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Sample records for triple-class antiretroviral drug

  1. TMC125 exerts similar initial antiviral potency as a five-drug, triple class antiretroviral regimen

    NARCIS (Netherlands)

    Sankatsing, Sanjay U. C.; Weverling, Gerrit J.; Peeters, Monika; van't Klooster, Gerben; Gruzdev, Boris; Rakhmanova, Aza; Danner, Sven A.; Jurriaans, Suzanne; Prins, Jan M.; Lange, Joep M. A.

    2003-01-01

    Objective: TMC125, a next generation, non-nucleoside reverse transcriptase inhibitor (NNRTI), demonstrated a remarkable decline of plasma HIV-1 RNA during a phase IIa study. We compared the initial rate of decline of plasma HIV-1 RNA achieved by TMC125 monotherapy with that of a triple class,

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

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Jørgensen, LB; Kronborg, G

    2007-01-01

    OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients...... 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 ... in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk...

  3. 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...

  4. Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years

    DEFF Research Database (Denmark)

    Lodwick, Rebecca; Costagliola, Dominique; Reiss, Peter

    2010-01-01

    /r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed. RESULTS: Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting...... ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according...... to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF. CONCLUSIONS: The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over...

  5. Antiretroviral therapy: current drugs.

    Science.gov (United States)

    Pau, Alice K; George, Jomy M

    2014-09-01

    The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

  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. 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 ...

  8. Examining the production costs of antiretroviral drugs.

    Science.gov (United States)

    Pinheiro, Eloan; Vasan, Ashwin; Kim, Jim Yong; Lee, Evan; Guimier, Jean Marc; Perriens, Joseph

    2006-08-22

    To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets. Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO). The calculated prices for antiretroviral drugs are compared with quoted prices offered by privately-owned, for-profit manufacturers. The API represents the largest component of direct manufacturing costs (55-99%), while other inputs, such as salaries, equipment costs, and scale of production, have a minimal impact. The calculated prices for most of the antiretroviral drugs studied fall within the lower quartile of the range of quoted prices in developing country markets. The exceptions are those drugs, primarily for second-line therapy, for which the API is either under patent, in short supply, or in limited use in developing countries (e.g. abacavir, lopinavir/ritonavir, nelfinavir, saquinavir). The availability of data on the cost of antiretroviral drug production and calculation of factory prices under a sustainable business model provide benchmarks that bulk purchasers of antiretroviral drugs could use to negotiate lower prices. While truly significant price decreases for antiretroviral drugs will depend largely on the future evolution of API prices, the present study demonstrates that for several antiretroviral drugs price reduction is currently possible. Whether or not these reductions materialize will depend on the magnitude of indirect cost and profit added by each supplier over the direct production costs. The ability to

  9. NEW DRUGS NEW TARGETS AND NOVEL ANTIRETROVIRALS

    African Journals Online (AJOL)

    2005-11-02

    Nov 2, 2005 ... Highly active antiretroviral therapy (HAART) has to date been based on use of a triple combination of drugs chosen from three classes of antiretrovirals (ARVs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs).

  10. 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 ...

  11. Interactions between recreational drugs and antiretroviral agents.

    Science.gov (United States)

    Antoniou, Tony; Tseng, Alice Lin-In

    2002-10-01

    To summarize existing data regarding potential interactions between recreational drugs and drugs commonly used in the management of HIV-positive patients. Information was obtained via a MEDLINE search (1966-August 2002) using the MeSH headings human immunodeficiency virus, drug interactions, cytochrome P450, medication names commonly prescribed for the management of HIV and related opportunistic infections, and names of commonly used recreational drugs. Abstracts of national and international conferences, review articles, textbooks, and references of all articles were also reviewed. Literature on pharmacokinetic interactions was considered for inclusion. Pertinent information was selected and summarized for discussion. In the absence of specific data, prediction of potential clinically significant interactions was based on pharmacokinetic and pharmacodynamic properties. All protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors are substrates and potent inhibitors or inducers of the cytochrome P450 system. Many classes of recreational drugs, including benzodiazepines, amphetamines, and opioids, are also metabolized by the liver and can potentially interact with antiretrovirals. Controlled interaction studies are often not available, but clinically significant interactions have been observed in a number of case reports. Overdoses secondary to interactions between the "rave" drugs methylenedioxymethamphetamine (MDMA) or gamma-hydroxybutyrate (GHB) and PIs have been reported. PIs, particularly ritonavir, may also inhibit metabolism of amphetamines, ketamine, lysergic acid diethylmide (LSD), and phencyclidine (PCP). Case series and pharmacokinetic studies suggest that nevirapine and efavirenz induce methadone metabolism, which may lead to symptoms of opiate withdrawal. A similar interaction may exist between methadone and the PIs ritonavir and nelfinavir, although the data are less consistent. Opiate metabolism can be inhibited or induced by

  12. 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 ...

  13. 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...

  14. 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.

  15. 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 ...

  16.  The potential nephrotoxicity of antiretroviral drugs

    Directory of Open Access Journals (Sweden)

    Zofia Marchewka

    2012-09-01

    Full Text Available  The intensive studies carried out in many scientific laboratories and the efforts of numerous pharmaceutical companies have led to the development of drugs which are able to effectively inhibitHIV proliferation. At present, a number of antiretroviral agents with different mechanisms of actionare available. Unfortunately, long-term use of antiretroviral drugs, however, does not remainindifferent to the patient and can cause significant side effects.In the present work, the antiretroviral drugs with a nephrotoxicity potential most commonly usedin clinical practice are described. In the review attention has also been focused on the nephropathyresulting from the HIV infection alone and the influence of genetic factors on the occurrenceof pathological changes in the kidney.

  17. [Sustainability of Brazilian policy for access to antiretroviral drugs].

    Science.gov (United States)

    Grangeiro, Alexandre; Teixeira, Luciana; Bastos, Francisco I; Teixeira, Paulo

    2006-04-01

    The expense of acquiring antiretroviral drugs in Brazil has given rise to debate about the sustainability of the policy of universal access to AIDS medications, despite the evident benefits. The objective of this study was to analyze the evolution of the Ministry of Health's spending on acquiring antiretroviral drugs from 1998 to 2005, the determining factors and the medium-term sustainability of this policy (2006-2008). The study on the evolution of spending on antiretrovirals included analysis of their prices, the year-by-year expenditure, the number of patients utilizing the medication, the mean expenditure per patient and the strategies for reducing the prices maintained during this period. To analyze the sustainability of the policy for access to antiretrovirals, the cost of acquiring the drugs over the period from 2006 to 2008 was estimated, along with the proportion of gross domestic product and federal health expenditure represented by this spending. The data were collected from the Ministry of Health, the Brazilian Institute for Geography and Statistics (IBGE) and the Ministry of Planning. The expenditure on antiretrovirals increased by 66% in 2005, breaking the declining trend observed over the period from 2000 to 2004. The main factors associated with this increase were the weakening of the national generics industry and the unsatisfactory results from the process of negotiating with pharmaceutical companies. The Brazilian policy for universal access is unsustainable at the present growth rates of the gross domestic product, unless the country compromises its investments in other fields.

  18. Quality of Life and Adherence to Antiretroviral Drugs

    African Journals Online (AJOL)

    Sitwala

    Department of Nursing Sciences, School of Medicine, University of Zambia, Lusaka, Zambia. ABSTRACT ... it is individually, socially and culturally determined. .... concept that is a semantic representation which .... antiretroviral drugs enhances quality of life and is clearly in keeping with the philosophy of palliative. 19 care .

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

    African Journals Online (AJOL)

    Method: It was an observational, longitudinal study in which 215 consenting HIV positive patients aged 18 to 65 years who were on antiretroviral drugs were recruited through systematic random sampling technique. Socio-demographic characteristics, clinical history and physical examination findings were documented for ...

  20. 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 ...

  1. 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 ...

  2. Antiretroviral adverse drug reactions and their management

    African Journals Online (AJOL)

    2011-06-02

    Jun 2, 2011 ... Nevirapine and efavirenz (and etravirine) can cause a drug hypersensitivity ... HLA-B*5701 are at high risk of ABC hypersensitivity, while those with other variants .... creatinine and the patient's body weight using the modified ...

  3. Evaluation of HIV/AIDS patients' knowledge on antiretroviral drugs

    Directory of Open Access Journals (Sweden)

    Regina Flávia de Castro Almeida

    Full Text Available Lack of information on antiretroviral drugs or the misunderstanding of available information can facilitate incorrect use of such drugs. This can result in non-adherence to the prescribed regimen, leading to a great possibility of a therapeutic failure. The aim of this study was to know which information HIV/AIDS patients, who receive their medicines at the pharmacy of a reference hospital in the northeast Brazil, have on the drugs they use, the source of this information and whether there is a need for additional information. A total of 195 HIV/AIDS patients, who were using either zidovudina + lamivudina 300+150mg (AZT+3TC, efavirenz 600mg (EFZ or lopinavir/ritonavir 133.33/33mg (LPV/r, were interviewed. The mean age was 41 years (SD = 9.55 and 70.8% were males. Of the total, 55.4% didn't know the effect of the drug in the organism; 35.9% were unaware of the necessity of taking antiretroviral drugs for the rest of their lives; only 14.4% knew how to proceed when a dosage was missed; 22.1% said they could die and the same number of individuals believed in aggravation of the disease in case of treatment interruption. The majority, 68.2%, considered it very necessary to receive drug information. The results show that there is an apparent lack of general information among users of antiretroviral drugs, and at the same time a need for it. It is necessary that all professionals involved in the health care of the patients agree that an efficient supply of information on prescribed drugs is an ethical component of the treatment that favors and fosters its adherence.

  4. Access to antiretroviral drugs and AIDS management in Senegal.

    Science.gov (United States)

    Desclaux, Alice; Ciss, Mounirou; Taverne, Bernard; Sow, Papa S; Egrot, Marc; Faye, Mame A; Lanièce, Isabelle; Sylla, Omar; Delaporte, Eric; Ndoye, Ibrahima

    2003-07-01

    Description and analysis of the Senegalese Antiretroviral Drug Access Initiative (ISAARV), the first governmental highly active antiretroviral therapy (HAART) treatment programme in Africa, launched in 1998. ISAARV was initially an experimental project designed to evaluate the feasibility, efficacy and acceptability of HAART in an African context. It was based on four principles: collective definition of the strategy, with involvement of the health professionals who would be called on to execute the programme; matching the objectives to available means (gradual enrollment according to drug availability); monitoring by several research programmes; and ongoing adaptation of treatment and follow-up according to the latest international recommendations. Persons qualifying for antiretroviral (ARV) therapy are selected on the basis of immunological and clinical criteria, regardless of economic and social considerations. A system of subsidies was created to favor access to ARV. Following the ARV price reductions that occurred in November 2000, 100% subsidies were created for the poorest participants. Optimal adherence was ensured by monthly follow-up by pharmacists and support groups held by social workers and patient associations. The chosen supply and distribution system allowed drug dispensing to be strictly controlled. The ISAARV programme demonstrates that HAART can be successfully prescribed in Africa. This experience has served as the basis for the creation of a national treatment programme in Senegal planned to treat 7000 patients by 2006.

  5. First-line antiretroviral drug discontinuations in children.

    Directory of Open Access Journals (Sweden)

    Melony Fortuin-de Smidt

    Full Text Available There are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010.We included children (<16 years at ART initiation who initiated ≥3 antiretrovirals between 2004-2014 with ≥1 follow-up visit on ART. We estimated the incidence of first antiretroviral discontinuation using Kaplan-Meier analysis. We determined the reasons for antiretroviral discontinuations using competing risks analysis. We used Cox regression to identify factors associated with treatment-limiting toxicity.We included 3579 children with median follow-up duration of 41 months (IQR 14-72. At ART initiation, median age was 44 months (IQR 13-89 and median CD4 percent was 15% (IQR 9-21%. At three and five years on ART, 72% and 26% of children respectively remained on their initial regimen. By five years on ART, the most common reasons for discontinuations were toxicity (32%, treatment failure (18%, treatment simplification (5%, drug interactions (3%, and other or unspecified reasons (18%. The incidences of treatment limiting toxicity were 50.6 (95% CI 46.2-55.4, 1.6 (0.5-4.8, 2.0 (1.2-3.3, and 1.3 (0.6-2.8 per 1000 patient years for stavudine, abacavir, efavirenz and lopinavir/ritonavir respectively.While stavudine was associated with a high risk of treatment-limiting toxicity, abacavir, lopinavir/ritonavir and efavirenz were well-tolerated. This supports the World Health Organization recommendation to replace stavudine with

  6. Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.

    Science.gov (United States)

    Eshleman, Susan H; Laeyendecker, Oliver; Parkin, Neil; Huang, Wei; Chappey, Colombe; Paquet, Agnes C; Serwadda, David; Reynolds, Steven J; Kiwanuka, Noah; Quinn, Thomas C; Gray, Ronald; Wawer, Maria

    2009-04-27

    To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment. Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA). Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype recombinant). Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) surveillance mutations. Other resistance-associated mutations were identified in some samples. However, none of the samples had a sufficient number of mutations to predict reduced antiretroviral drug susceptibility. Ten (9.6%) of the samples had reduced phenotypic susceptibility to at least one drug (one had partial susceptibility to didanosine, one had nevirapine resistance, and eight had resistance or partial susceptibility to at least one protease inhibitor). Fifty-three (51%) of the samples had hypersusceptibility to at least one drug (seven had zidovudine hypersusceptibility, 28 had NNRTI hypersusceptibility, 34 had protease inhibitor hypersusceptibility). Delavirdine hypersusceptibility was more frequent in subtype A than D. In subtype D, efavirenz hypersusceptibility was associated with substitutions at codon 11 in HIV-reverse transcriptase. Phenotyping detected reduced antiretroviral drug susceptibility and hypersusceptibility in HIV from some antiretroviral-naive Ugandan adults that was not predicted by genotyping. Phenotyping may complement genotyping for analysis of antiretroviral drug susceptibility in populations with nonsubtype B

  7. 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 ...

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

    African Journals Online (AJOL)

    African studies on effect of antiretroviral drugs on the kidney are limited resulting to scanty information on the safety of these drugs. This study was therefore designed to evaluate the effects of antiretroviral drugs arved®, on creatinine, urea, potassium and sodium ions as well as histological effect on the kidney. A total of fifty ...

  9. 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.

  10. Risk of triple-class virological failure in children with HIV: a retrospective cohort study

    DEFF Research Database (Denmark)

    Castro, Hannah; Judd, Ali; Gibb, Diana M

    2011-01-01

    In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological...... failure to the three original drugs classes in children....

  11. [Injecting drug users and antiretroviral therapy: perceptions of pharmacy teams].

    Science.gov (United States)

    Yokaichiya, Chizuru Minami; Figueiredo, Wagner dos Santos; Schraiber, Lilia Blima

    2007-12-01

    To understand the perceptions of pharmacy teams about their role in the healthcare assistance challenges and adherence to antiretroviral therapy by injecting drug users living with HIV/AIDS. Qualitative study through focus groups and thematic discourse analysis of pharmacists, technicians and assistants with more than six months of experience with medication supply, in 15 assisting units for STD/AIDS in the city of São Paulo, in 2002. Three groups were formed, totaling 29 participants, originating from 12 out of the 15 existing services, and including 12 university level professionals and 17 high-school level professionals. The groups concluded that the pharmacy has an important role in the antiretroviral drug supply, which is reflected in the treatment adherence, because trust-based relationships can be built up through their procedures. In spite of this, they pointed out that such building-up does not take place through excessively bureaucratic activities. This has negative repercussions for all patients, especially for injecting drug users, considered "difficult people". Such concept sums up their behavior: they are supposed to be confused and incapable to adhere to treatment, and have limited understanding. Staff members, however, affirm they treat these patients equally. They do not realize that, by this acting, the specific needs of injecting drug users may become invisible in the service. There is also the possibility that stigmatizing stereotypes may be created, resulting in yet another barrier to the work on adherence. Although the pharmacy is recommended as a potentially favorable place to listen to and form bonds with users, the results show objective and subjective obstacles to render it suitable for the work on adherence.

  12. 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 central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs. investigar potenciais interações droga-droga (PDDI) em pacientes infectados com HIV em terapia de antirretroviral. um estudo de corte transversal foi conduzido em 161 pessoas infectadas com o HIV. Dados de tratamentos clínicos, sociodemográficos e antirretrovirais foram coletados. Para analisar a possível interação medicamentosa, nós usamos o software Micromedex(r). A análise estatística foi feita por regressão logística binária, com um valor P de ≤0.05, considerado estatisticamente significativo. dos participantes, 52.2% foram expostos a potenciais interações droga-droga. No total, houve 218 interações droga-droga, das quais 79.8% ocorreram entre drogas usadas para a terapia antirretroviral. Houve uma associação entre o uso de cinco ou mais medicamentos e possíveis interações droga-droga (p = 0.000), e entre o período de tempo de terapia antirretroviral acima de seis anos e possíveis interações droga

  13. 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

  14. 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

  15. 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 pr...

  16. 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.

  17. 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

    AIM: We investigated the use of non-antiretroviral drugs in the HIV-infected compared to the general population. METHODS: From the Danish HIV Cohort Study, we identified all HIV-infected individuals older than 18 years at HIV diagnosis who received care in Denmark through 1995-2013 and reported...... 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...... to calendar time, age, time from initiation of combination antiretroviral therapy (cART) and stratified by gender, geographical origin and route of HIV transmission. We further analyzed the use of the 25 most used non-antiretroviral drug classes. RESULTS: We identified 4,928 HIV-infected individuals (median...

  18. 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...

  19. 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.

  20. 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 ...

  1. Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction.

    Directory of Open Access Journals (Sweden)

    Reneé de Waal

    Full Text Available BACKGROUND: Lipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART. Both are assumed to be antiretroviral adverse drug reactions. METHODS: We conducted a systematic review to determine whether fat loss or gain was more common in HIV-infected patients on ART than in uninfected controls; was associated with specific antiretrovirals; and would reverse after switching antiretrovirals. RESULTS: Twenty-seven studies met our inclusion criteria. One cohort study reported more lipoatrophy, less subcutaneous fat gain, but no difference in central fat gain in HIV-infected patients on ART than in controls. Randomised controlled trials (RCTs showed more limb fat loss (or less fat gain with the following regimens: stavudine (versus other nucleoside reverse transcriptase inhibitors (NRTIs; efavirenz (versus protease inhibitors (PIs; and NRTI-containing (versus NRTI-sparing. RCTs showed increased subcutaneous fat after switching to NRTI-sparing regimens or from stavudine/zidovudine to abacavir/tenofovir. There were no significant between-group differences in trunk and/or visceral fat gain in RCTs of various regimens, but results from efavirenz versus PI regimens were inconsistent. There was no significant between-group differences in central fat gain in RCTs switched to NRTI-sparing regimens, or from PI-containing regimens. CONCLUSIONS: There is clear evidence of a causal relationship between NRTIs (especially thymidine analogues and lipoatrophy, with concomitant PIs possibly having an ameliorating effect or efavirenz causing additive toxicity. By contrast, central fat gain appears to be a consequence of treating HIV infection, because it is not different from controls, is not linked to any antiretroviral class, and doesn't improve on switching.

  2. 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).

  3. 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.

  4. A Systematic Review of Antiretroviral Adherence Interventions for HIV-Infected People Who Use Drugs

    OpenAIRE

    CampBinford, Meredith; Kahana, Shoshana Y.; Altice, Frederick L.

    2012-01-01

    HIV-infected persons who use drugs (PWUDs) are particularly vulnerable for suboptimal combination antiretroviral therapy (cART) adherence. A systematic review of interventions to improve cART adherence and virologic outcomes among HIV-infected PWUDs was conducted. Among the 45 eligible studies, randomized controlled trials suggested directly administered antiretroviral therapy, medication-assisted therapy (MAT), contingency management, and multi-component, nurse-delivered interventions provid...

  5. 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

  6. Efficacy and durability of nevirapine in antiretroviral drug naive patients

    NARCIS (Netherlands)

    Lange, Joep M. A.

    2003-01-01

    Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that was first reported in the scientific literature in 1990. Varying doses of nevirapine (NVP) and a number of regimens containing this NNRTI have been studied in antiretroviral (ARV) naive patients. Four key studies have

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

    African Journals Online (AJOL)

    Efficacy of antiretroviral treatment in HIV/AIDS is showing inhibition of viral replication and reduction of viral load to a point where viral particles are undetectable in the blood of infected individuals. ... Quality of life is a complex broad ranging multidimensional concept defined in terms of individual's subjective experiences.

  8. The effect of individual antiretroviral drugs on body composition in HIV-infected persons initiating highly active antiretroviral therapy.

    Science.gov (United States)

    Shlay, Judith C; Sharma, Shweta; Peng, Grace; Gibert, Cynthia L; Grunfeld, Carl

    2009-07-01

    To examine the long-term effects of individual antiretroviral drugs on body composition among 416 persons initiating antiretroviral therapy (ART). In a substudy of a clinical trial of persons initiating ART, changes in body composition attributable to individual ART were examined. ARTs assessed were as follows: indinavir, ritonavir, nelfinavir, efavirenz, nevirapine, stavudine (d4T), zidovudine (ZDV), lamivudine (3TC), didanosine, and abacavir. Skinfolds and circumferences were measured at baseline and every 4 months. Mid arm, mid thigh, and waist subcutaneous tissue areas and nonsubcutaneous tissue areas were calculated. Rates of change per year of exposure to each individual ART drug were determined using multivariate longitudinal regression. d4T and ZDV use was associated with losses in subcutaneous tissue area and skinfold thickness. 3TC use was associated with gains in all subcutaneous tissue areas and skinfold thickness, whereas abacavir use was associated with an increase in waist subcutaneous tissue area. Indinavir was associated with gains in waist subcutaneous tissue area, whereas indinavir, efavirenz, and nevirapine were associated with increases in upper back skinfolds. d4T use was also associated with increases in all nonsubcutaneous tissue areas; 3TC use was associated with the greatest increase in waist nonsubcutaneous tissue area. In this prospective nonrandomized evaluation, the nucleoside reverse transcriptase inhibitors d4T and ZDV were associated with decreases in subcutaneous tissue areas, whereas 3TC use was associated with increased subcutaneous tissue areas and waist nonsubcutaneous tissue area.

  9. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe

    DEFF Research Database (Denmark)

    Judd, A; Lodwick, R; Noguera-Julian, A

    2017-01-01

    OBJECTIVES: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. METHODS...... compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART......: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged

  10. 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.

  11. Impact of Active Drug Use on Antiretroviral Therapy Adherence and Viral Suppression in HIV-infected Drug Users

    OpenAIRE

    Arnsten, Julia H; Demas, Penelope A; Grant, Richard W; Gourevitch, Marc N; Farzadegan, Homayoon; Howard, Andrea A; Schoenbaum, Ellie E

    2002-01-01

    Despite a burgeoning literature on adherence to HIV therapies, few studies have examined the impact of ongoing drug use on adherence and viral suppression, and none of these have utilized electronic monitors to quantify adherence among drug users. We used 262 electronic monitors to measure adherence with all antiretrovirals in 85 HIV-infected current and former drug users, and found that active cocaine use, female gender, not receiving Social Security benefits, not being married, screening po...

  12. 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

  13. Does Access to Antiretroviral Drugs Lead to an Increase in High ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    scale distribution of antiretroviral drugs needs to be critically examined – the positives have been outlined above so let us take a look at another potential facet altogether. First let us agree that the large-scale influx of ART is changing the perception of HIV: from a disease inevitably incurring suffering and death to a less ...

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

    NARCIS (Netherlands)

    Mocroft, Amanda; Kirk, Ole; Reiss, Peter; de Wit, Stephane; Sedlacek, Dalibor; Beniowski, Marek; Gatell, Jose; Phillips, Andrew N.; Ledergerber, Bruno; Lundgren, Jens D.; Losso, M.; Elias, C.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Suetnov, O.; Clumeck, N.; Poll, B.; Colebunders, R.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Rozsypal, H.; Sedlacek, D.; Nielsen, J.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A.-B. E.; Skinhøj, P.; Pedersen, C.; Oestergaard, L.; Zilmer, K.; Smidt, Jelena; Ristola, M.; Katlama, C.; Viard, J.-P.; Girard, P.-M.; Livrozet, J. M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Rockstroh, J.

    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 with at

  15. 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

  16. [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

  17. Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine.

    Science.gov (United States)

    das Neves, José; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

    2012-06-01

    To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(ε-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine. Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity. Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL. These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides.

  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. 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

    OBJECTIVES: Genotypic interpretation systems extrapolate observed associations in datasets to predict viral susceptibility to antiretroviral drugs (ARVs) for given isolates. We aimed to develop and validate an approach using artificial neural networks (ANNs) that employ descriptors...

  20. 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.

  1. 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 ...

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

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Reiss, P.; Sabin, C.A.

    2007-01-01

    of myocardial infarction, which is partly explained by dyslipidemia. We found no evidence of such an association for nonnucleoside reverse-transcriptase inhibitors; however, the number of person-years of observation for exposure to this class of drug was less than that for exposure to protease inhibitors...

  3. 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.

  4. Synergy against drug-resistant HIV-1 with the microbicide antiretrovirals, dapivirine and tenofovir, in combination.

    Science.gov (United States)

    Schader, Susan M; Colby-Germinario, Susan P; Schachter, Jordana R; Xu, Hongtao; Wainberg, Mark A

    2011-08-24

    To evaluate the candidate antiretroviral microbicide compounds, dapivirine (DAP) and tenofovir (TFV), alone and in combination against the transmission of wild-type and nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 from different subtypes. We determined single-drug efficacy of the RTIs, DAP and TFV, against subtype B and non-B wild-type and NNRTI-resistant HIV-1 in vitro. To assess breadth of activity, compounds were tested alone and in combination against wild-type and NNRTI-resistant subtype C primary HIV-1 isolates and complimentary clonal HIV-1 from subtypes B, C and CRF02_AG to control for viral variation. Early infection was quantified by counting light units emitted from TZM-bl cells less than 48-h postinfection. Combination ratios were based on drug inhibitory concentrations (IC(50)s) and combined effects were determined by calculating combination indices. Both candidate microbicide antiretrovirals demonstrated potent anti-NNRTI-resistant HIV-1 activity in vitro, albeit the combination protected better than the single-drug treatments. Of particular interest, the DAP with TFV combination exhibited synergy (50% combination index, CI(50) = 0.567) against subtype C NNRTI-resistant HIV-1, whereas additivity (CI(50) = 0.987) was observed against the wild-type counterpart from the same patient. The effect was not compounded by the presence of subdominant viral fractions, as experiments using complimentary clonal subtype C wild-type (CI(50) = 0.968) and NNRTI-resistant (CI(50) = 0.672) HIV-1, in lieu of the patient quasispecies, gave similar results. This study supports the notion that antiretroviral drug combinations may retain antiviral activity against some drug-resistant HIV-1 despite subtype classification and quasispecies diversity.

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

    Science.gov (United States)

    Le, Thuy; Chiarella, Jennifer; Simen, Birgitte B; Hanczaruk, Bozena; Egholm, Michael; Landry, Marie L; Dieckhaus, Kevin; Rosen, Marc I; Kozal, Michael J

    2009-06-29

    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. 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). 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 genotyping. The majority of unrecognized resistant mutations correlate with

  6. 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

  7. 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.

  8. HIV-1 drug resistance mutations among antiretroviral-naive HIV-1-infected patients in Asia: results from the TREAT Asia Studies to Evaluate Resistance-Monitoring Study.

    Science.gov (United States)

    Sungkanuparph, Somnuek; Oyomopito, Rebecca; Sirivichayakul, Sunee; Sirisanthana, Thira; Li, Patrick C K; Kantipong, Pacharee; Lee, Christopher K C; Kamarulzaman, Adeeba; Messerschmidt, Liesl; Law, Matthew G; Phanuphak, Praphan

    2011-04-15

    Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia.

  9. 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

  10. 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

  11. Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution

    Science.gov (United States)

    Kevadiya, Bhavesh D.; Woldstad, Christopher; Ottemann, Brendan M.; Dash, Prasanta; Sajja, Balasrinivasa R.; Lamberty, Benjamin; Morsey, Brenda; Kocher, Ted; Dutta, Rinku; Bade, Aditya N.; Liu, Yutong; Callen, Shannon E.; Fox, Howard S.; Byrareddy, Siddappa N.; McMillan, JoEllyn M.; Bronich, Tatiana K.; Edagwa, Benson J.; Boska, Michael D.; Gendelman, Howard E.

    2018-01-01

    RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal models. METHODS: Europium (Eu3+)- doped cobalt ferrite (CF) dolutegravir (DTG)- loaded (EuCF-DTG) nanoparticles were synthesized then fully characterized based on their size, shape and stability. These were then used as platforms for nanoformulated drug biodistribution. RESULTS: Folic acid (FA) decoration of EuCF-DTG (FA-EuCF-DTG) nanoparticles facilitated macrophage targeting and sped drug entry across cell barriers. Macrophage uptake was higher for FA-EuCF-DTG than EuCF-DTG nanoparticles with relaxivities of r2 = 546 mM-1s-1 and r2 = 564 mM-1s-1 in saline, and r2 = 850 mM-1s-1 and r2 = 876 mM-1s-1 in cells, respectively. The values were ten or more times higher than what was observed for ultrasmall superparamagnetic iron oxide particles (r2 = 31.15 mM-1s-1 in saline) using identical iron concentrations. Drug particles were detected in macrophage Rab compartments by dual fluorescence labeling. Replicate particles elicited sustained antiretroviral responses. After parenteral injection of FA-EuCF-DTG and EuCF-DTG into rats and rhesus macaques, drug, iron and cobalt levels, measured by LC-MS/MS, magnetic resonance imaging, and ICP-MS were coordinate. CONCLUSION: We posit that these theranostic nanoprobes can assess LASER ART drug delivery and be used as part of a precision nanomedicine therapeutic strategy. PMID:29290806

  12. Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the male and female genital tract.

    Science.gov (United States)

    Else, Laura J; Taylor, Stephen; Back, David J; Khoo, Saye H

    2011-01-01

    HIV resides within anatomical 'sanctuary sites', where local drug exposure and viral dynamics may differ significantly from the systemic compartment. Suboptimal antiretroviral concentrations in the genital tract may result in compartmentalized viral replication, selection of resistant mutations and possible re-entry of wild-type/resistant virus into the systemic circulation. Therefore, achieving adequate antiretroviral exposure in the genital tract has implications for the prevention of sexual and vertical transmission of HIV. Penetration of antiretrovirals in the genital tract is expressed by accumulation ratios derived from the measurement of drug concentrations in time-matched seminal plasma/cervicovaginal fluid and plasma samples. Penetration varies by gender and may be drug (as opposed to class) specific with high interindividual variability. Concentrations in seminal plasma are highest for nucleoside analogues and lowest for protease inhibitors and efavirenz. Seminal accumulation of newer agents, raltegravir and maraviroc, is moderate (rank order of accumulation is nucleoside/nucleotide reverse transcriptase inhibitors [lamivudine/zidovudine/tenofovir/didanosine > stavudine/abacavir] > raltegravir > indinavir/maraviroc/nevirapine > efavirenz/protease inhibitors [amprenavir/atazanavir/darunavir > lopinavir/ritonavir > saquinavir] > enfuvirtide). In the female genital tract, the nucleoside analogues exhibit high accumulation ratios, whereas protease inhibitors have limited penetration; however, substantial variability exists between individuals and study centres. Second generation non-nucleoside reverse transcriptase inhibitor etravirine, and maraviroc and raltegravir, demonstrate effective accumulation in cervicovaginal secretions (rank order of accumulation is nucleoside/nucleotide reverse transcriptase inhibitor [zidovudine/lamivudine/didanosine > emtricitabine/tenofovir] > indinavir > maraviroc/raltegravir/darunavir/etravirine > nevirapine

  13. 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.

  14. 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...... who were under follow-up on ART at 1 July 2008 was therefore developed by imputing data on patients with no prior resistance test results, based on the probability of detecting resistance in tested patients with similar profiles....

  15. 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.

  16. 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

  17. 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.

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

    Science.gov (United States)

    Hijazi, Karolin; Cuppone, Anna M; Smith, Kieron; Stincarelli, Maria A; Ekeruche-Makinde, Julia; De Falco, Giulia; Hold, Georgina L; Shattock, Robin; Kelly, Charles G; Pozzi, Gianni; Iannelli, Francesco

    2015-01-01

    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 expression of drug

  19. The Female Genital Tract Microbiome Is Associated With Vaginal Antiretroviral Drug Concentrations in Human Immunodeficiency Virus-Infected Women on Antiretroviral Therapy.

    Science.gov (United States)

    Donahue Carlson, Renee; Sheth, Anandi N; Read, Timothy D; Frisch, Michael B; Mehta, C Christina; Martin, Amy; Haaland, Richard E; Patel, Anar S; Pau, Chou-Pong; Kraft, Colleen S; Ofotokun, Igho

    2017-11-15

    The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT. Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT). Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002). Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  20. 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

  1. 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.

  2. The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

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    Tinashe Mudzviti

    2012-01-01

    Full Text Available Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART. Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2% of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%, Bidens pilosa (66.0%, Eucalyptus globulus (52.3%, Moringa oleifera (44.1%, Lippia javanica (36.3%, and Peltoforum africanum (34.3%. Two indigenous herbs, Musakavakadzi (OR=0.25; 95% CI 0.076–0.828 and Peltoforum africanum (OR=0.495; 95% CI 0.292–0.839 reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles.

  3. 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 ...

  4. 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

  5. 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.

  6. 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 Af...... mutations among failing patients justify increased vigilance by improving the availability and systematic use of VL testing to monitor ART response, and underlines the need for rapid, inexpensive tests to identify the most common drug resistance mutations....

  7. Palatability, adherence and prescribing patterns of antiretroviral drugs for children with human immunodeficiency virus infection in Canada.

    Science.gov (United States)

    Lin, Daren; Seabrook, Jamie A; Matsui, Doreen M; King, Susan M; Rieder, Michael J; Finkelstein, Yaron

    2011-12-01

    To assess the impact of perceived palatability of antiretroviral drugs on adherence to therapy of children infected by human immunodeficiency virus and on prescribing patterns by their caring physicians. Two arms--retrospective chart review and a cross-sectional survey. Tertiary-care pediatric human immunodeficiency virus clinic during a 17-year period. Children with human immunodeficiency virus infection and physicians actively caring for children with human immunodeficiency virus infection in seven provinces in Canada were surveyed regarding their perception of the palatability of 8-liquid and 15 non-liquid antiretroviral medications and its effect on drug selection. Effect of taste preferences of antiretroviral drugs on adherence to treatment by infected children and on drug selection by their caring physicians. Forty of 119 children (34%) refused at least once to an antiretroviral medication. In 5%, treatment was discontinued because of poor palatability. Ritonavir was the least palatable drug (50% of children; p = 0.01). Ritonavir use (OR 4.80 [95%CI 1.34-17.20]) and male gender (OR 7.25 [95%CI 2.30-22.90]) were independent predictors of drug discontinuation because of poor taste. Physicians also perceived liquid ritonavir as the least palatable (p = 0.01) and the most likely to be discontinued (p = 0.01). However, they commonly prescribed it as first-line therapy (p = 0.06). A third of children infected with human immunodeficiency virus fail to adhere to their treatment because of poor drug taste. Physicians are aware of that, but this does not prevent them from selecting the least palatable drugs as first-line therapy. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Drug-resistant tuberculosis among HIV-infected patients starting antiretroviral therapy in Durban, South Africa.

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    Jeffrey K Hom

    Full Text Available To estimate the prevalence of drug-resistant tuberculosis (TB and describe the resistance patterns in patients commencing antiretroviral therapy (ART in an HIV clinic in Durban, South Africa.Cross-sectional cohort study.Consecutive HIV-infected adults (≥ 18y/o initiating HIV care were enrolled from May 2007-May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium. Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed.1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42-150/µl. 267 subjects (26% reported a prior history of TB and 210 (20% were receiving TB treatment at enrollment; 191 (18% subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0-12.4. Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9-30.5 compared to 5.2% (95% CI 2.1-8.9 among those with no prior TB. 5.1% (95% CI 2.4-9.5 had rifampin or rifampin plus INH resistance.The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence.

  9. Derivative Spectrophotometric Method for Estimation of Antiretroviral Drugs in Fixed Dose Combinations

    Science.gov (United States)

    P.B., Mohite; R.B., Pandhare; S.G., Khanage

    2012-01-01

    Purpose: Lamivudine is cytosine and zidovudine is cytidine and is used as an antiretroviral agents. Both drugs are available in tablet dosage forms with a dose of 150 mg for LAM and 300 mg ZID respectively. Method: The method employed is based on first order derivative spectroscopy. Wavelengths 279 nm and 300 nm were selected for the estimation of the Lamovudine and Zidovudine respectively by taking the first order derivative spectra. The conc. of both drugs was determined by proposed method. The results of analysis have been validated statistically and by recovery studies as per ICH guidelines. Result: Both the drugs obey Beer’s law in the concentration range 10-50 μg mL-1,for LAM and ZID; with regression 0.9998 and 0.9999, intercept – 0.0677 and – 0.0043 and slope 0.0457 and 0.0391 for LAM and ZID, respectively.The accuracy and reproducibility results are close to 100% with 2% RSD. Conclusion: A simple, accurate, precise, sensitive and economical procedures for simultaneous estimation of Lamovudine and Zidovudine in tablet dosage form have been developed. PMID:24312779

  10. 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.

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

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    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

  12. Antiretroviral Drug Use in a Cohort of HIV-Uninfected Women in the United States: HIV Prevention Trials Network 064.

    Directory of Open Access Journals (Sweden)

    Iris Chen

    Full Text Available Antiretroviral (ARV drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009-2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2% of 1,806 participants: 27/181 (15% in Baltimore, MD and 12/179 (7% in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1-4 drugs/sample. These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals.

  13. High prevalence of antiretroviral drug resistance among HIV-1-untreated patients in Guinea-Conakry and in Niger.

    Science.gov (United States)

    Charpentier, Charlotte; Bellecave, Pantxika; Cisse, Mohamed; Mamadou, Saidou; Diakite, Mandiou; Peytavin, Gilles; Tchiombiano, Stéphanie; Teisseire, Pierre; Pizarro, Louis; Storto, Alexandre; Brun-Vézinet, Françoise; Katlama, Christine; Calvez, Vincent; Marcelin, Anne-Geneviève; Masquelier, Bernard; Descamps, Diane

    2011-01-01

    The aim of the study was to assess the prevalence of antiretroviral drug resistance mutations in HIV-1 from recently diagnosed and untreated patients living in Conakry, Guinea-Conakry and in Niamey, Niger. The study was performed in two countries of Western Africa - Guinea-Conakry and Niger - using the same survey method in both sites. All newly HIV-1 diagnosed patients, naive of antiretroviral drugs, were consecutively included during September 2009 in each of the two sites. Protease and reverse transcriptase sequencing was performed using the ANRS procedures. Drug resistance mutations were identified according to the 2009 update surveillance drug resistance mutations. In Conakry, 99 patients were included, most of whom (89%) were infected with CRF02_AG recombinant virus. Resistance analysis among the 93 samples showed that ≥1 drug resistance mutation was observed in 8 samples, leading to a prevalence of primary resistance of 8.6% (95% CI 2.91-14.29%). In Niamey, 96 patients were included; a high diversity in HIV-1 subtypes was observed with 47 (51%) patients infected with CRF02_AG. Resistance analysis performed among the 92 samples with successful genotypic resistance test showed that ≥1 drug resistance mutation was observed in 6 samples, leading to a prevalence of primary resistance of 6.5% (95% CI 1.50-11.50%). We reported the first antiretroviral drug resistance survey studies in antiretroviral-naive patients living in Guinea-Conakry and in Niger. The prevalence of resistance was between 6% and 9% in both sites, which is higher than most of the other countries from Western Africa region.

