province to determine the level of drug resistance (DR in HIV-1 infected patients and the correlates of DR in virological failures in 2012. Approximately 10.4% of the HIV-1 patients in the study experienced virological failure after one year of ART and were divided into drug sensitive and drug resistant groups based on genotype determination. The viral loads (VLs in the drug resistant group were significantly lower than the drug sensitive group. There were two independent predictors of virological failure: male gender and increasing duration of treatment. The primary mutations observed in the study were against nucleoside reverse transcriptase inhibitors (NRTIs which were M184V (79.45% and K103N (33.70% in nonnucleoside reverse transcriptase inhibitors (NNRTIs. The overall rate of DR in Jiangsu province is still relatively low among treated patients. However, close monitoring of drug resistance in male patients in the early stages of treatment is vital to maintaining and increasing the benefits of HIV ART achieved to date.

  6. Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies.

    Science.gov (United States)

    Hamers, Raph L; Sigaloff, Kim C E; Wensing, Annemarie M; Wallis, Carole L; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E; Wellington, Maureen; Osibogun, Akin; Stevens, Wendy S; Rinke de Wit, Tobias F; Schuurman, Rob

    2012-06-01

    Human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy (ART). This cohort study examined patterns of drug-resistance mutations (DRMs) in individuals with virological failure on first-line ART at 13 clinical sites in 6 African countries and predicted their impact on second-line drug susceptibility. A total of 2588 antiretroviral-naive individuals initiated ART consisting of different nucleoside reverse transcriptase inhibitor (NRTI) backbones (zidovudine, stavudine, tenofovir, or abacavir, plus lamivudine or emtricitabine) with either efavirenz or nevirapine. Population sequencing after 12 months of ART was retrospectively performed if HIV RNA was >1000 copies/mL. The 2010 International Antiviral Society-USA list was used to score major DRMs. The Stanford algorithm was used to predict drug susceptibility. HIV-1 sequences were generated for 142 participants who virologically failed ART, of whom 70% carried ≥1 DRM and 49% had dual-class resistance, with an average of 2.4 DRMs per sequence (range, 1-8). The most common DRMs were M184V (53.5%), K103N (28.9%), Y181C (15.5%), and G190A (14.1%). Thymidine analogue mutations were present in 8.5%. K65R was frequently selected by stavudine (15.0%) or tenofovir (27.7%). Among participants with ≥1 DRM, HIV-1 susceptibility was reduced in 93% for efavirenz/nevirapine, in 81% for lamivudine/emtricitabine, in 59% for etravirine/rilpivirine, in 27% for tenofovir, in 18% for stavudine, and in 10% for zidovudine. Early failure detection limited the accumulation of resistance. After stavudine failure in African populations, zidovudine rather than tenofovir may be preferred in second-line ART. Strategies to prevent HIV-1 resistance are a global priority.

  7. Potential impact of drugs of abuse on mother-to-child transmission (MTCT) of HIV in the era of highly active antiretroviral therapy (HAART).

    Science.gov (United States)

    Purohit, Vishnudutt; Rapaka, Rao S; Schnur, Paul; Shurtleff, David

    2011-05-23

    This report is a summary of a symposium entitled "Mother-to-Child Transmission (MTCT) of HIV and Drugs of Abuse in Highly Active Antiretroviral Therapy (HAART) Era," organized by The National Institute on Drug Abuse, National Institutes of Health in Rockville, Maryland, October 13, 2009. In the pre-HAART era, the prevalence of MTCT of HIV was about 25% and exposure of pregnant mothers to drugs of abuse (illicit drugs and tobacco smoking) was a significant factor in MTCT. However, with the introduction of HAART, the rate of MTCT of HIV has decreased to less that 2%. In the Unites States, it is estimated that currently about 5.1% of pregnant women use illicit drugs and 16.4% smoke tobacco. The residual prevalence of MTCT in the HAART era is still of concern and may be related to this continued prevalence of substance use among pregnant mothers. In this report, we review and present evidence that supports the hypothesis that drugs of abuse do have the potential to increase MTCT of HIV in the presence of HAART. Exposure to drugs of abuse during pregnancy may increase MTCT of HIV through a variety of mechanisms including possible damage to the placenta, induction of preterm birth, and increasing maternal plasma viral load through a variety of putative mechanisms such as: a) promoting HIV mutation and replication through non-adherence to HAART; b) impairing the efficacy of HAART through drug-drug interaction; and c) promoting HIV replication in monocyte/macrophages. Drugs of abuse may promote HIV replication by increasing the expression of CCR5 receptors, decreasing the expression of CCR5 receptor ligands, increasing the expression of CXCR4 receptors, increasing the expression of DC-SIGN, and possibly inducing epigenetic changes. Published by Elsevier Inc.

  8. AIDS Diarrhea and Antiretroviral Drug Concentrations: A Matched-Pair Cohort Study in Port au Prince, Haiti

    Science.gov (United States)

    Dillingham, Rebecca; Leger, Paul; Beauharnais, Carole-Anne; Miller, Erica; Kashuba, Angela; Jennings, Steven; Dupnik, Kathryn; Samie, Amidou; Eyma, Etna; Guerrant, Richard; Pape, Jean; Fitzgerald, Daniel

    2011-01-01

    Diarrhea in patients with acquired immunodeficiency syndrome (AIDS) may cause malabsorption of medications and failure of antiretroviral therapy (ART). We prospectively evaluated human immunodeficiency virus-1 (HIV-1)-infected patients with and without chronic diarrhea initiating ART in Haiti. We report mean plasma antiretroviral concentrations at 2 and 4 weeks. We measured plasma HIV-1 RNA levels at four points. Fifty-two HIV-1-infected patients (26 matched pairs) were enrolled. No differences in antiretroviral concentrations were detected. At week 24, 18/25 (72%) cases and 16/24 (68%) controls had undetectable plasma HIV-1 RNA levels (P = 0.69). Patients with plasma HIV-1 RNA levels > 50 copies/mL at week 24 had lower early efavirenz concentrations than patients with undetectable HIV-1 RNA (2,621 ng/mL versus 5,278 ng/mL; P = 0.02). Diarrhea at ART initiation does not influence plasma concentrations of the medications evaluated. Virologic outcome at Week 24 does correlate with efavirenz concentrations early in therapy but not with the presence of chronic diarrhea. PMID:21633022

  9. Serum lipid profile of anti-retroviral (ARV) naïve human ...

    African Journals Online (AJOL)

    Background: Human immunodeficiency virus infection has become pandemic in Nigeria and affects the immune system. Most HIV/ AIDS patients develop multiple metabolic abnormalities including insulin resistance, lipodystrophy and dyslipidemia leading to increased risk of cardiovascular disease (CVD). Objective: To ...

  10. CD4+ T cells spontaneously producing human immunodeficiency virus type I in breast milk from women with or without antiretroviral drugs

    Directory of Open Access Journals (Sweden)

    Rubbo Pierre-Alain

    2011-05-01

    Full Text Available Abstract Background Transmission of human immunodeficiency virus type 1 (HIV-1 through breast-feeding may involve both cell-free and cell-associated virus. This latter viral reservoir remains, however, to be fully explored. CD4+ T cell-associated virus production in breast milk was therefore investigated. Methods The ex vivo spontaneous production of HIV-1 antigen and HIV-1 RNA by CD4+ T cells was measured in paired blood and breast milk samples from 15 HIV-1 infected women treated or not with antiretroviral drugs. Spontaneous antigen secreting cells (HIV-1-AgSCs from breast milk and blood were enumerated by an ELISpot assay, and cell-associated HIV-1 RNA was quantified by real-time PCR in supernatants of CD4+ T cells cultured for 18 hours without addition of polyclonal activators. Results Among the CD4+ T cells present in breast milk, memory cells expressing high levels of cell-surface activation markers were predominant. Spontaneous HIV-1-AgSCs were detected and enumerated in the breast milk of all 15 women, with a median number of 13.0 and 9.5 HIV-1- AgSCs/106 CD4+ T cells in aviremic (n = 7 and viremic (n = 8 women, respectively. Cell- associated HIV-1 RNA was detected in cell-free supernatants from 4/7 aviremic and 5/8 viremic individuals at median levels of 190 and 245 copies/ml, respectively. Conclusions Activated CD4+ T cells producing HIV-1 are detected in the breast milk of untreated individuals as well as those receiving highly active antiretroviral therapy. This finding strongly suggests that HIV-1 replication occurs in latently infected CD4+ T cells that, upon spontaneous activation, revert to productively infected cells. These cells might be responsible for a residual breast milk transmission despite maternal highly active antiretroviral therapy.

  11. CD4+ T cells spontaneously producing human immunodeficiency virus type I in breast milk from women with or without antiretroviral drugs.

    Science.gov (United States)

    Valea, Diane; Tuaillon, Edouard; Al Tabaa, Yassine; Rouet, François; Rubbo, Pierre-Alain; Meda, Nicolas; Foulongne, Vincent; Bollore, Karine; Nagot, Nicolas; Van de Perre, Philippe; Vendrell, Jean-Pierre

    2011-05-13

    Transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding may involve both cell-free and cell-associated virus. This latter viral reservoir remains, however, to be fully explored. CD4+ T cell-associated virus production in breast milk was therefore investigated. The ex vivo spontaneous production of HIV-1 antigen and HIV-1 RNA by CD4+ T cells was measured in paired blood and breast milk samples from 15 HIV-1 infected women treated or not with antiretroviral drugs. Spontaneous antigen secreting cells (HIV-1-AgSCs) from breast milk and blood were enumerated by an ELISpot assay, and cell-associated HIV-1 RNA was quantified by real-time PCR in supernatants of CD4+ T cells cultured for 18 hours without addition of polyclonal activators. Among the CD4+ T cells present in breast milk, memory cells expressing high levels of cell-surface activation markers were predominant. Spontaneous HIV-1-AgSCs were detected and enumerated in the breast milk of all 15 women, with a median number of 13.0 and 9.5 HIV-1- AgSCs/106 CD4+ T cells in aviremic (n = 7) and viremic (n = 8) women, respectively. Cell- associated HIV-1 RNA was detected in cell-free supernatants from 4/7 aviremic and 5/8 viremic individuals at median levels of 190 and 245 copies/ml, respectively. Activated CD4+ T cells producing HIV-1 are detected in the breast milk of untreated individuals as well as those receiving highly active antiretroviral therapy. This finding strongly suggests that HIV-1 replication occurs in latently infected CD4+ T cells that, upon spontaneous activation, revert to productively infected cells. These cells might be responsible for a residual breast milk transmission despite maternal highly active antiretroviral therapy.

  12. Prevalence of transmitted HIV-1 drug resistance remains low in Guangxi, China, eight years after scale-up of highly-active antiretroviral therapy.

    Science.gov (United States)

    Li, Guojian; Liang, Shujia; Harrison, Tim J; Tang, Zhenzhu; Shen, Zhiyong; Wang, Xueyan; Wu, Xinghua; Liu, Wei; Liang, Fuxiong; Feng, Liushuai; Yang, Jinye; Fang, Zhongliao

    2014-01-01

    Highly-active antiretroviral therapy (HAART) was scaled up in Guangxi, China in 2005. The number of individuals receiving free HAART increased dramatically from June 2010 under the Guangxi Government's anti-HIV programme. We aimed to determine the prevalence of HIV-transmitted drug resistance (TDR) of Guangxi. HIV-positive, antiretroviral-naive individuals were recruited from the east (Hezhou), south (Qinzhou), west (Baise), north (Guilin) and centre (Laibin) of Guangxi. The pol gene of the virus from the individuals was analysed. The overall prevalence of HIV TDR was 3.2% (7/216, 95% CI 0.9-5.5). The prevalence rates in Baise, Guilin, Hezhou, Qinzhou and Laibin are 4.9% (2/41, 95% CI -1.7 to 11.5), 2.3% (1/44, 95% CI -2.1 to 5.7), 4.7% (2/43, 95% CI -1.6 to 11.0), 2.6% (1/38, 95% CI -2.5 to 7.7) and 2.0% (1/50, 95% CI -1.9 to 5.9), respectively. No significant difference in the prevalence was found among them. No factors were found to be associated with TDR, including CD4 cell counts, viral loads and genotypes. The subtypes CRF01_AE, CRF07_BC, CRF08_BC and B were found. Subtype CRF08_BC is the predominant subtype in Baise while CRF01_AE is the predominant subtype elsewhere in Guangxi. The prevalence of TDR in antiretroviral-naive patients in Guangxi remains low 8 years after scale-up of HAART. © 2014 S. Karger AG, Basel

  13. Clinical and virologic follow-up in perinatally HIV-1-infected children and adolescents in Madrid with triple-class antiretroviral drug-resistant viruses.

    Science.gov (United States)

    Rojas Sánchez, P; de Mulder, M; Fernandez-Cooke, E; Prieto, L; Rojo, P; Jiménez de Ory, S; José Mellado, M; Navarro, M; Tomas Ramos, J; Holguín, Á

    2015-06-01

    Drug resistance mutations compromise the success of antiretroviral treatment in human immunodeficiency virus type 1 (HIV-1)-infected children. We report the virologic and clinical follow-up of the Madrid cohort of perinatally HIV-infected children and adolescents after the selection of triple-class drug-resistant mutations (TC-DRM). We identified patients from the cohort carrying HIV-1 variants with TC-DRM to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors according to IAS-USA-2013. We recovered pol sequences or resistance profiles from 2000 to 2011 and clinical-immunologic-virologic data from the moment of TC-DRM detection until December 2013. Viruses harbouring TC-DRM were observed in 48 (9%) of the 534 children and adolescents from 2000 to 2011, rising to 24.4% among those 197 with resistance data. Among them, 95.8% were diagnosed before 2003, 91.7% were Spaniards, 89.6% carried HIV-1-subtype B and 75% received mono/dual therapy as first regimen. The most common TC-DRM present in ≥50% of them were D67NME, T215FVY, M41L and K103N (retrotranscriptase) and L90M (protease). The susceptibility to darunavir, tipranavir, etravirine and rilpivirine was 67.7%, 43.7%, 33.3% and 33.3%, respectively, and all reported high resistance to didanosine, abacavir and nelfinavir. Despite the presence of HIV-1 resistance mutations to the three main antiretroviral families in our paediatric cohort, some drugs maintained their susceptibility, mainly the new protease inhibitors (tipranavir and darunavir) and nonnucleoside reverse transcriptase inhibitors (etravirine and rilpivirine). These data will help to improve the clinical management of HIV-infected children with triple resistance in Spain. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  14. Tööpuudus hiilib kikivarvul Võrumaale / Arved Breidaks

    Index Scriptorium Estoniae

    Breidaks, Arved, 1975-

    2008-01-01

    Võrumaal on töötute arv eelmise aastaga võrreldes tõusma hakanud: mullu suvel maakonnas registreeritud 3,9%-line töötuse määr asendus tänavu juuli lõpus 5,4%-lise töötusega. Lisa: Töötus Võrumaal. Vt. samas: Kuidas iseloomustate olukorda Võrumaa tööjõuturul? Vastavad Martin Arula (AS Toftan), Kaido Mäesalu (AS Suwem), Meelis Munski (AS Semuehitus), Indrek Klampe (OÜ Selista Ehitus), Andres Visanpuu (Võru TÜ)

  15. Glycogen synthase kinase-3 inhibitors suppress the AR-V7-mediated transcription and selectively inhibit cell growth in AR-V7-positive prostate cancer cells.

    Science.gov (United States)

    Nakata, Daisuke; Koyama, Ryokichi; Nakayama, Kazuhide; Kitazawa, Satoshi; Watanabe, Tatsuya; Hara, Takahito

    2017-06-01

    Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system. The effects of a glycogen synthase kinase-3 (GSK3) inhibitor, LY-2090314, on endogenous AR-V7 signaling were evaluated in an AR-V7-positive cell line, JDCaP-hr, by quantitative reverse transcription polymerase chain reaction. The relationship between AR-V7 signaling and β-catenin signaling was assessed using RNA interference. The effect of LY-2090314 on cell growth in various prostate cancer cell lines was also evaluated. We identified GSK3 inhibitors as transcriptional suppressors of AR-V7 using a high-throughput screen with an AR-V7 reporter system. LY-2090314 suppressed the reporter activity and endogenous AR-V7 activity in JDCaP-hr cells. Because silencing of β-catenin partly rescued the suppression, it was evident that the suppression was mediated, at least partially, via the activation of β-catenin signaling. AR-V7 signaling and β-catenin signaling reciprocally regulate each other in JDCaP-hr cells, and therefore, GSK3 inhibition can repress AR-V7 transcriptional activity by accumulating intracellular β-catenin. Notably, LY-2090314 selectively inhibited the growth of AR-V7-positive prostate cancer cells in vitro. Our findings demonstrate the potential of GSK3 inhibitors in treating advanced prostate cancer driven by AR splice variants. In vivo evaluation of AR splice variant-positive prostate cancer models will help illustrate the overall significance of GSK3 inhibitors in treating prostate cancer. © 2017 Wiley Periodicals, Inc.

  16. Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

    DEFF Research Database (Denmark)

    Baxter, J D; Dunn, D; White, E

    2015-01-01

    of resistance testing in START trial participants. METHODS: In the Strategic Timing of AntiRetroviral Treatment (START) trial, baseline genotypic resistance testing results were collected at study entry and analysed centrally to determine the prevalence of TDR in the study population. Resistance was based...... on a modified 2009 World Health Organization definition to reflect newer resistance mutations. RESULTS: Baseline resistance testing was available in 1946 study participants. Higher rates of testing occurred in Europe (86.7%), the USA (81.3%) and Australia (89.9%) as compared with Asia (22.2%), South America (1...

  17. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis

    NARCIS (Netherlands)

    Gupta, Ravindra K.; Gregson, John; Parkin, Neil; Haile-Selassie, Hiwot; Tanuri, Amilcar; Andrade Forero, Liliana; Kaleebu, Pontiano; Watera, Christine; Aghokeng, Avelin; Mutenda, Nicholus; Dzangare, Janet; Hone, San; Hang, Zaw Zaw; Garcia, Judith; Garcia, Zully; Marchorro, Paola; Beteta, Enrique; Giron, Amalia; Hamers, Raph; Inzaule, Seth; Frenkel, Lisa M.; Chung, Michael H.; de Oliveira, Tulio; Pillay, Deenan; Naidoo, Kogie; Kharsany, Ayesha; Kugathasan, Ruthiran; Cutino, Teresa; Hunt, Gillian; Avila Rios, Santiago; Doherty, Meg; Jordan, Michael R.; Bertagnolio, Silvia

    2018-01-01

    Pretreatment drug resistance in people initiating or re-initiating antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income countries (LMICs). We aimed to assess the scale of this problem and whether

  18. Combination antiretroviral therapy improves cognitive performance and functional connectivity in treatment-naïve HIV-infected individuals.

    Science.gov (United States)

    Zhuang, Yuchuan; Qiu, Xing; Wang, Lu; Ma, Qing; Mapstone, Mark; Luque, Amneris; Weber, Miriam; Tivarus, Madalina; Miller, Eric; Arduino, Roberto C; Zhong, Jianhui; Schifitto, Giovanni

    2017-10-01

    Our study aimed to investigate the short-term effect of combination antiretroviral therapy (cART) on cognitive performance and functional and structural connectivity and their relationship to plasma levels of antiretroviral (ARV) drugs. Seventeen ARV treatment-naïve HIV-infected individuals (baseline mean CD4 cell count, 479 ± 48 cells/mm 3 ) were age matched with 17 HIV-uninfected individuals. All subjects underwent a detailed neurocognitive and functional assessment and magnetic resonance imaging. HIV-infected subjects were scanned before starting cART and 12 weeks after initiation of treatment. Uninfected subjects were assessed once at baseline. Functional connectivity (FC) was assessed within the default mode network while structural connectivity was assessed by voxel-wise analysis using tract-based spatial statistics (TBSS) and probabilistic tractography within the DMN. Tenofovir and emtricitabine blood concentration were measured at week 12 of cART. Prior to cART, HIV-infected individuals had significantly lower cognitive performance than control subjects as measured by the total Z-score from the neuropsychological tests assessing six cognitive domains (p = 0.020). After 12 weeks of cART treatment, there remained only a weak cognitive difference between HIV-infected and HIV-uninfected subjects (p = 0.057). Mean FC was lower in HIV-infected individuals compared with those uninfected (p = 0.008), but FC differences became non-significant after treatment (p = 0.197). There were no differences in DTI metrics between HIV-infected and HIV-uninfected individuals using the TBSS approach and limited evidence of decreased structural connectivity within the DMN in HIV-infected individuals. Tenofovir and emtricitabine plasma concentrations did not correlate with either cognitive performance or imaging metrics. Twelve weeks of cART improves cognitive performance and functional connectivity in ARV treatment-naïve HIV-infected individuals with relatively

  19. Antiretroviral Treatment Is Associated With Iron Deficiency in HIV-Infected Malawian Women That Is Mitigated With Supplementation, but Is Not Associated With Infant Iron Deficiency During 24 Weeks of Exclusive Breastfeeding.

    Science.gov (United States)

    Widen, Elizabeth M; Bentley, Margaret E; Chasela, Charles S; Kayira, Dumbani; Flax, Valerie L; Kourtis, Athena P; Ellington, Sascha R; Kacheche, Zebrone; Tegha, Gerald; Jamieson, Denise J; van der Horst, Charles M; Allen, Lindsay H; Shahab-Ferdows, Setareh; Adair, Linda S

    2015-07-01

    In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their infants (through fetal iron accretion) may be at risk of iron deficiency. We assessed the effects of maternal micronutrient-fortified lipid-based nutrient supplements (LNS) and maternal ARV treatment or infant ARV prophylaxis on maternal and infant iron status during exclusive breastfeeding from birth to 24 weeks. The Breastfeeding, Antiretrovirals, and Nutrition study was a randomized controlled trial conducted in Lilongwe, Malawi, from 2004 to 2010. HIV-infected mothers (CD4 >200 cells/μL) and their infants were randomly assigned to 28-week interventions: maternal LNS/maternal ARV (n = 424), maternal LNS/infant ARV (n = 426), maternal LNS (n = 334), maternal ARV (n = 425), infant ARV (n = 426), or control (n = 334). Longitudinal models tested intervention effects on hemoglobin (Hb). In a subsample (n = 537) with multiple iron indicators, intervention effects on Hb, transferrin receptors (TfR), and ferritin were tested with linear and Poisson regression. In longitudinal models, LNS effects on maternal and infant Hb were minimal. In subsample mothers, maternal ARVs were associated with tissue iron depletion (TfR >8.3 mg/L) (risk ratio: 3.1, P 0.1). In subsample infants, interventions were not associated with impaired iron status (all P > 0.1). Maternal ARV treatment with protease inhibitors is associated with maternal tissue iron depletion; but LNS mitigates adverse effects. ARVs do not seem to influence infant iron status; however, extended use needs to be evaluated.

  20. Potential Impact of a Free Online HIV Treatment Response Prediction System for Reducing Virological Failures and Drug Costs after Antiretroviral Therapy Failure in a Resource-Limited Setting

    Directory of Open Access Journals (Sweden)

    Andrew D. Revell

    2013-01-01

    Full Text Available Objective. Antiretroviral drug selection in resource-limited settings is often dictated by strict protocols as part of a public health strategy. The objective of this retrospective study was to examine if the HIV-TRePS online treatment prediction tool could help reduce treatment failure and drug costs in such settings. Methods. The HIV-TRePS computational models were used to predict the probability of response to therapy for 206 cases of treatment change following failure in India. The models were used to identify alternative locally available 3-drug regimens, which were predicted to be effective. The costs of these regimens were compared to those actually used in the clinic. Results. The models predicted the responses to treatment of the cases with an accuracy of 0.64. The models identified alternative drug regimens that were predicted to result in improved virological response and lower costs than those used in the clinic in 85% of the cases. The average annual cost saving was $364 USD per year (41%. Conclusions. Computational models that do not require a genotype can predict and potentially avoid treatment failure and may reduce therapy costs. The use of such a system to guide therapeutic decision-making could confer health economic benefits in resource-limited settings.

  1. Drug use and receipt of highly active antiretroviral therapy among HIV-infected persons in two U.S. clinic cohorts.

    Directory of Open Access Journals (Sweden)

    Catherine C McGowan

    2011-04-01

    Full Text Available Drug use and receipt of highly active antiretroviral therapy (HAART were assessed in HIV-infected persons from the Comprehensive Care Center (CCC; Nashville, TN and Johns Hopkins University HIV Clinic (JHU; Baltimore, MD between 1999 and 2005.Participants with and without injection drug use (IDU history in the CCC and JHU cohorts were evaluated. Additional analysis of persons with history of IDU, non-injection drug use (NIDU, and no drug use from CCC were performed. Activity of IDU and NIDU also was assessed for the CCC cohort. HAART use and time on HAART were analyzed according to drug use category and site of care.1745 persons were included from CCC: 268 (15% with IDU history and 796 (46% with NIDU history. 1977 persons were included from JHU: 731 (35% with IDU history. Overall, the cohorts differed in IDU risk factor rates, age, race, sex, and time in follow-up. In multivariate analyses, IDU was associated with decreased HAART receipt overall (OR = 0.61, 95% CI: [0.45-0.84] and OR = 0.58, 95% CI: [0.46-0.73], respectively for CCC and JHU and less time on HAART at JHU (0.70, [0.55-0.88], but not statistically associated with time on HAART at CCC (0.78, [0.56-1.09]. NIDU was independently associated with decreased HAART receipt (0.62, [0.47-0.81] and less time on HAART (0.66, [0.52-0.85] at CCC. These associations were not altered significantly whether patients at CCC were categorized according to historical drug use or drug use during the study period.Persons with IDU history from both clinic populations were less likely to receive HAART and tended to have less cumulative time on HAART. Effects of NIDU were similar to IDU at CCC. NIDU without IDU is an important contributor to HAART utilization.

