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
Mondy, Kristin; Tebas, Pablo
The use of highly active antiretroviral therapy (HAART) has resulted in sustained reductions in mortality from HIV infection. In recent years, HAART has also been associated with metabolic complications that may increase patients' cardiovascular disease risk. Recent studies have begun to support a more complex interaction between HAART, HIV infection itself, and other traditional social and immunologic factors that may predispose patients to premature cardiovascular disease. Substantial progress has been made in the development of newer antiretroviral therapies that have a better metabolic profile with respect to dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of metabolically neutral antiretroviral therapies, together with aggressive management of other modifiable coronary risk factors, may improve cardiovascular disease risk in the long term.
Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred M
, it remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/μl, or whether it is more advisable to defer initiation until the CD4 count has dropped to 350 cells/μl. The question of when the best time is to initiate ART during early HIV infection has......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...
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.
Full Text Available Patients with human immunodeficiency virus (HIV infection receiving antiretroviral therapy (ART, despite a reduced viral load and improved immune responses, may experience clinical deterioration. This so called "immune reconstitution inflammatory syndrome (IRIS" is caused by inflammatory response to both intact subclinical pathogens and residual antigens. Cytomegalovirus retinitis is common in HIV-infected patients on ART with a cluster differentiation 4 (CD4+ counts less than 50 cells/mm3. We reported a patient with blurred vision while receiving ART. She had an unmasking classic CMV retinitis after ART.
Borges, Álvaro H
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...... of Kaposi sarcoma and NHL also during early HIV infection before overt immunosuppression occurs. Long-term effects of cART exposure on cancer risk are not well defined; according to basic and epidemiological research, there might be specific associations of each cART class with distinct patterns of cancer...
Margaret (Maggie Williams
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.
OBJECTIVE: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. SUBJECTS:: Forty-nine thousand nine hundred and twenty-one antiretroviral......-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...... and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2-54.1%) and 59.2% (58.7-59.6%) had experienced a virological and immunological...
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.
Fitzgerald Daniel W
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.
Full Text Available Background: Acquired immune deficiency syndrome (AIDS is now considered as a manageable chronic illness. There has been a dramatic reduction in human immunodeficiency virus (HIV related morbidity and mortality due to antiretroviral therapy. A high level of adherence (>95% is required for antiretroviral therapy to be effective. There are many barriers to adherence in both developed and developing countries. Aim: The aim of our study was to determine adherence levels and factors influencing adherence to antiretroviral therapy among people living with HIV. Materials and Methods: Using a cross-sectional study design, 116 HIV positive patients receiving antiretroviral therapy for at least 1 year were interviewed using a semi structured questionnaire. The collected data was analyzed using Statistical Product and Service Solutions (SPSS version 11.5. Chi-square test was done. A P value of < 0.05 was considered statistically significant. Results: Of 116 participants, 63.7% reported adherence ≥ 95%. Mean adherence index was 91.25%. Financial constraints, forgetting to take medication, lack of family care, depression, alcohol use, social stigma and side effects to antiretroviral therapy were barriers for adherence in our study. Conclusion: Adherence to antiretroviral therapy in south India is suboptimal. Intensive adherence counseling should be provided to all patients before initiation ofantiretroviral therapy. Health care providers must identify possible barriers to adherence at the earliest and provide appropriate solutions.
Bruce L GILLIAM; Robert R REDFIELD
China has recognized the threat of HIV to its population and responded with a national antiretroviral treatment (ART)program. However, high ART failure rates and the spread of resistance within populations are important realities to consider when developing and managing ART programs in China and worldwide. Concepts which will define treatment success and local and national programmatic goals are 1) access to ART, 2) durability of ART at the patient level, 3)scalability of treatment modalities, and the 4) sustainability of the program at the community or national level. In the face of limited resources, China must also consider when to start ARV therapy, which agents to use, when to switch them, and how to treat highly experienced patients with drug resistance. The optimal ARV regimen to start with is changing frequently with the introduction of new agents and the presentation of new data. Currently, a regimen including tenofovir, emtricitabine or lamivudine and a nonnucleoside reverse transcriptase inhibitor appears to have optimal characteristics to treat HIV/AIDS in China. However, critical to all of these choices is the evaluation of programs implemented to insure wide scale success. China has wisely begun this process of evaluating the performance of local programs through systematic monitoring and evaluation of treatment outcomes. This will allow regimens and programs that work to be expanded, and programs with high failure rates to be eliminated. In the end,evidence based data supporting treatment strategies will allow China to successfully confront its AIDS epidemic early and prevent its tragic consequences
P.L.A. Fraaij (Pieter); J.J.A. van Kampen (Jeroen); D.M. Burger (David); R. de Groot (Ronald)
textabstractThe initiation of antiretroviral therapy has resulted in an impressive reduction in the rate of disease progression in AIDS and HIV-1-related deaths in children; however, there are still several major challenges to be faced in order to improve therapy. A major topic that needs to be deal
Michael N. Neely
Full Text Available Large populations of HIV-infected and exposed infants, children and adolescents are increasingly exposed to antiretroviral therapy throughout dramatic changes of the body composition and maturation process in utero, perinatally and during the later growth and development throughout childhood and puberty. The majority of HIV-infected children live in the resource-limited setting where the presence of other significant co-morbidities such as malnutrition, tuberculosis and malaria complicates the selection of the most effective, safe and least toxic combination of antiretroviral drug therapy. This review focuses on the role of the pharmacokinetic factors including clinically important drug-drug interactions on the therapeutic targets of antiretroviral therapy throughout childhood and adolescence. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research
Wendel Mombaque dos Santos
Full Text Available ABSTRACT Objective: to investigate potential drug-drug interactions (PDDI in patients with HIV infection on antiretroviral therapy. Methods: 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. Results: 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 < 0.00. The clinical impact was prevalent sedation and cardiotoxicity. Conclusions: the PDDI identified in this study of moderate and higher severity are events that not only affect the therapeutic response leading to toxicity in the central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs.
El-Sadr, W M; Grund, B; Neuhaus, J;
BACKGROUND: Episodic use of antiretroviral therapy guided by CD4+ cell counts is inferior to continuous antiretroviral therapy. OBJECTIVE: To determine whether reinitiating continuous antiretroviral therapy in patients who received episodic treatment reduces excess risk for opportunistic disease ...
Superior adherence to HIV-1 antiretroviral therapy is a mainstay of successful HIV management. Studies performed in the early era of highly active antiretroviral therapy demonstrated the need for > or =95% adherence in order to achieve and sustain viral suppression. High rates of viral suppression have been observed at more moderate levels of adherence with newer antiretroviral regimens. The term 'forgiveness' is being used to describe the ability of a regimen to achieve and sustain viral suppression, despite suboptimal adherence. A variety of pharmacological, viral and host properties determine the level of forgiveness of any specific regimen. As the choice of treatment options continues to expand, forgiveness of non-adherence is likely to emerge as an increasingly important factor in therapeutic decision-making.
Eduardo Milton Ramos-Sanchez
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.
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.
Reynolds, Nancy R; Testa, Marcia A; Marc, Linda G; Chesney, Margaret A; Neidig, Judith L; Smith, Scott R; Vella, Stefano; Robbins, Gregory K
It is widely recognized that adherence to antiretroviral therapy is critical to long-term treatment success, yet rates of adherence to antiretroviral medications are frequently subtherapeutic. Beliefs about antiretroviral therapy and psychosocial characteristics of HIV-positive persons naive to therapy may influence early experience with antiretroviral medication adherence and therefore could be important when designing programs to improve adherence to antiretroviral therapy. As part of a multicenter AIDS Clinical Trial Group (ACTG 384) study, 980 antiretroviral-naive subjects (82% male, 47% White, median age 36 years, and median CD4 cell count 278 cells/mm3) completed a self-administered questionnaire prior to random treatment assignment of initial antiretroviral medications. Measures of symptom distress, general health and well-being, and personal and situational factors including demographic characteristics, social support, self-efficacy, depression, stress, and current adherence to (nonantiretroviral) medications were recorded. Associations among variables were explored using correlation and regression analyses. Beliefs about the importance of antiretroviral adherence and ability to take antiretroviral medications as directed (adherence self-efficacy) were generally positive. Fifty-six percent of the participants were "extremely sure" of their ability to take all medications as directed and 48% were "extremely sure" that antiretroviral nonadherence would cause resistance, but only 37% were as sure that antiretroviral therapy would benefit their health. Less-positive beliefs about antiretroviral therapy adherence were associated with greater stress, depression, and symptom distress. More-positive beliefs about antiretroviral therapy adherence were associated with better scores on health perception, functional health, social-emotional-cognitive function, social support, role function, younger age, and higher education (r values = 0.09-0.24, all p < .001). Among
Full Text Available Study of plasma and intracellular concentrations of atazanavir, lopinavir, nevirapine, and efavirenz was conducted on 48 patients under short cycles of antiretroviral therapy. Intracellular concentrations (IC were still measurable for all drugs after 85 h or 110 h drug intake despite the absence of drug in plasma for atazanavir and lopinavir. A linear relationship between plasma and intracellular efavirenz was observed. Further studies to fully understand the impact of IC in the intermittent antiviral treatment are required.
Jordan, M R; Obeng-Aduasare, Y; Sheehan, H; Hong, S Y; Terrin, N; Duong, D V; Trung, N V; Wanke, C; Kinh, N V; Tang, A M
The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among injection drug users and commercial sex workers. Socio-demographics, substance use and clinical correlates of antiretroviral therapy non-adherence were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6 months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9 ± 4.9 years. The median duration on antiretroviral therapy was 16.2 ± 12.7 months; 83% reported 'very good' or 'perfect' adherence in the past 30 days on a subjective one-item Likert scale at time of study enrollment; 48% of participants reported drug use within the previous 6 months, with 22% reporting current drug use. Injection drug use with or without non-injection drug use in the past 6 months (95% C.I. 2.19, 1.30-3.69) and years on antiretroviral therapy (95% C.I. 1.43, 1.14-1.78) were correlated with suboptimal adherence. These findings support Vietnam's ongoing scale-up of harm reduction programmes for injection drug users and their integration with antiretroviral therapy delivery. Moreover, results highlight the need to identify and implement new ways to support high levels of antiretroviral therapy adherence as duration on antiretroviral therapy increases.
Koosha Paydary; Parisa Khaghani; Sahra Emamzadeh-Fard; SeyedAhmad SeyedAlinaghi; Kazem Baesi
After its identification in 1980s, HIV has infected more than 30 million people worldwide. In the era of highly active anti-retroviral therapy, anti-retroviral drug resistance results from insufficient anti-retroviral pressure, which may lead to treatment failure. Preliminary studies support the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developed world;however, a highly heterogeneous horde of viral quasi-species are currently circulating in developing nations. Thus, the prioritizing of strategies adopted in such two worlds should be quite different considering the varying anti-retroviral drug resistance prevalence. In this article, we explore differences in anti-retroviral drug resistance patterns between developed and developing countries, as they represent two distinct ecological niches of HIV from an evolutionary standpoint.
Tengiz Tsertsvadze; Nikoloz Chkhartishvili; Lali Sharvadze; Natia Dvali; Otar Chokoshvili; Pati Gabunia; Akaki Abutidze; Kenrad Nelson; Jack DeHovitz; Carlos del Rio
Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141 cells/mm3. During followup, 152 (...
Tavel, Jorge A; Babiker, Abdel; Fox, Lawrence;
BACKGROUND: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4(+) counts compared to no therapy. METHODOLOGY: Participants not on continuous ART...... with > or = 300 CD4(+) cells/mm(3) were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4(+) counts, HIV RNA, and HIV progression events were collected monthly. PRINCIPAL FINDINGS: A total...... of 267 participants were randomized. At week 32, the mean CD4(+) count was 134 cells greater in the IL-2 alone group (ptherapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group...
Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia
SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy.
Full Text Available Sclerosing colangitis (SC due to cytomegalovirus (CMV is very rare. It has been described mainly in immunocompromised patients. Currently, in HIV infected patients it is exceptional. The most of cases belong to pre-highly active antiretroviral therapy (pre-HAART and those cases were in stage AIDS with less than 100 CD4/μl. The most frequently involved pathogen in pre-HAART period was Cryptosporidium parvum (30-57% and CMV (10-30%; in late HAART period this information are unaware. CMV has been implicated as a possible etiological agent in primary SC partly because of the ability to cause liver damage and its relationship with smooth muscle antibodies. The most effective treatment for SC was the combination of antiretroviral therapy and endoscopic retrograde cholangiopancreatography with sphincterotomy and stent placement. Following, we present the first case of late HAART period which describes a SC extrahepatic without papillary stenosis with CMV as the only cause and clinical presentation of HIV infection in a woman with 177 CD4/μl.
Manuela G. Neuman
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.
Kimberly N. Capers
Full Text Available Guillain-Barré syndrome (GBS has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome.
Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred
BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS: We randomly assigned HIV...... entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients...... per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.)....
Dominique J Pepper
Full Text Available BACKGROUND: In the developing world, the principal cause of death among HIV-infected patients is tuberculosis (TB. The initiation of antiretroviral therapy (ART during TB therapy significantly improves survival, however it is not known which barriers prevent eligible TB patients from initiating life-saving ART. METHOD: Setting. A South African township clinic with integrated tuberculosis and HIV services. Design. Logistic regression analyses of a prospective cohort of HIV-1 infected adults (≥18 years who commenced TB therapy, were eligible for ART, and were followed for 6 months. FINDINGS: Of 100 HIV-1 infected adults eligible for ART during TB therapy, 90 TB patients presented to an ART clinic for assessment, 66 TB patients initiated ART, and 15 TB patients died. 34% of eligible TB patients (95%CI: 25-43% did not initiate ART. Male gender and younger age (<36 years were associated with failure to initiate ART (adjusted odds ratios of 3.7 [95%CI: 1.25-10.95] and 3.3 [95%CI: 1.12-9.69], respectively. Death during TB therapy was associated with a CD4+ count <100 cells/µL. CONCLUSION: In a clinic with integrated services for tuberculosis and HIV, one-third of eligible TB patients--particularly young men--did not initiate ART. Strategies are needed to promote ART initiation during TB therapy, especially among young men.
Full Text Available Abstract Background To increase access to antiretroviral therapy in resource-limited settings, several experts recommend "task shifting" from doctors to clinical officers, nurses and midwives. This study sought to identify task shifting that has already occurred and assess the antiretroviral therapy training needs among clinicians to whom tasks have shifted. Methods The Infectious Diseases Institute, in collaboration with the Ugandan Ministry of Health, surveyed health professionals and heads of antiretroviral therapy clinics at a stratified random sample of 44 health facilities accredited to provide this therapy. A sample of 265 doctors, clinical officers, nurses and midwives reported on tasks they performed, previous human immunodeficiency virus training, and self-assessment of knowledge of human immunodeficiency virus and antiretroviral therapy. Heads of the antiretroviral therapy clinics reported on clinic characteristics. Results Thirty of 33 doctors (91%, 24 of 40 clinical officers (60%, 16 of 114 nurses (14% and 13 of 54 midwives (24% who worked in accredited antiretroviral therapy clinics reported that they prescribed this therapy (p Conclusion Training initiatives should be an integral part of the support for task shifting and ensure that antiretroviral therapy is used correctly and that toxicity or drug resistance do not reverse accomplishments to date.
Full Text Available Abstract Background The scarcity of physicians in sub-Saharan Africa – particularly in rural clinics staffed only by non-physician health workers – is constraining access to HIV treatment, as only they are legally allowed to start antiretroviral therapy in the HIV-positive patient. Here we present a pilot study from Uganda assessing agreement between non-physician clinicians (nurses and clinical officers and physicians in their decisions as to whether to start therapy. Methods We conducted the study at 12 government antiretroviral therapy sites in three regions of Uganda, all of which had staff trained in delivery of antiretroviral therapy using the WHO Integrated Management of Adult and Adolescent Illness guidelines for chronic HIV care. We collected seven key variables to measure patient assessment and the decision as to whether to start antiretroviral therapy, the primary variable of interest being the Final Antiretroviral Therapy Recommendation. Patients saw either a clinical officer or nurse first, and then were screened identically by a blinded physician during the same clinic visit. We measured inter-rater agreement between the decisions of the non-physician health workers and physicians in the antiretroviral therapy assessment variables using simple and weighted Kappa analysis. Results Two hundred fifty-four patients were seen by a nurse and physician, while 267 were seen by a clinical officer and physician. The majority (> 50% in each arm of the study were in World Health Organization Clinical Stages I and II and therefore not currently eligible for antiretroviral therapy according to national antiretroviral therapy guidelines. Nurses and clinical officers both showed moderate to almost perfect agreement with physicians in their Final Antiretroviral Therapy Recommendation (unweighted κ = 0.59 and κ = 0.91, respectively. Agreement was also substantial for nurses versus physicians for assigning World Health Organization Clinical
El-Sadr, WM; Lundgren, Jens Dilling; Neaton, JD
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 wh...
Kirk, Ole; Reiss, Peter; Uberti-Foppa, Caterina;
BACKGROUND: The safety of interrupting maintenance therapy for previous opportunistic infections other than Pneumocystis carinii pneumonia among patients with HIV infection who respond to potent antiretroviral therapy has not been well documented. OBJECTIVE: To assess the safety of interrupting m...
Full Text Available Optic neuropathy in HIV-infected patients results from the HIV infection itself, post-infectious auto-immune disease, opportunistic infections and drugs. Nucleoside reverse transcriptase inhibitors (NRTIs such as zidovudine and stavudine have known mitochondrial toxicity and can cause mitochondrial myopathies, neuropathies, hyperlactataemia, and can induce mitochondrial genetic disorders. Individuals with the mutation for Leber’s hereditary optic neuropathy (LHON, a mitochondrial disorder, are usually asymptomatic but develop visual loss when exposed to external triggers such as smoking. We report on two HIV-infected patients with LHON mutations (m.14484T>C and m.11778G>A who developed profound visual loss with antiretroviral therapy. We postulate that the phenotypic expression of LHON in these genetically predisposed individuals was triggered by NRTI drugs lamivudine and tenofovir when used in combination, despite their relatively weak mitochondrial toxic effects.
Globally, 240,000 infants are newly infected with HIV-1 each year and 3.2 million children are living with the infection. Combination antiretroviral therapy (cART) has reduced HIV-1-related disease and mortality in children but is not curative owing to the early generation of a latent reservoir of long-lived memory CD4(+) T cells bearing replication-competent HIV-1 provirus integrated into cellular DNA. This review focuses on recent advances in our understanding of the establishment of HIV-1 persistence in children and how early initiation of cART in the setting of the developing infant immune system limits the formation of the long-lived latent CD4(+) cell reservoir that remains a barrier to remission or cure.
Lodi, Sara; Dray-Spira, Rosemary; Touloumi, Giota;
OBJECTIVES: In Europe and elsewhere, health inequalities among HIV-positive individuals are of concern. We investigated late HIV diagnosis and late initiation of combination antiretroviral therapy (cART) by educational level, a proxy of socioeconomic position. DESIGN AND METHODS: We used data from...... included individuals diagnosed with HIV between 1996 and 2011, aged at least 16 years, with known educational level and at least one CD4 cell count within 6 months of HIV diagnosis. We examined trends by education level in presentation with advanced HIV disease (AHD) (CD4 ... count at cART initiation was lower with poorer educational level. CONCLUSIONS: Socioeconomic inequalities in delayed HIV diagnosis and initiation of cART are present in European countries with universal healthcare systems and individuals with lower educational level do not equally benefit from timely c...
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 A C
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).
Full Text Available Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents 15.1-19 years (adolescents, 19.1-24 years (young adults and 24.1-29.9 years (older adults. Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008. Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35. Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52. This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults.
Full Text Available BACKGROUND: Access to highly active antiretroviral therapy (HAART is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. METHODS: Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. RESULTS: Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3% failed a second line regimen and 44 (0.8% received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18-2.00, p = 0.001, younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86-4.10, p<0.001, and prior AIDS (HR = 2.17, 95% CI 1.62-2.90, p<0.001. CONCLUSIONS: Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted.
Hansen, Birgitte Rønde; Petersen, J; Haugaard, S B;
OBJECTIVES: The prevalence of metabolic syndrome (MS) in HIV-infected patients on highly active antiretroviral therapy (HAART) is a subject of debate. We investigated the prevalence of MS in a cohort of Danish HIV-infected patients and estimated the effect of the various classes of antiretroviral...
Bannister, WP; Ruiz, L; Loveday, C;
BACKGROUND: Combination antiretroviral therapy (cART) may vary in ability to suppress viral load and increase CD4+ T-cell count in people infected with different HIV-1 subtypes, possibly due to differences in resistance development. Antiretroviral drugs have predominantly been developed in Western...
Objective:To investigate the prevalence of use of traditional medicines amongst patients with HIV infection receiving therapies of antiretroviral(ARV) drugs at the Aminu Kano Teaching Hospital(AKTH), Kano, Northwest Nigeria, and to assess the attitude of these patients to theirARV therapy.Methods: A cross sectional prospective study using pretested structured questionnaires administered on430 patients with antiretroviral therapy attending the AKTH between April and June2009. Data was collected on socio-demographic characteristics, use of traditional medicine and attitude to antiretroviral therapy.Results: A mean age of(33.6±8.4)years old was found with67.2% females and32.8% males. A total of29% had no formal education while 10.5% had postgraduate education;12% earned above 35 000 naira (230 USD) per month;63.8% were married;39.8% had at least2 sexual partners; 27.5% used traditional medicine before commencement of antiretroviral therapy (ART), but only4.25% of patients used ARV and traditional medicine concurrently. There was no significant difference in most of the socio-demographic indices between the concurrent users and other patients (P>0.05). A total of 28.8% HIV patients,14.6% patients used traditional medicine beforeART and29.4% concurrent users had missed at least a dose of theirARVs since commencement of therapy. 148 (37%) of the patients had their drug regimen changed at least once while23 (20.90%) patients receiving traditional medicine beforeARTand5 (29.41%) patients having two treatments had their drug regimen changed.Conclusions: A total of4.25% patients used ARV and traditional medicine concurrently. In conclusion, the widespread use of traditional medicine by patients living with HIV/AIDSshould be of concern to clinicians and policy makers.
Thompson, George R.; Patel, Payal K.; Kirkpatrick, William R.; Westbrook, Steven D.; Berg, Deborah; Erlandsen, Josh; Redding, Spencer W.; Patterson, Thomas F.
Oropharyngeal candidiasis (OPC) remains a common problem in the HIV-infected population despite the availability of antiretroviral therapy (ART). Although Candida albicans is the most frequently implicated pathogen, other Candida spp. may also cause infection. The emergence of antifungal resistance within these causative yeasts, especially in patients with recurrent oropharyngeal infection or with long-term use of antifungal therapies, requires a working knowledge of alternative antifungal agents. Identification of the infecting organism and antifungal susceptibility testing enhances the ability of clinicians to prescribe appropriate antifungal therapy. Characterization of the responsible mechanisms has improved our understanding of the development of antifungal resistance and could enhance the management of these infections. Immune reconstitution has been shown to reduce rates of oropharyngeal candidiasis but few studies have evaluated the current impact of ART on the epidemiology of oropharyngeal candidiasis and antifungal resistance in these patients. Preliminary results from an ongoing clinical study showed that in patients with advanced AIDS oral yeast colonization was extensive, occurring in 81.1% of the 122 patients studied and symptomatic infection occurred in a third. In addition, resistant yeasts were still common occurring in 25.3% of patients colonized with yeasts or with symptomatic infection. Thus, oropharyngeal candidasis remains a significant infection in advanced AIDS even with ART. Current knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and mechanisms of antifungal resistance observed in oropharyngeal candidiasis are important in managing patients with this infection and are the focus of this review. PMID:20156694
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.
Hansen, Birgitte R; Haugaard, Steen B; Iversen, Johan;
Following the introduction of highly active antiretroviral therapy (HAART), metabolic and morphological complications known as HIV associated lipodystrophy syndrome (HALS) have been increasingly common. The approaches to target these complications span from resistance exercise, diet and use...
Peluso, Michael J; Spudich, Serena
The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.
Walter de Araujo Eyer-Silva
Full Text Available Immune reconstitution inflammatory syndrome (IRIS in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.
Jiménez-Montero, Beatriz; Beceiro, José; de José-Gómez, M Isabel; González-Tomé, M Isabel; Gurbindo-Gutierrez, Dolores; Martínez-Pérez, Jorge; Mellado-Peña, M José; Navarro-Gómez, M Luisa; Roa-Francia, Miguel A; Rojo-Conejo, Pablo; Saavedra-Lozano, Jesús; Jiménez de Ory, Santiago; Ramos-Amador, José T
We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.
Mugavero, M.J.; May, M.; Harris, R.; Saag, M.S.; Costagliola, D.; Egger, M.; Phillips, A.; Gunthard, H.F.; Dabis, F.; Hogg, R.; Wolf, F. de; Fatkenheuer, G.; Gill, M.J.; Justice, A.; Monforte, A. D'Arminio; Lampe, F.; Miro, J.M.; Staszewski, S.; Sterne, J.A.
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-naive patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between Jan
NN, NN; Mugavero, Michael J; May, Margaret
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 ...
Nel, Adriaan; Kagee, Ashraf
This paper reviews the literature on various mental health problems and their impact on adherence to antiretroviral therapy (ART). Depression, anxiety disorders, and disorders related to substance abuse were identified as key role-players influencing adherence. The severity of symptoms related to these disorders was found to be inversely related to ART adherence, with the possible exception of post-traumatic stress disorder (PTSD). PTSD was found to have both positive and negative implications for adherence, with severity of symptoms ranging from health-protective concern to disabling distress. Possible solutions aimed at addressing the adverse effects of mental health problems on adherence are discussed. Routine screening in ART settings is suggested in settings where follow-up of positive screen scores are possible, along with the necessary interventions to resolve the disorder of concern. Suggested interventions include utilising psychotherapeutic treatment, both in isolation and in conjunction with medication, to address mental health problems. Furthermore, finding effective ways of marshalling social support is recommended for ensuring optimal adherence, and possibly mitigating the adverse effects of mental health problems. Further research is needed to find feasible ways of identifying, assessing and treating patients with mental health problems in resource-constrained settings where HIV prevalence is highest.
Cribbs, Sushma K; Fontenot, Andrew P
Despite the introduction of antiretroviral therapy (ART), human immunodeficiency virus-1 (HIV) continues to cause a major impact worldwide. HIV-induced lung disease continues to represent a significant source of morbidity and mortality, although the spectrum of pulmonary diseases has changed. HIV significantly affects the lung, causing acute and chronic cellular changes in the alveolar space. The impact of ART on lung immunology still needs to be fully elucidated. Similar to the periphery, ART affects HIV viral load and reconstitutes CD4(+) T cells in the lung. ART has been associated with significant decreases in bronchoalveolar lavage lymphocytes and increases in B-cell numbers and functionality, resulting in improved immune responses to vaccinations. There are substantial clinical implications of these ART-induced alterations, including the emergence of immune reconstitution inflammatory syndrome and the increased incidences of noninfectious lung diseases, such as lung cancer and chronic obstructive lung disease. There continues to be many unanswered questions regarding the effects of ART on lung health and, in particular, the immune system. Growing knowledge in this area will hopefully diminish the incidence of these noninfectious lung diseases and further improve the health of individuals living with HIV.
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
Stojanova Yancheva Nina
Full Text Available HIV-1 infection keeps on being a global problem because of its pandemic character and the impossibility for eradication. The combined antiretroviral therapy (АRТ remains the only treatment which has proven its effectiveness for maintaining the life of HIV positive patients. Because of long term (life time duration of this therapy, it is necessary to monitor patients for possible drug toxicity. The aim of our research is to evaluate the changes of basic laboratory examinations while conducting a long-term АRТ. We analyzed basic laboratory studies of 145 HIV-infected Bulgarian patients in the current research. The patients were separated into four groups according to their treatment regimen. They were on dispensary monitoring and were being treated in the Department for Patients with Acquired Immune Deficiency in the Specialized Hospital for Active Treatment of Infectious and Parasitic Diseases “Prof. Ivan Kirov” - Sofia. Our results showed that combined ART led to changes in blood count, alanin-aminotransferase (ALT, glucose and total cholesterol. Some of these changes are significant for some of the drugs administered. The current ART does not lead to severe toxicity and life-threatening conditions such as those which were observed in the first few years of ART introduction.