  14. 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

  15. Barriers to antiretroviral treatment access for injecting drug users living with HIV in Chennai, South India.

    Science.gov (United States)

    Chakrapani, Venkatesan; Velayudham, Jaikumar; Shunmugam, Murali; Newman, Peter A; Dubrow, Robert

    2014-01-01

    India's National AIDS Control Organization provides free antiretroviral treatment (ART) to people living with HIV (PLHIV), including members of marginalized groups such as injecting drug users (IDUs). To help inform development of interventions to enhance ART access, we explored barriers to free ART access at government ART centers for IDUs living with HIV in Chennai by conducting three focus groups (n = 19 IDUs) and four key informant interviews. Data were explored using framework analysis to identify categories and derive themes. We found interrelated barriers at the family and social, health-care system, and individual levels. Family and social level barriers included lack of family support and fear of societal discrimination, as well as unmet basic needs, including food and shelter. Health-care system barriers included actual or perceived unfriendly hospital environment and procedures such as requiring proof of address and identity from PLHIV, including homeless IDUs; provider perception that IDUs will not adhere to ART, resulting in ART not being initiated; actual or perceived inadequate counseling services and lack of confidentiality; and lack of effective linkages between ART centers, needle/syringe programs, and drug dependence treatment centers. Individual-level barriers included active drug use, lack of self-efficacy in ART adherence, low motivation to initiate ART stemming from a fatalistic attitude, and inadequate knowledge about ART. These findings indicate that to facilitate IDUs gaining access to ART, systemic changes are needed, including steps to make the environment and procedures at government ART centers more IDU-friendly and steps to decrease HIV- and drug use-related stigma and discrimination faced by IDUs from the general public and health-care providers. Housing support for homeless IDUs and linkage of IDUs with drug dependence treatment are also essential.

  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...... copies/ml in the time window between 0.5 and 2 years from starting antiretroviral therapy (baseline). Patients were grouped according to evidence of virological failure and whether there was detection of the International AIDS Society resistance mutations to one, two or three drug classes in the time...... or death was 20.3% (95% CI:17.7-22.9) in patients with no evidence of virological failure and 53% (39.3-66.7) in those with virological failure and mutations to three drug classes (P = 0.0001). An almost two-fold difference in risk was confirmed in the multivariable analysis (adjusted relative hazard = 1...

  17. 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...... (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...... January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance...

  18. 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

  19. 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...

  20. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe.

    Science.gov (United States)

    Judd, A; Lodwick, R; Noguera-Julian, A; Gibb, D M; Butler, K; Costagliola, D; Sabin, C; van Sighem, A; Ledergerber, B; Torti, C; Mocroft, A; Podzamczer, D; Dorrucci, M; De Wit, S; Obel, N; Dabis, F; Cozzi-Lepri, A; García, F; Brockmeyer, N H; Warszawski, J; Gonzalez-Tome, M I; Mussini, C; Touloumi, G; Zangerle, R; Ghosn, J; Castagna, A; Fätkenheuer, G; Stephan, C; Meyer, L; Campbell, M A; Chene, G; Phillips, A

    2017-03-01

    The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0-12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9-5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10-14 years when starting ART (27.7%; 95% CI 13.2-42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10-14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development. © 2016 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Gomes MJ

    2014-04-01

    Full Text Available Maria João Gomes,1 José das Neves,1,2 Bruno Sarmento1,2 1Instituto de Engenharia Biomédica (INEB, Porto, Portugal; 2Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS, Instituto Superior de Ciências da Saúde-Norte, CESPU, Gandra, Portugal Abstract: 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. Keywords: HIV/AIDS, blood–brain barrier, protease inhibitors, efflux transporters, drug targeting

  3. 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.

  4. Economic evaluation of 3-drug antiretroviral regimens for the prevention of mother-to-child HIV transmission in Thailand.

    Science.gov (United States)

    Werayingyong, Pitsaphun; Phanuphak, Nittaya; Chokephaibulkit, Kulkunya; Tantivess, Sripen; Kullert, Nareeluk; Tosanguan, Kakanang; Butchon, Rukmanee; Voramongkol, Nipunporn; Boonsuk, Sarawut; Pilasant, Songyot; Kulpeng, Wantanee; Teerawattananon, Yot

    2015-03-01

    The current program for prevention of mother-to-child HIV transmission in Thailand recommends a 2-drugs regimen for HIV-infected pregnant women with a CD4 count >200 cells/mm(3). This study assesses the value for money of 3 antiretroviral drugs compared with zidovudine (AZT)+single-dose nevirapine (sd-NVP). A decision tree was constructed to predict costs and outcomes using the governmental perspective for assessing cost-effectiveness of 3-drug regimens: (1) AZT, lamivudine, and efavirenz and (2) AZT, 3TC, and lopinavir/ritonavir, in comparison with the current protocol, AZT+sd-NVP. The 3-drug antiretroviral regimens yield lower costs and better health outcomes compared with AZT+sd-NVP. Although these 3-drug regimens offer higher program costs and health care costs for premature birth, they save money significantly in regard to pediatric HIV treatment and treatment costs for drug resistance in mothers. The 3-drug regimens are cost-saving interventions. The findings from this study were used to support a policy change in the national recommendation. © 2013 APJPH.

  5. 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.

  6. New and investigational antiretroviral drugs for HIV infection: mechanisms of action and early research findings.

    Science.gov (United States)

    Saag, Michael S

    2012-12-01

    Numerous investigational antiretroviral agents are in clinical development. Among them are festinavir (BMS986001), a thymidine analogue similar to stavudine with reduced potential for toxicity; GS-7340, a prodrug of tenofovir that achieves greater intracellular concentrations; MK-1439, a nonnucleoside analogue reverse transcriptase inhibitor (NNRTI) that retains activity against common NNRTI-associated resistance mutations; and albuvirtide, a long-acting parenteral fusion inhibitor. Investigational integrase strand transfer inhibitors (InSTIs) include elvitegravir, recently approved by the US Food and Drug Administration (FDA) as part of a once-daily, single-tablet formulation with cobicistat/tenofovir/emtricitabine; dolutegravir, which maintains some activity against raltegravir- and elvitegravir-resistant mutants; and S/GSK1265744, which also maintains some activity against resistance mutations in the integrase gene and is being developed as a long-lasting parenteral agent. Novel 2-(quinolin-3-yl)acetic acid derivatives (LEDGINs), agents that were originally thought to inhibit the interaction of integrase with its cofactor lens epithelium-derived growth factor p75 (LEDGF/p75), be active against InSTI-resistant mutants and to have additive activity when combined with InSTIs. This article summarizes a presentation by Michael S. Saag, MD, at the IAS-USA live Improving the Management of HCV Disease continuing medical education program held in New York in October 2012.

  7. [Antiretroviral drug supply in Argentina: National Program to Combat Human Retroviruses, AIDS, and STDs].

    Science.gov (United States)

    Colautti, Marisel; Luppi, Irene; Salamano, Mercedes; Traverso, María Luz; Botta, Carina; Palchik, Valeria

    2009-01-01

    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 from supply chain stakeholders. A study was carried out from April-September 2005 in the pharmacies of two hospitals in Rosario, Argentina, involving both a quantitative analysis of indicators and secondary sources and a qualitative evaluation using semistructured interviews. The indicators reveal the impact that interruptions in ARV supply stream from the Program (central level) have and the overstocking that takes place at the pharmacies (local level) to manage the shortages. Changes in ARV treatment account for over 50% of the prescriptions. Fulfillments fall short of the reference value. The interviewees shared possible strategies for overcoming the communication gaps between levels, for building-up stock, for guaranteeing availability, and for shortening waiting times; reached informal agreements to deal with the lack of policies and the shortage of staff; acknowledged the challenges facing the jurisdictions (central, intermediate, and local/community); and recognized local efforts to improve management. These challenges could be the starting point for building teams to work on effectively decentralizing the entire supply chain and allowing the Program to fulfill its much-needed oversight role.

  8. Hematological alterations and thymic function in newborns of HIV-infected mothers receiving antiretroviral drugs.

    Science.gov (United States)

    Wongnoi, Rotjanee; Penvieng, Nawaporn; Singboottra, Panthong; Kingkeow, Doungnapa; Oberdorfer, Peninnah; Sirivatanapa, Pannee; Pornprasert, Sakorn

    2013-06-08

    To investigate the effects of antiretroviral (ARV) drugs on hematological parameters and thymic function in HIV-uninfected newborns of HIV-infected mothers. Cross sectional study. Chiang-Mai University Hospital, Chiang-Mai, Thailand. 49 HIV-uninfected and 26 HIV-infected pregnancies. Cord blood samples of newborns from HIV-uninfected and HIV-infected mothers were collected. Hematological parameters were measured using automatic blood cell count. T-cell receptor excision circles (TRECs) levels in cord blood mononuclear cells (CBMCs), CD4+ and CD8+ T-cells were quantified using real-time PCR.. Hemotological parameters and thymic function. Newborn of HIV-infected mother tended to have lower mean levels of hemoglobin than those of HIV-uninfected mother (137 ±22 vs 146 ±17 g/L, P = 0.05). Furthermore, mean of red blood cell (RBC) counts and hematocrit and median of TRECs in CD4+ T-cells in the newborns of the former were significantly lower than those of the latter [3.6 ±0.7 vs 4.8 ±0.6 x 1012 cells/L, P cells) in HIV-uninfected newborns of HIV-infected mothers.

  9. 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.

  10. [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.

  11. 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

  12. 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.

  13. Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) - A Strategic Option for India.

    Science.gov (United States)

    Satyanarayana, Kanikaram; Srivastava, Sadhana

    2010-01-19

    The current HIV/AIDS scenario in India is quite grim with an estimated 2.4 million people living with HIV/AIDS (PLHA) in 2008, just behind South Africa and Nigeria. The anti-retroviral drugs (ARVs) remain the main stay of global HIV/AIDS treatment. Over 30 ARVs (single and FDCs) available under six categories viz., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), Protease inhibitors, the new Fusion inhibitors, Entry inhibitors-CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. The major originator companies for these ARVs are: Abbott, Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Gilead, GlaxoSmithKline (GSK), Merck, Pfizer, Roche, and Tibotec. Beginning with zidovidine in 1987, all the drugs are available in the developed countries. In India, about 30 ARVs are available as generics manufactured by Aurobindo, Hyderabad, Andhra Pradesh; Cipla Limited, Goa; Emcure Pharmaceuticals, Pune, Maharashtra; Hetero Drugs, Hyderabad, Andhra Pradesh; Macleods Pharmaceuticals, Daman; Matrix Laboratories, Nashik, Maharashtra; Ranbaxy, Sirmour, Himachal Pradesh; and Strides Arcolab, Bangalore, Karnataka. The National AIDS Control Organization (NACO) set up in 1992 by the Govt. of India provides free ARVs to HIV positive patients in India since 2004. The drugs available in India include both single drugs and FDCs covering both first line and second line ARVs. Even while there are claims of stabilization of the disease load, there is still huge gap of those who require ARVs as only about 150,000 PLHA receive the ARVs from the Govt. and other sources. Access to ARVs therefore is still a cause of serious concern ever since India became fully Trade Related Aspects of Intellectual Property Rights (TRIPS)-complaint in 2005. Therefore, the Indian pharmaceutical companies cannot make generics for those for drugs introduced post-2005 due to product patent regime. Other concerns include heat stable

  14. HIV-1 Drug Resistance Mutations Among Antiretroviral-Naïve HIV-1–Infected Patients in Asia: Results From the TREAT Asia Studies to Evaluate Resistance-Monitoring Study

    Science.gov (United States)

    Oyomopito, Rebecca; Sirivichayakul, Sunee; Sirisanthana, Thira; Kantipong, Pacharee; Lee, Christopher K. C.; Kamarulzaman, Adeeba; Messerschmidt, Liesl; Law, Matthew G.; Phanuphak, Praphan

    2011-01-01

    (See editorial commentary by Jordan on pages 1058–1060.) Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia. PMID:21460324

  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. 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...... who need it, here we examine whether IDUs in the 52 countries in the WHO European Region have equitable access to HAART and whether that access has changed over time between 2002 and 2004. We consider regional and country differences in IDU HAART access; examine preliminary data regarding...

  17. 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....

  18. 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

  19. 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.

  20. 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 ...

  1. Effects of antiretroviral drug recall on perception of therapy benefits and on adherence to antiretroviral treatment in HIV-infected children.

    Science.gov (United States)

    Giannattasio, Antonietta; Barbarino, Alessandro; Lo Vecchio, Andrea; Bruzzese, Eugenia; Mango, Carmela; Guarino, Alfredo

    2009-09-01

    In June 2007, the European Medicines Agency announced the recall by Roche of nelfinavir from European Union markets because of contamination of tablets with ethyl mesylate. Based on this event, we investigated the effect of switching therapy because of nelfinavir recall or for other reasons on the perception of therapy benefits and adherence to treatment in HIV-infected children and their caregivers. Thirty-eight children (mean age 12.1+/-6.7 years) were enrolled. A 35-item questionnaire was administered to the caregivers of enrolled children. Adherence was evaluated through a 4-day recall adherence instrument. Enrolled children were divided into 3 groups: patients who were shifted because of nelfinavir recall (group A, 8 patients); patients who were shifted for other reasons (group B, 12 patients); patients who were not shifted in the last 6 months (group C, 18 patients). All caregivers considered antiretroviral therapy necessary and effective for their children. However, drug shifting generated anxiety in most of them, irrespective of the reason for shifting. At baseline, 74% patients adhered to therapy. Adherence rate was related to the type of caregivers being higher in children cared for by foster parents than in children cared for by biological parents or second-degree relatives. Adherence rates did not change significantly in groups A and B after switching. Drug-switching raises concern in caregivers of HIV-infected children and induces a negative feeling irrespective of the reason for switching. However, switching, including the shift due to nelfinavir recall, did not affect adherence rates.

  2. 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...

  3. Surveillance of transmitted antiretroviral drug resistance among HIV-1 infected women attending antenatal clinics in Chitungwiza, Zimbabwe.

    Directory of Open Access Journals (Sweden)

    Mqondisi Tshabalala

    Full Text Available The rapid scale-up of highly active antiretroviral therapy (HAART and use of single dose Nevirapine (SD NVP for prevention of mother-to-child transmission (pMTCT have raised fears about the emergence of resistance to the first line antiretroviral drug regimens. A cross-sectional study was conducted to determine the prevalence of primary drug resistance (PDR in a cohort of young (<25 yrs HAART-naïve HIV pregnant women attending antenatal clinics in Chitungwiza, Zimbabwe. Whole blood was collected in EDTA for CD4 counts, viral load, serological estimation of duration of infection using the BED Calypte assay and genotyping for drug resistance. Four hundred and seventy-one women, mean age 21 years; SD: 2.1 were enrolled into the study between 2006 and 2007. Their median CD4 count was 371cells/µL; IQR: 255-511 cells/µL. Two hundred and thirty-six samples were genotyped for drug resistance. Based on the BED assay, 27% were recently infected (RI whilst 73% had long-term infection (LTI. Median CD4 count was higher (p<0.05 in RI than in women with LTI. Only 2 women had drug resistance mutations; protease I85V and reverse transcriptase Y181C. Prevalence of PDR in Chitungwiza, 4 years after commencement of the national ART program remained below WHO threshold limit (5%. Frequency of recent infection BED testing is consistent with high HIV acquisition during pregnancy. With the scale-up of long-term ART programs, maintenance of proper prescribing practices, continuous monitoring of patients and reinforcement of adherence may prevent the acquisition and transmission of PDR.

  4. Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: a multicentre cohort study

    NARCIS (Netherlands)

    Hamers, Raph L.; Schuurman, Rob; Sigaloff, Kim C. E.; Wallis, Carole L.; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E.; Wellington, Maureen; Osibogun, Akin; Wit, Ferdinand W.; van Vugt, Michèle; Stevens, Wendy S.; de Wit, Tobias F. Rinke

    2012-01-01

    Background The effect of pretreatment HIV-1 drug resistance on the response to first-line combination antiretroviral therapy (ART) in sub-Saharan Africa has not been assessed. We studied pretreatment drug resistance and virological, immunological, and drug-resistance treatment outcomes in a large

  5. 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.

  6. Evolution of antiretroviral drug costs in Brazil in the context of free and universal access to AIDS treatment.

    Science.gov (United States)

    Nunn, Amy S; Fonseca, Elize M; Bastos, Francisco I; Gruskin, Sofia; Salomon, Joshua A

    2007-11-13

    Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART) for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs), procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005. We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir-ritonavir (lopinavir/r) have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs: patented lopinavir

  7. Evolution of antiretroviral drug costs in Brazil in the context of free and universal access to AIDS treatment.

    Directory of Open Access Journals (Sweden)

    Amy S Nunn

    2007-11-01

    Full Text Available Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs, procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005.We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir-ritonavir (lopinavir/r have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs

  8. 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.

  9. 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

  10. Impact of use of alcohol and illicit drugs by AIDS patients on adherence to antiretroviral therapy in Bahia, Brazil.

    Science.gov (United States)

    Teixeira, Celia; Dourado, Maria De Lourdes; Santos, Marcio P; Brites, Carlos

    2013-05-01

    Use of alcohol and illicit drugs is a common finding among HIV-infected individuals, but there are many open questions about its impact on adherence to antiretroviral therapy and virological outcomes. Our study aimed to evaluate the impact of the use of alcohol and illicit drugs on the adherence to antiretroviral therapy (ART) among patients starting ART in Salvador, Brazil. We followed up 144 AIDS patients initiating ART for a 6-month period. At baseline, they were interviewed about demographics, behavior, and use of illicit drugs and alcohol. All of them had HIV-1 RNA plasma viral load and CD4(+)/CD8(+) cells count measured before starting therapy. After 60 days of treatment they were asked to answer a new questionnaire on adherence to ART. All patients were monitored during the following months, and new CD4(+) cell count/HIV-1 RNA plasma viral load determinations were performed after 6 months of therapy. Optimal adherence to therapy was defined by self-reported questionnaire, by 95% use of prescribed drug doses, and by using plasma HIV-1 RNA viral load as a biological marker. A total of 61 (42.4%) patients reported alcohol use, 7 (4.9%) used illicit drugs, and 17 (11.8%) used both alcohol and illicit drugs. Being in a steady relationship was protective to nonadherence (95% CI: 0.18-0.84). Missing more than two medical visits was also associated with a 68% higher likelihood of nonadherence (95% CI: 0.10-1.02). After logistic regression we detected a higher risk of nonadherence for patients declaring use of alcohol plus illicit drugs (odds ratio=6.0; 95% CI: 1.78-20.28) or high-intensity use of alcohol (odds ratio=3.29; 95% CI: 1.83-5.92). AIDS patients using alcohol and/or illicit drugs are socially vulnerable, and need specific and flexible programs, combining mental health care, harm reduction strategies, and assisted drug therapy to maximize the chances of successful use of ART.

  11. 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.

  12. 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...

  13. Drug resistance mutations in HIV type 1 isolates from naive patients eligible for first line antiretroviral therapy in JJ Hospital, Mumbai, India.

    Science.gov (United States)

    Deshpande, Alake; Karki, Surendra; Recordon-Pinson, Patricia; Fleury, Herve J

    2011-12-01

    More than 50 HIV-1-infected patients, naive of antiretroviral therapy (ART) but eligible for first line ART in JJ Hospital, Mumbai, India were investigated for surveillance drug resistance mutations (SDRMs); all but one virus belonged to subtype C; we could observe SDRMs to nonnucleoside reverse transcriptase inhibitors and protease inhibitors in 9.6% of the patients.

  14. 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.

  15. 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.

  16. 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.

  17. Antiretroviral drug expenditure, pricing and judicial demand: an analysis of federal procurement data in Brazil from 2004–2011

    Science.gov (United States)

    2014-01-01

    Background Previous studies have described expenditures for antiretroviral (ARV) medicines in Brazil through 2005. While prior studies examined overall expenditures, they have not have analyzed drug procurement data in order to describe the role of court litigation on access and pricing. Methods ARV drug procurement from private sector sources for the years 2004–2011 was obtained through the general procurement database of the Brazilian Federal Government (SIASG). Procurement was measured in Defined Daily Doses (DDD) per 1000 persons-under-treatment per day. Expenditures and price per DDD were calculated and expressed in U.S. Dollars. Justifications for ARV purchases were examined in order to determine the relationship between health litigation and incorporation into Brazil’s national treatment guidelines. Results Drug procurement of ARVs from private sources underwent marked expansion in 2005, peaked in 2009, and stabilized to 2008 levels by 2011. Expenditures followed procurement curves. Medications which were procured for the first time after 2007 cost more than medicines which were introduced before 2007. Judicial actions initially resulted in purchases of newer medications for a select number of patients in Brazil but ultimately expanded availability to a larger population through incorporation into the national treatment guidelines. Conclusions Drug procurement and expenditures for ARVs in Brazil varied between 2004–2011. The procurement of some drugs from the private sector ceased after public manufacturers started producing them locally. Judicial demand has resulted in the incorporation of newer drugs into the national treatment guidelines. In order for the AIDS treatment program to remain sustainable, efforts should be pursued to reduce prices through generic drugs, price negotiation and other public health flexibilities such as compulsory licensing. PMID:24735589

  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. HIV-1 drug resistance in recently HIV-infected pregnant mother's naïve to antiretroviral therapy in Dodoma urban, Tanzania.

    Science.gov (United States)

    Vairo, Francesco; Nicastri, Emanuele; Liuzzi, Giuseppina; Chaula, Zainab; Nguhuni, Boniface; Bevilacqua, Nazario; Forbici, Federica; Amendola, Alessandra; Fabeni, Lavinia; De Nardo, Pasquale; Perno, Carlo Federico; Cannas, Angela; Sakhoo, Calistus; Capobianchi, Maria Rosaria; Ippolito, Giuseppe

    2013-09-21

    HIV resistance affects virological response to therapy and efficacy of prophylaxis in mother-to-child-transmission. The study aims to assess the prevalence of HIV primary resistance in pregnant women naïve to antiretrovirals. Cross sectional baseline analysis of a cohort of HIV + pregnant women (HPW) enrolled in the study entitled Antiretroviral Management of Antenatal and Natal HIV Infection (AMANI, peace in Kiswahili language). The AMANI study began in May 2010 in Dodoma, Tanzania. In this observational cohort, antiretroviral treatment was provided to all women from the 28th week of gestation until the end of the breastfeeding period. Baseline CD4 cell count, viral load and HIV drug-resistance genotype were collected. Drug-resistance analysis was performed on 97 naïve infected-mothers. The prevalence of all primary drug resistance and primary non-nucleoside reverse-transcriptase inhibitors resistance was 11.9% and 7.5%, respectively. K103S was found in two women with no M184V detection. HIV-1 subtype A was the most commonly identified, with a high prevalence of subtype A1, followed by C, D, C/D recombinant, A/C recombinant and A/D recombinant. HIV drug- resistance mutations were detected in A1 and C subtypes. Our study reports an 11.9% prevalence rate of primary drug resistance in naïve HIV-infected pregnant women from a remote area of Tanzania. Considering that the non-nucleoside reverse-transcriptase inhibitors are part of the first-line antiretroviral regimen in Tanzania and all of Africa, resistance surveys should be prioritized in settings where antiretroviral therapy programs are scaled up.

  1. 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

    with at least three serum creatinine measurements and corresponding body weight measurements from 2004 onwards. METHODS:: CKD was defined as either confirmed (two measurements >/=3 months apart) estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m or below for persons with baseline eGFR of above...... cumulative exposure to tenofovir [incidence rate ratio (IRR) per year 1.16, 95% CI 1.06-1.25, P ... increased rate of CKD. Consistent results were observed in wide-ranging sensitivity analyses, although of marginal statistical significance for lopinavir/r. No other antiretroviral dugs were associated with increased incidence of CKD. CONCLUSION:: In this nonrandomized large cohort, increasing exposure...

  2. 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.

  3. The pricing and procurement of antiretroviral drugs: an observational study of data from the Global Fund.

    Science.gov (United States)

    Vasan, Ashwin; Hoos, David; Mukherjee, Joia S; Farmer, Paul E; Rosenfield, Allan G; Perriëns, Joseph H

    2006-05-01

    The Purchase price report released in August 2004 by the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund) was the first publication of a significant amount of real transaction purchase data for antiretrovirals (ARVs). We did an observational study of the ARV transaction data in the Purchase price report to examine the procurement behaviour of principal recipients of Global Fund grants in developing countries. We found that, with a few exceptions for specific products (e.g. lamivudine) and regions (e.g. eastern Europe), prices in low-income countries were broadly consistent or lower than the lowest differential prices quoted by the research and development sector of the pharmaceutical industry. In lower middle-income countries, prices were more varied and in several instances (lopinavir/ritonavir, didanosine, and zidovudine/lamivudine) were very high compared with the per capita income of the country. In all low- and lower middle-income countries, ARV prices were still significantly high given limited local purchasing power and economic strength, thus reaffirming the need for donor support to achieve rapid scale-up of antiretroviral therapy. However, the price of ARVs will have to decrease to render scale-up financially sustainable for donors and eventually for governments themselves. An important first step in reducing prices will be to make available in the public domain as much ARV transaction data as possible to provide a factual basis for discussions on pricing. The price of ARVs has considerable implications for the sustainability of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) treatment in the developing world.

  4. Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy.

    Science.gov (United States)

    Etiebet, Mary-Ann A; Shepherd, James; Nowak, Rebecca G; Charurat, Man; Chang, Harry; Ajayi, Samuel; Elegba, Olufunmilayo; Ndembi, Nicaise; Abimiku, Alashle; Carr, Jean K; Eyzaguirre, Lindsay M; Blattner, William A

    2013-02-20

    In resource-limited settings, HIV-1 drug resistance testing to guide antiretroviral therapy (ART) selection is unavailable. We retrospectively conducted genotypic analysis on archived samples from Nigerian patients who received targeted viral load testing to confirm treatment failure and report their drug resistance mutation patterns. Stored plasma from 349 adult patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens was assayed for HIV-1 RNA viral load, and samples with more than 1000 copies/ml were sequenced in the pol gene. Analysis for resistance mutations utilized the IAS-US 2011 Drug Resistance Mutation list. One hundred and seventy-five samples were genotyped; the majority of the subtypes were G (42.9%) and CRF02_AG (33.7%). Patients were on ART for a median of 27 months. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 97% had an NNRTI resistance mutation and 47% had at least two etravirine-associated mutations. In multivariate analysis tenofovir-based regimens were less likely to have at least three nucleoside reverse transcriptase inhibitor (NRTI) mutations after adjusting for subtype, previous ART, CD4, and HIV viral load [P < 0.001, odds ratio (OR) 0.04]. 70% of patients on tenofovir-based regimens had at least two susceptible NRTIs to include in a second-line regimen compared with 40% on zidovudine-based regimens (P = 0.04, OR = 3.4). At recognition of treatment failure, patients on tenofovir-based first-line regimens had fewer NRTI drug-resistant mutations and more active NRTI drugs available for second-line regimens. These findings can inform strategies for ART regimen sequencing to optimize long-term HIV treatment outcomes in low-resource settings.

  5. Drug transporter gene expression in human colorectal tissue and cell lines: modulation with antiretrovirals for microbicide optimization.

    Science.gov (United States)

    Mukhopadhya, Indrani; Murray, Graeme I; Berry, Susan; Thomson, John; Frank, Bruce; Gwozdz, Garry; Ekeruche-Makinde, Julia; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

    2016-02-01

    The objectives of this study were to comprehensively assess mRNA expression of 84 drug transporters in human colorectal biopsies and six representative cell lines, and to investigate the alteration of drug transporter gene expression after exposure to three candidate microbicidal antiretroviral (ARV) drugs (tenofovir, darunavir and dapivirine) in the colorectal epithelium. The outcome of the objectives informs development of optimal ARV-based microbicidal formulations for prevention of HIV-1 infection. Drug transporter mRNA expression was quantified from colorectal biopsies and cell lines by quantitative real-time PCR. Relative mRNA expression was quantified in Caco-2 cells and colorectal explants after induction with ARVs. Data were analysed using Pearson's product moment correlation (r), hierarchical clustering and principal component analysis (PCA). Expression of 58 of the 84 transporters was documented in colorectal biopsies, with genes for CNT2, P-glycoprotein (P-gp) and MRP3 showing the highest expression. No difference was noted between individual subjects when analysed by age, gender or anatomical site (rectum or recto-sigmoid) (r = 0.95-0.99). High expression of P-gp and CNT2 proteins was confirmed by immunohistochemical staining. Similarity between colorectal tissue and cell-line drug transporter gene expression was variable (r = 0.64-0.84). PCA showed distinct clustering of human colorectal biopsy samples, with the Caco-2 cells defined as the best surrogate system. Induction of Caco-2 cell lines with ARV drugs suggests that darunavir-based microbicides incorporating tenofovir may result in drug-drug interactions likely to affect distribution of individual drugs to sub-epithelial target cells. These findings will help optimize complex formulations of rectal microbicides to realize their full potential as an effective approach for pre-exposure prophylaxis against HIV-1 infection. © The Author 2015. Published by Oxford University Press on behalf of the

  6. HIV-1 drug resistance surveillance in antiretroviral treatment-naive individuals from a reference hospital in Guatemala, 2010-2013.

    Science.gov (United States)

    Avila-Ríos, Santiago; García-Morales, Claudia; Garrido-Rodríguez, Daniela; Tapia-Trejo, Daniela; Girón-Callejas, Amalia Carolina; Mendizábal-Burastero, Ricardo; Escobar-Urias, Ingrid Yessenia; García-González, Blanca Leticia; Navas-Castillo, Sabrina; Pinzón-Meza, Rodolfo; Mejía-Villatoro, Carlos Rodolfo; Reyes-Terán, Gustavo

    2015-04-01

    The recent expansion of antiretroviral treatment (ART) coverage in middle/low-income countries has been associated with increasing prevalence of HIV pre-ART drug resistance (PDR). We assessed PDR prevalence, patterns, and trends in Guatemala. Blood samples from 1,084 ART-naive individuals, enrolled from October 2010 to December 2013 at the Roosevelt Hospital in Guatemala City, were obtained. PDR was evaluated using the WHO mutation list for transmitted drug resistance (TDR) surveillance. An overall PDR prevalence of 7.3% (95% CI 5.8-9.0%) was observed for the whole study period. TDR to nonnucleoside reverse transcriptase inhibitors (NNRTI) was the highest (4.9%, p500 and 350-500 CD4(+) T cells/μl (7.4% and 8.7%, respectively) compared to individuals with Guatemala remains at an intermediate level. Nevertheless, we have shown evidence suggesting increasing trends in NNRTI PDR, which need to be taken into account in national HIV management policies.

  7. Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes

    DEFF Research Database (Denmark)

    Costagliola, Dominique; Ledergerber, Bruno; Torti, Carlo

    2013-01-01

    Low CD4(+) T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4(+) T-cell counts after triple-class virological failure....

  8. Transporters for Antiretroviral Drugs in Colorectal CD4+ T Cells and Circulating α4β7 Integrin CD4+ T Cells: Implications for HIV Microbicides.

    Science.gov (United States)

    Mukhopadhya, Indrani; Murray, Graeme I; Duncan, Linda; Yuecel, Raif; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

    2016-09-06

    CD4+ T lymphocytes in the colorectal mucosa are key in HIV-1 transmission and dissemination. As such they are also the primary target for antiretroviral (ARV)-based rectal microbicides for pre-exposure prophylaxis. Drug transporters expressed in mucosal CD4+ T cells determine ARV distribution across the cell membrane and, most likely, efficacy of microbicides. We describe transporters for antiretroviral drugs in colorectal mucosal CD4+ T lymphocytes and compare gene expression with circulating α4β7+CD4+ T cells, which traffic to the intestine and have been shown to be preferentially infected by HIV-1. Purified total CD4+ T cells were obtained from colorectal tissue and blood samples by magnetic separation. CD4+ T cells expressing α4β7 integrin were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells of healthy volunteers. Expressions of 15 efflux and uptake drug transporter genes were quantified using Taqman qPCR assays. Expression of efflux transporters MRP3, MRP5, and BCRP and uptake transporter CNT2 were significantly higher in colorectal CD4+ T cells compared to circulating CD4+ T cells (p = 0.01-0.03). Conversely, circulating α4β7+CD4+ T cells demonstrated significantly higher expression of OATPD compared to colorectal CD4+ T cells (p = 0.001). To the best of our knowledge this is the first report of drug transporter gene expression in colorectal CD4+ and peripheral α4β7+CD4+ T cells. The qualitative and quantitative differences in drug transporter gene expression profiles between α4β7+CD4+ T cells and total mucosal CD4+ T cells may have significant implications for the efficacy of rectally delivered ARV-microbicides. Most notably, we have identified efflux drug transporters that could be targeted by selective inhibitors or beneficial drug-drug interactions to enhance intracellular accumulation of antiretroviral drugs.

  9. Lower genetic variability of HIV-1 and antiretroviral drug resistance in pregnant women from the state of Pará, Brazil.

    Science.gov (United States)

    Machado, Luiz Fernando Almeida; Costa, Iran Barros; Folha, Maria Nazaré; da Luz, Anderson Levy Bessa; Vallinoto, Antonio Carlos Rosário; Ishak, Ricardo; Ishak, Marluisa Oliveira Guimarães

    2017-04-12

    The present study aimed to describe the genetic diversity of HIV-1, as well as the resistance profile of the viruses identified in HIV-1 infected pregnant women under antiretroviral therapy in the state of Pará, Northern Brazil. Blood samples were collected from 45 HIV-1 infected pregnant to determine the virus subtypes according to the HIV-1 protease (PR) gene and part of the HIV-1 reverse transcriptase (RT) gene by sequencing the nucleotides of these regions. Drug resistance mutations and susceptibility to antiretroviral drugs were analyzed by the Stanford HIV Drug Resistance Database. Out of 45 samples, only 34 could be amplified for PR and 30 for RT. Regarding the PR gene, subtypes B (97.1%) and C (2.9%) were identified; for the RT gene, subtypes B (90.0%), F (6.7%), and C (3.3%) were detected. Resistance to protease inhibitors (PI) was identified in 5.8% of the pregnant, and mutations conferring resistance to nucleoside reverse transcriptase inhibitors were found in 3.3%, while mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors were found in 3.3%. These results showed a low frequency of strains resistant to antiretroviral drugs, the prevalence of subtypes B and F, and the persistent low transmission of subtype C in pregnant of the state of Pará, Brazil.

  10. 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...... 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....

  11. Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors

    International Nuclear Information System (INIS)

    Pugach, Pavel; Ketas, Thomas J.; Michael, Elizabeth; Moore, John P.

    2008-01-01

    The small molecule CCR5 inhibitors are a new class of drugs for treating infection by human immunodeficiency virus type 1 (HIV-1). They act by binding to the CCR5 co-receptor and preventing its use during HIV-1-cell fusion. Escape mutants can be raised against CCR5 inhibitors in vitro and will arise when these drugs are used clinically. Here, we have assessed the responses of CCR5 inhibitor-resistant viruses to other anti-retroviral drugs that act by different mechanisms, and their sensitivities to neutralizing antibodies (NAbs). The rationale for the latter study is that the resistance pathway for CCR5 inhibitors involves changes in the HIV-1 envelope glycoproteins (Env), which are also targets for NAbs. The escape mutants CC101.19 and D1/85.16 were selected for resistance to AD101 and vicriviroc (VVC), respectively, from the primary R5 HIV-1 isolate CC1/85. Each escape mutant was cross-resistant to other small molecule CCR5 inhibitors (aplaviroc, maraviroc, VVC, AD101 and CMPD 167), but sensitive to protein ligands of CCR5: the modified chemokine PSC-RANTES and the humanized MAb PRO-140. The resistant viruses also retained wild-type sensitivity to the nucleoside reverse transcriptase inhibitor (RTI) zidovudine, the non-nucleoside RTI nevirapine, the protease inhibitor atazanavir and other attachment and fusion inhibitors that act independently of CCR5 (BMS-806, PRO-542 and enfuvirtide). Of note is that the escape mutants were more sensitive than the parental CC1/85 isolate to a subset of neutralizing monoclonal antibodies and to some sera from HIV-1-infected people, implying that sequence changes in Env that confer resistance to CCR5 inhibitors can increase the accessibility of some NAb epitopes. The need to preserve NAb resistance may therefore be a constraint upon how escape from CCR5 inhibitors occurs in vivo

  12. 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

  13. Budget impact analysis of antiretroviral less drug regimen simplification in HIV-positive patients on the Italian National Health Service

    Directory of Open Access Journals (Sweden)

    Restelli U

    2014-09-01

    Full Text Available Umberto Restelli,1,2 Massimo Andreoni,3 Andrea Antinori,4 Marzia Bonfanti,2 Giovanni Di Perri,5 Massimo Galli,6 Adriano Lazzarin,7 Giuliano Rizzardini,8,9 Davide Croce1,2 1Department of Community Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 2Centro di Ricerca in Economia e Management in Sanità e nel Sociale (CREMS, Università Carlo Cattaneo – LIUC, Castellanza (VA, Italy; 3Clinical Infectious Diseases, Tor Vergata University (PTV, Rome, Italy; 4Clinical Department, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy; 5Department of Medical Sciences, Infectious Diseases, Amedeo di Savoia Hospital, Turin, Italy; 6Third Division of Infectious Diseases, "Luigi Sacco" Hospital, Milan, Italy; 7Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; 8First and Second Divisions of Infectious Diseases, "Luigi Sacco" Hospital, Milan, Italy; 9School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Background: Deintensification and less drug regimen (LDR antiretroviral therapy (ART strategies have proved to be effective in terms of maintaining viral suppression in human immunodeficiency virus (HIV-positive patients, increasing tolerability, and reducing toxicity of antiretroviral drugs administered to patients. However, the economic impact of these strategies have not been widely investigated. The aim of the study is to evaluate the economic impact that ART LDR could have on the Italian National Health Service (INHS budget. Methods: A budget impact model was structured to assess the potential savings for the INHS by the use of ART LDR for HIV-positive patients with a 3 year perspective. Data concerning ART cost, patient distribution within different ARTs, and probabilities for patients to change ART on a yearly basis were collected within four Italian infectious diseases departments, providing

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

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    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

  15. 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

  16. Metronidazole or Cotrimoxazole therapy is associated with a decrease in intestinal bioavailability of common antiretroviral drugs.

    Directory of Open Access Journals (Sweden)

    Flore Dossou-Yovo

    Full Text Available Metronidazole (MTZ and Cotrimoxazole (CTX are used in HIV/AIDS patients eligible for antiretroviral treatment. The objective of this animal study was to determine whether pre-treatment with antibiotics affects the intestinal bioavailability of Atazanavir (ATV and Ritonavir (RTV. After oral administration of 1 mg MTZ and CTX for 7 days, the rat colonic mucosa were analyzed for mucus thickness or placed in Ussing chambers to measure ATV and RTV net transepithelial fluxes (Jnet. 1. In control rats, the mucus thickness was 43.3±7.6 µm and 40.7±6.9 µm, in proximal and distal colon, respectively. In proximal colon, the thickness was 57.2±8.8 and 58.2±6.9 µm after MTZ and CTX, respectively whereas in distal colon, the thickness was 121.1±38.4 and 170.5±35.0 µm (P<0.05 respectively. 2. Transepithelial conductance was reduced after MTZ or CTX in the proximal and distal colon. 3. In control, net ATV secretion was observed both in proximal (-0.36±0.02 µg.hr(-1 cm(-2 and distal colon (-0.30±0.08 µg.hr(-1 cm(-2. After MTZ and CTX, it was increased in the proximal colon by two 2 fold and 4 fold, respectively and in the distal colon by 3 fold and 5 fold, respectively. 4. In control, there was no net active RTV transport either in proximal (+0.01±0.01 µg.hr(-1 cm(-2 or distal colon (+0.04±0.01 µg.hr(-1 cm(-2. After MTZ and CTX, secretion was increased 5 fold and 10 fold, respectively, in the proximal colon and two fold and 5 fold, respectively in the distal colon (p<0.001. In conclusion, after MTZ and CTX therapy, the mucus layer was enlarged, passive permeability was decreased and ATV and RTV were actively secreted by the colonic epithelium suggesting that, in rat, the intestinal bioavailability of ATV and RTV is impaired after antibiotic therapy.

  17. 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

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

    African Journals Online (AJOL)

    ... with very little or no laboratory monitory, limited attention has been given to side effects ... A total of fifty two (52) albino rats were randomly divided into four groups ... The mean value of ALT activity for the drug in dose dependent manner was ...

  19. 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.

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

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    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.

  1. 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).

  2. Adherence to HIV/AIDS antiretroviral therapy among drug users: A qualitative study in Iran

    Directory of Open Access Journals (Sweden)

    Zahra Hosseini

    2016-01-01

    Conclusions: The obtained results indicated that adherence to the treatment of HIV is not constant and mono-dimensional, but is a function of different factors. Hence, an individual having feeble adherence in a specific time and under specific circumstances may show desirable adherence under a different circumstance. Thus, treatment of addicts living with HIV/AIDS requires physical, psychological, and social attention along with drug treatments.

  3. 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.

  4. Prevalence of possible drug-drug interactions between antiretroviral agents in different age groups in a section of the private health care sector setting in South Africa.