  2. Molecular mechanisms of serotonergic action of the HIV-1 antiretroviral efavirenz

    Science.gov (United States)

    Dalwadi, Dhwanil A.; Kim, Seongcheol; Amdani, Shahnawaz M.; Chen, Zhenglan; Huang, Ren-Qi

    2016-01-01

    Efavirenz is highly effective at suppressing HIV-1, and the WHO guidelines list it as a component of the first-line antiretroviral (ARV) therapies for treatment-naïve patients. Though the pharmacological basis is unclear, efavirenz is commonly associated with a risk for neuropsychiatric adverse events (NPAEs) when taken at the prescribed dose. In many patients these NPAEs appear to subside after several weeks of treatment, though long-term studies show that in some patients the NPAEs persist. In a recent study focusing on the abuse potential of efavirenz, its receptor psychopharmacology was reported to include interactions with a number of established molecular targets for known drugs of abuse, and it displayed a prevailing behavioral profile in rodents resembling an LSD-like activity. In this report, we discovered interactions with additional serotonergic targets that may be associated with efavirenz-induced NPAEs. The most robust interactions were with 5-HT3A and 5-HT6 receptors, with more modest interactions noted for the 5-HT2B receptor and monoamine oxidase A. From a molecular mechanistic perspective, efavirenz acts as a 5-HT6 receptor inverse agonist of Gs-signaling, 5-HT2A and 5-HT2C antagonist of Gq-signaling, and a blocker of the 5-HT3A receptor currents. Efavirenz also completely or partially blocks agonist stimulation of the M1 and M3 muscarinic receptors, respectively. Schild analysis suggests that efavirenz competes for the same site on the 5-HT2A receptor as two known hallucinogenic partial agonists (±)-DOI and LSD. Prolonged exposure to efavirenz reduces 5-HT2A receptor density and responsiveness to 5-HT. Other ARVs such as zidovudine, nevirapine and emtricitabine did not share the same complex pharmacological profile as efavirenz, though some of them weakly interact with the 5-HT6 receptor or modestly block GABAA currents. PMID:27157251

  3. AR Variant ARv567es Induces Carcinogenesis in a Novel Transgenic Mouse Model of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Gang Liu

    2013-09-01

    Full Text Available Androgen deprivation therapy remains the primary treatment modality for patients with metastatic prostate cancer but is uniformly marked by progression to castration-resistant prostate cancer (CRPC after a period of regression. Continued activation of androgen receptor (AR signaling is attributed as one of the most important mechanisms underlying failure of therapy. Recently, the discovery of constitutively active AR splice variants (AR-Vs adds more credence to this idea. Expression of AR-Vs in metastases portends a rapid progression of the tumor. However, the precise role of the AR-Vs in CRPC still remains unknown. ARv567es is one of the two AR variants frequently found in human CRPC xenografts and metastases. Herein, we developed a probasin (Pb promoter-driven ARv567es transgenic mouse, Pb-ARv567es, to evaluate the role of ARv567es in both autonomous prostate growth and progression to CRPC. We found that expression of ARv567es in the prostate results in epithelial hyperplasia by 16 weeks and invasive adenocarcinoma is evident by 1 year of age. The underlying genetic cellular events involved a cell cycle-related transcriptome and differential expression of a spectrum of genes that are critical for tumor initiation and progression. These findings indicate that ARv567es could induce tumorigenesis de novo and signifies the critical role of AR-Vs in CRPC. Thus, the Pb-ARv567es mouse could provide a novel model in which the role of AR variants in prostate cancer progression can be examined.

  4. Response to first-line antiretroviral treatment among human immunodeficiency virus-infected patients with and without a history of injecting drug use in Indonesia.

    Science.gov (United States)

    Wisaksana, Rudi; Indrati, Agnes K; Fibriani, Azzania; Rogayah, Ega; Sudjana, Primal; Djajakusumah, Tony S; Sumantri, Rachmat; Alisjahbana, Bachti; van der Ven, Andre; van Crevel, Reinout

    2010-06-01

    There is a common belief that injecting drug use (IDU) is associated with lower uptake, retention and success of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected patients. We examined this in an Indonesian setting, where IDU is the main risk factor for HIV infection. Patient characteristics and response to ART were recorded for all patients diagnosed with HIV infection in the referral hospital for West Java (40 million people). Kaplan-Meier estimates and Cox's regression were used to compare mortality, loss to follow-up and virological failure between patients with and without a history of IDU. A total of 773 adult HIV patients (81.9% IDUs) presented between January 1996 and April 2008. IDUs had a median CD4 cell count of 33 [interquartile ratio (IQR), 12-111] cells/mm(3) compared to 84 (IQR, 28-224) cells/mm(3) in non-IDUs. Among patients with a history of IDU, 87.7% were coinfected with hepatitis C (HCV). Mortality was associated strongly with CD4 count; after 6 months of ART, 18.3, 20.3, 7.1 and 0.7% of patients with CD4 cell counts or =200/mm(3) had died (P < 0.0001). Mortality [adjusted for CD4; hazard ratio (HR) = 0.65; 95% confidence interval (CI) 0.35-1.23], loss to follow-up (HR = 0.85, 95% CI 0.51-1.41) and virological failure (HR = 0.47, 95% CI 0.19-1.13) were not significantly different in IDUs and non-IDUs. Intravenous drug users (IDUs) in Indonesia with HIV/acquired immune deficiency syndrome tend to have more advanced disease but respond similarly to non-IDUs to antiretroviral therapy.

  5. Transmitted drug resistance among antiretroviral-naive patients with established HIV type 1 infection in Santo Domingo, Dominican Republic and review of the Latin American and Caribbean literature.

    Science.gov (United States)

    Myers, Julie E; Taylor, Barbara S; Rojas Fermín, Rita A; Reyes, Emily Virginia; Vaughan, Catherine; José, Lina; Javier, Carmen; Franco Estévez, Ramona; Donastorg Cabral, Yeycy; Batista, Arelis; Lie, Yolanda; Coakley, Eoin; Hammer, Scott M; Brudney, Karen

    2012-07-01

    Emergence of HIV resistance is a concerning consequence of global scale-up of antiretroviral therapy (ART). To date, there is no published information about HIV resistance from the Dominican Republic. The study's aim was to determine the prevalence of transmitted drug resistance (TDR) to reverse transcriptase and protease inhibitors in a sample of chronically HIV-1-infected patients in one clinic in Santo Domingo. The data are presented in the context of a review of the TDR literature from Latin America and the Caribbean. Genotype testing was successfully performed on 103 treatment-naive adults planning to initiate antiretroviral therapy; the World Health Organization (WHO) list of surveillance drug resistance mutations (SDRM) was used to determine the presence of TDR mutations. WHO SDRM were identified in eight patients (7.8%); none had received sdNVP. There were no significant differences in epidemiologic or clinical variables between those with or without WHO SDRM. The prevalence of WHO SDRM was 1.0% and 6.8% for nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, respectively. No WHO SDRMs for protease inhibitors were identified. Among 12 studies of TDR in the region with a sample size of at least 100 subjects, the reported prevalence of SDRM ranged from 2.8% to 8.1%. The most commonly identified SDRM was K103N. This information adds to our understanding of the epidemiology of TDR in the region and the possible role such mutations could play in undermining first-line treatment. Ongoing surveillance is clearly needed to better understand the TDR phenomenon in the Caribbean.

  6. Adherence to Antiretrovirals Among US Women During and After Pregnancy

    Science.gov (United States)

    Bardeguez, Arlene D.; Lindsey, Jane C.; Shannon, Maureen; Tuomala, Ruth E.; Cohn, Susan E.; Smith, Elizabeth; Stek, Alice; Buschur, Shelly; Cotter, Amanda; Bettica, Linda; Read, Jennifer S.

    2009-01-01

    Background Antiretrovirals (ARVs) are recommended for maternal health and to reduce HIV-1 mother-to-child transmission, but suboptimal adherence can counteract its benefits. Objectives To describe antepartum and postpartum adherence to ARV regimens and factors associated with adherence. Methods We assessed adherence rates among subjects enrolled in Pediatric AIDS Clinical Trials Group Protocol 1025 from August 2002 to July 2005 on tablet formulations with at least one self-report adherence assessment. Perfectly adherent subjects reported no missed doses 4 days before their study visit. Generalized estimating equations were used to compare antepartum with postpartum adherence rates and to identify factors associated with perfect adherence. Results Of 519 eligible subjects, 334/445 (75%) reported perfect adherence during pregnancy. This rate significantly decreased 6, 24, and 48 weeks postpartum [185/284 (65%), 76/118 (64%), and 42/64 (66%), respectively (P pregnancy (P pregnancy are needed. PMID:18614923

  7. Modeling trend of the immune system in HIV positive people treated with antiretroviral drugs, using Markov model

    Directory of Open Access Journals (Sweden)

    Sara Jambarsang

    2015-12-01

    Full Text Available Background: After primary infection, the number of CD4 T-cells decreases with disease progress. The patient’s immunological status could inform by The CD4 T-cell counts over the time. The main purpose of this study is to assess the trend of CD4 cell count in HIV+ patient that received Antiretroviral Therapy (ART by using a multistate Markov model to estimate transition intensities and transition probabilities among various states. Methods: A total of 122 HIV+ patients were included in this cohort study who are undergoing Antiretroviral Therapy treatment in the Iran AIDS center in Imam Khomeini Hospital in Tehran that inter during March 1995 to January 2005 and then fallow up to October 2014. All adults with at least two follow-up visits in addition to their pre-ART treatment were considered to be eligible for inclusion in the study. Continuous-time Markov processes are used to describe the evolution of a disease over different states. The mean sojourn time for each state was estimated by multi state Markov model. Results: Sample included 22 (18% female with a mean age of 43.32 (standard deviation 8.33 years and 100 (82% male with a mean age of 45.28 (standard deviation 8.34 year. Age was divided in to two categories, 40 years old and lower than that 66 (54.1 patents and persons older than 40 years old 56 (45.9 patents. A total of 122 patients were included. 29 patients died during follow-up. One year transition probability for staying in state 1 of CD4 cell count was 51%. This probability for six year was 33%. The mean sojourn time for sate 4 was 21 month. The hazard ratio of transition from state 3 to state 4 was 4.4 in men related to women. Conclusion: The use of antiretroviral therapy in the treatment of HIV infected persons reduce viral replication and increase in CD4 T lymphocyte count, and delay the progression of disease. This paper is shown the progression of this trend.

  8. The Impact of HIV/AIDS and ARV Treatment on Worker Absenteeism: Implications for African Firms

    Science.gov (United States)

    Habyarimana, James; Mbakile, Bekezela; Pop-Eleches, Cristian

    2010-01-01

    We characterize medium and long-run labor market impacts of HIV/AIDS and ARV treatment using unique panel data of worker absenteeism and information from an AIDS treatment program at a large mining firm in Botswana. We present robust evidence of an inverse-V shaped pattern in worker absenteeism around the time of ARV treatment inception.…

  9. HIV antiretroviral drug Efavirenz induces anxiety-like and depression-like behavior in rats: evaluation of neurotransmitter alterations in the striatum.

    Science.gov (United States)

    Cavalcante, Giuliana Ignácio Teixeira; Chaves Filho, Adriano José Maia; Linhares, Maria Isabel; de Carvalho Lima, Camila Nayane; Venâncio, Edith Teles; Rios, Emiliano Ricardo Vasconcelos; de Souza, Francisca Cléa Florenço; Vasconcelos, Silvânia Maria Mendes; Macêdo, Danielle; de França Fonteles, Marta Maria

    2017-03-15

    Efavirenz (EFV) is an effective antiretroviral drug with a favorable pharmacokinetic profile and widely used in combination regimens to treat HIV infection. However, there are major concerns about the safety of this drug. Patients treated with EFV often experience neuropsychiatric adverse effects, which frequently lead to switching to alternative EFV-free regimens. The mechanisms involved in the central action of EFV are intrinsically unclear. Thus, this study aimed to investigate the effects of acute and subchronic (2 weeks) EFV administration in a series of behavioral tests for anxiety-like and depression-like behavior in healthy rats. We also evaluated the effect of EFV treatment in striatal concentrations of monoamine neurotransmitters (serotonin, dopamine and noradrenaline) and their metabolites and the amino acid neurotransmitters glutamate and GABA. Our results showed that acute treatment with EFV induced an anxiogenic-like effect, while sub-chronic treatment induced both anxiogenic-like and depressive-like behavior which was dose related.. Additionally, EFV treatment caused marked alterations in the striatal concentrations of monoamines and their metabolites (and turnover rates) and the amino acid neurotransmitters glutamate and GABA. These changes were influenced by treatment duration and dose. These findings add more evidence about the neuropsychiatric adverse effects of EFV and propose potential new mechanisms for the toxic action of this drug in the central nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Delivery Unit Costs for Antiretroviral Treatment and Prevention of Mother-to-Child-Transmission of HIV

    Science.gov (United States)

    Galárraga, Omar; Wirtz, Veronika J.; Figueroa-Lara, Alejandro; Santa-Ana-Tellez, Yared; Coulibaly, Ibrahima; Viisainen, Kirsi; Medina-Lara, Antonieta; Korenromp, Eline L.

    2013-01-01

    Background As antiretroviral treatment (ART) for HIV/AIDS is scaled-up globally, information on per-person costs is critical to improve efficiency in service delivery and maximize coverage and health impact. Objective To review studies on delivery unit costs for adult and pediatric ART provision per-patient-year, and prevention of mother-to-child transmission (PMTCT) interventions per mother-infant pair screened or treated, in low- and middle-income countries. Methods Systematic review of English, French and Spanish publications from 2001 to 2009, reporting empirical costing that accounted for at least antiretroviral (ARV) medicines, laboratory testing and personnel. Expenditures were analyzed by country income level and cost component. All costs were standardized to 2009 US dollars. Results Analyses covered 29 eligible, comprehensive costing studies. In the base case, in low-income countries (LIC), median, ART cost per patient-year was $792 (mean: $839, range: $682-$1089); for lower-middle-income countries (LMIC), the median was $932 (mean: $1246, range: $156-$3904); and for upper-middle-income countries (UMIC) the median was $1454 (mean: $2783, range: $1230-$5667). ARV drugs were largest component of overall ART cost in all settings (62%, 50% and 47% in LIC, LMIC and UMIC respectively). Out of 26 ART studies, 14 report which drug regimes were used, and only one study explicitly reported second line treatment costs. The second cost driver was laboratory cost in LIC and LMIC (14% and 19.5%) whereas it was personnel costs in UMIC (26%). Two studies specified the types of laboratory tests costed, and three studies specifically included above-facility-level personnel costs. Three studies reported detailed PMTCT costs, and two studies reported on pediatric ART. Conclusions There is a paucity of data on the full ART and PMTCT delivery unit costs, in particular for low-and middle-income countries. Heterogeneity in activities costed and insufficient detail regarding

  11. Idiopathic intracranial hypertension associated with anaemia, secondary to antiretroviral drug in a human immunodeficiency virus positive patient

    Directory of Open Access Journals (Sweden)

    J Vijay Ananth

    2018-01-01

    Full Text Available Papilledema in a patient with human immunodeficiency virus (HIV/acquired immune deficiency syndrome is an alarming finding. Any condition giving rise to raised intracranial tension (ICT can cause papilledema, and in these patients, it could be secondary to opportunistic infections like meningitis to neoplasm. We report a case of a 28-year old female with HIV on antiretroviral therapy, who presented to us, with papilledema. Her fundus examination revealed superficial hemorrhages and Roth's spots along with papilledema. Patient was diagnosed with idiopathic intracranial hypertension (IIH, and all other possible systemic associations were ruled out. Her blood tests showed severe anemia. The papilledema and retinal changes resolved with treatment of anemia. This is a rare presentation of IIH in HIV positive patient due to anemia, secondary to zidovudine adverse effect.

  12. The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes

    NARCIS (Netherlands)

    Vijver, D.A. van de; Wensing, A.M.J.; Angarano, G.; Asjo, B.; Balotta, C.; Camacho, R.; Chaix, M.; Costagliola, D.; De Luca, A.; Derdelinckx, I.; Grossman, Z.; Hamouda, O.; Hatzakis, A.; Hemmer, R.; Hoepelman, A.I.M.; Horban, A.; Korn, K.; Kücherer, C.; Leitner, T.; Loveday, C.; MacRae, E.; Maljkovic, I.; Mendoza, C. de; Meyer, L.; Nielsen, C.; Op de Coul, E.L.M.; Omaasen, V.; Paraskevis, D.; Perrin, L.; Puchhammer-Stöckl, E.; Salminen, M.; Schmit, J.; Scheider, F.; Schuurman, R.; Soriano, V.; Stanczak, G.; Stanojevic, M.; Vandamme, A.; Laethem, K. van; Violin, M.; Wilde, K.; Yerly, S.; Zazzi, M.; Boucher, C.A.B.

    The genetic barrier, defined as the number of mutations required to overcome drug-selective pressure, is an important factor for the development of HIV drug resistance. Because of high variability between subtypes, particular HIV-1 subtypes could have different genetic barriers for drug

  13. Research on Fairing design and CFD Analysis of Submarine Pipeline Inspection ARV

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    Jin Xiaojian

    2017-01-01

    Full Text Available Along with the fast development of the ocean exploitation, the cost-effective requirement of autonomous & remotely operated vehicle (ARV, which can perform more complicated missions such as the oil exploitation and the inspection of the submarine pipeline is more urgent. The submarine pipeline inspection ARV can help us better understand, protect and efficiently utilize them for human welfare. Fairing design of a new detection ARV are introduced in this paper. In order to select an appropriate thruster that will achieve the required speed of the ARV, the ANSYS-CFX tools are used to predicted the drag force. The CFD results reveal the distribution of velocity and pressure values of the ARV. In order to verify the CFD modeling process, a towed body was developed and analyzed, compared against the corresponding physical test data.

  14. Novel Method for Simultaneous Quantification of Phenotypic Resistance to Maturation, Protease, Reverse Transcriptase, and Integrase HIV Inhibitors Based on 3′Gag(p2/p7/p1/p6)/PR/RT/INT-Recombinant Viruses: a Useful Tool in the Multitarget Era of Antiretroviral Therapy▿†

    Science.gov (United States)

    Weber, Jan; Vazquez, Ana C.; Winner, Dane; Rose, Justine D.; Wylie, Doug; Rhea, Ariel M.; Henry, Kenneth; Pappas, Jennifer; Wright, Alison; Mohamed, Nizar; Gibson, Richard; Rodriguez, Benigno; Soriano, Vicente; King, Kevin; Arts, Eric J.; Olivo, Paul D.; Quiñones-Mateu, Miguel E.

    2011-01-01

    Twenty-six antiretroviral drugs (ARVs), targeting five different steps in the life cycle of the human immunodeficiency virus type 1 (HIV-1), have been approved for the treatment of HIV-1 infection. Accordingly, HIV-1 phenotypic assays based on common cloning technology currently employ three, or possibly four, different recombinant viruses. Here, we describe a system to assess HIV-1 resistance to all drugs targeting the three viral enzymes as well as viral assembly using a single patient-derived, chimeric virus. Patient-derived p2-INT (gag-p2/NCp7/p1/p6/pol-PR/RT/IN) products were PCR amplified as a single fragment (3,428 bp) or two overlapping fragments (1,657 bp and 2,002 bp) and then recombined into a vector containing a near-full-length HIV-1 genome with the Saccharomyces cerevisiae uracil biosynthesis gene (URA3) replacing the 3,428 bp p2-INT segment (Dudley et al., Biotechniques 46:458–467, 2009). P2-INT-recombinant viruses were employed in drug susceptibility assays to test the activity of protease (PI), nucleoside/nucleotide reverse transcriptase (NRTI), nonnucleoside reverse transcriptase (NNRTI), and integrase strand-transfer (INSTI) inhibitors. Using a single standardized test (ViralARTS HIV), this new technology permits the rapid and automated quantification of phenotypic resistance for all known and candidate antiretroviral drugs targeting all viral enzymes (PR, RT, including polymerase and RNase H activities, and IN), some of the current and potential assembly inhibitors, and any drug targeting Pol or Gag precursor cleavage sites (relevant for PI and maturation inhibitors) This novel assay may be instrumental (i) in the development and clinical assessment of novel ARV drugs and (ii) to monitor patients failing prior complex treatment regimens. PMID:21628544

  15. Efeito das drogas anti-retrovirais sobre as taxas de fertilidade de ratas Wistar Effects of antiretroviral drugs on fertility of Wistar rats

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    Ernesto Antonio Figueiró Filho

    2002-12-01

    írus da imunodeficiência humana.PURPOSE: to evaluate experimentally the effects of antiretroviral drugs used alone and in association upon the fertility of pregnant Wistar rats and the perinatal effects on the offspring. METHODS: adult female pregnant Wistar rats weighing 200-230 g were used. The antiretroviral drugs zidovudine (AZT, lamivudine (3TC and nelfinavir (NFV were used alone and in association at daily doses of ten times the dose normally used in pregnant women, proportionally to the animal's body weight. Seven groups were studied, including the control one. The experiment started on day 0 and the pregnant animals were sacrificed on day 21. The alive and dead fetuses, the total implantation sites and the total numbers of corporea lutea were used to calculate the fertility values. The statistical analysis was performed by Student's t test and by the Mann-Whitney test. RESULTS: there were no significant statistical differences regarding preimplantation loss and implantation efficiency values of the rats treated with isolated and associated antiretroviral drugs. There was a significant increase in the postimplantation loss values (control group: 7.6%; drug groups variation: 20.2-26.7%, a decrease in the fetal viability values (control group: 92.4%, drug groups variation: 73.3-79.8%, and a decreasing number of fetuses per animal (control group: 14.7; drug groups variation: 11.1-12.7. There was a significant weight reduction of the female rats and of the offspring of animals treated with 3TC, AZT + 3TC and AZT + 3TC + NFV. CONCLUSION: with the administration of high antiretroviral doses, important fertility effects could be observed, which showed that less histotoxic antiretroviral drugs must be studied in order to warrant the safety of using these medicines in pregnant HIV-1 - infected women.

  16. Use of dried-blood-spot samples and in-house assays to identify antiretroviral drug resistance in HIV-infected children in resource-constrained settings.

    Science.gov (United States)

    Ziemniak, Carrie; Mengistu, Yohannes; Ruff, Andrea; Chen, Ya-Hui; Khaki, Leila; Bedri, Abubaker; Simen, Birgitte B; Palumbo, Paul; Eshleman, Susan H; Persaud, Deborah

    2011-12-01

    Monitoring HIV drug resistance is an important component of the World Health Organization's global HIV program. HIV drug resistance testing is optimal with commercially available clinically validated test kits using plasma; however, that type of testing may not be feasible or affordable in resource-constrained settings. HIV genotyping from dried blood spots (DBS) with noncommercial (in-house) assays may facilitate the capture of HIV drug resistance outcomes in resource-constrained settings but has had varying rates of success. With in-house assays for HIV reverse transcriptase, we evaluated the yield of genotyping DBS samples collected from HIV-infected children who were enrolled in two clinical trials conducted in sub-Saharan Africa (median HIV viral load, 5.88 log(10) HIV RNA copies/ml; range, 4.04 to 6.99). Overall, HIV genotypes were obtained for 94 (89.5%) of 105 samples tested (95% and 84% from clinical trials #1 and #2, respectively); however, successful analysis of 15 (16.1%) of the 94 samples required repeat testing using a different set of primers on previously synthesized cDNA. The yield of genotyping was lower on the DBS that were stored suboptimally from clinical trial #2 (56% versus 88% for optimally stored). Concordance with plasma genotypes derived using a clinically validated, commercial kit-based assay (ViroSeq HIV-1 genotyping system) was also assessed in a subset of children with paired testing. For 34 samples with paired DBS and plasma genotypes, there was 100% concordance for major drug resistance mutations. DBS genotyping using in-house assays provides an alternative for antiretroviral drug resistance testing in children in resource-constrained regions but may require region-specific optimization before widespread use.

  17. Use of Dried-Blood-Spot Samples and In-House Assays To Identify Antiretroviral Drug Resistance in HIV-Infected Children in Resource-Constrained Settings ▿

    Science.gov (United States)

    Ziemniak, Carrie; Mengistu, Yohannes; Ruff, Andrea; Chen, Ya-Hui; Khaki, Leila; Bedri, Abubaker; Simen, Birgitte B.; Palumbo, Paul; Eshleman, Susan H.; Persaud, Deborah

    2011-01-01

    Monitoring HIV drug resistance is an important component of the World Health Organization's global HIV program. HIV drug resistance testing is optimal with commercially available clinically validated test kits using plasma; however, that type of testing may not be feasible or affordable in resource-constrained settings. HIV genotyping from dried blood spots (DBS) with noncommercial (in-house) assays may facilitate the capture of HIV drug resistance outcomes in resource-constrained settings but has had varying rates of success. With in-house assays for HIV reverse transcriptase, we evaluated the yield of genotyping DBS samples collected from HIV-infected children who were enrolled in two clinical trials conducted in sub-Saharan Africa (median HIV viral load, 5.88 log10 HIV RNA copies/ml; range, 4.04 to 6.99). Overall, HIV genotypes were obtained for 94 (89.5%) of 105 samples tested (95% and 84% from clinical trials #1 and #2, respectively); however, successful analysis of 15 (16.1%) of the 94 samples required repeat testing using a different set of primers on previously synthesized cDNA. The yield of genotyping was lower on the DBS that were stored suboptimally from clinical trial #2 (56% versus 88% for optimally stored). Concordance with plasma genotypes derived using a clinically validated, commercial kit-based assay (ViroSeq HIV-1 genotyping system) was also assessed in a subset of children with paired testing. For 34 samples with paired DBS and plasma genotypes, there was 100% concordance for major drug resistance mutations. DBS genotyping using in-house assays provides an alternative for antiretroviral drug resistance testing in children in resource-constrained regions but may require region-specific optimization before widespread use. PMID:21956987

  18. Relationship between hunger, adherence to antiretroviral therapy and plasma HIV RNA suppression among HIV-positive illicit drug users in a Canadian setting.