M.C.F. Prosperi; M. Rosen-Zvi; A. Altman; M. Zazzi; S. Di Giambenedetto; R. Kaiser; E. Schülter; D. Struck; P. Sloot; D.A. van de Vijver; A.-M. Vandamme; A. Sönnerborg
Background: Although genotypic resistance testing (GRT) is recommended to guide combination antiretroviral therapy (cART), funding and/or facilities to perform GRT may not be available in low to middle income countries. Since treatment history (TH) impacts response to subsequent therapy, we investig
Ankrah, D.; Koster, E.S.; Teeuwisse, A.K.; Arhinful, D.K.; Agyepong, I.A.; Lartey, Margaret
INTRODUCTION: Adherence to antiretroviral therapy (ART) is known to be challenging among adolescents living with HIV/AIDS, notwithstanding the life-saving importance of this therapy. Of the global total number of adolescents living with HIV in 2013, 83% reside in sub-Saharan Africa. The study aimed
Addo-Atuah, Joyce; Gourley, Dick; Gourley, Greta; White-Means, Shelley I; Womeodu, Robin J; Faris, Richard J; Addo, Nii Akwei
The convenience of accessing antiretroviral therapy (ART) is important for initial access to care and subsequent adherence to ART. We conducted a qualitative study of people living with HIV/AIDS (PLWHA) and ART healthcare providers in Ghana in 2005. The objective of this study was to explore the participants' perceived convenience of accessing ART by PLWHA in Ghana. The convenience of accessing ART was evaluated from the reported travel and waiting times to receive care, the availability, or otherwise, of special considerations, with respect to the waiting time to receive care, for those PLWHA who were in active employment in the formal sector, the frequency of clinic visits before and after initiating ART, and whether the PLWHA saw the same or different providers at each clinic visit (continuity of care). This qualitative study used in-depth interviews based on Yin's case-study research design to collect data from 20 PLWHA and 24 ART healthcare providers as study participants. • Reported travel time to receive ART services ranged from 2 to 12 h for 30% of the PLWHA. • Waiting time to receive care was from 4 to 9 h. • While known government workers, such as teachers, were attended to earlier in some of the centres, this was not a consistent practice in all the four ART centres studied. • The PLWHA corroborated the providers' description of the procedure for initiating and monitoring ART in Ghana. • PLWHA did not see the same provider every time, but they were assured that this did not compromise the continuity of their care. Our study suggests that convenience of accessing ART is important to both PLWHA and ART healthcare providers, but the participants alluded to other factors, including open provider-patient communication, which might explain the PLWHA's understanding of the constraints under which they were receiving care. The current nation-wide coverage of the ART programme in Ghana, however, calls for the replication of this study to identify
Full Text Available 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
Full Text Available Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART, yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher's exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7% vs.11/153 (7.2%, p<0.001 and frank diabetes mellitus (27/150 (18.0% vs. 8/153 (5.2%, p = 0.001 than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78-11.77, p<0.001. Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%.HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.
Helen van der Plas
Full Text Available BACKGROUND: HIV-associated tuberculosis is a common coinfection in Sub-Saharan Africa, which causes high morbidity and mortality. A sub-set of HIV-associated tuberculosis patients require prolonged hospital admission, during which antiretroviral therapy initiation may be required. The aim of this study was to document the causes of clinical deterioration of hospitalised patients with HIV-associated tuberculosis starting antiretroviral therapy in order to inform healthcare practice in low- to middle-income countries. METHODS: Prospective, observational cohort study of adult inpatients with HIV-associated tuberculosis starting antiretroviral therapy in a dedicated tuberculosis hospital in Cape Town, South Africa. Causes of clinical deterioration and outcome were recorded in the first 12 weeks of antiretroviral therapy. Patients with rifampicin-resistant tuberculosis were excluded. RESULTS: Between May 2009 and November 2010, 112 patients (60% female, with a median age of 32 years were enrolled. At baseline the median CD4 count was 55 cells/mm3 (IQR 31-106 and HIV viral load 5.6 log copies/mL. All patients had significant comorbidity: 82% were bed-bound, 65% had disseminated tuberculosis and 27% had central nervous system tuberculosis. Seventy six patients (68% developed 144 clinical events after starting antiretroviral therapy. TB-IRIS, hospital-acquired infections and significant drug toxicities occurred in 42%, 20.5% and 15% of patients respectively. A new opportunistic disease occurred in 15% of patients and a thromboembolic event in 8%. Mortality during the 12 week period was 10.6%. CONCLUSIONS: High rates of TB-IRIS, hospital-acquired infections and drug toxicities complicate the course of patients with HIV-associated tuberculosis starting antiretroviral therapy in hospital. Despite the high morbidity, mortality was relatively low. Careful clinical management and adequate resources are needed in hospitalised HIV-TB patients in the 1(st three
Full Text Available Purpose: To study the various changes in the course of cytomegalovirus (CMV retinitis following combination antiretroviral treatment. Methods: Combination antiretroviral treatment was given to 12 patients with active CMV retinitis following which all anti-CMV medications were discontinued once the CD4 cell counts were> 100/mm3 for 3 months. Results: The median CD4 cell count increased from 36.5/mm3 (range, 3-74/mm3 at baseline to 175.5/mm3 (range, 97-410/mm3 at 3 months. No patient had reactivation of CMV retinitis or developed extraocular CMV infection during median follow-up of 16.7 months. In one patient with peripheral active CMV retinitis, the retinitis resolved completely and remained so throughout the follow-up period without specific anti-CMV treatment. Five (41.7% patients had immune recovery vitritis. Conclusion: Patients receiving combination antiretroviral treatment following treatment for CMV retinitis have better control of CMV retinitis but immune recovery vitritis is a common sequelae. Reactivation of CMV retinitis is common in patients who discontinue combination antiretroviral treatment
Lohse, N.; Ladefoged, K.; Obel, N.
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...
Friis-Moller, N; Sabin, CA; Weber, R; Monforte, AD; El-Sadr, WM; Reiss, P; Thiebaut, R; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Lundgren, JD; Lundgren, JD; Weber, R; Monteforte, AD; Bartsch, G; Reiss, P; Dabis, F; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Houyez, F; Loeliger, E; Tressler, R; Weller, I.; Friis-Moller, N; Sabin, CA; Sjol, A; Lundgren, JD; Sawitz, A; Rickenbach, M; Pezzotti, P; Krum, E; Meester, R; Lavignolle, V.; Sundstrom, A; Poll, B; Fontas, E; Torres, F; Petoumenos, K; Kjaer, J; Hammer, S; Neaton, J; Sjol, A; de Wolf, F; van der Ven, E; Zaheri, S; Van Valkengoed, L; Meester, R; Bronsveld, W; Weigel, H; Brinkman, K; Frissen, P; ten Veen, J; Hillbrand, M; Schieveld, S; Mulder, J; van Gorp, E; Meenhorst, P; Danner, S; Claessen, F; Perenboom, R; Schattenkerk, JKE; Godfried, M; Lange, J; Lowe, S; van der Meer, J; Nellen, F; Pogany, K; van der Poll, T; Reiss, R; Ruys, T; Wit, F; Richter, C; van Leusen, R; Vriesendorp, R; Jeurissen, F; Kauffmann, R; Koger, E; Brevenboer, B; Sprenger, HG; Law, G; ten Kate, RW; Leemhuis, M; Schippers, E; Schrey, G; van der Geest, S; Verbon, A; Koopmans, P; Keuter, M; Telgt, D; van der Ven, A; van der Ende, Marchina E.; Gyssens, I.; de Marie, S; Juttmann, J; van der Heul, C; Schneider, M; Borleffs, J; Hoepelman, I.; Jaspers, C; Matute, A; Schurink, C; Blok, W; Salamon, R; Beylot, J; Dupon, M; Le Bras, M; Pellegrin, JL; Ragnaud, JM; Dabis, F; Chene, G; Jacqmin-Gadda, H; Rhiebaut, R; Lawson-Ayayi, S; Lavignolle, V.; Balestre, E; Blaizeau, MJ; Decoin, M; Formaggio, AM; Delveaux, S; Labarerre, S; Uwamaliya, B; Vimard, E; Merchadou, L; Palmer, G; Touchard, D; Dutoit, D; Pereira, F; Boulant, B; Beylot, J; Morlat, P; Bonarek, M; Bonnet, F; Coadou, B; Gelie, P; Jaubert, D; Nouts, C; Lacoste, D; Dupon, M; Dutronc, H; Cipriano, G; Lafarie, S; Chossat, I.; Lacut, JY; Leng, B; Pellegrin, JL; Mercie, P; Viallard, JF; Faure, I.; Rispal, P; Cipriano, C; Tchamgoue, S; Le Bras, M; Djossou, F; Malvy, D; Pivetaud, JP; Ragnaud, JM; Chambon, D; De La Taille, C; Galperine, T; Lafarie, S; Neau, D; Ochoa, A; Beylot, C; Doutre, MS; Bezian, JH; Moreau, JF; Taupin, JL; Conri, C; Constans, J; Couzigou, P; Castera, L; Fleury, H; Lafon, ME; Masquelier, B; Pellegrin, I.; Trimoulet, P; Moreau, F; Mestre, C; Series, C; Taytard, A; Law, M; Petoumenos, K; Bal, J; Mijch, A; Watson, K; Roth, N; Wood, H; Austin, D; Gowers, A; Baker, B; McFarlane, R; Carr, A; Cooper, D; Chuah, J; Fankhauser, W; Mallal, S; Skett, J; Calvo, G; Torres, F; Mateau, S; Domingo, P; Sambeat, MA; Gatell, J; Del Cacho, E; Cadafalch, J; Fuster, M; Codina, C; Sirera, G; Vaque, A; Clumeck, N; De Wit, S; Gerard, M; Hildebrand, M; Kabeya, K; Konopnicki, D; Payen, MC; Poll, B; Van Laethem, Y; Neaton, J; Bartsch, G; El-Sadr, WM; Krum, E; Thompson, G; Wentworth, D; Luskin-Hawk, R; Telzak, E; El-Sadr, WM; Abrams, DI; Cohn, D; Markowitz, N; Arduino, R; Mushatt, D; Friedland, G; Perez, G; Tedaldi, E; Fisher, E; Gordin, F; Crane, LR; Sampson, J; Baxter, J; Kirk, O; Mocroft, A; Phillips, AN; Lundgren, JD; Vetter, N; Clumeck, N; Hermans, P; Colebunders, R; Machala, L; Nielsen, J; Benfield, T; Gerstoft, J; Katzenstein, T; Roge, B; Skinhoj, P; Pedersen, C; Katlama, C; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Miller, V.; Staszewski, S; Bieckel, M; Goebel, FD; Salzberger, B; Rockstroh, J; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Karydis, I.; Filandras, A; Banhegyi, D; Mulcahy, F; Yust, I.; Turner, D; Pollack, S; Ben-Ishai, Z; Bentwich, Z; Maayan, S; Vella, S; Chiesi, A; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Esposito, R; Bedini, A; Chirianni, A; Montesarchio, E; Vullo, V.; Santopadre, P; Narciso, P; Antinori, A; Franci, P; Zaccarelli, M; Lazzarin, A; Finazzi, R; Monforte, VO; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, V.; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Boron-Kaczmarska, A; Pnyka, M; Beniowski, M; Trocha, H; Antunes, F; Mansinho, K; Proenca, R; Gonzalez-Lahoz, J; Diaz, B; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, V.; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Blaxhult, A; Heidemann, B; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Telenti, A; Hirschel, B; Soravia-Dunand, V.; Furrer, H; Fisher, M; Brettle, R; Barton, S; Johnson, AM; Mercey, D; Loveday, C; Johnson, MA; Pinching, A; Parkin, J; Weber, J; Scullard, G; Morfeldt, L; Thulin, G; Sunstrom, A; Akerlund, B; Koppel, K; Karlsson, A; Flamholc, L; Hakangard, C; Monforte, AD; Pezzotti, P; Moroni, M; Monforte, AD; Cargnel, A; Merli, S; Vigevani, GM; Pastecchia, C; Lazzarin, A; Novati, R; Caggese, L; Moioli, C; Mura, MS; Mannazzu, M; Suter, F; Arici, C; Manconi, PE; Piano, P; Mazzotta, F; Lo Caputo, S; Poggio, A; Bottari, G; Pagano, G; Alessandrini, A; Scasso, A; Vincenti, A; Abbadesse, V.; Mancuso, S; Alberici, F; Ruggieri, A; Arlotti, M; Ortolani, P; De Lalla, F; Tositti, G; Piersantelli, N; Piscopo, R; Raise, E; Pasquinucci, S; Soscia, F; Tacconi, L; Tirelli, U; Nasti, G; Santoro, D; Pusterla, L; Carosi, G; Castelli, F; Cadeo, G; Vangi, D; Carnevale, G; Galloni, D; Filice, G; Bruno, R; Sinicco, A; Sciandra, M; Caramello, P; Gennero, L; Soranzo, ML; Bonasso, M; Rizzardini, G; Migliorino, G; Chiodo, F; Colangeli, V.; Magnani, G; Ursitti, M; Menichetti, F; Martinelli, C; Esposito, R; Mussini, C; Ghinelli, F; Sighinolfi, L; Coronado, O; Zauli, T; Ballardini, G; Montroni, M; Zoli, A; Petrelli, E; Cioppi, A; Ortona, L; De Luca, A; Petrosillo, N; Noto, P; Narciso, P; Salcuni, P; Antinori, A; De Longis, P; Vullo, V.; Lichtner, M; Pastore, G; Minafra, G; Chiriann, A; Loiacono, L; Piazza, M; Nappa, S; Abrescia, N; De Marco, M; Colomba, A; Prestileo, T; De Stefano, C; La Gala, A; Ferraro, T; Scerbo, A; Grima, P; Tundo, P; Pizzigallo, E; D'Alessandro, M; Grisorio, B; Ferrara, S; Pradier, C; Fontas, E; Caissotti, C; Dellamonica, P; Bentz, L; Bernard, E; Chaillou, S; De Salvador-Guillouet, F; Durant, J; Guttman, R; Heripret, L; Mondain-Miton, V.; Perbost, I.; Prouvost-Keller, B; Pugliese, P; Rahelinirina, V.; Roger, PM; Vandenbos, F; Bernasconi, E; Bucher, H; Burgisser, P; Cattacin, S; Egger, M; Erb, P; Fierz, W; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, HJ; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Ledergerber, B; Lauper, U; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schupbach, J; Speck, R; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; Ten Napel, C.
Background: It remains controversial whether exposure to combination antiretroviral treatment increases the risk of myocardial infarction. Methods: In this prospective observational study, we enrolled 23,468 patients from 11 previously established cohorts from December 1999 to April 2001 and collect
Baker, Jason V; Neuhaus, Jacqueline; Duprez, Daniel
Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (6 months or longer) at study entry, risk of AIDS and serious non-AIDS events were increased for participants who deferred ART compa...
Jarrin, Inma; Pantazis, Nikos; Gill, M John
We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART).......We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART)....
Bollerup, Annemarie R; Donoghoe, Martin C; Lazarus, Jeff
To assess changes in access to highly active antiretroviral therapy (HAART) between the end of 2002 and the end of 2005, and to review the capacity for further HAART scale-up in the then 52 Member States of the WHO European Region.......To assess changes in access to highly active antiretroviral therapy (HAART) between the end of 2002 and the end of 2005, and to review the capacity for further HAART scale-up in the then 52 Member States of the WHO European Region....
Full Text Available We report a case of Strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (HIV infection starting antiretroviral therapy, in whom Strongyloides stercoralis larvae and Cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. Our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. For this reason, we conclude that Strongyloides stercoralis infection should be suspected in HIV-infected patients starting antiretroviral therapy in order to avoid potential fatal outcomes.
Hogg Robert S
Full Text Available Abstract Background Barriers to HIV treatment among injection drug users (IDU are a major public health concern. However, there remain few long-term studies investigating key demographic and behavioral factors - and gender differences in particular - that may pose barriers to antiretroviral therapy (ART, especially in settings with universal healthcare. We evaluated access and adherence to ART in a long-term cohort of HIV-positive IDU in a setting where medical care and antiretroviral therapy are provided free of charge through a universal healthcare system. Methods We evaluated baseline antiretroviral use and subsequent adherence to ART among a Canadian cohort of HIV-positive IDU. We used generalized estimating equation logistic regression to evaluate factors associated with 95% adherence to antiretroviral therapy estimated based on prescription refill compliance. Results Between May 1996 and April 2008, 545 IDU participants were followed for a median of 23.8 months (Inter-quartile range: 8.5 - 91.6, among whom 341 (63% were male and 204 (37% were female. Within the six-month period prior to the baseline interview, 133 (39% men and 62 (30% women were on ART (p = 0.042. After adjusting for clinical characteristics as well as drug use patterns measured longitudinally throughout follow-up, female gender was independently associated with a lower likelihood of being 95% adherent to ART (Odds Ratio [OR] = 0.70; 95% Confidence Interval: 0.53-0.93. Conclusions Despite universal access to free HIV treatment and medical care, female IDU were less likely to access and adhere to antiretroviral therapy, a finding that was independent of drug use and clinical characteristics. These data suggest that interventions to improve access to HIV treatment among IDU must be tailored to address unique barriers to antiretroviral therapy faced by female IDU.
Doerfler, R Eric; Goodfellow, Linda
No study has tested the effectiveness of individualized cognitive behavioral therapy (CBT) interventions to reduce persistent nausea, pain, anxiety, and fatigue in patients on continuous antiretroviral therapy (ART). Our objective was to determine if CBT could reduce nausea, pain, anxiety, and fatigue in patients with HIV on ART. Men ages 40 to 56 years on ART (n = 18) at a suburban HIV clinic were randomly assigned to a control group or the CBT intervention. Usual adherence education and side-effect management were provided to both groups. Symptoms, health perception, medication adherence, and side-effect-reducing medication use were measured at four time points over 3 months. Participants in the intervention group rated usual fatigue and worst fatigue at 60 days, and nausea duration at 90 days significantly lower than controls (p HIV undergoing ART.
Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth
In order to achieve optimal benefits of antiretroviral therapy (ART), caregivers of children receiving ART are required to attend routine clinic visits monthly and administer medication to the child as prescribed. Yet, the level of adherence to these behaviours varies considerably in many settings. As a way to achieve optimal adherence in rural KwaZulu-Natal, caregivers are required to attend routine counselling sessions at HIV treatment clinics that are centred on imparting information, motivation, and behavioural skills related to medication administration. According to the information-motivation-behavioural skills model, information related to adherence, motivation, and behavioural skills are necessary and fundamental determinants of adherence to ART. The purpose of the study was to observe and document the content of adherence counselling sessions that caregivers attending rural clinics in KwaZulu Natal receive. We observed 25 adherence counselling sessions, which lasted on average 8.1 minutes. Counselling typically consisted of counsellors recording patient attendance, reporting CD4 count and viral load results to caregivers, emphasising dose times, and asking caregivers to name their medications and dosage amounts. Patients were seldom asked to demonstrate how they measure the medication. They were also not probed for problems regarding treatment, even when an unsuppressed VL was reported to a caregiver. This paper calls attention to the sub-optimal level of counselling provided to patients on ART and the urgent need to standardise and improve the training, support, and debriefing provided to counsellors.
Stegmann, Sophie; Manea, Maria Elena; Charpentier, Charlotte; Damond, Florence; Karmochkine, Marina; Laureillard, Didier; Si-Mohamed, Ali; Weiss, Laurence; Piketty, Christophe
Previous studies have suggested the efficacy of foscarnet combined with thymidine analogues as salvage therapy in late-stage HIV-1 infection. Here, we report on the first case of foscarnet therapy in a patient infected with HIV-2 exhibiting virologic failure. The patient was known to be HIV-2-infected since 1992 and had received 11 sequential lines of combined antiretroviral therapy (cART) with almost all the available antiretroviral agents including raltegravir. A marked decrease in HIV-2 plasma viral load of 1.48 log(10)copies/ml was observed at day 14 of foscarnet induction therapy associated with zidovudine and failing cART. An optimized cART was then introduced with lamivudine, zidovudine, lopinavir/r, etravirine and maraviroc. Four months after the end of foscarnet therapy, HIV-2 plasma viral load remained undetectable. This case report suggests that foscarnet may represent a therapeutic option for HIV-2-infected patients exhibiting multidrug resistance.
Jong, Eefje; Oudhoff, Lisanne A.; Epskamp, Cynthia; Wagener, Marlies N.; van Duijn, Miranda; Fischer, Steven; van Gorp, Eric C. M.
Objective To assess predictors and reported treatment strategies of HIV-related fatigue in the combined antiretroviral (cART) era. Method Five databases were searched and reference lists of pertinent articles were checked. Studies published since 1996 on predictors or therapy of HIV-related fatigue
Bannister, Wendy P; Cozzi-Lepri, Alessandro; Kjær, Jesper;
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...
Hartman, K.; Verweel, G.; Groot, R. de; Hartwig, N.G.
BACKGROUND: Highly active antiretroviral therapy has been associated with lipodystrophy in adults. Much is unknown about its characteristics, especially in children. OBJECTIVE: To obtain an objective case definition of the lipodystrophy syndrome. METHODS: This was a cross-sectional study. One invest
Kinabo, G.; Sprengers, M.; Msuya, L.J.; Shayo, A.M.; Asten, H.A.G.H. van; Dolmans, W.M.V.; Ven, A.J.A.M. van der; Warris, A.
OBJECTIVE: : Highly active antiretroviral therapy (HAART) has been associated with lipodystrophy (LD) in adults but data are more limited for children. The purpose of this study was to determine the prevalence of and risk factors for LD in Tanzanian children receiving HAART by clinical assessment an
Rodger, Alison J; Bruun, Tina; Vernazza, Pietro;
The results from the HPTN 052 trial have increased the focus on use of antiretroviral therapy (ART) for prevention of HIV transmission; however, condom use also effectively prevents HIV transmission. Studies in heterosexual serodiscordant couples with viral suppression have so far only reported...