    Science.gov (United States)

    Katende-Kyenda, N L; Lubbe, M S; Serfontein, J H P; Truter, I

    2008-08-01

    The chronic nature of human immunodeficiency virus (HIV) infection requires lifelong highly active antiretroviral (ARV) therapy (HAART) to continuously suppress HIV-1 viral replication, thus reducing morbidity and mortality. HAART is restricted by complex dosing, drug-drug interactions (DDIs) and toxicities. To determine the prevalence of possible DDIs between ARV drugs in different age groups in a section of the private primary health care sector in South Africa. A quantitative, retrospective drug utilization review was performed on 47 085 ARV prescriptions claimed through a national medicine claims database during 2006. Possible DDIs identified were classified according to a clinical significance rating as described by Tatro [Drug Interaction Facts 2005. St Louis, MO: Facts and Comparisons (2005)]. The total number of patients who received prescriptions that were claimed through the medicine claims database was 275 424, of whom 25.11% were males, 28.28% were females and the gender of 46.61% patients was unknown. Of the total number of patients, 3.27% were HIV patients of which an average of 5.23 +/- 3.86 ARV prescriptions (n = 47 085) per patient were claimed for representing 4.73% of the total number of prescriptions claimed during the study period (N = 993 804). HIV patients received an average of 2.36 +/- 0.61 ARVs per prescription. Only 4.95% of the prescriptions had one ARV medicine item, 56.04% two, 37.10% three, 1.75% four and 6 years and 12 and 60 years with patients <40 years and < or =60 years having the highest number of DDIs and patients older than 60 years the lowest. The majority of DDIs between the ARVs presented in significance levels 2 and 4. The most important interactions were between: indinavir (IDV) and ritonavir (n = 199); efavirenz (EFV) and lopinavir/ritonavir (n = 65) and EFV and IDV (n = 60) all interacting at level 2. The importance of using drug utilization study as an identification tool to provide insight into the prescribing and

  5. 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.

  6. 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.

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

    Science.gov (United States)

    Kioko, Mary T; Pertet, Anne M

    2017-07-31

    Antiretroviral (ARV) adherence of ≥ 95% is recommended for suppressing HIV. However, studies have shown that the ≥ 95% recommended level is rarely achieved. This cross-sectional community-based study sought to assess factors contributing to ARV drug adherence among adults living with HIV or AIDS. The study was conducted in a rural community in Machakos County, Kenya. 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. 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. The burden of side effects and being a divorcee are primary predictors of ARV adherence.

  8. Analysis of drug-drug interactions among patients receiving antiretroviral regimens using data from a large open-source prescription database.

    Science.gov (United States)

    Patel, Nimish; Borg, Peter; Haubrich, Richard; McNicholl, Ian

    2018-06-14

    Results of a study of contraindicated concomitant medication use among recipients of preferred antiretroviral therapy (ART) regimens are reported. A retrospective study was conducted to evaluate concomitant medication use in a cohort of previously treatment-naive, human immunodeficiency virus (HIV)-infected U.S. patients prescribed preferred ART regimens during the period April 2014-March 2015. Data were obtained from a proprietary longitudinal prescription database; elements retrieved included age, sex, and prescription data. The outcome of interest was the frequency of drug-drug interactions (DDIs) associated with concomitant use of contraindicated medications. Data on 25,919 unique treatment-naive patients who used a preferred ART regimen were collected. Overall, there were 384 instances in which a contraindicated medication was dispensed for concurrent use with a recommended ART regimen. Rates of contraindicated concomitant medication use differed significantly by ART regimen; the highest rate (3.2%) was for darunavir plus ritonavir plus emtricitabine-tenofovir disoproxil fumarate (DRV plus RTV plus FTC/TDF), followed by elvitegravir-cobicistat-emtricitabine-tenofovir disoproxil fumarate (EVG/c/FTC/TDF)(2.8%). The highest frequencies of DDIs were associated with ART regimens that included a pharmacoenhancing agent: DRV plus RTV plus FTC/TDF (3.2%) and EVG/c/FTC/TDF (2.8%). In a large population of treatment-naive HIV-infected patients, ART regimens that contained a pharmacoenhancing agent were involved most frequently in contraindicated medication-related DDIs. All of the DDIs could have been avoided by using therapeutic alternatives within the same class not associated with a DDI. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  9. 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

  10. 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...... were obtained from the Danish HIV Cohort Study and the Danish HIV Sequence Database. We included treatment-naive patients initiating HAART after December 1997 and computed time to first drug resistance mutation, identified as new mutations detected within 1 year after a 60-day period of treatment.......077). The IR of PI resistance decreased from 7.5 (1.4-21.8) in 1999 to 2.9 (0.7-11.4) in 2002-2003 (P=0.148). The IRs were low for specific resistance mutations, except for M184V (IR 5.6 [4.0-7.9]) and K103N (IR 8.2 [5.6-12.0]). CONCLUSIONS: The incidence of acquired drug resistance has decreased among HIV...

  11. Antiretroviral therapy drug adherence in Rwanda: perspectives from patients and healthcare workers using a mixed-methods approach

    NARCIS (Netherlands)

    Vyankandondera, Joseph; Mitchell, Kirstin; Asiimwe-Kateera, Brenda; Boer, Kimberly; Mutwa, Philippe; Balinda, Jean-Paul; van Straten, Masja; Reiss, Peter; van de Wijgert, Janneke

    2013-01-01

    Rwanda has achieved high enrollment into antiretroviral therapy (ART) programs but data on adherence after enrollment are not routinely collected. We used a mixed-methods approach (standardized questionnaires, pill counts, focus group discussions, and in-depth interviews) to determine levels of and

  12. 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

  13. 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

  14. Antiretroviral therapeutic drug monitoring

    African Journals Online (AJOL)

    Winnie

    hepatotoxicity, particularly among women with a lower body mass index, reported in ... limitations of TDM. Lastly, the potential role of TDM in southern Africa will be discussed. ... higher rates of virological suppression in the TDM arms. However ...

  15. 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

  16. 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.

  17. Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam

    Science.gov (United States)

    Jordan, Michael R; La, Hanh; Nguyen, Hien Duc; Sheehan, Heidi; Lien, Trinh Thi Minh; Van Dang, Duong; Hellinger, James; Wanke, Christine; Tang, Alice M

    2009-01-01

    Summary Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programs. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy (ART) for at least 6 months in Hanoi, Vietnam. Mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA 95% adherence (p<0.01) and current use of trimethoprim/sulfamethoxazole (p<0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (p=0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlights the need for adherence promotion, risk reduction programs, and population based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited. PMID:19451329

  18. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

    OpenAIRE

    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 failu...

  19. 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.

  20. 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

  1. Comparative analysis of drug resistance mutations in the human immunodeficiency virus reverse transcriptase gene in patients who are non-responsive, responsive and naive to antiretroviral therapy.

    Science.gov (United States)

    Misbah, Mohammad; Roy, Gaurav; Shahid, Mudassar; Nag, Nalin; Kumar, Suresh; Husain, Mohammad

    2016-05-01

    Drug resistance mutations in the Pol gene of human immunodeficiency virus 1 (HIV-1) are one of the critical factors associated with antiretroviral therapy (ART) failure in HIV-1 patients. The issue of resistance to reverse transcriptase inhibitors (RTIs) in HIV infection has not been adequately addressed in the Indian subcontinent. We compared HIV-1 reverse transcriptase (RT) gene sequences to identify mutations present in HIV-1 patients who were ART non-responders, ART responders and drug naive. Genotypic drug resistance testing was performed by sequencing a 655-bp region of the RT gene from 102 HIV-1 patients, consisting of 30 ART-non-responding, 35 ART-responding and 37 drug-naive patients. The Stanford HIV Resistance Database (HIVDBv 6.2), IAS-USA mutation list, ANRS_09/2012 algorithm, and Rega v8.02 algorithm were used to interpret the pattern of drug resistance. The majority of the sequences (96 %) belonged to subtype C, and a few of them (3.9 %) to subtype A1. The frequency of drug resistance mutations observed in ART-non-responding, ART-responding and drug-naive patients was 40.1 %, 10.7 % and 20.58 %, respectively. It was observed that in non-responders, multiple mutations were present in the same patient, while in responders, a single mutation was found. Some of the drug-naive patients had more than one mutation. Thymidine analogue mutations (TAMs), however, were found in non-responders and naive patients but not in responders. Although drug resistance mutations were widely distributed among ART non-responders, the presence of resistance mutations in the viruses of drug-naive patients poses a big concern in the absence of a genotyping resistance test.

  2. 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...

  3. 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.

  4. 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 dapivirine. The P app for tenofovir in Caco-2 cell monolayers was 0.10 ± 0.02 × 10 -6 cm/s, ER = 1. For dapivirine, P app was 32.2 ± 3.7 × 10 -6 cm/s, but the ER = 1.3 was lower than anticipated based on the in 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

  5. 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

  6. 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.

  7. Relationship between self-reported adherence, antiretroviral drug concentration measurement and self-reported symptoms in patients treated for HIV-1 infection.

    Science.gov (United States)

    Fabbiani, Massimiliano; Di Giambenedetto, Simona; Cingolani, Antonella; Fanti, Iuri; Colafigli, Manuela; Tamburrini, Enrica; Cauda, Roberto; Navarra, Pierluigi; De Luca, Andrea; Murri, Rita

    2016-01-01

    The aim of the study was to explore relationships between self-reported adherence, antiretroviral drug concentration measurement (TDM) and self-reported symptoms. We systematically administered to human immunodeficiency (HIV)-infected outpatients a questionnaire evaluating measures of self-reported adherence (missing doses during last week, deviations from the prescribed timing of therapy, self-initiated discontinuations for > 24 or 48 h, exhausting drugs and present sense of how patients are taking therapy) and a panel of referred symptoms (a symptom score was built summing self-reported scores for each listed symptom). We selected patients who completed the questionnaire and also had a TDM (mainly reflecting adherence in the past few days or weeks), thus comparing these two tools as measures of adherence. A total of 130 patients (64.6% males, median age 44 years, 76.2% with HIV RNA HIV RNA symptom score was associated with a lower self-reported adherence and with a higher proportion of undetectable drug levels. Self-reported adherence and TDM showed a correlation and seemed to be comparable tools for adherence estimation. Self-reported symptoms were associated with lower adherence and undetectable drug levels.

  8. 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.

    Science.gov (United States)

    Billong, Serge Clotaire; Fokam, Joseph; Penda, Calixte Ida; Amadou, Salmon; Kob, David Same; Billong, Edson-Joan; Colizzi, Vittorio; Ndjolo, Alexis; Bisseck, Anne-Cecile Zoung-Kani; Elat, Jean-Bosco Nfetam

    2016-11-15

    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. 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 (sampling strategy could be further strengthened for informed ART monitoring and HIVDR prevention perspectives.

  9. Association Between the Occurrence of Adverse Drug Events and Modification of First-Line Highly Active Antiretroviral Therapy in Ghanaian HIV Patients.

    Science.gov (United States)

    Tetteh, Raymond A; Nartey, Edmund T; Lartey, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Yankey, Barbara A; Dodoo, Alexander N O

    2016-11-01

    Patients initiated on highly active antiretroviral therapy (HAART) generally remain on medication indefinitely. A modification in the HAART regimen may become necessary because of possible acute or chronic toxicities, concomitant clinical conditions, development of virological failure or the advent of adverse drug events. The study documents adverse drug events of HIV-positive Ghanaian patients with HAART modifications. It also investigates the association between documented adverse drug events and HAART modification using an unmatched case-control study design. The study was conducted in the Fevers Unit of the Korle Bu Teaching Hospital and involved patients who attended the HIV Care Clinic between January 2004 and December 2009. Data from 298 modified therapy patients (cases) were compared with 298 continuing therapy patients (controls) who had been on treatment for at least 1 month before the end of study. Controls were sampled from the same database of a cohort of HIV-positive patients on HAART, at the time a case occurred, in terms of treatment initiation ±1 month. Data were obtained from patients' clinical folders and the HIV clinic database linked to the pharmacy database. The nature of the documented adverse drug events of the cases was described and the association between the documented adverse drug events and HAART modification was determined by logistic regression with reported odds ratios (ORs) and their 95 % confidence interval (CI). Among the 298 modified therapy patients sampled in this study, 52.7 % of them had at least one documented adverse drug event. The most documented adverse drug event was anaemia, recorded in 18.5 % of modified therapy patients, all of whom were on a zidovudine-based regimen. The presence of documented adverse drug events was significantly associated with HAART modification [adjusted OR = 2.71 (95 % CI 2.11-3.48), p < 0.001]. Among HIV patients on HAART, adverse drug events play a major role in treatment

  10. HIV-1 drug resistance genotyping from antiretroviral therapy (ART naïve and first-line treatment failures in Djiboutian patients

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    Elmi Abar Aden

    2012-10-01

    Full Text Available Abstract In this study we report the prevalence of antiretroviral drug resistant HIV-1 genotypes of virus isolated from Djiboutian patients who failed first-line antiretroviral therapy (ART and from ART naïve patients. Patients and methods A total of 35 blood samples from 16 patients who showed first-line ART failure (>1000 viral genome copies/ml and 19 ART-naïve patients were collected in Djibouti from October 2009 to December 2009. Both the protease (PR and reverse transcriptase (RT genes were amplified and sequenced using National Agency for AIDS Research (ANRS protocols. The Stanford HIV database algorithm was used for interpretation of resistance data and genotyping. Results Among the 16 patients with first-line ART failure, nine (56.2% showed reverse transcriptase inhibitor-resistant HIV-1 strains: two (12.5% were resistant to nucleoside (NRTI, one (6.25% to non-nucleoside (NNRTI reverse transcriptase inhibitors, and six (37.5% to both. Analysis of the DNA sequencing data indicated that the most common mutations conferring drug resistance were M184V (38% for NRTI and K103N (25% for NNRTI. Only NRTI primary mutations K101Q, K103N and the PI minor mutation L10V were found in ART naïve individuals. No protease inhibitor resistant strains were detected. In our study, we found no detectable resistance in ∼ 44% of all patients who experienced therapeutic failure which was explained by low compliance, co-infection with tuberculosis and malnutrition. Genotyping revealed that 65.7% of samples were infected with subtype C, 20% with CRF02_AG, 8.5% with B, 2.9% with CRF02_AG/C and 2.9% with K/C. Conclusion The results of this first study about drug resistance mutations in first-line ART failures show the importance of performing drug resistance mutation test which guides the choice of a second-line regimen. This will improve the management of HIV-infected Djiboutian patients. Virtual slides The virtual slide(s for this article can be found

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Antiretroviral Drug Activity in Macaques Infected during Pre-Exposure Prophylaxis Has a Transient Effect on Cell-Associated SHIV DNA Reservoirs.

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    Mian-Er Cong

    Full Text Available Pre-exposure prophylaxis (PrEP with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF is a novel HIV prevention strategy. Suboptimal PrEP adherence and HIV infection creates an opportunity for continued antiretroviral drug activity during undiagnosed infection. We previously showed that macaques infected with SHIV during PrEP with FTC/TDF display reduced acute plasma viremias and limited virus diversity. We investigated the effect of PrEP on acute SHIV DNA dynamics and on the size of the persistent virus reservoir in lymphoid tissues.Cell-associated SHIV DNA levels in PBMCs were measured in 8 macaques infected during PrEP with FTC/TDF or single-agent TAF and was compared to those seen in untreated infections (n = 10. PrEP breakthrough infections continued treatment with 1-2 weekly drug doses to model suboptimal drug exposure during undiagnosed HIV infection in humans. SHIV DNA was also measured in lymphoid tissues collected from FTC/TDF PrEP breakthroughs after 1 year of infection.Compared to untreated controls, PrEP infections had reduced plasma RNA viremias both at peak and throughout weeks 1-12 (p<0.005. SHIV DNA levels were also reduced at peak and during the first 12 weeks of infection (p<0.043 but not throughout weeks 12-20. At 1 year, SHIV DNA reservoirs in lymphoid tissues were similar in size among macaques that received PrEP or placebo.Antiviral drug activity due to PrEP limits acute SHIV replication but has only a transient effect on cell-associated SHIV DNA levels. Our model suggests that suboptimal drug exposure in persons that are taking PrEP and become infected with HIV may not be sufficient to reduce the pool of HIV-infected cells, and that treatment intensification may be needed to sustain potential virological benefits from the PrEP regimen.

  16. Genotypic Characterization of Human Immunodeficiency Virus Type 1 Derived from Antiretroviral Drug-Treated Individuals Residing in Earthquake-Affected Areas in Nepal.

    Science.gov (United States)

    Negi, Bharat Singh; Kotaki, Tomohiro; Joshi, Sunil Kumar; Bastola, Anup; Nakazawa, Minato; Kameoka, Masanori

    2017-09-01

    Molecular epidemiological data on human immunodeficiency virus type 1 (HIV-1) are limited in Nepal and have not been available in areas affected by the April 2015 earthquake. Therefore, we conducted a genotypic study on HIV-1 genes derived from individuals on antiretroviral therapy residing in 14 districts in Nepal highly affected by the earthquake. HIV-1 genomic fragments were amplified from 40 blood samples of HIV treatment-failure individuals, and a sequencing analysis was performed on these genes. In the 40 samples, 29 protease, 32 reverse transcriptase, 25 gag, and 21 env genes were sequenced. HIV-1 subtyping revealed that subtype C (84.2%, 32/38) was the major subtype prevalent in the region, while CRF01_AE (7.9%, 3/38) and other recombinant forms (7.9%, 3/38) were also detected. In addition, major drug resistance mutations were identified in 21.9% (7/32) of samples, indicating the possible emergence of HIV-1 drug resistance in earthquake-affected areas in Nepal.

  17. Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals

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    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.

  18. Plasma HIV-1 RNA viral load rebound among people who inject drugs receiving antiretroviral therapy (ART) in a Canadian setting: an ethno-epidemiological study.

    Science.gov (United States)

    Small, Will; Milloy, M J; McNeil, Ryan; Maher, Lisa; Kerr, Thomas

    2016-01-01

    People who inject drugs (PWID) living with HIV often experience sub-optimal antiretroviral therapy (ART) treatment outcomes, including HIV plasma viral load (PVL) rebound. While previous studies have identified risk factors for PVL rebound among PWID, no study has examined the perspectives of PWID who have experienced PVL rebound episodes. We conducted an ethno-epidemiological study to investigate the circumstances surrounding the emergence of rebound episodes among PWID in Vancouver, BC, Canada. Comprehensive clinical records linked to a community-based prospective observational cohort of HIV-positive drug users were used to identify PWID who had recently experienced viral rebound. In-depth qualitative interviews with 16 male and 11 female participants explored participant perspectives regarding the emergence of viral rebound. A timeline depicting each participant's HIV viral load and adherence to ART was used to elicit discussion of circumstances surrounding viral rebound. Viral rebound episodes were shaped by interplay between various individual, social, and environmental factors that disrupted routines facilitating adherence. Structural-environmental influences resulting in non-adherence included housing transitions, changes in drug use patterns and intense drug scene involvement, and inadequate care for co-morbid health conditions. Social-environmental influences on ART adherence included poor interactions between care providers and patients producing non-adherence, and understandings of HIV treatment that fostered intentional treatment discontinuation. This study describes key pathways which led to rebound episodes among PWID receiving ART and illustrates how environmental forces may increase vulnerability for non-adherence leading to treatment failure. Our findings have potential to help inform interventions and supports that address social-structural forces that foster non-adherence among PWID.

  19. Estimation of the standardized risk difference and ratio in a competing risks framework: application to injection drug use and progression to AIDS after initiation of antiretroviral therapy.

    Science.gov (United States)

    Cole, Stephen R; Lau, Bryan; Eron, Joseph J; Brookhart, M Alan; Kitahata, Mari M; Martin, Jeffrey N; Mathews, William C; Mugavero, Michael J

    2015-02-15

    There are few published examples of absolute risk estimated from epidemiologic data subject to censoring and competing risks with adjustment for multiple confounders. We present an example estimating the effect of injection drug use on 6-year risk of acquired immunodeficiency syndrome (AIDS) after initiation of combination antiretroviral therapy between 1998 and 2012 in an 8-site US cohort study with death before AIDS as a competing risk. We estimate the risk standardized to the total study sample by combining inverse probability weights with the cumulative incidence function; estimates of precision are obtained by bootstrap. In 7,182 patients (83% male, 33% African American, median age of 38 years), we observed 6-year standardized AIDS risks of 16.75% among 1,143 injection drug users and 12.08% among 6,039 nonusers, yielding a standardized risk difference of 4.68 (95% confidence interval: 1.27, 8.08) and a standardized risk ratio of 1.39 (95% confidence interval: 1.12, 1.72). Results may be sensitive to the assumptions of exposure-version irrelevance, no measurement bias, and no unmeasured confounding. These limitations suggest that results be replicated with refined measurements of injection drug use. Nevertheless, estimating the standardized risk difference and ratio is straightforward, and injection drug use appears to increase the risk of AIDS. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Usuários de drogas injetáveis e terapia anti-retroviral: percepções das equipes de farmácia Injecting drug users and antiretroviral therapy: perceptions of pharmacy teams

    Directory of Open Access Journals (Sweden)

    Chizuru Minami Yokaichiya

    2007-12-01

    adherence to antiretroviral therapy by injecting drug users living with HIV/AIDS. METHODS: Qualitative study through focus groups and thematic discourse analysis of pharmacists, technicians and assistants with more than six months of experience with medication supply, in 15 assisting units for STD/AIDS in the city of São Paulo, in 2002. RESULTS: Three groups were formed, totaling 29 participants, originating from 12 out of the 15 existing services, and including 12 university level professionals and 17 high-school level professionals. The groups concluded that the pharmacy has an important role in the antiretroviral drug supply, which is reflected in the treatment adherence, because trust-based relationships can be built up through their procedures. In spite of this, they pointed out that such building-up does not take place through excessively bureaucratic activities. This has negative repercussions for all patients, especially for injecting drug users, considered "difficult people". Such concept sums up their behavior: they are supposed to be confused and incapable to adhere to treatment, and have limited understanding. Staff members, however, affirm they treat these patients equally. They do not realize that, by this acting, the specific needs of injecting drug users may become invisible in the service. There is also the possibility that stigmatizing stereotypes may be created, resulting in yet another barrier to the work on adherence. CONCLUSIONS: Although the pharmacy is recommended as a potentially favorable place to listen to and form bonds with users, the results show objective and subjective obstacles to render it suitable for the work on adherence.

  1. 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, D.; Peters, L.; Rockstroh, J. K.

    2014-01-01

    HCV/HIV coinfected patients. Methods: EuroSIDA patients taking combination antiretroviral therapy were included. Poisson regression identified factors associated with antiretroviral treatment discontinuation. Results: A total of 9535 HIV-positive patients with known HCV status were included (6939...

  2. Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial.

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    Mark Holodniy

    2011-03-01

    Full Text Available Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR and limited retreatment options. We assessed two novel antiretroviral (ARV treatment approaches in this setting.We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count≤300 cells/µl who had ARV treatment (ART failure requiring retreatment, to two options (a re-treatment with either standard (≤4 ARVs or intensive (≥5 ARVs ART and b either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log(10 copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86-1.59, or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68-1.30, or in the rate of non-HIV associated serious adverse events between re-treatment options.We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options.Clinicaltrials.gov NCT00050089.

  3. 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 C K; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher K C; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    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. 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) failure and (2) factors associated with virological suppression after 12 months on second-line. A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥ 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥ 2 TAMs; and 32 with M184V+≥ 1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤ 200 cells/µL at genotyping (OR=4.43, 95% CI [1.59-12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39-16.36], pfailure 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.

  4. Dissimilarities in the metabolism of antiretroviral drugs used in HIV pre-exposure prophylaxis in colon and vagina tissues.

    Science.gov (United States)

    To, Elaine E; Hendrix, Craig W; Bumpus, Namandjé N

    2013-10-01

    Attempts to prevent HIV infection through pre-exposure prophylaxis (PrEP) include topical application of anti-HIV drugs to the mucosal sites of infection; however, a potential role for local drug metabolizing enzymes in modulating the exposure of the mucosal tissues to these drugs has yet to be explored. Here we present the first report that enzymes belonging to the cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) families of drug metabolizing enzymes are expressed and active in vaginal and colorectal tissue using biopsies collected from healthy volunteers. In doing so, we discovered that dapivirine and maraviroc, a non-nucleoside reverse transcriptase inhibitor and an entry inhibitor currently in development as microbicides for HIV PrEP, are differentially metabolized in colorectal tissue and vaginal tissue. Taken together, these data should help to guide the optimization of small molecules being developed for HIV PrEP. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. 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

  6. 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.

  7. 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.

  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) Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥2 TAMs; and 32 with M184V+≥1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤200 cells/µL at genotyping (OR=4.43, 95% CI [1.59–12.37], p=0.004) and ART duration >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

  9. 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.

  10. High HIV-1 Diversity and Prevalence of Transmitted Drug Resistance Among Antiretroviral-Naive HIV-Infected Pregnant Women from Rio de Janeiro, Brazil.

    Science.gov (United States)

    Delatorre, Edson; Silva-de-Jesus, Carlos; Couto-Fernandez, José Carlos; Pilotto, Jose H; Morgado, Mariza G

    2017-01-01

    Antiretroviral (ARV) resistance mutations in human immunodeficiency virus type 1 (HIV-1) infection may reduce the efficacy of prophylactic therapy to prevent mother-to-child transmission (PMTCT) and future treatment options. This study evaluated the diversity and the prevalence of transmitted drug resistance (TDR) in protease (PR) and reverse transcriptase (RT) regions of HIV-1 pol gene among 87 ARV-naive HIV-1-infected pregnant women from Rio de Janeiro, Brazil, between 2012 and 2015. The viral diversity comprised HIV-1 subtypes B (67.8%), F1 (17.2%), and C (4.6%); the circulating recombinant forms 12_BF (2.3%), 28/29_BF, 39_BF, 02_AG (1.1% each) and unique recombinants forms (4.5%). The overall prevalence of any TDR was 17.2%, of which 5.7% for nucleoside RT inhibitors, 5.7% for non-nucleoside RT inhibitors, and 8% for PR inhibitors. The TDR prevalence found in this population may affect the virological outcome of the standard PMTCT ARV-regimens, reinforcing the importance of continuous monitoring.

  11. 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

  12. 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.

  13. Emerging Trends of HIV Drug Resistance in Chinese HIV-Infected Patients Receiving First-Line Highly Active Antiretroviral Therapy: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Liu, Huixin; Ma, Ye; Su, Yingying; Smith, M. Kumi; Liu, Ying; Jin, Yantao; Gu, Hongqiu; Wu, Jing; Zhu, Lin; Wang, Ning

    2014-01-01

    Background. Highly active antiretroviral therapy (HAART) has led to a dramatic decrease in AIDS-related morbidity and mortality through sustained suppression of human immunodeficiency virus (HIV) replication and reconstitution of the immune response. Settings like China that experienced rapid HAART rollout and relatively limited drug selection face considerable challenges in controlling HIV drug resistance (DR). Methods. We conducted a systematic review and meta-analysis to describe trends in emergent HIV DR to first-line HAART among Chinese HIV-infected patients, as reflected in the point prevalence of HIV DR at key points and fixed intervals after treatment initiation, using data from cohort studies and cross-sectional studies respectively. Results. Pooled prevalence of HIV DR from longitudinal cohorts studies was 10.79% (95% confidence interval [CI], 5.85%–19.07%) after 12 months of HAART and 80.58% (95% CI, 76.6%–84.02%) after 72 months of HAART. The HIV DR prevalence from cross-sectional studies was measured in treatment intervals; during the 0–12-month HAART treatment interval, the pooled prevalence of HIV DR was 11.1% (95% CI, 7.49%–16.14%), which increased to 22.92% at 61–72 months (95% CI, 9.45%–45.86%). Stratified analyses showed that patients receiving a didanosine-based regimen had higher HIV DR prevalence than those not taking didanosine (15.82% vs 4.97%). Patients infected through former plasma donation and those receiving AIDS treatment at village clinics had higher HIV DR prevalence than those infected through sexual transmission or treated at a county-level hospital. Conclusions. Our findings indicate higher prevalence of HIV DR for patients with longer cumulative HAART exposure, highlighting important subgroups for future HIV DR surveillance and control. PMID:25053721

  14. 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.

  15. 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.

  16. 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....... Underlying monitoring strategies considered were based on clinical disease, CD4 count or viral load. Within each we considered a strategy in which no further measures are performed, one with a viral load measure to confirm failure, and one with both a viral load measure and a resistance test. Predicted...

  17. 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

    OBJECTIVES: HIV-1 transmitted drug resistance (TDR) in treatment-naïve individuals is a well-described phenomenon. Baseline genotypic resistance testing is considered standard of care in most developed areas of the world. The aim of this analysis was to characterize HIV-1 TDR and the use of resis......OBJECTIVES: HIV-1 transmitted drug resistance (TDR) in treatment-naïve individuals is a well-described phenomenon. Baseline genotypic resistance testing is considered standard of care in most developed areas of the world. The aim of this analysis was to characterize HIV-1 TDR and the use...... 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...

  18. 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.

  19. 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.

  20. 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.

  1. "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

    BACKGROUND: Little is known about how people living with human immunodeficiency virus (HIV) experience malaria and the concomitant use of anti-malarial treatments with anti-retrovirals (ARVs). An understanding of how patients make sense of these experiences is important to consider in planning......, 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...

  2. Individualization of antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Pavlos R

    2011-12-01

    Full Text Available Rebecca Pavlos, Elizabeth J PhillipsInstitute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, AustraliaAbstract: Antiretroviral therapy (ART has evolved considerably over the last three decades. From the early days of monotherapy with high toxicities and pill burdens, through to larger pill burdens and more potent combination therapies, and finally, from 2005 and beyond where we now have the choice of low pill burdens and once-daily therapies. More convenient and less toxic regimens are also becoming available, even in resource-poor settings. An understanding of the individual variation in response to ART, both efficacy and toxicity, has evolved over this time. The strong association of the major histocompatibility class I allele HLA-B*5701 and abacavir hypersensitivity, and its translation and use in routine HIV clinical practice as a predictive marker with 100% negative predictive value, has been a success story and a notable example of the challenges and triumphs in bringing pharmacogenetics to the clinic. In real clinical practice, however, it is going to be the exception rather than the rule that individual biomarkers will definitively guide patient therapy. The need for individualized approaches to ART has been further increased by the importance of non-AIDS comorbidities in HIV clinical practice. In the future, the ideal utilization of the individualized approach to ART will likely consist of a combined approach using a combination of knowledge of drug, virus, and host (pharmacogenetic and pharmacoecologic [factors in the individual's environment that may be dynamic over time] information to guide the truly personalized prescription. This review will focus on our knowledge of the pharmacogenetics of the efficacy and toxicity of currently available antiretroviral agents and the current and potential utility of such information and approaches in present and future HIV clinical care.Keywords: HIV

  3. 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

  4. HIV-1 anti-retroviral drug effect on the C. albicans hyphal growth rate by a Bio-Cell Tracer system Efeito da droga anti-retroviral HIV-1 no crescimento de hifas de C. albicans monitoradas pelo sistema "Bio-Cell Tracer"

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    Nadja Rodrigues de Melo

    2006-09-01

    Full Text Available Declining incidence of oropharyngeal candidosis and opportunistic infections over recent years can be attributed to the use of highly active anti-retroviral therapy (HAART. Infection with C. albicans generally involves adherence and colonization of superficial tissues. During this process, budding yeasts are able to transform to hyphae and penetrate into the deep tissue. Using the biocell tracer system, C. albicans hyphal growth was dynamically observed at the cellular level. Ritonavir was effective in the inhibition of hyphal growth with growth rate of 0.8 mum/min. This study showed the in vitro effect of HIV anti-retroviral drug on the growth rate of the C. albicans hyphae.O declínio na incidência de candidose orofaríngea e infecções oportunistas associadas a infecção pelo HIV tem sido atribuído a introdução da terapia antiretroviral combinada (HAART. Infecção por C. albicans envolve aderência e colonização da mucosa superficial. Durante este processo leveduras são capazes de transformar-se na forma de hifas e penetrar nos tecidos mais profundos. Usando o sistema "Bio-Cell Tracer", o crescimento de hifas de C. albicans foi observado dinamicamente a nível celular. Ritonavir, inibidor de protease do HIV, foi efetivo na inibição do crescimento de hifas com media de 0.8 mim/min.O presente estudo demonstrou o efeito in vitro de um agente anti-retroviral HIV sobre o crescimento de hifas de C. albicans.

  5. Evaluation of Different Antiretroviral Drug Protocols on Naturally Infected Feline Immunodeficiency Virus (FIV Cats in the late Phase of the Asymptomatic Stage of Infection

    Directory of Open Access Journals (Sweden)

    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.

  6. Prevalence and evolution of low frequency HIV drug resistance mutations detected by ultra deep sequencing in patients experiencing first line antiretroviral therapy failure.

    Science.gov (United States)

    Vandenhende, Marie-Anne; Bellecave, Pantxika; Recordon-Pinson, Patricia; Reigadas, Sandrine; Bidet, Yannick; Bruyand, Mathias; Bonnet, Fabrice; Lazaro, Estibaliz; Neau, Didier; Fleury, Hervé; Dabis, François; Morlat, Philippe; Masquelier, Bernard

    2014-01-01

    Clinical relevance of low-frequency HIV-1 variants carrying drug resistance associated mutations (DRMs) is still unclear. We aimed to study the prevalence of low-frequency DRMs, detected by Ultra-Deep Sequencing (UDS) before antiretroviral therapy (ART) and at virological failure (VF), in HIV-1 infected patients experiencing VF on first-line ART. Twenty-nine ART-naive patients followed up in the ANRS-CO3 Aquitaine Cohort, having initiated ART between 2000 and 2009 and experiencing VF (2 plasma viral loads (VL) >500 copies/ml or one VL >1000 copies/ml) were included. Reverse transcriptase and protease DRMs were identified using Sanger sequencing (SS) and UDS at baseline (before ART initiation) and VF. Additional low-frequency variants with PI-, NNRTI- and NRTI-DRMs were found by UDS at baseline and VF, significantly increasing the number of detected DRMs by 1.35 fold (plow-frequency DRMs modified ARV susceptibility predictions to the prescribed treatment for 1 patient at baseline, in whom low-frequency DRM was found at high frequency at VF, and 6 patients at VF. DRMs found at VF were rarely detected as low-frequency DRMs prior to treatment. The rare low-frequency NNRTI- and NRTI-DRMs detected at baseline that correlated with the prescribed treatment were most often found at high-frequency at VF. Low frequency DRMs detected before ART initiation and at VF in patients experiencing VF on first-line ART can increase the overall burden of resistance to PI, NRTI and NNRTI.

  7. Identification of Immunogenic Cytotoxic T Lymphocyte Epitopes Containing Drug Resistance Mutations in Antiretroviral Treatment-Naïve HIV-Infected Individuals.

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. 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

  10. 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.

  11. 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

    Directory of Open Access Journals (Sweden)

    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.

  12. Evaluation of patterns of liver toxicity in patients on antiretroviral and anti-tuberculosis drugs: a prospective four arm observational study in ethiopian patients.

    Directory of Open Access Journals (Sweden)

    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. 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 (p0.05). Stavudine at all doses reduced the litter weights (p<0.001); however, lamivudine at the usual and 3-times doses, delavirdine at 3-times dose, and amprenavir at 3-times dose increased the litter weight (p<0.001). In the maternal compartment, we observed lethal toxicity in the pregnant 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.

  14. 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...

  15. Nurses' perceptions about Botswana patients' anti-retroviral therapy ...

    African Journals Online (AJOL)

    Anti-retroviral drugs(ARVs) are supplied free of charge in Botswana. Lifelong adherence to antiretroviral therapy (ART) is vital to improve the patient's state of well-being and to prevent the development of strains of the human immunodefi ciency virus (HIV) that are resistant to ART. Persons with ART-resistant strains of HIV ...

  16. New targets and novel antiretrovirals | Wood | Southern African ...

    African Journals Online (AJOL)

    Highly active antiretroviral therapy (HAART) has to date been based on use of a triple combination of drugs chosen from three classes of antiretrovirals (ARVs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). These ARV classes ...

  17. Anti-retroviral therapy induced diabetes in a Nigerian | Bakari ...

    African Journals Online (AJOL)

    African Health Sciences ... Background:Anti-retroviral therapy (ART) using Highly Active Anti-retroviral Therapy (HAART) has led to ... HIV infected individuals on one hand, and side effects of chronic administration of these drugs on the other.

  18. Long-Acting Antiretrovirals: Where Are We now?

    Science.gov (United States)

    Nyaku, Amesika N; Kelly, Sean G; Taiwo, Babafemi O

    2017-04-01

    Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.

  19. 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 ...

  20. 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.

  1. CROI 2016: Advances in Antiretroviral Therapy.

    Science.gov (United States)

    Taylor, Barbara S; Olender, Susan A; Tieu, Hong-Van; Wilkin, Timothy J

    2016-01-01

    The 2016 Conference on Retroviruses and Opportunistic Infections highlighted exciting advances in antiretroviral therapy, including important data on investigational antiretroviral drugs and clinical trials. Clinical trials demonstrated benefits from a long-acting injectable coformulation given as maintenance therapy, examined intravenous and subcutaneous administration of a monoclonal antibody directed at the CD4 binding site of HIV-1, and provided novel data on tenofovir alafenamide. Several studies focused on the role of HIV drug resistance, including the significance of minority variants, transmitted drug resistance, use of resistance testing, and drug class-related resistance. Novel data on the HIV care continuum in low- and middle-income settings concentrated on differentiated HIV care delivery models and outcomes. Data on progress toward reaching World Health Organization 90-90-90 targets as well as outcomes related to expedited initiation of HIV treatment and adherence strategies were presented. Results from a trial in Malawi showed reduced rates of mother-to-child transmission among HIV-infected women who initiated antiretroviral therapy prior to pregnancy, and several studies highlighted the effect of antiretroviral therapy in pediatric populations. A special session was dedicated to the findings of studies of Ebola virus disease and treatment during the outbreak in West Africa.

  2. 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

  3. 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...

  4. Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA on SIV-infected Chinese rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Binhua Ling

    Full Text Available Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM treated with intensive combination antiretroviral therapy (cART and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA.SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations.Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters.The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

  5. Comparing two service delivery models for the prevention of mother-to-child transmission (PMTCT of HIV during transition from single-dose nevirapine to multi-drug antiretroviral regimens

    Directory of Open Access Journals (Sweden)

    Mugwaneza Placidie

    2010-12-01

    Full Text Available Abstract Background Mother-to-child transmission (MTCT of HIV has been eliminated from the developed world with the introduction of multi-drug antiretroviral (md-ARV regimens for the prevention of MTCT (PMTCT; but remains the major cause of HIV infection among sub-Saharan African children. This study compares two service delivery models of PMTCT interventions and documents the lessons learned and the challenges encountered during the transition from single-dose nevirapine (sd-nvp to md-ARV regimens in a resource-limited setting. Methods Program data collected from 32 clinical sites was used to describe trends and compare the performance (uptake of HIV testing, CD4 screening and ARV regimens initiated during pregnancy of sites providing PMTCT as a stand-alone service (stand-alone site versus sites providing PMTCT as well as antiretroviral therapy (ART (full package site. CD4 cell count screening, enrolment into ART services and the initiation of md-ARV regimens during pregnancy, including dual (zidovudine [AZT] +sd-nvp prophylaxis and highly active antiretroviral therapy (HAART were analysed. Results From July 2006 to December 2008, 1,622 pregnant women tested HIV positive (HIV+ during antenatal care (ANC. CD4 cell count screening during pregnancy increased from 60% to 70%, and the initiation of md-ARV regimens increased from 35.5% to 97% during this period. In 2008, women attending ANC at full package sites were 30% more likely to undergo CD4 cell count assessment during pregnancy than women attending stand-alone sites (relative risk (RR = 1.3; 95% confidence interval (CI: 1.1-1.4. Enrolment of HIV+ pregnant women in ART services was almost twice as likely at full package sites than at stand-alone sites (RR = 1.9; 95% CI: 1.5-2.3. However, no significant differences were detected between the two models of care in providing md-ARV (RR = 0.9; 95% CI: 0.9-1.0. Conclusions All sites successfully transitioned from sd-nvp to md-ARV regimens for PMTCT

  6. Adipocytes Impair Efficacy of Antiretroviral Therapy

    Science.gov (United States)

    Couturier, Jacob; Winchester, Lee C.; Suliburk, James W.; Wilkerson, Gregory K.; Podany, Anthony T.; Agarwal, Neeti; Chua, Corrine Ying Xuan; Nehete, Pramod N.; Nehete, Bharti P.; Grattoni, Alessandro; Sastry, K. Jagannadha; Fletcher, Courtney V.; Lake, Jordan E.; Balasubramanyan, Ashok; Lewis, Dorothy E.