    Science.gov (United States)

    Anema, Aranka; Kerr, Thomas; Milloy, M-J; Feng, Cindy; Montaner, Julio S G; Wood, Evan

    2014-04-01

    Food insecurity may be a barrier to achieving optimal HIV treatment-related outcomes among illicit drug users. This study therefore, aimed to assess the impact of severe food insecurity, or hunger, on plasma HIV RNA suppression among illicit drug users receiving antiretroviral therapy (ART). A cross-sectional Multivariate logistic regression model was used to assess the potential relationship between hunger and plasma HIV RNA suppression. A sample of n = 406 adults was derived from a community-recruited open prospective cohort of HIV-positive illicit drug users, in Vancouver, British Columbia (BC), Canada. A total of 235 (63.7%) reported "being hungry and unable to afford enough food," and 241 (59.4%) had plasma HIV RNA hunger was associated with lower odds of plasma HIV RNA suppression (Odds Ratio = 0.59, 95% confidence interval [CI]: 0.39-0.90, p = 0.015). In multivariate analyses, this association was no longer significant after controlling for socio-demographic, behavioral, and clinical characteristics, including 95% adherence (Adjusted Odds Ratio [AOR] = 0.65, 95% CI: 0.37-1.10, p = 0.105). Multivariate models stratified by 95% adherence found that the direction and magnitude of this association was not significantly altered by the adherence level. Hunger was common among illicit drug users in this setting. Although, there was an association between hunger and lower likelihood of plasma HIV RNA suppression, this did not persist in adjusted analyses. Further research is warranted to understand the social-structural, policy, and physical factors shaping the HIV outcomes of illicit drug users.

  19. FAKTOR –FAKTOR PENDUKUNG KEPATUHAN ORANG DENGAN HIV AIDS (ODHA DALAM MINUM OBAT ANTIRETROVIRAL DI KOTA BANDUNG DAN CIMAHI

    Directory of Open Access Journals (Sweden)

    Yuyun Yuniar

    2013-08-01

    Full Text Available Abstract Adherence to ARV (antiretroviral was aimed to siginificantly prolong the life expectancy of people living with HIV AIDS (PLHIV. ARVs fight against the infection by slowing down the reproduction of HIV in human body. This research aimed to identify the internal and external factors that support adherence to ARV therapy.  Submit : 25-05-2012  Review : 26-06-2012 Review : 10-07-2012 revisi : 10–09-2012 This research was a qualitative research conducted in Bandung and Cimahi districts, West Java province from September to November 2011. Data collected by doing in depth interview with related stakeholders, they were district health office staffs in Bandung and Cimahi, Local AIDS Commission staffs in Bandung and Cimahi, Bungsu hospital in Bandung, Cibabat hospital in Cimahi, NGO staff, and 10 PLHIVs who ever or still consuming ARV. Data were analyzed descriptively by triangulation and content analysis methods. It was concluded that the internal supporting factors of adherence to ARV were the motivation to live longer, the eagerness to get cured and to be healthy, considering ARV as vitamin, and the faith in their own religion. Besides, the availability of ARV and social supports were other supporting factors. The social supports were support from family, responsibility and affection for their children, willingness to get married, support from peer groups, NGO staffs, and religion figures, and good relationship with health provider staffs. The internal factors should be improved by motivating PLHIVs while external factors should include family, peer groups, NGO staff and health provider, provide better accessibility and affordability to ARV, and educate the society. Keywords: PLHIV, Adherence, ARV Abstrak Kepatuhan Penggunaan ARV (antiretroviral merupakan salah satu faktor yang dapat memperpanjang umur harapan hidup ODHA (orang dengan HIV AIDS secara bermakna. ARV bekerja melawan infeksi dengan cara memperlambat reproduksi HIV dalam tubuh

  20. Simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE): protocol for a randomised evaluation

    OpenAIRE

    Rosen, Sydney; Fox, Matthew P; Larson, Bruce A; Brennan, Alana T; Maskew, Mhairi; Tsikhutsu, Isaac; Bii, Margaret; Ehrenkranz, Peter D; Venter, WD Francois

    2017-01-01

    Introduction African countries are rapidly adopting guidelines to offer antiretroviral therapy (ART) to all HIV-infected individuals, regardless of CD4 count. For this policy of ‘treat all’ to succeed, millions of new patients must be initiated on ART as efficiently as possible. Studies have documented high losses of treatment-eligible patients from care before they receive their first dose of antiretrovirals (ARVs), due in part to a cumbersome, resource-intensive process for treatment initia...

  1. Prevention of perinatal HIV I transmission by protease inhibitor based triple drug antiretroviral therapy versus nevirapine as single dose at the time of delivery.

    Science.gov (United States)

    Bendle, Meenakshi; Bajpai, Smrati; Choudhary, Ashwini; Pazare, Amar

    2012-12-01

    In India, parent to child transmission is the most important source of HIV infection in children below fifteen years of age. Transmission of HIV from mother to child can occur even at low or undetectable HIV virus levels. CD4 count or HIV RNA levels should not be the determining factor when deciding whether to use antiretroviral drugs for prevention of perinatal transmission of HIV. Use of single dose nevirapine during labour, in prevention of parent to child transmission (PPTCT) programme for pregnant females with CD4 count > 250 cells/cumm has less efficacy in reducing perinatal transmission. And there are high chances of development of nevirapine resistance to both mother and baby after single dose nevirapine exposure. Short course Protease inhibitor(PI) based triple drug combination ART from 28 weeks till delivery for perinatal prophylaxis is effective in reducing perinatal HIV transmission. PI's are safe in pregnancy and also have less chances of development of resistance when used for perinatal prophylaxis and stopped post delivery.Hence, it is opined that PI based combination ART should be offered to pregnant females in PPTCT programme, thereby preventing occurrence of paediatric HIV infection in India. This can have significant impact on the society at large.

  2. Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals

    Directory of Open Access Journals (Sweden)

    Pauline Byakika-Kibwika

    2011-01-01

    Full Text Available Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART poses significant challenges. Artemether-lumefantrine (AL is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine are metabolized by hepatic cytochrome P450 (CYP450 enzymes which metabolize the protease inhibitors (PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs used for HIV treatment. Coadministration of NNRTIs and PIs with AL could potentially cause complex pharmacokinetic drug interactions. NNRTI by inducing CYP450 3A4 enzyme and PIs by inhibiting CYP450 3A4 enzymes could influence both artemether and lumefantrine concentrations and their active metabolites dihydroartemisinin and desbutyl-lumefantrine, predisposing patients to poor treatment response, toxicity, and risk for development of resistance. There are scanty data on these interactions and their consequences. Pharmacokinetic studies to evaluate these interactions in the target populations are urgently needed.

  3. Use of Antiretroviral HIV Post-Exposure Prophylaxis in Sexually Abused Children and Adolescents Treated in an Inner-City Pediatric Emergency Department

    Science.gov (United States)

    Fajman, Nancy; Wright, Richelle

    2006-01-01

    Background: In 2002, Georgia had the United States' eighth highest number of persons living with AIDS. Human immunodeficiency virus (HIV) transmission as a result of sexual abuse is uncommon but definitely occurs. In certain circumstances of sexual abuse, antiretroviral post-exposure prophylaxis (ARV-PEP) has been suggested as a means to decrease…

  4. Influence of Arvs on Some Biochemical Changes in Liver Non ...

    African Journals Online (AJOL)

    Dr. K.J. Umar

    patients as well as the new antiretroviral medications resulted in negative impacts on the clinical outcome of ... with liver disease include old age (Campos et al.,. 2002), female gender (Martín-Carbonero et al., 2003), .... the higher HIV infection in the middle age people among which include their physical strength and high.

  5. Effectiveness and tolerability of abacavir-lamivudine-nevirapine (ABC/3TC/NVP) in a multicentre cohort of HIV-infected, ARV-naïve patients.

    Science.gov (United States)

    Podzamczer, Daniel; Rojas, Jhon Fredy; Neves, Isabel; Ferrer, Elena; Llibre, Josep M; Leal, Manuel; Gorgolas, Miguel; Jose, Crusells M; Gatell, Josep M; Abreu, Ricardo Correia; Curto, Jordi; Domingo, Pere; Pilar, Barrufet M; Rozas, Nerea

    2014-01-01

    Very scarce information has been published to date with the combination of ABC/3TC/NVP but it is currently being used in clinical practice in Spain and Portugal. Our aim was to present the clinical experience with this regimen in a cohort of adult HIV-infected antiretroviral (ARV)-naïve patients. Retrospective, multicentre, cohort study. Consecutive adult HIV-infected ARV-naïve HLA-B*5701-negative patients, who started ABC/3TC/NVP between 2005-2013, with at least one follow-up visit, were included. Demographic, clinical and laboratory variables were assessed at baseline, month 1, and every three-four months thereafter. The primary end point was HIV-1 viral load (VL)<40 c/mL at 48 weeks. Data were analyzed by intent-to-treat (ITT) (switch=failure, and missing=failure) and on treatment (OT) analyses. 78 patients were included. Median follow up was 26 (0.1-84) months. 86% were male, median age 41 (23-69) years, 9% had AIDS, 8% were HCV+, baseline CD4 was 275 (10-724) cells/µL and median VL 4.58 (3.02-6.92) log. After 48 weeks, VL was<40 c/mL in 89.8% (OT), 79.7% (M=F) and 65.4% (S=F) and at 96 weeks in 88.5%, 78.9% and 61.6%, respectively. CD4 increased +246 (p<0.001) and +292 (p<0.001) cells/uL after 48 and 96 weeks, respectively. One or more drugs of the regimen were discontinued in 33 (42.3%) patients. In 15 (19.2%) patients (13 NVP, 2 ABC/3TC) therapy was stopped due to toxicity after a median of one month (in only two cases after six months of follow up): 80% of them had rash/liver toxicity. Six (7.7%) patients discontinued ART due to virologic failure, five (6.4%) because of other reasons and seven (9%) were lost to follow-up. ALT but not AST significantly increased (+0.07 ukat/L at 96 weeks, p=0.033). A significant increase of 25%, 26% and 42% in total cholesterol, LDLc and HDLc, respectively, and a significant decrease in TC/HDL ratio (6%, p=0.008) was observed after 96 weeks. Despite a considerable proportion of patients had to stop therapy due to toxicity

  6. HIV-1 drug-resistance surveillance among treatment-experienced and -naïve patients after the implementation of antiretroviral therapy in Ghana.

    Directory of Open Access Journals (Sweden)

    Nicholas I Nii-Trebi

    Full Text Available BACKGROUND: Limited HIV-1 drug-resistance surveillance has been carried out in Ghana since the implementation of antiretroviral therapy (ART. This study sought to provide data on the profile of HIV-1 drug resistance in ART-experienced and newly diagnosed individuals in Ghana. METHODS: Samples were collected from 101 HIV-1-infected patients (32 ART-experienced cases with virological failure and 69 newly diagnosed ART-naïve cases, including 11 children, in Koforidua, Eastern region of Ghana, from February 2009 to January 2010. The pol gene sequences were analyzed by in-house HIV-1 drug-resistance testing. RESULTS: The most prevalent HIV-1 subtype was CRF02_AG (66.3%, 67/101 followed by unique recombinant forms (25.7%, 26/101. Among 31 ART-experienced adults, 22 (71.0% possessed at least one drug-resistance mutation, and 14 (45.2% had two-class-resistance to nucleoside and non-nucleoside reverse-transcriptase inhibitors used in their first ART regimen. Importantly, the number of accumulated mutations clearly correlated with the duration of ART. The most prevalent mutation was lamivudine-resistance M184V (n = 12, 38.7% followed by efavirenz/nevirapine-resistance K103N (n = 9, 29.0%, and zidovudine/stavudine-resistance T215Y/F (n = 6, 19.4%. Within the viral protease, the major nelfinavir-resistance mutation L90M was found in one case. No transmitted HIV-1 drug-resistance mutation was found in 59 ART-naïve adults, but K103N and G190S mutations were observed in one ART-naïve child. CONCLUSIONS: Despite expanding accessibility to ART in Eastern Ghana, the prevalence of transmitted HIV-1 drug resistance presently appears to be low. As ART provision with limited options is scaled up nationwide in Ghana, careful monitoring of transmitted HIV-1 drug resistance is necessary.

  7. Promosi Kesehatan Nola Pender Berpengaruh Terhadap Pengetahuan dan Kepatuhan ODHA Minum ARV

    OpenAIRE

    Tuti Asrianti Utami

    2017-01-01

    The success rate of ARV therapy depends on the adherence of HIV-AIDS patients in ARV treatment. The purpose of this study was to analyze the effect of NolaPender health promotion to improve the knowledge and adherence of PLWHA (People living with HIV-AIDS) with ARV in SintCarolus Health Service (SCHS) and Persahabatan General Hospital (PGH). This study used a Pre-Post test Quasi Eksperimantal Non Equivalent Control Group and a total sample of 90 respondents were recruited through the use of c...

  8. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

    Science.gov (United States)

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    Introduction First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) 2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. Conclusions Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy. PMID:25141905

  9. A Longitudinal Analysis of Daily Pill Burden and Likelihood of Optimal Adherence to Antiretroviral Therapy Among People Living With HIV Who Use Drugs.

    Science.gov (United States)

    Mohd Salleh, Nur Afiqah; Richardson, Lindsey; Kerr, Thomas; Shoveller, Jean; Montaner, Julio; Kamarulzaman, Adeeba; Milloy, M-J

    2018-03-07

    Among people living with HIV (PLWH), high levels of adherence to prescribed antiretroviral therapy (ART) is required to achieve optimal treatment outcomes. However, little is known about the effects of daily pill burden on adherence amongst PLWH who use drugs. We sought to investigate the association between daily pill burden and adherence to ART among members of this key population in Vancouver, Canada. We used data from the AIDS Care Cohort to Evaluate Exposure to Survival Services study, a long-running community-recruited cohort of PLWH who use illicit drugs linked to comprehensive HIV clinical records. The longitudinal relationship between daily pill burden and the odds of ≥95% adherence to ART among ART-exposed individuals was analyzed using multivariable generalized linear mixed-effects modeling, adjusting for sociodemographic, behavioural, and structural factors linked to adherence. Between December 2005 and May 2014, the study enrolled 770 ART-exposed participants, including 257 (34%) women, with a median age of 43 years. At baseline, 437 (56.7%) participants achieved ≥95% adherence in the previous 180 days. Among all interview periods, the median adherence was 100% (interquartile range 71%-100%). In a multivariable model, a greater number of pills per day was negatively associated with ≥95% adherence (adjusted odds ratio [AOR] 0.87 per pill, 95% confidence interval [CI] 0.84-0.91). Further analysis showed that once-a-day ART regimens were positively associated with optimal adherence (AOR 1.39, 95% CI 1.07-1.80). In conclusion, simpler dosing demands (ie, fewer pills and once-a-day single tablet regimens) promoted optimal adherence among PLWH who use drugs. Our findings highlight the need for simpler dosing to be encouraged explicitly for PWUD with multiple adherence barriers.

  10. Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment: modelling study and economic analysis.

    Science.gov (United States)

    Phillips, Andrew N; Cambiano, Valentina; Miners, Alec; Revill, Paul; Pillay, Deenan; Lundgren, Jens D; Bennett, Diane; Raizes, Elliott; Nakagawa, Fumiyo; De Luca, Andrea; Vitoria, Marco; Barcarolo, Jhoney; Perriens, Joseph; Jordan, Michael R; Bertagnolio, Silvia

    2014-11-01

    With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial levels of transmitted drug resistance. We created a model of HIV transmission, progression, and the effects of ART, which accounted for resistance generation, transmission, and disappearance of resistance from majority virus in the absence of drug pressure. We simulated 5000 ART programmatic scenarios with different prevalence levels of detectable resistance in people starting ART in 2017 (t0) who had not previously been exposed to antiretroviral drugs. We used the model to predict cost-effectiveness of various potential changes in policy triggered by different prevalence levels of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) measured in the population starting ART. Individual-level resistance testing before ART initiation was not generally a cost-effective option, irrespective of the cost-effectiveness threshold. At a cost-effectiveness threshold of US$500 per quality-adjusted life-year (QALY), no change in policy was cost effective (ie, no change in policy would involve paying less than $500 per QALY gained), irrespective of the prevalence of pretreatment NNRTI resistance, because of the increased cost of the policy alternatives. At thresholds of $1000 or higher, and with the prevalence of pretreatment NNRTI resistance greater than 10%, a policy to measure viral load 6 months after ART initiation became cost effective. The policy option to change the standard first-line treatment to a boosted protease inhibitor regimen became cost effective at a prevalence of NNRTI resistance higher than 15%, for cost-effectiveness thresholds greater than $2000. Cost-effectiveness of potential policies to adopt in response to different levels of pretreatment HIV drug

  11. HIV drug resistance mutations in proviral DNA from a community treatment program.

    Directory of Open Access Journals (Sweden)

    Anne Derache

    Full Text Available Drug resistance mutations archived in resting memory CD4+ cells may persist despite suppression of HIV RNA to <50 copies/ml. We sequenced pol gene from proviral DNA among viremic and suppressed patients to identify drug resistance mutations.The Peninsula AIDS Research Cohort study enrolled and followed over 2 years 120 HIV infected patients from San Mateo and San Francisco Counties. HIV-1 pol genotyping by bulk sequencing was performed on 38 DNA and RNA from viremic patients and DNA only among 82 suppressed patients at baseline. Antiretroviral susceptibility was predicted by HIVDB.stanford.edu.Among 120 subjects, 81% were on antiretroviral therapy and had been treated for a median time of 7 years. Thirty-two viremic patients showed concordant RNA and DNA genotypes (84%; the discordant profiles were mainly observed in patients with low-level viremia. Among suppressed patients, 21 had drug resistance mutations in proviral DNA (26% with potential resistance to one, two or three ARV classes in 16, 4 and 1 samples respectively.The high level of genotype concordance between DNA and RNA in viremic patients suggested that DNA genotyping might be used to assess drug resistance in resource-limited settings, and further investigation of extracted DNA from dried blood spots is needed. Drug resistance mutations in proviral DNA in 26% of subjects with less than 50 copies/ml pose a risk for the transmission of drug resistant virus with virologic failure, treatment interruption or decreased adherence.

  12. High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa.

    Directory of Open Access Journals (Sweden)

    Justen Manasa

    Full Text Available To determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa.Cross-sectional study nested within HIV treatment programme.Adult (≥ 18 years HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART regimen and with evidence of virological failure (one viral load >1000 copies/ml were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS for standard second-line regimens were calculated using the Stanford HIVDB 6.0.5 algorithms.A total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%; and stavudine, lamivudine and nevirapine (24%. Median duration of ART was 42 months (interquartile range (IQR 32-53 and median duration of antiretroviral failure was 27 months (IQR 17-40. One hundred and ninety one (86% had at least one drug resistance mutation. For 34 individuals (15%, the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR 5.70, 95% confidence interval (CI 2.60-12.49.There are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved.

  13. Antiretroviral solid drug nanoparticles with enhanced oral bioavailability: production, characterization, and in vitro-in vivo correlation.

    Science.gov (United States)

    McDonald, Tom O; Giardiello, Marco; Martin, Philip; Siccardi, Marco; Liptrott, Neill J; Smith, Darren; Roberts, Phill; Curley, Paul; Schipani, Alessandro; Khoo, Saye H; Long, James; Foster, Alison J; Rannard, Steven P; Owen, Andrew

    2014-03-01

    Nanomedicine strategies have produced many commercial products. However, no orally dosed HIV nanomedicines are available clinically to patients. Although nanosuspensions of drug particles have demonstrated many benefits, experimentally achieving >25 wt% of drug relative to stabilizers is highly challenging. In this study, the emulsion-templated freeze-drying technique for nanoparticles formation is applied for the first time to optimize a nanodispersion of the leading non-nucleoside reverse transcriptase inhibitor efavirenz, using clinically acceptable polymers and surfactants. Dry monoliths containing solid drug nanoparticles with extremely high drug loading (70 wt% relative to polymer and surfactant stabilizers) are stable for several months and reconstitute in aqueous media to provide nanodispersions with z-average diameters of 300 nm. The solid drug nanoparticles exhibit reduced cytoxicity and increased in vitro transport through model gut epithelium. In vivo studies confirm bioavailability benefits with an approximately four-fold higher pharmacokinetic exposure after oral administration to rodents, and predictive modeling suggests dose reduction with the new formulation may be possible. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function

    DEFF Research Database (Denmark)

    Nielsen, Lene Ryom; Mocroft, A.; Kirk, O.

    2013-01-01

    Background. Several antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)-positive persons with initially normal renal function is unknown.Methods. D:A:D study participants with an estimated...... glomerular filtration rate (eGFR) of ≥90 mL/min after 1 January 2004 were followed until they had a confirmed eGFR of ≤70 mL/min (the threshold below which we hypothesized that renal interventions may begin to occur) or ≤60 mL/min (a value indicative of moderately severe chronic kidney disease [CKD...... [95% CI, 1.16-1.28], respectively). Associations were unaffected by censoring for concomitant ARV use but diminished after discontinuation of these ARVs.Conclusions. Tenofovir, ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir use were independent predictors of chronic renal impairment...

  15. Stigma trajectories among people living with HIV (PLHIV) embarking on a life time journey with antiretroviral drugs in Jinja, Uganda.

    Science.gov (United States)

    Mbonye, Martin; Nakamanya, Sarah; Birungi, Josephine; King, Rachel; Seeley, Janet; Jaffar, Shabbar

    2013-09-05

    Stigma is a barrier to HIV prevention and treatment. There is a limited understanding of the types of stigma facing people living with HIV (PLHIV) on antiretroviral therapy (ART). We describe the stigma trajectories of PLHIV over a 5-year period from the time they started ART. Longitudinal qualitative in-depth interviews were conducted with 41 members of The AIDS Support Organisation (TASO) from 2005 to 2008 in Jinja, Uganda, who were part of a pragmatic cluster-randomised trial comparing two different modes of ART delivery (facility and home). Participants were stratified by gender, ART delivery arm and HIV stage (early or advanced) and interviewed at enrolment on to ART and then after 3, 6, 18 and 30 months. Interviews focused on stigma and ART experiences. In 2011, follow-up interviews were conducted with 24 of the participants who could be traced. Transcribed texts were translated, coded and analyzed thematically. Stigma was reported to be very high prior to starting ART, explained by visible signs of long-term illnesses and experiences of discrimination and abuse. Early coping strategies included: withdrawal from public life, leaving work due to ill health and moving in with relatives. Starting ART led to a steady decline in stigma and allowed the participants to take control of their illness and manage their social lives. Better health led to resumption of work and having sex but led to reduced disclosure to employers, colleagues and new sexual partners. Some participants mentioned sero-sorting in order to avoid questions around HIV sero-status. A rise in stigma levels during the 18 and 30 month interviews may be correlated with decreased disclosure. By 2011, ART-related stigma was even more pronounced particularly among those who had started new sexual relationships, gained employment and those who had bodily signs from ART side-effects. This study has shown that while ART comes with health benefits which help individuals to get rid of previously

  16. Factors for incomplete adherence to antiretroviral therapy including drug refill and clinic visits among older adults living with human immunodeficiency virus - cross-sectional study in South Africa.

    Science.gov (United States)

    Barry, Abbie; Ford, Nathan; El-Khatib, Ziad

    2018-03-01

    To assess adherence outcomes to antiretroviral therapy (ART) of recipients ≥50 years in Soweto, South Africa. This was a secondary data analysis for a cross-sectional study at two HIV clinics in Soweto. Data on ART adherence and covariates were gathered through structured interviews with HIV 878 persons living with HIV (PLHIV) receiving ART. Logistic regression analysis was used to assess associations. PLHIV ≥50 years (n = 103) were more likely to miss clinic visits during the last six months than PLHIV aged 25-49 (OR 2.15; 95%CI 1.10-4.18). PLHIV ≥50 years with no or primary-level education were less likely to have missed a clinic visit during the last six months than PLHIV with secondary- or tertiary-level education in the same age category (OR 0.3; 95%CI 0.1-1.1), as were PLHIV who did not disclose their status (OR 0.2; 95%CI 0-1.1). There was no evidence of increased risk for non-adherence to ART pills and drug refill visits among older PLHIV. Missing a clinic visit was more common among older PLHIV who were more financially vulnerable. Further studies are needed to verify these findings and identify new risk factors associated with ART adherence. © 2017 John Wiley & Sons Ltd.

  17. Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China

    Science.gov (United States)

    2012-01-01

    Background The emergence of an HIV-1 epidemic in China was first recognized in Dehong, western Yunnan. Due to its geographic location, Dehong contributed greatly in bridging HIV-1 epidemics in Southeast Asia and China through drug trafficking and injection drug use; and also extensively to the HIV genetic diversity in Yunnan and China. We attempt to monitor HIV-1 in this area by studying the HIV-1 genetic distribution and transmitted drug resistance (TDR) in various at-risk populations. Methods Blood samples from a total of 320 newly HIV-1 diagnosed individuals, who were antiretroviral therapy (ART)-naive, were collected from January 2009 to December 2010 in 2 counties in Dehong. HIV-1 subtypes and pol gene drug resistance (DR) mutations were genotyped. Results Among 299 pol sequences successfully genotyped (93.4%), subtype C accounted for 43.1% (n=129), unique recombinant forms (URFs) for 18.4% (n=55), CRF01_AE for 17.7% (n=54), B for 10.7% (n=32), CRF08_BC for 8.4% (n=25) and CRF07_BC for 1.7% (n=5). Subtype distribution in patients infected by different transmission routes varied. In contract to the previous finding of CRF01_AE predominance in 2002-2006, subtype C predominated in both injecting drug users (IDUs) and heterosexually transmitted populations in this study. Furthermore, we found a high level of BC, CRF01_AE/C and CRF01_AE/B/C recombinants suggesting the presence of active viral recombination in the area. TDR associated mutations were identified in 4.3% (n=13) individuals. A total of 1.3% of DR were related to protease inhibitors (PIs), including I85IV, M46I and L90M; 0.3% to nucleoside reverse transcriptase inhibitors (NRTIs), including M184I; and 2.7% to non-nucleoside reverse transcriptase inhibitors (NNRTIs), including K103N/S, Y181C, K101E and G190A. Conclusion Our work revealed diverse HIV-1 subtype distributions and intersubtype recombinations. We also identified a low but significant TDR mutation rate among ART-naive patients. These findings

  18. Kalvi Kõva : dzhiibi arvelevõtu tasu võiks olla 100 000 krooni / Arved Breidaks

    Index Scriptorium Estoniae

    Breidaks, Arved, 1975-

    2008-01-01

    Sotsiaaldemokraat, parlamendiliige Kalvi Kõva soovitab automaksu plaanival valitsusel tõsta autode registreerimise tasu maasturite puhul kuni 100 000 kroonini. Lisa: Esmakordselt registreeritud uued sõiduautod. Vt. samas: Arved Breidaks. Võrumaa autostub.