Lodi, Sara; Del Amo, Julia; Moreno, Santiago; Bucher, Heiner C.; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Olson, Ashley; Van Sighem, Ard; Reiss, Peter; Sabin, Caroline; Jose, Sophie; Justice, Amy; Goulet, Joseph; Miró, José M.; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Vourli, Georgia; Antoniadou, Anastasia; Dabis, Francois; Vandenhede, Mari-Anne; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A.; Hernan, Miguel; Bansi, L.; Hill, T.; Sabin, C.; Dunn, D.; Porter, K.; Glabay, A.; Orkin, C.; Thomas, R.; Jones, K.; Fisher, M.; Perry, N.; Pullin, A.; Churchill, D.; Gazzard, B.; Nelson, M.; Asboe, D.; Bulbeck, S.; Mandalia, S.; Clarke, J.; Delpech, V.; Anderson, J.; Munshi, S.; Post, F.; Easterbrook, P.; Khan, Y.; Patel, P.; Karim, F.; Duffell, S.; Gilson, R.; Man, S.-L.; Williams, I.; Gompels, M.; Dooley, D.; Schwenk, A.; Ainsworth, J.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Ismajani Puradiredja, D.; Bansi, L.; Hill, T.; Phillips, A.; Sabin, C.; Walsh, J.; Weber, J.; Kemble, C.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Bezemer, D.O.; Gras, L.A.J.; Kesselring, A.M.; Van Sighem, A.I.; Zaheri, S.; Van Twillert, G.; Kortmann, W.; Branger, J.; Prins, J.M.; Kuijpers, T.W.; Scherpbier, H.J.; Van Der Meer, J.T.M.; Wit, F.W.M.N.; Godfried, M.H.; Reiss, P.; Van Der Poll, T.; Nellen, F.J.B.; Lange, J.M.A.; Geerlings, S.E.; Van Vugt, M.; Pajkrt, D.; Bos, J.C.; van der Valk, M.; Grijsen, M.L.; Wiersinga, W.J.; Brinkman, K.; Blok, W.L.; Frissen, P.H.J.; Schouten, W.E.M.; Van Den Berk, G.E.L.; Veenstra, J.; Lettinga, K.D.; Mulder, J.W.; Vrouenraets, S.M.E.; Lauw, F.N.; Van Eeden, A.; Verhagen, D.W.M.; Van Agtmael, M.A.; Perenboom, R.M.; Claessen, F.A.P.; Bomers, M.; Peters, E.J.G.; Richter, C.; Van Der Berg, J.P.; Gisolf, E.H.; Schippers, E.F.; Van Nieuwkoop, C.; Van Elzakker, E.P.; Leyten, E.M.S.; Gelinck, L.B.S.; Pronk, M.J.H.; Bravenboer, B.; Kootstra, G.J.; Delsing, C.E.; Sprenger, H.G.; Doedens, R.; Scholvinck, E.H.; Van Assen, S.; Bierman, W.F.W.; Soetekouw, R.; Ten Kate, R.W.; Van Vonderen, M.G.A.; Van Houte, D.P.F.; Kroon, F.P.; Van Dissel, J.T.; Arend, S.M.; De Boer, M.G.J.; Jolink, H.; Ter Vollaard, H.J.M.; Bauer, M.P.; Weijer, S.; El Moussaoui, R.; Lowe, S.; Schreij, G.; Oude Lashof, A.; Posthouwer, D.; Koopmans, P.P.; Keuter, M.; Van Der Ven, A.J.A.M.; Ter Hofstede, H.J.M.; Dofferhoff, A.S.M.; Warris, A.; Van Crevel, R.; van der Ende, Marchina E.; De Vries-Sluijs, T.E.M.S.; Schurink, C.A.M.; Nouwen, J.L.; Nispen Tot Pannerden, M.H.; Verbon, A.; Rijnders, B.J.A.; Van Gorp, E.C.M.; Hassing, R.J.; Smeulders, A.W.M.; Hartwig, N.G.; Driessen, G.J.A.; Den Hollander, J.G.; Pogany, K.; Juttmann, J.R.; Van Kasteren, M.E.E.; Hoepelman, A.I.M.; Mudrikova, T.; Schneider, M.M.E.; Jaspers, C.A.J.J.; Ellerbroek, P.M.; Oosterheert, J.J.; Arends, J.E.; Wassenberg, M.W.M.; Barth, R.E.; Geelen, S.P.M.; Wolfs, T.F.W.; Bont, L.J.; Van Den Berge, M.; Stegeman, A.; Groeneveld, P.H.P.; Alleman, M.A.; Bouwhuis, J.W.; Barin, F.; Burty, C.; Duvivier, C.; Enel, P.; Fredouille-Heripret, L.; Gasnault, J.; Khuong, M.A.; Mahamat, A.; Pilorgé, F.; Tattevin, P.; Salomon, Valérie; Jacquemet, N.; Abgrall, S.; Costagliola, D.; Grabar, S.; Guiguet, M.; Lanoy, E.; Lièvre, L.; Mary-Krause, M.; Selinger-Leneman, H.; Lacombe, J.M.; Potard, V.; Bricaire, F.; Herson, S.; Katlama, C.; Simon, A.; Desplanque, N.; Girard, P.M.; Meynard, J.L.; Meyohas, M.C.; Picard, O.; Cadranel, J.; Mayaud, C.; Pialoux, G.; Clauvel, J.P.; Decazes, J.M.; Gerard, L.; Molina, J.M.; Diemer, M.; Sellier, P.; Bentata, M.; Honoré, P.; Jeantils, V.; Tassi, S.; Mechali, D.; Taverne, B.; Bouvet, E.; Crickx, B.; Ecobichon, J.L.; Matheron, S.; Picard-Dahan, C.; Yeni, P.; Berthé, H.; Dupont, C.; Chandemerle, C.; Mortier, E.; De Truchis, P.; Tisne-Dessus, D.; Weiss, L.; Salmon, D.; Auperin, I.; Gilquin, J.; Roudière, L.; Viard, J.P.; Boué, F.; Fior, R.; Delfraissy, J.F.; Goujard, C.; Jung, C.; Lesprit, Ph.; Vittecoq, D.; Fraisse, P.; Lang, J.M.; Rey, D.; Beck-Wirth, G.; Stahl, J.P.; Lecercq, P.; Gourdon, F.; Laurichesse, H.; Fresard, A.; Lucht, F.; Bazin, C.; Verdon, R.; Chavanet, P.; Arvieux, C.; Michelet, C.; Choutet, P.; Goudeau, A.; Maître, M.F.; Hoen, B.; Eglinger, P.; Faller, J.P.; Borsa-Lebas, F.; Caron, F.; Reynes, J.; Daures, J.P.; May, T.; Rabaud, C.; Berger, J.L.; Rémy, G.; Arlet-Suau, E.; Cuzin, L.; Massip, P.; Thiercelin Legrand, M.F.; Pontonnier, G.; Viget, N.; Yasdanpanah, Y.; Dellamonica, P.; Pradier, C.; Pugliese, P.; Aleksandrowicz, K.; Quinsat, D.; Ravaux, I.; Tissot-Dupont, H.; Delmont, J.P.; Moreau, J.; Gastaut, J.A.; Poizot-Martin, I.; Retornaz, F.; Soubeyrand, J.; Galinier, A.; Ruiz, J.M.; Allegre, T.; Blanc, P.A.; Bonnet-Montchardon, D.; Lepeu, G.; Granet-Brunello, P.; Esterni, J.P.; Pelissier, L.; Cohen-Valensi, R.; Nezri, M.; Chadapaud, S.; Laffeuillade, A.; Billaud, E.; Raffi, F.; Boibieux, A.; Peyramond, D.; Livrozet, J.M.; Touraine, J.L.; Cotte, L.; Trepo, C.; Strobel, M.; Bissuel, F.; Pradinaud, R.; Sobesky, M.; Cabié, A.; Gaud, C.; Contant, M.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Haerry, D.; Fux, C.A.; Gorgievski, M.; Günthard, H.; Hasse, B.; Hirsch, H.H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez De Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.; Casabona, J.; Gallois, A.; Esteve, A.; Podzamczer, D.; Murillas, J.; Gatell, J.M.; Manzardo, C.; Tural, C.; Clotet, B.; Ferrer, E.; Riera, M.; Segura, F.; Navarro, G.; Force, L.; Vilaró, J.; Masabeu, A.; García, I.; Guadarrama, M.; Cifuentes, C.; Dalmau, D.; Jaen, À.; Agustí, C.; Montoliu, A.; Pérez, I.; Gargoulas, Freyra; Blanco, J.L.; Garcia-Alcaide, F.; Martínez, E.; Mallolas, J.; López-Dieguez, M.; García-Goez, J.F.; Sirera, G.; Romeu, J.; Jou, A.; Negredo, E.; Miranda, C.; Capitan, M.C.; Saumoy, M.; Imaz, A.; Tiraboschi, J.M.; Murillo, O.; Bolao, F.; Peña, C.; Cabellos, C.; Masó, M.; Vila, A.; Sala, M.; Cervantes, M.; Jose Amengual, Ma.; Navarro, M.; Penelo, E.; Barrufet, P.; Bejarano, G.; Molina, J.; Guadarrama, M.; Alvaro, M.; Mercadal, J.; Fernandez, Juanse; Ospina, Jesus E.; Muñoz, M.A.; Caro-Murillo, A.M.; Sobrino, P.; Jarrín, I.; Gomez Sirvent, J.L.; Rodríguez, P.; Aleman, M.R.; Alonso, M.M.; Lopez, A.M.; Hernandez, M.I.; Soriano, V.; Labarga, P.; Barreiro, P.; Medrano, J.; Rivas, P.; Herrero, D.; Blanco, F.; Vispo, M.E.; Martín, L.; Ramírez, G.; De Diego, M.; Rubio, R.; Pulido, F.; Moreno, V.; Cepeda, C.; Hervás, Rl.; Iribarren, J.A.; Arrizabalaga, J.; Aramburu, M.J.; Camino, X.; Rodrí-guez-Arrondo, F.; Von Wichmann, M.A.; Pascual, L.; Goenaga, M.A.; Gutierrez, F.; Masia, M.; Ramos, J.M.; Padilla, S.; Sanchez-Hellín, V.; Bernal, E.; Escolano, C.; Montolio, F.; Peral, Y.; Berenguer, J.; Lopez, J.C.; Miralles, P.; Cosín, J.; Sanchez, M.; Gutierrez, I.; Ramírez, M.; Padilla, B.; Vidal, F.; Sanjuan, M.; Peraire, J.; Veloso, S.; Vilades, C.; Lopez-Dupla, M.; Olona, M.; Vargas, M.; Aldeguer, J.L.; Blanes, M.; Lacruz, J.; Salavert, M.; Montero, M.; Cuéllar, S.; De Los Santos, I.; Sanz, J.; Oteo, J.A.; Blanco, J.R.; Ibarra, V.; Metola, L.; Sanz, M.; Pérez-Martínez, L.; Sola, J.; Uriz, J.; Castiello, J.; Reparaz, J.; Arriaza, M.J.; Irigoyen, C.; Moreno, S.; Antela, A.; Casado, J.L.; Dronda, F.; Moreno, A.; Pérez, M.J.; López, D.; Gutiérrez, C.; Hernández, B.; Pumares, M.; Martí, P.; García, L.; Page, C.; García, F.; Hernández, J.; Peña, A.; Muñoz, L.; Parra, J.; Viciana, P.; Leal, M.; López-Cortés, L.F.; Trastoy, M.; Mata, R.; Justice, A.C.; Fiellin, D.A.; Rimland, D.; Jones-Taylor, C.; Oursler, K.A.; Titanji, R.; Brown, S.; Garrison, S.; Rodriguez-Barradas, M.; Masozera, N.; Goetz, M.; Leaf, D.; Simberkoff, M.; Blumenthal, D.; Leung, J.; Butt, A.; Hoffman, E.; Gibert, C.; Peck, R.; Mattocks, K.; Braithwaite, S.; Brandt, C.; Bryant, K.; Cook, R.; Conigliaro, J.; Crothers, K.; Chang, J.; Crystal, S.; Day, N.; Erdos, J.; Freiberg, M.; Kozal, M.; Gandhi, N.; Gaziano, M.; Gerschenson, M.; Good, B.; Gordon, A.; Goulet, J.L.; Hernán, M.A.; Kraemer, K.; Lim, J.; Maisto, S.; Miller, P.; Mole, L.; O'Connor, P.; Papas, R.; Robins, J.M.; Rinaldo, C.; Roberts, M.; Samet, J.; Tierney, B.; Whittle, J.; Babiker, A.; Brettle, R.; Darbyshire, J.; Gilson, R.; Goldberg, D.; Hawkins, D.; Jaffe, H.; Johnson, A.; McLean, K.; Pillay, D.; Cursley, Adam; Ewings, Fiona; Fairbrother, Keith; Louisa Gnatiuc, S.L.; Murphy, Brendan; Douglas, G.; Kennedy, N.; Pritchard, J.; Andrady, U.; Rajda, N.; Maw, R.; McKernan, S.; Drake, S.; Gilleran, G.; White, D.; Ross, J.; Toomer, S.; Hewart, R.; Wilding, H.; Woodward, R.; Dean, G.; Heald, L.; Horner, P.; Glover, S.; Bansaal, D.; Eduards, S.; Carne, C.; Browing, M.; Das, R.; Stanley, B.; Estreich, S.; Magdy, A.; O'Mahony, C.; Fraser, P.; Hayman, B.; Jebakumar, S.P.R.; Joshi, U.; Ralph, S.; Wade, A.; Mette, R.; Lalik, J.; Summerfield, H.; El-Dalil, A.; France, J.A.; White, C.; Robertson, R.; Gordon, S.; McMillan, S.; Morris, S.; Lean, C.; Vithayathil, K.; McLean, L.; Winter, A.; Gale, D.; Jacobs, S.; Tayal, S.; Short, L.; Roberts, M.; Green, S.; Williams, G.; Sivakumar, K.; Bhattacharyya, N.D.; Monteiro, E.; Minton, J.; Dhar, J.; Nye, F.; De Souza, C.B.; Isaksen, A.; McDonald, L.; McLean, K.; Franca, A.; Hawkins, D.; William, L.; Jendrulek, I.; Peters, B.; Shaunak, S.; El-Gadi, S.; Easterbrook, P.J.; Mazhude, C.; Gilson, R.; Johnstone, R.; Fakoya, A.; McHale, J.; Waters, A.; Kegg, S.; Mitchell, S.; Byrne, P.; Johnson, M.; Rice, P.; Fidler, S.; Mullaney, S.A.; McCormack, S.; David, D.; Melville, R.; Phillip, K.; Balachandran, T.; Mabey-Puttock, S.; Sukthankar, A.; Murphy, C.; Wilkins, E.; Ahmad, S.; Tayal, S.; Haynes, J.; Evans, E.; Ong, E.; Das, R.; Grey, R.; Meaden, J.; Bignell, C.; Loay, D.; Peacock, K.; Girgis, M.R.; Morgan, B.; Palfreeman, A.; Wilcox, J.; Tobin, J.; Tucker, L.; Saeed, A.M.; Chen, F.; Deheragada, A.; Williams, O.; Lacey, H.; Herman, S.; Kinghorn, D.; Devendra, V.S.; Wither, J.; Dawson, S.; Rowen, D.; Harvey, J.; Wilkins, E.; Bridgwood, A.; Singh, G.; Chauhan, M.; Kellock, D.; Young, S.; Dannino, S.; Kathir, Y.; Rooney, G.; Currie, J.; Fitzgerald, M.; Devendra, S.; Keane, F.; Booth, G.; Green, T.; Arumainayyagam, J.; Chandramani, S.; Rajamanoharan, S.; Robinson, T.; Curless, E.; Gokhale, R.; Tariq, A.; Roberts, M.; Williams, O.; Luzzi, G.; FitzGerald, M.; Fairley, I.; Wallis, F.; Smit, E.; Ward, F.; Molina, J.M.; Loze, B.; Morlat, P.; Bonarek, M.; Bonnet, F.; Nouts, C.; Louis, I.; Raffi, F.; Reliquet, V.; Sauser, F.; Biron, C.; Mounoury, O.; Hue, H.; Brosseau, D.; Delfraissy, J.F.; Goujard, C.; Ghosn, J.; Rannou, M.T.; Bergmann, J.F.; Badsi, E.; Rami, A.; Diemer, M.; Parrinello, M.; Girard, P.M.; Samanon-Bollens, D.; Campa, P.; Tourneur, M.; Desplanques, N.; Livrozet, J.M.; Jeanblanc, F.; Chiarello, P.; Makhloufi, D.; Blanc, A.P.; Allègre, T.; Reynes, J.; Baillat, V.; Lemoing, V.; Merle De Boever, C.; Tramoni, C.; Cabié, A.; Sobesky, G.; Abel, S.; Beaujolais, V.; Pialoux, G.; Slama, L.; Chakvetadze, C.; Berrebi, V.; Yeni, P.; Bouvet, E.; Fournier, I.; Gerbe, J.; Trepo, C.; Koffi, K.; Augustin-Normand, C.; Miailhes, P.; Thoirain, V.; Brochier, C.; Thomas, R.; Souala, F.; Ratajczak, M.; Beytoux, J.; Jacomet, C.; Gourdon, F.; Rouveix, E.; Morelon, S.; Dupont, C.; Olivier, C.; Lortholary, O.; Dupont, B.; Viard, J.P.; Maignan, A.; Ragnaud, J.M.; Raymond, I.; Leport, C.; Jadand, C.; Jestin, C.; Longuet, P.; Boucherit, S.; Sereni, D.; Lascoux, C.; Prevoteau, F.; Sobel, A.; Levy, Y.; Lelièvre, J.D.; Lascaux, A.S.; Dominguez, S.; Dumont, C.; Aumâitre, H.; Delmas, B.; Saada, M.; Medus, M.; Guillevin, L.; Salmon, D.; Tahi, T.; Yazdanpanah, Y.; Pavel, S.; Marien, M.C.; Drenou, B.; Beck-Wirth, G.; Beck, C.; Benomar, M.; Katlama, C.; Tubiana, R.; Ait Mohand, H.; Chermak, A.; Ben Abdallah, S.; Bentata, M.; Touam, F.; Hoen, B.; Drobacheff, C.; Folzer, A.; Massip, P.; Obadia, M.; Prudhomme, L.; Bonnet, E.; Balzarin, F.; Pichard, E.; Chennebault, J.M.; Fialaire, P.; Loison, J.; Galanaud, P.; Boué, F.; Bornarel, D.; Verdon, R.; Bazin, C.; Six, M.; Ferret, P.; Weiss, L.; Batisse, D.; Gonzales-Canali, G.; Tisne-Dessus, D.; Devidas, A.; Chevojon, P.; Turpault, I.; Lafeuillade, A.; Cheret, A.; Philip, G.; Morel, P.; Timsit, J.; Herson, S.; Amirat, N.; Simon, A.; Brancion, C.; Cabane, J.; Picard, O.; Tredup, J.; Stein, A.; Ravault, I.; Chavanet, C.; Buisson, M.; Treuvetot, S.; Choutet, P.; Nau, P.; Bastides, F.; May, T.; Boyer, L.; Wassoumbou, S.; Oksenhendeler, E.; Gérard, L.; Bernard, L.; De Truchis, P.; Berthé, H.; Domart, Y.; Merrien, D.; Greder Belan, A.; Gayraud, M.; Bodard, L.; Meudec, A.; Beuscart, C.; Daniel, C.; Pape, E.; Vinceneux, P.; Simonpoli, A.M.; Zeng, A.; Fournier, L.; Fuzibet, J.G.; Sohn, C.; Rosenthal, E.; Quaranta, M.; Dellamonica, P.; Chaillou, S.; Sabah, M.; Audhuy, B.; Schieber, A.; Moreau, P.; Niault, M.; Vaillant, O.; Huchon, G.; Compagnucci, A.; De Lacroix Szmania, I.; Richier, L.; Lamaury, I.; Saint-Dizier, F.; Garipuy, D.; Gastaut, J.A.; Drogoul, M.P.; Poizot Martin, I.; Fabre, G.; Lambert De Cursay, G.; Abraham, B.; Perino, C.; Lagarde, P.; David, F.; Roche-Sicot, J.; Saraux, J.L.; Leprêtre, A.; Fampin, B.; Uludag, A.; Morin, A.S.; Bletry, O.; Zucman, D.; Regnier, A.; Girard, J.J.; Quinsat, D.T.; Heripret, L.; Grihon, F.; Houlbert, D.; Ruel, M.; Chemlal, K.; Caron, F.; Debab, Y.; Tremollieres, F.; Perronne, V.; Lepeu, G.; Slama, B.; Perré, P.; Miodovski, C.; Guermonprez, G.; Dulioust, A.; Boudon, P.; Malbec, D.; Patey, O.; Semaille, C.; Deville, J.; Remy, G.; Béguinot, I.; Galanaud, P.; Boue, F.; Chambrin, V.; Pignon, C.; Estocq, G.A.; Levy, A.; Delfraissy, J.F.; Goujard, C.; Duracinsky, M.; Le Bras, P.; Ngussan, M.S.; Peretti, D.; Medintzeff, N.; Lambert, T.; Segeral, O.; Lezeau, P.; Laurian, Y.; Weiss, L.; Buisson, M.; Piketty, C.; Karmochkine, M.; Batisse, D.; Eliaszewitch, M.; Jayle, D.; Tisne-Dessus, D.; Kazatchkine, M.; Leport, C.; Colasante, U.; Jadand, C.; Jestin, C.; Duval, X.; Nouaouia, W.; Boucherit, S.; Vilde, J.L.; Girard, P.M.; Bollens, D.; Binet, D.; Diallo, B.; Meyohas, M.C.; Fonquernie, L.; Lagneau, J.L.; Salmon, D.; Guillevin, L.; Tahi, T.; Launay, O.; Pietrie, M.P.; Sicard, D.; Stieltjes, N.; Michot, J.; Sobel, A.; Levy, Y.; Bourdillon, F.; Lascaux, A.S.; Lelievre, J.D.; Dumont, C.; Dupont, B.; Obenga, G.; Viard, J.P.; Maignan, A.; Vittecoq, D.; Escaut, L.; Bolliot, C.; Bricaire, F.; Katlama, C.; Schneider, L.; Herson, S.; Simon, A.; Iguertsira, M.; Stein, A.; Tomei, C.; Ravaux, I.; Dhiver, C.; Tissot Dupont, H.; Vallon, A.; Gallais, J.; Gallais, H.; Gastaut, J.A.; Drogoul, M.P.; Fabre, G.; Dellamonica, P.; Durant, J.; Mondain, V.; Perbost, I.; Cassuto, J.P.; Karsenti, J.M.; Venti, H.; Fuzibet, J.G.; Rosenthal, E.; Ceppi, C.; Quaranta, M.; Krivitsky, J.A.; Bentata, M.; Bouchaud, O.; Honore, P.; Sereni, D.; Lascoux, C.; Delgado, J.; Rouzioux, C.; Burgard, M.; Boufassa, L.; Peynet, J.; Pérez-Hoyos, S.; Del Amo, J.; Alvarez, D.; Monge, S.; Muga, R.; Sanvisens, A.; Clotet, B.; Tor, J.; Bolao, F.; Rivas, I.; Vallecillo, G.; Del Romero, J.; Raposo, P.; Rodríguez, C.; Vera, M.; Hurtado, I.; Belda, J.; Fernandez, E.; Alastrue, I.; Santos, C.; Tasa, T.; Juan, A.; Trullen, J.; Garcia De Olalla, P.; Cayla, J.; Masdeu, E.; Knobel, H.; Mirò, J.M.; Sambeat, M.A.; Guerrero, R.; Rivera, E.; Guerrero, R.; Marco, A.; Quintana, M.; Gonzalez, C.; Castilla, J.; Guevara, M.; De Mendoza, C.; Zahonero, N.; Ortíz, M.; Paraskevis, D.; Touloumi, G.; Pantazis, N.; Bakoyannis, G.; Gioukari, V.; Antoniadou, A.; Papadopoulos, A.; Petrikkos, G.; Daikos, G.; Psichogiou, M.; Gargalianos-Kakolyris, P.; Xylomenos, G.; Katsarou, O.; Kouramba, A.; Ioannidou, P.; Kordossis, T.; Kontos, A.; Lazanas, M.; Chini, M.; Tsogas, N.; Panos, G.; Paparizos, V.; Leuow, K.; Kourkounti, S.; Sambatakou, H.; Mariolis, I.; Skoutelis, A.; Papastamopoulos, V.; Baraboutis, I.
Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacteri
Lazarus, Jeffrey V; Safreed-Harmon, Kelly; Nicholson, Joey
OBJECTIVES: In response to the lack of evidence-based guidance for how to continue scaling up antiretroviral therapy (ART) in ways that make optimal use of limited resources, to assess comparative studies of ART service delivery models implemented in sub-Saharan Africa. METHODS: A systematic lite...
Full Text Available It is generally accepted that oxidative stress is involved in HIV infection. However, the role in oxidative balance of Highly Active Antiretroviral Therapy (HAART is still debated. In our study we assessed serum oxidant and antioxidant levels in an HIV-1-infected population treated with HAART, and compared them with those of untreated HIV-1 patients and HIV-1-negative subjects. The study included 116 HIV-1-infected patients (86 HAART-treated and 30 untreated, and 46 HIV-negative controls. Serum oxidant levels were significantly higher in the HIV-1 treated group as compared to untreated and control groups. In addition, a decrease of serum total antioxidant status was observed in the HIV-1 treated group. To be noted is that patients who rigorously follow antiretroviral therapy (optimal HAART adherence have significantly higher oxidative status than those who do not closely follow the therapy (poor HAART adherence. Analysis of variance revealed no significant further increase in oxidative status in HIV-1-infected patients taking antiretroviral and other drugs with the exception of psychiatric drugs (e.g. anxiolytics or antidepressants. Taken together, our results indicate that HAART may affect oxidative stress in HIV-1-infected patients and suggest that antiretroviral therapy plays an important role in the synergy of HIV infection and oxidative stress.
Rönsholt, Frederikke F; Ostrowski, Sisse Rye; Katzenstein, Terese Lea;
Immune activation is decreased by combination antiretroviral therapy (cART) in patients infected with human immunodeficiency virus (HIV), but residual activation remains and has been proposed as a cause of premature aging and death, but data are lacking. We analyzed the relationship between T...
Mocroft, Amanda; Sterne, Jonathan A C; Egger, Matthias
BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started...
Uldrick, Thomas S.; Wyvill, Kathleen M.; Kumar, Pallavi; O'Mahony, Deirdre; Bernstein, Wendy; Aleman, Karen; Polizzotto, Mark N.; Steinberg, Seth M.; Pittaluga, Stefania; Marshall, Vickie; Whitby, Denise; Little, Richard F.; Yarchoan, Robert
Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T1), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients. PMID:22430271
Bannister, Wendy P; Kirk, Ole; Gatell, Jose M;
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......: Virologic response (viral load Virologic.......026) and time (P virologic response after adjustment for confounders. Stratified by period, regional differences were less evident (early cART, P = 0.967; mid cART, P = 0.291; late cART, P = 0.163). Stratified by region, temporal changes were observed (south, P = 0.061; central west, P
Bannister, W; Kirk, O; Gatell, J;
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......: Virologic response (viral load Virologic.......026) and time (P virologic response after adjustment for confounders. Stratified by period, regional differences were less evident (early cART, P = 0.967; mid cART, P = 0.291; late cART, P = 0.163). Stratified by region, temporal changes were observed (south, P = 0.061; central west, P
Kesselring, Anouk M; Wit, Ferdinand W; Sabin, Caroline A;
BACKGROUND: This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc). METHODS: Patients starting NVPc after 1...... to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year...... of starting NVPc and mode of transmission. RESULTS: Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high...
Pasternak, A.O.; Jurriaans, S.; Bakker, M.; Prins, J.M.; Berkhout, B.; Lukashov, V.V.
Background: Combination antiretroviral therapy (cART), the standard of care for HIV-1 infection, is considered to be successful when plasma viremia remains below the detection limit of commercial assays. Yet, cART fails in a substantial proportion of patients after the apparent success. No laborator
Eaton, Jeffrey W; Menzies, Nicolas A; Stover, John
BACKGROUND: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral th...
Nyirenda, Christopher; Zulu, Isaac; Kabagambe, Edmond K; Bagchi, Shashwatee; Potter, Dara; Bosire, Claire; Krishnasami, Zipporah; Heimburger, Douglas C
High mortality rates have been reported in the first 90 days of antiretroviral therapy in Zambia and other low-income countries. We report a case of acute hypophosphataemia and hypokalaemia in the first week of antiretroviral therapy in a patient with extreme AIDS wasting. Given its occurrence in an extremely wasted patient, it may be physiologically similar to refeeding syndrome but other causes could be relevant as well. Acute hypophosphataemia may contribute to early antiretroviral therapy associated mortality in low-income countries.
Caitlin J McCabe
Full Text Available BACKGROUND: In HIV-infected pregnant women, viral suppression prevents mother-to-child HIV transmission. Directly observed highly-active antiretroviral therapy (HAART enhances virological suppression, and could prevent transmission. Our objective was to project the effectiveness and cost-effectiveness of directly observed administration of antiretroviral drugs in pregnancy. METHODS AND FINDINGS: A mathematical model was created to simulate cohorts of one million asymptomatic HIV-infected pregnant women on HAART, with women randomly assigned self-administered or directly observed antiretroviral therapy (DOT, or no HAART, in a series of Monte Carlo simulations. Our primary outcome was the quality-adjusted life expectancy in years (QALY of infants born to HIV-infected women, with the rates of Caesarean section and HIV-transmission after DOT use as intermediate outcomes. Both self-administered HAART and DOT were associated with decreased costs and increased life-expectancy relative to no HAART. The use of DOT was associated with a relative risk of HIV transmission of 0.39 relative to conventional HAART; was highly cost-effective in the cohort as a whole (cost-utility ratio $14,233 per QALY; and was cost-saving in women whose viral loads on self-administered HAART would have exceeded 1000 copies/ml. Results were stable in wide-ranging sensitivity analyses, with directly observed therapy cost-saving or highly cost-effective in almost all cases. CONCLUSIONS: Based on the best available data, programs that optimize adherence to HAART through direct observation in pregnancy have the potential to diminish mother-to-child HIV transmission in a highly cost-effective manner. Targeted use of DOT in pregnant women with high viral loads, who could otherwise receive self-administered HAART would be a cost-saving intervention. These projections should be tested with randomized clinical trials.
Mijiti, Peierdun; Yuexin, Zhang; Min, Liu; Wubuli, Maimaitili; Kejun, Pan; Upur, Halmurat
We retrospectively analysed routinely collected baseline data of 2252 patients with HIV infection registered in the National Free Antiretroviral Treatment Program in Xinjiang province, China, from 2006 to 2011 to estimate the prevalence and predictors of anaemia at the initiation of combined antiretroviral therapy. Anaemia was diagnosed using the criteria set forth by the World Health Organisation, and univariate and multivariate logistic regression analyses were performed to determine its predictors. The prevalences of mild, moderate, and severe anaemia at the initiation of combined antiretroviral therapy were 19.2%, 17.1%, and 2.6%, respectively. Overall, 38.9% of the patients were anaemic at the initiation of combined antiretroviral therapy. The multivariate logistic regression analysis indicated that Uyghur ethnicity, female gender, lower CD4 count, lower body mass index value, self-reported tuberculosis infection, and oral candidiasis were associated with a higher prevalence of anaemia, whereas higher serum alanine aminotransferase level was associated with a lower prevalence of anaemia. The results suggest that the overall prevalence of anaemia at the initiation of combined antiretroviral therapy in patients with HIV infection is high in Xinjiang, China, but severe anaemia is uncommon. Patients in China should be routinely checked for anaemia prior to combined antiretroviral therapy initiation, and healthcare providers should carefully select the appropriate first-line combined antiretroviral therapy regimens for anaemic patients.
Newcomb, Michael E.; Bedoya, C. Andres; Blashill, Aaron J.; Lerner, Jonathan A.; O’Cleirigh, Conall; Pinkston, Megan M.; Safren, Steven A.
There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depres...
Full Text Available Pharmaceutical care (PC has been shown to improve the outcome of drug therapy in many disease conditions.HIV/AIDS is one of the disease conditions that are fraught with many problems that can benefit from this new emphasis of pharmacy practice also known as ‘pharmacists care’. This study is designed to determine the number and types of drug therapy problems occurring in the drug therapy of HIV patients receiving treatment at a tertiary hospital in southeast Nigeria and to evaluate the impact of pharmaceutical care activities on the occurrence of these drug therapy problems (DTPs. The components of the American society of health-system pharmacists (ASHP guidelines on ‘standardized method for pharmaceutical care’ was used as a data collection instrument to evaluate, document and intervene in the antiretroviral therapy of about one thousand four hundred and seventy three (1,473 patients. The study showed significant reduction in the incidence of drug therapy problems following the Pharmacist’s intervention activities. The study found out that eighty-nine percent (89% of the prescriptions had potential drug therapy problems before the interventions which were reduced by 12% to seventy-seven percent (77% after the intervention. The study also identified seventeen (17 different potential drug therapy problems prior to the interventions. A re - evaluation of these potential drug therapy problems after the interventions showed the very significant percentage reductions in the occurrence of each DTP. The study showed that pharmacists’ interventions in antiretroviral drug therapy through Pharmaceutical care can significantly reduce the occurrence of drug therapy problems associated with antiretroviral drug therapy.
Full Text Available Background. With the increase in scaling up of antiretroviral therapy (ART, knowledge of the need for adherence to ART is pivotal for successful treatment outcomes. Design and Methods. A cross-sectional study was carried out between October and December 2013. We administered theory of planned behaviour (TPB and adherence questionnaires to 358 women aged 18-49 years, from a rural and urban ART-clinics in southern Malawi. Hierarchical linear regression models were used to predict intentions to adhere to ART. Results. Regression models showed that attitude (β=0.47, subjective norm (β=0.31, and perceived behavioral control (β=0.12 explain 55% of the variance in intentions to adhere to ART. The relationship between both food insecurity and perceived side effects with intentions to adhere to ART is mediated by attitude, subjective norm, and perceived behavioural control. Household (r=0.20 and individual (r=0.21 food insecurity were positively and significantly correlated with perceived behavioural control. Household food insecurity had a negative correlation with perceived side effects (r=-0.11. Perceived side effects were positively correlated with attitude (r=0.25. There was no statistically significant relationship between intentions to adhere to ART in the future and one month self-report of past month adherence. These interactions suggest that attitude predicted adherence only when food insecurity is high or perception of side effects is strong.Conclusions. This study shows that modification might be needed when using TPB constructs in resource constraint environments
Brouwer, A.E.; Koopmans, P.P.; Hofstede, H.J. ter; Keuter, M.; Ven, A.J. van der; Groot, R. de
BACKGROUND: The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We a
del Amo, Julia; Moreno, Santiago; Bucher, Heiner C; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Lodi, Sara; van Sighem, Ard; de Wolf, Wolf; Sabin, Caroline; Bansi, Loveleen; Justice, Amy; Goulet, Joseph; Miró, José M; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Toulomi, Giota; Gargalianos, Panagiotis; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A; Schölvinck, Elisabeth H.