    2018-01-01

    Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. PMID:29630975

  7. '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.

  8. 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.

  9. 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.

  10. 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.

  11. 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)

  12. 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)

  13. [Current situation related to antiretroviral therapy and related influential factors on HIV infected injection drug users in the methadone maintenance treatment clinics].

    Science.gov (United States)

    Cheng, Xiao-Qing; Pang, Lin; Cao, Xiao-Bin; Wang, Chang-He; Luo, Wei; Zhang, Bo; Wang, Hua; Li, Rong-Jian; Rou, Ke-Ming; Wu, Zun-You

    2013-08-01

    To find out the current coverage of antiretroviral therapy (ART) among HIV positive subjects and to identify the major influential factors associated with the participation in ART among them. 291 HIV positive subjects from 6 methadone maintenance treatment (MMT) clinics in Guangxi and Yunnan province were surveyed by questionnaires. 217 males (74.6%) and 74 females (25.4%) were under investigation, with the average age of 38.4 +/- 5.9. Most of them received less than senior high school education, married and unemployed. Results from the single factor logistic regression analysis showed that: working status, living alone, self-reported history of drinking alcohol in the last month, negative attitude towards MMT among family members,poor self-reported compliance to MMT in the last month,lack of incentives in the MMT clinics, reluctance on disclosure of their own HIV status, good self-perception on their health status, lack of communication on ART related topics among family members in the last 6 months, lack of correct attitude and knowledge on ART etc. appeared as the main factors that influencing the participation in ART program among the patients. Data from the multivariate logistic regression analysis showed that factors as: living alone, unwilling to tell others about the status of HIV infection, poor self-perception on HIV infection, lack of discussion of ART related topics within family members in the last 6 months and poor awareness towards ART among the family members etc., were associated with the low participation rate of ART. Conclusion Strengthening the publicity and education programs on HIV positive patients and their family members at the MMT clinics seemed to be effective in extending the ART coverage. Attention should also be paid to increase the family support to the patients.

  14. 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

  15. 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.

  16. Multidrug-resistant and extensively drug-resistant tuberculosis: implications for the HIV epidemic and antiretroviral therapy rollout in South Africa.

    Science.gov (United States)

    Andrews, Jason R; Shah, N Sarita; Gandhi, Neel; Moll, Tony; Friedland, Gerald

    2007-12-01

    Drug-resistant tuberculosis (TB) is emerging as a major clinical and public health challenge in areas of sub-Saharan Africa where there is a high prevalence of human immunodeficiency virus (HIV) infection. TB drug-resistance surveillance in this region has been limited by laboratory capacity and the public health infrastructure; however, with the maturation of the HIV epidemic, the burden of drug-resistant TB is increasing rapidly. The recent discovery of large numbers of cases of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB in South Africa likely represents an unrecognized and evolving epidemic rather than sporadic, localized outbreaks. The combination of a large population of HIV-infected susceptible hosts with poor TB treatment success rates, a lack of airborne infection control, limited drug-resistance testing, and an overburdened MDR-TB treatment program provides ideal conditions for an MDR-TB and XDR-TB epidemic of unparalleled magnitude. In the present article, we review the history of drug-resistant TB in South Africa, describe its interaction with the HIV epidemic and the resultant consequences, and suggest measures necessary for controlling MDR-TB and XDR-TB in this context. A successful response to the emergence of MDR-TB and XDR-TB will necessitate increased resources for and collaboration between TB and HIV programs.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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....

  2. Low Prevalence of Transmitted HIV Type 1 Drug Resistance Among Antiretroviral-Naive Adults in a Rural HIV Clinic in Kenya

    NARCIS (Netherlands)

    Hassan, Amin S.; Mwaringa, Shalton M.; Obonyo, Clare A.; Nabwera, Helen M.; Sanders, Eduard J.; Rinke de Wit, Tobias F.; Cane, Patricia A.; Berkley, James A.

    2013-01-01

    Low levels of HIV-1 transmitted drug resistance (TDR) have previously been reported from many parts of sub-Saharan Africa (sSA). However, recent data, mostly from urban settings, suggest an increase in the prevalence of HIV-1 TDR. Our objective was to determine the prevalence of TDR mutations among

  3. 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

  4. Determinants of adherence to antiretroviral drugs among people living with HIV/AIDS in the Ife-Ijesa zone of Osun state, Nigeria

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    Muhammed O. Afolabi

    2009-04-01

    Method: 120 subjects who received ARV drugs at a federal government-designated ART site located within the Obafemi Awolowo University Teaching Hospital complex, (OAUTHC, Ile-Ife, and a community-based non-governmental organisation, Living Hope Care (LIHOC, Ilesa, from February to May 2006 were serially recruited and studied. Relevant data were collected using an interviewer-administered, patient medication adherence questionnaire. Focus group discussions were also held among the subjects to further elicit qualitative information on factors influencing adherence to ART. Results: The age of participants ranged from 21 to 65 years with a mean age of 40.2 + 10.3 years. Participants had been on ARV drugs for a period ranging between three and 60 months. The overall adherence rate in the study population was 44%. 66% of participants who accessed ARV drugs from LIHOC, Ilesa, had good adherence while only 14% of participants who accessed ARV drugs from OAUTHC, Ile-Ife, had good adherence. Participants with good adherence did not pay funds for the preliminary ARV eligibility investigations and they were also offered regular adherence counselling. These facilities were barely available in the group with poor adherence. Demographic factors such as age, gender and marital status did not seem to have any significant association with adherence level (p > 0.05. Conclusion: The level of adherence was high in a cohort of PLWHA accessing ARV drugs in Ilesa while it was low among PLWHA receiving ART in Ife. The most important reasons for this difference were lack of funds for investigations and poor psycho-social counselling.

  5. CD4+ Count-Guided Interruption of Antiretroviral Treatment. The Strategies for Mangement of Antiretroviral Therapy (SMART) Study Group

    DEFF Research Database (Denmark)

    El-Sadr, WM; Lundgren, Jens Dilling; Neaton, JD

    2006-01-01

    had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less......BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who...... the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society....

  6. Challenges in Initiating Antiretroviral Therapy in 2010

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    Cécile L Tremblay

    2010-01-01

    Full Text Available Many clinical trials have shown that initiating antiretroviral therapy (ART at higher rather than lower CD4 T cell-positive counts results in survival benefit. Early treatment can help prevent end-organ damage associated with HIV replication and can decrease infectivity. The mainstay of treatment is either a non-nucleoside reverse transcriptase inhibitor or a ritonavir-boosted protease inhibitor in combination with two nucleoside reverse transcriptase inhibitors. While effective at combating HIV, ART can produce adverse alterations of lipid parameters, with some studies suggesting a relationship between some anti-retroviral agents and cardiovascular disease. As the HIV-positive population ages, issues such as hypertension and diabetes must be taken into account when initiating ART. Adhering to ART can be difficult; however, nonoptimal adherence to ART can result in the development of resistance; thus, drug characteristics and the patient’s preparedness to begin therapy must be considered. Reducing the pill burden through the use of fixed-dose antiretroviral drug combinations can facilitate adherence.

  7. The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters

    NARCIS (Netherlands)

    Martinez, Esteban; Visnegarwala, Fehmida; Grund, Birgit; Thomas, Avis; Gibert, Cynthia; Shlay, Judith; Drummond, Fraser; Pearce, Daniel; Edwards, Simon; Reiss, Peter; El-Sadr, Wafaa; Carr, Andrew

    2010-01-01

    Objective: To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters. Design: Substudy of the Strategies for Management of Anti-Retroviral Therapy study, in which participants were randomized to intermittent CD4-guided [Drug Conservation (DC) group] or

  8. Regional changes over time in initial virologic response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Kirk, Ole; Gatell, Jose M

    2006-01-01

    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS: Vi...... rates Udgivelsesdato: 2006/6...

  9. Adverse effects of antiretroviral therapy for HIV infection: a review of selected topics

    NARCIS (Netherlands)

    Nolan, David; Reiss, Peter; Mallal, Simon

    2005-01-01

    In the current era of HIV treatment, the toxicity profiles of antiretroviral drugs have increasingly emerged as a basis for selecting initial antiretroviral regimens as well as a reason for switching therapy in treatment-experienced patients. In this respect, an intensive research effort involving

  10. Adherence to On-Time ART Drug Pick-Up and Its Association with CD4 Changes and Clinical Outcomes Amongst HIV Infected Adults on First-Line Antiretroviral Therapy in Nigerian Hospitals.

    Science.gov (United States)

    Anoje, Chukwuemeka; Agu, Kenneth Anene; Oladele, Edward A; Badru, Titilope; Adedokun, Oluwasanmi; Oqua, Dorothy; Khamofu, Hadiza; Adebayo, Olufunso; Torpey, Kwasi; Chabikuli, Otto Nzapfurundi

    2017-02-01

    Medication adherence is a major determinant of antiretroviral treatment (ART) success. Promptness in medication refill pick-ups may give an indication of medication adherence. This study determined medication refill adherence among HIV positive patients on ART and its association with treatment outcomes in HIV treatment centers in Nigeria. This retrospective multi-center cohort study involved a review of ART refill records for 3534 HIV-positive patients aged 18-60 years who initiated first-line ART between January 2008 and December 2009 and were on therapy for ≥18 months after ART initiation. Drug refill records of these patients for 10 consecutive refill visits after ART initiation were analyzed. The first ten consecutive refill appointment-keeping rates after ART initiation ranged from 64.3 % to 76.1 % which decreased with successive visits. Altogether, 743 (21.1 %) patients were deemed adherent, meaning they picked up their drugs within 7 days of the drug refill appointment date on at least nine out of ten refill visits. The adherent group of patients had a mean CD4 cells increase of 206 ± 6.1 cells/dl after 12 months of ART compared to 186 ± 7.1 cells/dl reported among the nonadherent group (p = 0.0145). The proportion of patients in the adherent category who showed no OIs after 12 months on ART (81 %) was significantly higher when compared to the proportion in the non-adherent category (23.5 %), (p = 0.008). The multivariate analysis showed that the odds of being adherent was 2-3 times more in patients who had a baseline CD4 count of less than 200 cells/dl compared to those with a baseline CD4 of >350 cells/dl. (AOR 2.43, 95 % CI 1.62-3.66). In addition, for patients with baseline CD4 cell count of 201-350 cells/dl, the odds of being adherent was found to be 1.9 compared to those with baseline CD4 of greater than 350 cells/dl (AOR 1.93, 95 % CI 1.27-2.94). Pharmacy refill data can serve as an adherence measure. Adherence to on-time drug

  11. In vivo assessment of antiretroviral therapy-associated side effects

    Directory of Open Access Journals (Sweden)

    Eduardo Milton Ramos-Sanchez

    2014-07-01

    Full Text Available Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.

  12. 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.

  13. Antiretroviral Tissue Kinetics: In Vivo Imaging Using Positron Emission Tomography▿

    OpenAIRE

    Di Mascio, Michele; Srinivasula, Sharat; Bhattacharjee, Abesh; Cheng, Lily; Martiniova, Lucia; Herscovitch, Peter; Lertora, Juan; Kiesewetter, Dale

    2009-01-01

    Our current knowledge on the antiviral efficacy, dosing, and toxicity of available highly active antiretroviral therapy regimens is mostly derived from plasma or blood kinetics of anti-human immunodeficiency virus (anti-HIV) drugs. However, the blood comprises only 2% of the total target cells in the body. Tissue drug levels may differ substantially from corresponding plasma levels, and drug distribution processes may be characterized by high intertissue variability, leading to suboptimal tar...

  14. Knowledge and attitudes of HIV-infected patients on antiretroviral therapy regarding adverse drug reactions (ADRs in selected hospitals in Nigeria

    Directory of Open Access Journals (Sweden)

    Kenneth Anene Agu

    2012-01-01

    Full Text Available Purpose: The study evaluated the knowledge and attitudes of HIV-infected patients on ART regarding ADRs following routine patient counseling and education in selected hospitals in Nigeria. Materials and Methods: From 36,459 HIV-infected patients on ART in the 36 selected hospitals, a study-specific instrument was administered to 3,650 patients in a cross-sectional study. Patients were provided counseling and education on ADRs before and after commencing ART. Factor analysis was performed using principal components extraction. Item score means above midpoint (3.7 on a 5-point scale were regarded as positive attitudes and below as negative attitudes. A chi-square test was used for inferential statistics; P3.7 which denotes positive attitudes to ADRs. Three extracted factors accounted for 73.1% of cumulative variability. All attitude items had very significant loadings of ≥0.5. Conclusion: Overall, participants reported good knowledge and positive attitudes to adverse effects of their medicines compared to what was reported previously. The patient counseling and education on drug therapy provided to patients may have contributed to these findings and are highly recommended.

  15. Delays by people living with HIV/AIDS in accessing antiretroviral ...

    African Journals Online (AJOL)

    Objective: To understand, by qualitative enquiry, the underlying reasons and narratives ... denial, practical clinic constraints and appropriate types of health education. Keywords: qualitative research, delays, access, antiretroviral drugs, ARVs ...

  16. Population-based monitoring of emerging HIV-1 drug resistance on antiretroviral therapy and associated factors in a sentinel site in Cameroon: low levels of resistance but poor programmatic performance.

    Directory of Open Access Journals (Sweden)

    Serge C Billong

    Full Text Available BACKGROUND: Scale-up of antiretroviral therapy (ART in resource-limited settings has drastically reduced HIV-related morbidity and mortality. However, challenges in long-term ART, adherence and HIV drug resistance (HIVDR itself, require monitoring to limit HIVDR emergence among ART-experienced populations, in order to ensure regimen efficacy. METHODS: A longitudinal study was conducted from 2009-2011 in a cohort of 141 HIV-infected adult patients (aged >21 at the national social insurance centre hospital in Yaounde, Cameroon. As per-WHO HIVDR protocol, HIV-1 protease-reverse transcriptase genotyping was performed at baseline and at endpoint (12 months on first-line ART using ViroSeq™ Genotyping kit. RESULTS: At baseline, a prevalence of 3.6% (5/139 HIVDR was observed [protease inhibitors M46I (1/5, G73A (1/5, L90LM (1/5; nucleoside reverse transcriptase inhibitors: M184V (1/5, T215F (1/5; non-nucleoside reverse transcriptase inhibitors: K103N (1/5, Y181Y/C (2/5, M230ML (1/5]. At endpoint, 54.0% (76 patients were followed-up, 9.2% (13 died, and 3.5% (5 transferred, 38.5% (47 lost to follow-up (LTFU. 69.7% (53/76 of those followed-up had viremia <40 copies/ml and 90.8% (69/76 <1000 copies/ml. 4/7 patients with viremia ≥1000 copies/ml harbored HIVDR (prevalence: 5.3%; 4/76, with M184V/I (4/4 and K103K/N (3/4 being the most prevalent mutations. LTFU was favored by costs for consultation/laboratory tests, drug shortages, workload (physician/patient ratio: 1/180 and community disengagement. CONCLUSIONS: Low levels of HIVDR at baseline and at endpoint suggest a probable effectiveness of ART regimens used in Cameroon. However the possible high rate of HIVDR among LTFUs limited the strengths of our findings. Evaluating HIVDR among LTFU, improving adherence, task shifting, subsidizing/harmonizing costs for routine follow-up, are urgent measures to ensure an improved success of the country ART performance.

  17. Assessment of the World Health Organization's HIV Drug Resistance Early Warning Indicators in Main and Decentralized Outreach Antiretroviral Therapy Sites in Namibia.

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    Nicholus Mutenda

    Full Text Available The World Health Organization (WHO early warning indicators (EWIs of HIV drug resistance (HIVDR assess factors at individual ART sites that are known to create situations favourable to the emergence of HIVDR.In 2014, the Namibia HIV care and treatment program abstracted the following adult and pediatric EWIs from all public ART sites (50 main sites and 143 outreach sites: On-time pill pick-up, Retention in care, Pharmacy stock-outs, Dispensing practices, and Viral load suppression. Comparisons were made between main and outreach sites and between 2014 and 2012 using the Wilcoxon signed-rank test in a matched analysis.The national estimates were: On-time pill pick-up 81.9% (95% CI 81.1-82.8 for adults and 82.4% (81.3-83.4 for pediatrics, Retention in care 79% retained on ART after 12 months for adults and 82% for pediatrics, Pharmacy stock-outs 94% of months without a stock-out for adults and 88% for pediatrics, and Dispensing practices 0.01% (0.001-0.056 dispensed mono- or dual-therapy for adults and 0.01% (0.001-0.069 for pediatrics. Viral load suppression was significantly affected by low rates of Viral load completion. Main sites had higher On-time pill pick-up than outreach sites for adults (p<0.001 and pediatrics (p<0.001, and no difference between main and outreach sites for Retention in care for adults (p = 0.761 or pediatrics (p = 0.214. From 2012 to 2014 in adult sites, On-time pill pick-up (p = 0.001, Retention in care (p<0.001, and Pharmacy stock-outs (p = 0.002 worsened. In pediatric sites, On-time pill pick-up (p<0.001 and Pharmacy stock-outs (p = 0.012 worsened.Results of EWIs monitoring in Namibia provide evidence about ART programmatic functioning and contextualize results from national surveys of HIVDR. These results are worrisome as they show a decline in program performance over time. The national ART program is taking steps to minimize the emergence of HIVDR by strengthening adherence and retention of patients on ART

  18. Accessibility of antiretroviral therapy in Ghana: Convenience of access

    African Journals Online (AJOL)

    Joyce Addo-Atuah * Joyce Addo-Atuah, BPharm, MSc, PhD, Assistant Professor, Touro College of Pharmacy, New York, USA. She was a PhD candidate at the University of Tennessee (UT), Memphis, USA, when the study was undertaken in Ghana. joyce.addo-atuah@touro.edu, Dick Gourley Dick Gourley, PharmD, Professor and Dean, UT College of Pharmacy during the study and major research advisor. , Greta Gourley Greta Gourley, PharmD/PhD, retired Associate Professor of Pharmaceutical Sciences at UT College of Pharmacy and research advisor. , Shelley I. White-Means Shelley I. White-Means, PhD, Professor and Chair, Health Outcomes and Policy Research Division of UT College of Pharmacy at time of the study and research advisor. , Robin J. Womeodu Robin J. Womeodu, MD, F.A.C.P., Associate Professor of Internal Medicine and Preventive Medicine at UT College of Medicine at time of study and research advisor. , Richard J. Faris Richard J. Faris, Assistant Professor at UT College of Pharmacy at time of study and research advisor. &

    2012-05-30

    May 30, 2012 ... The accuracy of any instructions, formulae, and drug doses ... The convenience of accessing antiretroviral therapy (ART) is ...... tious diseases, paediatrics, chest diseases, dermatology, public .... CD4 count, (2) a full blood count, (3) a liver function test, (4) ..... America: measures of the African brain drain.

  19. Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.

    Science.gov (United States)

    Mbuagbaw, Lawrence; Mursleen, Sara; Irlam, James H; Spaulding, Alicen B; Rutherford, George W; Siegfried, Nandi

    2016-12-10

    The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. This systematic review was first published in 2010. To determine which non-nucleoside reverse transcriptase inhibitor, either EFV or NVP, is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children. We attempted to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings up to 12 August 2016. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov to 12 August 2016. We searched LILACS (Latin American and Caribbean Health Sciences Literature) and the Web of Science from 1996 to 12 August 2016. We checked the National Library of Medicine (NLM) Gateway from 1996 to 2009, as it was no longer available after 2009. We included all randomized controlled trials (RCTs) that compared EFV to NVP in people with HIV without prior exposure to ART, irrespective of the dosage or NRTI's given in combination.The primary outcome of interest was virological success. Other primary outcomes included mortality, clinical progression to AIDS, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were change in CD4 count, treatment failure

  20. The Effect of a Multi-Level Intervention on the Initiation of Antiretroviral Therapy (ART) among HIV-Infected Men Who Inject Drugs and Were Diagnosed Late in Thai Nguyen, Vietnam

    Science.gov (United States)

    Zelaya, Carla E.; Le Minh, Nguyen; Lau, Bryan; Latkin, Carl A.; Viet Ha, Tran; Minh Quan, Vu; Mo, Thi Tran; Sripaipan, Teerada; Davis, Wendy W.; Celentano, David D.; Frangakis, Constantine; Go, Vivian F.

    2016-01-01

    Background In Vietnam, an estimated 256,000 people are living with HIV, and 58% of HIV-infections reported are among people who inject drugs (PWID). While antiretroviral therapy (ART) is widely available in Vietnam, marginalized hard-to-reach male PWID, demonstrate significantly reduced and delayed access to ART. Methods We investigated the effect of a randomized four-arm multi-level intervention trial on ART initiation among male PWID. Our analysis was conducted among a subset of trial participants (n = 136), who were newly diagnosed as HIV-infected, treatment naïve, and eligible for ART (baseline late diagnosis). The trial arms included: 1, standard of care (HIV testing and counseling); 2, structural-level intervention (door-to-door communications and community video screenings); 3, individual-level intervention (counseling plus group support); and 4, individual-level plus structural-level intervention. In a time-to-event analysis, we used a non-parametric approach for competing risks to estimate cumulative incidence function (CIF) for ART initiation (event of interest) by arm and the difference in CIF for each trial arm as compared to Arm 1. Follow-up was conducted at 6, 12, 18 and 24 months. Data collection occurred from 2009 to 2013. Findings By 24-months, 61.0% initiated ART, and 30.9% had died prior to ART initiation. In the first 6 months, participants in arm 4 (individual plus community intervention) had a 28% (95% confidence interval (CI): 6–50%) increased probability of initiating ART. Despite increasing coverage of ART in all arms throughout follow-up, participants in arm 4 retained a 31% (95% CI: 5–56%) increased probability of initiating ART. The individual and community components of the intervention were only effective when delivered together. Conclusions Marginalized, hard-to-reach men, who do not routinely engage in HIV services, and therefore come into care late, may benefit significantly from both individual counseling and group support, in

  1. Types of HIV/AIDS Antiretroviral Drugs

    Science.gov (United States)

    ... Relations Cyber Infrastructure Computational Biology Equal Employment Opportunity Ethics Global Research Office of Mission Integration and Financial Management Strategic Planning Workforce Effectiveness Workplace Solutions Technology Transfer Intellectual Property Division of AIDS ...

  2. 3-12 Detection and Management of Adverse Drug React

    African Journals Online (AJOL)

    MINA SAN

    Detection and Management of Adverse Drug Reactions Related to Antiretroviral Drugs among. HIV/AIDS Patients in Kiambu ... of various adverse drug reactions associated with antiretroviral drugs occurring in patients attending Comprehensive Care .... educational level, perception of ADRs, knowledge of ADRs, detection ...

  3. Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

    Directory of Open Access Journals (Sweden)

    Balkundi S

    2011-12-01

    Full Text Available Shantanu Balkundi1, Ari S Nowacek1, Ram S Veerubhotla1, Han Chen2, Andrea Martinez-Skinner1, Upal Roy1, R Lee Mosley1,3, Georgette Kanmogne1, Xinming Liu1,3,4, Alexander V Kabanov3,4, Tatiana Bronich3,4, JoEllyn McMillan1, Howard E Gendelman1,31Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA; 2Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA; 3Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE, USA; 4Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility.Keywords: human immunodeficiency virus type one, nanotoxicology, monocyte-derived macrophage, nanoformulated antiretroviral therapy, manufacturing techniques

  4. Efek Samping Obat terhadap Kepatuhan Pengobatan Antiretroviral Orang dengan HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Fachri Latif

    2014-12-01

    Full Text Available Tingkat kepatuhan pengobatan antiretroviral di Indonesia sangat rendah, yaitu 40 - 70%, yang masih di bawah target nasional dengan tingkat kepatuhan 95%. Berbeda dengan rata-rata nasional, Puskesmas Jumpandang Baru justru memiliki tingkat kepatuhan pengobatan antiretroviral pasien HIV/AIDS di atas 95%. Penelitian ini bertujuan untuk menganalisis faktor yang paling berpengaruh terhadap kepatuhan pengobatan antiretroviral orang dengan HIV/AIDS (ODHA. Jenis penelitian bersifat observasional analitik dengan pendekatan potong lintang. Populasi penelitian adalah 121 ODHA yang aktif menjalani pengobatan antiretroviral di Puskesmas Jumpandang Baru yang dipilih dengan menggunakan teknik exhaustive sampling. Sampel dalam penelitian ini adalah 121 sampel. Penelitian dilakukan pada 22 April hingga 28 Juni 2014 di klinik Voluntary Counseling and Test Puskesmas Jumpandang Baru Makassar. Analisis data menggunakan uji kai kuadrat dan regresi logistik. Hasil uji kai kuadrat menunjukkan ada hubungan antara pengetahuan, persepsi, riwayat efek samping obat, dukungan keluarga dan teman, serta interaksi antara pasien dengan petugas layanan antiretroviral terhadap kepatuhan pengobatan antiretroviral ODHA. Analisis regresi logistik menunjukan bahwa pengetahuan yang baik, persepsi positif terhadap pengobatan, serta efek samping obat yang tidak dirasakan adalah faktor yang berhubungan dengan kepatuhan pengobatan antiretroviral. Penelitian ini menunjukkan ODHA yang tidak merasakan efek samping obat memiliki kecenderungan terbesar untuk patuh terhadap pengobatan antiretroviral dengan OR sebesar 13,452. Drug Side Effects on Adherence to Antiretroviral Treatment among People Living with HIV/AIDS The rate of adherence to antiretroviral treatment in Indonesia is very low, at 40 - 70%, which is still below our national target (95%. Different phenomena happens at Jumpandang Baru Primary Health Care, whose level of antiretroviral treatment adherence above 95%. This study aimed to

  5. 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

  6. Quality of life of people living with HIV and AIDS and antiretroviral therapy

    OpenAIRE

    Oguntibeju, Oluwafemi

    2012-01-01

    Oluwafemi O OguntibejuOxidative Stress Research Centre, Cape Peninsula University of Technology, Bellville, South AfricaAbstract: The development of antiretroviral drugs has significantly changed the perception of HIV/AIDS from a very fatal to a chronic and potentially manageable disease, and the availability and administration of antiretroviral therapy (ART) has significantly reduced mortality and morbidity associated with HIV and AIDS. There is a relationship between ART and quality of life...

  7. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection

    DEFF Research Database (Denmark)

    Cooper, David A; Steigbigel, Roy T; Gatell, Jose M

    2008-01-01

    BACKGROUND: We evaluated the efficacy of raltegravir and the development of viral resistance in two identical trials involving patients who were infected with human immunodeficiency virus type 1 (HIV-1) with triple-class drug resistance and in whom antiretroviral therapy had failed. METHODS: We c...

  8. Current status of topical antiretroviral chemoprophylaxis.

    Science.gov (United States)

    Van Damme, Lut; Szpir, Michael

    2012-11-01

    Recent studies suggest that the vaginal delivery of antiretroviral (ARV) agents - such as tenofovir, dapivirine and UC781 - may be a promising way to reduce the high rates of HIV infection among women in developing countries. This review examines these developments. The Microbicide Trials Network 003 study, a large phase IIb trial, was unable to show that daily dosing with 1% tenofovir vaginal gel was effective for HIV prevention. Nevertheless, preclinical and early-phase clinical trials suggest that ARV drugs - formulated in vaginal gels, rings, films, tablets and diaphragms - could be effective for HIV chemoprophylaxis. Investigations of topical chemoprophylaxis methods have seen mixed results in the past 12-18 months. Product adherence may prove to be one of the field's greatest challenges. Phase II and III trials continue to explore different dosing strategies for topical products that contain one or more ARV agents.

  9. Challenges and perspectives of compliance with pediatric antiretroviral therapy in Sub-Saharan Africa.

    Science.gov (United States)

    Dahourou, D L; Leroy, V

    2017-12-01

    More than 3 million children aged less than 15years are infected with HIV worldwide, mainly in Sub-Saharan Africa. The survival of HIV-infected children depends on their access to antiretroviral therapy whose success mainly depends on a good life-long compliance with antiretroviral therapy. Given its complexity and specificity, assessment and monitoring of pediatric compliance with antiretroviral therapy is a major challenge. There is no consensus on a gold standard for monitoring compliance with antiretroviral therapy. Compliance is also influenced by many factors related to the child, the caregiver, the healthcare staff, the healthcare system, and antiretroviral drugs. This review aimed to assess scientific knowledge on pediatric compliance with antiretroviral therapy in Sub-Saharan Africa, and to identify areas for future interventions to improve compliance. Good compliance is essential to achieve the "90% coverage of children on antiretroviral therapy" gold standard of the World Health Organization, and to eliminate HIV infection by 2030. Copyright © 2017. Published by Elsevier SAS.

  10. The cost of antiretroviral therapy in Haiti

    Directory of Open Access Journals (Sweden)

    Fitzgerald Daniel W

    2008-02-01

    Full Text Available Abstract Background We determined direct medical costs, overhead costs, societal costs, and personnel requirements for the provision of antiretroviral therapy (ART to patients with AIDS in Haiti. Methods We examined data from 218 treatment-naïve adults who were consecutively initiated on ART at the GHESKIO Center in Port-au-Prince, Haiti between December 23, 2003 and May 20, 2004 and calculated costs and personnel requirements for the first year of ART. Results The mean total cost of treatment per patient was $US 982 including $US 846 in direct costs, $US 114 for overhead, and $US 22 for societal costs. The direct cost per patient included generic ART medications $US 355, lab tests $US 130, nutrition $US 117, hospitalizations $US 62, pre-ART evaluation $US 58, labor $US 51, non-ART medications $US 39, outside referrals $US 31, and telephone cards for patient retention $US 3. Higher treatment costs were associated with hospitalization, change in ART regimen, TB treatment, and survival for one year. We estimate that 1.5 doctors and 2.5 nurses are required to treat 1000 patients in the first year after initiating ART. Conclusion Initial ART treatment in Haiti costs approximately $US 1,000 per patient per year. With generic first-line antiretroviral drugs, only 36% of the cost is for medications. Patients who change regimens are significantly more expensive to treat, highlighting the need for less-expensive second-line drugs. There may be sufficient health care personnel to treat all HIV-infected patients in urban areas of Haiti, but not in rural areas. New models of HIV care are needed for rural areas using assistant medical officers and community health workers.

  11. 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.

  12. 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.

  13. When to start antiretroviral therapy

    DEFF Research Database (Denmark)

    Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred M

    2013-01-01

    Strategies for use of antiretroviral therapy (ART) have traditionally focused on providing treatment to persons who stand to benefit immediately from initiating the therapy. There is global consensus that any HIV+ person with CD4 counts less than 350 cells/μl should initiate ART. However, it rema...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... people on HAART (highly active antiretroviral therapy), for example, who continue to misuse drugs. The Learn the Link public service campaign is just one example of how NIDA continues to respond to the ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Search Publications Orderable DrugFacts Research Reports Mind Over Matter Science of Addiction Funding Funding Opportunities Clinical Research ... is largely because of treatment with HAART (highly active antiretroviral therapy), a combination of three or more ...

  16. Treatment and prevention of HIV infection with long-acting antiretrovirals.

    Science.gov (United States)

    Benítez-Gutiérrez, Laura; Soriano, Vicente; Requena, Silvia; Arias, Ana; Barreiro, Pablo; de Mendoza, Carmen

    2018-05-01

    Current antiretroviral therapy allows to achieve and sustain maximal suppression of HIV replication in most treated patients. As result, the life expectancy of HIV-infected persons has improved dramatically and is nowadays similar to that of the HIV-negative population. However, oral antiretrovirals have to be taken daily and indefinitely to avoid resumption of HIV replication and selection of drug resistance. Unfortunately, drug adherence is often suboptimal and tends to decline over time. Areas covered: New drugs, formulations and delivery systems are being developed for extended-release of antiretrovirals. At this time, intramuscular cabotegravir and rilpivirine, dapivirine vaginal rings and tenofovir alafenamide subdermal implants are the products in more advanced stages of clinical development. Their pharmacokinetics/dynamics and safety/efficacy are reviewed. Expert commentary: In the absence of eradicative therapy for individuals with HIV infection and protective vaccines for persons at risk, long-term antiretroviral therapy is the best approach for preventing disease progression in patients and halting transmissions, either as result of 'treatment as prevention' for HIV carriers or 'pre-exposure prophylaxis' for uninfected individuals at risk. In all these scenarios, the advent of long-acting antiretrovirals will expand options for overcoming the challenge of suboptimal drug adherence and reduce the burden of HIV infection.

  17. Renal impairment in a rural African antiretroviral programme

    Directory of Open Access Journals (Sweden)

    Lessells Richard J

    2009-08-01

    Full Text Available Abstract Background There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes Methods (i Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ≤ 30 mls/min/1.73 m2 and 30–60 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR of significantly impaired renal function (combining severe and moderate impairment. Co-variates for analysis were age, sex and CD4 count at initiation. Results (i There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8–1.8 whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6–14.5 with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/μl. In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54–6.1, male gender (aOR 1.89, 95% C.I. 1.39–2.56 and CD4 Conclusion In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited.

  18. Untangling the cost-effectiveness knot: who is oral antiretroviral HIV pre-exposure prophylaxis really for?

    NARCIS (Netherlands)

    Hankins, Catherine A.

    2014-01-01

    Clinical trials of HIV pre-exposure prophylaxis (PrEP) antiretroviral drugs have shown excellent protection against HIV acquisition when plasma drug levels are detectable, indicating good adherence. Cost-effectiveness depends on epidemic context, adherence, drug cost, and other factors. For

  19. Análisis costo-efectividad de la farmacoterapia antirretroviral para los pacientes VIH/SIDA en Cuba Cost-effectiveness analysis of the antiretroviral drug therapy for HIV/AIDS patients in Cuba

    Directory of Open Access Journals (Sweden)

    Manuel Miguel Collazo Herrera

    2005-04-01

    Full Text Available Se determinó el impacto económico-social en términos de salud por el empleo de los antirretrovirales extranjeros durante un año, y su comparación con la ausencia de este tratamiento. Otro aspecto fue la comparación en cuanto a costos y a eficiencia de estos esquemas de tratamiento, con la incorporación de los antirretrovirales de producción nacional, bajo la premisa de presentar una similar efectividad. Se realizó un estudio retrospectivo con 59 historias clínicas para la determinación de la efectividad, medida por la supervivencia de los pacientes, y expresada por el año de vida ganado, así como por su mejoría clínica e inmunológica. Se estimaron los costos incurridos con el empleo de la farmacoterapia y la hospitalización, y se realizó la evaluación económica mediante las técnicas de análisis costo-efectividad, y de minimización de costos para distintas alternativas de tratamiento. Se obtuvo una supervivencia del 96,6 % de los pacientes, así como resultados favorables del 81,4 % en la mejoría clínica e inmunológica de los casos, pero a un elevado costo promedio de US $ 5 523.7/paciente, para una relación costo-efectividad de $ 5 717.6/año de vida ganado y de $ 6 789.6/caso mejorado. El empleo de los antirretrovirales extranjeros producen unos beneficios en la salud, pero incrementan los costos de la farmacoterapia, aspecto que conspira en contra de la eficiencia del tratamiento. Por esto, se reafirma la conveniencia económica de la producción nacional de los antirretrovirales, ya que se podrá obtener este beneficio sobre la salud de los pacientes, a un costo más razonable para el país.The economic and social impact in terms of health due to the use of foreign antiretrovirals for a year was determined and a comparison with the absence of this treatment was made. Another aspect was the comparison as regards costs and efficiency of these treatment schemes, with the incorporation of antiretrovirals of national

  20. Opportunistic disease and mortality in patients coinfected with hepatitis B or C virus in the strategic management of antiretroviral therapy (SMART) study

    DEFF Research Database (Denmark)

    Tedaldi, Ellen; Peters, Lars; Neuhaus, Jacquie

    2008-01-01

    BACKGROUND: In the Strategic Management of Antiretroviral Therapy (SMART) study, the risk of opportunistic disease (OD) and/or death due to any cause was elevated in the drug conservation (i.e., interrupt antiretroviral therapy until the CD4(+) cell count is

  1. Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration.

    Directory of Open Access Journals (Sweden)

    Rami Kantor

    2005-04-01

    Full Text Available The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate.To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80% of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates.Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

  2. Análisis de la problemática para la adquisición de los antirretrovirales VIH/SIDA en los países del Tercer Mundo Analysis of the problem to acquire HIV/AIDS antiretroviral drugs in the Third World countries

    Directory of Open Access Journals (Sweden)

    Manuel M. Collazo Herrera

    2004-08-01

    the existing problem for the acquisition of the HIV/AIDS antiretroviral drugs in the world context, mainly with the situation of the developing countries, which have to invest enough economic resources in the health sphere that are not available at present in the poorest countries in order to obtain global acces to treatment. This is motivated by the high prices of the antiretroviral drugs set by the pharmaceutical transnationals at the world market This aspect has a considerable impact in the increase of the treatment costs and it is one of the main obstacles for their availabilty in the Third World countries. Due to the dramatic panorama of HIV/AIDS in the world, the international community has pronounced itself in favor of reaching different agreements between the antiretroviral drugs producers and the goverments of the developing countries to attain an important reduction of the antiretroviral treatment cost. There are also local initiatives of some underdeveloped nations to produce these drugs to guarantee a sustained global access of patients to this therapy. All these efforts are directed to a common purpose: to have the greatest amount of antiretrovirals in the therapeutic arsenal for treating HIV/AIDS, as well as to look for different ways for the acquisition of these drugs under more favorable economic conditions than the existing at the international pharmaceutical market for the poorest countries, making possible the obtention of the health benefit for patients at a more reasonable cost for the damaged economies of the underdeveloped countrties.

  3. Cost-Effectiveness of Antiretroviral Therapy for Multidrug-Resistant HIV: Past, Present, and Future

    Directory of Open Access Journals (Sweden)

    Marianne Harris

    2012-01-01

    Full Text Available In the early years of the highly active antiretroviral therapy (HAART era, HIV with resistance to two or more agents in different antiretroviral classes posed a significant clinical challenge. Multidrug-resistant (MDR HIV was an important cause of treatment failure, morbidity, and mortality. Treatment options at the time were limited; multiple drug regimens with or without enfuvirtide were used with some success but proved to be difficult to sustain for reasons of tolerability, toxicity, and cost. Starting in 2006, data began to emerge supporting the use of new drugs from the original antiretroviral classes (tipranavir, darunavir, and etravirine and drugs from new classes (raltegravir and maraviroc for the treatment of MDR HIV. Their availability has enabled patients with MDR HIV to achieve full and durable viral suppression with more compact and cost-effective regimens including at least two and often three fully active agents. The emergence of drug-resistant HIV is expected to continue to become less frequent in the future, driven by improvements in the convenience, tolerability, efficacy, and durability of first-line HAART regimens. To continue this trend, the optimal rollout of HAART in both rich and resource-limited settings will require careful planning and strategic use of antiretroviral drugs and monitoring technologies.

  4. HIV-Antiretroviral Therapy Induced Liver, Gastrointestinal, and Pancreatic Injury

    Directory of Open Access Journals (Sweden)

    Manuela G. Neuman

    2012-01-01

    Full Text Available The present paper describes possible connections between antiretroviral therapies (ARTs used to treat human immunodeficiency virus (HIV infection and adverse drug reactions (ADRs encountered predominantly in the liver, including hypersensitivity syndrome reactions, as well as throughout the gastrointestinal system, including the pancreas. Highly active antiretroviral therapy (HAART has a positive influence on the quality of life and longevity in HIV patients, substantially reducing morbidity and mortality in this population. However, HAART produces a spectrum of ADRs. Alcohol consumption can interact with HAART as well as other pharmaceutical agents used for the prevention of opportunistic infections such as pneumonia and tuberculosis. Other coinfections that occur in HIV, such as hepatitis viruses B or C, cytomegalovirus, or herpes simplex virus, further complicate the etiology of HAART-induced ADRs. The aspect of liver pathology including liver structure and function has received little attention and deserves further evaluation. The materials used provide a data-supported approach. They are based on systematic review and analysis of recently published world literature (MedLine search and the experience of the authors in the specified topic. We conclude that therapeutic and drug monitoring of ART, using laboratory identification of phenotypic susceptibilities, drug interactions with other medications, drug interactions with herbal medicines, and alcohol intake might enable a safer use of this medication.

  5. Preliminary investigation of adherence to antiretroviral therapy ...

    African Journals Online (AJOL)

    Treatment of HIV with highly active antiretroviral therapy (HAART) has resulted in declining morbidity and mortality rates from HIV-associated diseases, but concerns regarding access and adherence are growing. To determine the adherence level and the reasons for non-adhering to antiretroviral therapy (ART) among ...