  19. Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections.

    Science.gov (United States)

    Roy, Upal; Barber, Paul; Tse-Dinh, Yuk-Ching; Batrakova, Elena V; Mondal, Debasis; Nair, Madhavan

    2015-01-01

    Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9) have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function, and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.

  20. Role of MRP Transporters in Regulating Antimicrobial Drug Inefficacy and Oxidative Stress-induced Pathogenesis during HIV-1 and TB Infections

    Directory of Open Access Journals (Sweden)

    Upal eRoy

    2015-09-01

    Full Text Available Multi-Drug Resistance Proteins (MRPs are members of the ATP binding cassette (ABC drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV used in highly active antiretroviral therapy (HAART and antibacterial agents used in Tuberculus Bacilli (TB therapy. Due to their role in efflux of glutathione (GSH conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9 have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.

  1. Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, Alessandro; Phillips, Andrew N; Ruiz, Lidia

    2007-01-01

    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...

  2. Humanized mice recapitulate key features of HIV-1 infection: a novel concept using long-acting anti-retroviral drugs for treating HIV-1.

    Directory of Open Access Journals (Sweden)

    Marc Nischang

    Full Text Available BACKGROUND: Humanized mice generate a lymphoid system of human origin subsequent to transplantation of human CD34+ cells and thus are highly susceptible to HIV infection. Here we examined the efficacy of antiretroviral treatment (ART when added to food pellets, and of long-acting (LA antiretroviral compounds, either as monotherapy or in combination. These studies shall be inspiring for establishing a gold standard of ART, which is easy to administer and well supported by the mice, and for subsequent studies such as latency. Furthermore, they should disclose whether viral breakthrough and emergence of resistance occurs similar as in HIV-infected patients when ART is insufficient. METHODS/PRINCIPAL FINDINGS: NOD/shi-scid/γ(cnull (NOG mice were used in all experimentations. We first performed pharmacokinetic studies of the drugs used, either added to food pellets (AZT, TDF, 3TC, RTV or in a LA formulation that permitted once weekly subcutaneous administration (TMC278: non-nucleoside reverse transcriptase inhibitor, TMC181: protease inhibitor. A combination of 3TC, TDF and TMC278-LA or 3TC, TDF, TMC278-LA and TMC181-LA suppressed the viral load to undetectable levels in 15/19 (79% and 14/14 (100% mice, respectively. In successfully treated mice, subsequent monotherapy with TMC278-LA resulted in viral breakthrough; in contrast, the two LA compounds together prevented viral breakthrough. Resistance mutations matched the mutations most commonly observed in HIV patients failing therapy. Importantly, viral rebound after interruption of ART, presence of HIV DNA in successfully treated mice and in vitro reactivation of early HIV transcripts point to an existing latent HIV reservoir. CONCLUSIONS/SIGNIFICANCE: This report is a unique description of multiple aspects of HIV infection in humanized mice that comprised efficacy testing of various treatment regimens, including LA compounds, resistance mutation analysis as well as viral rebound after treatment

  3. Twelve years of follow-up for patients treated with ARVs in Senegal (ANRS Cohort 1215): description of population and methodology.

    Science.gov (United States)

    Ndoye, I; Taverne, B

    2014-10-01

    The ANRS Cohort 1215 brought together the first 400 patients receiving antiretroviral treatments through the government program for ARV treatment in Senegal. These people, infected with HIV-1, began their treatment between 1998 and 2002; they were treated with 2 NRTI + 1 PI or NNRTI. This prospective observational cohort received follow-up over the course of 12 years, from 1999 to 2010, and was one of the earliest established cohorts in Africa and providing the longest duration of ART follow-up. A series of interdisciplinary studies was conducted among these patients to assess the medical and social as well as the individual and collective impact of these treatments over the long term. This article presents the cohort's key methodological characteristics.

  4. Promosi Kesehatan Nola Pender Berpengaruh Terhadap Pengetahuan dan Kepatuhan ODHA Minum ARV

    Directory of Open Access Journals (Sweden)

    Tuti Asrianti Utami

    2017-05-01

    Full Text Available The success rate of ARV therapy depends on the adherence of HIV-AIDS patients in ARV treatment. The purpose of this study was to analyze the effect of NolaPender health promotion to improve the knowledge and adherence of PLWHA (People living with HIV-AIDS with ARV in SintCarolus Health Service (SCHS and Persahabatan General Hospital (PGH. This study used a Pre-Post test Quasi Eksperimantal Non Equivalent Control Group and a total sample of 90 respondents were recruited through the use of consecutive sampling with inclusion criteria where 45 respondents served as intervention group in SCHS and the remaining as control group in PGH from May-June 2016. The result showed most respondents were in the late adulthood stage (36-55 years old, male, having advanced education, working, exposed to counseling service, having family support as well as peer group support, easy in reaching health service and with health insurance. NolaPender health promotion increased the knowledge of ARV (mean score pre intervention was 5.31 to post intervention 7.04, and improving the adherence of taking ARV from moderate to good adherence as many as 51.1%. There was an effect of Nola Pender health promotion using booklet to respondents’ knowledge (p-value=0.000 from 13.3% to 91.1% and also effect of knowledge improvement of ARV to the adherence of taking ARV, with the support from peer group from 30.2% to 87.2%. The study recommends to continue this program of Nola Pender health promotion for PLWHA taking ARV in a structured and well planned system.

  5. High rates of regimen change due to drug toxicity among a cohort of South Indian adults with HIV infection initiated on generic, first-line antiretroviral treatment.

    Science.gov (United States)

    Sivadasan, Ajith; Abraham, O C; Rupali, Priscilla; Pulimood, Susanne A; Rajan, Joyce; Rajkumar, S; Zachariah, Anand; Kannangai, Rajesh; Kandathil, Abraham Joseph; Sridharan, G; Mathai, Dilip

    2009-05-01

    To determine the rates, reasons and predictors of treatment change of the initial antiretroviral treatment (ART) regimen in HIV-infected south Indian adults. In this prospective cohort study, ART-naive adults initiated on generic, fixed dose combination ART as per the National AIDS Control Organization guidelines were followed up at an academic medical center. Treatment change was defined as any event which necessitated a change in or discontinuation of the initial ART regimen. Two hundred and thirty persons with HIV infection (males 74.8% and median age 37 years) were followed up for median duration of 48 weeks. The majority (98.7%) had acquired HIV infection through the heterosexual route. Most (70.4%) had advanced IV infection (WHO clinical stage 3 or 4) and 78% had CD4+ T-lymphocyte counts below 200 cells/microL. The initial ART regimens used were: Lamivudine (3TC) with Stavudine (d4T) (in 76%) or Azidothymidine (AZT) and Nevirapine (NVP) (in 86%) or Efavirenz (EFV). The cumulative incidence of treatment change was 39.6% (91 patients). Drug toxicity (WHO grade 3 or 4) was the reason for treatment change among 62 (27%) (incidence rate 35.9/100 person-years). The most common toxicities were attributable to the thymidine analogue nucleoside reverse transcriptase inhibitors (NRTIs), d4T and AZT [lactic acidosis (8.7%), anemia (7%) and peripheral neuropathy (5.2%)]. The other toxicities were rash (3.9%) and hepatitis (1.3%) due to NVP. The mortality (4.6/100 person-years) and disease progression rates (4.1/100 person-years) were low. The ART regimens used in this study were effective in decreasing disease progression and death. However, they were associated with high rates of drug toxicities, particularly those attributable to thymidine analogue NRTI. As efforts are made to improve access to ART, treatment regimens chosen should not only be potent, but also safe.

  6. Population-based surveillance of HIV drug resistance emerging on treatment and associated factors at sentinel antiretroviral therapy sites in Namibia.

    Science.gov (United States)

    Hong, Steven Y; Jonas, Anna; DeKlerk, Michael; Shiningavamwe, Andreas; Desta, Tiruneh; Badi, Alfons; Morris, Lynn; Hunt, Gillian M; Ledwaba, Johanna; Sheehan, Heidi B; Lau, Kiger; Trotter, Andrew; Tang, Alice M; Wanke, Christine; Jordan, Michael R

    2015-04-01

    The World Health Organization (WHO) prospective surveys of acquired HIV drug resistance (HIVDR) evaluate HIVDR emerging after the first year of antiretroviral therapy (ART) and associated factors. Consecutive ART starters in 2009 were enrolled at 3 sentinel sites in Namibia. Genotyping was performed at start and after 12 months in patients with HIV viral load (VL) >1000 copies per mL. HIVDR outcomes were: HIVDR prevention (VL ≤1000 copies/mL), possible HIVDR (VL >1000 copies/mL without detectable HIVDR or loss to follow-up or ART stop), and HIVDR (VL >1000 copies/mL with detectable HIVDR). Adherence was assessed using medication possession ratio (MPR). Of 394 starters, at 12 months, 80% were on first-line ART, 1% died, 4% transferred out, 1% stopped ART, <1% switched to second-line, and 15% were lost to follow-up. Among patients on first-line, 77% had VL testing, and 94% achieved VL ≤1000 copies per mL. At baseline, 7% had HIVDR. After 12 months, among patients with VL testing, 5% had HIVDR. A majority of patients failing therapy had high-level resistance to nonnucleoside reverse transcriptase inhibitors but none to protease inhibitors. All sites achieved the WHO target of ≥70% HIVDR prevention. Factors associated with not achieving HIVDR prevention were: baseline resistance to nonnucleoside reverse transcriptase inhibitors [odds ratio (OR) 3.0, P = 0.023], WHO stage 3 or 4 at baseline (OR 2.0, P = 0.012), and MPR <75% (OR 4.9, P = 0.021). Earlier ART initiation and removal of barriers to on-time drug pickups may help to prevent HIVDR. These data inform decisions at national and global levels on the effectiveness of first- and second-line regimens.

  7. Decreasing rate of multiple treatment modifications among individuals who initiated antiretroviral therapy in 1997-2009 in the Danish HIV Cohort Study

    DEFF Research Database (Denmark)

    Helleberg, Marie; Kronborg, Gitte; Larsen, Carsten S

    2012-01-01

    BACKGROUND: We hypothesized that rates and reasons for treatment modifications have changed since the implementation of combination antiretroviral therapy (cART) due to improvements in therapy. METHODS: From a nationwide population-based cohort study we identified all HIV-1 infected adults who...... initiated cART in Denmark 1997-2009 and were followed (3)1 year. Incidence rate ratios (IRR) and reasons for treatment modifications were estimated and compared between patients, who initiated treatment in 1997-1999, 2000-2004 and 2005-2009. Rates of discontinuation of individual antiretroviral drugs (ARVs......) were evaluated. RESULTS: 3,107 patients were followed median 7.3 years (IQR 3.8-10.8). Rates of first treatment modification ≤1 year after cART initiation did not change (IRR 0.88 (95% CI 0.78-1.01) and 1.03 (95% CI 0.90-1.18) in 2000-2004 and 2005-2009 compared to 1997-1999). Rates of multiple...

  8. Interactions between antifungal and antiretroviral agents.

    Science.gov (United States)

    Hughes, Christine A; Foisy, Michelle; Tseng, Alice

    2010-09-01

    Since the advent of combination antiretroviral therapy, the incidence of opportunistic infections has declined and the life expectancy of HIV-infected people has significantly increased. However, opportunistic infections, including fungal diseases, remain a leading cause of hospitalizations and mortality in HIV-infected people. With the availability of several new antiretroviral and antifungal agents, drug-drug interactions emerge as a potential safety concern. Relevant literature was identified using a Medline search of articles published up to March 2010 and a review of conference abstracts. Search terms included HIV, antifungal agents and drug interactions. Original papers and relevant citations were considered for this review. Readers will gain an understanding of the pharmacokinetic properties of antiretroviral and antifungal agents, and insight into significant drug-drug interactions which may require dosage adjustments or a change in therapy. Azole antifungal drugs, with the exception of fluconazole, pose the greatest risk of two-way interactions with antiretroviral drugs through CYP450 enzymes effects. Limited studies suggest the risk of interactions between antiretroviral drugs and echinocandins is much lower. The combination of tenofovir and amphotericin B should be used with caution and close monitoring of renal function is required.

  9. Cost-effectiveness of HIV drug resistance testing to inform switching to second line antiretroviral therapy in low income settings

    DEFF Research Database (Denmark)

    Phillips, Andrew; Cambiano, Valentina; Nakagawa, Fumiyo

    2014-01-01

    BACKGROUND: To guide future need for cheap resistance tests for use in low income settings, we assessed cost-effectiveness of drug resistance testing as part of monitoring of people on first line ART - with switching from first to second line ART being conditional on NNRTI drug resistance mutations...... being identified. METHODS: An individual level simulation model of HIV transmission, progression and the effect of ART which accounts for adherence and resistance development was used to compare outcomes of various potential monitoring strategies in a typical low income setting in sub-Saharan Africa...... outcomes were assessed over 2015-2025 in terms of viral suppression, first line failure, switching to second line regimen, death, HIV incidence, disability-adjusted-life-years averted and costs. Potential future low costs of resistance tests ($30) were used. RESULTS: The most effective strategy, in terms...

  10. HIV drug resistance testing among patients failing second line antiretroviral therapy. Comparison of in-house and commercial sequencing.

    Science.gov (United States)

    Chimukangara, Benjamin; Varyani, Bhavini; Shamu, Tinei; Mutsvangwa, Junior; Manasa, Justen; White, Elizabeth; Chimbetete, Cleophas; Luethy, Ruedi; Katzenstein, David

    2017-05-01

    HIV genotyping is often unavailable in low and middle-income countries due to infrastructure requirements and cost. We compared genotype resistance testing in patients with virologic failure, by amplification of HIV pol gene, followed by "in-house" sequencing and commercial sequencing. Remnant plasma samples from adults and children failing second-line ART were amplified and sequenced using in-house and commercial di-deoxysequencing, and analyzed in Harare, Zimbabwe and at Stanford, U.S.A, respectively. HIV drug resistance mutations were determined using the Stanford HIV drug resistance database. Twenty-six of 28 samples were amplified and 25 were successfully genotyped. Comparison of average percent nucleotide and amino acid identities between 23 pairs sequenced in both laboratories were 99.51 (±0.56) and 99.11 (±0.95), respectively. All pairs clustered together in phylogenetic analysis. Sequencing analysis identified 6/23 pairs with mutation discordances resulting in differences in phenotype, but these did not impact future regimens. The results demonstrate our ability to produce good quality drug resistance data in-house. Despite discordant mutations in some sequence pairs, the phenotypic predictions were not clinically significant. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Development of drug resistance mutations in patients on highly active antiretroviral therapy: does competitive advantage drive evolution.

    Science.gov (United States)

    Kolber, Michael A

    2007-01-01

    Most physicians that treat individuals with HIV-1 disease are able to successfully suppress viral replication with the pharmacologic armamentarium available today. For the majority of patients this results in immune reconstitution and improved quality of life. However, a large fraction of these patients have transient elevations in their viral burden and even persistence of low-level viremia. In fact, many individuals whose viral load is suppressed to < 50 c/ml have evidence of low-level viral replication. The impact of low-level viremia and persistent viral replication is an area of significant study and interest owing to the potential for the development of drug resistance mutations. Here the fundamental question is whether and perhaps what factors provide a venue for the development of resistant virus. The concern is clearly the eventual progression of disease with the exhaustion of treatment options. The purpose of this review is to evaluate the current literature regarding the effect of low-level viremia on the development of drug resistance mutations. Herein, we discuss the impact of different levels of viral suppression on the development of mutations. In addition, we look at the role that resistance and fitness play in determining the survival of a breakthrough mutation within the background of drug.

  12. Single Nucleotide Polymorphisms in Cellular Drug Transporters Are Associated with Intolerance to Antiretroviral Therapy in Brazilian HIV-1 Positive Individuals.

    Directory of Open Access Journals (Sweden)

    Mônica Barcellos Arruda

    Full Text Available Adverse reactions are the main cause of treatment discontinuation among HIV+ individuals. Genes related to drug absorption, distribution, metabolism and excretion (ADME influence drug bioavailability and treatment response. We have investigated the association between single nucleotide polymorphisms (SNPs in 29 ADME genes and intolerance to therapy in a case-control study including 764 individuals. Results showed that 15 SNPs were associated with intolerance to nucleoside and 11 to non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, and 8 to protease inhibitors (PIs containing regimens under alpha = 0.05. After Bonferroni adjustment, two associations remained statistically significant. SNP rs2712816, at SLCO2B1 was associated to intolerance to NRTIs (ORGA/AA = 2.37; p = 0.0001, while rs4148396, at ABCC2, conferred risk of intolerance to PIs containing regimens (ORCT/TT = 2.64; p = 0.00009. Accordingly, haplotypes carrying rs2712816A and rs4148396T alleles were also associated to risk of intolerance to NRTIs and PIs, respectively. Our data reinforce the role of drug transporters in response to HIV therapy and may contribute to a future development of personalized therapies.

  13. Early warning indicators for HIV drug resistance in Cameroon during the year 2010.

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    Serge C Billong

    Full Text Available BACKGROUND: Rapid scale-up of antiretroviral therapy (ART in resource-limited settings is accompanied with an increasing risk of HIV drug resistance (HIVDR, which in turn could compromise the performance of national ART rollout programme. In order to sustain the effectiveness of ART in a resource-limited country like Cameroon, HIVDR early warning indicators (EWI may provide relevant corrective measures to support the control and therapeutic management of AIDS. METHODS: A retrospective study was conducted in 2010 among 40 ART sites (12 Approved Treatment Centers and 28 Management Units distributed over the 10 regions of Cameroon. Five standardized EWIs were selected for the evaluation using data from January through December, among which: (1 Good ARV prescribing practices: target = 100%; (2 Patient lost to follow-up: target ≤ 20%; (3 Patient retention on first line ART: target ≥ 70%; (4 On-time drug pick-up: target ≥ 90%; (5 ARV drug supply continuity: target = 100%. Analysis was performed using a Data Quality Assessment tool, following WHO protocol. RESULTS: THE NUMBER OF SITES ATTAINING THE REQUIRED PERFORMANCE ARE: 90% (36/40 for EWI(1, 20% (8/40 for EWI(2; 20% (8/40 for EWI(3; 0% (0/37 for EWI(4; and 45% (17/38 for EWI 5. ARV prescribing practices were in conformity with the national guidelines in almost all the sites, whereas patient adherence to ART (EWI(2, EWI(3, and EWI(4 was very low. A high rate of patients was lost-to-follow-up and others failing first line ART before 12 months of initiation. Discontinuity in drug supply observed in about half of the sites may negatively impact ARV prescription and patient adherence. These poor ART performances may also be due to low number of trained staff and community disengagement. CONCLUSIONS: The poor performance of the national ART programme, due to patient non-adherence and drug stock outs, requires corrective measures to limit risks of HIVDR emergence in Cameroon.

  14. Evolving Human Rights and the Science of Antiretroviral Medicine.

    Science.gov (United States)

    Kavanagh, Matthew; Cohn, Jennifer; Mabote, Lynette; Meier, Benjamin Mason; Williams, Brian; Russell, Asia; Sikwese, Kenly; Baker, Brook

    2015-06-11

    Recent years have seen significant advances in the science of using antiretroviral medicines (ARVs) to fight HIV. Where not long ago ARVs were used late in disease to prevent sick people from dying, today people living with HIV can use ARVs to achieve viral suppression early in the course of disease. This article reviews the mounting new scientific evidence of major clinical and prevention ARV benefits. This has changed the logic of the AIDS response, eliminating competition between "treatment" and "prevention" and encouraging early initiation of treatment for individual and public health benefit. These breakthroughs have implications for the health-related human rights duties of States. With medical advance, the "highest attainable standard" of health has taken a leap, and with it the rights obligations of States. We argue that access to early treatment for all is now a core State obligation and restricting access to, or failing to provide accurate information about, it violates both individual and collective rights. In a context of real political and technical challenges, however, in this article we review the policy implications of evolving human rights obligations given the new science. National and international legal standards require action on budget, health and intellectual property policy, which we outline. Copyright 2015 Kavanagh et al. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

  15. Fixed-dose combination for adults accessing antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    SA HIV Clinicians Society

    2013-02-01

    Full Text Available This document serves to guide clinicians and programme managers on how to switch from 3 separate antiretroviral (ARV drugs to the new, single, fixed-dose combination (FDC tablet containing tenofovir (TDF, emtricitabine (FTC and efavirenz (EFV. Summary Transitioning from individual drugs to an FDC tablet needs to be managed carefully, particularly regarding stock management, ordering processes, supply-chain integrity and comprehensive patient counselling. Priority groups • Initially, FDC supply will be insufficient to provide for all FDC-suitable patients • Therefore, the National Department of Health (NDoH has recommended that the following patient groups be prioritized for FDC initiation/switch: • Priority group 1: All HIV-positive patients newly initiating ART – adults, adolescents and pregnant women (regardless of CD4 count (amendment to the guidelines for the prevention of mother-to-child transmission of HIV (PMTCT anticipated in April 2013 – and who do not have contra-indications to the FDC component drugs • Priority group 2: HIV-positive pregnant women and breastfeeding mothers currently stable on lamivudine (3TC, TDF and EFV • Priority group 3: Virologically suppressed patients on a stavudine (d4T-based regimen and who have normal renal function • Priority group 4: Stable patients receiving individual TDF, 3TC and EFV and who have tuberculosis (TB co-infection • Priority group 5: Stable patients receiving individual TDF, 3TC and EFV and who have other co-morbidites (e.g. hypertension, diabetes • Priority group 6: Patients receiving individual TDF, 3TC and EFV and who request to switch to the FDC treatment • Priority group 7: Patients receiving individual TDF, 3TC and EFV and who, after counselling, agree to switch to the FDC treatment. Important: Clinic staff must co-ordinate this process and only switch as many patients to the FDC tablet as stock allows. This should avoid patients being switched back and forth

  16. Antiretroviral treatment of adult HIV infection - 2008 recommendations of the International AIDS Society USA panel

    NARCIS (Netherlands)

    Hammer, Scott M.; Eron, Joseph J.; Reiss, Peter; Schooley, Robert T.; Thompson, Melanie A.; Walmsley, Sharon; Cahn, Pedro; Fischl, Margaret A.; Gatell, Jose M.; Hirsch, Martin S.; Jacobsen, Donna M.; Montaner, Julio S. G.; Richman, Douglas D.; Yeni, Patrick G.; Volberding, Paul A.

    2008-01-01

    Context The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral- naive and - experienced patients warrant an update of the International AIDS Society - USA guidelines for the use of antiretroviral therapy

  17. Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia.

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    Hubert Barennes

    Full Text Available INTRODUCTION: In resource limited settings, patients entering an antiretroviral therapy (ART program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. METHODS: This retrospective study, conducted in 2010-2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia assessed virological failure (VF rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF (>1,000 copies/ml underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms. RESULTS: On a total of 209 patients, 164 (78.4% were naive and 45 (21.5% were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30-194 and 279 cells/mm3 (IQR: 103-455 (p<0.001, respectively. Twenty seven patients (12.9% exhibited VF (95% CI: 8.6-18.2%, including 10 naive (10/164, 6.0% and 17 pre-treated (17/45, 37.8% patients (p<0.001. Among these viremic patients, twenty-two (81.4% were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3% harbored ≥1 drug resistance mutations (DRMs whereas 3 (all belonging to pre-treated patients harbored wild-types viruses. The most frequent DRMs were M184V (86.3%, K103N (45.5% and thymidine analog mutations (TAMs (40.9%. Two (13.3% pre-treated patients harbored viruses that showed a multi-nucleos(tide resistance including Q151M, K65R, E33A/D, E44A/D mutations. CONCLUSION: In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre

  18. Effect of six antiretroviral drugs (delavirdine, stavudine, lamivudine, nelfinavir, amprenavir and lopinavir/ritonavir in association) on albino pregnant rats (Rattus norvegicus Albinus, Rodentia, Mammalia): biological assay.

    Science.gov (United States)

    Nakamura, M U; Araujo Júnior, E; Simões, J M; Oliveria, R M Filho; Kulay, L Júnior

    2014-08-01

    To compare the chronic effects of antiretrovirals (lamivudine, stavudine, delavirdine, nelfinavir, amprenavir and an association of lopinavir/ritonavir) on albino pregnant rats. Review. Department of Obstetrics, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. This was a comparative retrospective study formed by 18 groups of 10 pregnant rats each, which were nearly three months of age and weighed 200 g. All of them were medicated every day using a stomach probe, while the control group was given 1 mL of distilled water. The study groups received lamivudine (at 5, 15 and 45 mg/kg/day); stavudine (at 1, 3 and 9 mg/kg/day); nelfinavir (at 40, 120 and 360 mg/kg/day); amprenavir (at 46, 138 and 414 mg/kg/day); lopinavir/ritonavir (at 12.8/3.2, 38.4/9.6 and 115/28.8 mg/kg/day) and delavirdine (at 20 and 60 mg/kg/day). These represented 1, 3 and 9 times the human therapeutic dose, except for the last drug, for which the 9-times dose was not used. Maternal, litter and placental weights, implantation and reabsorption numbers, major external fetal malformations and fetal and maternal deaths were evaluated. The Kruskal-Wallis test was used to compare quantitative variables and the chi-square test was used to compare qualitative variables. At all three doses, stavudine increased the maternal weight (p=0.001), while lamivudine at 3- and 9-times doses reduced it (pdrugs studied were harmful with regard to implantation, reabsorption, teratogenity and mortality (p>0.05). Stavudine at all doses reduced the litter weights (ppregnant rats that received amprenavir and ritonavir/lopinavir; and maternal weight change with lamivudine and stavudine. In the fetal compartment, adverse effects were observed in relation to litter weight from stavudine, lamivudine, delavirdine and amprenavir.