BACKGROUND: The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We a
Full Text Available To fully define clinical efficacy of highly active antiretroviral therapy for AIDS, analyze patients’ survival time and treatment mode after receiving treatment, and provide scientific theory to guide improvement of antiviral therapy, this paper selected 3100 cases of patients diagnosed with AIDS during April 2006 and April 2014 as object of this study. All patients were treated with highly active antiretroviral therapy. The main analysis contents of this study include CD4 + T lymphocyte count, viral load changes, incidence of opportunistic infections, specific cause of death and the like. The results show that patients’ CD4 + T lymphocyte levels are significantly increased 3, 18, and 24 months after treatment, difference between the situation after and before receiving treatment, P < 0.05, with statistically significant difference. Analyzed from effective inhibition of virus, effective inhibition rate is 72.58.0% (2250/3100. Main causes of death in patients is usually respiratory failure. It thus can be concluded that highly active antiretroviral therapy for AIDS is with good clinical effect, which can effectively improve survival time of patients. So it enjoys application value of being widely used in clinical treatment of AIDS.
Mocroft, Amanda; Bannister, Wendy P; Kirk, Ole
The aim of this study was to determine whether there is a protective effect of combination antiretroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression.......The aim of this study was to determine whether there is a protective effect of combination antiretroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression....
Li, Nan; Sando, Mary Mwanyika; Spiegelman, Donna; Hertzmark, Ellen; Liu, Enju; Sando, David; Machumi, Lameck; Chalamilla, Guerino; Fawzi, Wafaie
Although the beneficial effects of antiretroviral (ARV) therapy for preventing mother-to-child transmission are indisputable, studies in developed and developing countries have reported conflicting findings on the association between ARV exposure and adverse birth outcomes. We conducted a prospective observational study at 10 human immunodeficiency virus (HIV) care and treatment centers in Dar es Salaam, Tanzania. Multivariate log-binomial regression was used to investigate the associations between ARV use and adverse birth outcomes among HIV-negative HIV-exposed infants. Our findings demonstrate an increased risk of adverse birth outcomes associated with the use of highly active antiretroviral therapy during pregnancy. Further studies are needed to investigate the underlying mechanisms and identify the safest ARV regimens for use during pregnancy.
Lawn, Stephen D; Wilkinson, Robert J; Lipman, Marc C. I.; Wood, Robin
Tuberculosis (TB) is the most common opportunistic disease in HIV-infected patients during the initial months of antiretroviral therapy (ART) and presents a great challenge to ART programs in resource-limited settings. The mechanisms underlying development of TB in this period are complex. Some cases may represent progression of undiagnosed subclinical disease present before starting ART, emphasizing the importance of careful screening strategies for TB. It has been suggested that progression...
Gustavo Romero‐Velez, MD
Conclusions: ED is highly prevalent in HIV patients. Dyslipidemia should be considered as a risk factor for ED in HIV patients. Romero‐Velez G, Lisker‐Cervantes A, Villeda‐Sandoval CI, Sotomayor de Zavaleta M, Olvera‐Posada D, Sierra‐Madero JG, Arreguin‐Camacho LO, and Castillejos‐Molina RA. Erectile dysfunction among HIV patients undergoing highly active antiretroviral therapy: Dyslipidemia as a main risk factor. Sex Med 2014;2:24–30.
Kamini Tyagi; Veena Gupta
Background: The study was conducted to evaluate safety and tolerability of different components of combined antiretroviral therapy (CART) in pregnant and non-pregnant women and to find out substitute of the drug causing intolerance. Methods: An observational study on 75 pregnant and 125 non pregnant, HIV infected women receiving CART, over a period of 1 year (Jan 2013-Jan 20140 in SRN Hospital affiliated to MLN Medical college, Allahabad. All women were examined clinically and investigated...
BACKGROUND: Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European...... factor, detectable HIV-1 RNA viral load becomes an increasingly important risk factor in patients who started cART several years earlier, independently of immunodeficiency....
Ugwu, Rosemary; Eneh, Augusta
Introduction The efficiency of antiretroviral therapy (ART) depends on a near-perfect level of patient's adherence. Adherence in children poses peculiar challenges. The aim of the study was to determine the adherence level and factors influencing adherence among HIV-infected children and adolescents in University of Port Harcourt Teaching Hospital, Nigeria. Methods A cross-sectional survey of HIV-infected children and adolescents on ART using self-report by the caregiver/child in the past one...
Bamba, Sanata; Lortholary, Olivier; Sawadogo, Adrien; Millogo, Athanase; Guiguemdé, Robert T; Bretagne, Stéphane
Cryptococcosis remains a major opportunistic infection in AIDS in sub-Saharan Africa, but few data exist from its western part. We report data from Bobo Dioulasso University Hospital, Bobo-Dioulasso, Burkina Faso, with a steady decline from 14 to two cases per year from 2002 to 2010 which contrasts with the increase (from 147 to 3940) of patients on antiretroviral therapy (ART). Better ART availability decreases the incidence of cryptococcosis in Burkina Faso.
Kavita S. Joshi; Rohit R. Shriwastav
Background: HIV is now considered as chronic disease than a fatal disease. HIV infected individual is having normal life expectancy post highly active antiretroviral therapy (HAART) era. Liver disease is the major cause of morbidity and mortality in HIV infected patients. The objective was to study the prevalence, clinical profile of various liver diseases in HIV infected individuals on HAART and also to study aetiologies of liver involvement in HIV patients. Methods: It was a cross secti...
Mosoko Jembia J; Akam Wilfred; Weidle Paul J; Brooks John T; Aweh Asabi J; Kinge Thompson N; Pals Sherri; Raghunathan Pratima L
Abstract Background In 2002, Cameroon initiated scale up of antiretroviral therapy (ART); on 1 October 2004, a substantial reduction in ART cost occurred. We assessed the impact of this event and other factors on enrolment and retention in care among HIV-infected patients initiating ART from February 2002 to December 2005 at the single ART clinic serving the Southwest Region in Limbe, Cameroon. Methods We retrospectively analyzed clinical and pharmacy payment records of HIV-infected patients ...
Dikman, Andrew E.; Schonfeld, Emily; Srisarajivakul, Nalinee C.; Poles, Michael A
Over half of patients with human immunodeficiency virus (HIV) experience diarrhea that contributes negatively to quality of life and adherence to antiretroviral therapy (ART). Opportunistic infectious agents that cause diarrhea in patients with HIV span the array of protozoa, fungi, viruses, and bacteria. With global use of ART, the incidence of diarrhea because of opportunistic infections has decreased; however, the incidence of noninfectious diarrhea has increased. The etiology of noninfect...
Herasimtschuk, Anna A; Hansen, Birgitte R; Langkilde, Anne;
Recombinant human growth hormone (rhGH) administered to combination antiretroviral therapy (cART)-treated human immunodeficiency virus-1 (HIV-1)-infected individuals has been found to reverse thymic involution, increase total and naïve CD4 T-cell counts, and to reduce the expression of activation...... were used to enumerate HIV-1-specific IFN-γ-producing T cells at baseline and week 40. Individuals who received rhGH demonstrated increased responses to HIV-1 Gag overlapping 20mer and Gag 9mer peptide pools at week 40 compared to baseline, whereas subjects who received placebo showed no functional...
Full Text Available BACKGROUND: Substantial resources and patient commitment are required to successfully scale-up antiretroviral therapy (ART and provide appropriate HIV management in resource-limited settings. We used pharmacy refill records to evaluate risk factors for loss to follow-up (LTFU and non-adherence to ART in a large treatment cohort in Nigeria. METHODS AND FINDINGS: We reviewed clinic records of adult patients initiating ART between March 2005 and July 2006 at five health facilities. Patients were classified as LTFU if they did not return >60 days from their expected visit. Pharmacy refill rates were calculated and used to assess non-adherence. We identified risk factors associated with LTFU and non-adherence using Cox and Generalized Estimating Equation (GEE regressions, respectively. Of 5,760 patients initiating ART, 26% were LTFU. Female gender (p 350 and 2 hours to the clinic (p = 0.03, had total ART duration of >6 months (p200 at ART initiation were at a higher risk of non-adherence. Patients who disclosed their HIV status to spouse/family (p = 0.01 and were treated with tenofovir-containing regimens (p < or = 0.001 were more likely to be adherent. CONCLUSIONS: These findings formed the basis for implementing multiple pre-treatment visit preparation that promote disclosure and active community outreaching to support retention and adherence. Expansion of treatment access points of care to communities to diminish travel time may have a positive impact on adherence.
SA HIV Clinicians Society
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
Ian R Grubb
Full Text Available Introduction: Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART, and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Discussion: Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Conclusions: Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including
Full Text Available Objectives: We describe the frequency and types of drug therapy problems (DTPs, and interventions carried out to resolve them, among a cohort of HIV- infected patients on ART in Jos, Nigeria. Methods: A prospective pharmacists’ intervention study was conducted between January and August 2012 at the outpatient HIV clinic of the Jos University Teaching Hospital (JUTH. Pharmacists identified DTPs and made recommendations to resolve them. The main outcome measures were number of DTPs encountered, interventions proposed and acceptance rate of recommendations. Results: A total of 42,416 prescriptions were dispensed to 9339 patients during the eight months study. A total of 420 interventions (Intervention rate of 1 per 100 prescriptions were made to resolve DTPs in 401 (4.3% patients with a mean age of 41 (SD=10 years, and made up of 73% females. DTPs encountered were drug omission (n=89, 21.2%, unnecessary drug (n=55, 13.1% and wrong drug indication (n=55, 13.1%. Recommendations offered included; Addition of another drug to the therapy (n=87, 20.7%, rectification of incomplete prescriptions (n=85, 20.2%, change of drug or dosage (n=67, 16.0%, and discontinuation of the offending drug (n=59, 14.0%. A total of 389 (93% out of 420 of the recommendations were accepted. In all, 50.4% (212 of the problematic prescriptions were changed and dispensed, 22.2% (89 were clarified and dispensed, while wrong identities were corrected in 11.7% (49. However, 7.5% (30 prescriptions were dispensed as prescribed, 5.2% (21 were not dispensed, and 3% (12 were unresolved. Conclusion: Our findings suggest that pharmacists-initiated interventions can ameliorate DTPs in patients receiving ART given the high intervention acceptance rate recorded. The implication of this finding is that pharmacists with requisite training in HIV pharmacotherapy are an excellent resource in detecting and minimizing the effect of antiretroviral drug-related errors.
Dahab, Maysoon; Kielmann, Karina; Charalambous, Salome; Karstaedt, Alan S; Hamilton, Robin; La Grange, Lettie; Fielding, Katherine L; Churchyard, Gavin J; Grant, Alison D
Abstract We investigated reasons for clinical follow-up and treatment discontinuation among HIV-infected individuals receiving antiretroviral therapy (ART) in a public-sector clinic and in a workplace clinic in South Africa. Participants in a larger cohort study who had discontinued clinical care by the seventh month of treatment were traced using previously provided locator information. Those located were administered a semistructured questionnaire regarding reasons for discontinuing clinical follow-up. Participants who had discontinued antiretroviral therapy were invited to participate in further in-depth qualitative interviews. Fifty-one of 144 (35.4%) in the workplace cohort had discontinued clinical follow-up by the seventh month of treatment. The median age of those who discontinued follow-up was 46 years and median educational level was five years. By contrast, only 16.5% (44/267) of the public-sector cohort had discontinued follow-up. Among them the median age was 37.5 years and median education was 11 years. Qualitative interviews were conducted with 17 workplace participants and 10 public-sector participants. The main reasons for attrition in the workplace were uncertainty about own HIV status and above the value of ART, poor patient-provider relationships and workplace discrimination. In the public sector, these were moving away and having no money for clinic transport. In the workplace, efforts to minimize the time between testing and treatment initiation should be balanced with the need to provide adequate baseline counseling taking into account existing concepts about HIV and ART. In the public sector, earlier diagnosis and ART initiation may help to reduce early mortality, while links to government grants may reduce attrition.
N.Y. Rakhmanina (Natella)
textabstractHIV infection became a newly recognized disease in the mid 1980s. High morbidity and mortality associated with it prompted the urgent development of new therapeutic agents and combination therapies. Throughout the next 20 years the hopes for cure have risen and fallen, and the vaccine re
Wyatt, Christina M.; Morgello, Susan; Katz-Malamed, Rebecca; Wei, Catherine; Klotman, Mary E.; Klotman, Paul E.; D’Agati, Vivette D.
With prolonged survival and aging of the HIV-infected population in the era of antiretroviral therapy, biopsy series have found a broad spectrum of HIV-related and co-morbid kidney disease in these patients. Our study describes the variety of renal pathology found in a prospective cohort of antiretroviral-experienced patients (the Manhattan HIV Brain Bank) who had consented to postmortem organ donation. Nearly one-third of 89 kidney tissue donors had chronic kidney disease, and evidence of some renal pathology was found in 75. The most common diagnoses were arterionephrosclerosis, HIV-associated nephropathy and glomerulonephritis. Other diagnoses included pyelonephritis, interstitial nephritis, diabetic nephropathy, fungal infection and amyloidosis. Excluding 2 instances of acute tubular necrosis, slightly over one-third of the cases would have been predicted using current diagnostic criteria for chronic kidney disease. Based on semi-quantitative analysis of stored specimens, pre-mortem microalbuminuria testing could have identified an additional 12 cases. Future studies are needed to evaluate the cost-effectiveness of more sensitive methods for defining chronic kidney disease, in order to identify HIV-infected patients with early kidney disease who may benefit from antiretroviral therapy and other interventions known to delay disease progression and prevent complications. PMID:19052538
Liana Aguiar Braga
Full Text Available Objective: To evaluate nutritional and metabolic changes in HIV infected (HIV+ patients on use of antiretroviral therapy. Methods: A cross-sectional descriptive study involving HIV+ patients on use of Highly Active Antiretroviral Therapy (HAART. The demographic data studied were gender, birth date and time of use of antiretroviral medication. Anthropometric variables were weight and height with calculation of body mass index (BMI. Biochemical data were lipid profile, blood glucose, renal function, albumin, uric acid, oxalacetic and pyruvic transaminases and red blood cells count. Results: The study population comprised 70 patients, 36 (51.4% men and 34 (48.6% women with an average time of HAART-use of 34.5 + 16.5 months. We observed a prevalence of 42 (60% healthy weight for BMI, changes in lipid profile and reduction of lean mass in 18 (50% men and increased abdominal obesity in 23 (67.7% women. Conclusion: The studied subjects in use of HAART showed to have loss of subcutaneous fat, lipid changes and higher prevalence of abdominal obesity in women.
Dinoso, J B; Kim, S Y; Wiegand, A M; Palmer, S E; Gange, S J; Cranmer, L; O'Shea, A; Callender, M; Spivak, A; Brennan, T; Kearney, M F; Proschan, M A; Mican, J M; Rehm, C A; Coffin, J M; Mellors, J W; Siliciano, R F; Maldarelli, F
In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.
Borges, Álvaro H; Neuhaus, Jacqueline; Babiker, Abdel G;
BACKGROUND: In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts...... and human immunodeficiency virus (HIV) RNA between the study arms. METHODS: Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline...... covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART. RESULTS: There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23...
Bannister, WP; Ruiz, L; Loveday, C;
BACKGROUND: Combination antiretroviral therapy (cART) may vary in ability to suppress viral load and increase CD4+ T-cell count in people infected with different HIV-1 subtypes, possibly due to differences in resistance development. Antiretroviral drugs have predominantly been developed in Western......, observational cohort with 11,928 HIV-1-infected patients. METHODS: Response to cART was analysed in patients with subtypes determined pre-cART, via multivariable logistic regression on the first measurements 6–12 months after starting cART. A virological response was defined as a viral load ...-B-infected patients (P=0.334). After adjustment, there was no significant difference in odds of an immunological response (OR: 1.17, 95% CI: 0.73–1.87, P=0.524). CONCLUSIONS: There was no evidence of significant differences in virological or immunological response to cART between patients infected with HIV-1 B...
May, Margaret T.; Vehreschild, Janne; Obel, Niels; Gill, Michael John; Crane, Heidi; Boesecke, Christoph; Samji, Hasina; Grabar, Sophie; Cazanave, Charles; Cavassini, Matthias; Shepherd, Leah; d’Arminio Monforte, Antonella; Smit, Colette; Saag, Michael; Lampe, Fiona; Hernando, Vicky; Montero, Marta; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy; Miro, Jose; Ingle, Suzanne; Sterne, Jonathan A. C.
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 mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years. Conclusions Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes. PMID:27525413
Scott, Christopher; Staughton, Richard C D; Bunker, Christopher J; Asboe, David
Immune reconstitution disease (IRD) has been widely reported following the commencement of antiretrovirals. We report a case series from a cohort of HIV-1-infected patients of whom four developed acne vulgaris and one developed acne rosacea after the initiation of antiretroviral therapy. Acne vulgaris, as part of IRD, has been reported only once in the literature, whereas acne rosacea has not, to our knowledge, previously been described. This serves as a reminder not to overlook dermatological manifestations of disease in patients with HIV infection after starting antiretrovirals.
Full Text Available Purpose of the study Previous investigation into antiretroviral (ARV therapy switches in our HIV cohort suggested an annual switch rate of 20% in 2006 with 60% of switches being secondary to toxicity . The purpose of this study was to investigate whether this switch rate has changed in recent years, determine reasons why patients change regimens, and identify which ARVs are most likely to be switched for toxicity concerns. Methods The electronic patient database was reviewed to identify all patients within our HIV cohort who switched ARV therapy between 1st December 2009 and 31st May 2011. Details of which ARVs were switched and the reasons why were recorded. Any switches due to toxicity were investigated further to identify the actual or perceived adverse effect. Summary of results Nine hundred and twenty-three regimens were switched over 18 months affecting 12% (n = 722 of patients on treatment during this time. The most common reason for switching medication was due to toxicity, occurring in 452 (49% cases. Other reasons included simplification (15%, clinical trials (8%, virological failure (8% and drug interactions (4%. The remaining 16% switched for various reasons including pregnancy and co-morbidities. Of 452 switches for toxicity (or perceived toxicity, 122 (27% were due to CNS side effects (89 out of a total of 122 were related to efavirenz, 64 (14% gastrointestinal disturbances (38/64 related to protease inhibitors, 54 (12% actual/perceived cardiovascular risk (21/54 related to abacavir and 21/54 related to saquinavir, 54 (12% hepatotoxicity (21/54 related to atazanavir and 14/54 related to efavirenz, 42 (9% metabolic concerns (24/42 related to protease inhibitors and 38 (8% renal toxicity (28/38 related to tenofovir. Other toxicities accounted for 78 (18% switches. An observed toxicity switch rate (OTSR per 1000 patient years (95% CI was calculated for each ARV. Conclusions 12% of patients switched therapy in 18 months, predicting
Spivak, Adam M.; Andrade, Adriana; Eisele, Evelyn; Hoh, Rebecca; Bacchetti, Peter; Bumpus, Namandjé N.; Emad, Fatemeh; Buckheit, Robert; McCance-Katz, Elinore F.; Lai, Jun; Kennedy, Margene; Chander, Geetanjali; Siliciano, Robert F.; Siliciano, Janet D.; Deeks, Steven G.
Background. Transcriptionally silent human immunodeficiency virus type 1 (HIV-1) DNA persists in resting memory CD4+ T cells despite antiretroviral therapy. In a primary cell model, the antialcoholism drug disulfiram has been shown to induce HIV-1 transcription in latently infected resting memory CD4+ T cells at concentrations achieved in vivo. Methods. We conducted a single-arm pilot study to evaluate whether 500 mg of disulfiram administered daily for 14 days to HIV-1–infected individuals on stable suppressive antiretroviral therapy would result in reversal of HIV-1 latency with a concomitant transient increase in residual viremia or depletion of the latent reservoir in resting memory CD4+ T cells. Results. Disulfiram was safe and well tolerated. There was a high level of subject-to-subject variability in plasma disulfiram levels. The latent reservoir did not change significantly (1.16-fold change; 95% confidence interval [CI], .70- to 1.92-fold; P = .56). During disulfiram administration, residual viremia did not change significantly compared to baseline (1.53-fold; 95% CI, .88- to 2.69-fold; P = .13), although residual viremia was estimated to increase by 1.88-fold compared to baseline during the postdosing period (95% CI, 1.03- to 3.43-fold; P = .04). In a post hoc analysis, a rapid and transient increase in viremia was noted in a subset of individuals (n = 6) with immediate postdose sampling (HIV-1 RNA increase, 2.96-fold; 95% CI, 1.29- to 6.81-fold; P = .01). Conclusions. Administration of disulfiram to patients on antiretroviral therapy does not reduce the size of the latent reservoir. A possible dose-related effect on residual viremia supports future studies assessing the impact of higher doses on HIV-1 production. Disulfiram affects relevant signaling pathways and can be safely administered, supporting future studies of this drug. PMID:24336828
Full Text Available Abstract Background The devastating impact of AIDS in the world especially in sub-Saharan Africa has led to an unprecedented global effort to ensure access to antiretroviral (ARV drugs. Given that medication-taking behavior can immensely affect an individual's response; ART adherence is now widely recognized as an 'Achilles heel' for the successful outcome. The present study was undertaken to investigate the rate and predictors of adherence to antiretroviral therapy among HIV-infected persons in southwest Ethiopia. Methods The study was conducted in the antiretroviral therapy unit of Jimma University Specialized Hospital. A prospective study was undertaken on a total of 400 HIV infected person. Data were collected using a pre-tested interviewer-administered structured questionnaire at first month (M0 and third month (M3 follow up visits. Results A total of 400 and 383 patients at baseline (M0 and at follow up visit (M3 respectively were interviewed. Self-reported dose adherence in the study area was 94.3%. The rate considering the combined indicator (dose, time and food was 75.7%. Within a three month follow up period, dose adherence decreased by 2% and overall adherence rate decreased by more than 3%. Adherence was common in those patients who have a social support (OR, 1.82, 95%CI, 1.04, 3.21. Patients who were not depressed were two times more likely to be adherent than those who were depressed (OR, 2.13, 95%CI, 1.18, 3.81. However, at the follow up visit, social support (OR, 2.42, 95%CI, 1.29, 4.55 and the use of memory aids (OR, 3.29, 95%CI, 1.44, 7.51 were found to be independent predictors of adherence. The principal reasons reported for skipping doses in this study were simply forgetting, feeling sick or ill, being busy and running out of medication in more than 75% of the cases. Conclusion The self reported adherence rate was high in the study area. The study showed that adherence is a dynamic process which changes overtime and cannot
Chaillon, Antoine; Gianella, Sara; Vazquez, Homero; Ignacio, Caroline; Zweig, Adam C; Richman, Douglas D; Smith, Davey M
We investigated the pol genotype in two phylogenetically and epidemiologically linked partners, who were both experiencing persistent low-level viremia during antiretroviral therapy. In one partner we identified a new residue insertion between codon 248 and 249 of the HIV-1 RNA reverse transcriptase (RT) coding region (HXB2 numbering). We then investigated the potential impact of identified mutations in RT and antiretroviral binding affinity using a novel computational approach.
González, Ramón E. R.; Coutinho, Sérgio; Zorzenon dos Santos, Rita Maria; de Figueirêdo, Pedro Hugo
The dynamics of human immunodeficiency virus infection under antiretroviral therapy is investigated using a cellular automata model where the effectiveness of each drug is self-adjusted by the concentration of CD4+ T infected cells present at each time step. The effectiveness of the drugs and the infected cell concentration at the beginning of treatment are the control parameters of the cell population’s dynamics during therapy. The model allows describing processes of mono and combined therapies. The dynamics that emerges from this model when considering combined antiretroviral therapies reproduces with fair qualitative agreement the phases and different time scales of the process. As observed in clinical data, the results reproduce the significant decrease in the population of infected cells and a concomitant increase of the population of healthy cells in a short timescale (weeks) after the initiation of treatment. Over long time scales, early treatment with potent drugs may lead to undetectable levels of infection. For late treatment or treatments starting with a low density of CD4+ T healthy cells it was observed that the treatment may lead to a steady state in which the T cell counts are above the threshold associated with the onset of AIDS. The results obtained are validated through comparison to available clinical trial data.
Conclusions: HBV co-infection can affect late immunological and virological responses to ART and increase the risk of hepatotoxicity. Mortality due to liver disease was high among HIV/HBV co-infected individuals in this study, despite HBV-active ART. As long as HIV/HBV co-infected persons need anti-HBV therapy, they should be recommended ART that includes agents with activity against both HIV and HBV, regardless of the CD4 cell count level.
Paula Virginia Michelon Toledo
Full Text Available Antiretroviral therapy (ART has reduced morbidity and mortality related to human immunodeficiency virus (HIV infection, but in spite of this advance, HIV mutations decrease antiretroviral susceptibility, thus contributing to treatment failure in patients. Genotyping HIV-1 allows the selection of new drugs after initial drug failure. This study evaluated the genotypic profile of HIV-1 isolates from treated (drug-experienced patients in Paraná, Brazil. The prevalence of mutations in reverse transcriptase (RT and protease (PR genes were assessed. We analyzed 467 genotypes of patients with HIV-1 viral loads above 1,000 copies/mL. Mutations at HIV-1 RT and PR genes and previously used ART regimens were recorded. The most prevalent RT mutations were: 184V (68.31%, 215YF (51.6%, 103NS (46%, 41L (39.4%, 67N (38.54%, 210W (23.5%, 190ASE (23.2%, and 181C (17.4%. PR mutations were 90M (33.33%, 82ATFS (29%, 46I (26.8% and 54V (22.2%. The prevalence of mutations was in line with previous national and international reports, except to nonnucleoside analogue reverse transcriptase inhibitors related mutations, which were more prevalent in this study. Previous exposure to antiretroviral drugs was associated with genotypic resistance to specific drugs, leading to treatment failure in HIV patients.
Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults : 48-week results from the antiretroviral regimen evaluation study (ARES)
Lowe, SH; Wensing, AMJ; Hassink, EAM; ten Kate, RW; Richter, C; Schreij, G; Koopmans, PP; Juttmann, J.; van der Tweel, I.; Lange, JMA; Borleffs, JCC
Background: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. Method: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida
Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults: 48-week results from the Antiretroviral Regimen Evaluation Study (ARES).
Lowe, S.H.; Wensing, B.M.; Hassink, E.A.M.; Kate, R.W. ten; Richter, C.; Schreij, G.; Koopmans, P.P.; Juttmann, J.R.; Tweel, I. van de; Lange, J.M.A.; Borleffs, J.C.
BACKGROUND: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. METHOD: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida
Full Text Available Abstract Background Adequate antiretroviral drug potency is essential for obtaining therapeutic benefit, however, the behavioral aspects of proper adherence and readiness to medication, often determine therapeutic outcome. Therefore, this study aimed to assess the level and determinants of nonadherence and nonreadiness to highly active antiretroviral therapy (HAART among people living with HIV/AIDS (PLWHA at Gondar University Teaching Hospital and Felege Hiwot Hospital in Northwest Ethiopia. Methods A cross-sectional study was conducted between July and September 2008 using structured interviewer-administered questionnaire. All consecutive adult outpatients who were receiving antiretroviral treatment for at least three months, seen at both hospitals during the study period and able to give informed consent were included in the study. Multivariate logistic regression was used to determine factors associated with nonadherence and nonreadiness. Results A total of 504 study subjects were included in this study. The prevalence rates of nonadherence and nonreadiness to HAART were 87 (17.3% and 70 (13.9% respectively. Multivariate logistic regression analysis revealed that medication adverse effects, nonreadiness to HAART, contact with psychiatric care service and having no goal had statistically significant association with nonadherence. Moreover, unwillingness to disclose HIV status was significantly associated with nonreadiness to HAART. Conclusions In this study the level of nonadherence and nonreadiness to HAART seems to be encouraging. Several factors associated with nonadherance and nonreadiness to HAART were identified. Efforts to minimize nonadherence and nonreadiness to HAART should be integrated in to regular clinical follow up of patients.