  6. Interruption of antiretroviral therapy is associated with increased plasma cystatin C

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Wyatt, Christina; Szczech, Lynda

    2009-01-01

    BACKGROUND: Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4 cell count (drug conservation) had altered cystatin C levels compared with those randomized to contin...

  7. When to start antiretroviral therapy and what to start with - A european perspective

    NARCIS (Netherlands)

    Wit, Ferdinand W. N. M.; Reiss, Peter

    2003-01-01

    Although antiretroviral combination therapy has greatly improved the life expectancy of HIV-infected individuals, its use is hampered by considerable toxicity, the need for life-long near-perfect adherence to strict dosing regimens in order to avoid the emergence of drug resistance, and high cost.

  8. Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis

    NARCIS (Netherlands)

    Gupta, Ravindra K.; Jordan, Michael R.; Sultan, Binta J.; Hill, Andrew; Davis, Daniel H. J.; Gregson, John; Sawyer, Anthony W.; Hamers, Raph L.; Ndembi, Nicaise; Pillay, Deenan; Bertagnolio, Silvia

    2012-01-01

    Background The emergence and spread of high levels of HIV-1 drug resistance in resource-limited settings where combination antiretroviral treatment has been scaled up could compromise the effectiveness of national HIV treatment programmes. We aimed to estimate changes in the prevalence of HIV-1 drug

  9. Prices of second-line antiretroviral treatment for middle-income countries inside versus outside sub-Saharan Africa.

    Science.gov (United States)

    Simmons, Bryony; Hill, Andrew; Ford, Nathan; Ruxrungtham, Kiat; Ananworanich, Jintanat

    2014-01-01

    Antiretrovirals are available at low prices in sub-Saharan Africa, but these prices may not be consistently available for middle-income countries in other regions with large HIV epidemics. Over 30% of HIV infected people live in countries outside sub-Saharan Africa. Several key antiretrovirals are still on patent, with generic production restricted. We assessed price variations for key antiretroviral drugs inside versus outside sub-Saharan Africa. HIV drug prices used in national programmes (2010-2014) were extracted from the WHO Global Price Reporting Mechanism database for all reporting middle-income countries as classified by the World Bank. Treatment costs (branded and generic) were compared for countries inside sub-Saharan Africa versus those outside. Five key second-line antiretrovirals were analysed: abacavir, atazanavir, darunavir, lopinavir/ritonavir, raltegravir. Prices of branded antiretrovirals were significantly higher outside sub-Saharan Africa (psub-Saharan Africa versus $4689 (IQR $4075-5717) in non-African middle-income countries, an increase of 541%. However, when supplied by generic companies, most antiretrovirals were similarly priced between countries in sub-Saharan Africa and other regions. Pharmaceutical companies are selling antiretrovirals to non-African middle-income countries at prices 74-541% higher than African countries with similar gross national incomes. However, generic companies are selling most of these drugs at similar prices across regions. Mechanisms to ensure fair pricing for patented antiretrovirals across both African and non-African middle-income countries need to be improved, to ensure sustainable treatment access.

  10. Antiretroviral treatment switch strategies for lowering the costs of antiretroviral therapy in subjects with suppressed HIV-1 viremia in Spain

    Directory of Open Access Journals (Sweden)

    Llibre JM

    2013-05-01

    Full Text Available Josep M Llibre,1,2 Gloria Cardona,3 José R Santos,2 Angels Andreu,3 Josep O Estrada,4 Jordi Ara,4 Xavier Bonafont,3 Bonaventura Clotet1,21HIV Unit, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 2Lluita contra la SIDA Foundation, Badalona, Barcelona, Spain; 3Hospital Pharmacy, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 4Hospital Management, University Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainBackground: The current economic recession in European countries has forced governments to design emergency measures to reduce spending on drugs, including antiretroviral therapy (ART. Switching antiretroviral drugs for others that have the same efficacy and safety profile at a lower cost (cost-reduction measures, CRM could prove to be a valid means of generating savings.Methods: Descriptive study of prospective consensus-based CRM undertaken in 2011 in a Catalonian hospital HIV unit among patients with prolonged plasma HIV-1 RNA <50 copies/mL.Results: During the study period, we made 673 switches (87.5% more than the previous year, of which 378 (56.2% were CRM (16% of all patients treated, leading to a savings of €87,410/month. Switching tenofovir/emtricitabine for abacavir/lamivudine was the most common CRM (129, 31.3%, followed by simplification to boosted protease inhibitor monotherapy (bPImono, 102, 26%. The CRM that generated the greatest saving were switching to bPImono (38%, withdrawal or replacement of raltegravir (24%, switching tenofovir/emtricitabine for abacavir/lamivudine (13%, and switching to nevirapine (5%. Cost savings with CRM were slightly higher than those achieved with medication paid for by clinical trial sponsors (€80,333/month or through discount arrangements (€76,389/month.Conclusion: Proactively switching antiretroviral therapy in selected treated patients with sustained virological suppression can generate significant cost savings in pharmacy spending in

  11. Scaling-up antiretroviral therapy in Malawi.

    Science.gov (United States)

    Jahn, Andreas; Harries, Anthony D; Schouten, Erik J; Libamba, Edwin; Ford, Nathan; Maher, Dermot; Chimbwandira, Frank

    2016-10-01

    In Malawi, health-system constraints meant that only a fraction of people infected with human immunodeficiency virus (HIV) and in immediate need of antiretroviral treatment (ART) received treatment. In 2004, the Malawian Ministry of Health launched plans to scale-up ART nationwide, adhering to the principle of equity to ensure fair geographical access to therapy. A public health approach was used with standardized training and treatment and regular supervision and monitoring of the programme. Before the scale-up, an estimated 930 000 people in Malawi were HIV-infected, with 170 000 in immediate need of ART. About 3000 patients were on ART in nine clinics. By December 2015, cumulatively 872 567 patients had been started on ART from 716 clinics, following national treatment protocols and using the standard monitoring system. Strong national leadership allowed the ministry of health to implement a uniform system for scaling-up ART and provided benchmarks for implementation on the ground. New systems of training staff and accrediting health facilities enabled task-sharing and decentralization to peripheral health centres and a standardized approach to starting and monitoring ART. A system of quarterly supervision and monitoring, into which operational research was embedded, ensured stocks of drug supplies at facilities and adherence to national treatment guidelines.

  12. 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.

  13. Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons

    DEFF Research Database (Denmark)

    Nielsen, Lene Ryom; Lundgren, Jens Dilling; De Wit, Stéphane

    2016-01-01

    OBJECTIVES: Although several antiretroviral drugs, including the d-drugs stavudine (d4T) and didanosine (ddI), may cause biomarker-defined hepatotoxicity, their association with clinically defined end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) remains unknown. DESIGN: Prospective...

  14. Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons

    NARCIS (Netherlands)

    Ryom, Lene; Lundgren, Jens Dilling; de Wit, Stéphane; Kovari, Helen; Reiss, Peter; Law, Matthew; El-Sadr, Wafa; Monforte, Antonella D.'Arminio; Mocroft, Amanda; Smith, Colette; Fontas, Eric; Dabis, Francois; Phillips, Andrew; Sabin, Caroline

    2016-01-01

    Although several antiretroviral drugs, including the d-drugs stavudine (d4T) and didanosine (ddI), may cause biomarker-defined hepatotoxicity, their association with clinically defined end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) remains unknown. Prospective cohort study. Data

  15. Regional changes over time in initial virological response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, W; Kirk, O; Gatell, J

    2006-01-01

    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS.......026) and time (P changes were observed (south, P = 0.061; central west, P ....001; north: P = 0.070; east, P = 0.001). CONCLUSIONS: There was some evidence of regional differences in initial virologic response to cART. Improvements over time were observed, suggesting that so far, the effect of primary resistance has not been of sufficient magnitude to prevent increasing suppression...

  16. The Impact of Non-Antiretroviral Polypharmacy on the Continuity of Antiretroviral Therapy (ART) Among HIV Patients.

    Science.gov (United States)

    Krentz, Hartmut B; Gill, M John

    2016-01-01

    Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy.

  17. Effects of antiretroviral therapy on immunity in patients infected with HIV.

    Science.gov (United States)

    Feola, D J; Thornton, A C; Garvy, B A

    2006-01-01

    Drug therapy for human immunodeficiency virus (HIV) is highly effective in suppressing viral replication and restoring immune function in patients with HIV. However, this same treatment can also be associated with immunotoxicity. For example, zidovudine and various other antiretroviral agents are capable of causing bone marrow suppression. Agents used to treat opportunistic infections in these individuals, including ganciclovir, foscarnet, and sulfamethoxazole-trimethoprim, can cause additional hematotoxicity. Drug-drug interactions must also be considered and managed in order to control iatrogenic causes of immunotoxicity. In this review, we examine the normal immune response to HIV, and the benefits of antiretroviral therapy in prolonging immune function. We then discuss immune-related adverse effects of drugs used to treat HIV and the opportunistic infections that are common among these patients. Finally, we address in vitro, animal, and clinical evidence of toxicity associated with various combination use of these agents.

  18. Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review.

    Science.gov (United States)

    Cysique, Lucette A; Brew, Bruce J

    2009-06-01

    This article presents a review of studies that have investigated the neuropsychological effects of antiretroviral treatment (ART) for HIV-1 infection. It provides a brief overview of the era of monotherapy, dual-therapy, and an extended overview of the current era of combination antiretroviral therapy (CART). This review highlights that while CART has had a dramatic effect on the incidence and the severity of HIV-associated neurocognitive disorders (HAND), HAND, in its mild form, still remains prevalent. New causes of this sustained prevalence are poor CNS penetration of some antiretroviral agents, drug resistance, poor adherence, potential neurotoxicity, co-morbidities such as the long-term CART side effects in relation to cardio-vascular disease, and chronic HIV brain infection that may facilitate the expression of new forms of neurodegenerative processes. The review emphasizes the need to address methodological limitations of published studies and the need for large and representative cross-disciplinary longitudinal investigations across the HIV illness span.

  19. Antiretroviral therapy during pregnancy and the risk of an adverse outcome.

    Science.gov (United States)

    Tuomala, Ruth E; Shapiro, David E; Mofenson, Lynne M; Bryson, Yvonne; Culnane, Mary; Hughes, Michael D; O'Sullivan, M J; Scott, Gwendolyn; Stek, Alice M; Wara, Diane; Bulterys, Marc

    2002-06-13

    Some studies suggest that combination antiretroviral therapy in pregnant women with human immunodeficiency virus type 1 (HIV-1) infection increases the risk of premature birth and other adverse outcomes of pregnancy. We studied pregnant women with HIV-1 infection who were enrolled in seven clinical studies and delivered their infants from 1990 through 1998. The cohort comprised 2123 women who received antiretroviral therapy during pregnancy (monotherapy in 1590, combination therapy without protease inhibitors in 396, and combination therapy with protease inhibitors in 137) and 1143 women who did not receive antiretroviral therapy. After standardization for the CD4+ cell count and use or nonuse of tobacco, alcohol, and illicit drugs, the rate of premature delivery (women who received antiretroviral therapy and those who did not (16 percent and 17 percent, respectively); the rate of low birth weight (women who received combination therapy with protease inhibitors (5 percent) had infants with very low birth weight, as compared with nine women who received combination therapy without protease inhibitors (2 percent) (adjusted odds ratio, 3.56; 95 percent confidence interval, 1.04 to 12.19). As compared with no antiretroviral therapy or monotherapy, combination therapy for HIV-1 infection in pregnant women is not associated with increased rates of premature delivery or with low birth weight, low Apgar scores, or stillbirth in their infants. The association between combination therapy with protease inhibitors and an increased risk of very low birth weight requires confirmation.

  20. Platelet count kinetics following interruption of antiretroviral treatment.

    Science.gov (United States)

    Zetterberg, Eva; Neuhaus, Jacqueline; Baker, Jason V; Somboonwit, Charurut; Llibre, Josep M; Palfreeman, Adrian; Chini, Maria; Lundgren, Jens D

    2013-01-02

    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. SMART patients from sites that determined platelets routinely. Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2. Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: -24 000/μl (-54 000 to 4000) vs. 3000 (-22 000 to 24 000), respectively, P conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2-2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = -0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels. Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study.

  1. ORIGINAL ARTICLES Antiretroviral treatment for children

    African Journals Online (AJOL)

    Kaplan-Meier survival estimate for 407 children at 1 year was. 84% (95% ... highly active antiretroviral therapy (HAART) to 3 million people living with HIV I AIDS in ... 5 Furthermore, improvements in growth and body composition parameters,.

  2. ORIGINAL ARTICLES Estimation of adult antiretroviral treatment ...

    African Journals Online (AJOL)

    workplace treatment programmes (WPTPs) and NGO ..... Our analysis also demonstrates significant inequality .... paying for their own treatment outside of DMPs,15 which may ... of antiretroviral coverage in men and women and to develop.

  3. Hospitalization due to Adverse Drug Reactions and Drug Interactions before and after HAART

    Directory of Open Access Journals (Sweden)

    Michelle M Foisy

    2000-01-01

    Full Text Available OBJECTIVE: To characterize and compare the rates of adverse drug reactions (ADRs and interactions on admission in two, one-year periods: pre-highly active antiretroviral therapy (HAART (phase 1 and post-HAART (phase 2.

  4. North-South Corridor Demonstration Project: Ethical and Logistical Challenges in the Design of a Demonstration Study of Early Antiretroviral Treatment for Long Distance Truck Drivers along a Transport Corridor through South Africa, Zimbabwe, and Zambia

    NARCIS (Netherlands)

    Gomez, G. B.; Venter, W. D. F.; Lange, J. M. A.; Rees, H.; Hankins, C.

    2013-01-01

    Background. Long-distance truck drivers are at risk of acquiring and transmitting HIV and have suboptimal access to care. New HIV prevention strategies using antiretroviral drugs to reduce transmission risk (early antiretroviral therapy (ART) at CD4 count >350 cells/ μ L) have shown efficacy in

  5. Therapeutic drug monitoring of atazanavir/ritonavir in pregnancy.

    LENUS (Irish Health Repository)

    Else, L J

    2014-11-01

    Pregnant women experience physiological changes during pregnancy that can have a significant impact on antiretroviral pharmacokinetics. Ensuring optimal plasma concentrations of antiretrovirals is essential for maternal health and to minimize the risk of vertical transmission. Here we describe atazanavir\\/ritonavir (ATV\\/r) plasma concentrations in a cohort of pregnant women undergoing routine therapeutic drug monitoring (TDM).

  6. Antiretroviral changes during the first year of therapy

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Policarpo Carmo Sá Bandeira

    Full Text Available Summary Introduction: The Brazilian HIV/AIDS management and treatment guideline (PCDT, published in 2013, recommends and standardizes the use of highly active antiretroviral therapy (HAART in all adult patients, in spite of LTCD4 count. This study aimed to analyze the first year of HAART use in patients from a reference center on HIV/AIDS management in Fortaleza, Ceará. Method: This descriptive study reviewed all prescription forms of antiretroviral regimens initiation and changes from January to July 2014. All antiretroviral regimen changes that occurred during the first year of therapy were evaluated. Data were analyzed with SPSS version 20. Mean, standard deviation and frequency, Student’s t and Mann-Whitney tests calculations were used, with significance at p<0.05. Results: From 527 patients initiating HAART, 16.5% (n=87 had a regimen change in the first year. These patients were mostly male (59.8%; n=52, aged 20 to 39 years, with only one HAART change (72.4%; n=63. Efavirenz was the most often changed drug, followed by tenofovir, zidovudine and lopinavir/ritonavir. Mean time of HAART changes was 120 days, with adverse reactions as the most prevalent cause. HAART was effective in decreasing viral load since second month of treatment (p=0.003 and increasing LTCD4 lymphocytes since fifth month (p<0.001. Conclusion: The main cause of initial HAART changes was adverse reaction and most patients had only one change in the HAART regimen. HAART prescription was in accordance to the PCDT from 2013.

  7. Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Paul W Denton

    2010-01-01

    Full Text Available Successful antiretroviral pre-exposure prophylaxis (PrEP for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT. BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003 and intravenous (Chi square = 13, df = 1, p = 0.0003 HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS.

  8. The association between HIV, antiretroviral therapy, and gestational diabetes mellitus

    NARCIS (Netherlands)

    Soepnel, Larske M; Norris, Shane A; Schrier, Verena J M M; Browne, Joyce L; Rijken, Marcus J; Gray, Glenda; Klipstein-Grobusch, Kerstin

    2017-01-01

    OBJECTIVES: The widespread, chronic use of antiretroviral therapy raises questions concerning the metabolic consequences of HIV infection and treatment. Antiretroviral therapy, and specifically protease inhibitors, has been associated with hyperglycemia. As pregnant women are vulnerable to

  9. Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

    Science.gov (United States)

    Hitti, Jane; Halvas, Elias K; Zheng, Lu; Panousis, Constantinos G; Kabanda, Joseph; Taulo, Frank; Kumarasamy, Nagalingeswaran; Pape, Jean William; Lalloo, Umesh; Sprenger, Heather; Klingman, Karin L; Chan, Ellen S; McMahon, Deborah; Mellors, John W

    2014-11-01

    Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

  10. ADHERENCE TO ANTIRETROVIRAL THERAPY IN A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Muralidhara Panigrahi

    2017-03-01

    Full Text Available BACKGROUND The Million Death Study Collaborators in the British Medical Journal have estimated that the people living with HIV/AIDS population to be between 1.4-1.6 million. Development of Antiretroviral Therapy (ART has been one of the dramatic advances in the history of medicine. Among several factors that can affect the ART outcome, adherence to the ART has been cited as a major factor associated with poor outcomes. For ART to have maximum effect greater than 95%, adherence has been suggested. Additionally, non adherence to ART is a major cause of HIV drug resistance. Especially, in the Indian context, adherence to ART is very important due to the sheer number of HIV/AIDS cases, the socioeconomic status, diversity of the population and regions. That is, the socioeconomic challenges faced by patients contribute to nonadherence to ART in India. With this background, this study was done with the primary objective of assessing the level of adherence to the given regimen of ART as per the NACO guidelines and factors influencing adherence. MATERIALS AND METHODS This is a prospective patient record-based study conducted in the Antiretroviral Therapy Centre at MKCG Medical College, Berhampur, from January 2016 to June 2016. Simple random sampling technique was used to select 150 patients’ records from the ART Centre of the medical college. The data was collected in a predesigned case record form from the patient card available at antiretroviral therapy centre. The patients were followed up through the patient card for six months from their recruitment. The adherence to treatment was evaluated using the adherence score adopted by NACO where a score of 1, 2 and 3 implied that 95%, 80-95% and 95% medication taken. Persons with primary education, married individuals and persons without employment had better improvement in adherence score than other groups. Anaemia was the predominant adverse drug reaction encountered. CONCLUSION The findings of this

  11. Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Trickey, Adam; May, Margaret T; Vehreschild, Jorg-Janne

    2016-01-01

    OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing to the Antiretro......OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing...... to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. RESULTS: During 50,593 person...... years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict...

  12. Antiretroviral therapy programme on control of HIV transmission in ...

    African Journals Online (AJOL)

    Antiretroviral therapy programme on control of HIV transmission in Morogoro municipality, Tanzania: A challenge for development. ... The government and partners should improve access to ART services to enable many PLHIV to access the services. Key words: Antiretroviral Therapy, Highly Active Antiretroviral Treatment, ...

  13. A first-line antiretroviral therapy-resistant HIV patient with rhinoentomophthoromycosis

    Directory of Open Access Journals (Sweden)

    Rachita Dhurat

    2018-01-01

    Full Text Available The Conidiobolus coronatus-related rhinoentomophthoromycosis in immunocompetent and immunocompromised (HIV negative individuals has been treated successfully with antifungal drugs. However, C. coronatus infections in first-line antiretroviral therapy (ART-resistant (HIV infected individuals particularly with rhinoentomophthoromycosis have not been reported previously. Here, we describe a case of itraconazole non-responding rhinoentomophthoromycosis in an HIV-infected patient with first-line antiretroviral (ART drug resistance which was successfully managed through systematic diagnostic and therapeutic approaches in dermatologic setting. A 32-year-old HIV-1-infected man presented with painless swelling, nasal redness and respiratory difficulty. The patient was receiving first-line ART and had a history of traumatic injury before the onset of nasopharyngeal manifestations. The patient's previous history included oral candidiasis and pulmonary tuberculosis.

  14. HIV genotype resistance testing in antiretroviral (ART) exposed Indian children--a need of the hour.

    Science.gov (United States)

    Shah, Ira; Parikh, Shefali

    2013-04-01

    Development of drug resistance in HIV infected children with treatment failure is a major impediment to selection of appropriate therapy. HIV genotype resistance assays predict drug resistance on the basis of mutations in the viral genome. However, their clinical utility, especially in a resource limited setting is still a subject of debate. The authors report two cases in which both the children suffered from treatment failure of various antiretroviral therapy regimes. In both the cases, Genotype Resistance Testing (GRT) prompted a radical change from proposed failure therapy as per existing guidelines. GRT was specifically important for the selection of a new dual Nucleoside reverse transcriptase inhibitors (NRTI) component of failure regimen by identifying TAMS and M184V mutations in the HIV genome. These case reports highlight the importance of GRT in children failing multiple antiretroviral regimes; and emphasizes the need to recognize situations where GRT is absolutely essential to guide appropriate therapy, even in a resource limited setting.

  15. Predictors of having a resistance test following confirmed virological failure of combination antiretroviral therapy: data from EuroSIDA

    DEFF Research Database (Denmark)

    Fox, Zoe V; Cozzi-Lepri, Alessandro; D'Arminio Monforte, Antonella

    2011-01-01

    these recommendations. Methods: In EuroSIDA, virological failure (VF) was defined as confirmed VL>1,000 copies/ml after =4 months continuous use of any antiretroviral in a =3-drug regimen started during or after 2002. We assessed whether a resistance test was performed around VF (from 4 months before to 1 year after VF...

  16. Human resources needs for universal access to antiretroviral therapy in South Africa: a time and motion study

    NARCIS (Netherlands)

    Hontelez, J.A.C.; Newell, M.L.; Bland, R.M.; Munnelly, K.; Lessells, R.J.; Barnighausen, T.

    2012-01-01

    ABSTRACT: BACKGROUND: Although access to life-saving treatment for patients infected with HIV patients in South Africa has improved substantially since 2004, treating all eligible patients (universal access) remains elusive. As the prices of antiretroviral drugs have dropped over the past years,

  17. Determinants of adherence to antiretroviral therapy among HIV-positive adults in sub-Saharan Africa: a systematic review

    NARCIS (Netherlands)

    Heestermans, Tessa; Browne, Joyce L; Aitken, Susan C; Vervoort, Sigrid C; Klipstein-Grobusch, Kerstin

    2016-01-01

    Objective The rapid scale up of antiretroviral treatment (ART) in sub-Saharan Africa (SSA) has resulted in an increased focus on patient adherence. Non-adherence can lead to drug-resistant HIV caused by failure to achieve maximal viral suppression. Optimal treatment requires the identification of

  18. Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

    DEFF Research Database (Denmark)

    NN, NN; Mugavero, Michael J; May, Margaret

    2008-01-01

    , nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation.......58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1......OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between...

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

    OpenAIRE

    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

    Objective. 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. Materials and methods. 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 P...

  20. [Policy dilemmas in providing antiretroviral treatment in Brazil].

    Science.gov (United States)

    do Lago, Regina Ferro; Costa, Nilson do Rosário

    2010-11-01

    This paper addresses institutional constraints that have affected Brazilian politics regarding provision of anti-retroviral treatment (ART) to HIV/Aids patients. We analyzed the normative conflict resulting from international agreements on intellectual property rights, especially patent protection, and the constitutional rights of Brazilian patients to universal and free access to ART. These constraints have not substantially changed the Brazilian public policy yet, but they may impact the future sustainability of this policy. As the main barrier to the production of patented drugs is not technological but institutional, Brazilian government faces a dilemma. It may either abide by existing monopolistic restrictions or it may incite competitiveness of domestic industries and developing countries in the pharmaceutical market.

  1. Identification of 1-Aryl-1H-1,2,3-triazoles as Potential New Antiretroviral Agents.

    Science.gov (United States)

    Gonzaga, Daniel T G; Souza, Thiago M L; Andrade, Viviane M M; Ferreira, Vitor F; de C da Silva, Fernando

    2018-01-01

    Low molecular weight 1-Aryl-1H-1,2,3-triazoles are endowed with various types of biological activities, such as against cancer, HIV and bacteria. Despite the existence of six different classes of antiretroviral drugs in clinical use, HIV/AIDS continue to be an on growing public health problem. In the present study, we synthesized and evaluated thirty 1-Aryl-1H-1,2,3-triazoles against HIV replication. The compounds were prepared by Huisgen 1,3-dipolar cycloaddition protocol catalyzed by Cu(I) between aryl azides and propargylic alcohol followed by further esterification and etherification from a nucleophilic substitution with acid chlorides or alkyl bromides in good yields. The compounds were submitted to the inhibition of HIV replication and evaluation of their cytotoxicity. Initially, the compounds were screened at 10 µM and the most active were further evaluated in order to obtain some pharmacological parameters. Thirty molecules were evaluated, six were selected - because they inhibited more than 80% HIV replication. We further showed that two of these compounds are 8-times more potent, and less cytotoxic, than nevirapine, an antiretroviral drug in clinical use. We identified very simple triazoles with promissing antiretroviral activities that led to the development of new drugs against AIDS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Antiretroviral therapy programme outcomes in Tshwane district ...

    African Journals Online (AJOL)

    Objectives. To ascertain patient retention on ART after 5 years on treatment in one district of Gauteng Province, SA, establish the number of patients ... A retrospective cohort study of patients initiated on highly active antiretroviral therapy (HAART) between January and March .... ferred-out patients from the total of 381 leaves.

  3. The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study.

    Science.gov (United States)

    Estill, Janne; Ford, Nathan; Salazar-Vizcaya, Luisa; Haas, Andreas D; Blaser, Nello; Habiyambere, Vincent; Keiser, Olivia

    2016-03-01

    The number of patients in need of second-line antiretroviral drugs is increasing in sub-Saharan Africa. We aimed to project the need of second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030. We developed a simulation model for HIV and applied it to each sub-Saharan African country. We used the WHO country intelligence database to estimate the number of adult patients receiving antiretroviral therapy from 2005 to 2014. We fitted the number of adult patients receiving antiretroviral therapy to observed estimates, and predicted first-line and second-line needs between 2015 and 2030. We present results for sub-Saharan Africa, and eight selected countries. We present 18 scenarios, combining the availability of viral load monitoring, speed of antiretroviral scale-up, and rates of retention and switching to second-line. HIV transmission was not included. Depending on the scenario, 8·7-25·6 million people are expected to receive antiretroviral therapy in 2020, of whom 0·5-3·0 million will be receiving second-line antiretroviral therapy. The proportion of patients on treatment receiving second-line therapy was highest (15·6%) in the scenario with perfect retention and immediate switching, no further scale-up, and universal routine viral load monitoring. In 2030, the estimated range of patients receiving antiretroviral therapy will remain constant, but the number of patients receiving second-line antiretroviral therapy will increase to 0·8-4·6 million (6·6-19·6%). The need for second-line antiretroviral therapy was two to three times higher if routine viral load monitoring was implemented throughout the region, compared with a scenario of no further viral load monitoring scale-up. For each monitoring strategy, the future proportion of patients receiving second-line antiretroviral therapy differed only minimally between countries. Donors and countries in sub-Saharan Africa should prepare for a substantial increase in the need for second

  4. Acute Liver Failure among Patients on Efavirenz-Based Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Innocent Lule Segamwenge

    2018-01-01

    Full Text Available Objectives. To describe the clinical characteristics of patients presenting with fulminant liver failure after varying periods of exposure to Efavirenz containing antiretroviral medications. Methods. We report a series of 4 patients with human immunodeficiency virus (HIV infection who were admitted with acute liver failure (ALF over a 6-month period. All these patients had been treated with a range of Efavirenz containing antiretroviral regimens and were negative for hepatitis A, B, and C infections as well as other opportunistic infections, all were negative for autoimmune hepatitis, and none had evidence of chronic liver disease or use of alcohol or herbal medications. Information on patient clinical characteristics, current antiretroviral regimen, CD4 count, HIV-1 RNA levels, and clinical chemistry parameters was collected. Informed consent was provided. Results. During a 6-month period, four patients without other known risk factors for acute hepatitis presented with symptomatic drug-induced liver injury with varying symptoms and outcomes. The pattern of liver injury was hepatocellular for all the 4 cases. Liver biopsies were done for all the four cases and the results showed a heavy mixed inflammatory cell infiltrate with eosinophils. For three patients withdrawal of Efavirenz from their antiretroviral regimen was sufficient to restore transaminase levels to normal and led to improvement of clinical symptoms. For one patient his clinical course was characterized by fulminant liver failure and fluctuating episodes of hepatic encephalopathy which ultimately resulted in his death. Conclusion. Hepatotoxicity of Efavirenz is not as rare as previously described in the literature and does actually present with fatal outcomes. The key message to note is that frequent monitoring of liver enzymes should be done at initiation of antiretroviral therapy and should continue throughout the treatment period.

  5. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy.

    Science.gov (United States)

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory's development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery.

  6. AND Ca(II) COMPLEXES WITH AN ANTIRETROVIRAL DRUG

    African Journals Online (AJOL)

    Metal ions perform range of functions such as iron containing protein; the haemoglobin binds with the oxygen to carry ... into an AZT-resistant form [12, 13]. ..... Das, R.; Pitre, K.S. Bioinorganic studies on nickel(II)-zidovudine complex. J. Indian ...

  7. reasons for change of anti-retroviral therapy (art) drugs

    African Journals Online (AJOL)

    2013-12-01

    Dec 1, 2013 ... these factors that have a bearing on compliance and success of treatment. Objective: To determine ... Steven Johnson Syndrome, pancreatitis) and probable failure of to HAART. CD4+ cell ... Indeed,. HAART has transformed HIV disease into a chronic .... Factors independently associated with a greater risk.

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

    African Journals Online (AJOL)

    2012-03-01

    Mar 1, 2012 ... baby-friendly principles in the health services, strengthening community-based ... which to make any decision about public health, it is extraordinary that they .... safe – the acronym summarising the criteria that were proposed at that time ..... is wrong. Moreover, Saloojee et al. fail to mention children's rights,.

  9. Social, Cultural, and Environmental Challenges Faced by Children on Antiretroviral Therapy in Zimbabwe: a Mixed-Method Study

    Science.gov (United States)

    Macherera, Margaret; Moyo, Lindani; Ncube, Mkhanyiseli; Gumbi, Angella

    2012-01-01

    Objectives Despite the advent of antiretroviral therapy (ART), many children, particularly in the rural communities of Zimbabwe, remain vulnerable. The purpose of this study was to determine the factors and challenges facing children on antiretroviral therapy (ART) in Brunapeg area of Mangwe District, Zimbabwe. Methods A mixed-method approach involving interviewer-guided focus group discussions and piloted semi-structured questionnaires was utilized to collect data from different key population groups. The data obtained were analyzed through content coding procedures based on a set of predetermined themes of interest. Results A number of challenges emerged as barriers to the success of antiretroviral therapy for children. Primary care givers were less informed about HIV and AIDS issues for people having direct impact on the success of antiretroviral therapy in children whilst some were found to be taking the antiretroviral drugs meant for the children. It also emerged that some primary care givers were either too young or too old to care for the children while others had failed to disclose to the children why they frequently visited the Opportunistic Infections (OI) clinic. Most primary care givers were not the biological parents of the affected children. Other challenges included inadequate access to health services, inadequate food and nutrition and lack of access to clean water, good hygiene and sanitation. The lack of community support and stigma and discrimination affected their school attendance and hospital visits. All these factors contributed to non-adherence to antiretroviral drugs. Conclusions and Public Health Implications Children on ART in rural communities in Zimbabwe remain severely compromised and have unique problems that need multi-intervention strategies both at policy and programmatic levels. Effective mitigating measures must be fully established and implemented in rural communities of developing countries in the fight for universal

  10. Social, Cultural, and Environmental Challenges Faced by Children on Antiretroviral Therapy in Zimbabwe: a Mixed Method Study

    Directory of Open Access Journals (Sweden)

    Margaret Macherera, MSc

    2012-11-01

    Full Text Available Objectives:Despite the advent of antiretroviral therapy (ART, many children, particularly in the rural communities of Zimbabwe, remain vulnerable. The purpose of this study was to determine the factors and challenges facing children on antiretroviral therapy (ART in Brunapeg area of Mangwe District, Zimbabwe.Methods:A mixed-method approach involving interviewer-guided focus group discussions and piloted semi-structured questionnaires was utilized to collect data from different key population groups. The data obtained were analyzed through content coding procedures based on a set of predetermined themes of interest.Results:A number of challenges emerged as barriers to the success of antiretroviral therapy for children. Primary care givers were less informed about HIV and AIDS issues for people having direct impact on the success of antiretroviral therapy in children whilst some were found to be taking the antiretroviral drugs meant for the children. It also emerged that some primary care givers were either too young or too old to care for the children while others had failed to disclose to the children why they frequently visited the Opportunistic Infections (OI clinic. Most primary care givers were not the biological parents of the affected children. Other challenges included inadequate access to health services, inadequate food and nutrition and lack of access to clean water, good hygiene and sanitation. The lack of community support and stigma and discrimination affected their school attendance and hospital visits. All these factors contributed to non-adherence to antiretroviral drugs.Conclusions and Public Health Implications:Children on ART in rural communities in Zimbabwe remain severely compromised and have unique problems that need multi-intervention strategies both at policy and programmatic levels. Effective mitigating measures must be fully established and implemented in rural communities of developing countries in the fight for

  11. Differences in Lipid Measurements by Antiretroviral Regimen Exposure in Cohorts from Asia and Australia

    Directory of Open Access Journals (Sweden)

    Amit C. Achhra

    2012-01-01

    Full Text Available We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol according to exposure to different combination antiretroviral regimens in Asian (n=2051 and Australian (predominantly Caucasian, n=794 cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs and either of at least one protease inhibitor (PI or non-nucleoside-reverse transcriptases (NNRTIs. We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both; and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: 0.05. The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations.

  12. 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.

  13. Kinetics and Determining Factors of the Virologic Response to Antiretrovirals during Pregnancy

    Directory of Open Access Journals (Sweden)

    Adriana Weinberg

    2009-01-01

    Full Text Available HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at delivery pose a minimal risk of vertical transmission. We studied the kinetics and the determinants of the virologic response to antiretroviral therapy in 117 consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL decrease of 2 and 2.5 log10 after 4 and 24 weeks, respectively. Therapeutic drug monitoring (TDM of the protease inhibitors administered in doses recommended for nonpregnant adults resulted in below-target concentrations in 29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but low drug concentrations did not correlate with virologic failure. Demographic characteristics, antiretroviral experience prior to pregnancy, baseline VL, or use of specific antiretrovirals did not affect the virologic response. Adherence to ≥95% of prescribed doses and utilization of psychosocial services were associated with undetectable plasma HIV RNA at delivery. In conclusion, the virologic responses of pregnant and nonpregnant adults share similar charactersitics.

  14. Health and federal budgetary effects of increasing access to antiretroviral medications for HIV by expanding Medicaid.

    Science.gov (United States)

    Kahn, J G; Haile, B; Kates, J; Chang, S

    2001-09-01

    OBJECTIVES. This study modeled the health and federal fiscal effects of expanding Medicaid for HIV-infected people to improve access to highly active antiretroviral therapy. A disease state model of the US HIV epidemic, with and without Medicaid expansion, was used. Eligibility required a CD4 cell count less than 500/mm3 or viral load greater than 10,000, absent or inadequate medication insurance, and annual income less than $10,000. Two benefits were modeled, "full" and "limited" (medications, outpatient care). Federal spending for Medicaid, Medicare, AIDS Drug Assistance Program, Supplemental Security Income, and Social Security Disability Insurance were assessed. An estimated 38,000 individuals would enroll in a Medicaid HIV expansion. Over 5 years, expansion would prevent an estimated 13,000 AIDS diagnoses and 2600 deaths and add 5,816 years of life. Net federal costs for all programs are $739 million (full benefits) and $480 million (limited benefits); for Medicaid alone, the costs are $1.43 and $1.17 billion, respectively. Results were sensitive to awareness of serostatus, highly active antiretroviral therapy cost, and participation rate. Strategies for federal cost neutrality include Medicaid HIV drug price reductions as low as 9% and private insurance buy-ins. Expansion of the Medicaid eligibility to increase access to antiretroviral therapy would have substantial health benefits at affordable costs.

  15. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

    NARCIS (Netherlands)

    Hofstra, L. Marije; Sauvageot, Nicolas; Albert, Jan; Alexiev, Ivailo; Garcia, Federico; Struck, Daniel; Van De Vijver, David A M C; Åsjö, Birgitta; Beshkov, Danail; Coughlan, Suzie; Descamps, Diane; Griskevicius, Algirdas; Hamouda, Osamah; Horban, Andrzej; Van Kasteren, Marjo; Kolupajeva, Tatjana; Kostrikis, Leontios G.; Liitsola, Kirsi; Linka, Marek; Mor, Orna; Nielsen, Claus; Otelea, Dan; Paraskevis, Dimitrios; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Van Laethem, Kristel; Zazzi, Maurizio; Lepej, Snjezana Zidovec; Boucher, Charles A B; Schmit, Jean Claude; Wensing, Annemarie M J; Puchhammer-Stockl, E.; Sarcletti, M.; Schmied, B.; Geit, M.; Balluch, G.; Vandamme, A. M.; Vercauteren, J.; Derdelinckx, I.; Sasse, A.; Bogaert, M.; Ceunen, H.; De Roo, A.; De Wit, S.; Echahidi, F.; Fransen, K.; Goffard, J. C.; Goubau, P.; Goudeseune, E.; Yombi, J. C.; Lacor, P.; Liesnard, C.; Moutschen, M.; Pierard, D.; Rens, R.; Schrooten, Y.; Vaira, D.; Vandekerckhove, L. P R; Van Den Heuvel, A.; Van Der Gucht, B.; Van Ranst, M.; Van Wijngaerden, E.; Vandercam, B.; Vekemans, M.; Verhofstede, C.; Clumeck, N.; Van Laethem, K.; Beshkov, D.; Alexiev, I.; Lepej, S. Zidovec; Begovac, J.; Kostrikis, Leontios G.; Demetriades, I.; Kousiappa, I.; Demetriou, V.; Hezka, J.; Linka, M.; Maly, M.; Machala, L.; Nielsen, C.; Jørgensen, L. B.; Gerstoft, J.; Mathiesen, L.; Pedersen, C.; Nielsen, H.; Laursen, A.; Kvinesdal, B.; Liitsola, K.; Ristola, M.; Suni, J.; Sutinen, J.; Descamps, D.; Assoumou, L.; Castor, G.; Grude, M.; Flandre, P.; Storto, A.; Hamouda, O.; Kücherer, C.; Berg, T.; Braun, P.; Poggensee, G.; Däumer, M.; Eberle, J.; Heiken, H.; Kaiser, R.; Knechten, H.; Korn, K.; Müller, H.; Neifer, S.; Schmidt, B.; Walter, H.; Gunsenheimer-Bartmeyer, B.; Harrer, T.; Paraskevis, D.; Hatzakis, A.; Zavitsanou, A.; Vassilakis, A.; Lazanas, M.; Chini, M.; Lioni, A.; Sakka, V.; Kourkounti, S.; Paparizos, V.; Antoniadou, A.; Papadopoulos, A.; Poulakou, G.; Katsarolis, I.; Protopapas, K.; Chryssos, G.; Drimis, S.; Gargalianos, P.; Xylomenos, G.; Lourida, G.; Psichogiou, M.; Daikos, G. L.; Sipsas, N. V.; Kontos, A.; Gamaletsou, M. N.; Koratzanis, G.; Sambatakou, E.; Mariolis, H.; Skoutelis, A.; Papastamopoulos, V.; Georgiou, O.; Panagopoulos, P.; Maltezos, E.; Coughlan, S.; De Gascun, C.; Byrne, C.; Duffy, M.; Bergin, C.; Reidy, D.; Farrell, G.; Lambert, J.; O'Connor, E.; Rochford, A.; Low, J.; Coakely, P.; O'Dea, S.; Hall, W.; Mor, O.; Levi, I.; Chemtob, D.; Grossman, Z.; Zazzi, M.; De Luca, A.; Balotta, C.; Riva, C.; Mussini, C.; Caramma, I.; Capetti, A.; Colombo, M. C.; Rossi, C.; Prati, F.; Tramuto, F.; Vitale, F.; Ciccozzi, M.; Angarano, G.; Rezza, G.; Kolupajeva, T.; Kolupajeva, T.; Vasins, O.; Griskevicius, A.; Lipnickiene, V.; Schmit, J. C.; Struck, D.; Sauvageot, N.; Hemmer, R.; Arendt, V.; Michaux, C.; Staub, T.; Sequin-Devaux, C.; Wensing, A. M J; Boucher, C. A B; Van Kessel, A.; Van Bentum, P. H M; Brinkman, K.; Connell, B. J.; Van Der Ende, M. E.; Hoepelman, I. M.; Van Kasteren, M.; Kuipers, M.; Langebeek, N.; Richter, C.; Santegoets, R. M W J; Schrijnders-Gudde, L.; Schuurman, R.; Van De Ven, B. J M; Åsjö, B.; Kran, A. M Bakken; Ormaasen, V.; Aavitsland, P.; Horban, A.; Stanczak, J. J.; Stanczak, G. P.; Firlag-Burkacka, E.; Wiercinska-Drapalo, A.; Jablonowska, E.; Maolepsza, E.; Leszczyszyn-Pynka, M.; Szata, W.; Camacho, R.; Palma, C.; Borges, F.; Paixão, T.; Duque, V.; Araújo, F.; Otelea, D.; Paraschiv, S.; Tudor, A. M.; Cernat, R.; Chiriac, C.; Dumitrescu, F.; Prisecariu, L. J.; Stanojevic, M.; Jevtovic, Dj; Salemovic, D.; Stanekova, D.; Habekova, M.; Chabadová, Z.; Drobkova, T.; Bukovinova, P.; Shunnar, A.; Truska, P.; Poljak, M.; Lunar, M.; Babic, D.; Tomazic, J.; Vidmar, L.; Vovko, T.; Karner, P.; Garcia, F.; Paredes, R.; Monge, S.; Moreno, S.; Del Amo, J.; Asensi, V.; Sirvent, J. L.; De Mendoza, C.; Delgado, R.; Gutiérrez, F.; Berenguer, J.; Garcia-Bujalance, S.; Stella, N.; De Los Santos, I.; Blanco, J. R.; Dalmau, D.; Rivero, M.; Segura, F.; Elías, M. J Pérez; Alvarez, M.; Chueca, N.; Rodríguez-Martín, C.; Vidal, C.; Palomares, J. C.; Viciana, I.; Viciana, P.; Cordoba, J.; Aguilera, A.; Domingo, P.; Galindo, M. J.; Miralles, C.; Del Pozo, M. A.; Ribera, E.; Iribarren, J. A.; Ruiz, L.; De La Torre, J.; Vidal, F.; Clotet, B.; Albert, J.; Heidarian, A.; Aperia-Peipke, K.; Axelsson, M.; Mild, M.; Karlsson, A.; Sönnerborg, A.; Thalme, A.; Navér, L.; Bratt, G.; Karlsson, A.; Blaxhult, A.; Gisslén, M.; Svennerholm, B.; Bergbrant, I.; Björkman, P.; Säll, C.; Lindholm, A.; Kuylenstierna, N.; Montelius, R.; Azimi, F.; Johansson, B.; Carlsson, M.; Johansson, E.; Ljungberg, B.; Ekvall, H.; Strand, A.; Mäkitalo, S.; Öberg, S.; Holmblad, P.; Höfer, M.; Holmberg, H.; Josefson, P.; Ryding, U.