  19. Identification of Immunogenic Cytotoxic T Lymphocyte Epitopes Containing Drug Resistance Mutations in Antiretroviral Treatment-Naïve HIV-Infected Individuals.

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    Juan Blanco-Heredia

    Full Text Available Therapeutic HIV vaccines may prove helpful to intensify antiretroviral treatment (ART efficacy and may be an integral part of future cure strategies.We examined IFN-gamma ELISpot responses to a panel of 218 HIV clade B consensus-based HIV protease-reverse transcriptase peptides, designed to mimic previously described and predicted cytotoxic T lymphocyte epitopes overlapping drug resistance (DR positions, that either included the consensus sequence or the DR variant sequence, in 49 ART-naïve HIV-infected individuals. Next generation sequencing was used to assess the presence of minority DR variants in circulating viral populations.Although a wide spectrum of differential magnitudes of response to DR vs. WT peptide pairs was observed, responses to DR peptides were frequent and strong in the study cohort. No difference between the median magnitudes of response to DR vs. WT peptides was observed. Interestingly, of the 22 peptides that were recognized by >15% of the participants, two-thirds (64% corresponded to DR peptides. When analysing responses per peptide pair per individual, responses to only WT (median 4 pairs/individual or DR (median 6 pairs/individual were more common than responses to both WT and DR (median 2 pairs/individual; p<0.001. While the presence of ELISpot responses to WT peptides was frequently associated with the presence of the corresponding peptide sequence in the patient's virus (mean 68% of cases, responses to DR peptides were generally not associated with the presence of DR mutations in the viral population, even at low frequencies (mean 1.4% of cases; p = 0.0002.Our data suggests that DR peptides are frequently immunogenic and raises the potential benefit of broadening the antigens included in a therapeutic vaccine approach to immunogenic epitopes containing common DR sequences. Further studies are needed to assess the quality of responses elicited by DR peptides.

  20. Evaluation of Different Antiretroviral Drug Protocols on Naturally Infected Feline Immunodeficiency Virus (FIV Cats in the late Phase of the Asymptomatic Stage of Infection

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    Paola B. Pisano

    2012-05-01

    Full Text Available The aim of this study was to evaluate the efficacy of the antiretrovirals: Zidovudine (ZDV alone; ZDV + Recombinant Human Interferon-α (rHuIFN-α; ZDV + Lamivudine (3TC and ZDV + valproic acid (Valp on naturally feline immunodeficiency virus (FIV-infected cats, in the late phase of the asymptomatic stage of infection. The follow-up was performed over one year, through clinical evaluation and the determination of viral loads and CD4+/CD8+ ratios. Neurological signs were studied by visual and auditory evoked potentials (VEP, AEP and the responses were abnormal in 80% of the FIV-infected cats. After one year, an improvement in VEP and AEP was observed in the ZDV + Valp group and a worsening in the group receiving ZDV + rHuIFN-α. The CD4+/CD8+ ratio showed a significant increase (both intra and inter-groups only in ZDV and ZDV + 3TC, between their pre-treatment and one year values, as well as among the other groups. Viral load only showed a significant decrease in ZDV and ZDV + 3TC groups, when comparing the values at one year of treatment vs. pre-treatment values and when the different groups were compared. In addition, the viral load decrease was significantly more pronounced in the ZDV + 3TC vs. ZDV group. We conclude that ZDV and ZDV + 3TC produce significant reductions in viral load and stimulate a recovery of the CD4+/CD8+ ratio, compared with the other protocols. It is clear that the addition of 3TC resulted in a greater reduction in viral load than use of ZDV as a single drug. Therefore, the combination ZDV + 3TC could be more effective than the sole use of ZDV.

  1. A pharmacogenetic study of CD4 recovery in response to HIV antiretroviral therapy in two South African population groups.

    Science.gov (United States)

    Parathyras, John; Gebhardt, Stefan; Hillermann-Rebello, Renate; Grobbelaar, Nelis; Venter, Mauritz; Warnich, Louise

    2009-05-01

    South Africa, like many other Southern African countries, has one of the highest HIV infection rates in the world and many individuals consequently receive antiretroviral therapy (ART). However, knowledge regarding (i) the prevalence of functional single nucleotide polymorphisms (SNPs) in pharmacologically relevant genes, and (ii) variance in pharmacotherapy both within and between different populations and ethnic groups is limited. The aim of this study was to determine whether selected polymorphisms in cytochrome P450 (CYP) genes (CYP2B6 and CYP3A4) and the multidrug-resistance 1 (ABCB1) gene underlie altered antiretroviral (ARV) drug response in two South African populations. DNA samples from 182 HIV-positive individuals of Mixed-Ancestry and Xhosa ethnicity on ART were genotyped for the A-392G SNP in CYP3A4, the G516T and A785G SNPs in CYP2B6, and the T-129C, C1236T, G2677T/A and C3435T SNPs in ABCB1. Univariate two-way analysis of variance (ANOVA) testing revealed no apparent effect of ethnicity on immune recovery (in terms of CD4-cell count) in response to ART. Univariate one-way ANOVA testing revealed a discernible effect of genotype on immune recovery in the cases of the T-129C (P=0.03) and G2677A (P<0.01) polymorphisms in the ABCB1 gene. This study serves as a basis for better understanding and possible prediction of pharmacogenetic risk profiles and drug response in individuals and ethnic groups in South Africa.

  2. Loss of Subcellular Lipid Transport Due to ARV1 Deficiency Disrupts Organelle Homeostasis and Activates the Unfolded Protein Response*

    Science.gov (United States)

    Shechtman, Caryn F.; Henneberry, Annette L.; Seimon, Tracie A.; Tinkelenberg, Arthur H.; Wilcox, Lisa J.; Lee, Eunjee; Fazlollahi, Mina; Munkacsi, Andrew B.; Bussemaker, Harmen J.; Tabas, Ira; Sturley, Stephen L.

    2011-01-01

    The ARV1-encoded protein mediates sterol transport from the endoplasmic reticulum (ER) to the plasma membrane. Yeast ARV1 mutants accumulate multiple lipids in the ER and are sensitive to pharmacological modulators of both sterol and sphingolipid metabolism. Using fluorescent and electron microscopy, we demonstrate sterol accumulation, subcellular membrane expansion, elevated lipid droplet formation, and vacuolar fragmentation in ARV1 mutants. Motif-based regression analysis of ARV1 deletion transcription profiles indicates activation of Hac1p, an integral component of the unfolded protein response (UPR). Accordingly, we show constitutive splicing of HAC1 transcripts, induction of a UPR reporter, and elevated expression of UPR targets in ARV1 mutants. IRE1, encoding the unfolded protein sensor in the ER lumen, exhibits a lethal genetic interaction with ARV1, indicating a viability requirement for the UPR in cells lacking ARV1. Surprisingly, ARV1 mutants expressing a variant of Ire1p defective in sensing unfolded proteins are viable. Moreover, these strains also exhibit constitutive HAC1 splicing that interacts with DTT-mediated perturbation of protein folding. These data suggest that a component of UPR induction in arv1Δ strains is distinct from protein misfolding. Decreased ARV1 expression in murine macrophages also results in UPR induction, particularly up-regulation of activating transcription factor-4, CHOP (C/EBP homologous protein), and apoptosis. Cholesterol loading or inhibition of cholesterol esterification further elevated CHOP expression in ARV1 knockdown cells. Thus, loss or down-regulation of ARV1 disturbs membrane and lipid homeostasis, resulting in a disruption of ER integrity, one consequence of which is induction of the UPR. PMID:21266578

  3. Role of HIV Subtype Diversity in the Development of Resistance to Antiviral Drugs

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    Bluma G. Brenner

    2010-11-01

    Full Text Available Despite the fact that over 90% of HIV-1 infected people worldwide harbor non‑subtype B variants of HIV-1, knowledge of resistance mutations in non-B HIV-1 and their clinical relevance is limited. Due to historical delays in access to antiretroviral therapy (ART on a worldwide basis, the vast majority of reports on drug resistance deal with subtype B infections in developed countries. However, both enzymatic and virological data support the concept that naturally occurring polymorphisms among different nonB subtypes can affect HIV-1 susceptibility to antiretroviral drugs (ARVs, the magnitude of resistance conferred by major mutations, and the propensity to acquire some resistance mutations. Tools need to be optimized to assure accurate measurements of drug susceptibility of non-B subtypes. Furthermore, there is a need to recognize that each subtype may have a distinct resistance profile and that differences in resistance pathways may also impact on cross-resistance and the selection of second-line regimens. It will be essential to pay attention to newer drug combinations in well designed long-term longitudinal studies involving patients infected by viruses of different subtypes.

  4. Evolution of primary HIV drug resistance in a subtype C dominated epidemic in Mozambique.

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    Dulce Celina Adolfo Bila

    Full Text Available In Mozambique, highly active antiretroviral treatment (HAART was introduced in 2004 followed by decentralization and expansion, resulting in a more than 20-fold increase in coverage by 2009. Implementation of HIV drug resistance threshold surveys (HIVDR-TS is crucial in order to monitor the emergence of transmitted viral resistance, and to produce evidence-based recommendations to support antiretroviral (ARV policy in Mozambique.World Health Organization (WHO methodology was used to evaluate transmitted drug resistance (TDR in newly diagnosed HIV-1 infected pregnant women attending ante-natal clinics in Maputo and Beira to non-nucleoside reverse transcriptase inhibitors (NNRTI, nucleoside reverse transcriptase inhibitors (NRTI and protease inhibitors (PI. Subtypes were assigned using REGA HIV-1 subtyping tool and phylogenetic trees constructed using MEGA version 5.Although mutations associated with resistance to all three drug were detected in these surveys, transmitted resistance was analyzed and classified as <5% in Maputo in both surveys for all three drug classes. Transmitted resistance to NNRTI in Beira in 2009 was classified between 5-15%, an increase from 2007 when no NNRTI mutations were found. All sequences clustered with subtype C.Our results show that the epidemic is dominated by subtype C, where the first-line option based on two NRTI and one NNRTI is still effective for treatment of HIV infection, but intermediate levels of TDR found in Beira reinforce the need for constant evaluation with continuing treatment expansion in Mozambique.

  5. Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya.

    Science.gov (United States)

    Brooks, Katherine; Diero, Lameck; DeLong, Allison; Balamane, Maya; Reitsma, Marissa; Kemboi, Emmanuel; Orido, Millicent; Emonyi, Wilfred; Coetzer, Mia; Hogan, Joseph; Kantor, Rami

    2016-01-01

    Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya. We determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients' characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests. Among 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations. In this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for

  6. Urban planning and interactions with atmospheric pollution in Arve valley

    Science.gov (United States)

    Langlois de Septenville, William; Cossart, Étienne

    2017-04-01

    Atmospheric pollution is a major concern of urbanised areas and territory managers have to conduct efficient policies to decrease population exposure and vulnerability. Even if pollution peaks are subject to an important mediatisation and to a large part of preventive actions, background pollution remains responsible of the largest sanitary effects. They depend on (1) the concentration and the duration of the exposure and (2) to the kind of pollutants considered. Many sources of pollutants can be identified in urban areas as heating, industry or traffic; and each of them generates specific particles. Currently, the major part of pollution risk studies focuses on modelling particle emissions and their dissemination in the environment. These kinds of studies highlight the hazard intensity and its spatiality, commonly named the hazard exposure. Another part of risk studies, less frequent, considers the vulnerability. Vulnerability is a complex concept that involves a wide range of scales and objects ranging from biophysical parameters to social characteristics. They notably concern accessibility to information, knowledge and perceptions about the risk. The Arve valley (south-east of France) is subject to heavy pollution concentrations. High levels recording in this area have imposed the implementation of an Atmosphere Protection Plan. This type of plan is triggered if a peak occurs and enforces provisional binding measures for polluters, such as highway speed limitation for traffic emissions. These measures are only focused on emissions and have no effect for reducing vulnerability and exposition, for a long- and short-term time scales. An opportunity to ensure this objective is to consider how local urban morphologies can combine exposition and vulnerability situations. Indeed, cities have been planned without taking into account atmospheric pollution and morphologies. This context may conduct to the increase in both of these two risk components and producing

  7. Comparison of anti-retroviral therapy treatment strategies in prevention of mother-to-child transmission in a teaching hospital in Ethiopia

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    Kumela K

    2015-06-01

    Full Text Available Background: More than 90% of Human immunodeficiency virus (HIV infection in children is acquired due to mother-to-child transmission, which is spreading during pregnancy, delivery or breastfeeding. Objective: To determine the effectiveness of highly active antiretroviral and short course antiretroviral regimens in prevention of mother-to-child transmission of HIV and associated factors Jimma University Specialized Hospital (JUSH. Method: A hospital based retrospective cohort study was conducted on HIV infected pregnant mothers who gave birth and had follow up at anti-retroviral therapy (ART clinic for at least 6 months during a time period paired with their infants. The primary and secondary outcomes were rate of infant infection by HIV at 6 weeks and 6 months respectively. The Chi-square was used for the comparison of categorical data multivariate logistic regression model was used to identify the determinants of early mother-to-child transmission of HIV at 6 weeks. Cox proportional hazard model was used to analyze factors that affect the 6 month HIV free survival of infants born to HIV infected mothers. Results: A total of 180 mother infant pairs were considered for the final analysis, 90(50% mothers received single dose nevirapine (sdNVP designated as regimen-3, 67 (37.2% mothers were on different types of ARV regimens commonly AZT + 3TC + NVP (regimen-1, while the rest 23 (12.8% mothers were on short course dual regimen AZT + 3TC + sdNVP (regimen-2. Early mother-to-child transmission rate at 6 weeks for regimens 1, 2 and 3 were 5.9% (4/67, 8.6% (2/23, and 15.5% (14/90 respectively. The late cumulative mother-to-child transmission rate of HIV at 6 months regardless of regimen type was 15.5% (28/180. Postnatal transmission at 6 months was 28.5% (8/28 of infected children. Factors that were found to be associated with high risk of early mother-to-child transmission of HIV include duration of ARV regimen shorter than 2 months during pregnancy

  8. Multi-state models for the analysis of time-to-treatment modification among HIV patients under highly active antiretroviral therapy in Southwest Ethiopia.

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    Birlie, Belay; Braekers, Roel; Awoke, Tadesse; Kasim, Adetayo; Shkedy, Ziv

    2017-06-27

    Highly active antiretroviral therapy (HAART) has shown a dramatic change in controlling the burden of HIV/AIDS. However, the new challenge of HAART is to allow long-term sustainability. Toxicities, comorbidity, pregnancy, and treatment failure, among others, would result in frequent initial HAART regimen change. The aim of this study was to evaluate the durability of first line antiretroviral therapy and to assess the causes of initial highly active antiretroviral therapeutic regimen changes among patients on HAART. A Hospital based retrospective study was conducted from January 2007 to August 2013 at Jimma University Hospital, Southwest Ethiopia. Data on the prescribed ARV along with start date, switching date, and reason for change was collected. The primary outcome was defined as the time-to-treatment change. We adopted a multi-state survival modeling approach assuming each treatment regimen as state. We estimate the transition probability of patients to move from one regimen to another. A total of 1284 ART naive patients were included in the study. Almost half of the patients (41.2%) changed their treatment during follow up for various reasons; 442 (34.4%) changed once and 86 (6.69%) changed more than once. Toxicity was the most common reason for treatment changes accounting for 48.94% of the changes, followed by comorbidity (New TB) 14.31%. The HAART combinations that were robust to treatment changes were tenofovir (TDF) + lamivudine (3TC)+ efavirenz (EFV), tenofovir + lamivudine (3TC) + nevirapine (NVP) and zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP) with 3.6%, 4.5% and 11% treatment changes, respectively. Moving away from drugs with poor safety profiles, such as stavudine(d4T), could reduce modification rates and this would improve regimen tolerability, while preserving future treatment options.

  9. AR Variant ARv567es Induces Carcinogenesis in a Novel Transgenic Mouse Model of Prostate Cancer12

    Science.gov (United States)

    Liu, Gang; Sprenger, Cynthia; Sun, Shihua; Epilepsia, Kathryn Soriano; Haugk, Kathleen; Zhang, Xiaotun; Coleman, Ilsa; Nelson, Peter S; Plymate, Stephen

    2013-01-01

    Androgen deprivation therapy remains the primary treatment modality for patients with metastatic prostate cancer but is uniformly marked by progression to castration-resistant prostate cancer (CRPC) after a period of regression. Continued activation of androgen receptor (AR) signaling is attributed as one of the most important mechanisms underlying failure of therapy. Recently, the discovery of constitutively active AR splice variants (AR-Vs) adds more credence to this idea. Expression of AR-Vs in metastases portends a rapid progression of the tumor. However, the precise role of the AR-Vs in CRPC still remains unknown. ARv567es is one of the two AR variants frequently found in human CRPC xenografts and metastases. Herein, we developed a probasin (Pb) promoter-driven ARv567es transgenic mouse, Pb-ARv567es, to evaluate the role of ARv567es in both autonomous prostate growth and progression to CRPC. We found that expression of ARv567es in the prostate results in epithelial hyperplasia by 16 weeks and invasive adenocarcinoma is evident by 1 year of age. The underlying genetic cellular events involved a cell cycle-related transcriptome and differential expression of a spectrum of genes that are critical for tumor initiation and progression. These findings indicate that ARv567es could induce tumorigenesis de novo and signifies the critical role of AR-Vs in CRPC. Thus, the Pb-ARv567es mouse could provide a novel model in which the role of AR variants in prostate cancer progression can be examined. PMID:24027426

  10. Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco

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    Ana Maria Salustiano Cavalcanti

    2012-06-01

    Full Text Available Determining the prevalence and type of antiretroviral (ARV resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV/acquired immune deficiency syndrome (AIDS were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR, Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%, as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2% based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06 and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho (p = 0.046. The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.

  11. Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco.

    Science.gov (United States)

    Cavalcanti, Ana Maria Salustiano; Brito, Ana Maria de; Salustiano, Daniela Medeiros; Lima, Kledoaldo Oliveira de; Silva, Sirleide Pereira da; Diaz, Ricardo Sobhie; Lacerda, Heloisa Ramos

    2012-06-01

    Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.

  12. Evaluation of patterns of liver toxicity in patients on antiretroviral and anti-tuberculosis drugs: a prospective four arm observational study in ethiopian patients.

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    Getnet Yimer

    Full Text Available OBJECTIVES: To evaluate the incidence, type, severity and predictors of antiretroviral and/or anti-tuberculosis drugs induced liver injury (DILI. METHODS: A total of 1,060 treatment naive patients were prospectively enrolled into four treatment groups: HIV patients receiving efavirenz based HAART alone (Arm-1; TB-HIV co-infected patients with CD4≤200 cells/μL, receiving concomitant rifampicin based anti-TB and efavirenz based HAART (Arm-2; TB-HIV co-infected patients with CD4>200 cells/μL, receiving anti-TB alone (Arm-3; TB patients taking rifampicin based anti-TB alone (Arm-4. Liver enzyme levels were monitored at baseline, 1st, 2nd, 4th, 8th, 12th and 24th weeks during treatment. CD4 and HIV viral load was measured at baseline, 24th and 48th weeks. Data were analyzed using multivariate Cox Proportional Hazards Model. RESULTS: A total of 159 patients (15% developed DILI with severity grades 1, 2, 3 and 4 of 53.5%, 32.7%, 11.3% and 2.5% respectively. The incidence of cholestatic, hepatocellular or mixed pattern was 61%, 15% and 24%, respectively. Incidence of DILI was highest in Arm-2 (24.2%>Arm-3 (10.8%>Arm-1 (8.8%>Arm-4 (2.9%. Concomitant anti-TB-HIV therapy increased the risk of DILI by 10-fold than anti-TB alone (p<0.0001. HIV co-infection increased the risk of anti-TB DILI by 4-fold (p = 0.004. HAART associated DILI was 3-fold higher than anti-TB alone, (p = 0.02. HAART was associated with cholestatic and grade 1 DILI whereas anti-TB therapy was associated with hepatocellular and grade ≥ 2. Treatment type, lower CD4, platelet, hemoglobin, higher serum AST and direct bilirubin levels at baseline were significant DILI predictors. There was no effect of DILI on immunologic recovery or virologic suppression rate of HAART. CONCLUSION: HAART associated DILI is mainly cholestatic and mild whereas hepatocellular or mixed pattern with high severity grade is more common in anti-tuberculosis DILI. TB-HIV co-infection, disease severity

  13. Predictors of poor retention on antiretroviral therapy as a major HIV drug resistance early warning indicator in Cameroon: results from a nationwide systematic random sampling

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    Serge Clotaire Billong

    2016-11-01

    Full Text Available Abstract Background Retention on lifelong antiretroviral therapy (ART is essential in sustaining treatment success while preventing HIV drug resistance (HIVDR, especially in resource-limited settings (RLS. In an era of rising numbers of patients on ART, mastering patients in care is becoming more strategic for programmatic interventions. Due to lapses and uncertainty with the current WHO sampling approach in Cameroon, we thus aimed to ascertain the national performance of, and determinants in, retention on ART at 12 months. Methods Using a systematic random sampling, a survey was conducted in the ten regions (56 sites of Cameroon, within the “reporting period” of October 2013–November 2014, enrolling 5005 eligible adults and children. Performance in retention on ART at 12 months was interpreted following the definition of HIVDR early warning indicator: excellent (>85%, fair (85–75%, poor (<75; and factors with p-value < 0.01 were considered statistically significant. Results Majority (74.4% of patients were in urban settings, and 50.9% were managed in reference treatment centres. Nationwide, retention on ART at 12 months was 60.4% (2023/3349; only six sites and one region achieved acceptable performances. Retention performance varied in reference treatment centres (54.2% vs. management units (66.8%, p < 0.0001; male (57.1% vs. women (62.0%, p = 0.007; and with WHO clinical stage I (63.3% vs. other stages (55.6%, p = 0.007; but neither for age (adults [60.3%] vs. children [58.8%], p = 0.730 nor for immune status (CD4351–500 [65.9%] vs. other CD4-staging [59.86%], p = 0.077. Conclusions Poor retention in care, within 12 months of ART initiation, urges active search for lost-to-follow-up targeting preferentially male and symptomatic patients, especially within reference ART clinics. Such sampling strategy could be further strengthened for informed ART monitoring and HIVDR prevention perspectives.

  14. Comprehension and acceptability of a patient information leaflet (pil for antiretroviral therapy

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    Betty Mwingira

    2006-11-01

    Full Text Available The patient information leaflet (PIL is recognised as playing a key role in informing patients about their medicines. The objectives of this research were to evaluate the readability and understanding of a PIL for the first-line ARV (antiretroviral regimen available in the South African public health sector, and investigate its acceptability in the target Xhosa population. Opsomming Daar word algemeen aanvaar dat die pasiëntinligtingsblaadjie (PIB ‘n sleutelrol speel in die oordra van inligting ten opsigte van medikasie aan pasiënte. Die doelwitte van hierdie navorsing was om die leesbaarheid en begrip van ‘n PIB vir die eerste-linie antiretrovirale (ARV regimen wat in die Suid-Afrikaanse openbare gesondheidsektor beskikbaar is, te evalueer, en om die aanvaarbaarheid daarvan in ‘n teiken-Xhosabevolking te ondersoek. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.

  15. Antiretroviral drug-related liver mortality among HIV-positive persons in the absence of hepatitis B or C virus coinfection

    DEFF Research Database (Denmark)

    Kovari, Helen; Sabin, Caroline A; Ledergerber, Bruno

    2013-01-01

    Liver diseases are the leading causes of death in human immunodeficiency virus (HIV)-positive persons since the widespread use of combination antiretroviral treatment (cART). Most of these deaths are due to hepatitis C (HCV) or B (HBV) virus coinfections. Little is known about other causes...

  16. Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe

    DEFF Research Database (Denmark)

    Nakagawa, Fumiyo; Lodwick, Rebecca; Costagliola, Dominique

    2012-01-01

    Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF...

  17. Antiretroviral Resistance in HIV/AIDS Patients

    Science.gov (United States)

    Manosuthi, W.; MD

    2018-03-01

    The higher prevalence of HIV drug resistance was observed in areas with greater ART coverage. The HIV resistance-associated mutations occur when people have inadequate levels of antiretroviral drugs as well as inadequate potency, inadequate adherence, and preexisting resistance. The degree to drug cross-resistance is observed depends on the specific mutations and number of mutation accumulation. In the Southeast Asia region, the challenging of people with treatment failure is the availability and accessibility to subsequent new antiretroviral drugs to construct he second and salvage regimen. Genotypic resistance testing is a useful tool because it can identify the existing drug resistance-associated mutations under the selective drug pressure. Thus, understanding the basic interpretation of HIV drug resistance- associated mutation is useful in guiding clinical decisions for treatment-experienced people living with HIV.