Xin-ping LI; Hai-wei ZHOU; Jiang-hong HUANG; Hong PENG; Peng-fei MA; Yi-ming SHAO; Hui XING; Zhe WANG; Xue-feng SI; Lian-en WANG; Hua CHENG; Wei-guo CUI; Shu-lin JIANG; Ling-jie LIAO
To investigate the prevalence of drug-resistance mutations, resistance to antiretroviral drugs, and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV/AIDS in Henan, China, a total of 431 plasma samples were collected in Queshan county between 2003 and 2004, from patients undergoing the antiretroviral regimen Zidovudine + Didanosine + Nevirapine (Azt+Ddi+Nvp). Personal information was collected by face to face interview. Viral load and genotypic drug resistance were tested. Drug resistance mutation data were obtained by analyzing patient-derived sequences through the HIVdb Program (http://hivdb.stanford.edu). Overall, 38.5% of treatment-naive patients had undetectable plasma viral load (VL), the rate significantly increased to 61.9% in 0 to 6 months treatment patients (mean 3 months) (P＜0.005) but again significantly decrease to 38.6% in 6 to 12 months treatment patients (mean 9 months) (P＜0.001) and 40.0% in patients receiving more than 12 months treatment (mean 16 months) (P＜0.005). The prevalence of drug resistance in patients who had a detectable VL and available sequences were 7.0%, 48.6%, 70.8%, 72.3% in treatment-na(1)ve, 0 to 6 months treatment, 6 to 12 months treatment, and treatment for greater than 12 months patients, respectively. No mutation associated with resistance to Protease inhibitor (PI) was detected in this study. Nucleoside RT inhibitor (NRTI) mutations always emerged after non-nucleoside RT inhibitor (NNRTI) mutations, and were only found in patients treated for more than 6 months, with a frequency less than 5%, with the exception of mutation T215Y (12.8%, 6/47) which occurred in patients treated for more than 12 months. NNRTI mutations emerged quickly after therapy begun, and increased significantly in patients treated for more than 6 months (P＜0.005), and the most frequent mutations were K103N, V106A, Y181C, G190A. There had been optimal viral suppression in
Shigdel R; Klouman E; Bhandari A; Ahmed LA
Rajesh Shigdel,1 Elise Klouman,2 Anita Bhandari,2 Luai A Ahmed11Department of Health and Care Sciences, 2Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, NorwayPurpose: There are a high number of HIV-infected patients receiving antiretroviral therapy (ART) in the Kathmandu District of Nepal, but information on adherence and factors influencing it are scarce in this population. The present study aimed to estimate ART adherence am...
Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo
Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART.
Thorsteinsson, Kristina; Ladelund, Steen; Jensen-Fangel, Søren;
ABSTRACT: BACKGROUND: Impact of gender on time to initiation, response to and risk of modification of highly active antiretroviral therapy (HAART) in HIV-1 infected individuals is still controversial. METHODS: From a nationwide cohort of Danish HIV infected individuals we identified all heterosex......ABSTRACT: BACKGROUND: Impact of gender on time to initiation, response to and risk of modification of highly active antiretroviral therapy (HAART) in HIV-1 infected individuals is still controversial. METHODS: From a nationwide cohort of Danish HIV infected individuals we identified all...... counts (adjusted p=0.21). We observed no delay in time to initiation of HAART in women compared to men (HR 0.91, 95% CI 0.79-1.06). There were no gender differences in risk of treatment modification of the original HAART regimen during the first year of therapy for either toxicity (IRR 0.97 95% CI 0.......66-1.44) or other/unknown reasons (IRR 1.18 95% CI 0.76-1.82). Finally, CD4 counts and the risk of having a detectable viral load at 1, 3 and 6 years did not differ between genders. CONCLUSIONS: In a setting with free access to healthcare and HAART, gender does neither affect time from eligibility to HAART...
Nyanzi-Wakholi, Barbara; Lara, Antonieta Medina; Munderi, Paula; Gilks, Charles
Antiretroviral therapy (ART) improves the quality of life of people living with HIV/AIDS. However, adherence remains a challenge. A total of eight focus group discussions (FGD) were conducted with participants from a randomised controlled trial that monitored strategies for managing ART in African adults: Development of Antiretroviral Therapy. All FGD participants had received ART for at least one year. Perceived benefits of ART were key motivators for adherence. These benefits included improved physical health, restored self-esteem, acceptance in the community and hope for a longer and healthier life and reduced fear of HIV/AIDS-related death. Barriers to adherence included a high pill burden, ART side effects and socio-economic constraints, including lack of food and safe water for taking the pills. Visible ART side effects and involvement in an exclusively HIV/AIDS clinic could expose their HIV status, thus exacerbating stigma. Gender and socio-economic differences were found in the variety of strategies employed to ensure adherence. ART was perceived as improving the overall quality of life of recipients; however, it is crucial for ART programmes to be gender and socio-economic cognizant in order to enhance adherence to a lifelong therapy.
Kirk, Ole; Reiss, Peter; Uberti-Foppa, Caterina;
maintenance therapy for cytomegalovirus (CMV) end-organ disease, disseminated Mycobacterium avium complex (MAC) infection, cerebral toxoplasmosis, and extrapulmonary cryptococcosis in patients receiving antiretroviral therapy. DESIGN: Observational study. SETTING: Seven European HIV cohorts. PATIENTS: 358...... identified: 162 for CMV disease, 103 for MAC infection, 75 for toxoplasmosis, and 39 for cryptococcosis. During 781 person-years of follow-up, five patients had relapse. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted when the CD4 lymphocyte....... One relapse (toxoplasmosis) was diagnosed after maintenance therapy interruption at a CD4 lymphocyte count greater than 200 x 10(6) cells/L for 15 months. The overall incidences of recurrent CMV disease, MAC infection, toxoplasmosis, and cryptococcosis were 0.54 per 100 person-years (95% CI, 0.07 to 1...
Nabeta, Henry W; Okia, Richard; Rhein, Joshua; Lukande, Robert
Histoplasmosis is the most common endemic mycoses among HIV-infected people. Patients with suppressed cell immunity mainly due to HIV are at increased risk of disseminated disease. Dermatological manifestations of immune reconstitution inflammatory syndrome (IRIS) and cutaneous manifestations of histoplasmosis similar to an IRIS event have been previously described. We report the case of a 43-year-old male who presented with cutaneous disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum 4 months after the onset of the antiretroviral therapy and some improvement in the immune reconstitution. After 2 weeks of amphotericin B and itraconazole therapy, the scheduled treatment involved fluconazole maintenance therapy, which resulted in an improvement of his skin lesions. PMID:28210571
Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSION: Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.
Full Text Available A case-cohort study, within a multi-country trial of antiretroviral therapy (ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS, was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO stage 3, 4 or death by 96 weeks or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR: 57.28–99.89 and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L of serum selenium, we observed increased hazards (adjusted hazards ratio (HR: 3.50; 95% confidence intervals (CI: 1.30–9.42 of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium.
Reekie, J; Mocroft, A; Ledergerber, B
OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategies....... METHODS: A total of 1827 patients on cART starting at least one new antiretroviral from 1 January 2000 while maintaining a suppressed viral load were included in the analysis. Poisson regression analysis identified factors predictive of virological failure after baseline in addition to traditional...... demographic variables. Baseline was defined as the date of starting new antiretrovirals. RESULTS: Four hundred and fifty-one patients (24.7%) experienced virological failure, with an incidence rate (IR) of 7.3 per 100 person-years of follow-up (PYFU) [95% confidence interval (CI) 6.7-8.0]. After adjustment...
Bazin, Gabriela Ricordi; Gaspar, Mariza Curto Saavedra; Silva, Nicole Carvalho Xavier Micheloni da; Mendes, Carolina da Costa; Oliveira, Cora Pichler de; Bastos, Leonardo Soares; Cardoso, Claudete Aparecida Araújo
This study aims to evaluate antiretroviral therapy in children and adolescents with AIDS. We selected 247 abstracts published from 1983 to 2013, collected from the PubMed and LILACS databases. Sixty-nine articles were selected. Attention to research in the pediatric age bracket in 30 years of the epidemic is explained by the age group's immunological characteristics, since AIDS progresses faster in children than in adults. Recent studies focus on the initiation of highly active antiretroviral therapy before the onset of symptoms. Early introduction of combination antiretroviral therapy has been implemented effectively and safely in populations with limited resources, leading to significantly improved survival. The current challenge is to manage a chronic disease with acute complications. New studies should focus on population specificities and identify the individual needs of pediatric patients.
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
Full Text Available BACKGROUND: Adherence is central to the success of antiretroviral therapy. Supporting adherence has gained importance in HIV care in many national treatment programs. The ubiquity of mobile phones, even in resource-constrained settings, has provided an opportunity to utilize an inexpensive, contextually feasible technology for adherence support in HIV in these settings. We aimed to assess the influence of mobile phone reminders on adherence to antiretroviral therapy in South India. Participant experiences with the intervention were also studied. This is the first report of such an intervention for antiretroviral adherence from India, a country with over 800 million mobile connections. METHODS: STUDY DESIGN: Quasi-experimental cohort study involving 150 HIV-infected individuals from Bangalore, India, who were on antiretroviral therapy between April and July 2010. The intervention: All participants received two types of adherence reminders on their mobile phones, (i an automated interactive voice response (IVR call and (ii A non-interactive neutral picture short messaging service (SMS, once a week for 6 months. Adherence measured by pill count, was assessed at study recruitment and at months one, three, six, nine and twelve. Participant experiences were assessed at the end of the intervention period. RESULTS: The mean age of the participants was 38 years, 27% were female and 90% urban. Overall, 3,895 IVRs and 3,073 SMSs were sent to the participants over 6 months. Complete case analysis revealed that the proportion of participants with optimal adherence increased from 85% to 91% patients during the intervention period, an effect that was maintained 6 months after the intervention was discontinued (p = 0.016. Both, IVR calls and SMS reminders were considered non-intrusive and not a threat to privacy. A significantly higher proportion agreed that the IVR was helpful compared to the SMS (p<0.001. CONCLUSION: Mobile phone reminders may improve
De Clercq, Erik
In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.
Stengaard, Annemarie Rinder; Lazarus, Jeff; Donoghoe, Martin C
Objective. To assess the level of access to highly active antiretroviral therapy (HAART) for women and children in the WHO European Region. Methods. Analysis of data from three national surveys of 53 WHO European Member States. The comparative level of access to HAART for women and children...... was assessed by comparing the percentage of reported HIV cases with the percentage of HAART recipients in women at the end of 2002 and 2006 and in children at the end of 2004 and 2006. Findings. Overall, the data suggest that there is equivalence of access to antiretroviral therapy by gender and age in Europe...
Porco, Travis C.; Martin, Jeffrey N.; Page-Shafer, Kimberly A.; Cheng, Amber; Charlebois, Edwin; Grant, Robert M.; Osmond, Dennis H.
Objective Little is known about the degree to which widespread use of antiretroviral therapy in a community reduces uninfected individuals’ risk of acquiring HIV. We estimated the degree to which the probability of HIV infection from an infected partner (the infectivity) declined following the introduction of highly active antiretroviral therapy (HAART) in San Francisco. Design Homosexual men from the San Francisco Young Men’s Health Study, who were initially uninfected with HIV, were asked about sexual practices, and tested for HIV antibodies at each of four follow-up visits during a 6-year period spanning the advent of widespread use of HAART (1994 to 1999). Methods We estimated the infectivity of HIV (per-partnership probability of transmission from an infected partner) using a probabilistic risk model based on observed incident infections and self-reported sexual risk behavior, and tested the hypothesis that infectivity was the same before and after HAART was introduced. Results A total of 534 homosexual men were evaluated. Decreasing trends in HIV seroincidence were observed despite increases in reported number of unprotected receptive anal intercourse partners. Conservatively assuming a constant prevalence of HIV infection between 1994 and 1999, HIV infectivity decreased from 0.120 prior to widespread use of HAART, to 0.048 after the widespread use of HAART – a decline of 60% (P = 0.028). Conclusions Use of HAART by infected persons in a community appears to reduce their infectiousness and therefore may provide an important HIV prevention tool. PMID:15090833
Sadikalmahdi Hussen Abdella
Full Text Available Background: The combination of antiretroviral therapy is the corner stone of management of patients with human immune deficiency virus infection. Although antiretroviral therapy can reduce viral load to undetectable level, improve the immunity and prolong survival of patients, antiretroviral drugs are associated with many adverse effects that may be severe and affect patient adherence and quality of life. Aims : The aim of this study was to assess management strategies under taken in patient′s experienced common adverse effects of highly active antiretroviral therapy in Goba Hospital antiretroviral clinic. Patients and Methods: A cross sectional study of patient record chart of patients who had follow-up during data collection period was done followed by patient interview. Data was filled on well structured questionnaire and analyzed using SPSS for window version 16.0. Results: The common adverse effects were Rash (48.8%, Peripheral neuropathy (36.9% and Anemia (20.24%. The rate of management was 39.3%. Pyridoxine (36.8% was commonly prescribed drug for management of Peripheral neuropathy. Chlorphenarimine gel and Iron gluconate were common drugs for management of Rash and Anemia respectively. Use of traditional healers (57.7% was leading reason for non-management. Conclusion: Rate of management for common adverse effect is low. Education should be given on adverse effects for patients.
Nam, Nguyen Thi Thu; Bygbjerg, Ib Christian; Mogensen, Hanne Overgaard;
In Vietnam, ARV access has been scaled up since 2005 in high HIV prevalence areas in order to meet increasing demands for HIV treatment. This paper aims to estimate ARV unmet need and its associated socio-demographic characteristics among HIV-positive women in Haiphong, Vietnam. A cross...
Montoya Carlos J
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
Lisa B Haddad
Full Text Available Programs for integration of family planning into HIV care must recognize current practices and desires among clients to appropriately target and tailor interventions. We sought to evaluate fertility intentions, unintended pregnancy, contraceptive and condom use among a cohort of HIV-infected women seeking family planning services within an antiretroviral therapy (ART clinic.200 women completed an interviewer-administered questionnaire during enrollment into a prospective contraceptive study at the Lighthouse Clinic, an HIV/ART clinic in Lilongwe, Malawi, between August and December 2010.Most women (95% did not desire future pregnancy. Prior reported unintended pregnancy rates were high (69% unplanned and 61% unhappy with timing of last pregnancy. Condom use was inconsistent, even among couples with discordant HIV status, with lack of use often attributed to partner's refusal. Higher education, older age, lower parity and having an HIV negative partner were factors associated with consistent condom usage.High rates of unintended pregnancy among these women underscore the need for integ rating family planning, sexually transmitted infection (STI prevention, and HIV services. Contraceptive access and use, including condoms, must be improved with specific efforts to enlist partner support. Messages regarding the importance of condom usage in conjunction with more effective modern contraceptive methods for both infection and pregnancy prevention must continue to be reinforced over the course of ongoing ART treatment.
Williams, Ian; Churchill, Duncan; Anderson, Jane; Boffito, Marta; Bower, Mark; Cairns, Gus; Cwynarski, Kate; Edwards, Simon; Fidler, Sarah; Fisher, Martin; Freedman, Andrew; Geretti, Anna Maria; Gilleece, Yvonne; Horne, Rob; Johnson, Margaret; Khoo, Saye; Leen, Clifford; Marshall, Neal; Nelson, Mark; Orkin, Chloe; Paton, Nicholas; Phillips, Andrew; Post, Frank; Pozniak, Anton; Sabin, Caroline; Trevelion, Roy; Ustianowski, Andrew; Walsh, John; Waters, Laura; Wilkins, Edmund; Winston, Alan; Youle, Mike
The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection with antiretroviral therapy (ART). The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii)support of patients on treatment; (iii) management of patients experiencing virological failure; and (iv) recommendations in specific patient populations where other factors need to be taken into consideration. The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection and at community advocates responsible for promoting the best interests and care of HIV-positive adults. They should be read in conjunction with other published BHIVA guidelines.
Winckelmann, Anni; Barton, Kirston; Hiener, Bonnie; Schlub, Timothy E.; Shao, Wei; Rasmussen, Thomas A.; Østergaard, Lars; Søgaard, Ole S.; Tolstrup, Martin; Palmer, Sarah
Objective: To investigate the origin of the HIV-1 viremia induced by the latency-reversing agent romidepsin. Design: Six individuals on suppressive antiretroviral therapy received romidepsin administered intravenously once weekly for 3 consecutive weeks. CD4+ T cells were obtained at baseline, following the second and third romidepsin infusion, and 10 weeks after the final romidepsin treatment. Plasma samples were collected 24 and 72 h after romidepsin infusions. Methods: Single-genome sequencing of the env and p24-RT region was used to genetically characterize the virus from proviral DNA, the transcribed cell-associated RNA and the plasma RNA pool. Results: In three of six participants with available plasma samples we identified plasma HIV-1 RNA sequences that were identical to DNA and/or cell-associated RNA sequences from peripheral blood CD4+ T cells. In two participants, plasma RNA sequences contained expansions of identical sequences, corresponding to 62 and 100% of the total sequences, respectively. Plasma HIV-1 RNA had very low amounts of defective viruses compared to cell-associated RNA (odds ratio 20.85, P < 0.001) and to DNA (odds ratio 7.07, P = 0.011) during romidepsin therapy. Conclusions: Romidepsin induced transcription from proviruses in peripheral blood cells, which contributed to viremia in patients on suppressive therapy. The intermingling of these cell-associated HIV-1 RNA with DNA sequences indicates transcription from a diverse range of proviruses, but the expansions of identical viral plasma sequences with few defects indicate that the romidepsin-induced viremia arises from intact proviruses with highly similar or identical genetic backgrounds. PMID:28272134
Full Text Available Michael L Scanlon,1,2 Rachel C Vreeman1,21Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; 2USAID, Academic Model Providing Access to Healthcare (AMPATH Partnership, Eldoret, KenyaAbstract: The rollout of antiretroviral therapy (ART significantly reduced human immunodeficiency virus (HIV-related morbidity and mortality, but good clinical outcomes depend on access and adherence to treatment. In resource-limited settings, where over 90% of the world’s HIV-infected population resides, data on barriers to treatment are emerging that contribute to low rates of uptake in HIV testing, linkage to and retention in HIV care systems, and suboptimal adherence rates to therapy. A review of the literature reveals limited evidence to inform strategies to improve access and adherence with the majority of studies from sub-Saharan Africa. Data from observational studies and randomized controlled trials support home-based, mobile and antenatal care HIV testing, task-shifting from doctor-based to nurse-based and lower level provider care, and adherence support through education, counseling and mobile phone messaging services. Strategies with more limited evidence include targeted HIV testing for couples and family members of ART patients, decentralization of HIV care, including through home- and community-based ART programs, and adherence promotion through peer health workers, treatment supporters, and directly observed therapy. There is little evidence for improving access and adherence among vulnerable groups such as women, children and adolescents, and other high-risk populations and for addressing major barriers. Overall, studies are few in number and suffer from methodological issues. Recommendations for further research include health information technology, social-level factors like HIV stigma, and new research directions in cost-effectiveness, operations, and implementation. Findings from this review make a
Mattia C F Prosperi
Full Text Available BACKGROUND: Although genotypic resistance testing (GRT is recommended to guide combination antiretroviral therapy (cART, funding and/or facilities to perform GRT may not be available in low to middle income countries. Since treatment history (TH impacts response to subsequent therapy, we investigated a set of statistical learning models to optimise cART in the absence of GRT information. METHODS AND FINDINGS: The EuResist database was used to extract 8-week and 24-week treatment change episodes (TCE with GRT and additional clinical, demographic and TH information. Random Forest (RF classification was used to predict 8- and 24-week success, defined as undetectable HIV-1 RNA, comparing nested models including (i GRT+TH and (ii TH without GRT, using multiple cross-validation and area under the receiver operating characteristic curve (AUC. Virological success was achieved in 68.2% and 68.0% of TCE at 8- and 24-weeks (n = 2,831 and 2,579, respectively. RF (i and (ii showed comparable performances, with an average (st.dev. AUC 0.77 (0.031 vs. 0.757 (0.035 at 8-weeks, 0.834 (0.027 vs. 0.821 (0.025 at 24-weeks. Sensitivity analyses, carried out on a data subset that included antiretroviral regimens commonly used in low to middle income countries, confirmed our findings. Training on subtype B and validation on non-B isolates resulted in a decline of performance for models (i and (ii. CONCLUSIONS: Treatment history-based RF prediction models are comparable to GRT-based for classification of virological outcome. These results may be relevant for therapy optimisation in areas where availability of GRT is limited. Further investigations are required in order to account for different demographics, subtypes and different therapy switching strategies.
Fox, Zoe V; Cozzi-Lepri, Alessandro; D'Arminio Monforte, Antonella;
Background: Guidelines suggest that patients on continuous antiretroviral therapy for >4 months with current viral load (VL)>1,000 copies/ml should be tested for resistance. There are limited data showing the frequency of resistance testing in routine clinical practice following these recommendat......Background: Guidelines suggest that patients on continuous antiretroviral therapy for >4 months with current viral load (VL)>1,000 copies/ml should be tested for resistance. There are limited data showing the frequency of resistance testing in routine clinical practice following...... 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...
Friis-Møller, Nina; Weber, Rainer; Reiss, Peter;
OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD...... to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs......, a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral...
Márcia Cristina Fraga Silva
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
Margaret Macherera, MSc
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
Mohr, David C.; Carmody, Timothy; Erickson, Lauren; Jin, Ling; Leader, Julie
Objective: Multiple trials have found telephone-administered cognitive behavioral therapy (T-CBT) to be effective for the treatment of depression. The aim of this study was to evaluate T-CBT for the treatment of depression among veterans served by community-based outpatient clinics (CBOCs) outside of major urban areas. Method: Eighty-five veterans…
Nguyen Thi Ngoc Lan
Full Text Available BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. METHODS: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066. Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. RESULTS: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 - 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had
Full Text Available Background: A high level of adherence is required to achieve the desired outcomes of antiretroviral therapy. There is paucity of information about adherence to combined antiretroviral therapy in Bayelsa State of southern Nigeria. Objectives: The objectives of the study were to determine the level of adherence to combined antiretroviral therapy among the patients, evaluate the improvement in their immune status and identify reasons for sub-optimal adherence to therapy. Methods: The cross-sectional study involved administration of an adapted and pretested questionnaire to 601 consented patients attending the two tertiary health institutions in Bayesla State, Nigeria: The Federal Medical Centre, Yenagoa and the Niger-Delta University Teaching Hospital Okolobiri. The tool was divided into various sections such as socio-demographic data, HIV knowledge and adherence to combined antiretroviral therapy. Information on the patient's CD4+ T cells count was retrieved from their medical records. Adherence was assessed by asking patients to recall their intake of prescribed doses in the last fourteen days and subjects who had 95-100% of the prescribed antiretroviral drugs were considered adherent. Results: Three hundred and forty eight (57.9% of the subjects were females and 253 (42.1% were males. The majority of them, 557 (92.7% have good knowledge of HIV and combined anti-retroviral therapy with a score of 70.0% and above. A larger proportion of the respondents, 441 (73.4%, had ≥95% adherence. Some of the most important reasons giving for missing doses include, “simply forgot” 147 (24.5%, and “wanted to avoid the side-effects of drugs” 33(5.5%. There were remarkable improvements in the immune status of the subjects with an increment in the proportion of the subjects with CD4+ T cells count of greater than 350 cells/mm3 from 33 (5.5% at therapy initiation to 338 (56.3% at study period (p<0.0001. Conclusion: The adherence level of 73.4% was low
Eichler, K; Bickel, T M; Klauke, S; Eisen, J; Vogl, T J; Zangos, S
We evaluated retrospectively an automated method for the separate detection of subcutaneous and visceral fat in the abdominal region by magnetic resonance studies in HIV-positive patients on highly active antiretroviral therapy. The patients were divided into four different groups: lipoatrophy, lipohypertrophy, mixed and the control group. The use of software for the automated detection of abdominal compartment visceral adipose tissue (VAT), total adipose tissue (TAT) and subcutaneous adipose tissue (SAT) was compared to manual evaluation methods (fuzzy C-mean). The results of ROC analysis showed that the parameters, particularly the VAT, are better than the VAT/TAT and at identifying patients with the symptoms of abdominal fat accumulation. A sensitivity of 80.3% and a specificity of 79.5% resulted from a threshold VAT value of >87 cm(2). Moreover, the manual evaluation method was shown to provide greater values for VAT and the VAT/TAT ratio than those given by the automated method. In the present study, a rapid MRI protocol for the detection and assessment of the course of lipodystrophy was presented and tested on a group of patients with signs of HALS, as well as on an antiretroviral naïve control group.
Kessler Harold A
Full Text Available Abstract The development and widespread clinical use of coformulated abacavir/lamivudine/zidovudine (ABC/3TC/ZDV as Trizivir represented an important advance in the management of HIV-infected patients, especially those with adherence challenges. With a low pill burden, no food restrictions, limited drug-drug interactions, and a favorable resistance profile, ABC/3TC/ZDV remains an alternative option in the US Department of Health and Human Services Consensus Panel Guidelines as initial treatment in antiretroviral-naive patients. Recent data have shown ABC/3TC/ZDV to be less efficacious in suppressing and/or maintaining suppression of virologic replication compared with efavirenz-containing antiretroviral therapy. Although triple-nucleoside/nucleotide reverse transcriptase inhibitor (t-NRTI combinations that do not contain a thymidine analog (ZDV or stavudine have recently shown high virologic failure rates in clinical trials and clinical practice, t-NRTI regimens containing a thymidine analog have consistently been shown to be efficacious.
Full Text Available Injection drug users (IDUs continue to comprise a major risk group for HIV infection throughout the world and represent the focal population for HIV epidemics in Asia and Eastern Europe/Russia. HIV prevention programs have ranged from HIV testing and counseling, education, behavioral and network interventions, drug abuse treatment, bleach disinfection of needles, needle exchange and expanded syringe access, as well as reducing transition to injection and primary substance abuse prevention. With the advent of highly active antiretroviral therapy (HAART in 1996, dramatic clinical improvements have been seen. In addition, the treatment's impact on reducing HIV viral load (and therefore transmission by all routes provides a stronger rationale for an expansion of the focus on prevention to emphasize early identification and treatment of HIV infected individuals. However, treatment of IDUs has many challenges including adherence, resistance and relapse to high risk behaviors, all of which impact issues of access and ultimately effectiveness of potent antiretroviral treatment. A major current challenge in addressing the HIV epidemic revolves around an appropriate approach to HIV treatment for IDUs.
Dhasmana, Devesh J; Dheda, Keertan; Ravn, Pernille;
The use of antiretroviral therapy (ART) to treat HIV infection, by restoring CD4+ cell count and immune function, is associated with significant reductions in morbidity and mortality. Soon after ART initiation, there is a rapid phase of restoration of pathogen-specific immunity. In certain patien...
Filteau, Suzanne; PrayGod, George; Kasonka, Lackson;
BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study was ...
Leeming, Diana J; Anadol, Evrim; Schierwagen, Robert
OBJECTIVES: Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade ...
Full Text Available Cryptococcosis is the most common cause of meningitis in Africa due to the high burden of HIV. Immune reconstitution inflammatory syndrome (IRIS is a frequent and deadly complication of cryptococcal meningitis. We report a fatal case of cryptococcal-IRIS in a pregnant woman that began after starting antiretroviral therapy (unmasking IRIS and markedly worsened postpartum after delivery (paradoxical IRIS.
Lyimo, R.A.; Boogaard, van den J.; Msoka, E.; Hospers, H.J.; Ven, van der A.A.; Mushi, D.; Bruin, de M.