    2016-01-01

    Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline

  16. Adherence to antiretroviral therapy and its determinants in AIDS patients: review article

    Directory of Open Access Journals (Sweden)

    Hajiabdolbaghi M

    2008-10-01

    known to overestimate adherence. Some determinants are associated with adherence include: age, gender, addiction specially injection drug users, alcohol consumption, depression, social support, level of education, work situation, adverse antiretroviral effects, pregnancy, type of antiretroviral drug regimen, number of pills and daily doses received, severe traumas, social and psychological factors, and relationship between clinician and patient.0 "nKeywords: Adherence, antiretroviral therapy, AIDS, treatment.

  17. Biomedicine, public health, and citizenship in the advent of antiretrovirals in Botswana.

    Science.gov (United States)

    Chabrol, Fanny

    2014-08-01

    Often celebrated as a model of development in Africa, Botswana nonetheless endured a severe HIV epidemic. This article describes the singularity of the Botswana experience in facing AIDS and creating the widest possible access to antiretroviral medications for its citizens. Through exploration of different sets of actors and the construction of their ethics of treatment, it is possible to examine how free and universal access was created within the national antiretroviral program. This article underscores the importance of the site and the local dynamics in the advent of an ethics of access to treatment for Botswana citizens. At the intersection of national citizenship, pharmaceutical philanthropy, and biomedical collaborations, Botswana is an exemplary case (one of the first and unique in its kind) of global health programs for access to drugs in which patients' rights are tied to science and pharmaceutical development. As such it also bears some limitations and concerns over its sustainability. © 2014 John Wiley & Sons Ltd.

  18. Antiretroviral chemoprophylaxis in children and adolescents victims of rape in Abidjan.

    Science.gov (United States)

    Ehui, E; Couitchéré, L S; Kouakou, G A; Doumbia, A; Kassi, A N; Mossou, C M; Guié, P Y; Eholié, S

    2015-08-01

    We described the use of antiretroviral drugs to prevent HIV transmission among children and adolescents victims of rape in Abidjan (Ivory Coast). We conducted a retrospective and descriptive study on children (0-9 years) and adolescents (10-19 years) victims of rape between 2000 and 2013. We analyzed the patients' socio-demographic characteristics and the modality of the chemoprophylaxis. We included 10 children and 89 adolescents in the study. The median age was 16 years old (3-19 years). The median time to consultation was 23.5 hours (5-152 hours). The antiretroviral chemoprophylaxis was administered to 92 patients (93%). No HIV and HBV seroconversion was observed after a 3-month follow-up. A better management of rape victims is required in Abidjan. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Triple Active Antiretroviral Regimen Including Enfuvirtide Via the Biojector is Effective and Safe

    Directory of Open Access Journals (Sweden)

    Mona Loutfy

    2007-01-01

    Full Text Available For full HIV virological suppression, three fully active antiretroviral agents are required. New drug classes should be included to ensure that agents are fully active. The addition of enfuvirtide and efavirenz to the present patient’s new antiretroviral regimen ensured that two fully active agents were in use in the setting of a moderate degree of nucleoside resistance and a high level of protease resistance, and where non-nucleoside reverse transcriptase inhibitors were still fully active. Both viral load and CD4 count responded favourably to this regimen. The patient received support from physicians and clinic staff in the introduction and use of enfuvirtide. To reduce injection site reactions, a needle-free injection system (Biojector proved effective.

  20. Quality of life of people living with HIV and AIDS and antiretroviral therapy.

    Science.gov (United States)

    Oguntibeju, Oluwafemi O

    2012-01-01

    The development of antiretroviral drugs has significantly changed the perception of HIV/AIDS from a very fatal to a chronic and potentially manageable disease, and the availability and administration of antiretroviral therapy (ART) has significantly reduced mortality and morbidity associated with HIV and AIDS. There is a relationship between ART and quality of life of people living with HIV and AIDS, and several studies have reported a strong positive association between ART and improved quality of life in different domains among people living with HIV and AIDS in both developed and developing countries. However, a few studies have reported on the negative effects of ART, which directly or indirectly relate to the quality of life and longevity of HIV-infected persons. In this review, the effects and benefits of ART on people living with HIV and AIDS based on studies done in developed and developing countries is examined.

  1. Quality of antiretroviral therapy in public health facilities in Nigeria and perceptions of end users.

    Science.gov (United States)

    Chiegil, Robert J; Zungu, Lindiwe I; Jooste, Karien

    2014-04-01

    This paper describes perceptions of the end users on quality of antiretroviral therapy (ART) in public health facilities in Nigeria. Health care services in Nigeria face challenges of meeting end users' requirements and expectations for quality ART service provision. A qualitative design was followed. Unstructured focus group discussions were conducted with end users (n = 64) in six locations across the six geopolitical zones of Nigeria. The findings indicate that end users were satisfied with uninterrupted antiretroviral drug supplies, courtesy treatment, volunteerism of support group members and quality counselling services. End users expect effective collaboration between healthcare providers and support group members, to enhance the quality of life of people living with HIV. A best practice guideline for the provision of end user focused ART service provision was developed for nurse managers. © 2013 John Wiley & Sons Ltd.

  2. Quality of life of people living with HIV and AIDS and antiretroviral therapy

    Science.gov (United States)

    Oguntibeju, Oluwafemi O

    2012-01-01

    The development of antiretroviral drugs has significantly changed the perception of HIV/AIDS from a very fatal to a chronic and potentially manageable disease, and the availability and administration of antiretroviral therapy (ART) has significantly reduced mortality and morbidity associated with HIV and AIDS. There is a relationship between ART and quality of life of people living with HIV and AIDS, and several studies have reported a strong positive association between ART and improved quality of life in different domains among people living with HIV and AIDS in both developed and developing countries. However, a few studies have reported on the negative effects of ART, which directly or indirectly relate to the quality of life and longevity of HIV-infected persons. In this review, the effects and benefits of ART on people living with HIV and AIDS based on studies done in developed and developing countries is examined. PMID:22893751

  3. Cohort Profile: Antiretroviral Therapy Cohort Collaboration (ART-CC)

    Science.gov (United States)

    May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D’Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan AC

    2014-01-01

    The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70 000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org). PMID:23599235

  4. 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.

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

    Science.gov (United States)

    Lazenby, Gweneth B; Mmeje, Okeoma; Fisher, Barbra M; Weinberg, Adriana; Aaron, Erika K; Keating, Maria; Luque, Amneris E; Willers, Denise; Cohan, Deborah; Money, Deborah

    2016-01-01

    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 χ (2) 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.

  6. Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee.

    Science.gov (United States)

    Rouleau, Danielle; Fortin, Claude; Trottier, Benoît; Lalonde, Richard; Lapointe, Normand; Côté, Pierre; Routy, Jean-Pierre; Matte, Marie-France; Tsarevsky, Irina; Baril, Jean-Guy

    2011-01-01

    The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients' comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication.

  7. Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee

    Directory of Open Access Journals (Sweden)

    Danielle Rouleau

    2011-01-01

    Full Text Available The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients’ comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication.

  8. Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee

    Science.gov (United States)

    Rouleau, Danielle; Fortin, Claude; Trottier, Benoît; Lalonde, Richard; Lapointe, Normand; Côté, Pierre; Routy, Jean-Pierre; Matte, Marie-France; Tsarevsky, Irina; Baril, Jean-Guy

    2011-01-01

    The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients’ comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication. PMID:22654926

  9. Complications of HIV Disease and Antiretroviral Therapy

    OpenAIRE

    Luetkemeyer, Anne F.; Havlir, Diane V.; Currier, Judith S.

    2010-01-01

    There is growing interest in the pathogenesis, treatment, and prevention of long-term complications of HIV disease and its therapies. Specifically, studies focused on cardiovascular, renal, bone, and fat abnormalities were prominent at the 17th Conference on Retroviruses and Opportunistic Infections. Although enthusiasm about the effectiveness of current antiretroviral therapy remains strong, collectively, the ongoing work in the area of HIV disease and treatment complications appears to refl...

  10. Brazil may stop HIV drug access; problems also reported from Argentina.

    Science.gov (United States)

    1999-09-03

    Brazil's financial crisis is threatening its HIV treatment programs, as well as programs for other diseases such as hemophilia, tuberculosis, diabetes, and malaria. The government is expected to stop providing antiretroviral therapy through the public health system in October. Meanwhile, the Argentine government stopped providing antiretroviral medications in August. Drug recycling programs are also discussed. Contact information is provided.

  11. Thymidine analogue-sparing highly active antiretroviral therapy (HAART).

    Science.gov (United States)

    Nolan, David; Mallal, Simon

    2003-02-01

    The use of alternative nucleoside reverse transcriptase inhibitors (NRTIs) to the thymidine analogues stavudine (d4T) and zidovudine(ZDV) has been advocated as a means of limiting long-term NRTI-associated toxicity, particularly the development of lipoatrophy or fat wasting. This approach reflects an increasing knowledge of the distinct toxicity profiles of NRTI drugs. However, recent clinical trials have demonstrated that the use of thymidine analogue NRTIs and newer alternative backbone NRTIs, such as tenofovir (TNF) and abacavir (ABC), is associated with comparable short-term efficacy and tolerability. Given the importance of toxicity profile differences in determining clinical management, it is important to recognise that d4T and ZDV cary significantly different risks for long-term NRTI toxicity. Recognising that all NRTIs, including thymidine analogues, have individual toxicity profiles provides a more appropriate basis for selecting optimal antiretroviral therapy. The safety and efficacy of TNF and ABC are also reviewed here, although the available data provide only limited knowledge of the long-term effects of these drugs in terms of toxicity and antiviral durability.

  12. Anti-Retroviral Lectins Have Modest Effects on Adherence of Trichomonas vaginalis to Epithelial Cells In Vitro and on Recovery of Tritrichomonas foetus in a Mouse Vaginal Model

    Science.gov (United States)

    Chatterjee, Aparajita; Ratner, Daniel M.; Ryan, Christopher M.; Johnson, Patricia J.; O’Keefe, Barry R.; Secor, W. Evan; Anderson, Deborah J.; Robbins, Phillips W.; Samuelson, John

    2015-01-01

    Trichomonas vaginalis causes vaginitis and increases the risk of HIV transmission by heterosexual sex, while Tritrichomonas foetus causes premature abortion in cattle. Our goals were to determine the effects, if any, of anti-retroviral lectins, which are designed to prevent heterosexual transmission of HIV, on adherence of Trichomonas to ectocervical cells and on Tritrichomonas infections in a mouse model. We show that Trichomonas Asn-linked glycans (N-glycans), like those of HIV, bind the mannose-binding lectin (MBL) that is part of the innate immune system. N-glycans of Trichomonas and Tritrichomonas bind anti-retroviral lectins (cyanovirin-N and griffithsin) and the 2G12 monoclonal antibody, each of which binds HIV N-glycans. Binding of cyanovirin-N appears to be independent of susceptibility to metronidazole, the major drug used to treat Trichomonas. Anti-retroviral lectins, MBL, and galectin-1 cause Trichomonas to self-aggregate and precipitate. The anti-retroviral lectins also increase adherence of ricin-resistant mutants, which are less adherent than parent cells, to ectocervical cell monolayers and to organotypic EpiVaginal tissue cells. Topical application of either anti-retroviral lectins or yeast N-glycans decreases by 40 to 70% the recovery of Tritrichomonas from the mouse vagina. These results, which are explained by a few simple models, suggest that the anti-retroviral lectins have a modest potential for preventing or treating human infections with Trichomonas. PMID:26252012

  13. Anti-Retroviral Lectins Have Modest Effects on Adherence of Trichomonas vaginalis to Epithelial Cells In Vitro and on Recovery of Tritrichomonas foetus in a Mouse Vaginal Model.

    Directory of Open Access Journals (Sweden)

    Aparajita Chatterjee

    Full Text Available Trichomonas vaginalis causes vaginitis and increases the risk of HIV transmission by heterosexual sex, while Tritrichomonas foetus causes premature abortion in cattle. Our goals were to determine the effects, if any, of anti-retroviral lectins, which are designed to prevent heterosexual transmission of HIV, on adherence of Trichomonas to ectocervical cells and on Tritrichomonas infections in a mouse model. We show that Trichomonas Asn-linked glycans (N-glycans, like those of HIV, bind the mannose-binding lectin (MBL that is part of the innate immune system. N-glycans of Trichomonas and Tritrichomonas bind anti-retroviral lectins (cyanovirin-N and griffithsin and the 2G12 monoclonal antibody, each of which binds HIV N-glycans. Binding of cyanovirin-N appears to be independent of susceptibility to metronidazole, the major drug used to treat Trichomonas. Anti-retroviral lectins, MBL, and galectin-1 cause Trichomonas to self-aggregate and precipitate. The anti-retroviral lectins also increase adherence of ricin-resistant mutants, which are less adherent than parent cells, to ectocervical cell monolayers and to organotypic EpiVaginal tissue cells. Topical application of either anti-retroviral lectins or yeast N-glycans decreases by 40 to 70% the recovery of Tritrichomonas from the mouse vagina. These results, which are explained by a few simple models, suggest that the anti-retroviral lectins have a modest potential for preventing or treating human infections with Trichomonas.

  14. Impact of injecting drug use on mortality in Danish HIV-infected patients: a nation-wide population-based cohort study

    DEFF Research Database (Denmark)

    Larsen, Mette V; Omland, Lars H; Gerstoft, Jan

    2010-01-01

    To estimate the impact of injecting drug use (IDU) on mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era.......To estimate the impact of injecting drug use (IDU) on mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era....

  15. Effect of antiretroviral drugs on maternal CD4 lymphocyte counts, HIV-1 RNA levels, and anthropometric parameters of their neonates Efeito das drogas anti-retrovirais sobre os valores dos linfócitos TCD4, RNA do HIV-1 e parâmetros antropométricos de neonatos de gestantes portadoras do HIV-1

    Directory of Open Access Journals (Sweden)

    Patrícia El Beitune

    2005-06-01

    Full Text Available PURPOSE: To study the effect of antiretroviral drugs administered during pregnancy on CD4 lymphocyte counts and HIV-1 RNA levels of pregnant women and on the anthropometric parameters of their neonates. METHODS: A prospective study was conducted on 57 pregnant women and their neonates divided into 3 groups: ZDV Group, HIV-infected mothers taking zidovudine (n = 20; triple therapy (TT Group, mothers taking zidovudine + lamivudine + nelfinavir (n = 25, and Control Group, normal women (n = 12. CD4 lymphocyte counts and HIV-1 RNA levels of pregnant women were analyzed during two periods of pregnancy. The perinatal prognosis took into account preterm rates, birth weight, intrauterine growth restriction, perinatal death, and vertical transmission of HIV-1. Data were analyzed statistically using the nonparametric chi-square, Mann-Whitney, Friedman, Kruskal-Wallis, and Wilcoxon matched pairs tests, with the level of significance set at P OBJETIVOS: Estudar o efeito das drogas anti-retrovirais sobre a quantificação dos linfócitos TCD4 e RNA do HIV-1 de gestantes portadoras do HIV-1 e parâmetros antropométricos de seus neonatos. MÉTODOS: Estudo prospectivo avaliando 57 gestantes e seus neonatos em três grupos: Grupo AZT, gestantes portadoras do HIV utilizando zidovudina (n=20; Grupo TT, mães utilizando zidovudina+lamivudina+nelfinavir (n=25, e Grupo Controle, mulheres saudáveis (n=12. A quantificação dos linfócitos TCD4 e RNA do HIV-1 de gestantes portadoras do HIV foi analisada em dois períodos durante a gestação. O prognóstico perinatal levou em consideração as taxas de pré-termos, restrição de crescimento intra-útero, mortalidade perinatal e transmissão vertical do HIV-1. Os dados foram analisados utilizando-se testes não paramétricos de qui-quadrado, Mann-Whitney, Friedman, Kruskal-Wallys e Wilcoxon para amostras pareadas, considerando-se significativos valores associados a p<0,05. RESULTADOS: Observou-se homogeneidade entre

  16. Proposed methodology for monitoring antiretroviral drugs price negotiations in Latin America and the Caribbean Propuesta de metodología para monitorear la negociación de precios de los medicamentos antirretrovirales en América Latina y el Caribe

    Directory of Open Access Journals (Sweden)

    Claudia G. S. Osorio-de-Castro

    2009-08-01

    Full Text Available OBJECTIVES: The spread of HIV/AIDS challenges governments to provide antiretroviral (ARV treatment at affordable prices, and various initiatives have been developed with that intent. In Latin America and the Caribbean, four subregional negotiations were conducted during 2002-2005 to reduce drug prices and thus broaden access to ARVs. Studies were carried out to monitor the negotiations, and the development of a monitoring methodology was recommended. The objective of the current study was to develop and describe a potential methodology for monitoring ARV price negotiations. METHODS: The study, carried out in 2006-2007, consisted of a design phase and validation phase. The design phase included an extensive literature review and development of a theoretical framework. Validation was performed using health professional consensus and pilot studies in three countries-Barbados, Honduras, and Peru-representing the Caribbean, Central American, and Andean subregions. RESULTS: The results included a detailed logic model and a 40-indicator framework. Both were tested in the field. Indicators were evaluated for feasibility, pertinence, and sensitivity, based on the outcome of the pilot study. CONCLUSIONS: This monitoring methodology is designed to help countries self-evaluate progress toward implementation of ARV price negotiations. The results of the pilot study indicate that its implementation in the field helped elucidate the ARV price negotiation process by identifying local conditions and indirectly measuring countries' negotiating capacities.OBJETIVO: La diseminación del VIH/sida exige de los gobiernos suministrar el tratamiento antirretroviral (ARV a precios asequibles y se han desarrollado varias iniciativas con ese fin. En América Latina y el Caribe se han realizado cuatro negociaciones subregionales entre 2002 y 2005 para reducir los precios de los medicamentos y así ampliar el acceso a los ARV. Se han realizado estudios para monitorear las

  17. Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study: a phase-II randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Montoya Carlos J

    2009-06-01

    Full Text Available Abstract Background Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection. Methods/design Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients or placebo (55 patients. Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals. Discussion Preliminary descriptive studies have suggested that statins (lovastatin may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on

  18. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents.

    Science.gov (United States)

    Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K

    2002-09-03

    The availability of an increasing number of antiretroviral agents and the rapid evolution of new information have introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR. 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. In general

  19. Follow-up on long-term antiretroviral therapy for cats infected with feline immunodeficiency virus.

    Science.gov (United States)

    Medeiros, Sheila de Oliveira; Abreu, Celina Monteiro; Delvecchio, Rodrigo; Ribeiro, Anísia Praxedes; Vasconcelos, Zilton; Brindeiro, Rodrigo de Moraes; Tanuri, Amilcar

    2016-04-01

    Feline immunodeficiency virus (FIV) is a lentivirus that induces AIDS-like disease in cats. Some of the antiretroviral drugs available to treat patients with HIV type 1 are used to treat FIV-infected cats; however, antiretroviral therapy (ART) is not used in cats as a long-term treatment. In this study, the effects of long-term ART were evaluated in domestic cats treated initially with the nucleoside transcriptase reverse inhibitor (NTRI) zidovudine (AZT) over a period ranging from 5-6 years, followed by a regimen of the NTRI lamivudine (3TC) plus AZT over 3 years. Viral load, sequencing of pol (reverse transcriptase [RT]) region and CD4:CD8 lymphocyte ratio were evaluated during and after treatment. Untreated cats were evaluated as a control group. CD4:CD8 ratios were lower, and uncharacterized resistance mutations were found in the RT region in the group of treated cats. A slight increase in viral load was observed in some cats after discontinuing treatment. The data strongly suggest that treated cats were resistant to therapy, and uncharacterized resistance mutations in the RT gene of FIV were selected for by AZT. Few studies have been conducted to evaluate the effect of long-term antiretroviral therapy in cats. To date, resistance mutations have not been described in vivo. © ISFM and AAFP 2015.

  20. Antiretroviral Therapy during the Neonatal Period | Nuttall | Southern ...

    African Journals Online (AJOL)

    Initiation of combination antiretroviral therapy (cART) at 6–9 weeks of age has been shown to reduce early infant mortality by 76% and HIV progression by 75% compared with cART deferred until clinical or CD4 criteria were met. In the landmark Children with HIV Early Antiretroviral Therapy (CHER) trial, although the ...

  1. Exploration of pain in children on antiretroviral treatment in a ...

    African Journals Online (AJOL)

    Exploration of pain in children on antiretroviral treatment in a regional hospital in South Africa. M Azam, L Campbell, A Ross. Abstract. Background: Patients with human immunodeficiency virus (HIV) disease on antiretroviral therapy (ART) may experience pain for a variety of reasons, including the effects of the virus itself, ...

  2. Delivery of antiretroviral treatment services in India: Estimated costs incurred under the National AIDS Control Programme.

    Science.gov (United States)

    Agarwal, Reshu; Rewari, Bharat Bhushan; Shastri, Suresh; Nagaraja, Sharath Burugina; Rathore, Abhilakh Singh

    2017-04-01

    Competing domestic health priorities and shrinking financial support from external agencies necessitates that India's National AIDS Control Programme (NACP) brings in cost efficiencies to sustain the programme. In addition, current plans to expand the criteria for eligibility for antiretroviral therapy (ART) in India will have significant financial implications in the near future. ART centres in India provide comprehensive services to people living with HIV (PLHIV): those fulfilling national eligibility criteria and receiving ART and those on pre-ART care, i.e. not on ART. ART centres are financially supported (i) directly by the NACP; and (ii) indirectly by general health systems. This study was conducted to determine (i) the cost incurred per patient per year of pre-ART and ART services at ART centres; and (ii) the proportion of this cost incurred by the NACP and by general health systems. The study used national data from April 2013 to March 2014, on ART costs and non-ART costs (human resources, laboratory tests, training, prophylaxis and management of opportunistic infections, hospitalization, operational, and programme management). Data were extracted from procurement records and reports, statements of expenditure at national and state level, records and reports from ART centres, databases of the National AIDS Control Organisation, and reports on use of antiretroviral drugs. The analysis estimates the cost for ART services as US$ 133.89 (?8032) per patient per year, of which 66% (US$ 88.66, ?5320) is for antiretroviral drugs and 34% (US$ 45.23, ?2712) is for non-ART recurrent expenditure, while the cost for pre-ART care is US$ 33.05 (?1983) per patient per year. The low costs incurred for patients in ART and pre-ART care services can be attributed mainly to the low costs of generic drugs. However, further integration with general health systems may facilitate additional cost saving, such as in human resources.

  3. Lack of correlation between length variation in the DNA polymerase gamma gene CAG repeat and lactic acidosis or neuropathy during antiretroviral treatment

    NARCIS (Netherlands)

    Chen, Xianghong; Goudsmit, Jaap; van der Kuyl, Antoinette C.

    2002-01-01

    Antiretroviral therapy, although successful in reducing HIV load and accordingly decreasing the incidence of HIV infection-related symptoms, has its drawbacks in the form of severe side effects. Recognized drug-related side effects are, for example, nausea, fatigue, lactic acidosis, neuropathy,

  4. 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 ...

  5. Risk-factors for non-adherence to antiretroviral therapy Fatores preditivos de não-adesão à terapia antiretroviral

    Directory of Open Access Journals (Sweden)

    Márcia Cristina Fraga Silva

    2009-06-01

    Full Text Available Cross-sectional study analyzed as case-control to identify risk factors for non-adherence to antiretroviral therapy. We studied 412 out-clinics HIV infected subjects of three public hospitals of Recife, Pernambuco. The objective was to examine the association between non-adherence to the antiretroviral therapy and biological, social-behavior and demographics and economic factors, factors related to the disease and/or treatment, factors related to life habits and depression symptoms. Variables significantly associated with non-adherence to antiretroviral therapy were: time elapsed since HIV diagnosis (p = 0.002, daily dose (p = 0.046, use of alcohol (p = 0.030 and past drug use (p = 0.048, and borderline p-values were found for educational level (p = 0.093 and family monthly income (p = 0.08. In the multivariable analysis, the factors that remained in the final model were family monthly income, time period with HIV infection and use of alcohol. No association was observed between non-adherence to antiretroviral therapy and gender, age, sexual orientation, marital status, educational level and place of residence. Based on our results and the local situation we suggest: assessment of social needs; training of partners and/or families on supporting adherence, creation of "adherence groups" to motivate and to reassure patients on the benefits of treatment; counseling and/or psychotherapy for alcohol drinkers.Estudo transversal com análise tipo caso-controle, que avaliou 412 pacientes de hospitais públicos do Recife - PE, com o objetivo de identificar fatores preditivos de não adesão à terapia antiretroviral. Verificou-se associação entre não adesão à terapia antiretroviral e aspectos biológicos, sócio-comportamentais e demográficos, econômicos, relacionados à doença e ao tratamento, aos hábitos de vida e aos distúrbios do humor. Variáveis com associação estatisticamente significante com não adesão na análise univariada foram

  6. Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation

    DEFF Research Database (Denmark)

    Desmonde, Sophie; Eboua, François T; Malateste, Karen

    2015-01-01

    BACKGROUND: We described reasons for switching to second-line antiretroviral treatment (ART) and time to switch in HIV-infected children failing first-line ART in West Africa. METHODS: We included all children aged 15 years or less, starting ART (at least three drugs) in the paediatric Ie...... post-ART initiation, 188 (7%) had switched to second-line. The most frequent reasons were drug stock outs (20%), toxicity (18%), treatment failure (16%) and poor adherence (8%). Over the 24-month follow-up period, 322 (12%) children failed first-line ART after a median time of 7 months...... rare and switches after an immunological failure were insufficient. These gaps reveal that it is crucial to advocate for both sustainable access to first-line and alternative regimens to provide adequate roll-out of paediatric ART programmes....

  7. Accessing antiretroviral therapy for children: Caregivers' voices

    Directory of Open Access Journals (Sweden)

    Margaret (Maggie Williams

    2016-10-01

    Full Text Available Despite efforts to scale up access to antiretroviral therapy (ART, particularly at primary health care (PHC facilities, antiretroviral therapy (ART continues to be out of reach formany human immunodeficiency virus (HIV-positive children in sub-Saharan Africa. In resource limited settings decentralisation of ART is required to scale up access to essential medication. Traditionally, paediatric HIV care has been provided in tertiary care facilities which have better human and material resources, but limited accessibility in terms of distance for caregivers of HIV-positive children. The focus of this article is on the experiences of caregivers whilst accessing ART for HIV-positive children at PHC (decentralised care facilities in Nelson Mandela Bay (NMB in the Eastern Cape, South Africa. A qualitative, explorative, descriptive and contextual research design was used. The target population comprised caregivers of HIV-positive children. Data were collected by means of indepth individual interviews, which were thematically analysed. Guba's model was usedto ensure trustworthiness. Barriers to accessing ART at PHC clinics for HIV-positive children included personal issues, negative experiences, lack of support and finance, stigma and discrimination. The researchers recommend standardised programmes be developed and implemented in PHC clinics to assist in providing treatment, care and support for HIV positive children.

  8. Accessing antiretroviral therapy for children: Caregivers' voices

    Directory of Open Access Journals (Sweden)

    Margaret (Maggie Williams

    2016-12-01

    Full Text Available Despite efforts to scale up access to antiretroviral therapy (ART, particularly at primary health care (PHC facilities, antiretroviral therapy (ART continues to be out of reach for many human immunodeficiency virus (HIV-positive children in sub-Saharan Africa. In resource limited settings decentralisation of ART is required to scale up access to essential medication. Traditionally, paediatric HIV care has been provided in tertiary care facilities which have better human and material resources, but limited accessibility in terms of distance for caregivers of HIV-positive children. The focus of this article is on the experiences of caregivers whilst accessing ART for HIV-positive children at PHC (decentralised care facilities in Nelson Mandela Bay (NMB in the Eastern Cape, South Africa. A qualitative, explorative, descriptive and contextual research design was used. The target population comprised caregivers of HIV-positive children. Data were collected by means of in-depth individual interviews, which were thematically analysed. Guba's model was used to ensure trustworthiness. Barriers to accessing ART at PHC clinics for HIV-positive children included personal issues, negative experiences, lack of support and finance, stigma and discrimination. The researchers recommend standardised programmes be developed and implemented in PHC clinics to assist in providing treatment, care and support for HIV-positive children.

  9. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignanci......ART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.......PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk...

  10. Cost-savings accruable to removing value added tax from antiretrovirals in the South African private health sector

    Directory of Open Access Journals (Sweden)

    Varsha Bangalee

    2017-10-01

    Full Text Available Background: Despite the important and essential role that medicines play in any society, all medicines, including those identified as essential, are uniformly subjected to 14% value added tax (VAT, regardless of their therapeutic value in the private healthcare sector of South Africa. The aim of this article is to demonstrate the potential cost-saving attained from the removal of VAT from the private sector pricing of essential medicines, using antiretroviral treatment as an example. Methods: An empirical analysis was undertaken to illustrate the potential cost-saving achieved by removing VAT from the Single Exit Price and the dispensing fee of essential medicines. This outcome was demonstrated by applying the methodology to an adult fixed dose combination 1st line antiretroviral regimen as well as to a group of 3rd line antiretroviral medicines. Results: The potential saving for the lowest priced generic and originator 1st line antiviral regimen accrued to ZAR 693.84 and ZAR 1085.04 over a year respectively. Regarding the 3rd line antiretroviral drugs, results yielded an annual saving of ZAR 1678.68 (darunavir, ZAR5741.04 (maraviroc and ZAR 159.48 (rilpivirine. Conclusions: Lobbying for the removal of VAT from the supply chain of medicines should be intensified. Policy development to monitor and recover lost government revenue through the removal of taxes should be explored.

  11. Early Warning Indicators for Population-Based Monitoring of HIV Drug Resistance in 6 African Countries

    NARCIS (Netherlands)

    Sigaloff, Kim C. E.; Hamers, Raph L.; Menke, Jack; Labib, Moheb; Siwale, Margaret; Ive, Prudence; Botes, Mariette E.; Kityo, Cissy; Mandaliya, Kishor; Wellington, Maureen; Osibogun, Akin; Geskus, Ronald B.; Stevens, Wendy S.; van Vugt, Michèle; Rinke de Wit, Tobias F.

    2012-01-01

    Human immunodeficiency virus (HIV) RNA testing and HIV drug resistance (HIVDR) testing are not routinely available for therapeutic monitoring of patients receiving antiretroviral therapy (ART) in resource-limited settings. World Health Organization HIVDR early warning indicators (EWIs) assess ART

  12. Review of differentiated approaches to antiretroviral therapy distribution.

    Science.gov (United States)

    Davis, Nicole; Kanagat, Natasha; Sharer, Melissa; Eagan, Sabrina; Pearson, Jennifer; Amanyeiwe, Ugochukwu Ugo

    2018-02-22

    In response to global trends of maximizing the number of patients receiving antiretroviral therapy (ART), this review summarizes literature describing differentiated models of ART distribution at facility and community levels in order to highlight promising strategies and identify evidence gaps. Databases and gray literature were searched, yielding thirteen final articles on differentiated ART distribution models supporting stable adult patients. Of these, seven articles focused on distribution at facility level and six at community level. Findings suggest that differentiated models of ART distribution contribute to higher retention, lower attrition, and less loss to follow-up (LTFU). These models also reduced patient wait time, travel costs, and time lost from work for drug pick-up. Facility- and community-level ART distribution models have the potential to extend treatment availability, enable improved access and adherence among people living with HIV (PLHIV), and facilitate retention in treatment and care. Gaps remain in understanding the desirability of these models for PLHIV, and the need for more information the negative and positive impacts of stigma, and identifying models to reach traditionally marginalized groups such as key populations and youth. Replicating differentiated care so efforts can reach more PLHIV will be critical to scaling these approaches across varying contexts.

  13. Generic substitution of antiretrovirals: patients' and health care providers' opinions.

    Science.gov (United States)

    Kieran, Jennifer A; O'Reilly, Eimear; O'Dea, Siobhan; Bergin, Colm; O'Leary, Aisling

    2017-10-01

    There is interest in introducing generic antiretroviral drugs (ARVs) into high-income countries in order to maximise efficiency in health care budgets. Studies examining patients' and providers' knowledge and attitudes to generic substitution in HIV are few. This was a cross-sectional, observational study with a convenience sample of adult HIV-infected patients and health care providers (HCPs). Data on demographics, knowledge of generic medicine and facilitators of generic substitution were collected. Descriptive and univariate analysis was performed using SPSS V.23™. Questionnaires were completed by 66 patients. Seventy-one per cent would have no concerns with the introduction of generic ARVs. An increase in frequency of administration (61%) or pill burden (53%) would make patients less likely to accept generic ARVs. There were 30 respondents to the HCP survey. Concerns included the supply chain of generics, loss of fixed dose combinations, adherence and use of older medications. An increase in dosing frequency (76%) or an increase in pill burden (50%) would make HCPs less likely to prescribe a generic ARV. The main perceived advantage was financial. Generic substitution of ARVs would be acceptable to the majority of patients and HCPs. Reinvesting savings back into HIV services would facilitate the success of such a programme.

  14. Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral agents in HIV-2 infection: a review

    Directory of Open Access Journals (Sweden)

    Maia Hightower

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 and type 2 (HIV-2 are the causative agents of AIDS. HIV-2 is prevalent at moderate to high rates in West African countries, such as Senegal, Guinea, Gambia, and Cape Verde. Diagnosis of HIV-2 is made with a positive HIV-1/HIV-2 ELISA or simple/rapid assay, followed by one or two confirmatory tests specific for HIV-2. Following CD4+ T cell counts, HIV-2 viral burden and clinical signs and symptoms of immunodeficiency are beneficial in monitoring HIV-2 disease progression. Although non-nucleoside reverse transcriptase inhibitors are ineffective in treating HIV-2, nucleoside reverse transcriptase inhibitors and protease inhibitors can be effective in dual and triple antiretroviral regimens. Their use can decrease HIV-2 viral load, increase CD4+ T cell counts and improve AIDS-related symptoms. HIV-2 resistance to various nucleoside reverse transcriptase inhibitors and protease inhibitors, including zidovudine, lamivudine, ritonavir and indinavir, has been identified in some HIV-2 infected patients on antiretroviral therapy. The knowledge of HIV-2 peculiarities, when compared to HIV-1, is crucial to helping diagnose and guide the clinician in the choice of the initial antiretroviral regimen and for monitoring therapy success.

  15. Southern African HIV Clinicians Society adult antiretroviral therapy guidelines: Update on when to initiate antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Graeme Meintjes

    2015-12-01

    Full Text Available The most recent version of the Southern African HIV Clinicians Society’s adult antiretroviral therapy (ART guidelines was published in December 2014. In the 27 August 2015 edition of the New England Journal of Medicine, two seminal randomised controlled trials that addressed the optimal timing of ART in HIV-infected patients with high CD4 counts were published: Strategic timing of antiretroviral therapy (START and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults. The findings of these two trials were consistent: there was significant individual clinical benefit from starting ART immediately in patients with CD4 counts higher than 500 cells/μL rather than deferring until a certain lower CD4 threshold or clinical indication was met. The findings add to prior evidence showing that ART reduces the risk of onward HIV transmission. Therefore, early ART initiation has the public health benefits of potentially reducing both HIV incidence and morbidity. Given this new and important evidence, the Society took the decision to provide a specific update on the section of the adult ART guidelines relating to when ART should be initiated.

  16. Identifying the composition of street drug Nyaope using two different ...

    African Journals Online (AJOL)

    The constituents consistently detected in all samples were caffeine, drugs of abuse such as opiates, codeine, morphine, methyl-dioxy amphetamine (MDA) and heroin. Some samples contained antibiotics (citroflex) and antiretroviral drugs (zidovudine). Central nervous system (CNS) depressants such as phenobarbitone ...

  17. Detection and Management of Adverse Drug Reactions Related to ...

    African Journals Online (AJOL)

    The objective of this study was to establish the detection, prevalence and management of various adverse drug reactions associated with antiretroviral drugs occurring in patients attending Comprehensive Care Centre (CCC) of Kiambu District Hospital. The study was a cross sectional survey where the patients included ...

  18. Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals.

    Science.gov (United States)

    McCormack, Shelley A; Best, Brookie M

    2014-11-01

    Maternal-to-fetal transfer of antiretroviral drugs contributes to prevention of vertical transmission of HIV. This systematic review discusses published studies containing data pertaining to the pharmacokinetics of placental transfer of antiretrovirals in humans, including paired cord and maternal plasma samples collected at the time of delivery as well as ex vivo placental perfusion models. Articles pertaining to placental transfer of antiretrovirals were identified from PubMed, from references of included articles, and from US Department of Health and Human Services Panel on Treatment of HIV-infected Pregnant Women and Prevention of Perinatal Transmission guidelines. Articles from non-human animal models or that had no original maternal-to-fetal transfer data were excluded. PRISMA guidelines were followed. A total of 103 published studies were identified. Data across studies appeared relatively consistent for the nucleoside reverse transcriptase inhibitors (NRTIs) and the non-nucleotide reverse transcriptase inhibitors (NNRTIs), with cord to maternal ratios approaching 1 for many of these agents. The protease inhibitors atazanavir and lopinavir exhibited consistent maternal-to-fetal transfer across studies, although the transfer may be influenced by variations in drug-binding proteins. The protease inhibitors indinavir, nelfinavir, and saquinavir exhibited unreliable placental transport, with cord blood concentrations that were frequently undetectable. Limited data, primarily from case reports, indicate that darunavir and raltegravir provide detectable placental transfer. These findings appear consistent with current guidelines of using two NRTIs plus an NNRTI, atazanavir/ritonavir, or lopinavir/ritonavir to maximize placental transfer as well as to optimally suppress maternal viral load. Darunavir/ritonavir and raltegravir may reasonably serve as second-line agents.