  18. Iatrogenic Cushing's syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies.

    Science.gov (United States)

    Elliot, Emilie R; Theodoraki, Aikaterini; Jain, Lakshmi R; Marshall, Neal J; Boffito, Marta; Baldeweg, Stephanie E; Waters, Laura J

    2016-10-01

    Ritonavir and cobicistat, used as pharmacokinetic enhancers in combination with some antiretrovirals (ARVs) for the treatment of HIV, are potent inhibitors of the CYP3A4 isoenzyme. Most glucocorticoids are metabolised via the CYP3A4 pathway and iatrogenic Cushing's syndrome (ICS), with possible secondary adrenal insufficiency (SAI), is a recognised complication following co-administration with ritonavir or cobicistat. A structured approach for identifying and managing potentially affected individuals has not been established.We systematically identified patients with ICS/SAI and found substantial heterogeneity in clinical practice across three large London HIV centres. While this significant drug interaction and its complications are now well-recognised, it is apparent that there is no standardised approach to management or guidance for the general physician. Here we describe the management of ICS/SAI in our current practice, review the available evidence and suggest practice recommendations. © Royal College of Physicians 2016. All rights reserved.

  19. Effectiveness of multidrug antiretroviral regimens to prevent mother-to-child transmission of HIV-1 in routine public health services in Cameroon.

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    Patrice Tchendjou

    Full Text Available BACKGROUND: Multidrug antiretroviral (ARV regimens including HAART and short-course dual antiretroviral (sc-dARV regimens were introduced in 2004 to improve Prevention of Mother-to-Child Transmission (PMTCT in Cameroon. We assessed the effectiveness of these regimens from 6-10 weeks and 12 months of age, respectively. METHODOLOGY/FINDINGS: We conducted a retrospective cohort study covering the period from October 2004 to March 2008 in a reference hospital in Cameroon. HIV-positive pregnant women with CD4 or = 37 weeks, women received sd-NVP during labour [regimen 4]. Infants received sd-NVP plus ZDV and 3TC for 7 days or 30 days. Early diagnosis (6-10 weeks was done, using b-DNA and subsequently RT-PCR. We determined early MTCT rate and associated risk factors using logistic regression. The 12-month HIV-free survival was assessed using Cox regression. Among 418 mothers, 335 (80% received multidrug ARV regimens (1, 2, and 3 and MTCT rate with multidrug regimens was 6.6% [95%CI: 4.3-9.6] at 6 weeks, without any significant difference between regimens. Duration of mother's ARV regimen < 4 weeks [OR = 4.7, 95%CI: 1.3-17.6], mother's CD4 < 350 cells/mm(3 [OR = 6.4, 95%CI: 1.8-22.5] and low birth weight [OR = 4.0, 95%CI: 1.4-11.3] were associated with early MTCT. By 12 months, mixed feeding [HR = 8.7, 95%CI: 3.6-20.6], prematurity [HR = 2.3, 95%CI: 1.2-4.3] and low birth weight were associated with children's risk of progressing to infection or death. CONCLUSIONS: Multidrug ARV regimens for PMTCT are feasible and effective in routine reference hospital. Early initiation of ARV during pregnancy and proper obstetrical care are essential to improve PMTCT.

  20. Metabolic disorders and cardiovascular risk in people living with HIV/AIDS without the use of antiretroviral therapy

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    Mariana Amaral Raposo

    Full Text Available Abstract INTRODUCTION: Metabolic disorders in people living with HIV/AIDS (PLH have been described even before the introduction of antiretroviral (ARV drugs in the treatment of HIV infection and are risk factors for cardiovascular diseases. Based on this, the purpose of this study was to assess metabolic disorders and cardiovascular risk in PLH before the initiation of antiretroviral treatment (ART. METHODS: This was a cross-sectional descriptive study of 87 PLH without the use of ART, which was carried out between January and September 2012 at a specialized infectious diseases center in Minas Gerais, Brazil. RESULTS: The main metabolic disorders in the population were low serum levels of HDL-cholesterol, hypertriglyceridemia and abdominal obesity. Dyslipidemia was prevalent in 62.6% of the study population, whereas metabolic syndrome (MS was prevalent in 11.5% of patients assessed by the International Diabetes Federation (IDF criteria and 10.8% assessed by the National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATPIII criteria. Regarding cardiovascular risk, 89.7% of the population presented a low coronary risk according to the Framingham Risk Score. A greater proportion of patients diagnosed with MS presented low cardiovascular risk (80% assessed by IDF criteria and 77.8% assessed by NCEP-ATPIII criteria. CONCLUSIONS: Metabolic disorders in this population may be due to HIV infection or lifestyle (smoking, sedentary lifestyle and inadequate diet. The introduction of ART can enhance dyslipidemia, increasing cardiovascular risk, especially among those who have classic risks of cardiovascular disease.

  1. Determinants of survival in adult HIV patients on antiretroviral therapy in Eastern Uttar Pradesh: A prospective study

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    Jaya Chakravarty

    2014-01-01

    Full Text Available Background & objectives: The National AIDS Control Organization (NACO of India has been providing free ARV (antiretroviral drugs since 2004. b0 y 2012, 486,173 patients had received treatment through the antiretroviral therapy (ART centres. The objective of this observational study was to assess the factors determining survival of patients on ART under routine programme conditions in an ART centre in north India five years after its inception. Methods: Treatment naive HIV positive patients who were enrolled in the ART centre between May 2009 and May 2010 and started on ART as per the Revised NACO guidelines 2009, were included in the study and outcome was assessed after two years of follow up. Results: A total of 1689 patients were included in the analysis, of whom 272 (16.10% expired, 205 (12.13% were lost to follow up (LFU, 526 (31.14% were transferred out to other facilities and 686 (40.63% were alive at the end of two years. Majority (92% of the deaths occurred in the first six months of therapy. Age >30 yr, male gender, poor functional status, haemoglobin level <11 g/dl, body weight <45 kg and CD4 count <100/μl at baseline had significantly higher relative hazard of death. Most LFU also occurred in the first six months and these patients had significantly low CD4 count, weight, haemoglobin level and higher number of patients in Stages III and IV as compared to those who survived. Interpretation & conclusions: The study findings revealed poor survival in the first six months of therapy especially in those with severe immunosuppression. This emphasizes the need for early enrolment into the programme. The high LFU occurring early after initiation of therapy suggests the urgent need to build an efficient patient retrieval system in the programme.

  2. Poor functional immune recovery in aged HIV-1-infected patients following successfully treatment with antiretroviral therapy.

    Science.gov (United States)

    Kasahara, Taissa M; Hygino, Joana; Andrade, Regis M; Monteiro, Clarice; Sacramento, Priscila M; Andrade, Arnaldo F B; Bento, Cleonice A M

    2015-10-01

    Aging is now a well-recognized characteristic of the HIV-infected population and both AIDS and aging are characterized by a deficiency of the T-cell compartment. The objective of the present study was to evaluate the impact of antiretroviral (ARV) therapy in recovering functional response of T cells to both HIV-1-specific ENV peptides (ENV) and tetanus toxoid (TT), in young and aged AIDS patients who responded to ARV therapy by controlling virus replication and elevating CD4(+) T cell counts. Here, we observed that proliferative response of T-cells to either HIV-1-specific Env peptides or tetanus toxoid (TT) was significantly lower in older antiretroviral (ARV)-treated patients. With regard to cytokine profile, lower levels of IFN-γ, IL-17 and IL-21, associated with elevated IL-10 release, were produced by Env- or TT-stimulated T-cells from older patients. The IL-10 neutralization by anti-IL-10 mAb did not elevate IFN-γ and IL-21 release in older patients. Finally, even after a booster dose of TT, reduced anti-TT IgG titers were quantified in older AIDS patients and it was related to both lower IL-21 and IFN-γ production and reduced frequency of central memory T-cells. Our results reveal that ARV therapy, despite the adequate recovery of CD4(+) T cell counts and suppression of viremia, was less efficient in recovering adequate immune response in older AIDS patients. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  3. Platelet count kinetics following interruption of antiretroviral treatment

    DEFF Research Database (Denmark)

    Zetterberg, Eva; Neuhaus, Jacqueline; Baker, Jason V

    2013-01-01

    To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow......-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART....

  4. Evaluation of antiretroviral therapy results in Blantyre, Malawi | van ...

    African Journals Online (AJOL)

    We performed a cross sectional study to evaluate treatment results of the paying antiretroviral therapy clinic of Queen Elizabeth Central Hospital, Blantyre. The only antiretroviral therapy was a fixed drug combination of stavudine, lamivudine and nevirapine. Methods: Interviews, laboratory tests (CD4 count, viral load, ...

  5. Determinants of retention in care in an antiretroviral therapy (ART ...

    African Journals Online (AJOL)

    raoul

    Abstract. Background: Retention in long-term antiretroviral therapy (ART) program remains a major challenge for effective management of HIV infected people in sub-Saharan Africa. Highly Active Antiretroviral Therapy (ART) discontinuation raises concerns about drug resistance and could negate much of the benefit sought ...

  6. Association between prenatal exposure to antiretroviral therapy and birth defects: an analysis of the French perinatal cohort study (ANRS CO1/CO11.

    Directory of Open Access Journals (Sweden)

    Jeanne Sibiude

    2014-04-01

    Full Text Available BACKGROUND: Antiretroviral therapy (ART has major benefits during pregnancy, both for maternal health and to prevent mother-to-child transmission of HIV. Safety issues, including teratogenic risk, need to be evaluated. We estimated the prevalence of birth defects in children born to HIV-infected women receiving ART during pregnancy, and assessed the independent association of birth defects with each antiretroviral (ARV drug used. METHODS AND FINDINGS: The French Perinatal Cohort prospectively enrolls HIV-infected women delivering in 90 centers throughout France. Children are followed by pediatricians until 2 y of age according to national guidelines. We included 13,124 live births between 1994 and 2010, among which, 42% (n = 5,388 were exposed to ART in the first trimester of pregnancy. Birth defects were studied using both European Surveillance of Congenital Anomalies (EUROCAT and Metropolitan Atlanta Congenital Defects Program (MACDP classifications; associations with ART were evaluated using univariate and multivariate logistic regressions. Correction for multiple comparisons was not performed because the analyses were based on hypotheses emanating from previous findings in the literature and the robustness of the findings of the current study. The prevalence of birth defects was 4.4% (95% CI 4.0%-4.7%, according to the EUROCAT classification. In multivariate analysis adjusting for other ARV drugs, maternal age, geographical origin, intravenous drug use, and type of maternity center, a significant association was found between exposure to zidovudine in the first trimester and congenital heart defects: 2.3% (74/3,267, adjusted odds ratio (AOR = 2.2 (95% CI 1.3-3.7, p = 0.003, absolute risk difference attributed to zidovudine +1.2% (95% CI +0.5; +1.9%. Didanosine and indinavir were associated with head and neck defects, respectively: 0.5%, AOR = 3.4 (95% CI 1.1-10.4, p = 0.04; 0.9%, AOR = 3.8 (95% CI 1.1-13.8, p = 0

  7. Comparing antiretroviral treatment outcomes between a prospective community-based and hospital-based cohort of HIV patients in rural Uganda

    Directory of Open Access Journals (Sweden)

    Alibhai Arif

    2011-11-01

    Full Text Available Abstract Background Improved availability of antiretroviral therapy in sub-Saharan Africa is intended to benefit all eligible HIV-infected patients; however in reality antiretroviral services are mainly offered in urban hospitals. Poor rural patients have difficulty accessing the drugs, making the provision of antiretroviral therapy inequitable. Initial tests of community-based treatment programs in Uganda suggest that home-based treatment of HIV/AIDS may equal hospital-based treatment; however the literature reveals limited experiences with such programs. The research This intervention study aimed to; 1 assess the effectiveness of a rural community-based ART program in a subcounty (Rwimi of Uganda; and 2 compare treatment outcomes and mortality in a rural community-based antiretroviral therapy program with a well-established hospital-based program. Ethics approvals were obtained in Canada and Uganda. Results and outcomes Successful treatment outcomes after two years in both the community and hospital cohorts were high. All-cause mortality was similar in both cohorts. However, community-based patients were more likely to achieve viral suppression and had good adherence to treatment. The community-based program was slightly more cost-effective. Per capita costs in both settings were unsustainable, representing more than Uganda’s Primary Health Care Services current expenditures per person per year for all health services. The unpaid community volunteers showed high participation and low attrition rates for the two years that this program was evaluated. Challenges and successes Key successes of this study include the demonstration that antiretroviral therapy can be provided in a rural setting, the creation of a research infrastructure and culture within Kabarole’s health system, and the establishment of a research collaboration capable of enriching the global health graduate program at the University of Alberta. Challenging questions about the

  8. Tööõnnetuste arv Ida-Virus väheneb / Erika Prave

    Index Scriptorium Estoniae

    Prave, Erika, 1970-

    2004-01-01

    Ilmunud ka: Severnoje Poberezhje, 7. dets. 2004, lk. 3. Tööinspektsiooni viimase üheksa aasta statistikast järeldub, et tööõnnetuste arv on Ida-Virumaal aastatega vähenenud peaaegu poole võrra

  9. A novel rudivirus, ARV1, of the hyperthermophilic archaeal genus Acidianus

    DEFF Research Database (Denmark)

    Vestergaard, Gisle Alberg; Häring, Monika; Peng, Xu

    2005-01-01

    Virus ARV1, the first member of the family Rudiviridae infecting hyperthermophilic archaea of the genus Acidianus, was isolated from a hot spring in Pozzuoli, Italy. The rod-shaped virions, 610 +/- 50 nm long and 22 +/- 3 nm wide, are non-enveloped and carry a helical nucleoprotein core, with three...

  10. Püsiühenduste arv kasvas aastaga poole võrra / Tõnu Vare

    Index Scriptorium Estoniae

    Vare, Tõnu, 1947-

    2005-01-01

    Uuringufirma Point Topic andmetel oli 30. septembri 2004. a. seisuga Interneti püsiühenduste arv maailmas 136,4 miljonit. Diagrammid: Püsiühendustega leibkondade osakaal (%) Euroopas; 512 Kb/s allalaadimiskiirusega püsiühenduse kuutasu (eurodes)

  11. Pharmaceutical Equivalence of Distributed Generic Antiretroviral (ARV) in Asian Settings: The Cross-Sectional Surveillance Study - PEDA Study

    NARCIS (Netherlands)

    Sapsirisavat, Vorapot; Vongsutilers, Vorasit; Thammajaruk, Narukjaporn; Pussadee, Kanitta; Riyaten, Prakit; Kerr, Stephen; Avihingsanon, Anchalee; Phanuphak, Praphan; Ruxrungtham, Kiat

    2016-01-01

    Ensuring that medicines meet quality standards is mandatory for ensuring safety and efficacy. There have been occasional reports of substandard generic medicines, especially in resource-limiting settings where policies to control quality may be less rigorous. As HIV treatment in Thailand depends

  12. Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and Sequence-Level Meta-Analysis

    Science.gov (United States)

    Rhee, Soo-Yon; Blanco, Jose Luis; Jordan, Michael R.; Taylor, Jonathan; Lemey, Philippe; Varghese, Vici; Hamers, Raph L.; Bertagnolio, Silvia; de Wit, Tobias F. Rinke; Aghokeng, Avelin F.; Albert, Jan; Avi, Radko; Avila-Rios, Santiago; Bessong, Pascal O.; Brooks, James I.; Boucher, Charles A. B.; Brumme, Zabrina L.; Busch, Michael P.; Bussmann, Hermann; Chaix, Marie-Laure; Chin, Bum Sik; D’Aquin, Toni T.; De Gascun, Cillian F.; Derache, Anne; Descamps, Diane; Deshpande, Alaka K.; Djoko, Cyrille F.; Eshleman, Susan H.; Fleury, Herve; Frange, Pierre; Fujisaki, Seiichiro; Harrigan, P. Richard; Hattori, Junko; Holguin, Africa; Hunt, Gillian M.; Ichimura, Hiroshi; Kaleebu, Pontiano; Katzenstein, David; Kiertiburanakul, Sasisopin; Kim, Jerome H.; Kim, Sung Soon; Li, Yanpeng; Lutsar, Irja; Morris, Lynn; Ndembi, Nicaise; NG, Kee Peng; Paranjape, Ramesh S.; Peeters, Martine; Poljak, Mario; Price, Matt A.; Ragonnet-Cronin, Manon L.; Reyes-Terán, Gustavo; Rolland, Morgane; Sirivichayakul, Sunee; Smith, Davey M.; Soares, Marcelo A.; Soriano, Vincent V.; Ssemwanga, Deogratius; Stanojevic, Maja; Stefani, Mariane A.; Sugiura, Wataru; Sungkanuparph, Somnuek; Tanuri, Amilcar; Tee, Kok Keng; Truong, Hong-Ha M.; van de Vijver, David A. M. C.; Vidal, Nicole; Yang, Chunfu; Yang, Rongge; Yebra, Gonzalo; Ioannidis, John P. A.; Vandamme, Anne-Mieke; Shafer, Robert W.

    2015-01-01

    Background Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. Methods and Findings We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05–1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06–1.25), North America (OR = 1.19; 95% CI: 1.12–1.26), Europe (OR = 1.07; 95% CI: 1.01–1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12–1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92–1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four

  13. Computer-based intervention in HIV clinical care setting improves antiretroviral adherence: the LifeWindows Project.

    Science.gov (United States)

    Fisher, Jeffrey D; Amico, K Rivet; Fisher, William A; Cornman, Deborah H; Shuper, Paul A; Trayling, Cynthia; Redding, Caroline; Barta, William; Lemieux, Anthony F; Altice, Frederick L; Dieckhaus, Kevin; Friedland, Gerald

    2011-11-01

    We evaluated the efficacy of LifeWindows, a theory-based, computer-administered antiretroviral (ARV) therapy adherence support intervention, delivered to HIV + patients at routine clinical care visits. 594 HIV + adults receiving HIV care at five clinics were randomized to intervention or control arms. Intervention vs. control impact in the intent-to-treat sample (including participants whose ARVs had been entirely discontinued, who infrequently attended care, or infrequently used LifeWindows) did not reach significance. Intervention impact in the On Protocol sample (328 intervention and control arm participants whose ARVs were not discontinued, who attended care and were exposed to LifeWindows regularly) was significant. On Protocol intervention vs. control participants achieved significantly higher levels of perfect 3-day ACTG-assessed adherence over time, with sensitivity analyses maintaining this effect down to 70% adherence. This study supports the utility of LifeWindows and illustrates that patients on ARVs who persist in care at clinical care sites can benefit from adherence promotion software.

  14. Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results.

    Science.gov (United States)

    Floris-Moore, Michelle A; Mollan, Katie; Wilkin, Aimee M; Johnson, Marc A; Kashuba, Angela Dm; Wohl, David A; Patterson, Kristine B; Francis, Owen; Kronk, Catherine; Eron, Joseph J

    2016-01-01

    Etravirine (ETR), a non-nucleoside reverse transcriptase inhibitor approved for 200 mg twice-daily dosing in conjunction with other antiretrovirals (ARVs), has pharmacokinetic properties which support once-daily dosing. In this single-arm, open-label study, 79 treatment-naive HIV-infected adults were assigned to receive ETR 400 mg plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300/200 mg once daily to assess antiviral activity, safety and tolerability. ARV activity at 48 weeks was determined by proportion of subjects with HIV-1 RNAE138K (one alone and one with additional mutations). Median (95% CI) CD4(+) cell count increase was 163 (136, 203) cells/µl. Fifteen (19.0%) participants reported a new sign/symptom or lab abnormality ≥ Grade 3 and three participants (3.8%) permanently discontinued ETR due to toxicity. Two participants had psychiatric symptoms of any grade. There were no deaths. In this study of ARV-naive HIV-positive adults, once-daily ETR with TDF/FTC had acceptable antiviral activity and was well-tolerated. Once-daily ETR may be a plausible option as part of a combination ARV regimen for treatment-naive individuals. ClinicalTrials.gov NCT00959894.

  15. Preferences for antiretroviral therapy services: Qualitative evidence ...

    African Journals Online (AJOL)

    AUGUSTINE TANLE

    2015-09-14

    Sep 14, 2015 ... create an environment conducive for the delivery of effective HIV and AIDS services. It stimulated the ... counselling in ART; direction on logistics management and information for Antiretroviral drugs. ..... basis because they cannot afford the cost of transport involved (Female, PLHIV, 37 years). My problem is ...

  16. Dual antiretroviral therapy for HIV infection.

    Science.gov (United States)

    Soriano, Vicente; Fernandez-Montero, Jose Vicente; Benitez-Gutierrez, Laura; Mendoza, Carmen de; Arias, Ana; Barreiro, Pablo; Peña, José M; Labarga, Pablo

    2017-08-01

    For two decades, triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy. At this time, combinations of dolutegravir plus rilpivirine represent the best dual regimen. Longer follow-up and larger study populations are needed before supporting dolutegravir plus lamivudine. In contrast, dual therapy based on maraviroc is less effective. Although dual regimens with boosted protease inhibitors plus either lamivudine or raltegravir may be effective, they are penalized by metabolic side effects and risk for drug interactions. The newest dual regimens could save money, reduce toxicity and spare drug options for the future. For the first time in HIV therapeutics, less can be more. Dual therapy switching has set up a new paradigm in HIV treatment that uses induction-maintenance.

  17. Perceived stigma and highly active antiretroviral treatment ...

    African Journals Online (AJOL)

    Perceived stigma and highly active antiretroviral treatment adherence among persons living with HIV/AIDS in the University of Port Harcourt Teaching Hospital. ... Data on socio-demographic characteristics, stigma and adherence to drug regimen were collected using a validated self-administered questionnaire. Data were ...

  18. Evaluating adherence to highly active antiretroviral therapy with use of pill counts and viral load measurement in the drug resources enhancement against AIDS and malnutrition program in Mozambique.

    Science.gov (United States)

    San Lio, Massimo Magnano; Carbini, Riccardo; Germano, Paola; Guidotti, Giovanni; Mancinelli, Sandro; Magid, Noorjehan Abdul; Narciso, Pasquale; Palombi, Leonardo; Renzi, Elsa; Zimba, Ines; Marazzi, Maria Cristina

    2008-05-15

    Maintaining treatment adherence among the growing number of patients receiving antiretroviral treatment in Africa is a dramatic challenge. The objective of our study was to explore the results of a computerized pill count method and to test the validity, sensitivity, and specificity of this method with respect to viral load measurement in an African setting. We performed a prospective, observational study involving patients who received first-line highly active antiretroviral therapy in Mozambique from 1 April 2005 through 31 March 2006. Enrolled patients had received treatment for at least 3 months before the study. For defining treatment adherence levels, pill counts were used, and the results were analyzed with viral load measurements at the end of the observation period. The study involved 531 participants. During the 12 months of observation, 137 patients left the program or discontinued first-line therapy. Of the remaining 394 patients, 284 (72.1%) had >95% treatment adherence; of those 284 patients, 274 (96.5%) had a final viral load 95% treatment adherence and the final viral load was closer than that between >90% treatment adherence and viral load. Treatment adherence >95% maximizes the results of the nonnucleoside reverse-transcriptase inhibitor-based regimen. The pill count method appears to be a reliable and economic tool for monitoring treatment adherence in resource-limited settings.

  19. Pregnancy may be followed by an inflexion of the immune reconstitution in HIV-infected women who receive antiretroviral drugs before conception

    Science.gov (United States)

    Le-Moing, Vincent; Taieb, Audrey; Longuet, Pascale; Lewden, Charlotte; Delcey, Véronique; Drobacheff, Marie Christine; Chêne, Geneviève; Leport, Catherine; the ANRS CO8 (APROCO-COPILOTE) study-group

    2008-01-01

    Summary Background Whether pregnancy has an impact on evolution of CD4+ cell counts in women treated with highly potent antiretrovirals before conception remains largely unknown. Methods Among patients enrolled in the ANRS CO8 (APROCO/COPILOTE) cohort, we selected all women aged between 18 and 50 years at initiation of combination antiretroviral therapy (cART). Slopes of CD4+ cell counts during follow-up were estimated using mixed longitudinal models with time-dependent indicators for pregnancy and delivery. Results Among the 260 selected HIV-infected women, a pregnancy occurred among 39 during a median follow-up of 66 months. Women who became pregnant had higher CD4+ cell count at baseline but this difference was progressively blurred during follow-up because they had a slower increase than women who did not become pregnant. The estimated slope of CD4+ cell count decreased significantly from +2.3 cells/mm3/month before pregnancy and in women who did not become pregnant to − 0.04 cells/mm3/month after delivery (p = 0.0003). Conclusion A significant increase in CD4+ cell count may be preferable before pregnancy in women treated with cART, in order to overcome the evolution observed after pregnancy. PMID:18795961

  20. Profil Lipodistrofi dan Dislipidemia pada Pasien Prepubertas dengan HIV yang Mendapat Terapi ARV di Rumah Sakit Cipto Mangunkusumo

    Directory of Open Access Journals (Sweden)

    Yessi Yuniarti

    2016-11-01

    Kesimpulan. Prevalensi lipodistrofi dan dislipidemia cukup tinggi pada pasien prepubertas dengan HIV yang mendapatkan terapi ARV. Mayoritas subyek yang mengalami lipodistrofi memiliki massa lemak tubuh, TLK triceps dan subscapular yang normal.