An often-used tool to measure adherence to antiretroviral therapy (ART) is the Medication Event Monitoring System (MEMS), an electronic pill-cap that registers date and time of pill-bottle openings. Despite its strengths, MEMS-data can be compromised by inaccurate use and acceptability problems due
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 i
Hart, Anna B; Samuels, David C; Hulgan, Todd
Mitochondrial toxicity is implicated in some treatment-limiting antiretroviral therapy complications, and reports of mitochondrial dysfunction in untreated HIV infection suggest antiretroviral therapy independent effects of HIV. Several studies have explored associations between mtDNA haplogroups (patterns of mtDNA polymorphisms) and outcomes of HIV infection and/or antiretroviral therapy, but findings have been inconsistent. We systematically reviewed published studies examining mtDNA haplogroups in HIV-infected persons to summarize reported outcome associations, and to highlight potential future research directions. We identified 21 articles published from 2005-2013. Multiple different phenotypes were studied; most were antiretroviral therapy associated metabolic outcomes (e.g. lipodystrophy, insulin resistance, and dyslipidemia). Haplogroup H was associated with the most outcomes, including AIDS progression, CD4 T-cell recovery, cirrhosis (in hepatitis C coinfection), and metabolic outcomes. This review is the first to focus on the emerging area of mtDNA haplogroups in HIV, and summarizes the published literature on associations between mtDNA haplogroups and clinical outcomes in populations of European and African descent. Several reported associations require replication and ideally biological verification before definitive conclusions can be drawn, but research in this area has the potential to explain outcome disparities and impact clinical management of patients.
Despite treatment with combined antiretroviral therapy (cART), patients may experience viraemia at different levels and for varying periods of time, and CD4 count recovery, even in patients with sustained virus suppression, frequently remains suboptimal. We studied the characteristics of episodes of
Kirk, O; Pedersen, C; Cozzi-Lepri, A;
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 inc...
Mutwa, P.R.; Ilo van Nuil, J.; Asiimwe-Kateera, B.; Kestelyn, E.; Vyankandondera, J.; Pool, R.; Ruhirimbura, J.; Kanakuze, C.; Reiss, P.; Geleen, S.; van de Wijgert, J.; Boer, K.R.
Introduction Adherence to combination antiretroviral therapy (cART) is vital for HIV-infected adolescents for survival and quality of life. However, this age group faces many challenges to remain adherent. We used multiple data sources (role-play, focus group discussions (FGD), and in-depth intervie
Bech, A.; Bentum, P. van; Telting, D.; Gisolf, J.; Richter, C.; Boer, H. de
BACKGROUND: Hypophosphatemia and bone disease are common in HIV-positive (HIV+) patients on tenofovir disoproxil fumarate-containing antiretroviral therapy (TDF-containing ART). The underlying etiology is not completely understood. OBJECTIVE: To examine the effects of treatment of calcium and vitami
Haugaard, Steen B; Andersen, Ove; Pedersen, Steen B;
hyperlactatemia is associated with depletion of skeletal muscle (sm)-mtDNA and decreased oxidative capacity in HIV-infected patients on NRTI based highly active antiretroviral therapy (HAART) and whether HIV infection itself is associated with sm-mtDNA depletion. Sm-mtDNA was determined in 42 HIV...... in part could be mediated through an enhanced pro-inflammatory response....
Kristoffersen, U S; Kofoed, K; Kronborg, G;
OBJECTIVES: To investigate, using a longitudinal design, whether biomarkers of cardiovascular risk change after a switch to an abacavir (ABC)-containing regimen in HIV-1-infected individuals already receiving combination antiretroviral therapy (ART). METHODS: Thirty-five HIV-1-infected individuals...
Trickey, Adam; May, Margaret T; Vehreschild, Janne
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...
Lundgren, Jens Dilling; Mocroft, Amanda; Gatell, Jose M;
The risk of clinical progression for human immunodeficiency virus (HIV)-infected persons receiving treatment with highly active antiretroviral therapy (HAART) is poorly defined. From an inception cohort of 8457 HIV-infected persons, 2027 patients who started HAART during prospective follow-up wer...
Andersen, Ove; Eugen-Olsen, Jesper; Kofoed, Kristian;
Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV-infected...
Tramarin, A; Parise, N; Campostrini, S; Yin, DD; Postma, MJ; Lyu, R; Grisetti, R; Capetti, A; Cattelan, AM; Di Toro, MT; Mastroianni, A; Pignattari, E; Mondardini, [No Value; Calleri, G; Raise, E; Starace, F
Diarrhea is a common symptom that many HIV patients experience either as a consequence of HIV infection or of highly active antiretroviral therapy (HAART). A multicenter, prospective observational study was conducted in 11 AIDS clinics in Italy to determine the effect of diarrhea on health-related q
Mocroft, Amanda; Phillips, Andrew N; Ledergerber, Bruno;
BACKGROUND: Patients receiving combination antiretroviral therapy (cART) might continue treatment with a virologically failing regimen. We sought to identify annual change in CD4(+) T-cell count according to levels of viraemia in patients on cART. METHODS: A total of 111,371 CD4(+) T-cell counts ...
May, Margaret; Sterne, Jonathan A C; Shipley, Martin;
Many HIV-infected patients on highly active antiretroviral therapy (HAART) experience metabolic complications including dyslipidaemia and insulin resistance, which may increase their coronary heart disease (CHD) risk. We developed a prognostic model for CHD tailored to the changes in risk factors...
Meloni, Seema T.; Chang, Charlotte A.; Eisen, Geoffrey; Jolayemi, Toyin; Banigbe, Bolanle; Okonkwo, Prosper I.; Kanki, Phyllis J.
Background While there has been a rapid global scale-up of antiretroviral therapy programs over the past decade, there are limited data on long-term outcomes from large cohorts in resource-constrained settings. Our objective in this evaluation was to measure multiple outcomes during first-line antiretroviral therapy in a large treatment program in Nigeria. Methods We conducted a retrospective multi-site program evaluation of adult patients (age ≥15 years) initiating antiretroviral therapy between June 2004 and February 2012 in Nigeria. The baseline characteristics of patients were described and longitudinal analyses using primary endpoints of immunologic recovery, virologic rebound, treatment failure and long-term adherence patterns were conducted. Results Of 70,002 patients, 65.2% were female and median age was 35 (IQR: 29–41) years; 54.7% were started on a zidovudine-containing and 40% on a tenofovir-containing first-line regimen. Median CD4+ cell counts for the cohort started at 149 cells/mm3 (IQR: 78–220) and increased over duration of ART. Of the 70,002 patients, 1.8% were reported as having died, 30.1% were lost to follow-up, and 0.1% withdrew from treatment. Overall, of those patients retained and with viral load data, 85.4% achieved viral suppression, with 69.3% achieving suppression by month 6. Of 30,792 patients evaluated for virologic failure, 24.4% met criteria for failure and of 45,130 evaluated for immunologic failure, 34.0% met criteria for immunologic failure, with immunologic criteria poorly predicting virologic failure. In adjusted analyses, older age, ART regimen, lower CD4+ cell count, higher viral load, and inadequate adherence were all predictors of virologic failure. Predictors of immunologic failure differed slightly, with age no longer predictive, but female sex as protective; additionally, higher baseline CD4+ cell count was also predictive of failure. Evaluation of long-term adherence patterns revealed that the majority of patients
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
Full Text Available Franco Maggiolo,1 Giorgio L Colombo,2,3 Sergio Di Matteo,3 Giacomo M Bruno,3 Noemi Astuti,1 Elisa Di Filippo,1 Giulia Masini,1 Claudia Bernardini1 1Division of Infectious Diseases, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; 2University of Pavia, Department of Drug Sciences, Pavia, Italy; 3SAVE Studi Analisi Valutazioni Economiche, Milan, Italy Objectives: Costs may play a role in deciding how and when to start highly active antiretroviral therapy (HAART in a naïve patient. The aim of the present study was to assess the cost- effectiveness of treatment with HAART in a large clinical cohort of naïve adults to determine the potential role of single-tablet regimens in the management of patients with human immunodeficiency virus (HIV. An incremental cost-effectiveness ratio analysis was performed, including a quality-adjusted life year approach. Results: In total, 741 patients (females comprising 25.5% were retrospectively included. The mean age was 39 years, the mean CD4 cell count was 266 cells/µL, and the mean viral load was 192,821 copies/mL. The most commonly used backbone was tenofovir + emtricitabine (77.6%; zidovudine + lamivudine was used in 10%, lamivudine + abacavir in 3%, and other nucleoside reverse transcriptase inhibitor (NRTI or NRTI-free regimens in 9.4% of patients. NNRTIs were used in 52.8% of cases, boosted protease inhibitors in 44.1%, and unboosted protease inhibitors and integrase inhibitors in 0.7% and 2.4%, respectively. Starting therapy at CD4 >500 cells/µL and CD4 351–500 cells/µL rather than at <201 cells/µL was the more cost-effective approach. The same consideration was not true comparing current indications with the possibility to start HAART at any CD4 value (eg, >500 cells per µL; in this case, the incremental cost-effectiveness ratio value was €199,130 per quality-adjusted life year gained, a higher value than the one suggested in guidelines. The single-tablet regimen (STR invariably
Koneru, Rajeth; Olive, M Foster; Tyor, William R
The role of brain HIV load in the pathogenesis of HIV-associated neurocognitive disorders (HAND) is unclear. To try and determine if the amount of HIV drives the severity of pathology, a severe combined immunodeficient (SCID) mouse model of HIV encephalitis (HIVE) was utilized to determine the effectiveness of a systemically administered combined antiretroviral (cART) regimen. SCID mice were inoculated intracerebrally with HIV-infected or uninfected (control) human macrophages and treated subcutaneously with cART or saline for 10 days. Immunohistochemistry was then used to examine gliosis and neuronal damage. Drug levels were measured in brain and plasma using high-performance liquid chromatography. Peak plasma and brain levels of atazanavir, tenofovir, and emtricitabine were determined to be 1 h post-injection of cART therapy. cART significantly reduced neuropathological features of HIVE, including astrogliosis and the presence of mononuclear phagocytes, and ameliorated reduced MAP2 (neuronal integrity) staining. However, cART did not eradicate HIV from the brain. Using this animal model of HIVE, these data indicate effective penetration of cART reduces brain viral loads and HIV pathology, possibly by eliminating the production of HIV proteins, virus infected cells, or both. Importantly, these data suggest that viral load directly affects the extent of pathology seen in the brain, particularly neuronal damage, which implies that more effective suppression of HIV in the CNS could reduce currently highly prevalent forms of HAND. However, these data also strongly suggest that cART will not eliminate HIV from the brain and that adjunctive therapies must be developed.
Full Text Available Pharmacist’s interventions (also known as pharmaceutical care plans are means of solving the drug therapy problems identified in pharmaceutical care. Outcomes are the results of pharmacists’ intervention activities. Patients’ satisfaction refers to patients’ feeling of fulfillment, pleasure or happiness with the services they have received. This study was designed to determine the types of pharmacist interventions applied in the pharmaceutical care of HIV patients receiving treatment at a tertiary hospital in southeast Nigeria, the types of outcomes of such interventions and level of patients’ satisfaction with their drug therapy. The components of the American society of health-system pharmacists (ASHP guidelines on ‘standardized method for pharmaceutical care was used as a data collection instrument to evaluate, document and intervene in the antiretroviral therapy of about one thousand four hundred and seventy three (1,473 patients. The results showed significant reductions in the frequency of the various interventions and parameters measured after the interventions. The study concluded that pharmaceutical interventions influences patients’ adherence, optimizes their drug therapy and improves rational prescribing and care resulting in significant improvements in the outcomes of their treatment and levels of satisfaction.
Landauer, N; Goebel, F D
In addition to readily controllable short-term side effects, highly active antiretroviral therapy (HAART) also has long-term side effects: lipodystrophy syndrome, hyperlipoproteinemia, insulin resistance, elevated glucose tolerance sometimes leading to diabetes mellitus and lactic acidosis. The pathogenesis remains uncertain although various hypotheses have been advanced. A number of approaches for the treatment of lipodystrophy are available, the effects of which, however, have not been confirmed by study results. Hyperlipoproteinemia probably means an increased cardiovascular risk, but a final pronouncement on this is not yet possible. Fibrates and statins are currently applied for treatment, but interactions with HAART medicaments have to be considered. HAART-induced diabetes mellitus presents clinically as type 2 diabetes, and is treated accordingly.
Vivian Petersen Wagner
Full Text Available Plasmablastic lymphoma (PBL represents a rare type of non-Hodgkin lymphoma associated with human immunodeficiency virus (HIV infection. The impact of highly active antiretroviral therapy (HAART in this tumor is poorly known due to its small incidence. This study reports a case of a 33-year-old HIV-positive woman who was referred to the Stomatology Department complaining about a painful gingival growth and cervical nodule both with 20 days of evolution. The lesions appeared 7 months after the patient stopped HAART. The final diagnosis was PBL. After resuming HAART for 45 days, the gingival lesion presented complete remission. The patient continued with HAART alongside chemotherapy. At 24 months follow-up, the patient was stable. The dental surgeon plays an essential role in orientation and retention in care of HIV patients once the adherence of HAART seems to play an important role in PBL development and response to treatment.
Mansor, Samreen; Breiting, Vibeke Bro; Dahlstrøm, Karin
been used successfully in HIV patients abroad. This article describes the results of a Danish study. METHODS: Forty HIV patients recruited from two major referral hospitals in the capitol area of Copenhagen, Denmark, each received a series of PAAG gel injections (small deposits in several sessions......) with a 14-day interval. Patient satisfaction, injector's evaluation, evaluation by an external specialist in plastic surgery, and long-term aesthetic effect and complications were registered with follow-up until 2 years. RESULTS: All patients were very satisfied or satisfied with the result. The injector......BACKGROUND: Today, highly active antiretroviral therapy is lifesaving for most HIV-infected patients, but the treatment can result in facial lipoatrophy, which changes the face so radically that patients may develop severe psychological and social problems. Since 2001 polyacrylamide gel (PAAG) has...
Rouzier, Vanessa; Farmer, Paul E; Pape, Jean W; Jerome, Jean-Gregory; Van Onacker, Joelle Deas; Morose, Willy; Joseph, Patrice; Leandre, Fernet; Severe, Patrice; Barry, Donna; Deschamps, Marie-Marcelle; Koenig, Serena P
Haiti is the poorest country in the Western Hemisphere and has the highest number of people living with HIV in the Caribbean, the region most impacted by HIV outside of Africa. Despite continuous political, socioeconomic and natural catastrophes, Haiti has mounted a very successful response to the HIV epidemic. Prevention and treatment strategies implemented by the government in collaboration with non-governmental organizations have been instrumental in decreasing the national HIV prevalence from a high of 6.2% in 1993 to 2.2% in 2012. We describe the history and epidemiology of HIV in Haiti and the expansion of antiretroviral therapy (ART) over the past decade, with the achievement of universal access to ART for patients meeting the 2010 World Health Organization guidelines. We also describe effective models of care, successes and challenges of international funding, and current challenges in the provision of ART. We are optimistic that the goal of providing ART for all in need remains in reach.
Knudsen, Andreas; Christensen, Thomas E; Ghotbi, Adam Ali
Studies have found HIV-infected patients to be at increased risk of myocardial infarction, which may be caused by coronary microvascular dysfunction. For the first time among HIV-infected patients, we assessed the myocardial flow reserve (MFR) by Rubidium-82 (82Rb) positron emission tomography (PET......), which can quantify the coronary microvascular function. MFR has proved highly predictive of future coronary artery disease and cardiovascular events in the general population.In a prospective cross-sectional study, HIV-infected patients all receiving antiretroviral therapy (ART) with full viral...... suppression and HIV-uninfected controls were scanned using 82Rb PET/computed tomography at rest and adenosine-induced stress, thereby obtaining the MFR (stress flow/rest flow), stratified into low ≤1.5, borderline >1.5 to 2.0, or normal >2.0.Fifty-six HIV-infected patients and 25 controls were included...
Lebech, Anne-Mette; Kristoffersen, Ulrik Sloth; Mehlsen, Jesper;
BACKGROUND: The presence of autonomic dysfunction in HIV patients is largely unknown. Early studies found autonomic dysfunction in patients with AIDS. Introduction of highly active antiretroviral combination therapy (ART) has dramatically changed the course of the disease and improved prognosis...... and decreased morbidity. At present it is not known whether introduction of ART also has decreased autonomic dysfunction. AIM: To evaluate whether autonomic dysfunction is present in an ART-treated HIV population. METHODS: HIV patients receiving ART for at least 3 years (n = 16) and an age-matched control group...... guidelines and data reported as median (interquartile range). RESULTS: The resting heart rate was higher in HIV patients compared with controls [69 (62-74) versus 57 (52-60); PHIV group compared with the controls...
Lozupone, Catherine A; Rhodes, Matthew E; Neff, Charles P; Fontenot, Andrew P; Campbell, Thomas B; Palmer, Brent E
Consistent with an important role for adaptive immunity in modulating interactions between intestinal bacteria and host, dramatic alteration in the composition of gut microbes during chronic HIV infection was recently reported by ourselves and independently by four other research groups. Here we evaluate our results in the context of these other studies and delve into the effects of antiretroviral therapy (ART). Although gut microbiota of HIV-positive individuals on ART usually does not resemble that of HIV-negative individuals, the degree to which ART restores health-associated prevalence varies across bacterial taxa. Finally, we discuss potential drivers and health consequences of gut microbiota alterations. We propose that understanding the mechanism of HIV-associated gut microbiota changes will elucidate the role of adaptive immunity in shaping gut microbiota composition, and lay the foundation for therapeutics targeting the microbiota to attenuate HIV disease progression and reduce the risk of gut-linked disease in people with HIV.
Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum
This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.
Lebech, Anne-Mette; Wiinberg, Niels; Kristoffersen, Ulrik Sloth
INTRODUCTION: Increased cardiovascular risk in HIV patients in antiretroviral therapy (ART) may be due to HIV infection, direct effect of ART or dyslipidaemia induced by ART. Our aim was to study the relative importance of HIV, ART and dyslipidaemia on atherosclerosis, assessed by the comparison...... of carotid artery intima-media thickness (IMT) in non-smoking HIV patients with high or low serum cholesterol levels as well as in healthy volunteers. METHODS: HIV patients in ART with normal cholesterol (or=6 x 5 mmol l(-1); n=12) as well as healthy controls (n=14) were included. All were non...... on these observations, one could speculate whether selective lowering of LDL cholesterol will be successful in reducing cardiovascular risk in non-smoking HIV patients....
Stephen, Hobokela; Roberts, Bayard
Tanzania is host to one of the highest refugee populations in the world, with over half a million refugees in 2006. The purpose of this case study was to explore the application of the UNHCR ART policy for the provision of therapeutic, long-term antiretroviral therapy (ART) to refugees in Tanzania. A case study method was used and 18 semistructured key-informants interviews were conducted in July 2007 with a cross-section of stakeholders involved in provision of ART to refugees in Tanzania. The results suggest positive implementation of the key principles of the UNHCR policy. Some differing opinions existed between respondents over the key principles of considering ART provision at earliest possible stage of displacement, and the criteria for repatriation of refugees. The right of refugees to access ART is increasingly accepted and Tanzania provides a positive example of how ART services can be scaled up for refugees.
Campos, Lorenza Nogueira; Guimarães, Mark Drew Crosland; Remien, Robert H
Depression and anxiety are common among HIV-infected people and rank among the strongest predictors of non-adherence to antiretroviral therapy (ART). This longitudinal study aimed to assess whether symptoms of anxiety and depression are predictors of non-adherence among patients initiating ART at two public referral centers (n = 293) in Belo Horizonte, Brazil. Prevalence of severe anxiety and depression symptoms before starting ART was 12.6% and 5.8%, respectively. Severe anxiety was a predictor of non-adherence to ART during follow-up period (RH = 1.87; 95% CI = 1.14-3.06) adjusted for low education, unemployment, alcohol use in the last month and symptoms of AIDS; while a history of injection drug use had borderline statistical significance with non-adherence. These findings suggest that using a brief screening procedure to assess anxiety and depression symptoms before initiating ART help identify individuals for interventions to improve adherence and quality of life.
Wang, Charlene; Abdel-Mohsen, Mohamed; Strain, Matthew C; Lada, Steven M; Yukl, Steven; Cockerham, Leslie R; Pilcher, Christopher D; Hecht, Frederick M; Sinclair, Elizabeth; Liegler, Teri; Richman, Douglas D; Deeks, Steven G; Pillai, Satish K
Individuals who are heterozygous for the CCR5-Δ32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Δ32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P=.035), RNA to DNA transcriptional ratios (P=.013), and frequency of detectable HIV 2-long terminal repeat circular DNA (P=.013) were significantly lower in CD4+ T cells from CCR5-Δ32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4+ T cells (r2=0.136; P=.002). Our findings suggest that curative strategies should further explore manipulation of CCR5.
How might we understand and respond to the new forms of hunger that arise with the massive rollout of antiretroviral therapy (ART) for HIV in southern Africa? Rather than 'merely' a technical problem of measurement, medicine or infrastructure, I suggest that a philosophical question arises concerning the relationship between the experience of hunger, the utterances that communicate that experience, and the bodily regimes of well-being and ill-being indexed by such utterances. Taking the gut as a particular kind of mediator of experience, I draw on ethnographic fieldwork conducted in KwaZulu-Natal, South Africa to open up a set of questions on acknowledgment and avoidance. The central question concerns the divergent concepts of 'grammar' that confront the relationship between hunger and ART.
Kouéta, F; Yé, D; Zoungrana, A; Sacko, A; Ouédraogo-Traoré, R; Kafando, E; Ouédraogo, S
Approximately one-fourth of the estimated 10,000 HIV-infected children in Burkina Faso are undergoing antiretroviral (ARV) therapy. At the Charles de Gaulle Pediatric Hospital Center in Ouagadougou, Burkina Faso, Support for ARV therapy began in July 2003 and a total of 250 children were undergoing treatment in late 2007. The purpose of this retrospective case-control study conducted over a period of 54 months from July 2003 to December 2007 was to investigate cases involving failure of first-line ARV therapy in particular with regard to cause. All patients (n = 32) showing poor virological, immunological, and/or clinical response to ARV therapy were considered as failures and thus included in the case group. The control group (n = 160) consisted of patients with good responses to treatment. Cases and controls were compared using the Chi-square test and odds ratio (OR) technique with a confidence interval at 95%. The failure rate was 12.8%. Failure was significantly correlated with low socioeconomic level (OR = 3), orphan status (OR = 4), age over 10 years (OR = 5), male gender (OR = 3), baseline viral load > or = 1,000,000 copies/mL (OR = 9), and poor compliance (OR = 37). Mortality in children who failed to respond to first-line ARV therapy was 25% due to the unavailability of a national second-line ARV therapy program. This study underlines the need for patient education to promote compliance and for creation of reference centers to prescribe ARV therapy to HIV-infected children including second-line ARV and genotyping.
Claudia P Cortes
Full Text Available BACKGROUND: Antiretroviral therapy (ART decreases mortality risk in HIV-infected tuberculosis patients, but the effect of the duration of anti-tuberculosis therapy and timing of anti-tuberculosis therapy initiation in relation to ART initiation on mortality, is unclear. METHODS: We conducted a retrospective observational multi-center cohort study among HIV-infected persons concomitantly treated with Rifamycin-based anti-tuberculosis therapy and ART in Latin America. The study population included persons for whom 6 months of anti-tuberculosis therapy is recommended. RESULTS: Of 253 patients who met inclusion criteria, median CD4+ lymphocyte count at ART initiation was 64 cells/mm(3, 171 (68% received >180 days of anti-tuberculosis therapy, 168 (66% initiated anti-tuberculosis therapy before ART, and 43 (17% died. In a multivariate Cox proportional hazards model that adjusted for CD4+ lymphocytes and HIV-1 RNA, tuberculosis diagnosed after ART initiation was associated with an increased risk of death compared to tuberculosis diagnosis before ART initiation (HR 2.40; 95% CI 1.15, 5.02; P = 0.02. In a separate model among patients surviving >6 months after tuberculosis diagnosis, after adjusting for CD4+ lymphocytes, HIV-1 RNA, and timing of ART initiation relative to tuberculosis diagnosis, receipt of >6 months of anti-tuberculosis therapy was associated with a decreased risk of death (HR 0.23; 95% CI 0.08, 0.66; P=0.007. CONCLUSIONS: The increased risk of death among persons diagnosed with tuberculosis after ART initiation highlights the importance of screening for tuberculosis before ART initiation. The decreased risk of death among persons receiving > 6 months of anti-tuberculosis therapy suggests that current anti-tuberculosis treatment duration guidelines should be re-evaluated.
Despite treatment with combined antiretroviral therapy (cART), patients may experience viraemia at different levels and for varying periods of time, and CD4 count recovery, even in patients with sustained virus suppression, frequently remains suboptimal. We studied the characteristics of episodes of low- and high-level viraemia, including during cART interruption, and evaluated their immunologic, virologic and clinical impact in patients enrolled in the AIDS Therapy Evaluation in the Netherla...
Full Text Available Abstract Background Efforts to increase access to life-saving treatment, including antiretroviral therapy (ART, for people living with HIV/AIDS in resource-limited settings has been the growing focus of international efforts. One of the greatest challenges to scaling up will be the limited supply of adequately trained human resources for health, including doctors, nurses, pharmacists and other skilled providers. As national treatment programmes are planned, better estimates of human resource needs and improved approaches to assessing the impact of different staffing models are critically needed. However there have been few systematic assessments of staffing patterns in existing programmes or of the estimates being used in planning larger programmes. Methods We reviewed the published literature and selected plans and scaling-up proposals, interviewed experts and collected data on staffing patterns at existing treatment sites through a structured survey and site visits. Results We found a wide range of staffing patterns and patient-provider ratios in existing and planned treatment programmes. Many factors influenced health workforce needs, including task assignments, delivery models, other staff responsibilities and programme size. Overall, the number of health care workers required to provide ART to 1000 patients included 1–2 physicians, 2–7 nurses, Discussion These data are consistent with other estimates of human resource requirements for antiretroviral therapy, but highlight the considerable variability of current staffing models and the importance of a broad range of factors in determining personnel needs. Few outcome or cost data are currently available to assess the effectiveness and efficiency of different staffing models, and it will be important to develop improved methods for gathering this information as treatment programmes are scaled up.
Ana Celia Oliveira dos Santos
Full Text Available Introduction Even with current highly active antiretroviral therapy, individuals with AIDS continue to exhibit important nutritional deficits and reduced levels of albumin and hemoglobin, which may be directly related to their cluster of differentiation 4 (CD4 cell counts. The aim of this study was to characterize the nutritional status of individuals with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS and relate the findings to the albumin level, hemoglobin level and CD4 cell count. Methods Patients over 20 years of age with AIDS who were hospitalized in a university hospital and were receiving antiretroviral therapy were studied with regard to clinical, anthropometric, biochemical and sociodemographic characteristics. Body mass index, percentage of weight loss, arm circumference, triceps skinfold and arm muscle circumference were analyzed. Data on albumin, hemoglobin, hematocrit and CD4 cell count were obtained from patient charts. Statistical analysis was performed using Fisher's exact test, Student's t-test for independent variables and the Mann-Whitney U-test. The level of significance was set to 0.05 (α = 5%. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS 17.0 software for Windows. Results Of the 50 patients evaluated, 70% were male. The prevalence of malnutrition was higher when the definition was based on arm circumference and triceps skinfold measurement. The concentrations of all biochemical variables were significantly lower among patients with a body mass index of less than 18.5kg/m2. The CD4 cell count, albumin, hemoglobin and hematocrit anthropometric measures were directly related to each other. Conclusions These findings underscore the importance of nutritional follow-up for underweight patients with AIDS, as nutritional status proved to be related to important biochemical alterations.
Full Text Available Abstract Background Successful treatment of HIV-positive children requires a high level of adherence (at least 95% to highly active antiretroviral therapy. Adherence is influenced by factors related to the child and caregivers. Objectives To evaluate children and caregivers characteristics associated to children's adherence. Methods Cross-sectional study, from September 2013 to June 2015, comprising a sample of caregivers of perinatally HIV-infected children, in the age group of 1–12 years, under antiretroviral therapy for at least 6 months and on follow-up in two AIDS reference centers in Salvador, Bahia. Caregiver self-reports were the sole source of 4 days adherence and sociodemographic information. Study participants who reported an intake >95% of prescribed medication were considered adherents. A variable, (“Composed Adherence”, was created to better evaluate adherence. Results We included 77 children and their caregivers. 88.3% of the caregivers were female, the median age was 38.0 years (IQR 33.5–47.5, 48.1% were white or mixed, 72.7% lived in Salvador and 53.2% had no fixed income. The 4 days child's adherence was associated only to caregivers that received less than a minimum salary (p < 0.05, 70.1% of the caregivers had less than four years of formal education, 81.8% were children's relative and 53.2% of the caregivers were HIV positive. The caregiver's pharmacy refill, long-term adherence and 4 days adherence, were significantly associated with composed adherence (p < 0.05. Child's long-term adherence was strongly associated to the 4 days child's adherence referred by caregiver (p < 0.001. Conclusions Our results suggest the need of improvement in HIV-infected children adherence, through reinforcement of the caregivers own adherence.