  19. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Li T

    2015-06-01

    Full Text Available Tianyuzi Li,1 Howard E Gendelman,1,2 Gang Zhang,1 Pavan Puligujja,1 JoEllyn M McMillan,1 Tatiana K Bronich,2 Benson Edagwa,1 Xin-Ming Liu,1,2 Michael D Boska3 1Department of Pharmacology and Experimental Neuroscience, 2Department of Pharmaceutical Sciences, 3Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA Abstract: Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART. Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK, pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO] particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. Keywords: folic acid, decorated nanoparticles, magnetite, theranostics, magnetic resonance imaging

  20. 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

  1. Mortality predictors of HIV-infected patients on antiretroviral therapy in Debre Tabor General Hospital and Woreta Health Center, South Gondar Zone, Northwest Ethiopia

    Directory of Open Access Journals (Sweden)

    Mekonnen Assefa Ahunie

    2017-02-01

    Full Text Available Objective: To investigate the mortality predictors of HIV-infected individuals who were receiving antiretroviral treatment. Methods: Data were extracted from medical records of 698 antiretroviral therapy (ART users enrolled at Debre Tabor General Hospital and Woreta Health Center from January 2005 to June 2014 and sociodemographic, clinical and ART-related data were collected. Mortality was compared by using time-to-event Kaplan-Meier method and log rank test and Cox regression analysis were used to identify the predictors of mortality. Results: The overall mortality rate was 1.5 per 100 persons per year. Ambulatory and bedridden patients had four- and seven-fold higher risk of death [adjusted hazard ratio (HR = 4.2, 95% confidence interval (CI: 1.7–10.7 and adjusted HR = 6.5, 95% CI: 2.0–20.7, respectively] as compared to those patients who had worked functional status. Patients who had poor antiretroviral drug adherence had five times higher risk of death (adjusted HR = 5.1, 95% CI: 1.6–16.3 than patients who had good antiretroviral adherence. Conclusions: Mortality rate was highly observed in the early phase of antiretroviral treatment. Poor ART adherence, being ambulatory and bedridden functional status was independent predictors of mortality.

  2. Manifestações otoneurológicas associadas à terapia anti-retroviral Otoneurological manifestations associated with antiretroviral therapy

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    Andrêza Batista Cheloni Vieira

    2008-02-01

    Full Text Available Ototoxicidade e terapia anti-retroviral parecem estar associadas. O objetivo desse estudo foi avaliar essa possível correlação. Foram avaliados 779 prontuários médicos de pacientes infectados pelo HIV e regularmente acompanhados, sendo 162 tratados com terapia anti-retroviral e 122 não tratados (controle. Pacientes em tratamento eram mais velhos (média 42 anos, com maior tempo de confirmação sorológica (80 meses e com menor carga viral (p=0,00. CD4+ foi semelhante entre os grupos (P=0,60. No grupo tratado, três (1,8% casos de perda auditiva idiopática e dois (1,3% de perda auditiva relacionada a otosclerose foram observadas e ambas iniciadas após terapia anti-retroviral. Nenhuma diferença estatística relacionada à perda auditiva idiopática foi encontrada entre os grupos. Enquanto estudos descritivos consideram possível ototoxidade associada à terapia anti-retroviral, esse possível efeito adverso não foi relacionado à terapia anti-retroviral neste estudo. Contrariamente, otosclerose poderia estar correlacionada à terapia anti-retroviral. Este assunto merece ser estudado.Ototoxicity and antiretroviral therapy seem to be associated. The aim of this study was to evaluate this possible correlation. Evaluations were carried out on 779 medical records from HIV-infected patients who were being regularly followed up, of whom 162 were being treated with antiretroviral therapy and 122 were untreated (controls. The patients undergoing treatment were older (mean: 42 years, had had serological confirmation for longer times (80 months and had smaller viral loads (P = 0.00. CD4+ was similar between the groups (P = 0.60. In the treated group, three cases (1.8% of idiopathic hearing loss and two (1.3% of otosclerosis-related hearing loss were observed, which both started after antiretroviral therapy. No statistical difference relating to idiopathic hearing loss was found between the groups. While descriptive studies consider possible

  3. 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.

  4. The effects of enhanced access to antiretroviral therapy: a qualitative ...

    African Journals Online (AJOL)

    The effects of enhanced access to antiretroviral therapy: a qualitative study of community perceptions in ... Twenty FGDs comprising of 190 participants and 12 KI interviews were conducted. ... All data was tape recorded with consent from

  5. Short-term treatment outcomes of children starting antiretroviral ...

    African Journals Online (AJOL)

    Short-term treatment outcomes of children starting antiretroviral therapy in the intensive care unit, general medical wards and outpatient HIV clinics at Red Cross War Memorial Children's Hospital, Cape Town, South Africa: A retrospective cohort study.

  6. Adherence to antiretrovirals in refugees and asylum seekers.

    Science.gov (United States)

    Nwoguh, Francisca

    Adherence to antiretroviral regimes is essential in effective management of HIV. The cultural, social, religious and immigration status of refugees and asylum seekers can have an impact on their understanding of their care needs and maintenance of their treatment regimen.

  7. Roles of family dynamics on adherence to highly active antiretroviral ...

    African Journals Online (AJOL)

    EB

    Background: Adherence to highly active antiretroviral therapy (HAART) has been proven .... Table 1: Relationship between socio-demographic characteristics and HAART adherence among ... constraints (44%), stigma (15%), travel/migration.

  8. Determination of eligibility to antiretroviral therapy in resource ...

    African Journals Online (AJOL)

    admin

    Objective: This study was to determine eligibility for antiretroviral therapy in resource-limited settings using total lymphocyte .... ART until CD4+ T cell counts fall below 200 cells/mm3 ... (Abbott Cell Dyne Operators manual) were checked for.

  9. Why HIV Positive Patients on Antiretroviral Treatment and/or ...

    African Journals Online (AJOL)

    Why HIV Positive Patients on Antiretroviral Treatment and/or Cotrimoxazole Prophylaxis Use Traditional Medicine: Perceptions of Health Workers, Traditional Healers and Patients: A Study in Two Provinces of South Africa.

  10. Antiretroviral therapy in a community clinic - early lessons from a ...

    African Journals Online (AJOL)

    Antiretroviral therapy in a community clinic - early lessons from a pilot project. ... The HIV Research Unit, University of Cape Town, supplied training and ... Attention must be given to the diagnosis of tuberculosis during screening and early ART ...

  11. 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 ...

  12. Scientific Production about the Adherence to Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Regina Célia De Oliveira

    2017-09-01

    Full Text Available Objective: To identify the elite of authors about the subject adherence to antiretroviral therapy; to identify the journals turned to publishing articles about adherence to antiretroviral therapy; and to identify and analyze the most commonly used words in abstracts of articles about adherence to antiretroviral therapy. Method: A bibliometric study conducted through the Scopus base. We used articles published between 1996 and 2014, after application of the eligibility criteria, there were composed the sample with 24 articles. The data were analyzed descriptively. Were used the laws of bibliometric (Lotka, Bradford and Zipf and the conceptual cloud map of words, through the program Cmap tools. Results: Lotka's Law identified the 5 authors more productive (46% of the total published. Bradford is impaired in this study. Concerning Zipf, 3 zones were determined, 31.47% of the words with in the first zone, 26.46% in the second and 42.06% in the third. In the conceptual map, the words/factors that positively and negatively influence adherence were emphasized, among them the need for more research in the health services. Conclusion: There are few publications about the accession to antiretroviral therapy, and the scientific production is in the process of maturation. One can infer that the theme researched is not yet an obsolete topic. It should be noted that the Bibliometric was a relevant statistic tool to generate information about the publications about the antiretroviral therapy. Descriptors: Antiretroviral Therapy, Highly Active; Medication Adherence; Bibliometric; HIV; Acquired Immunodeficiency Syndrome

  13. Dyslipidemia in HIV Infected Children Receiving Highly Active Antiretroviral Therapy.

    Science.gov (United States)

    Mandal, Anirban; Mukherjee, Aparna; Lakshmy, R; Kabra, Sushil K; Lodha, Rakesh

    2016-03-01

    To assess the prevalence of dyslipidemia and lipodystrophy in Indian children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI) based highly active antiretroviral therapy (HAART) and to determine the associated risk factors for the same. The present cross-sectional study was conducted at a Pediatric Clinic of a tertiary care teaching center in India, from May 2011 through December 2012. HIV infected children aged 5-15 y were enrolled if they did not have any severe disease or hospital admission within last 3 mo or receive any medications known to affect the lipid profile. Eighty-one children were on highly active antiretroviral therapy (HAART) for at least 6 mo and 16 were receiving no antiretroviral therapy (ART). Participants' sociodemographic, nutritional, clinical, and laboratory data were recorded in addition to anthropometry and evidence of lipodystrophy. Fasting lipid profile, apolipoprotein A1 and B levels were done for all the children. Among the children on highly active antiretroviral therapy (HAART), 38.3 % had dyslipidemia and 80.2 % had lipodystrophy, while 25 % antiretroviral therapy (ART) naïve HIV infected children had dyslipidemia. No clinically significant risk factors could be identified that increased the risk of dyslipidemia or lipodystrophy in children on highly active antiretroviral therapy (HAART). There is a high prevalence of dyslipidemia and lipodystrophy in Indian children with HIV infection with an imminent need to establish facilities for testing and treatment of these children for metabolic abnormalities.

  14. Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption

    DEFF Research Database (Denmark)

    Dore, Gregory J; Soriano, Vicente; Rockstroh, Jürgen

    2010-01-01

    .0002), nondetectable HBV DNA at baseline (P = 0.007), and black race (P = 0.03). Time to ART reinitiation was shorter (7.5, 15.6, and 17.8 months; P hepatitis C virus-positive and non-HBV/hepatitis...... C virus participants in the drug conservation arm. No hepatic decompensation events occurred among HBV-positive participants in either arm. CONCLUSION: HBV DNA rebound following ART interruption is common and may be associated with accelerated immune deficiency in HIV-HBV-coinfected patients.......BACKGROUND: The impact of antiretroviral therapy (ART) interruption in HIV-hepatitis B virus (HBV)-coinfected patients was examined in the Strategic Management of AntiRetroviral Therapy (SMART) study. METHODS: Plasma HBV DNA was measured in all hepatitis B surface antigen-positive (HBV...

  15. Antiretroviral treatment response of HIV-infected children after prevention of mother-to-child transmission in West Africa

    DEFF Research Database (Denmark)

    Ndondoki, Camille; Dicko, Fatoumata; Ahuatchi Coffie, Patrick

    2014-01-01

    INTRODUCTION: We assessed the rate of treatment failure of HIV-infected children after 12 months on antiretroviral treatment (ART) in the Paediatric IeDEA West African Collaboration according to their perinatal exposure to antiretroviral drugs for preventing mother-to-child transmission (PMTCT......). METHODS: A retrospective cohort study in children younger than five years at ART initiation between 2004 and 2009 was nested within the pWADA cohort, in Bamako-Mali and Abidjan-Côte d'Ivoire. Data on PMTCT exposure were collected through a direct review of children's medical records. The 12-month Kaplan....... Immunological failure was defined according to the 2006 World Health Organization age-related immunological thresholds for severe immunodeficiency. RESULTS: Among the 1035 eligible children, PMTCT exposure was only documented for 353 children (34.1%) and remained unknown for 682 (65.9%). Among children...

  16. Rapid onset of rhabdomyolysis after switching to a raltegravir-based antiretroviral regimen.

    Science.gov (United States)

    Tsai, Wan-Jung; Lee, Susan Shin-Jung; Tsai, Hung-Chin; Sy, Cheng-Len; Chen, Jui-Kuang; Wu, Kuang-Sheng; Wang, Yung-Hsin; Chen, Yao-Shen

    2016-04-01

    Raltegravir is the first integrase inhibitor antiretroviral agent that has been demonstrated to have antiviral efficacy and safety. However, the US Food and Drug Administration has recommended use with caution in patients with risk factors for rhabdomyolysis, based on four case reports of rhabdomyolysis in patients with identifiable risk factors. We present a 32-year-old Asian man with human immunodeficiency virus (HIV), but without other underlying diseases, who developed rapid-onset, raltegravir-associated rhabdomyolysis and hyperlactatemia. Our patient lacked predisposing factors for rhabdomyolysis, and the rapid onset time of 4 days was the shortest reported. Therefore, clinicians should exercise caution when using raltegravir and closely monitor all patients for the symptoms of muscle pain and weakness. This case has been reported to the National Adverse Drug Reactions Reporting System of the Department of Health in Taiwan. Copyright © 2013. Published by Elsevier B.V.

  17. Tissue Pharmacologic and Virologic Determinants of Duodenal and Rectal Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution in HIV-Infected Patients Initiating Antiretroviral Therapy.

    Science.gov (United States)

    Asmuth, David M; Thompson, Corbin G; Chun, Tae-Wook; Ma, Zhong-Min; Mann, Surinder; Sainz, Talia; Serrano-Villar, Sergio; Utay, Netanya S; Garcia, Juan Carlos; Troia-Cancio, Paolo; Pollard, Richard B; Miller, Christopher J; Landay, Alan; Kashuba, Angela D

    2017-10-17

    Plasma, duodenal, and rectal tissue antiretroviral therapy (ART) drug concentrations, human immunodeficiency virus (HIV) RNA and HIV DNA copy numbers, and recovery of mucosal immunity were measured before and 9 months after initiation of 3 different ART regimens in 26 subjects. Plasma and tissue HIV RNA correlated at baseline and when 9-month declines were compared, suggesting that these compartments are tightly associated. Antiretroviral tissue:blood penetration ratios were above the 50% inhibitory concentration values in almost 100% of cases. There were no correlations between drug concentrations and HIV DNA/RNA. Importantly, no evidence was found for residual viral replication or deficient tissue drug penetration to account for delayed gastrointestinal-associated lymphoid tissue immune recovery. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  18. Cholelithiasis and Nephrolithiasis in HIV-Positive Patients in the Era of Combination Antiretroviral Therapy.

    Directory of Open Access Journals (Sweden)

    Kuan-Yin Lin

    Full Text Available This study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy.We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT 1A1*28 and multidrug resistance gene 1 (MDR1 G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed.During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9% with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%, unboosted atazanavir (34.4%, ritonavir-boosted lopinavir (20.4%, and ritonavir-boosted atazanavir (5.5%. The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12-35.16 and older age (AOR, 1.04; 95% CI, 1.00-1.09. The positive association between duration of exposure to ritonavir-boosted atazanavir and incident

  19. Clinical Management of HIV Drug Resistance

    Science.gov (United States)

    Cortez, Karoll J.; Maldarelli, Frank

    2011-01-01

    Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. PMID:21994737

  20. Modification of First-line Antiretroviral Therapy in Treatment-naive, HIV Positive Patients

    Directory of Open Access Journals (Sweden)

    Smita Shenoy

    2017-10-01

    Full Text Available Introduction: Modification of initial Antiretroviral Therapy (ART program is an important issue in HIV infected patients as the number of ART regimens available is limited. Hence, there is a need to understand the factors that affect modification and therefore, the durability of the initial antiretroviral regimen. Aim: To study the type of modification of first line ART in treatment-naive HIV positive patients and factors influencing it. Materials and Methods: A retrospective observational study was carried out in the HIV clinic of a tertiary care hospital, using data obtained from the case records of the subjects who were initiated on ART between January 2012 to December 2014. Data on patient baseline characteristics, proportion of patients who required modification, type and time of modification was collected. The determinants of time to modification were analysed using Chi-square test. Binomial logistic regression was utilized to assess independent risk factors for change in regimen. Results: Out of 200 case records analysed, 54 patients had to undergo a modification in their initial regimen. The mean age of patients was 44.68 ± 11.31 years. Majority of the patients were males. The most common reason for modification was Adverse Drug Reactions (ADRs (79.63% followed by treatment failure (9.25%. In 85.18% cases, modification involved substitution. Occurrence of ADRs and non-tenofovir based first-line regimens were associated with higher likelihood of substitution in regimen (p<0.05. The median time (IQR to modification was 173 (152.25, 293.50 days. Conclusion: ADRs and the use of non-tenofovir based regimens resulted in significantly higher rates of modification of antiretroviral therapy. There should be monitoring of patients on ART to detect ADRs at the earliest and to obtain increased use of single tablet containing tenofovir based regimen to improve durability of first line regimens.

  1. Information and communication technologies for adherence to antiretroviral treatment in adults with HIV/AIDS.

    Science.gov (United States)

    Lima, Ivana Cristina Vieira de; Galvão, Marli Teresinha Gimeniz; Alexandre, Herta de Oliveira; Lima, Francisca Elisângela Teixeira; Araújo, Thelma Leite de

    2016-08-01

    Information and communication technologies support interventions directed at the prevention of HIV transmission and patient monitoring by promoting improved accessibility and quality of care. To evaluate the efficacy of information and communication technologies in the adherence to antiretroviral treatment in adults with HIV/AIDS. Systematic review conducted from March to May of 2015 in three databases-the Cumulative Index to Nursing and Allied Health Literature (CINAHL); the Latin-American and Caribbean Literature in Health Sciences (LILACS/BIREME) and SCOPUS; and the Cochrane library and the Medical Literature Analysis and Retrieval System Online portal (MEDLINE/PubMed). The sample consisted of nine randomized clinical trials based on the use of information and communication technologies for adherence to antiretroviral treatment in adults with HIV/AIDS. Three studies analysed the use of a short message service - SMS - two phone calls, two alarm devices, one web-enabled Hand-held device and one web electronic intervention. Improvements in the levels of adherence in the group subjected to the intervention were identified in seven studies. The phone was the type of information and communication technology with proven efficacy with respect to adherence. It was used to make calls, as well as to send alert messages and reminders about taking medications. Pagers were not considered to be effective regarding adherence to antiretroviral therapy. The integrated use of information and communication technologies with standard care promotes increased access to care, strengthening the relationship between patients and health services, with the possibility of mitigating the difficulties experienced by people with HIV in achieving optimal levels of adherence to drug therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

    Science.gov (United States)

    Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W

    2015-06-01

    CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir.

  3. Economic evaluation of weekends-off antiretroviral therapy for young people in 11 countries.

    Science.gov (United States)

    Tierrablanca, Luis Enrique; Ochalek, Jessica; Ford, Deborah; Babiker, Ab; Gibb, Diana; Butler, Karina; Turkova, Anna; Griffin, Susan; Revill, Paul

    2018-02-01

    To analyze the cost effectiveness of short-cycle therapy (SCT), where patients take antiretroviral (ARV) drugs 5 consecutive days a week and have 2 days off, as an alternative to continuous ARV therapy for young people infected with human immunodeficiency virus (HIV) and taking efavirenz-based first-line ARV drugs. We conduct a hierarchical cost-effectiveness analysis based on data on clinical outcomes and resource use from the BREATHER trial. BREATHER is a randomized trial investigating the effectiveness of SCT and continuous therapy in 199 participants aged 8 to 24 years and taking efavirenz-based first-line ARV drugs in 11 countries worldwide. Alongside nationally representative unit costs/prices, these data were used to estimate costs and quality adjusted life years (QALYs). An incremental cost-effectiveness comparison was performed using a multilevel bivariate regression approach for total costs and QALYs. Further analyses explored cost-effectiveness in low- and middle-income countries with access to low-cost generic ARV drugs and high-income countries purchasing branded ARV drugs, respectively. At 48 weeks, SCT offered significant total cost savings over continuous therapy of US dollar (USD) 41 per patient in countries using generic drugs and USD 4346 per patient in countries using branded ARV drugs, while accruing nonsignificant total health benefits of 0.008 and 0.009 QALYs, respectively. Cost-effectiveness estimates were similar across settings with access to generic ARV drugs but showed significant variation among high-income countries where branded ARV drugs are purchased. SCT is a cost-effective treatment alternative to continuous therapy for young people infected with HIV in countries where viral load monitoring is available.

  4. The incidence and types of medication errors in patients receiving antiretroviral therapy in resource-constrained settings.

    Directory of Open Access Journals (Sweden)

    Kenneth Anene Agu

    Full Text Available This study assessed the incidence and types of medication errors, interventions and outcomes in patients on antiretroviral therapy (ART in selected HIV treatment centres in Nigeria.Of 69 health facilities that had program for active screening of medication errors, 14 were randomly selected for prospective cohort assessment. All patients who filled/refilled their antiretroviral medications between February 2009 and March 2011 were screened for medication errors using study-specific pharmaceutical care daily worksheet (PCDW. All potential or actual medication errors identified, interventions provided and the outcomes were documented in the PCDW. Interventions included pharmaceutical care in HIV training for pharmacists amongst others. Chi-square was used for inferential statistics and P0.05. The major medications errors identified were 26.4% incorrect ART regimens prescribed; 19.8% potential drug-drug interaction or contraindication present; and 16.6% duration and/or frequency of medication inappropriate. Interventions provided included 67.1% cases of prescriber contacted to clarify/resolve errors and 14.7% cases of patient counselling and education; 97.4% of potential/actual medication error(s were resolved.The incidence rate of medication errors was somewhat high; and majority of identified errors were related to prescription of incorrect ART regimens and potential drug-drug interactions; the prescriber was contacted and the errors were resolved in majority of cases. Active screening for medication errors is feasible in resource-limited settings following a capacity building intervention.

  5. Regulatory challenges in developing long-acting antiretrovirals for treatment and prevention of HIV infection.

    Science.gov (United States)

    Arya, Vikram; Au, Stanley; Belew, Yodit; Miele, Peter; Struble, Kimberly

    2015-07-01

    To outline some of the regulatory challenges inherent to the development of long-acting antiretrovirals (ARVs) for the treatment or prevention of HIV infection. Despite advances in drug development that have reduced ARV dosing to once daily, suboptimal drug adherence remains an obstacle to successful HIV treatment. Further, large randomized trials of once daily oral ARVs for preexposure prophylaxis (PrEP) have shown that drug adherence correlates strongly with prophylactic effect and study outcomes. Thus, the prospect of developing long-acting ARVs, which may mitigate drug adherence issues, has attracted considerable attention lately. Because of their pharmacokinetic properties, the development of long-acting ARVs can present novel regulatory challenges. Chief among them is determining the appropriate dosing regimen, the need for an oral lead-in, and whether existing data with an approved oral agent, if available, can be leveraged for a treatment or prevention indication. For PrEP, because validated biomarkers are lacking, additional nonclinical studies and evaluation of tissue concentrations in multiple compartments may be necessary to identify optimal dosages. Study design and choice of controls for registrational trials of new long-acting PrEP agents might also prove challenging following the availability of an oral PrEP drug.

  6. [Predictive factors of clinically significant drug-drug interactions among regimens based on protease inhibitors, non-nucleoside reverse transcriptase inhibitors and raltegravir].

    Science.gov (United States)

    Cervero, Miguel; Torres, Rafael; Jusdado, Juan José; Pastor, Susana; Agud, Jose Luis

    2016-04-15

    To determine the prevalence and types of clinically significant drug-drug interactions (CSDI) in the drug regimens of HIV-infected patients receiving antiretroviral treatment. retrospective review of database. Centre: Hospital Universitario Severo Ochoa, Infectious Unit. one hundred and forty-two participants followed by one of the authors were selected from January 1985 to December 2014. from their outpatient medical records we reviewed information from the last available visit of the participants, in relation to HIV infection, comorbidities, demographics and the drugs that they were receiving; both antiretroviral drugs and drugs not related to HIV infection. We defined CSDI from the information sheet and/or database on antiretroviral drug interactions of the University of Liverpool (http://www.hiv-druginteractions.org) and we developed a diagnostic tool to predict the possibility of CSDI. By multivariate logistic regression analysis and by estimating the diagnostic performance curve obtained, we identified a quick tool to predict the existence of drug interactions. Of 142 patients, 39 (29.11%) had some type of CSDI and in 11.2% 2 or more interactions were detected. In only one patient the combination of drugs was contraindicated (this patient was receiving darunavir/r and quetiapine). In multivariate analyses, predictors of CSDI were regimen type (PI or NNRTI) and the use of 3 or more non-antiretroviral drugs (AUC 0.886, 95% CI 0.828 to 0.944; P=.0001). The risk was 18.55 times in those receiving NNRTI and 27,95 times in those receiving IP compared to those taking raltegravir. Drug interactions, including those defined as clinically significant, are common in HIV-infected patients treated with antiretroviral drugs, and the risk is greater in IP-based regimens. Raltegravir-based prescribing, especially in patients who receive at least 3 non-HIV drugs could avoid interactions. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  7. Self-perception of knowledge and adherence reflecting the effectiveness of antiretroviral therapy.

    Science.gov (United States)

    Dagli-Hernandez, Carolina; Lucchetta, Rosa Camila; de Nadai, Tales Rubens; Galduróz, José Carlos Fernandez; Mastroianni, Patricia de Carvalho

    2016-01-01

    To evaluate which indirect method for assessing adherence best reflects highly active antiretroviral therapy (HAART) effectiveness and the factors related to adherence. This descriptive, cross-sectional study was performed in 2012 at a reference center of the state of São Paulo. Self-report (simplified medication adherence questionnaire [SMAQ]) and drug refill parameters were compared to the viral load (clinical parameter of the effectiveness of pharmacotherapy [EP]) to evaluate the EP. The "Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral" (CEAT-VIH) was used to evaluate factors related to adherence and the EP and, complementarily, patient self-perception of adherence was compared to the clinical parameter of the EP. Seventy-five patients were interviewed, 60 of whom were considered as adherent from the clinical parameter of the EP and ten were considered as adherent from all parameters. Patient self-perception about adherence was the instrument that best reflected the EP when compared to the standardized self-report questionnaire (SMAQ) and drug refill parameter. The level of education and the level of knowledge on HAART were positively correlated to the EP. Forgetfulness, alcohol use, and lack of knowledge about the medications were the factors most frequently reported as a cause of nonadherence. A new parameter of patient self-perception of adherence, which is a noninvasive, inexpensive instrument, could be applied and assessed as easily as self-report (SMAQ) during monthly drug refill, since it allows monitoring adherence through pharmaceutical assistance. Therefore, patient adherence to HAART could be evaluated using self-perception (CEAT-VIH) and the viral load test.

  8. Calculation of direct antiretroviral treatment costs and potential cost savings by using generics in the German HIV ClinSurv cohort.

    Directory of Open Access Journals (Sweden)

    Matthias Stoll

    Full Text Available UNLABELLED: BACKGROUND/AIM OF THE STUDY: The study aimed to determine the cost impacts of antiretroviral drugs by analysing a long-term follow-up of direct costs for combined antiretroviral therapy, cART, -regimens in the nationwide long-term observational multi-centre German HIV ClinSurv Cohort. The second aim was to develop potential cost saving strategies by modelling different treatment scenarios. METHODS: Antiretroviral regimens (ART from 10,190 HIV-infected patients from 11 participating ClinSurv study centres have been investigated since 1996. Biannual data cART-initiation, cART-changes, surrogate markers, clinical events and the Centre of Disease Control- (CDC-stage of HIV disease are reported. Treatment duration was calculated on a daily basis via the documented dates for the beginning and end of each antiretroviral drug treatment. Prices were calculated for each individual regimen based on actual office sales prices of the branded pharmaceuticals distributed by the license holder including German taxes. RESULTS: During the 13-year follow-up period, 21,387,427 treatment days were covered. Cumulative direct costs for antiretroviral drugs of €812,877,356 were determined according to an average of €42.08 per day (€7.52 to € 217.70. Since cART is widely used in Germany, the costs for an entire regimen increased by 13.5%. Regimens are more expensive in the advanced stages of HIV disease. The potential for cost savings was calculated using non-nucleotide-reverse-transcriptase-inhibitor, NNRTI, more frequently instead of ritonavir-boosted protease inhibitor, PI/r, in first line therapy. This calculation revealed cumulative savings of 10.9% to 19.8% of daily treatment costs (50% and 90% substitution of PI/r, respectively. Substituting certain branded drugs by generic drugs showed potential cost savings of between 1.6% and 31.8%. CONCLUSIONS: Analysis of the data of this nationwide study reflects disease-specific health services research

  9. Calculation of direct antiretroviral treatment costs and potential cost savings by using generics in the German HIV ClinSurv cohort.

    Science.gov (United States)

    Stoll, Matthias; Kollan, Christian; Bergmann, Frank; Bogner, Johannes; Faetkenheuer, Gerd; Fritzsche, Carlos; Hoeper, Kirsten; Horst, Heinz-August; van Lunzen, Jan; Plettenberg, Andreas; Reuter, Stefan; Rockstroh, Jürgen; Stellbrink, Hans-Jürgen; Hamouda, Osamah; Bartmeyer, Barbara

    2011-01-01

    BACKGROUND/AIM OF THE STUDY: The study aimed to determine the cost impacts of antiretroviral drugs by analysing a long-term follow-up of direct costs for combined antiretroviral therapy, cART, -regimens in the nationwide long-term observational multi-centre German HIV ClinSurv Cohort. The second aim was to develop potential cost saving strategies by modelling different treatment scenarios. Antiretroviral regimens (ART) from 10,190 HIV-infected patients from 11 participating ClinSurv study centres have been investigated since 1996. Biannual data cART-initiation, cART-changes, surrogate markers, clinical events and the Centre of Disease Control- (CDC)-stage of HIV disease are reported. Treatment duration was calculated on a daily basis via the documented dates for the beginning and end of each antiretroviral drug treatment. Prices were calculated for each individual regimen based on actual office sales prices of the branded pharmaceuticals distributed by the license holder including German taxes. During the 13-year follow-up period, 21,387,427 treatment days were covered. Cumulative direct costs for antiretroviral drugs of €812,877,356 were determined according to an average of €42.08 per day (€7.52 to € 217.70). Since cART is widely used in Germany, the costs for an entire regimen increased by 13.5%. Regimens are more expensive in the advanced stages of HIV disease. The potential for cost savings was calculated using non-nucleotide-reverse-transcriptase-inhibitor, NNRTI, more frequently instead of ritonavir-boosted protease inhibitor, PI/r, in first line therapy. This calculation revealed cumulative savings of 10.9% to 19.8% of daily treatment costs (50% and 90% substitution of PI/r, respectively). Substituting certain branded drugs by generic drugs showed potential cost savings of between 1.6% and 31.8%. Analysis of the data of this nationwide study reflects disease-specific health services research and will give insights into the cost impacts of

  10. Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Bernaschi Massimo

    2009-10-01

    Full Text Available Abstract Background The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Methods We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART. Results Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy. In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase. Conclusion Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment.

  11. Quality of life of people living with HIV and AIDS and antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Oguntibeju OO

    2012-08-01

    Full Text Available Oluwafemi O OguntibejuOxidative Stress Research Centre, Cape Peninsula University of Technology, Bellville, South AfricaAbstract: The development of antiretroviral drugs has significantly changed the perception of HIV/AIDS from a very fatal to a chronic and potentially manageable disease, and the availability and administration of antiretroviral therapy (ART has significantly reduced mortality and morbidity associated with HIV and AIDS. There is a relationship between ART and quality of life of people living with HIV and AIDS, and several studies have reported a strong positive association between ART and improved quality of life in different domains among people living with HIV and AIDS in both developed and developing countries. However, a few studies have reported on the negative effects of ART, which directly or indirectly relate to the quality of life and longevity of HIV-infected persons. In this review, the effects and benefits of ART on people living with HIV and AIDS based on studies done in developed and developing countries is examined.Keywords: benefits, negative effects, oxidative stress, treatment, modifications of desires

  12. [Adverse side effects of antiretroviral therapy: relationship between patients' perception and adherence].

    Science.gov (United States)

    Martín, María Teresa; del Cacho, Elena; López, Ester; Codina, Carles; Tuset, Montserrat; de Lazzari, Elisa; Miró, Josep M; Gatell, Josep M; Ribas, Josep

    2007-06-23

    To evaluate the relationship between perceived adverse side effects (AE) and non-adherence associated with highly active antiretroviral therapy (HAART). For 6 consecutive months, patients taking HAART who came to the Pharmacy Department were interviewed. In the questionnaire they had to answer if they had experienced any AE over the past 6 months, what did they do in response to AE and what was the clinical evolution. Adherence was measured by pill counts or by pharmacy records (when pill counts were not possible). Of 1,936 interviewed patients, 661 (34.1%) reported AE over the past 6 months. The type of antiretroviral drug regimen and starting, re-starting or changing HAART over the past 6 months were significantly associated with AE. Patients who reported AE were 1.4 times more likely to be non-adherents. The most frequently reported AE were diarrhea followed by central nervous system abnormalities and by other gastrointestinal disturbances. In patients starting HAART, 62% of AE improved or disappeared during the first 4 weeks of therapy. Patients who report AE have worst adherence. AE are more frequent in patients starting HAART but in most cases they improve with time and/or symptomatic therapy.

  13. Pooled nucleic acid testing to identify antiretroviral treatment failure during HIV infection.

    Science.gov (United States)

    May, Susanne; Gamst, Anthony; Haubrich, Richard; Benson, Constance; Smith, Davey M

    2010-02-01

    Pooling strategies have been used to reduce the costs of polymerase chain reaction-based screening for acute HIV infection in populations in which the prevalence of acute infection is low (less than 1%). Only limited research has been done for conditions in which the prevalence of screening positivity is higher (greater than 1%). We present data on a variety of pooling strategies that incorporate the use of polymerase chain reaction-based quantitative measures to monitor for virologic failure among HIV-infected patients receiving antiretroviral therapy. For a prevalence of virologic failure between 1% and 25%, we demonstrate relative efficiency and accuracy of various strategies. These results could be used to choose the best strategy based on the requirements of individual laboratory and clinical settings such as required turnaround time of results and availability of resources. Virologic monitoring during antiretroviral therapy is not currently being performed in many resource-constrained settings largely because of costs. The presented pooling strategies may be used to significantly reduce the cost compared with individual testing, make such monitoring feasible, and limit the development and transmission of HIV drug resistance in resource-constrained settings. They may also be used to design efficient pooling strategies for other settings with quantitative screening measures.

  14. HIV INFECTION, ANTIRETROVIRAL THERAPY AND CARDIOVASCULAR RISK

    Directory of Open Access Journals (Sweden)

    Katleen de Gaetano Donati

    2010-11-01

    Full Text Available In the last 15 years, highly active antiretroviral therapy (HAART has determined a dramatic reduction of both morbidity and mortality in human immunodeficiency virus (HIV-infected subjects, transforming this infection in a chronic and manageable disease. Patients surviving with HIV in the developed world, in larger number men,  are becoming aged. As it would be expected for a population of comparable age, many HIV-infected individuals report a family history of cardiovascular disease, a small proportion have already experienced a cardiovascular event and an increasing proportion has diabetes mellitus. Smoking rate is very high while an increasing proportion of HIV-infected individuals have dyslipidaemia. Studies suggest that these traditional risk factors could play an important  role in the development of cardiovascular disease in these patients as they do in the general population. Thus, whilst the predicted 10-year cardiovascular disease risk remains relatively low at present, it will likely increase in relation to the progressive aging of  this patient population. Thus, the long-term follow-up of HIV infected patients has to include co-morbidity management such as cardiovascular disease prevention and treatment. Two intriguing aspects related to the cardiovascular risk in patients with HIV infection are the matter of current investigation: 1 while these subjects share many cardiovascular risk factors with the general population, HIV infection itself increases cardiovascular risk; 2 some HAART regimens too influence atherosclerotic profile, partly due to lipid changes. Although the mechanisms involved in the development of cardiovascular complications in HIV-infected patients remain to be fully elucidated, treatment guidelines recommending interventions to prevent cardiovascular disease in these individuals are already available; however, their application is still limited.

  15. Factors influencing global antiretroviral procurement prices.

    Science.gov (United States)

    Wirtz, Veronika J; Forsythe, Steven; Valencia-Mendoza, Atanacio; Bautista-Arredondo, Sergio

    2009-11-18

    Antiretroviral medicines (ARVs) are one of the most costly parts of HIV/AIDS treatment. Many countries are struggling to provide universal access to ARVs for all people living with HIV and AIDS. Although substantial price reductions of ARVs have occurred, especially between 2002 and 2008, achieving sustainable access for the next several decades remains a major challenge for most low- and middle-income countries. The objectives of the present study were twofold: first, to analyze global ARV prices between 2005 and 2008 and associated factors, particularly procurement methods and key donor policies on ARV procurement efficiency; second, to discuss the options of procurement processes and policies that should be considered when implementing or reforming access to ARV programs. An ARV-medicines price-analysis was carried out using the Global Price Reporting Mechanism from the World Health Organization. For a selection of 12 ARVs, global median prices and price variation were calculated. Linear regression models for each ARV were used to identify factors that were associated with lower procurement prices. Logistic regression models were used to identify the characteristics of those countries which procure below the highest and lowest direct manufactured costs. Three key factors appear to have an influence on a country's ARV prices: (a) whether the product is generic or not; (b) the socioeconomic status of the country; (c) whether the country is a member of the Clinton HIV/AIDS Initiative. Factors which did not influence procurement below the highest direct manufactured costs were HIV prevalence, procurement volume, whether the country belongs to the least developed countries or a focus country of the United States President's Emergency Plan For AIDS Relief. One of the principal mechanisms that can help to lower prices for ARV over the next several decades is increasing procurement efficiency. Benchmarking prices could be one useful tool to achieve this.

  16. Impact of antiretroviral therapy on pregnancy outcomes

    African Journals Online (AJOL)

    However, there are mixed data regarding the impact of ART on pregnancy outcomes. .... to point out that the use of illicit drugs, alcohol abuse and cigarette ... Carceller A, Ferreira E, Alloul S, Lapointe N. Lack of effect on prematurity, birth.

  17. Pillbox organizers are associated with improved adherence to HIV antiretroviral therapy and viral suppression: a marginal structural model analysis.

    Science.gov (United States)

    Petersen, Maya L; Wang, Yue; van der Laan, Mark J; Guzman, David; Riley, Elise; Bangsberg, David R

    2007-10-01

    Pillbox organizers are inexpensive and easily used; however, their effect on adherence to antiretroviral medications is unknown. Data were obtained from an observational cohort of 245 human immunodeficiency virus (HIV)-infected subjects who were observed from 1996 through 2000 in San Francisco, California. Adherence was the primary outcome and was measured using unannounced monthly pill counts. Plasma HIV RNA level was considered as a secondary outcome. Marginal structural models were used to estimate the effect of pillbox organizer use on adherence and viral suppression, adjusting for confounding by CD4+ T cell count, viral load, prior adherence, recreational drug use, demographic characteristics, and current and past treatment. Pillbox organizer use was estimated to improve adherence by 4.1%-4.5% and was associated with a decrease in viral load of 0.34-0.37 log10 copies/mL and a 14.2%-15.7% higher probability of achieving a viral load organizers appear to significantly improve adherence to antiretroviral therapy and to improve virologic suppression. We estimate that pillbox organizers may be associated with a cost of approximately $19,000 per quality-adjusted life-year. Pillbox organizers should be a standard intervention to improve adherence to antiretroviral therapy.

  18. Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis.

    Science.gov (United States)

    Gupta, Ravindra K; Jordan, Michael R; Sultan, Binta J; Hill, Andrew; Davis, Daniel H J; Gregson, John; Sawyer, Anthony W; Hamers, Raph L; Ndembi, Nicaise; Pillay, Deenan; Bertagnolio, Silvia

    2012-10-06

    The emergence and spread of high levels of HIV-1 drug resistance in resource-limited settings where combination antiretroviral treatment has been scaled up could compromise the effectiveness of national HIV treatment programmes. We aimed to estimate changes in the prevalence of HIV-1 drug resistance in treatment-naive individuals with HIV since initiation of rollout in resource-limited settings. We did a systematic search for studies and conference abstracts published between January, 2001, and July, 2011, and included additional data from the WHO HIV drug resistance surveillance programme. We assessed the prevalence of drug-resistance mutations in untreated individuals with respect to time since rollout in a series of random-effects meta-regression models. Study-level data were available for 26,102 patients from sub-Saharan Africa, Asia, and Latin America. We recorded no difference between chronic and recent infection on the prevalence of one or more drug-resistance mutations for any region. East Africa had the highest estimated rate of increase at 29% per year (95% CI 15 to 45; p=0·0001) since rollout, with an estimated prevalence of HIV-1 drug resistance at 8 years after rollout of 7·4% (4·3 to 12·7). We recorded an annual increase of 14% (0% to 29%; p=0·054) in southern Africa and a non-significant increase of 3% (-0·9 to 16; p=0·618) in west and central Africa. There was no change in resistance over time in Latin America, and because of much country-level heterogeneity the meta-regression analysis was not appropriate for Asia. With respect to class of antiretroviral, there were substantial increases in resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) in east Africa (36% per year [21 to 52]; pAfrica (23% per year [7 to 42]; p=0·0049). No increase was noted for the other drug classes in any region. Our findings suggest a significant increase in prevalence of drug resistance over time since antiretroviral rollout in regions of sub

  19. Response to combination antiretroviral therapy: variation by age

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2008-01-01

    -naive individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults...... and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. CONCLUSION: Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy...