  1. Adherence to antiretroviral therapy: a qualitative study with physicians from Rio de Janeiro, Brazil Aderência à terapia anti-retroviral: um estudo qualitativo com médicos no Rio de Janeiro, Brasil

    Directory of Open Access Journals (Sweden)

    Monica Malta

    2005-10-01

    Full Text Available Brazil provides free antiretroviral (ARV therapy to some 150,000 individuals living with HIV/ AIDS. ARV regimens require optimal adherence to achieve undetectable viral loads and to avoid viral resistance. Physicians play a key role to foster ARV adherence, but until now little is known about the communication between physicians/ people living with HIV/AIDS in this setting. In-depth interviews were conducted with 40 physicians treating people living with HIV/AIDS at six public reference centers in Rio de Janeiro, Brazil. Interview topics included: experiences in the treatment of people living with HIV/AIDS, relationship and dialogue with patients, barriers/facilitators to adherence, and effectiveness of available services. Barriers to ARV adherence were mainly related to the low quality of patient-provider relationship. Other barriers were related to "chaotic" patients' lifestyles, and inadequate knowledge and/or negative beliefs about HIV/AIDS and ARV effectiveness. It is necessary to improve networking between services, establish agile referral systems, and improve health professionals' integration. These structural changes could contribute to improved adherence, resulting in improved quality of life for people living with HIV/AIDS.O Brasil fornece gratuitamente terapia anti-retroviral (ARV para cerca de 150 mil pessoas vivendo com HIV/ AIDS. A terapia ARV requer aderência ótima, visando alcançar carga viral indetectável e evitar resistência viral. Os médicos desempenham papel central quanto à aderência à ARV, mas há escassa informação sobre a comunicação entre médicos/pessoas vivendo com HIV/ AIDS. Entrevistas em profundidade foram realizadas com 40 médicos assistentes de seis hospitais de referência do Rio de Janeiro, Brasil. Tópicos da entrevista incluíram: experiências relativas ao tratamento de pessoas vivendo com HIV/AIDS, relacionamento/diálogo com pacientes, barreiras/facilitadores para aderência aos servi

  2. Antiretroviral Drug-Related Liver Mortality Among HIV-Positive Persons in the Absence of Hepatitis B or C Virus Coinfection: The Data Collection on Adverse Events of Anti-HIV Drugs Study

    NARCIS (Netherlands)

    Kovari, Helen; Sabin, Caroline A.; Ledergerber, Bruno; Ryom, Lene; Worm, Signe W.; Smith, Colette; Phillips, Andrew; Reiss, Peter; Fontas, Eric; Petoumenos, Kathy; de Wit, Stéphane; Morlat, Philippe; Lundgren, Jens D.; Weber, Rainer

    2013-01-01

    Background. Liver diseases are the leading causes of death in human immunodeficiency virus (HIV)-positive persons since the widespread use of combination antiretroviral treatment (cART). Most of these deaths are due to hepatitis C (HCV) or B (HBV) virus coinfections. Little is known about other

  3. Predictors of adherence to antiretroviral therapy among HIV-infected persons: a prospective study in Southwest Ethiopia

    Directory of Open Access Journals (Sweden)

    Girma Belaineh

    2008-07-01

    Full Text Available Abstract Background The devastating impact of AIDS in the world especially in sub-Saharan Africa has led to an unprecedented global effort to ensure access to antiretroviral (ARV drugs. Given that medication-taking behavior can immensely affect an individual's response; ART adherence is now widely recognized as an 'Achilles heel' for the successful outcome. The present study was undertaken to investigate the rate and predictors of adherence to antiretroviral therapy among HIV-infected persons in southwest Ethiopia. Methods The study was conducted in the antiretroviral therapy unit of Jimma University Specialized Hospital. A prospective study was undertaken on a total of 400 HIV infected person. Data were collected using a pre-tested interviewer-administered structured questionnaire at first month (M0 and third month (M3 follow up visits. Results A total of 400 and 383 patients at baseline (M0 and at follow up visit (M3 respectively were interviewed. Self-reported dose adherence in the study area was 94.3%. The rate considering the combined indicator (dose, time and food was 75.7%. Within a three month follow up period, dose adherence decreased by 2% and overall adherence rate decreased by more than 3%. Adherence was common in those patients who have a social support (OR, 1.82, 95%CI, 1.04, 3.21. Patients who were not depressed were two times more likely to be adherent than those who were depressed (OR, 2.13, 95%CI, 1.18, 3.81. However, at the follow up visit, social support (OR, 2.42, 95%CI, 1.29, 4.55 and the use of memory aids (OR, 3.29, 95%CI, 1.44, 7.51 were found to be independent predictors of adherence. The principal reasons reported for skipping doses in this study were simply forgetting, feeling sick or ill, being busy and running out of medication in more than 75% of the cases. Conclusion The self reported adherence rate was high in the study area. The study showed that adherence is a dynamic process which changes overtime and cannot

  4. Sensitivity analysis of the parameters of an HIV/AIDS model with condom campaign and antiretroviral therapy

    Science.gov (United States)

    Marsudi, Hidayat, Noor; Wibowo, Ratno Bagus Edy

    2017-12-01

    In this article, we present a deterministic model for the transmission dynamics of HIV/AIDS in which condom campaign and antiretroviral therapy are both important for the disease management. We calculate the effective reproduction number using the next generation matrix method and investigate the local and global stability of the disease-free equilibrium of the model. Sensitivity analysis of the effective reproduction number with respect to the model parameters were carried out. Our result shows that efficacy rate of condom campaign, transmission rate for contact with the asymptomatic infective, progression rate from the asymptomatic infective to the pre-AIDS infective, transmission rate for contact with the pre-AIDS infective, ARV therapy rate, proportion of the susceptible receiving condom campaign and proportion of the pre-AIDS receiving ARV therapy are highly sensitive parameters that effect the transmission dynamics of HIV/AIDS infection.

  5. Survival of HIV/AIDS patients with antiretroviral therapy in association with first-line regimens from 2007 – 2010 in Haji AdamMalik general hospital Medan

    Science.gov (United States)

    Kembaren, T.; Ginting, Y.; Saragih, R. H.

    2018-03-01

    The mortality related to AIDS have decreased dramatically among HIV infected patients taking HAART. HAART is the combination of at least 3 antiretroviral drugs based on the recommendation of WHO. The recent guideline for 1st line therapy recommended by the Indonesian Ministry of Health was Zidovudine/Lamivudine/Nevirapine (ZDV+3TC+NVP), Zidovudine/Lamivudine/Efavirenz (ZDV+3TC+EFV), Stavudine/Lamivudine/Nevirapine (d4T+3TC+NVP), Stavudine/Lamivudine/Efavirenz (d4T+3TC+EFV). Due to a side effect of Stavudine, Ministry of Health plan to pass out Stavudin from the regimens for 1stline therapy.We wanted to evaluate the survival of HIV/AIDS patients with first-line regimens in HAM general hospital Medan. A cohort retrospective study was conducted to evaluate the survival of HIV/AIDS patients taking a combination of 1st line antiretroviral therapy between January 2007 and December 2010. From 2007-2010, among 609 HIV/AIDS patients with first-line ARV medication, 77.5% were male, and 22.5% were female. The most common risk infection was heterosexual. The majority of the patients were in 25-34 years old group. Most of the patients with CD4 1-50 cell/mm3. 2 years survival rate in HIV/AIDS patients taking ZDV+3TC+NVP, ZDV+3TC+EFV, d4T+3TC+NVP, d4T+3TC+EFV were 61.5%, 61.2%, 57.5% and 59.3% respectively. There were no significant differences of 24 months survival in both regiment with or without d4T, 61.8% vs 63.6%.

  6. Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Sterne, Jonathan A C; Egger, Matthias

    2009-01-01

    BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started...... combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting...... combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in

  7. Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children - a EuroCoord-CHAIN-EPPICC joint project

    DEFF Research Database (Denmark)

    Ngo-Giang-Huong, Nicole; Wittkop, Linda; Judd, Ali

    2016-01-01

    BACKGROUND: Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association...... algorithm to infer resistance to prescribed drugs. Time to virological failure (VF) was defined as the first of two consecutive HIV-RNA > 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology.......7-5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5-10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4-23.9). Cumulative risk for VF tended...

  8. Immunomodulation of antiretroviral drug-suppressed chronic HIV-1 infection in an oral probiotic double-blind placebo-controlled trial.

    Science.gov (United States)

    Yang, Otto O; Kelesidis, Theodoros; Cordova, Robert; Khanlou, Homayoon

    2014-10-01

    A putative source of inappropriate immune activation that drives human immunodeficiency virus (HIV)-1 immunopathogenesis is the gastrointestinal tract. Even with effective antiretroviral treatment, residual activation persists. We hypothesized that an oral probiotic could improve the residual immune activation in chronic treated HIV-1 infection, and tested a Bacillus coagulans GBI-30, 6086 capsule probiotic in HIV-1-infected persons with suppressed viremia on stable antiretroviral therapy in a 3-month double-blind placebo-controlled trial (10 probiotic, 7 placebo). The Gastrointestinal Symptom Rating Scale (GSRS) was administered monthly. Blood was tested at the start and end of placebo/probiotic administration for viremia, CD4(+) T cell percentage/concentration, soluble (s)CD14, soluble intestinal fatty acid binding protein, sCD163, D-dimer, C-reactive protein (CRP), interleukin-8, and tumor necrosis factor-α. All participants maintained viremia probiotic was safe and well tolerated, and appeared to improve chronic gastrointestinal symptoms. Its administration was associated with a significant increase in the percentage of blood CD4(+) T cells compared to placebo (+2.8% versus -1.8%, p=0.018) although CD4(+) T cell concentrations were generally unchanged in both groups. None of the biomarkers showed significant changes on probiotic treatment or between-group differences in change (although significance was borderline for a greater sCD163 drop in the probiotic versus placebo group, p=0.05). Some biomarkers showed significant correlations to each other, particularly D-dimer with CRP and sCD14 with tumor necrosis factor (TNF)-α. These data demonstrate the safety and possible benefit of this probiotic for residual inflammation in treated HIV-1 infection, although further study will be required to determine the immune pathways involved.

  9. The Advanced Re-Entry Vehicle (ARV) a Development Step from ATV Toward Manned Transportation Systems

    Science.gov (United States)

    Bottacini, M.; Berthe, P.; Vo, X.; Pietsch, K.

    2011-08-01

    The Advanced Re-entry Vehicle (ARV) programme has been undertaken by Europe with the objective to contribute to the preparation of a future European crew transportation system, while providing a valuable logistic support to the ISS through an operational cargo return system. This development would allow: - the early acquisition of critical technologies; - the design, development and testing of elements suitable for the follow up human rated transportation system. These vehicles should also serve future LEO infrastructures and exploration missions. With the aim to satisfy the above objectives a team composed by major European industries and led by EADS Astrium Space Transportation is currently conducting the phase A of the programme under contract with the European Space Agency (ESA). Two vehicle versions are being investigated: a Cargo version, transporting cargo only to/from the ISS, and a Crew version, which will allow the transfer of both crew and cargo to/from the ISS. The ARV Cargo version, in its present configuration, is composed of three modules. The Versatile Service Module (VSM) provides to the system the propulsion/GNC for orbital manoeuvres and attitude control and the orbital power generation. Its propulsion system and GNC shall be robust enough to allow its use for different launch stacks and different LEO missions in the future. The Un-pressurised Cargo Module (UCM) provides the accommodation for about 3000 kg of un-pressurised cargo and is to be sufficiently flexible to ensure the transportation of: - orbital infrastructure components (ORU's); - scientific / technological experiments; - propellant for re-fuelling, re-boost (and deorbiting) of the ISS. The Re-entry Module (RM) provides a pressurized volume to accommodate active/passive cargo (2000 kg upload/1500 kg download). It is conceived as an expendable conical capsule with spherical heat- hield, interfacing with the new docking standard of the ISS, i.e. it carries the IBDM docking system, on a

  10. Enfuvirtide antiretroviral therapy in HIV-1 infection

    Science.gov (United States)

    Kitchen, Christina MR; Nuño, Miriam; Kitchen, Scott G; Krogstad, Paul

    2008-01-01

    It has been over 25 years since the first diagnosis of what would be known as AIDS. Although great strides in anti-HIV therapeutics have been made, there is still a great need for antiretrovirals that are effective against drug-resistant HIV. Enfuvirtide (ENF) is the first of a new class of fusion inhibitors to be approved by the US Food and Drug Administration for use in combination with other antiretroviral agents among HIV-1 infected patients with previous treatment experience. The inclusion of enfuvirtide in an optimized antiretroviral background regimen for the treatment of HIV-1 infected (treatment-experienced) patients followed the success of two critical clinical trials (TORO: T20 vs Optimized Regimen Only I and II). Even though injection-site reactions persisted in these trials, improved virological and immunological responses were observed among patients. Challenges associated with ENF treatment include the high cost of the drug, injection-site reactions, determining the optimal time to initiate treatment, and the potential for the selection of drug resistant mutants and viral evolution. ENF is a promising novel treatment for HIV infected individuals whose choices for effective treatment are limited by previous treatment and resistance. Understanding the implications of viral fitness and evolution in the presence of ENF treatment is crucial in determining effective and safe treatment regimens, particularly among treatment-experienced patients. PMID:18728846

  11. 'These people who dig roots in the forests cannot treat HIV': Women and men in Durban, South Africa, reflect on traditional medicine and antiretroviral drugs.

    Science.gov (United States)

    Weintraub, Amy; Mantell, Joanne E; Holt, Kelsey; Street, Renée A; Wilkey, Catriona; Dawad, Suraya; Masvawure, Tsitsi B; Hoffman, Susie

    2018-01-01

    Relatively few empirical investigations of the intersection of HIV biomedical and traditional medicine have been undertaken. As part of preliminary work for a longitudinal study investigating health-seeking behaviours among newly diagnosed individuals living with HIV, we conducted semi-structured interviews with 24 urban South Africans presenting for HIV testing or newly enrolled in HIV care; here we explored participants' views on African traditional medicine (TM) and biomedical HIV treatment. Notions of acceptance/non-acceptance were more nuanced than dichotomous, with participants expressing views ranging from favourable to reproachful, often referring to stories they had heard from others rather than drawing from personal experience. Respect for antiretrovirals and biomedicine was evident, but indigenous beliefs, particularly about the role of ancestors in healing, were common. Many endorsed the use of herbal remedies, which often were not considered TM. Given people's diverse health-seeking practices, biomedical providers need to recognise the cultural importance of traditional health practices and routinely initiate respectful discussion of TM use with patients.

  12. Increasing risk behaviour can outweigh the benefits of antiretroviral drug treatment on the HIV incidence among men-having-sex-with-men in Amsterdam

    Directory of Open Access Journals (Sweden)

    Zhu Yifan

    2011-05-01

    Full Text Available Abstract Background The transmission through contacts among MSM (men who have sex with men is one of the dominating contributors to HIV prevalence in industrialized countries. In Amsterdam, the capital of the Netherlands, the MSM risk group has been traced for decades. This has motivated studies which provide detailed information about MSM's risk behavior statistically, psychologically and sociologically. Despite the era of potent antiretroviral therapy, the incidence of HIV among MSM increases. In the long term the contradictory effects of risk behavior and effective therapy are still poorly understood. Methods Using a previously presented Complex Agent Network model, we describe steady and casual partnerships to predict the HIV spreading among MSM. Behavior-related parameters and values, inferred from studies on Amsterdam MSM, are fed into the model; we validate the model using historical yearly incidence data. Subsequently, we study scenarios to assess the contradictory effects of risk behavior and effective therapy, by varying corresponding values of parameters. Finally, we conduct quantitative analysis based on the resulting incidence data. Results The simulated incidence reproduces the ACS historical incidence well and helps to predict the HIV epidemic among MSM in Amsterdam. Our results show that in the long run the positive influence of effective therapy can be outweighed by an increase in risk behavior of at least 30% for MSM. Conclusion We recommend, based on the model predictions, that lowering risk behavior is the prominent control mechanism of HIV incidence even in the presence of effective therapy.

  13. Antiretroviral drug regimens to prevent mother-to-child transmission of HIV: a review of scientific, program, and policy advances for sub-Saharan Africa.

    Science.gov (United States)

    Chi, Benjamin H; Stringer, Jeffrey S A; Moodley, Dhayendre

    2013-06-01

    Considerable advances have been made in the effort to prevent mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Clinical trials have demonstrated the efficacy of antiretroviral regimens to interrupt HIV transmission through the antenatal, intrapartum, and postnatal periods. Scientific discoveries have been rapidly translated into health policy, bolstered by substantial investment in health infrastructure capable of delivering increasingly complex services. A new scientific agenda is also emerging, one that is focused on the challenges of effective and sustainable program implementation. Finally, global campaigns to "virtually eliminate" pediatric HIV and dramatically reduce HIV-related maternal mortality have mobilized new resources and renewed political will. Each of these developments marks a major step in regional PMTCT efforts; their convergence signals a time of rapid progress in the field, characterized by an increased interdependency between clinical research, program implementation, and policy. In this review, we take stock of recent advances across each of these areas, highlighting the challenges--and opportunities--of improving health services for HIV-infected mothers and their children across the region.

  14. Social arv

    DEFF Research Database (Denmark)

    Jensen, Bente

    Arbejdspapir som er udarbejdet i forbindelse med HPA-projektet og brugt i en anden udgivelse fra 2007. Nu genudgivet med nyt forord og ISBN nummer, samt udgive via DPU's forlag som e-bog......Arbejdspapir som er udarbejdet i forbindelse med HPA-projektet og brugt i en anden udgivelse fra 2007. Nu genudgivet med nyt forord og ISBN nummer, samt udgive via DPU's forlag som e-bog...

  15. Chemical interactions study of antiretroviral drugs efavirenz and lamivudine concerning the development of stable fixed-dose combination formulations for AIDS treatment

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Elionai C. de L.; Mussel, Wagner N.; Resende, Jarbas M.; Yoshida, Maria I., E-mail: mirene@ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Instituto de Ciencias Exatas. Departamento de Quimica; Fialho, Silvia L.; Barbosa, Jamile; Fialho, Silvia L. [Fundacao Ezequiel Dias, Belo Horizonte, MG (Brazil)

    2013-04-15

    Lamivudine and efavirenz are among the most worldwide used drugs for acquired immune deficiency syndrome (AIDS) treatment. Solid state nuclear magnetic resonance (ssNMR), Fourier-transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo-optical analysis (TOA) were used to study possible interactions between these drugs, aiming the development of a fixed-dose drug combination. DSC and TOA have evidenced significant shifts on the melting points of both drugs in the mixture, which may be due to interaction between them. Although DSC and TOA results indicated incompatibility between the drugs, FTIR spectra were mostly unmodified due to overlapping peaks. The ssNMR analyses showed significant changes in chemical shifts values of the mixture when compared with spectra of pure drugs, especially in the signals relating to the deficient electron carbon atoms of both drugs. These results confirm the interactions suggested by DSC and TOA, which is probably due to acid-base interactions between electronegative and deficient electron atoms of both lamivudine and efavirenz. (author)

  16. Chemical interactions study of antiretroviral drugs efavirenz and lamivudine concerning the development of stable fixed-dose combination formulations for AIDS treatment

    International Nuclear Information System (INIS)

    Gomes, Elionai C. de L.; Mussel, Wagner N.; Resende, Jarbas M.; Yoshida, Maria I.

    2013-01-01

    Lamivudine and efavirenz are among the most worldwide used drugs for acquired immune deficiency syndrome (AIDS) treatment. Solid state nuclear magnetic resonance (ssNMR), Fourier-transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo-optical analysis (TOA) were used to study possible interactions between these drugs, aiming the development of a fixed-dose drug combination. DSC and TOA have evidenced significant shifts on the melting points of both drugs in the mixture, which may be due to interaction between them. Although DSC and TOA results indicated incompatibility between the drugs, FTIR spectra were mostly unmodified due to overlapping peaks. The ssNMR analyses showed significant changes in chemical shifts values of the mixture when compared with spectra of pure drugs, especially in the signals relating to the deficient electron carbon atoms of both drugs. These results confirm the interactions suggested by DSC and TOA, which is probably due to acid-base interactions between electronegative and deficient electron atoms of both lamivudine and efavirenz. (author)

  17. HIV-1 RNA levels and antiretroviral drug resistance in blood and non-blood compartments from HIV-1-infected men and women enrolled in AIDS clinical trials group study A5077.

    Directory of Open Access Journals (Sweden)

    Rami Kantor

    Full Text Available Detectable HIV-1 in body compartments can lead to transmission and antiretroviral resistance. Although sex differences in viral shedding have been demonstrated, mechanisms and magnitude are unclear. We compared RNA levels in blood, genital-secretions and saliva; and drug resistance in plasma and genital-secretions of men and women starting/changing antiretroviral therapy (ART in the AIDS Clinical Trials Group (ACTG 5077 study.Blood, saliva and genital-secretions (compartment fluids were collected from HIV-infected adults (≥ 13 years at 14 United-States sites, who were initiating or changing ART with plasma viral load (VL ≥ 2,000 copies/mL. VL testing was performed on all compartment fluids and HIV resistance genotyping on plasma and genital-secretions. Spearman rank correlations were used to evaluate concordance and Fisher's and McNemar's exact tests to compare VL between sexes and among compartments.Samples were available for 143 subjects; 36% treated (23 men, 29 women and 64% 'untreated' (40 men, 51 women. RNA detection was significantly more frequent in plasma (100% than genital-secretions (57% and saliva (64% (P<0.001. A higher proportion of men had genital shedding versus women (78% versus 41%, and RNA detection was more frequent in saliva versus genital-secretions in women when adjusted for censoring at the limit of assay detection. Inter-compartment fluid VL concordance was low in both sexes. In 22 (13 men, 9 women paired plasma-genital-secretion genotypes from treated subjects, most had detectable resistance in both plasma (77% and genital-secretions (68%. Resistance discordance was observed between compartments in 14% of subjects.HIV shedding and drug resistance detection prior to initiation/change of ART in ACTG 5077 subjects differed among tissues and between sexes, making the gold standard blood-plasma compartment assessment not fully representative of HIV at other tissue sites. Mechanisms of potential sex-dependent tissue

  18. Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis

    Directory of Open Access Journals (Sweden)

    Jiamsakul Awachana

    2012-10-01

    Full Text Available Abstract Background Accurate interpretation of HIV drug resistance (HIVDR testing is challenging, yet important for patient care. We compared genotyping interpretation, based on the Stanford University HIV Drug Resistance Database (Stanford HIVdb, and virtual phenotyping, based on the Janssen Diagnostics BVBA’s vircoTYPE™ HIV-1, and investigated their level of agreement in antiretroviral (ARV naive patients in Asia, where non-B subtypes predominate. Methods Sequences from 1301 ARV-naive patients enrolled in the TREAT Asia Studies to Evaluate Resistance – Monitoring Study (TASER-M were analysed by both interpreting systems. Interpretations from both Stanford HIVdb and vircoTYPE™ HIV-1 were initially grouped into 2 levels: susceptible and non-susceptible. Discrepancy was defined as a discordant result between the susceptible and non-susceptible interpretations from the two systems for the same ARV. Further analysis was performed when interpretations from both systems were categorised into 3 levels: susceptible, intermediate and resistant; whereby discrepancies could be categorised as major discrepancies and minor discrepancies. Major discrepancy was defined as having a susceptible result from one system and resistant from the other. Minor discrepancy corresponded to having an intermediate interpretation in one system, with a susceptible or resistant result in the other. The level of agreement was analysed using the prevalence adjusted bias adjusted kappa (PABAK. Results Overall, the agreement was high, with each ARV being in “almost perfect agreement”, using Landis and Koch’s categorisation. Highest discordance was observed for efavirenz (75/1301, 5.8%, all arising from susceptible Stanford HIVdb versus non-susceptible vircoTYPE™ HIV-1 predictions. Protease Inhibitors had highest level of concordance with PABAKs all above 0.99, followed by Nucleoside Reverse Transcriptase Inhibitors with PABAKs above 0.97 and non-NRTIs with the

  19. Barriers and facilitators of adherence to antiretroviral drug therapy and retention in care among adult HIV-positive patients: a qualitative study from Ethiopia.

    Directory of Open Access Journals (Sweden)

    Woldesellassie M Bezabhe

    Full Text Available BACKGROUND: Antiretroviral therapy (ART has been life saving for hundreds of thousands of Ethiopians. With increased availability of ART in recent years, achievement of optimal adherence and patient retention are becoming the greatest challenges in the management of HIV/AIDS in Ethiopia. However, few studies have explored factors influencing medication adherence to ART and retention in follow-up care among adult Ethiopian HIV-positive patients, especially in the Amhara region of the country, where almost one-third of the country's ART is prescribed. The aim of this qualitative study was to collect such data from patients and healthcare providers in the Amhara region of Ethiopia. METHODS: Semi-structured interviews were conducted with 24 patients, of whom 11 had been lost to follow-up and were non-persistent with ART. In addition, focus group discussions were performed with 15 ART nurses and 19 case managers. All interviews and focus groups were audio-recorded, transcribed, and coded for themes and patterns in Amharic using a grounded theory approach. The emergent concepts and categories were translated into English. RESULTS: Economic constraints, perceived stigma and discrimination, fasting, holy water, medication side effects, and dissatisfaction with healthcare services were major reasons for patients being non-adherent and lost to follow-up. Disclosure of HIV status, social support, use of reminder aids, responsibility for raising children, improved health on ART, and receiving education and counseling emerged as facilitators of adherence to ART. CONCLUSIONS: Improving adherence and retention requires integration of enhanced treatment access with improved job and food security. Healthcare providers need to be supported to better equip patients to cope with the issues associated with ART. Development of social policies and cooperation between various agencies are required to facilitate optimal adherence to ART, patient retention, and improved

  20. Barriers and facilitators of adherence to antiretroviral drug therapy and retention in care among adult HIV-positive patients: a qualitative study from Ethiopia.

    Science.gov (United States)

    Bezabhe, Woldesellassie M; Chalmers, Leanne; Bereznicki, Luke R; Peterson, Gregory M; Bimirew, Mekides A; Kassie, Desalew M

    2014-01-01

    Antiretroviral therapy (ART) has been life saving for hundreds of thousands of Ethiopians. With increased availability of ART in recent years, achievement of optimal adherence and patient retention are becoming the greatest challenges in the management of HIV/AIDS in Ethiopia. However, few studies have explored factors influencing medication adherence to ART and retention in follow-up care among adult Ethiopian HIV-positive patients, especially in the Amhara region of the country, where almost one-third of the country's ART is prescribed. The aim of this qualitative study was to collect such data from patients and healthcare providers in the Amhara region of Ethiopia. Semi-structured interviews were conducted with 24 patients, of whom 11 had been lost to follow-up and were non-persistent with ART. In addition, focus group discussions were performed with 15 ART nurses and 19 case managers. All interviews and focus groups were audio-recorded, transcribed, and coded for themes and patterns in Amharic using a grounded theory approach. The emergent concepts and categories were translated into English. Economic constraints, perceived stigma and discrimination, fasting, holy water, medication side effects, and dissatisfaction with healthcare services were major reasons for patients being non-adherent and lost to follow-up. Disclosure of HIV status, social support, use of reminder aids, responsibility for raising children, improved health on ART, and receiving education and counseling emerged as facilitators of adherence to ART. Improving adherence and retention requires integration of enhanced treatment access with improved job and food security. Healthcare providers need to be supported to better equip patients to cope with the issues associated with ART. Development of social policies and cooperation between various agencies are required to facilitate optimal adherence to ART, patient retention, and improved patient outcomes.