Full Text Available The objective of the present study was to evaluate the duodenal mucosa of HIV-infected patients during antiretroviral therapy. This was an observational study conducted on HIV-positive patients and a control group. Group 1 comprised 22 HIV-negative individuals while 38 HIV-positive individuals were classified according to the CDC 1993 classification into group 2 (A1 or A2 or group 3 (B2, A3, B3, C2, C3. All subjects were submitted to upper gastrointestinal endoscopy with duodenal biopsies. Qualitative, semi-quantitative and quantitative histological analyses were performed. Results were considered significant when P < 0.05. A higher prevalence of inflammatory infiltrate and eosinophilia was observed in the HIV group, together with a reduction in mucosal CD4+ lymphocyte (L counts [median (lower-upper quartiles, 12.82 (8.30-20.33, 6.36 (1.75-11.66 and 1.75 (0.87-3.14 in groups 1, 2 and 3, respectively] which was not correlated with disease stage. The extent of CD4+L count reduction was similar in blood and duodenal mucosa. Normal CD8+L and CD45RO+L counts, and normal numbers of macrophages and antigen-presenting cells were also found in the HIV patients. The cytokine pattern did not differ among groups. Tissue HIV, assessed by p24 antigen, correlated with a higher CD45RO+L count (77.0 (61-79.8 and 43.6 (31.7-62.8 in p24+ and p24-, respectively, P = 0.003, and IL-4 positivity (100 and 48.2% in p24+ and p24-, respectively, P = 0.005. The duodenal mucosa of HIV+ patients showed a relatively preserved histological architecture. This finding may be characteristic of a population without opportunistic infections and treated with potent antiretroviral therapy, with a better preservation of the immune status.
Full Text Available Katie Yoganathan1, David Brown2, Kathir Yoganathan31Cardiff Medical School, Cardiff, Wales, UK; 2Virus Reference Department, Microbiology Services, Health Protection Agency, London, UK; 3Singleton Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UKAbstract: A 43-year-old Caucasian homosexual man with AIDS presented with blurring of vision, change of personality, and memory loss in March 1999. He had first been admitted 2 months previously for treatment of Pneumocystis jiroveci pneumonia. A magnetic resonance imaging scan on admission showed multiple white matter lesions involving both subcortical cerebral hemispheres and cerebellar regions, with no mass effect or surrounding edema. JC virus was detected by nested polymerase chain reaction in the cerebrospinal fluid. These findings were diagnostic of progressive multifocal leukoencephalopathy (PML. His CD4 count was 34 cells/mL, and his HIV ribonucleic acid level was 800,789 copies/mL. He was treated with a combination antiretroviral therapy. He was last reviewed in October 2011. He was fully independent socially and mentally, but he still had some residual neurologic signs with right-sided homonymous hemianopia and visual agnosia. His HIV ribonucleic acid level was undetectable, and his CD4 count was 574 cells/mm3. Although the median survival of patients with PML was poor before the antiretroviral therapy era, our patient, who is now aged 55 years, is still alive 12 years after the diagnosis. The diagnosis of PML and differential diagnosis of focal neurologic signs in HIV-positive patients are discussed in this case report.Keywords: HIV, focal neurologic signs, cerebral toxoplasmosis, primary brain lymphoma, ischaemic stroke
Full Text Available Introduction: These guidelines are part of the French Experts’ recommendations for the management of people living with HIV/AIDS, which were made public and submitted to the French health authorities in September 2013. The objective was to provide updated recommendations for antiretroviral treatment (ART of HIV-positive adults. Guidelines included the following topics: when to start, what to start, specific situations for the choice of the first session of antiretroviral therapy, optimization of antiretroviral therapy after virologic suppression, and management of virologic failure. Methods: Ten members of the French HIV 2013 expert group were responsible for guidelines on ART. They systematically reviewed the most recent literature. The chairman of the subgroup was responsible for drafting the guidelines, which were subsequently discussed within, and finalized by the whole expert group to obtain a consensus. Recommendations were graded for strength and level of evidence using predefined criteria. Economic considerations were part of the decision-making process for selecting preferred first-line options. Potential conflicts of interest were actively managed throughout the whole process. Results: ART should be initiated in any HIV-positive person, whatever his/her CD4 T-cell count, even when >500/mm3. The level of evidence of the individual benefit of ART in terms of mortality or progression to AIDS increases with decreasing CD4 cell count. Preferred initial regimens include two nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine plus a non-nucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine, or a ritonavir-boosted protease inhibitor (atazanavir or darunavir. Raltegravir, lopinavir/r, and nevirapine are recommended as alternative third agents, with specific indications and restrictions. Specific situations such as HIV infection in women, primary HIV infection, severe immune suppression
Full Text Available BACKGROUND: By the end of 2011 Global Fund investments will be supporting 3.5 million people on antiretroviral therapy (ART in 104 low- and middle-income countries. We estimated the cost and health impact of continuing treatment for these patients through 2020. METHODS AND FINDINGS: Survival on first-line and second-line ART regimens is estimated based on annual retention rates reported by national AIDS programs. Costs per patient-year were calculated from country-reported ARV procurement prices, and expenditures on laboratory tests, health care utilization and end-of-life care from in-depth costing studies. Of the 3.5 million ART patients in 2011, 2.3 million will still need treatment in 2020. The annual cost of maintaining ART falls from $1.9 billion in 2011 to $1.7 billion in 2020, as a result of a declining number of surviving patients partially offset by increasing costs as more patients migrate to second-line therapy. The Global Fund is expected to continue being a major contributor to meeting this financial need, alongside other international funders and domestic resources. Costs would be $150 million less in 2020 with an annual 5% decline in first-line ARV prices and $150-370 million less with a 5%-12% annual decline in second-line prices, but $200 million higher in 2020 with phase out of stavudine (d4T, or $200 million higher with increased migration to second-line regimens expected if all countries routinely adopted viral load monitoring. Deaths postponed by ART correspond to 830,000 life-years saved in 2011, increasing to around 2.3 million life-years every year between 2015 and 2020. CONCLUSIONS: Annual patient-level direct costs of supporting a patient cohort remain fairly stable over 2011-2020, if current antiretroviral prices and delivery costs are maintained. Second-line antiretroviral prices are a major cost driver, underscoring the importance of investing in treatment quality to improve retention on first-line regimens.
Krentz, Hartmut B; Gill, M John
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.
Brites, Carlos; Nóbrega, Isabella; Martins Netto, Eduardo
Antiretroviral therapy has significantly evolved in the last decade, with an increasing number of new drugs and classes. Currently, even heavily experienced patients can be successfully treated with new regimens. In Brazil, the recent incorporation of some new antiretroviral drugs made it possible to suppress HIV plasma viremia in most treated patients, with significant benefits in terms of quality of life and survival. However, little has been published on outcomes of patients under new drugs-based regimens. We reviewed the safety and efficacy of antiretroviral regimens using recently introduced drugs in Bahia. Our results confirm that patients using darunavir, raltegravir, enfuvirtide, or etravirine presented with a high rate of virological suppression without significant adverse events, after one year of follow-up.
Carlos Diógenes Pinheiro Neto
Full Text Available A associação dos inibidores de protease (IP à terapia anti-retroviral provocou mudanças importantes na morbidade e mortalidade de pacientes infectados pelo HIV. OBJETIVOS: Avaliar o impacto desta associação na prevalência de rinossinusite (RS e na contagem sérica de linfócitos CD4 em crianças infectadas pelo HIV. CASUÍSTICA E MÉTODOS: A forma de estudo foi cross-sectional com 471 crianças infectadas pelo HIV. Em 1996, inibidores de protease foram liberados para terapia anti-retroviral. Desta forma, dois grupos de crianças foram formados: as que não fizeram uso de IP e as que fizeram uso desta droga após 1996. A prevalência de RS e a contagem sérica de linfócitos CD4 foram comparadas entre estes grupos. RESULTADOS: 14,4% das crianças infectadas pelo HIV apresentaram RS. A RS crônica foi mais prevalente que a RS aguda em ambos os grupos. Crianças menores de 6 anos tratadas com a associação de IP apresentaram maior prevalência de RS aguda. A associação de IP esteve associada à maior contagem de linfócitos CD4 séricos com menor prevalência de RS crônica. CONCLUSÕES: A terapia com IP esteve associada ao aumento na contagem de linfócitos CD4. Crianças abaixo dos 6 anos em uso de IP apresentaram menor tendência à cronificação da doença.The association of protease inhibitors (PI to antiretroviral therapy has generated sensible changes in morbidity and mortality of HIV-infected patients. AIM: Aims at evaluating the impact of this association on the prevalence of rhinosinusitis (RS and CD4+ lymphocyte count in HIV-infected children. METHODS: Retrospective cross-sectional study of the medical charts of 471 HIV-infected children. In 1996, protease inhibitors were approved for use as an association drug in antiretroviral therapy. Children were divided into two groups: one which did not receive PI and another which received PI after 1996. The prevalence of RS and CD4+ lymphocyte counts were compared between these groups
Eaton, J.W.; Menzies, N.A.; Stover, J.; Cambiano, V.; Chindelevitch, L.; Cori, A.; Hontelez, J.A.; Humair, S.; Kerr, C.C.; Klein, D.J.; Mishra, S.; Mitchell, K.M.; Nichols, B.E.; Vickerman, P.; Bakker, R; Barnighausen, T.; Bershteyn, A.; Bloom, D.E.; Boily, M.C.; Chang, S.T.; Cohen, T.; Dodd, P.J.; Fraser, C.; Gopalappa, C.; Lundgren, J.; Martin, N.K.; Mikkelsen, E.; Mountain, E.; Pham, Q.D.; Pickles, M.; Phillips, A.; Platt, L.; Pretorius, C.; Prudden, H.J.; Salomon, J.A.; Vijver, D.A. van de; Vlas, S.J. de; Wagner, B.G.; White, R.G.; Wilson, D.P.; Zhang, L.; Blandford, J.; Meyer-Rath, G.; Remme, M.; Revill, P.; Sangrujee, N.; Terris-Prestholt, F.; Doherty, M.; Shaffer, N.; Easterbrook, P.J.; Hirnschall, G.; Hallett, T.B.
BACKGROUND: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per muL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral ther
Winston, A; Stöhr, W; Antinori, A;
OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence...... Nationale de Recherche sur le SIDA (ANRS) 143 study. METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean...... and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models. RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile...
Full Text Available THIS ARTICLE WAS RETRACTED AFTER A PLAGIARISM INVESTIGATIONObjective: To assess the incidence, severity pattern, causality, predictability and preventability of adverse drug reactions (ADRs and to identify risk factors for adverse drug reactions in highly active antiretroviral therapy.Methods: Enrolled patients were intensively monitored for ADRs to highly active antiretroviral therapy. Predictability was assessed based on history of previous exposure to the drug or literature incidence of ADRs. Preventability was assessed using Schumock and Thornton criteria and severity was assessed using modified Hartwig and Siegel scale. Multivariate logistic regressions were used to identify the risk factors for ADRs.Results: Monitoring of 130 retropositive patients by active pharmacovigilance identified 74 ADRs from 57 patients. Anemia and hepatotoxicity were the most commonly observed ADRs. The organ system commonly affected by ADR was red blood cell (21.4%.The ADRs were moderate in 77% of cases. Type A reactions (77% were more common. A total of 10.8% ADRs were definitely preventable. The incidence rate of ADRs (65.9% was highest with Zidovudine + Lamivudine + Nevirapine combination. A total of 84% interruptions to highly active antiretroviral therapy were due to toxicity. CD4 less than 200 cells/µl, female gender and tuberculosis were observed as risk factors for ADRs.Conclusion: Incidence of ADRs in intensively monitored patients was found to be 43.8%. Anemia in HIV patients is an influential risk factor for occurrence of ADRs. With the increasing access to antiretroviral in India, clinicians must focus on early detection and prevention of ADRs to highly active antiretroviral therapy.
Lindhardt, Bjarne Ø.; Kronborg, Gitte; Hansen, Ann-Brit E.;
BACKGROUND: Coinfection with hepatitis C virus (HCV) in human immunodeficiency virus (HIV) type 1-infected patients may decrease the effectiveness of highly active antiretroviral therapy. We determined the impact of HCV infection on response to highly active antiretroviral therapy and outcome among...... Danish patients with HIV-1 infection. METHODS: This prospective cohort study included all adult Danish HIV-1-infected patients who started highly active antiretroviral therapy from 1 January 1995 to 1 January 2004. Patients were classified as HCV positive (positive HCV serological test and/or HCV PCR...... results [443 patients [16%
Weis, Nina Margrethe; Lindhardt, Bjarne Ø.; Kronborg, Gitte;
BACKGROUND: Coinfection with hepatitis C virus (HCV) in human immunodeficiency virus (HIV) type 1-infected patients may decrease the effectiveness of highly active antiretroviral therapy. We determined the impact of HCV infection on response to highly active antiretroviral therapy and outcome among...... Danish patients with HIV-1 infection. METHODS: This prospective cohort study included all adult Danish HIV-1-infected patients who started highly active antiretroviral therapy from 1 January 1995 to 1 January 2004. Patients were classified as HCV positive (positive HCV serological test and/or HCV PCR...... results [443 patients [16%
Shin, Sonya; Muñoz, Maribel; Zeladita, Jhon; Slavin, Sam; Caldas, Adolfo; Sanchez, Eduardo; Callacna, Miriam; Rojas, Christian; Arevalo, Jorge; Sebastian, Jose Luis; Bayona, Jaime
From December 2005 through August 2008, we provided community-based accompaniment with supervised antiretroviral therapy (CASA) to impoverished individuals starting highly active antiretroviral therapy. Adherence support was provided for 18 months by a community-based team comprised of several nurses and two types of community health workers: field supervisors and directly observed therapy (DOT) volunteers. To complement our quantitative data collection in 2008 using purposive sampling, we conducted two gender-mixed focus group discussions with 13 CASA patient participants and 13 DOT volunteers from Lima, Peru to identify the mediating mechanisms by which CASA improved well-being, and to understand the benefits of the intervention, as perceived by these individuals. Using standard qualitative methods for the review and analysis of transcripts and interview notes, we identified central themes and developed a coding scheme for categorising participants' statements. Two individuals blinded to each other's coding, coded interview transcripts for theme and content from which a third reviewer compared their coding to arbitrate discrepancies. Additional domains were added if necessary and all domains were integrated into a theoretical scheme. Among the forms of support delivered by the CASA team, DOT volunteers reported emotional support, instrumental support, directly observed therapy, building trust, education, advocacy, exercise of moral authority and preparation for transition off CASA support. CASA participants described outcomes of improved adherence, ability to resume social roles, increased self-efficacy, hopefulness, changes in non-HIV-related behaviour, reduced internalised and externalised stigma, as well as ability to disclose. Both sets of focus group participants highlighted remaining challenges after completion of CASA support: stigma in the community, difficulties achieving economic recovery and persistent barriers to health services. Based on our prior
Wakibi Samwel N
Full Text Available Abstract Background Antiretroviral therapy (ART requires high-level (> 95% adherence. Kenya is rolling out ART access programmes and, issue of adherence to therapy is therefore imperative. However, published data on adherence to ART in Kenya is limited. This study assessed adherence to ART and identified factors responsible for non adherence in Nairobi. Methods This is a multiple facility-based cross-sectional study, where 416 patients aged over 18 years were systematically selected and interviewed using a structured questionnaire about their experience taking ART. Additional data was extracted from hospital records. Patients were grouped into adherent and non-adherent based on a composite score derived from a three questions adherence tool developed by Center for Adherence Support Evaluation (CASE. Multivariate regression model was used to determine predictors of non-adherence. Results Overall, 403 patients responded; 35% males and 65% females, 18% were non-adherent, and main (38% reason for missing therapy were being busy and forgetting. Accessing ART in a clinic within walking distance from home (OR = 2.387, CI.95 = 1.155-4.931; p = 0.019 and difficulty with dosing schedule (OR = 2.310, CI.95 = 1.211-4.408, p = 0.011 predicted non-adherence. Conclusions The study found better adherence to HAART in Nairobi compared to previous studies in Kenya. However, this can be improved further by employing fitting strategies to improve patients' ability to fit therapy in own lifestyle and cue-dose training to impact forgetfulness. Further work to determine why patients accessing therapy from ARV clinics within walking distance from their residence did not adhere is recommended.
Török, M. Estee; Yen, Nguyen Thi Bich; Chau, Tran Thi Hong; Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Mai, Pham Phuong; Dung, Nguyen Thi; Van Vinh Chau, Nguyen; Bang, Nguyen Duc; Tien, Nguyen Anh; Minh, N. H.; Hien, Nguyen Quang; Thai, Phan Vuong Khac; Dong, Doan The; Anh, Do Thi Tuong; Thoa, Nguyen Thi Cam; Hai, Nguyen Ngoc; Lan, Nguyen Ngoc; Lan, Nguyen Thi Ngoc; Quy, Hoang Thi; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Simmons, Cameron Paul; de Jong, Menno; Wolbers, Marcel; Farrar, Jeremy James
Background The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–associated tuberculous meningitis is unknown. Methods We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses. Results A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81–1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87–1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration ISRCTN63659091. PMID:21596680
Larson, Erica C.; Hathaway, Laura B.; Lamb, John G.; Pond, Chris D.; Rai, Prem P.; Matainaho, Teatulohi K.; Piskaut, Pius; Barrows, Louis R.; Franklin, Michael R.
Ethnopharmacological relevance A substantial proportion of the population in Papua New Guinea (PNG) lives with human immunodeficiency virus (HIV). Treatment requires lifelong use of antiretroviral therapy (ART). The majority of people in PNG use traditional medicines (TM) derived from plants for all types of health promotions. Consequently, there is a concern that herb-drug interactions may impact the efficacy of ART. Herb-drug, or drug-drug, interactions occur at the level of metabolism through two major mechanisms: enzyme induction or enzyme inhibition. In this study, extracts of commonly-used medicinal plants from PNG were screened for herb-drug interactions related to cytochrome P450s (CYPs). Materials and Methods Sixty nine methanol extracts of TM plants were screened for their ability to induce CYPs by human aryl hydrocarbon receptor- (hAhR-) and human pregnane X receptor- (hPXR-) dependent mechanisms, utilizing a commercially available cell-based luciferase reporter system. Inhibition of three major CYPs, CYP1A2, CYP3A4, and CYP2D6, was determined using human liver microsomes and enzyme-selective model substrates. Results Almost one third of the TM plant extracts induced the hAhR-dependent expression of CYP1A2, the hPXR-dependent expression of CYP3A4, or both. Almost two thirds inhibited CYP1A2, CYP3A4, or CYP2D6, or combinations thereof. Many plant extracts exhibited both induction and inhibition properties. Conclusions We demonstrated that the potent and selective ability of extracts from PNG medicinal plants to affect drug metabolizing enzymes through induction and/or inhibition is a common phenomenon. Use of traditional medicines concomitantly with ART could dramatically alter the concentrations of antiretroviral drugs in the body; and their efficacy. PNG healthcare providers should counsel HIV patients because of this consequence. PMID:25138353
Full Text Available As antiretroviral therapy (ART for HIV becomes increasingly available in low and middle income countries (LMICs, understanding reasons for lack of adherence is critical to stemming the tide of infections and improving health. Understanding the effect of psychosocial experiences and mental health symptomatology on ART adherence can help maximize the benefit of expanded ART programs by indicating types of services, which could be offered in combination with HIV care.The Coping with HIV/AIDS in Tanzania (CHAT study is a longitudinal cohort study in the Kilimanjaro Region that included randomly selected HIV-infected (HIV+ participants from two local hospital-based HIV clinics and four free-standing voluntary HIV counselling and testing sites. Baseline data were collected in 2008 and 2009; this paper used data from 36 month follow-up interviews (N = 468. Regression analyses were used to predict factors associated with incomplete self-reported adherence to ART.Incomplete art adherence was significantly more likely to be reported amongst participants who experienced a greater number of childhood traumatic events: sexual abuse prior to puberty and the death in childhood of an immediate family member not from suicide or homicide were significantly more likely in the non-adherent group and other negative childhood events trended toward being more likely. Those with incomplete adherence had higher depressive symptom severity and post-traumatic stress disorder (PTSD. In multivariable analyses, childhood trauma, depression, and financial sacrifice remained associated with incomplete adherence.This is the first study to examine the effect of childhood trauma, depression and PTSD on HIV medication adherence in a low income country facing a significant burden of HIV. Allocating spending on HIV/AIDS toward integrating mental health services with HIV care is essential to the creation of systems that enhance medication adherence and maximize the potential of
Jeannette Y. Lee
Full Text Available The objective of this study was to explore the cancer incidence rates among HIV-infected persons with commercial insurance who were on antiretroviral therapy and compare them with those rates in the general population. Paid health insurance claims for 63,221 individuals 18 years or older, with at least one claim with a diagnostic code for HIV and at least one filled prescription for an antiretroviral medication between January 1, 2006, and September 30, 2012, were obtained from the LifeLink® Health Plan Claims Database. The expected number of cancer cases in the general population for each gender-age group (60 years was estimated using incidence rates from the Surveillance Epidemiology and End Results (SEER program. Standardized incidence ratios (SIRs were estimated using their 95% confidence intervals (CIs. Compared to the general population, incidence rates for HIV-infected adults were elevated (SIR, 95% CI for Kaposi sarcoma (46.08; 38.74–48.94, non-Hodgkin lymphoma (4.22; 3.63–4.45, Hodgkin lymphoma (9.83; 7.45–10.84, and anal cancer (30.54; 25.62–32.46 and lower for colorectal cancer (0.69; 0.52–0.76, lung cancer (0.70; 0.54, 0.77, and prostate cancer (0.54; 0.45–0.58. Commercially insured, treated HIV-infected adults had elevated rates for infection-related cancers, but not for common non-AIDS defining cancers.
Ferretti, Francesca; Gianotti, Nicola; Lazzarin, Adriano; Cinque, Paola
Less-drug regimens (LDR) refer to combinations of either two antiretroviral drugs or ritonavir-boosted protease inhibitor (PI) monotherapy. They may represent a simplification strategy in patients with persistently suppressed human immunodeficiency virus (HIV) viremia, with the main benefits of reducing drug-related toxicities and costs. Systemic virological efficacy of LDR is slightly lower as compared with combined antiretroviral therapy (cART), but patients with failure do not usually develop drug resistance and resuppress HIV replication after reintensification. A major concern of LDR is the lower efficacy in the virus reservoirs, especially in the central nervous system (CNS), where viral compartmentalization and independent evolution of infection may lead to CNS viral escape, often associated with neurologic symptoms. The authors reviewed studies of virological and functional CNS efficacy of LDR, particularly of boosted PI monotherapy regimens, for which more information is available. Symptomatic viral CSF escape was observed mainly in PI/r monotherapy patients with plasma failure and low nadir CD4+ cell counts, and resolved upon reintroduction of triple drug cART, whereas asymptomatic viral failure in CSF was not significantly more frequent in patients on PI/r monotherapy compared with patients on standard cART. In addition, there was no difference in functional outcomes between PI monotherapy and cART patients, irrespective of CSF viral escape. More data are needed on the CNS effect of dual ART regimens and, in general, on long-term efficacy of LDR. Simplification with LDR may be an attractive option in patients with suppressed viral load, if they are well selected and monitored for potential CNS complications.
Zhao, Yan; Sun, Xin; He, Yun; Tang, Zhirong; Peng, Guoping; Liu, Aiwen; Qiao, Xiaochun; Li, Huiqin; Chen, Zhiqiang; Dou, Zhihui; Ma, Ye; Liu, Zhongfu; Zhang, Fujie
In 2003, the Chinese Government initiated a free antiretroviral therapy (ART) program focusing on adult AIDS patients. Pediatric antiretroviral (ARV) formulations were yet unavailable. It was not until July 2005, with the initiation of a two-stage program implemented by the Chinese Ministry of Health, that pediatric formulations became accessible in China. Initially, the pediatric ART program was piloted in six provinces with the highest incidences of pediatric HIV/AIDS. The pilot stage allowed the Chinese Center for Disease Control and Prevention (CCDC) to finalize entry criteria, treatment regimen, and patient monitoring and follow-up procedures. The second stage commenced at the end of 2006 when the program was scaled-up nationally. In order to guarantee treatment of pediatric patients, extensive training in the selection of appropriate ARV drug regimen and dosage was provided to doctors, often through on-site collaboration with domestic and international experts. The CCDC simultaneously established a pediatric ARV management system and a pediatric ART information system. CD4 count and other laboratory tests are being routinely performed on these pediatric patients. By the end of June 2009, 1529 pediatric patients had received ARV under the national program. However, challenges remain. Firstly, many children infected with HIV/AIDS live in rural areas where the treatment quality is hindered by the limited number of medical facilities and skilled medical workers. Secondly, much of the pediatric ARV drug supply depends on donation. An effort needs to be made by the Chinese Government to establish China's own drug procurement and supply system.
van der Merwe Karin
Full Text Available Abstract Background Use of highly active antiretroviral therapy (HAART, a triple-drug combination, in HIV-infected pregnant women markedly reduces mother to child transmission of HIV and decreases maternal morbidity. However, there remains uncertainty about the effects of in utero exposure to HAART on foetal development. Methods Our objectives were to investigate whether in utero exposure to HAART is associated with low birth weight and/or preterm birth in a population of South African women with advanced HIV disease. A retrospective observational study was performed on women with CD4 counts ≤250 cells/mm3 attending antenatal antiretroviral clinics in Johannesburg between October 2004 and March 2007. Low birth weight ( Results Among HAART-unexposed infants, 27% (60/224 were low birth weight compared with 23% (90/388 of early HAART-exposed (exposed 3 increase, 95% CI 0.45-0.71, p 3 increase, 95% CI 0.55-0.85, p = 0.001. HAART exposure was associated with an increased preterm birth rate (15%, or 138 of 946, versus 5%, or seven of 147, in unexposed infants, p = 0.001, with early nevirapine and efavirenz-based regimens having the strongest associations with preterm birth (AOR 5.4, 95% CI 2.1-13.7, p Conclusions In this immunocompromised cohort, in utero HAART exposure was not associated with low birth weight. An association between NNRTI-based HAART and preterm birth was detected, but residual confounding is plausible. More advanced immunosuppression was a risk factor for low birth weight and preterm birth, highlighting the importance of earlier HAART initiation in women to optimize maternal health and improve infant outcomes.
Claudia Daniele Tavares Dutra
Full Text Available A terapia anti-retroviral altamente ativa, usada contra o Vírus da Imunodeficiência Humana, vem possibilitando a melhora do quadro clínico-laboratorial de portadores da Síndrome da Imunodeficiência Adquirida. Contudo, alterações metabólicas e complicações morfológicas, associadas ao uso da terapia, vêm sendo investigadas. A utilização prolongada desta terapia tem um impacto importante sobre o estado nutricional dos pacientes. Antes da sua utilização, a perda de peso e a desnutrição, conseqüências das infecções oportunistas, eram os maiores problemas nutricionais. Atualmente, o foco principal das discussões têm sido as complicações metabólicas e morfológicas, dentre elas a lipodistrofia, com a dislipidemia, a resistência à insulina, a osteopenia, e a distribuição alterada da gordura corporal, aumentando assim os riscos de doenças cardiovasculares. A nutrição desempenha um papel fundamental no suporte da saúde desses pacientes, integrando as equipes multiprofissionais, promovendo a melhora da adesão à terapia anti-retroviral e do prognóstico da doença. No entanto, para que se tenha mais conhecimento sobre a terapia, as proporções de seus efeitos adversos, e o perfil nutricional desses pacientes, a curto e a longo prazos, é de suma importância que se estude mais sobre este assunto, a fim de permitir perspectivas de um regime terapêutico mais seguro dentro de seus alcances metodológicos, proporcionando uma melhor qualidade de vida aos pacientes.The highly active antiretroviral therapy used against Human Immunodeficiency Virus provides an improvement in laboratory and clinical findings of patients with Acquired Immunodeficiency Syndrome. However, metabolic and morphologic disturbances associated with the therapy are being investigated. The drawn out use of these therapy has an important impact on the nutritional status of the patients. Before the use of this therapy, weight loss and malnutrition caused by
Full Text Available Abstract Background In many preclinical AIDS research studies, antiretroviral therapy (ART is administered to experimentally simian immunodeficiency (SIV-infected rhesus macaques for reduction of viral load to undetectable levels. Prolonged treatment of macaques with a high dose of PMPA (9-[2-(r-(phosphonomethoxy propyl] adenine or tenofovir; 30 mg/kg of body weight subcutaneously once daily can result in proximal renal tubular dysfunction, a Fanconi-like syndrome characterized by glucosuria, aminoaciduria, hypophosphatemia, and bone pathology. In contrast, chronic administration of a low dose of PMPA (10 mg/kg subcutaneously once daily starting at birth does not seem to be associated with any adverse health effects within 3 years of treatment. In contrast to PMPA, limited information on systemic toxicity in rhesus monkeys is available for FTC (5-fluoro-1-(2R,5S-[2-(hydroxymethyl-1,3-oxathiolan-5-yl]cytosine; emtricitabine and stavudine (d4T. Results In this study, the clinical and biochemical correlates of tubular nephrosis in SIV-infected rhesus macaques associated with systemic administration of high-dose ART consisting of the three nucleoside analog inhibitors PMPA, FTC, and d4T were investigated. It was found that acute renal failure was uncommon (7.1% of treated animals and that morphologic evidence of nephropathy, which persisted for more than 300 days following discontinuation of the drug cocktail, was more frequent (52.4% of treated animals. While parameters from single time points lacked predictive value, biochemical alterations in Blood Urea Nitrogen (BUN and phosphorus were frequently identified longitudinally in the blood of ART-treated animals that developed evidence of nephropathy, and these longitudinal changes correlated with disease severity. Conclusions Recommendations are proposed to limit the impact of drug-induced renal disease in future SIV macaque studies.