  20. In vivo mitochondrial function in HIV-infected persons treated with contemporary anti-retroviral therapy: a magnetic resonance spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Brendan A I Payne

    Full Text Available Modern anti-retroviral therapy is highly effective at suppressing viral replication and restoring immune function in HIV-infected persons. However, such individuals show reduced physiological performance and increased frailty compared with age-matched uninfected persons. Contemporary anti-retroviral therapy is thought to be largely free from neuromuscular complications, whereas several anti-retroviral drugs previously in common usage have been associated with mitochondrial toxicity. It has recently been established that patients with prior exposure to such drugs exhibit irreversible cellular and molecular mitochondrial defects. However the functional significance of such damage remains unknown. Here we use phosphorus magnetic resonance spectroscopy ((31P-MRS to measure in vivo muscle mitochondrial oxidative function, in patients treated with contemporary anti-retroviral therapy, and compare with biopsy findings (cytochrome c oxidase (COX histochemistry. We show that dynamic oxidative function (post-exertional ATP (adenosine triphosphate resynthesis was largely maintained in the face of mild to moderate COX defects (affecting up to ∼10% of fibers: τ½ ADP (half-life of adenosine diphosphate clearance, HIV-infected 22.1±9.9 s, HIV-uninfected 18.8±4.4 s, p = 0.09. In contrast, HIV-infected patients had a significant derangement of resting state ATP metabolism compared with controls: ADP/ATP ratio, HIV-infected 1.24±0.08×10(-3, HIV-uninfected 1.16±0.05×10(-3, p = 0.001. These observations are broadly reassuring in that they suggest that in vivo mitochondrial function in patients on contemporary anti-retroviral therapy is largely maintained at the whole organ level, despite histochemical (COX defects within individual cells. Basal energy requirements may nevertheless be increased.

  1. Rationale and uses of a public HIV drug-resistance database.

    Science.gov (United States)

    Shafer, Robert W

    2006-09-15

    Knowledge regarding the drug resistance of human immunodeficiency virus (HIV) is critical for surveillance of drug resistance, development of antiretroviral drugs, and management of infections with drug-resistant viruses. Such knowledge is derived from studies that correlate genetic variation in the targets of therapy with the antiretroviral treatments received by persons from whom the variant was obtained (genotype-treatment), with drug-susceptibility data on genetic variants (genotype-phenotype), and with virological and clinical response to a new treatment regimen (genotype-outcome). An HIV drug-resistance database is required to represent, store, and analyze the diverse forms of data underlying our knowledge of drug resistance and to make these data available to the broad community of researchers studying drug resistance in HIV and clinicians using HIV drug-resistance tests. Such genotype-treatment, genotype-phenotype, and genotype-outcome correlations are contained in the Stanford HIV RT and Protease Sequence Database and have specific usefulness.

  2. The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

    Directory of Open Access Journals (Sweden)

    Sinha Sanjeev

    2011-11-01

    Full Text Available Abstract Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV and tuberculosis (TB co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART when co-administered with rifampicin-containing antituberculosis treatment (ATT and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1% patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83 at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10, 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08, 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10 respectively and 3.04 μg/ml (in cases. Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in

  3. Antiretroviral activity of protease inhibitors against Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Lianet Monzote

    2013-02-01

    Full Text Available The introduction of highly active antiretroviral therapy (HAART has caused a marked reduction in the occurrence and severity of parasitic infections, including the toxoplasmic encephalitis (TE. These changes have been attributed to the restoration of cell-mediated immunity. This study was developed to examine the activity of six antiretroviral protease inhibitors (API on Toxoplasma gondii tachyzoites. The six API showed anti-Toxoplasma activity, with IC50 value between 1.4 and 6.6 µg/mL. Further studies at the molecular level should be performed to clarify if the use of API could be beneficial or not for AIDS patients with TE.

  4. Avances recientes en VIH/SIDA: Terapia antiretroviral.

    Directory of Open Access Journals (Sweden)

    Ernesto Scerpella

    1997-01-01

    Full Text Available Recent advances in our understanding of HIV infection in patients with the acquired immunodeficiency syndrome (AIDS are leading us to explore new treatment strategies, including the use of combination antiretroviral therapy. In this review, we present information from recently completed clinical trials explore the use of combination therapy, including ACTG 175, the Delta studies, and the NUCA studies. In addition, we present preliminary about use of protease inhibitors, the newest class of antiretrovirals. (Rev Med Hered 1997; 8: 23-31.

  5. Scaling up stigma? The effects of antiretroviral roll-out on stigma and HIV testing. Early evidence from rural Tanzania

    Science.gov (United States)

    Roura, M; Urassa, M; Busza, J; Mbata, D; Wringe, A; Zaba, B

    2009-01-01

    Objective: To investigate the interplay between antiretroviral therapy (ART) scale-up, different types of stigma and Voluntary Counselling and Testing (VCT) uptake 2 years after the introduction of free ART in a rural ward of Tanzania. Methods: Qualitative study using in-depth interviews and group activities with a purposive sample of 91 community leaders, 77 ART clients and 16 health providers. Data were analysed for recurrent themes using NVIVO-7 software. Results: The complex interplay between ART, stigma and VCT in this setting is characterised by two powerful but opposing dynamics. The availability of effective treatment has transformed HIV into a manageable condition which is contributing to a reduction in self-stigma and is stimulating VCT uptake. However, this is counterbalanced by the persistence of blaming attitudes and emergence of new sources of stigma associated with ART provision. The general perception among community leaders was that as ART users regained health, they increasingly engaged in sexual relations and “spread the disease.” Fears were exacerbated because they were perceived to be very mobile and difficult to identify physically. Some leaders suggested giving ART recipients drugs “for impotence,” marking them “with a sign” and putting them “in isolation camps.” In this context, traditional beliefs about disease aetiology provided a less stigmatised explanation for HIV symptoms contributing to a situation of collective denial. Conclusion: Where anticipated stigma prevails, provision of antiretroviral drugs alone is unlikely to have sufficient impact on VCT uptake. Achieving widespread public health benefits of ART roll-out requires community-level interventions to ensure local acceptability of antiretroviral drugs. PMID:19036776

  6. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial

    NARCIS (Netherlands)

    Raffi, François; Babiker, Abdel G.; Richert, Laura; Molina, Jean-Michel; George, Elizabeth C.; Antinori, Andrea; Arribas, Jose R.; Grarup, Jesper; Hudson, Fleur; Schwimmer, Christine; Saillard, Juliette; Wallet, Cédrick; Jansson, Per O.; Allavena, Clotilde; van Leeuwen, Remko; Delfraissy, Jean-François; Vella, Stefano; Chêne, Geneviève; Pozniak, Anton; Dedes, Nikos; Autran, Brigitte; Bucciardini, Raffaella; Horban, Andrzej; Arribas, José; Boffito, Marta; Pillay, Deenan; Franquet, Xavier; Schwarze, Siegfried; Fischer, Aurélie; Diallo, Alpha; Moecklinghoff, Christiane; Stellbrink, Hans-Jürgen; Gatell, José; Sandström, Eric; Flepp, Markus; Ewings, Fiona; Pearce, Gillian; Quercia, Romina; Rogatto, Felipe; Leavitt, Randi; Nguyen, Bach-Yen; Goebel, Frank; Marcotullio, Simone; Kaur, Navrup; Sasieni, Peter; Spencer-Drake, Christina; Peto, Tim; Miller, Veronica; Arnault, Fabien; Boucherie, Céline; Jean, Delphine; Paniego, Virginie; Paraina, Felasoa; Rouch, Elodie; Soussi, Malika; Taieb, Audrey; Touzeau, Guillaume; Cursley, Adam; Dodds, Wendy; Hoppe, Anne; Kummeling, Ischa; Pacciarini, Filippo; Paton, Nick; Russell, Charlotte; Taylor, Kay; Ward, Denise; Aagaard, Bitten; Eid, Marius; Gey, Daniela; Jensen, Birgitte Gram; Jakobsen, Marie-Louise; Jensen, Karoline; Joensen, Zillah Maria; Larsen, Ellen Moseholm; Pahl, Christiane; Pearson, Mary; Nielsen, Birgit Riis; Reilev, Søren Stentoft; Christ, Ilse; Lathouwers, Desiree; Manting, Corry; Mendy, Bienvenu Yves; Metro, Annie; Couffin-Cadiergues, Sandrine; Knellwolf, Anne-Laure; Palmisano, Lucia; Aznar, Esther; Barea, Cristina; Cotarelo, Manuel; Esteban, Herminia; Girbau, Iciar; Moyano, Beatriz; Ramirez, Miriam; Saiz, Carmen; Sanchez, Isabel; Yllescas, Maria; Binelli, Andrea; Colasanti, Valentina; Massella, Maurizio; Anagnostou, Olga; Gioukari, Vicky; Touloumi, Giota; Schmied, Brigitte; Rieger, Armin; Vetter, Norbert; de Wit, Stephane; Florence, Eric; Vandekerckhove, Linos; Gerstoft, Jan; Mathiesen, Lars; Katlama, Christine; Cabie, André; Cheret, Antoine; Dupon, Michel; Ghosn, Jade; Girard, Pierre-Marie; Goujard, Cécile; Lévy, Yves; Morlat, Philippe; Neau, Didier; Obadia, Martine; Perre, Philippe; Piroth, Lionel; Reynes, Jacques; Tattevin, Pierre; Raffi, Francois; Ragnaud, Jean Marie; Weiss, Laurence; Yazdanpanah, Yazdan; Yeni, Patrick; Zucman, David; Behrens, Georg; Esser, Stefan; Fätkenheuer, Gerd; Hoffmann, Christian; Jessen, Heiko; Rockstroh, Jürgen; Schmidt, Reinhold; Stephan, Christoph; Unger, Stefan; Hatzakis, Angelos; Daikos, George L.; Papadopoulos, Antonios; Skoutelis, Athamasios; Banhegyi, Denes; Mallon, Paddy; Mulcahy, Fiona; Andreoni, Massimo; Bonora, Stefano; Castelli, Francesco; Monforte, Antonella D.'Arminio; Galli, Massimo; Lazzarin, Adriano; Mazzotta, Francesco; Vullo, Vincenzo; Prins, Jan; Richter, Clemens; Verhagen, Dominique; Eeden, Van; Doroana, Manuela; Antunes, Francisco; Maltez, Fernando; Sarmento-Castro, Rui; Gonzalez Garcia, Juan; López Aldeguer, José; Clotet, Bonaventura; Domingo, Pere; Gatell, Jose M.; Knobel, Hernando; Marquez, Manuel; Pilar Miralles, Martin; Portilla, Joaquin; Soriano, Vicente; Tellez, Maria-Jesus; Thalme, Anders; Blaxhult, Anders; Gisslen, Magnus; Winston, Alan; Fox, Julie; Gompels, Mark; Herieka, Elbushra; Johnson, Margaret; Leen, Clifford; Teague, Alastair; Williams, Ian; Boyd, Mark Alastair; Møller, Nina Friis; Larsen, Ellen Frøsig Moseholm; Le Moing, Vincent; Wit, Ferdinand W. N. M.; Kowalska, Justyna; Berenguer, Juan; Moreno, Santiago; Müller, Nicolas J.; Török, Estée; Post, Frank; Angus, Brian; Boucher, Charles; Calvez, Vincent; Collins, Simon; Dunn, David; Fox, Zoe; Perno, Carlo Federico; Ammassari, Adriana; Stoehr, Wolgang; Schmidt, Reinhold Ernst; Odermarsky, Michal; Smith, Colette; Thiébaut, Rodolphe; Arribas, Jose; de La Serna, Jose Ignacio Bernardino; Castagna, Antonella; Furrer, Hans-Jackob; Mocroft, Amanda; Reiss, Peter; Fragola, Vincenzo; Lauriola, Marco; Murri, Rita; Nieuwkerk, Pythia; Spire, Bruno; Volny-Anne, Alain; West, Brian; Amieva, Hélène; Llibre Codina, Josep Maria

    2014-01-01

    Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. Between August, 2010, and September, 2011, we

  7. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  8. SCAlING UP THE USE OF ANTIRETROVIRAlS IN THE PUBLIC ...

    African Journals Online (AJOL)

    2003-08-01

    Aug 1, 2003 ... access also has to grapple with the challenge of ensuring that people take drugs ... scaling up procurement: provision of affordable drugs, and ... outside government. ... South Africa provide useful models for the design of an.

  9. Pronounced in vitro and in vivo antiretroviral activity of 5-substituted 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy] pyrimidines

    Czech Academy of Sciences Publication Activity Database

    Balzarini, J.; Schols, D.; Van Laethem, K.; De Clercq, E.; Hocková, Dana; Masojídková, Milena; Holý, Antonín

    2007-01-01

    Roč. 59, č. 1 (2007), s. 80-86 ISSN 0305-7453 R&D Projects: GA MŠk 1M0508; GA AV ČR IBS4055109; GA AV ČR 1QS400550501 Grant - others:ISEP/FORTIS(XE) GOA/2005/19 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antiretroviral drugs * HIV * MSV * PMEO-DAPy Subject RIV: CC - Organic Chemistry Impact factor: 4.038, year: 2007

  10. 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...

  11. Impact of Human Immunodeficiency Virus Type-1 Sequence Diversity on Antiretroviral Therapy Outcomes

    Directory of Open Access Journals (Sweden)

    Allison Langs-Barlow

    2014-10-01

    Full Text Available Worldwide circulating HIV-1 genomes show extensive variation represented by different subtypes, polymorphisms and drug-resistant strains. Reports on the impact of sequence variation on antiretroviral therapy (ART outcomes are mixed. In this review, we summarize relevant published data from both resource-rich and resource-limited countries in the last 10 years on the impact of HIV-1 sequence diversity on treatment outcomes. The prevalence of transmission of drug resistant mutations (DRMs varies considerably, ranging from 0% to 27% worldwide. Factors such as geographic location, access and availability to ART, duration since inception of treatment programs, quality of care, risk-taking behaviors, mode of transmission, and viral subtype all dictate the prevalence in a particular geographical region. Although HIV-1 subtype may not be a good predictor of treatment outcome, review of emerging evidence supports the fact that HIV-1 genome sequence-resulting from natural polymorphisms or drug-associated mutations-matters when it comes to treatment outcomes. Therefore, continued surveillance of drug resistant variants in both treatment-naïve and treatment-experienced populations is needed to reduce the transmission of DRMs and to optimize the efficacy of the current ART armamentarium.

  12. Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum.

    Science.gov (United States)

    Ellis, Giovanina M; Huang, Sharon; Hitti, Jane; Frenkel, Lisa M

    2011-11-01

    Compare the risk of HIV drug resistance in women stopping suppressive nelfinavir (NFV)-based or Nevirapine (NVP)-based antiretroviral therapy (ART) after pregnancy. Specimens collected after stopping ART were tested for drug resistance by an oligonucleotide ligation assay and consensus sequencing. When postpartum drug resistance was detected, specimens obtained at study entry and during ART were evaluated. Sixteen of 38 women with ART-induced suppression of viral replication suspended ART postpartum. Resistance mutations were detected in 75% who stopped NFV-ART and in 50% who stopped NVP-ART. M184V, associated with Lamivudine resistance, was more frequent among those randomized to NFV-ART compared with NVP-ART (6 of 8 versus 1 of 8; P = 0.04), and nonnucleoside reverse transcriptase inhibitor resistance was detected in 4 of 8 stopping NVP-ART. HIV drug resistance was frequently observed among women who stopped suppressive NVP-ART or NFV-ART postpartum. This suggests that NFV-ART may have suboptimal potency, that staggering discontinuation of NVP-ART may be warranted, and/or ART adherence may be lax in women who choose to stop ART postpartum.

  13. Non-Hodgkin lymphoma in HIV-infected patients in the era of highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Kirk, O.; Pedersen, C.; Cozzi-Leori, A.

    2001-01-01

    This study was designed to assess the influence of highly active antiretroviral therapy (HAART) on non-Hodgkin lymphoma (NHL) among patients infected with human immunodeficiency virus (HIV). Within EuroSIDA, a multicenter observational cohort of more than 8500 patients from across Europe......, the incidences of NHL and subtypes (Burkitt, immunoblastic, primary brain lymphoma [PBL], and other/unknown histology) were determined according to calendar time of follow-up, and for those who initiated HAART (> or =3 drugs) also time on HAART. Potential predictive factors of NHL were evaluated in Cox...

  14. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1

    DEFF Research Database (Denmark)

    Raffi, François; Babiker, Abdel G; Richert, Laura

    2014-01-01

    BACKGROUND: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. METHODS: Between August, 2010......-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL. FUNDING: European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories....

  15. Bilateral Mastectomy as Radical Treatment of Gynecomastia Secondary to Antiretroviral Therapy in a Low-Income Setting: A Case Report.

    Science.gov (United States)

    Antunes, Mario; Schiavone, Marcella; Pizzol, Damiano; Di Gennaro, Francesco; Ludovico, Rossana; De Palma, Angela

    2018-05-11

    Gynecomastia is a common finding in males, with an incidence that varies widely globally. In 10-25% of cases, it is caused by drugs. Its pathophysiologic mechanism includes exposure to exogenous estrogens and medications that cause hypogonadism, antiandrogenic effects and hyperprolactinemia. Gynecomastia is associated with exposure to antiretroviral therapy (ART), particularly efavirenz. Sometimes surgery may be required as treatment. We report a case of a 46-year-old man receiving ART presenting with a marked bilateral breast enlargement who underwent bilateral mastectomy as the only successful treatment in a low-income setting.

  16. Differences in Salivary Flow Level, Xerostomia, and Flavor Alteration in Mexican HIV Patients Who Did or Did Not Receive Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Sandra López-Verdín

    2013-01-01

    Full Text Available Introduction. Objective and subjective alterations related to salivary flow have been reported in patients infected with human immunodeficiency virus (HIV, and these alterations are associated with the introduction of antiretroviral therapy. The aim of the current study was to discern whether these alterations are disease induced or secondary to drug therapy. Objective. The objective was to determine the relationships between low salivary flow, xerostomia, and flavor alterations in HIV patients who did or did not receive antiretroviral therapy. Materials and Methods. In this cross-sectional study, HIV patients were divided into two groups based on whether they had received antiretroviral therapy. Those patients with a previous diagnosis of any salivary gland disease were excluded. A survey was used to assess subjective variables, and colorimetry and salivary flow rates were measured using the Schirmer global test. Results. A total of 293 patients were included. The therapy group showed a significantly lower average salivary flow than did the group without therapy, and we observed that the flow rate tended to decrease after one year of therapy. The results were not conclusive, despite significant differences in xerostomia and flavor alteration between the groups. Conclusion. The study results suggest that antiretroviral therapy can cause cumulative damage that affects the amount of salivary flow.

  17. Prognosis of HIV-associated non-Hodgkin lymphoma in patients starting combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Bohlius, Julia; Schmidlin, Kurt; Costagliola, Dominique

    2009-01-01

    OBJECTIVE: We examined survival and prognostic factors of patients who developed HIV-associated non-Hodgkin lymphoma (NHL) in the era of combination antiretroviral therapy (cART). DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. METHODS: We included all cART-naive patients......-seven patients (72%) from 22 cohorts met inclusion criteria. Survival at 1 year was 66% [95% confidence interval (CI) 63-70%] for systemic NHL (n = 763) and 54% (95% CI: 43-65%) for primary brain lymphoma (n = 84). Risk factors for death included low nadir CD4 cell counts and a history of injection drug use...... with primary brain lymphoma. More advanced immunodeficiency is the dominant prognostic factor for mortality in patients with HIV-related NHL....

  18. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013

    DEFF Research Database (Denmark)

    Trickey, Adam; May, Margaret T.; Vehreschild, Jorg Janne

    2017-01-01

    Background Health care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost importance to patients, clinicians, and health-care planners. We examined changes in 3 year...... survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013. Methods We analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between...... ART initiation in four calendar periods (1996–99, 2000–03 [comparator], 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART. Findings 88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second...

  19. Tenofovir treatment in an unselected cohort of highly antiretroviral experienced HIV positive patients

    DEFF Research Database (Denmark)

    Lerbaek, Anne; Kristiansen, Thomas B; Katzenstein, Terese L

    2004-01-01

    The aim of the present study was to explore the treatment effect of tenofovir as implemented in clinical practice. Data are presented on 34 patients. 11 patients had tenofovir added to a stable anti-retroviral treatment (ART) and 23 patients had drugs other than tenofovir. CD4 counts, HIV......-RNA levels and genotypic resistance were determined at baseline and after 3 and 6 months. After initiation of tenofovir treatment, a mean decrease in HIV-RNA for all 34 patients was observed (-0.43 log1o copies/ml (+/- 1.22) and -0.49 log10 copies/ml (+/- 1.36) after 3 and 6 months, respectively, (p = 0...... initiation of tenofovir treatment, no significant increases in CD4 count were observed. All new NRTI-associated mutations could be explained by the background treatment. In conclusion, we observed a significant decrease in HIV-RNA only when tenofovir was prescribed, in conjunction with other anti...

  20. Caenorhabditis elegans as a Model System for Studying Drug Induced Mitochondrial Toxicity.

    Directory of Open Access Journals (Sweden)

    Richard de Boer

    Full Text Available Today HIV-1 infection is recognized as a chronic disease with obligatory lifelong treatment to keep viral titers below detectable levels. The continuous intake of antiretroviral drugs however, leads to severe and even life-threatening side effects, supposedly by the deleterious impact of nucleoside-analogue type compounds on the functioning of the mitochondrial DNA polymerase. For detailed investigation of the yet partially understood underlying mechanisms, the availability of a versatile model system is crucial. We therefore set out to develop the use of Caenorhabditis elegans to study drug induced mitochondrial toxicity. Using a combination of molecular-biological and functional assays, combined with a quantitative analysis of mitochondrial network morphology, we conclude that anti-retroviral drugs with similar working mechanisms can be classified into distinct groups based on their effects on mitochondrial morphology and biochemistry. Additionally we show that mitochondrial toxicity of antiretroviral drugs cannot be exclusively attributed to interference with the mitochondrial DNA polymerase.

  1. Factors associated with suboptimal adherence to antiretroviral therapy in Asia

    Science.gov (United States)

    Jiamsakul, Awachana; Kumarasamy, Nagalingeswaran; Ditangco, Rossana; Li, Patrick CK; Phanuphak, Praphan; Sirisanthana, Thira; Sungkanuparph, Somnuek; Kantipong, Pacharee; Lee, Christopher KC; Mustafa, Mahiran; Merati, Tuti; Kamarulzaman, Adeeba; Singtoroj, Thida; Law, Matthew

    2014-01-01

    Introduction Adherence to antiretroviral therapy (ART) plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh) in the first 24 months of ART in an Asian HIV cohort. Methods As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M) collected patients’ adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i) 14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results Out of 1316 patients, 32% ever reported 2 assessments per patient per year had an odds ratio (OR)=0.7 (95% confidence interval (CI) (0.55 to 0.90), p=0.006), compared to sites with ≤2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs) (OR=1.92, 95% CI (1.23 to 3.00), p=0.004) and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71), p<0.001). Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI) combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67), p=0.001) compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI) combination. SubAdh decreased with increasing time on ART (all p<0.001). Similar associations were found with adherence <95% as the outcome. Conclusions We found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social

  2. 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.

  3. Using cost-effectiveness analyses to inform policy: the case of antiretroviral therapy in Thailand

    Directory of Open Access Journals (Sweden)

    Walt Gill

    2006-12-01

    Full Text Available Abstract Background: Much emphasis is put on providing evidence to assist policymakers in priority setting and investment decisions. Assessing the cost-effectiveness of interventions is one technique used by policymakers in their decisions around the allocation of scarce resources. However, even where such evidence is available, other considerations may also be taken into account, and even over-ride technical evidence. Antiretroviral therapy (ART is the most effective intervention to reduce HIV-related morbidity and prolong mortality. However, treatment provision in the developing world has been hindered by the high costs of services and drugs, casting doubts on its cost-effectiveness. This paper looks at Thailand's publicly-funded antiretroviral initiative which was first introduced in 1992, and explores the extent to which cost-effectiveness evidence influenced policy. Methods: This article reviews the development of the national ART programme in Thailand between 1992 and 2004. It examines the roles of cost-effectiveness information in treatment policy decisions. Qualitative approaches including document analysis and interview of key informants were employed. Results: Two significant policy shifts have been observed in government-organised ART provision. In 1996, service-based therapy for a few was replaced by a research network to support clinical assessments of antiretroviral medication in public hospitals. This decision was taken after a domestic study illustrated the unaffordable fiscal burden and inefficient use of resources in provision of ART. The numbers of treatment recipients was maintained at 2,000 per year throughout the 1990s. It was not until 2001 that a new government pledged to extend the numbers receiving the service, as part of its commitment to universal coverage. Several elements played a role in this decision: new groups of dominant actors, drug price reductions, a pro-active civil society movement, lessons from experience

  4. Guidelines for antiretroviral therapy in adults

    African Journals Online (AJOL)

    2012-09-02

    Sep 2, 2012 ... time of seropositive HIV test) is a sufficient criterion for ART, but not .... Active depression or substance abuse should be dealt with. • A personal treatment ... specifying drug storage, strategies for missed doses and how to integrate ...... Analysis for serum creatinine and urine proteinuria must be performed.

  5. Pharmacists' Intervention to Reduce Drug Related Problems in HIV ...

    African Journals Online (AJOL)

    Despite advances in the use of highly active antiretroviral therapy (HAART) in the management of HIV/AIDS, drug-related problems (DRPs) still remain an issue, particularly in developing countries. This study evaluated the incidence of DRPs among HIV/AIDS patients in a HIV/AIDS care centre in southern Nigeria and the ...

  6. Personal barriers to antiretroviral therapy adherence: Case studies ...

    African Journals Online (AJOL)

    Personal barriers to antiretroviral therapy adherence: Case studies from a rural Uganda prospective clinical cohort. ... Journal Home > Vol 13, No 2 (2013) > ... should target specific personal barriers to ART adherence like: lack of family support, health and sexual life concerns, desire to have children and family instability.

  7. Case Report: A man on antiretroviral therapy with painful thighs

    African Journals Online (AJOL)

    A 54 year old man presented with increasing pain in both thighs for three months during a follow up visit at the antiretroviral therapy (ART) clinic of Queen Elizabeth. Central Hospital. He was first seen at the same clinic three years and eight months before the current presentation, when he started. ART with ...

  8. Effect Of Acess To Antiretroviral Therapy On Stigma, Jimma

    African Journals Online (AJOL)

    JU

    with HIV/AIDS was low 45 (16.6%) when compared with the fear of being stigmatized (perceived stigma) which was195 (72.2%). ... attitudinal change on stigma with access to antiretroviral treatment. There was a statistically significant association ..... All other ethnicities and nationalities. § PLWHA on follow up but not started ...

  9. Providing insecticide treated bed nets in antiretroviral treatment ...

    African Journals Online (AJOL)

    HIV-replication.5-13 Mathematical models show that repeated ... antiretroviral treatment clinics in Malawi: a pilot ... related disease or AIDS.3 In addition, there are between 300 - ... and growing evidence of interactive pathology.1,2. HIV ..... by the HIV Unit and its partners. ... procurement and supply chain systems developed.

  10. When to start antiretroviral therapy in infants and children | Cotton ...

    African Journals Online (AJOL)

    We review the background and key studies that inform decisions on when to initiate antiretroviral therapy (ART) in infants and children. The World Health Organization staging system from 2006 was based on conditions commonly seen in Africa and provided an impetus for advancing ART in children. Because of poor ...

  11. When to start antiretroviral therapy in infants and children

    Directory of Open Access Journals (Sweden)

    Mark F Cotton

    2009-12-01

    Full Text Available This articles provides a background for antiretroviral therapy in infants and children, incorporating both old and new data. There is increasing data favouring early therapy for all age groups. Below a year of age, all HIV-infected infants should commence therapy and thereafter at higher CD4 thresholds than previous recommendations

  12. HIV Testing and Antiretroviral Therapy Initiation at Birth: Views from ...

    African Journals Online (AJOL)

    HIV Testing and Antiretroviral Therapy Initiation at Birth: Views from a Primary Care Setting in Khayelitsha. A Nelson, J Maritz, J Giddy, L Frigati, H Rabie, G van Cutsem, T Mutseyekwa, N Jange, J Bernheimer, M Cotton, V Cox ...

  13. Religion, authority and their interplay in the shaping of antiretroviral ...

    African Journals Online (AJOL)

    The article explores how religious actors have increasingly shaped the nature of antiretroviral treatment (ART) services in Kabarole district, western Uganda. As have the regular health services, Christian donors, non-governmental organisations (NGOs), and churches in the district have also stepped up to provide money for ...

  14. 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 ...... Fear/worry. 14.2. 22. 2.5. 20 ..... Internalized Stigma, Discrimination, and Depression among Men and.

  15. The influence of antiretroviral treatment on willingness to test: a ...

    African Journals Online (AJOL)

    Previous quantitative studies suggest a mutually reinforcing relationship between HIV counselling and testing (HCT) and antiretroviral treatment (ART). HCT is the entry into ART, and access to ART appears to increase HIV-testing uptake in settings with historically low uptake. Adopting a qualitative approach, this study ...

  16. Assessment of antiretroviral treatment outcome in public hospitals ...

    African Journals Online (AJOL)

    Bernt Lindtjørn

    2009-01-31

    Jan 31, 2009 ... CD4 cell count is less than 350 and all WHO stage IV and CD4 cell count ..... Katherine H, et al: Antiretroviral therapy and early mortality in South ... Evan W, Robert S, Benita Y, Richard H, Michael V. Julio SG. ... Kara W, Silvester K, Lameck D, Abraham S, John S,. Constantin T ... Janet G, et al. Predicators of ...

  17. The intersection of antiretroviral therapy, peer support programmes ...

    African Journals Online (AJOL)

    Evidence suggests that interventions for people living with HIV infection that include, in combination, antiretroviral therapy (ART), peer support and economic empowerment are likely to be more effective than if used alone. We report a qualitative study in West Nile Uganda that explored perceptions of HIV stigma among ...

  18. End-user centeredness in antiretroviral therapy services in Nigerian ...

    African Journals Online (AJOL)

    Objective: To describe the perception of end users with regard to end-user centeredness in antiretroviral therapy (ART) service provision in Nigerian public health facilities. Design: A qualitative design was followed. Subjects and setting: Unstructured focus group discussions were conducted with end users (n = 64) in six ...

  19. Christian identity and men's attitudes to antiretroviral therapy in ...

    African Journals Online (AJOL)

    Increasing access to antiretroviral therapy (ART), especially in urban areas in Zambia, has transformed the landscape of the HIV epidemic to include hope. Drawing upon long-term ethnographic research, this article briefly describes the religious ideas of a cohort of former students of a Catholic mission boarding school for ...

  20. Correlates of highly active antiretroviral therapy adherence among ...

    African Journals Online (AJOL)

    Correlates of highly active antiretroviral therapy adherence among urban Ethiopian clients. ... clients' self-reported adherence to HAART medication, a descriptive, comparative cross-sectional study was carried out among adults receiving HAART medication at the Zewditu Memorial Hospital ART clinic in Addis Ababa.

  1. Timing of antiretroviral therapy initiation in adults with HIV ...

    African Journals Online (AJOL)

    Timing of antiretroviral therapy initiation in adults with HIV-associated tuberculosis: Outcomes of therapy in an urban hospital in KwaZulu-Natal. ... We aimed to compare clinical outcomes of patients with HIV-associated TB who commenced ART at different stages of TB therapy. Methods. A retrospective chart review was ...

  2. Malarial infection among HIV Patients on Antiretroviral Therapy (ART)

    African Journals Online (AJOL)

    Malarial infection among patients on antiretroviral therapy (ART) attending Federal Medical Centre, Makurdi, Benue State was investigated between April and August 2008 to determine the level of malaria infection in HIV/AIDS patients on ART and those not on ART with respect to CD4+ counts, age and gender. A total of ...

  3. Differences in access and patient outcomes across antiretroviral ...

    African Journals Online (AJOL)

    Objective. To assess differences in access to antiretroviral treatment (ART) and patient outcomes across public sector treatment facilities in the Free State province, South Africa. Design. Prospective cohort study with retrospective database linkage. We analysed data on patients enrolled in the treatment programme across ...

  4. Patients' perceptions of a rural decentralised anti-retroviral therapy ...

    African Journals Online (AJOL)

    Background: Geographical and financial barriers hamper accessibility to HIV services for rural communities. The government has introduced the nurse initiated management of anti-retroviral therapy at primary health care level, in an effort to improve patient access and reduce patient loads on facilities further up the system.

  5. Delays in switching patients onto second-line antiretroviral treatment ...

    African Journals Online (AJOL)

    Background: South Africa has one of the largest antiretroviral treatment (ART) programmes globally. In addition to increasing access to ART, it is important that the health system also focuses on the appropriate management of patients who fail first-line ART. Delays in switching patients onto second-line ART can adversely ...

  6. Modelling the relationship between antiretroviral treatment and HIV ...

    African Journals Online (AJOL)

    This paper shows how two publicly available epidemiological modelling packages, namely the Spectrum AIDS Impact Model and the ASSA2003 AIDS and Demographic Model, predict very different impacts from rolling out highly active antiretroviral treatment (HAART) on new HIV infections. Using South Africa as a case ...

  7. Estimates of eligibility for antiretroviral treatment (ART) and ...

    African Journals Online (AJOL)

    The study assessed the proportion of HIV-infected educators that need antiretroviral treatment (ART) according to current criteria, and estimated the impact of ART on AIDS mortality by modelling scenarios with and without access to ART. Specimens for HIV testing were obtained from 17 088 educators and a sub-sample of ...

  8. adherence to antiretroviral treatment in Zambia: a qualitative study

    African Journals Online (AJOL)

    Patients\\' adherence to antiretroviral therapy (ART) is important for effective medical treatment of HIV/AIDS. We conducted a qualitative interview study in the Copperbelt Province of Zambia in 2006. The aim of the study was to explore patients\\' and health care professionals\\' perceived barriers and facilitators to patients\\' ...

  9. Implementation and effectiveness of antiretroviral therapy in Greenland

    DEFF Research Database (Denmark)

    Lohse, N.; Ladefoged, K.; Obel, N.

    2008-01-01

    Analyses from the Danish HIV Cohort Study showed that, despite comparable economic means and general education of healthcare personnel, antiretroviral treatment of HIV in Greenland began later and has been implemented at a slower pace with lower therapeutic effectiveness than in Denmark. However...

  10. Roles of family dynamics on adherence to highly active antiretroviral ...

    African Journals Online (AJOL)

    Background: Adherence to highly active antiretroviral therapy (HAART) has been proven to be the only effective treatment for HIV/AIDS worldwide. Good adherence to HAART might require good family support. Objective: To determine the family dynamics and social support of people living with HIV/AIDS (PLWHA) and its ...

  11. Malaria in immuno-suppressed individuals on antiretroviral therapy ...

    African Journals Online (AJOL)

    Malaria in immuno-suppressed individuals on antiretroviral therapy (ART) in north-central Nigeria. C.R. Pam, B.T. Abubakar, G.O. Inwang, G.A. Amuga. Abstract. The immune deficiency caused by HIV infection reduces the immune response to malaria parasitaemia and therefore leads to an increased frequency of clinical ...

  12. Estimation of adult antiretroviral treatment coverage in South Africa ...

    African Journals Online (AJOL)

    The unmet need for treatment in adults is estimated using a Markov model of HIV progression in adults, combined with estimates of annual new HIV infections from a national AIDS and demographic model. Results. By the middle of 2008, 568 000 adults and children were receiving antiretroviral treatment in South Africa, ...

  13. Influence of highly active antiretroviral therapy (HAART) on the ...

    African Journals Online (AJOL)

    This report is part of the ongoing highly active antiretroviral therapy (HAART) trial, 167 patients were enlisted, but current analysis was restricted to 107 patients that were about a year old on the programme. The baseline weight, CD4+ cell count and serum albumin of 59 males and 48 females age 15-60 years, were ...

  14. 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...

  15. A qualitative analysis of the barriers to antiretroviral therapy initiation ...

    African Journals Online (AJOL)

    A qualitative analysis of the barriers to antiretroviral therapy initiation among children 2 to 18 months of age in Swaziland. Charisse V Ahmed, Pauline Jolly, Luz Padilla, Musa Malinga, Chantal Harris, Nobuhle Mthethwa, Inessa Ba, Amy Styles, Sarah Perry, Raina Brooks, Florence Naluyinda-Kitabire, Makhosini Mamba, ...

  16. among People Receiving Antiretroviral Treatment in Western Uganda

    African Journals Online (AJOL)

    In this paper, we use survey (n=87) and interview (n=30) data to investigate orientations towards future childbearing among people receiving antiretroviral treatment and their family members in western Uganda. We investigate how reproductive options are perceived, by those receiving treatment and those closest to them, ...

  17. Can measuring immunity to HIV during antiretroviral therapy (ART ...

    African Journals Online (AJOL)

    The vexing issue of whether the immune system can be reconstituted during HIV infection by supplying antiretroviral therapy (ART) has been a question asked about HIV-infected adults and children receiving therapy.1-9 Knowing that the immune system is sufficiently plastic in adults to show restoration of specific and ...

  18. Antiretroviral treatment uptake in patients with HIV associated TB ...

    African Journals Online (AJOL)

    Background. Delivery of integrated care for patients with HIV-associated TB is challenging. We assessed the uptake and timing of antiretroviral treatment (ART) among eligible patients attending a primary care service with co-located ART and TB clinics. Methods. In a retrospective cohort study, all HIV-associated TB patients ...

  19. Determinants of Adherence to Antiretroviral Treatment among HIV ...

    African Journals Online (AJOL)

    This study investigated factors of adherence to Antiretroviral Treatment (ART), factors or variables that can discriminate between adherent and non-adherent patients on ART were selected. Simple structured questionnaire was employed. The study sample consisted of 145 HIV patients who received ART in the Shashemene ...

  20. Update on HIV-1 acquired and transmitted drug resistance in Africa.

    Science.gov (United States)

    Ssemwanga, Deogratius; Lihana, Raphael W; Ugoji, Chinenye; Abimiku, Alash'le; Nkengasong, John; Dakum, Patrick; Ndembi, Nicaise

    2015-01-01

    The last ten years have witnessed a significant scale-up and access to antiretroviral therapy in Africa, which has improved patient quality of life and survival. One major challenge associated with increased access to antiretroviral therapy is the development of antiretroviral resistance due to inconsistent drug supply and/or poor patient adherence. We review the current state of both acquired and transmitted drug resistance in Africa over the past ten years (2001-2011) to identify drug resistance associated with the different drug regimens used on the continent and to help guide affordable strategies for drug resistance surveillance. A total of 161 references (153 articles, six reports and two conference abstracts) were reviewed. Antiretroviral resistance data was available for 40 of 53 African countries. A total of 5,541 adult patients from 99 studies in Africa were included in this analysis. The pooled prevalence of drug resistance mutations in Africa was 10.6%, and Central Africa had the highest prevalence of 54.9%. The highest prevalence of nucleoside reverse transcriptase inhibitor mutations was in the west (55.3%) and central (54.8%) areas; nonnucleoside reverse transcriptase inhibitor mutations were highest in East Africa (57.0%) and protease inhibitors mutations highest in Southern Africa (16.3%). The major nucleoside reverse transcriptase inhibitor mutation in all four African regions was M184V. Major nonnucleoside reverse transcriptase inhibitor as well as protease inhibitor mutations varied by region. The prevalence of drug resistance has remained low in several African countries although the emergence of drug resistance mutations varied across countries. Continued surveillance of antiretroviral therapy resistance remains crucial in gauging the effectiveness of country antiretroviral therapy programs and strategizing on effective and affordable strategies for successful treatment.