  1. Choice of initial antiretroviral drugs and treatment outcomes among HIV-infected patients in sub-Saharan Africa: systematic review and meta-analysis of observational studies.

    Science.gov (United States)

    Ayele, Tadesse Awoke; Worku, Alemayehu; Kebede, Yigzaw; Alemu, Kassahun; Kasim, Adetayo; Shkedy, Ziv

    2017-08-25

    The effectiveness of antiretroviral therapy (ART) depends on the choice of regimens during initiation. Most evidences from developed countries indicated that there is difference between efavirenz (EFV) and nevirapine (NVP). However, the evidences are limited in resource poor countries particularly in Africa. Thus, this systematic review and meta-analysis was carried out to summarize reported long-term treatment outcomes among people on first line therapy in sub-Saharan Africa. Observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio to compare risk of treatment failure among HIV/AIDS patients who initiated ART with EFV versus NVP were systematically searched. Searches were conducted using the MEDLINE database within PubMed, Google Scholar, HINARI, and Research Gates between 2007 and 2016. Information was extracted using standardized form. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using random-effect, generic inverse variance method. A total of 6394 articles were identified, of which, 29 were eligible for review and abstraction in sub-Saharan Africa. Seventeen articles were used for the meta-analysis. Of a total of 121,092 independent study participants, 76,719 (63.36%) were females. Of these, 40,480 (33.43%) initiated with NVP containing regimen. Two studies did not report the median CD4 cell counts at initiation. Patients who have low CD4 cell counts initiated with EFV containing regimen. The pooled effect size indicated that treatment failure was reduced by 15%, 0.85 (95%CI: 0.75-0.98), and non-nucleoside reverse transcriptase inhibitor (NNRTI) switch was reduced by 43%, 0.57 (95%CI: 0.37-0.89). The risk of treatment failure and NNRTI switch were lower in patients who initiated with EFV than NVP-containing regimen. The review suggests that initiation of patients with EFV-containing regimen will reduce treatment failure and NNRTI switch.

  2. The role of drugs in HIV prevention

    Science.gov (United States)

    Kembaren, T.

    2018-03-01

    WHO reports 36.7 million people are living with Human Immunodeficiency Virus (HIV) worldwide by 2016 with about 1.8 million new infections each year. It will be a specific health problem for the world in both developed and developing countries so it is necessary strategies to reduce HIV transmission to the community. HIV transmission in people with risk factors is largely determined by the amount of virus in the blood of people who are the source of infection. Antiretroviral (ARV) therapy has long been used in HIV patients, which serves to suppress viral replication so that the patient’s immunity increases; opportunistic infections are resolved and prolong the lifespan and lower transmission rates. In the HIV Prevention Trials Network (HPTN) study 052 there was a 96% reduction in transmission in earlier antiretroviral. ARV is also used in the prevention of transmission in people exposed to HIV virus that is Postexposure Prophylaxis as well as in people at risk before exposure (Pre-exposure Prophylaxis). Three prevention strategies with the provision of ARV is expected to be guided as a means of prevention of transmission in addition to behavioral changes has long been declared since the beginning of the HIV epidemic.

  3. The prevalence of antiretroviral multidrug resistance in highly active antiretroviral therapy-treated patients with HIV/AIDS between 2004 and 2009 in South Korea.

    Science.gov (United States)

    Choi, Ju-yeon; Kwon, Oh-Kyung; Choi, Byeong-Sun; Kee, Mee-Kyung; Park, Mina; Kim, Sung Soon

    2014-06-01

    Highly active antiretroviral therapy (HAART) including protease inhibitors (PIs) has been used in South Korea since 1997. Currently, more than 20 types of antiretroviral drugs are used in the treatment of human immunodeficiency virus-infected/acquired immune deficiency syndrome patients in South Korea. Despite the rapid development of various antiretroviral drugs, many drug-resistant variants have been reported after initiating HAART, and the efficiency of HAART is limited by these variants. To investigate and estimate the annual antiretroviral drug resistance and prevalence of antiretroviral multi-class drug resistance in Korean patients with experience of treatment. The amplified HIV-1 pol gene in 535 patients requested for genotypic drug resistance testing from 2004 to 2009 by the Korea Centers for Disease Control and Prevention was sequenced and analyzed annually and totally. The prevalence of antiretroviral drug resistance was estimated based on "SIR" interpretation of the Stanford sequence database. Of viruses derived from 787 specimens, 380 samples (48.3%) showed at least one drug class-related resistance. Predicted NRTI drug resistance was highest at 41.9%. NNRTI showed 27.2% resistance with 23.3% for PI. The percent of annual drug resistance showed similar pattern and slightly declined except 2004 and 2005. The prevalence of multi-class drug resistance against each drug class was: NRTI/NNRTI/PI, 9.8%; NRTI/PI, 21.9%; NNRTI/PI, 10.4%; and NRTI/NNRTI, 21.5%. About 50% and less than 10% of patients infected with HIV-1 have multidrug and multiclass resistance linked to 16 antiretroviral drugs, respectively. The significance of this study lies in its larger-scale examination of the prevalence of drug-resistant variants and multidrug resistance in HAART-experienced patients in South Korea. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Brazilian network for HIV Drug Resistance Surveillance (HIV-BresNet): a survey of treatment-naive individuals.

    Science.gov (United States)

    Arruda, Monica B; Boullosa, Lídia T; Cardoso, Cynthia C; da Costa, Carolina M; Alves, Carlos Rb; de Lima, Shirlene Ts; Kaminski, Helena T; Aleixo, Agdemir W; Esposito, Ana Op; Cavalcanti, Ana Ms; Riedel, Maristela; Couto-Fernandez, José C; Ferreira, Selma B; de Oliveira, Ivi Cm; Portal, Loreci E; Wolf, Hilda Hc; Fernandes, Sandra B; de M C Pardini, Maria I; Feiteiro, Manoel Vc; Tolentino, Fernanda M; Diaz, Ricardo S; Lopes, Giselle Isl; Francisco, Roberta Bl; Véras, Nazle Mc; Pires, Ana F; Franchini, Miriam; Mesquita, Fábio; Tanuri, Amilcar

    2018-03-01

    In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015. The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing. We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs); 1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails. To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in São Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass

  5. INITIATING ANTIRETROVIRAL THERAPY

    African Journals Online (AJOL)

    annaline

    2005-09-02

    Sep 2, 2005 ... than if they had started ART immediately', because most patients will eventually fail therapy. Therefore I do ... deal with those who are suffering most. REFERENCES. 1. Cole S, Li R, Anastos K, Detels ... Antiretroviral therapy (ART) programmes are a part of the response to the massive mortality occurring in ...

  6. Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission.

    Science.gov (United States)

    Hauser, Andrea; Kuecherer, Claudia; Kunz, Andrea; Dabrowski, Piotr Wojtek; Radonić, Aleksandar; Nitsche, Andreas; Theuring, Stefanie; Bannert, Norbert; Sewangi, Julius; Mbezi, Paulina; Dugange, Festo; Harms, Gundel; Meixenberger, Karolin

    2015-01-01

    Pregnant HIV-infected women were screened for the development of HIV-1 drug resistance after implementation of a triple-antiretroviral transmission prophylaxis as recommended by the WHO in 2006. The study offered the opportunity to compare amplicon-based 454 ultra-deep sequencing (UDS) and allele-specific real-time PCR (ASPCR) for the detection of drug-resistant minor variants in the HIV-1 reverse transcriptase (RT). Plasma samples from 34 Tanzanian women were previously analysed by ASPCR for key resistance mutations in the viral RT selected by AZT, 3TC, and NVP (K70R, K103N, Y181C, M184V, T215Y/F). In this study, the RT region of the same samples was investigated by amplicon-based UDS for resistance mutations using the 454 GS FLX System. Drug-resistant HIV-variants were identified in 69% (20/29) of women by UDS and in 45% (13/29) by ASPCR. The absolute number of resistance mutations identified by UDS was twice that identified by ASPCR (45 vs 24). By UDS 14 of 24 ASPCR-detected resistance mutations were identified at the same position. The overall concordance between UDS and ASPCR was 61.0% (25/41). The proportions of variants quantified by UDS were approximately 2-3 times lower than by ASPCR. Amplicon generation from samples with viral loads below 20,000 copies/ml failed more frequently by UDS compared to ASPCR (limit of detection = 650 copies/ml), resulting in missing or insufficient sequence coverage. Both methods can provide useful information about drug-resistant minor HIV-1 variants. ASPCR has a higher sensitivity than UDS, but is restricted to single resistance mutations. In contrast, UDS is limited by its requirement for high viral loads to achieve sufficient sequence coverage, but the sequence information reveals the complete resistance patterns within the genomic region analysed. Improvements to the UDS limit of detection are in progress, and UDS could then facilitate monitoring of drug-resistant minor variants in the HIV-1 quasispecies.

  7. Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission.

    Directory of Open Access Journals (Sweden)

    Andrea Hauser

    Full Text Available Pregnant HIV-infected women were screened for the development of HIV-1 drug resistance after implementation of a triple-antiretroviral transmission prophylaxis as recommended by the WHO in 2006. The study offered the opportunity to compare amplicon-based 454 ultra-deep sequencing (UDS and allele-specific real-time PCR (ASPCR for the detection of drug-resistant minor variants in the HIV-1 reverse transcriptase (RT.Plasma samples from 34 Tanzanian women were previously analysed by ASPCR for key resistance mutations in the viral RT selected by AZT, 3TC, and NVP (K70R, K103N, Y181C, M184V, T215Y/F. In this study, the RT region of the same samples was investigated by amplicon-based UDS for resistance mutations using the 454 GS FLX System.Drug-resistant HIV-variants were identified in 69% (20/29 of women by UDS and in 45% (13/29 by ASPCR. The absolute number of resistance mutations identified by UDS was twice that identified by ASPCR (45 vs 24. By UDS 14 of 24 ASPCR-detected resistance mutations were identified at the same position. The overall concordance between UDS and ASPCR was 61.0% (25/41. The proportions of variants quantified by UDS were approximately 2-3 times lower than by ASPCR. Amplicon generation from samples with viral loads below 20,000 copies/ml failed more frequently by UDS compared to ASPCR (limit of detection = 650 copies/ml, resulting in missing or insufficient sequence coverage.Both methods can provide useful information about drug-resistant minor HIV-1 variants. ASPCR has a higher sensitivity than UDS, but is restricted to single resistance mutations. In contrast, UDS is limited by its requirement for high viral loads to achieve sufficient sequence coverage, but the sequence information reveals the complete resistance patterns within the genomic region analysed. Improvements to the UDS limit of detection are in progress, and UDS could then facilitate monitoring of drug-resistant minor variants in the HIV-1 quasispecies.

  8. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

    NARCIS (Netherlands)

    Ledergerber, B; Lundgren, JD; Walker, AS; Sabin, C; Justice, A; Reiss, P; Mussini, C; Wit, F; Monforte, AD; Weber, R; Fusco, G; Staszewski, S; Law, M; Hogg, R; Lampe, F; Gill, MJ; Castelli, F; Phillips, AN; Castelli, F; Fusco, GP; Gill, MJ; Hogg, R; Lampe, F; Law, M; Ledergerber, B; Lundgren, JD; Monforte, AD; Mussini, C; Phillips, AN; Reiss, P; Staszewski, S; Walker, AS; Rooney, P; Taylor, S; Couldwell, D; Austin, D; Block, M; Clemons, J; Finlayson, R; Law, M; Petoumenos, K; Quan, D; Smith, D; O'Connor, C; Gorton, C; Allen, D; Mulhall, B; Mutimer, K; Smith, D; Keeffe, N; Cooper, D; Carr, A; Miller, J; Pell, C; Ellis, D; Baker, D; Kidd, J; McFarlane, R; Liang, MT; Brown, K; Huffam, S; Savage, J; Morgan, S; Knibbs, P; Sowden, D; Walker, A; Orth, D; Lister, G; Chuah, J; Fankhauser, W; Dickson, B; Bradford, D; Wilson, C; Ree, H; Magon, H; Moore, R; Russell, D; McGovern, G; McNair, R; Bal, J; Fairley, K; Roth, N; Eu, B; Strecker, S; Russell, D; Wood, H; Mijch, A; Hoy, J; Pierce, A; McCormack, C; Watson, K; Medland, N; Daye, J; Mallal, S; French, M; Skett, J; Maxwel, D; Cain, A; Montroni, M; Scalise, G; Costantini, A; Giacometti, A; Tirelli, U; Nasti, G; Pastore, G; Ladisa, N; Perulli, ML; Suter, F; Arici, C; Chiodo, F; Gritti, FM; Colangeli, [No Value; Fiorini, C; Guerra, L; Carosi, G; Cadeo, GP; Castelli, F; Minardi, C; Vangi, D; Rizzardini, G; Migliorino, G; Manconi, PE; Piano, P; Ferraro, T; Scerbo, A; Pizzigallo, E; Ricci, F; Santoro, D; Pusterla, L; Carnevale, G; Galloni, D; Vigano, P; Mena, M; Ghinelli, F; Sighinolfi, L; Leoncini, F; Mazzotta, F; Pozzi, M; Lo Caputo, S; Angarano, G; Grisorio, B; Ferrara, S; Grima, P; Tundo, P; Pagano, G; Piersantelli, N; Alessandrini, A; Piscopo, R; Toti, M; Chigiotti, S; Soscia, F; Taccooni, L; Orani, A; Perini, P; Scasso, A; Vincenti, A; Scalzini, A; Fibbia, G; Moroni, M; Lazzarin, A; Cargnel, A; Vigevani, GM; Caggese, L; Monforte, AD; Tordato, F; Novati, R; Galli, A; Merli, S; Pastecchia, C; Moioli, C; Esposito, R; Mussini, C; Abrescia, N; 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Cattacin, S; Egger, M; Erb, P; Fierz, W; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, HJ; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Ledergerber, B; Lauper, U; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schupbach, J; Speck, R; Tarr, P; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; de Wolf, F; van Sighem, AI; van Valkengoed, [No Value; Gras, L; Bronsveld, W; Prins, JM; Bos, JC; Schattenkerk, JKME; Godfried, MH; Lange, JMA; Lowe, SH; van der Meer, JTM; Nellen, FJB; Pogany, K; van der Poll, T; Reiss, P; Ruys, TA; Sankatsing, S; van der Valk, M; van Vonderen, MGA; Wit, FWMN; ten Veen, JH; van Dam, PS; Hillebrand-Haverkort, ME; Brinkman, K; Frissen, PHJ; Weigel, HM; Mulder, JW; van Gorp, ECM; Meenhorst, PL; Mairuhu, ATA; Veenstra, J; Danner, SA; Van Agtmael, MA; Claessen, FAP; Geerlings, SE; Perenboom, RM; Richter, C; van der Berg, J; van Leusen, R; Vriesendorp, R; Jeurissen, FJF; Kauffmann, RH; Koger, ELW; Bravenboer, B; Mudrikova, T; Sprenger, HG; Miesen, WMAJ; ten Kate, RW; van Houte, DPF; Leemhuis, MP; Pole, M; Schippers, EF; Schreij, G; van de Geest, S; Verbon, A; Koopmans, PP; Telgt, M; van der Ven, AJAM; van der Ende, Marchina E.; Gyssens, IC; de Marie, S; Nouwen, JL; Juttmann, [No Value; Schneider, MME; Bonten, MJM; Borleffs, JCC; Hoepelman, IM; Jaspers, CAJJ; Schouten, [No Value; Schurink, CAM; Blok, WL; Groenveld, PHP; Jurriaans, S; Back, NKT; Cuijpers, T; Rietra, PJGM; Roozendaal, KJ; Pauw, W; van Zanten, AP; Smits, PHM; von Blomberg, BME; Savelkoul, P; Zaaijer, H; Swanink, C; Franck, PFH; Lampe, AS; Jansen, CL; Hendriks, R; Schirm, J; Benne, D; Veenendaal, D; Storm, H; van Zeijl, JH; Claas, HCJ; Bruggeman, CAMVA; Goossens, VJ; Galama, JMD; Poort, YAGM; Niesters, MG; Osterhaus, ADME; Buiting, AGM; Swaans, CAM; Boucher, CAB; Schuurman, R; Boel, E; Jansz, AF; Veldkamp, A; Beijnen, JH; Crommentuyn, KML; Huitema, ADR; Kappelhoff, B; de Maat, MMR; Burger, DM; Hugen, PWH; Dabis, F; Thiebaut, R; Chene, G; Lawson-Ayayi, S; Meyer, L; Boufassa, F; Hamouda, O; Pezzotti, P; Rezza, G; Touloumi, G; Hatzakis, A; Karafoulidou, A; Katsarou, O; Brettle, R; Del Amo, J; del Romero, J; van Asten, L; van Benthem, B; Prins, M; Coutinho, R; Kirk, O; Pedersen, C; Aguado, IH; Perez-Hoyos, S; Eskild, A; Bruun, JN; Sannes, M; Sabin, C; Lee, C; Johnson, AM; Phillips, AN; Babiker, A; Darbyshire, J; Gill, N; Porter, K; Francioli, P; Vanhems, P; Egger, M; Rickenbach, M; Cooper, D; Kaldor, J; Ashton, L; Cooper, D; Kaldor, J; Ashton, L; Cooper, D; Vizzard, J; Muga, R; Vanhems, P; Gill, J; Cayla, J; de Olalla, PG; Day, NE; De Angelis, D; Porter, K; Babiker, A; Walker, S; Darbyshire, J; Tyrer, F; Beral, [No Value; Coutinho, R; Darbyshire, J; Del Amo, J; Gill, N; Lee, C; Meyer, L; Rezza, G; Raffanti, S; Becker, S; Scarsella, A; Braun, J; Justice, A; Fusco, G; Most, B; Balu, R; Gilbert, L; Fleenor, R; Ising, T; Dieterich, D; Fusco, J; Losso, M; Duran, A; Vetter, N; Clumeck, N; De Wit, S; Kabeya, K; Poll, B; Colebunders, R; Machala, L; Rozsypal, H; Nielsen, J; Lundgren, J; Kirk, O; Olsen, CH; Gerstoft, J; Katzenstein, T; Hansen, ABE; Skinhoj, P; Pedersen, C; Zilmer, K; Rauka, M; Katlama, C; De Sa, M; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Stellbrink, HJ; Miller, [No Value; Staszewski, S; Goebel, FD; Salzberger, B; Rockstroh, J; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Filandras, A; Banhegyi, D; Mulcahy, F; Yust, [No Value; Burke, M; Pollack, S; Hassoun, J; Sthoeger, Z; Maayan, S; Vella, S; Chiesi, A; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Esposito, R; Bedini, A; Chirianni, A; Montesarchio, E; Vullo, [No Value; Santopadre, P; Narciso, P; Antinori, A; Franci, P; Zaccarelli, M; Lazzarin, A; Castagna, A; Monforte, AD; Viksna, L; Rozentale, B; Chaplinskas, S; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, [No Value; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Wiercinska-Drapalo, A; Boron-Kaczmarska, A; Pynka, M; Beniowski, M; Trocha, H; Smiatacz, T; Antunes, F; Mansinho, K; Maltez, F; Duiculescu, D; Streinu-Cercel, A; Mokras, M; Stanekova, D; Gonzalez-Lahoz, J; Diaz, B; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, [No Value; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Zamora, L; Blaxhult, A; Karlsson, A; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Hirschel, B; Schiffer, [No Value; Furrer, H; Chentsova, N; Barton, S; Johnson, AM; Mercey, D; Phillips, A; Youle, M; Johnson, MA; Mocroft, A; Murphy, M; Weber, J; Scullard, G; Fisher, M; Brettle, R; Loveday, C; Clotet, B; Ruiz, L; Staszewski, S; Helm, EB; Carlebach, A; Mosch, M; Muller, A; Haberl, A; Korn, S; Stephan, C; Bickel, M; Gute, P; Locher, L; Lutz, T; Klauke, S; Doerr, HW; Sturmer, M; Sabin, C; Dauer, B; Jennings, B; Alexander, C; Braitstein, P; Chan, K; Cote, H; Gataric, N; Harrigan, PR; Harris, M; Bonner, S; Hogg, R; Montaner, J; O'Shaughnessy, M; Wood, E; Yip, B; Lampe, F; Chaloner, C; Gumley, H; Ransom, D; Sabin, CA; Mocroft, A; Lipman, M; Phillips, AN; Youle, M; Johnson, M; Gill, J; Read, R; Carosi, G; Castelli, F; Paraninfo, G; Casari, S; Pan, A; Patroni, A; Torti, C; Quiros-Roldan, E; Tomasoni, L; Moretti, F; Nasta, P; Uccelli, MC; Cadeo, GP; Bertelli, D; Orani, A; Perini, P; Nigro, M; Rizzardini, G; Migliorino, M; Abeli, C; Mazzotta, F; Suter, F; Maggiolo, F; Arici, C; Ghinelli, F; Sighinolfi, L; Minoli, L; Maserati, R; Novati, S; Tinelli, C; Pastore, G; Ladisa, N; Carnevale, G; Poggio, A; Riccio, G; Mussini, C; Borghi, [No Value; Bedini, A; Esposito, R; ten Napel, C.H.

    2004-01-01

    Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological

  9. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

    DEFF Research Database (Denmark)

    Ledergerber, Bruno; Lundgren, Jens D; Walker, A Sarah

    2014-01-01

    Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure....

  10. HIV-1 subtypes and mutations associated to antiretroviral drug resistance in human isolates from Central Brazil Subtipos e mutações associadas à resistência aos anti-retrovirais em isolados de HIV-1 do Distrito Federal

    Directory of Open Access Journals (Sweden)

    Daniela Marreco Cerqueira

    2004-09-01

    Full Text Available The detection of polymorphisms associated to HIV-1 drug-resistance and genetic subtypes is important for the control and treatment of HIV-1 disease. Drug pressure selects resistant variants that carry mutations in the viral reverse transcriptase (RT and protease (PR genes. For a contribution to the public health authorities in planning the availability of therapeutic treatment, we therefore described the genetic variability, the prevalence of mutations associated to drug resistance and the antiretroviral resistance profile in HIV-1 isolates from infected individuals in Central Brazil. Nineteen HIV-1 RNA samples from a Public Health Laboratory of the Federal District were reversely transcribed and cDNAs were amplified by nested PCR. One fragment of 297 bp coding the entire protease gene, and another of 647 bp, corresponding to the partial RT gene (codons 19-234, were obtained. Automated sequencing and BLAST analysis revealed the presence of 17 B and 2 F1 HIV-1 subtypes. The amino acid sequences were analyzed for the presence of resistance-associated mutations. A total of 6 PR mutations, 2 major and 4 accessory, and 8 RT mutations related to drug resistance were found. Our data suggest a high prevalence of HIV-1 B subtype in the studied population of Federal District as well as the presence of genetically-resistant strains in individuals failing treatment.A detecção de polimorfismos do HIV-1 que estejam associados à resistência às drogas anti-retrovirais e aos subtipos genéticos é importante para o controle e tratamento da infecção pelo HIV-1. A pressão exercida pela terapia anti-retroviral seleciona variantes resistentes com mutações nos genes virais da transcriptase reversa (RT e da protease (PR. Assim, visando contribuir com as autoridades de saúde pública na perspectiva de planejar a disponibilidade de um tratamento terapêutico, nós descrevemos a variabilidade genética e a prevalência de mutações associadas à resist

  11. A Mathematical Model of Antiretroviral Therapy Evaluation for HIV Type 1

    Science.gov (United States)

    Raimundo, Silvia Martorano; Venturino, Ezio; Mo Yang, Hyun

    2009-09-01

    Treating HIV-infected patients with a combination of several antiretroviral drugs can lead to emergence of the drug-resistant strain. This work proposes a mathematical model to evaluate the emergence of HIV-1 drug resistant during antiretroviral therapy. The model assumes that all susceptible individuals who can be infected by the wildtype strain (sensible to the treatment) or by drug-resistant virus receive antiretroviral therapy. Patients on treatment regimen can evolve to a state of success or failure and for the individuals in therapeutic fail the therapeutic schema is changed. The analysis of system is performed. The existence and stability of the steady states are considered. We address an analytical expression for the reproductive number in a community where antiretroviral therapy are widely used to treat HIV and where both drug sensitive and drug resistant strains are co-circulating.

  12. Improving adherence to antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Nischal K

    2005-01-01

    Full Text Available Antiretroviral therapy (ART has transformed HIV infection into a treatable, chronic condition. However, the need to continue treatment for decades rather than years, calls for a long-term perspective of ART. Adherence to the regimen is essential for successful treatment and sustained viral control. Studies have indicated that at least 95% adherence to ART regimens is optimal. It has been demonstrated that a 10% higher level of adherence results in a 21% reduction in disease progression. The various factors affecting success of ART are social aspects like motivation to begin therapy, ability to adhere to therapy, lifestyle pattern, financial support, family support, pros and cons of starting therapy and pharmacological aspects like tolerability of the regimen, availability of the drugs. Also, the regimen′s pill burden, dosing frequency, food requirements, convenience, toxicity and drug interaction profile compared with other regimens are to be considered before starting ART. The lack of trust between clinician and patient, active drug and alcohol use, active mental illness (e.g. depression, lack of patient education and inability of patients to identify their medications, lack of reliable access to primary medical care or medication are considered to be predictors of inadequate adherence. Interventions at various levels, viz. patient level, medication level, healthcare level and community level, boost adherence and overall outcome of ART.

  13. Adherence to On-Time ART