Julian H Elliott
Full Text Available Human immunodeficiency virus (HIV persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART. The primary endpoint was change in cell associated unspliced (CA-US HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065. Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90% with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1. CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells.ClinicalTrials.gov NCT01365065.
Full Text Available Abstract Background Rhodococcus equi (R.equi is an acid fast, GRAM + coccobacillus, which is widespread in the soil and causes pulmonary and extrapulmonary infections in immunocompromised people. In the context of HIV infection, R.equi infection (rhodococcosis is regarded as an opportunistic disease, and its outcome is influenced by highly active antiretroviral therapy (HAART. Case presentation We report two cases of HIV-related rhodococcosis that disseminated despite suppressive HAART and anti-rhodococcal treatment; in both cases there was no immunological recovery, with CD4+ cells count below 200/μL. In the first case, pulmonary rhodococcosis presented 6 months after initiation of HAART, and was followed by an extracerebral intracranial and a cerebral rhodococcal abscess 1 and 8 months, respectively, after onset of pulmonary infection. The second case was characterized by a protracted course with spread of infection to various organs, including subcutaneous tissue, skin, colon and other intra-abdominal tissues, and central nervous system; the spread started 4 years after clinical resolution of a first pulmonary manifestation and progressed over a period of 2 years. Conclusions Our report highlights the importance of an effective immune recovery, despite fully suppressive HAART, along with anti-rhodococcal therapy, in order to clear rhodococcal infection.
Full Text Available BACKGROUND: In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR and their ligands class I human leukocyte antigen (HLA, could influence immunological response to cART. METHODS: KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4(+ T-cell count 350/mm(3. Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics. RESULTS: The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005. The functional compound genotype HLA-C1(+/KIR2DL3(+, even at multivariable analysis, when adjusted for nadir CD4(+ T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals 0.34 (0.13-0.88, P = 0.03. CONCLUSIONS: Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy.
Full Text Available A problem of highly active antiretroviral therapy (HAART in HIV patients is their adherence to treatment. The aim of this study was to compare the schemes adopted in the initial therapy of these treatments with their adherence, changes in HAART schemes and treatment costs. The study included patients over 16 years old, HIV positive, in treatment for more than 30 days. Adherence to HAART was calculated based on the withdrawal of the drug, which was related to the total treatment time. We evaluated how many patients changed HAART. The costs of each regimen were also estimated and related to the benefit of each treatment. 142 patients who were between 38 and 1,150 days of treatment were included (57.7% women. The schemes with lower costs, highest adherence and greater benefit were efavirenz with biovir and efavirenz with lamivudine and tenofovir. This study suggested the advantageous therapeutic regimens to start of treatment, both from the point of view of patients and the health system. This information can serve as a subsidy to clinicians in the decision of starting HAART.
Butler, Scott L; Valdez, Hernan; Westby, Michael; Perros, Manos; June, Carl H; Jacobson, Jeffrey M; Levy, Yves; Cooper, David A; Douek, Daniel; Lederman, Michael M; Tebas, Pablo
Chronic HIV infection is associated with persistent immune activation and inflammation even among patients virologically suppressed on antiretroviral therapy for years. Chronic immune activation has been associated with poor outcomes--both AIDS-defining and non-AIDS-defining clinical events--and persistent CD4 T-cell depletion. The cause of chronic immune activation in well-controlled HIV infection is unknown. Proposed drivers include residual viral replication, microbial translocation, and coinfecting pathogens. Therapeutic interventions targeting immune activation are emerging, from approaches that interfere directly with activation and inflammatory pathways to those that prevent microbial translocation or decrease the availability of host target cells for the virus. In the context of the disappointing results of the interleukin-2 trials, the main challenges to developing these disease-modifying therapies include identifying an adequate target population and choosing surrogate endpoints that will provide positive proof-of-concept that the interventions will translate into long-term clinical benefit before embarking on large clinical endpoint trials.
Rehman, Andrea M; Woodd, Susannah; PrayGod, George;
BACKGROUND:: The evidence base for effects of nutritional interventions for malnourished HIV-infected patients starting antiretroviral therapy (ART) is limited and inconclusive. OBJECTIVE:: We hypothesised that both vitamin and mineral deficiencies and poor appetite limit weight gain in malnouris...
Magidson, Jessica F; Saal, Wylene; Nel, Adriaan; Remmert, Jocelyn E; Kagee, Ashraf
Despite the prevalence of depression and alcohol use among HIV-infected individuals, few studies have examined their association together in relation to nonadherence to antiretroviral therapy in sub-Saharan Africa. This study examined depressive symptoms, alcohol use, and other psychosocial factors (stigma, demographic characteristics) in relation to nonadherence to antiretroviral therapy among clinic-attending, HIV-infected individuals in South Africa (n = 101). Nonadherence was assessed using event-level measurement (missed doses over the past weekend). Multivariable logistic regression analyses revealed that only alcohol use, over and above depressive symptoms and education level, was associated with antiretroviral therapy nonadherence(AOR = 1.15; 95%CI = 1.02-1.29; p < .05). Findings point to the independent association of alcohol use and nonadherence to antiretroviral therapy above and beyond depressive symptoms.
Lavoie, Monica; Routhier, Sonia; Légaré, Annie; Macoir, Joël
Aphasia is a chronic condition that usually requires long-term rehabilitation. However, even if many effective treatments can be offered to patients and families, speech therapy services for individuals with aphasia often remain limited because of logistical and financial considerations, especially more than 6 months after stroke. Therefore, the need to develop tools to maximize rehabilitation potential is unquestionable. The aim of this study was to test the efficacy of a self-administered treatment delivered with a smart tablet to improve written verb naming skills in CP, a 63-year-old woman with chronic aphasia. An ABA multiple baseline design was used to compare CP's performance in verb naming on three equivalent lists of stimuli trained with a hierarchy of cues, trained with no cues, and not trained. Results suggest that graphemic cueing therapy, done four times a week for 3 weeks, led to better written verb naming compared to baseline and to the untrained list. Moreover, generalization of the effects of treatment was observed in verb production, assessed with a noun-to-verb production task. Results of this study suggest that self-administered training with a smart tablet is effective in improving naming skills in chronic aphasia. Future studies are needed to confirm the effectiveness of new technologies in self-administered treatment of acquired language deficits.
Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.......Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load....
Feller, L; Khammissa, R A G; Wood, N H; Malema, V; Meyerov, R; Lemmer, J
Focal epithelial hyperplasia is increasingly frequently observed in rural South African communities. HIV-seropositive subjects have a higher prevalence of oral human papillomavirus (HPV) infections than immunocompetent subjects; and paradoxically, the introduction of highly active antiretroviral therapy for treatment of HIV-seropositive subjects is associated with increased frequency of focal epithelial hyperplasia. We describe a case of focal epithelial hyperplasia in an HIV-seropositive child receiving highly active antiretroviral therapy, who was successfully treated by using diode laser ablation.
PrayGod, George; Blevins, M; Woodd, Susannah;
Antiretroviral therapy (NUSTART) trial in Tanzania and Zambia from 2011 to 2013. SUBJECTS/METHODS: HIV-infected, ART-eligible adults with body mass index (BMI) of ...BACKGROUND/OBJECTIVES: The effects of inflammation on nutritional rehabilitation after starting antiretroviral therapy (ART) are not well understood. We assessed the relationship between inflammation and body composition among patients enrolled in the Nutritional Support for African Adults Starting...
CCL3L1- CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1- infected individuals. Nat Med 2008, 14:413...Riley ED, Bangsberg DR: Food insecurity is associated with incomplete HIV RNA suppression among homeless and marginally housed HIV- infected ...increases in HIV- infected adults experiencing 4 years of viral suppression on antiretroviral therapy. Aids 2003, 17:1907-1915. 48. Kaufmann GR, Furrer
Holly E Rawizza
Full Text Available BACKGROUND: To date, antiretroviral therapy (ART guidelines and programs in resource-limited settings (RLS have focused on 1(st- and 2(nd-line (2 L therapy. As programs approach a decade of implementation, policy regarding access to 3(rd-line (3 L ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR mutations. METHODS AND FINDINGS: From 2004-2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI-based ART, 673 (10.0% met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for 24 months. Patients developed a median of 0.6 (IQR: 0-1.4 IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir. CONCLUSIONS: This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access.
González, Ramón E. R.; de Figueirêdo, Pedro Hugo; Coutinho, Sérgio
We study a cellular automata model to test the timing of antiretroviral therapy strategies for the dynamics of infection with human immunodeficiency virus (HIV). We focus on the role of virus diffusion when its population is included in previous cellular automata model that describes the dynamics of the lymphocytes cells population during infection. This inclusion allows us to consider the spread of infection by the virus-cell interaction, beyond that which occurs by cell-cell contagion. The results show an acceleration of the infectious process in the absence of treatment, but show better efficiency in reducing the risk of the onset of AIDS when combined antiretroviral therapies are used even with drugs of low effectiveness. Comparison of results with clinical data supports the conclusions of this study.
Dore, Gregory J; Soriano, Vicente; Rockstroh, Jürgen
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.......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....
Friis-Møller, Nina; Weber, Rainer; Reiss, Peter;
to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs...... of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated total cholesterol level. CONCLUSION: HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially......OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD...
Full Text Available Carolina Dagli-Hernandez,1 Rosa Camila Lucchetta,1 Tales Rubens de Nadai,2 José Carlos Fernandez Galduróz,3 Patricia de Carvalho Mastroianni1 1Department of Drugs and Medications, School of Pharmaceutical Sciences of the UNESP – Univ Estadual Paulista, Araraquara, 2Department of Surgery and Anatomy, Americo Brasiliense State Hospital, 3Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP, São Paulo, Brazil Objectives: To evaluate which indirect method for assessing adherence best reflects highly active antiretroviral therapy (HAART effectiveness and the factors related to adherence. Method: 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. Results: 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. Conclusion: A new parameter of patient self-perception of adherence, which is a noninvasive, inexpensive instrument, could be applied and assessed as easily as self
Christopher J Miller
Full Text Available BACKGROUND: Non-AIDS conditions such as cardiovascular disease and non-AIDS defining cancers dominate causes of morbidity and mortality among persons with HIV on suppressive combination antiretroviral therapy. Accurate estimates of disease incidence and of risk factors for these conditions are important in planning preventative efforts. METHODS: With use of medical records, serious non-AIDS events, AIDS events, and causes of death were adjudicated using pre-specified criteria by an Endpoint Review Committee in two large international trials. Rates of serious non-AIDS which include cardiovascular disease, end-stage renal disease, decompensated liver disease, and non-AIDS cancer, and other serious (grade 4 adverse events were determined, overall and by age, over a median follow-up of 4.3 years for 3,570 participants with CD4+ cell count ≥300 cells/mm³ who were taking antiretroviral therapy and had an HIV RNA level ≤500 copies/mL. Cox models were used to examine the effect of age and other baseline factors on risk of a composite outcome of all-cause mortality, AIDS, or serious non-AIDS. RESULTS: Five-year Kaplan-Meier estimates of the composite outcome, overall and by age were 8.3% (overall, 3.6% (<40, 8.7% (40-49 and 16.1% (≥50, respectively (p<0.001. In addition to age, smoking and higher levels of interleukin-6 and D-dimer were significant predictors of the composite outcome. The composite outcome was dominated by serious non-AIDS events (overall 65% of 277 participants with a composite event. Most serious non-AIDS events were due to cardiovascular disease and non-AIDS cancers. CONCLUSIONS: To date, few large studies have carefully collected data on serious non-AIDS outcomes. Thus, reliable estimates of event rates are scarce. Data cited here, from a geographically diverse cohort, will be useful for planning studies of interventions aimed at reducing rates of serious non-AIDS events among people with HIV.
Tatiana Paschoalette Rodrigues Bachur
Full Text Available Enteroparasites are related to gastrointestinal alterations among patients with HIV/AIDS, some causing severe manifestations in the period before the institution of the highly active antiretroviral therapy (HAART. The prevalence of enteroparasitoses in patients with HIV/AIDS seen at two hospitals in Ceará , Brazil, was compared in the pre-HAART (Group 1; n = 482 and HAART (Group 2; n = 100 eras. Fecal parasitologic examinations (FPE were performed using the direct, Lutz, Baermann-Moraes and modified Ziehl-Neelsen methods. The following parasites were detected in Groups 1 and 2, respectively: Strongyloides stercoralis - 30.1% and 11% (p<0.0001, Ascaris lumbricoides - 15.6% and 2% (p<0.0001, hookworms - 13.7% and 2% (p<0.0001, Trichuris trichiura - 13.1% and 1% (p<0.0001, Hymenolepis nana - 0 and 1% (p = 0.1718, Giardia duodenalis - 7.9% and 1% (p = 0.0076, Entamoeba histolytica/dispar - 3.3% and 1% (p = 0.3301, Isospora belli - 4.8% and 1% (p = 0.0993, Cryptosporidium sp. - 8.1% and 0 (p = 0.0007, and non-pathogenic protozoans as well. There was a significant reduction in the prevalence of enteroparasites between the eras (63.9% to 24%; p<0.0001. In the HAART era, the following observations were made: greater frequency of enteroparasites in patients without antiretroviral therapy (p = 0.0575, as in those with AIDS (p = 0.08, and diarrhea (36% of the patients; lack of association with positive FPE (p = 0.626; and non-detection of Cryptosporidium sp. Strongyloides stercoralis showed an elevated prevalence in the two eras and was more frequent in men (32.41% than women (19.04% of Group 1 (p = 0.018, a finding suggesting the transmission of the helminth through sodomy. The advent of the HAART modified the profile of opportunistic infections, including parasites, probably due to the reconstitution of cellular immunity and the direct action of HAART on the parasites.
Full Text Available Daniel NA Ankrah,1,2 Ellen S Koster,2 Aukje K Mantel-Teeuwisse,2 Daniel K Arhinful,3 Irene A Agyepong,4 Margaret Lartey5,6 1Pharmacy Department, Korle-Bu Teaching Hospital, Accra, Ghana; 2Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS, Utrecht, the Netherlands; 3Noguchi Memorial Institute for Medical Research, University of Ghana (Legon, 4Health Policy, Planning and Management, University of Ghana School of Public Health, 5Department of Medicine, University of Ghana Medical School, 6Department of Medicine and Therapeutics, Korle-Bu Teaching Hospital, Accra, Ghana Introduction: Adherence to antiretroviral therapy (ART is known to be challenging among adolescents living with HIV/AIDS, notwithstanding the life-saving importance of this therapy. Of the global total number of adolescents living with HIV in 2013, 83% reside in sub-Saharan Africa. The study aimed to identify facilitators of and barriers to antiretroviral treatment adherence among adolescents in Ghana. Methods: A cross-sectional qualitative study using semi-structured interviews for data collection was carried out among adolescents (aged 12–19 years at the adolescents HIV clinic at the Korle-Bu Teaching Hospital in Ghana. Predominantly open-ended questions relating to ART were used. Interviews were done until saturation. In total, 19 interviews were conducted. Analysis was done manually to maintain proximity with the text. Findings: The main facilitators were support from health care providers, parental support, patient’s knowledge of disease and self-motivation, patient’s perceived positive outcomes, and dispensed formulation. The identified barriers were patient’s forgetfulness to take medicines, perceived stigmatization due to disclosure, financial barriers, and adverse effects of ART. Support from health care workers was the most frequently mentioned facilitator, and patient’s forgetfulness and perceived
Patro, Sean C; Azzoni, Livio; Joseph, Jocelin; Fair, Matthew G; Sierra-Madero, Juan G; Rassool, Mohammed S; Sanne, Ian; Montaner, Luis J
Reversal of monocyte and macrophage activation and the relationship to viral suppression and T cell activation are unknown in patients with advanced HIV-1 infection, initiating antiretroviral therapy. This study aimed to determine whether reduction in biomarkers of monocyte and macrophage activation would be reduced in conjunction with viral suppression and resolution of T cell activation. Furthermore, we hypothesized that the addition of CCR5 antagonism (by maraviroc) would mediate greater reduction of monocyte/macrophage activation markers than suppressive antiretroviral therapy alone. In the CCR5 antagonism to decrease the incidence of immune reconstitution inflammatory syndrome study, antiretroviral therapy-naïve patients received maraviroc or placebo in addition to standard antiretroviral therapy. PBMCs and plasma from 65 patients were assessed during 24 wk of antiretroviral therapy for biomarkers of monocyte and macrophage activation. Markers of monocyte and macrophage activation were reduced significantly by 24 wk, including CD14(++)CD16(+) intermediate monocytes (P CCR5-positive monocytes in PBMC. HIV-1 suppression after 24 wk of antiretroviral therapy, with or without maraviroc, demonstrates robust recovery in monocyte subset activation markers, whereas soluble markers of activation demonstrate minimal decrease, qualitatively differentiating markers of monocyte/macrophage activation in advanced disease.
Kalanda, Boniface; Makwiza, Ireen; Kemp, Julia
Universal provision of antiretroviral therapy (ART), while feasible, is expensive. In light of this limitation, the World Health Organisation (WHO) has launched the 3 × 5 initiative, to provide ART to 3 million people by the end of the year 2005. In Southern Africa, large-scale provision of ART will likely be achieved through fragile public health systems. ART programmes should therefore be developed and expanded in ways that will not aggravate inequities or result in the inappropriate withdr...
Devendra, A; Makawa, A; Kazembe, PN; Calles, NR; Kuper, H. (Harm)
BACKGROUND: As paediatric antiretroviral therapy (ART) is rapidly scaled up in Southern Africa, Human Immunodeficiency Virus (HIV) infection is becoming a chronic illness. Children growing up with HIV may begin to encounter disabilities. The relationship between HIV, disability and the need for rehabilitation has added an additional element that needs to be addressed by paediatric HIV treatment programmes. STUDY OBJECTIVES: 1) Estimate the prevalence of disabilities in HIV-infected and HIV-un...
Mayer, Kenneth H.; McMahon, James H.; Jordan, Michael R.; Kelley, Karen; Bertagnolio, Silvia; Hong, Steven Y.; Wanke, Christine A.; Sharon R Lewin; Elliott, Julian H.
Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medica...
Wondifraw Baynes H; Tegene B; Gebremichael M; Birhane G; Kedir W; Biadgo B
Habtamu Wondifraw Baynes,1 Birhanemeskel Tegene,2 Mikiyas Gebremichael,3 Gebrehawaria Birhane,3 Wabe Kedir,3 Belete Biadgo1 1Department of Clinical Chemistry, 2Department of Medical Microbiology, 3Department of Medical Laboratory Science, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia Background: The emergence of highly active antiretroviral therapy (HAART) has dramatically improved quality of life in prolonging su...
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
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
Rönsholt, Frederikke F; Ullum, Henrik; Katzenstein, Terese L;
The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART).......The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART)....
Sheri D Weiser
Full Text Available BACKGROUND: Food insecurity is emerging as an important barrier to antiretroviral (ARV adherence in sub-Saharan Africa and elsewhere, but little is known about the mechanisms through which food insecurity leads to ARV non-adherence and treatment interruptions. METHODOLOGY: We conducted in-depth, open-ended interviews with 47 individuals (30 women, 17 men living with HIV/AIDS recruited from AIDS treatment programs in Mbarara and Kampala, Uganda to understand how food insecurity interferes with ARV therapy regimens. Interviews were transcribed, coded for key themes, and analyzed using grounded theory. FINDINGS: Food insecurity was common and an important barrier to accessing medical care and ARV adherence. Five mechanisms emerged for how food insecurity can contribute to ARV non-adherence and treatment interruptions or to postponing ARV initiation: 1 ARVs increased appetite and led to intolerable hunger in the absence of food; 2 Side effects of ARVs were exacerbated in the absence of food; 3 Participants believed they should skip doses or not start on ARVs at all if they could not afford the added nutritional burden; 4 Competing demands between costs of food and medical expenses led people either to default from treatment, or to give up food and wages to get medications; 5 While working for food for long days in the fields, participants sometimes forgot medication doses. Despite these obstacles, many participants still reported high ARV adherence and exceptional motivation to continue therapy. CONCLUSIONS: While reports from sub-Saharan Africa show excellent adherence to ARVs, concerns remain that these successes are not sustainable in the presence of widespread poverty and food insecurity. We provide further evidence on how food insecurity can compromise sustained ARV therapy in a resource-limited setting. Addressing food insecurity as part of emerging ARV treatment programs is critical for their long-term success.
Lewis, J M; Stott, K E; Monnery, D; Seden, K; Beeching, N J; Chaponda, M; Khoo, S; Beadsworth, M B J
Drug-drug interactions between antiretroviral therapy and other drugs are well described. Gastric acid-reducing agents are one such class. However, few data exist regarding the frequency of and indications for prescription, nor risk assessment in the setting of an HIV cohort receiving antiretroviral therapy. To assess prevalence of prescription of gastric acid-reducing agents and drug-drug interaction within a UK HIV cohort, we reviewed patient records for the whole cohort, assessing demographic data, frequency and reason for prescription of gastric acid-reducing therapy. Furthermore, we noted potential drug-drug interaction and whether risk had been documented and mitigated. Of 701 patients on antiretroviral therapy, 67 (9.6%) were prescribed gastric acid-reducing therapy. Of these, the majority (59/67 [88.1%]) were prescribed proton pump inhibitors. We identified four potential drug-drug interactions, which were appropriately managed by temporally separating the administration of gastric acid-reducing agent and antiretroviral therapy, and all four of these patients remained virally suppressed. Gastric acid-reducing therapy, in particular proton pump inhibitor therapy, appears common in patients prescribed antiretroviral therapy. Whilst there remains a paucity of published data, our findings are comparable to those in other European cohorts. Pharmacovigilance of drug-drug interactions in HIV-positive patients is vital. Education of patients and staff, and accurate data-gathering tools, will enhance patient safety.
Okome-Nkoumou, Madeleine; Guiyedi, Vincent; Ondounda, Magloire; Efire, Nora; Clevenbergh, Philippe; Dibo, Mireille; Dzeing-Ella, Arnaud
Opportunistic diseases cause substantial morbidity and mortality to human immunodeficiency virus (HIV)-infected patients. Highly active antiretroviral therapy (HAART) leading to immune reconstitution is the most effective treatment of preventing opportunistic diseases. This retrospective study established an epidemiologic profile of opportunistic diseases 10 years after the introduction of HAART. The HIV antiretroviral therapy-naive patients matching inclusion criteria were included. The primary outcome was the prevalence of opportunistic diseases. From January 1, 2002 to September 30, 2010, 654 opportunistic diseases were identified in 458 patients. Pulmonary tuberculosis, herpes zoster, cerebral toxoplasmosis, oral candidiasis, and severe pneumonia accounted for 22.05%, 15.94%, 14.19%, 14.19%, and 9.39%, respectively. Cryptococcal meningitis and pneumocystosis accounted for 0.44% and 0.21%, respectively. The prevalence of opportunistic diseases in Gabon remains high. New guidelines emphasize the importance of initiating antiretroviral therapy early to reconstitute the immune system, and reduce disease risk, and treat the primary opportunistic infection of pulmonary tuberculosis.
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.
Clarke, Amanda; Kerr, Stephen; Honeybrook, Adam; Cooper, David A; Avihingsanon, Anchalee; Duncombe, Chris; Phanuphak, Praphan; Ruxrungtham, Kiat; Ananworanich, Jintanat; Kaldor, John
It could be postulated that due to lifestyle factors, patients with poor antiretroviral therapy (ART) adherence may also have risky sexual behaviour potentially leading to HIV transmission. There are limited data regarding unprotected sex risk and ART adherence in resource limited settings and our study set out to investigate these in an HIV clinic in Bangkok. Patients completed an anonymous questionnaire regarding their relationship details, ART adherence, sexual behaviour, alcohol and drug use and HIV transmission beliefs. Laboratory findings and medical history were also collected. Unprotected sex risk (USR) was defined as inconsistent condom use with a partner of negative or unknown HIV status. Five hundred and twelve patients completed the questionnaire. Fifty seven per cent of patients reported having taken ARV >95% of the time in the last month and 58% had been sexually active in the previous 30 days. Only 27 patients (5%) were classified as having USR in our cohort. Multivariate analysis showed USR was associated with female gender (OR 2.9, 95% CI 1.2-7.0, p0.02) but not with adherence, age, type or number of partners, recreational drug or alcohol use nor beliefs about HIV transmission whilst taking ART. Levels of USR in this resource limited setting were reassuringly low and not associated with poor ART adherence; as all USR patients had undetectable viral loads onward HIV transmission risk is likely to be low but not negligible. Nonetheless condom negotiation techniques, particularly in women, may be useful in this group.
Full Text Available It is unclear whether antiretroviral therapy (ART should be initiated during acute HIV infection. Most recent data provides evidence of benefits of early ART.We retrospectively compared the clinical and immunological course of individuals with acute HIV infection, who received ART within 3 months (group A or not (group B after diagnosis.Among the 84 individuals with acute HIV infection, 57 (68% received ART within 3 months (A whereas 27 (32% did not receive ART within 3 months (B, respectively. Clinical progression to CDC stadium B or C within 5 years after the diagnosis of HIV was less common in (A when compared to (B (P = 0.002. After twelve months, both the mean increase in CD4+ T cell count and the mean decrease in viral load was more pronounced in (A, when compared to (B (225 vs. 87 cells/μl; P = 0.002 and -4.19 vs. -1.14 log10 copies/mL; P<0.001. Twenty-four months after diagnosis the mean increase from baseline of CD4+ T cells was still higher in group A compared to group B (251 vs. 67 cells/μl, P = 0.004.Initiation of ART during acute HIV infection is associated with a lower probability of clinical progression to more advanced CDC stages and significant immunological benefits.
Houston, Eric; McKirnan, David J; Cervone, Daniel; Johnson, Matthew S; Sandfort, Theo G M
Using multidimensional scaling (MDS) analysis, this study examined how patient conceptualisations of treatment motivation compare with theoretically based assumptions used in current assessment approaches. Patients undergoing antiretroviral therapy for HIV/AIDS (n=39) rated for similarity between all possible pairings of 23 treatment descriptions, including descriptors of intrinsic, extrinsic, approach and avoidance motivation. MDS analyses revealed that patient perceptions of intrinsic and extrinsic motivations often differ from those based on definitions derived from common interpretations of self-determination theory. Findings also showed that patients reported motivation for avoiding treatment when they associated their medication regimens with side effects and other negatively valenced outcomes. The study describes new applications of MDS in assessing how patients perceive the relationship between treatment behaviours and specific forms of motivation, such as intrinsic and extrinsic motivations. In addition, the study suggests how MDS may be used to develop behavioural strategies aimed at helping patients follow their regimens consistently by identifying treatment conceptualisations and contexts that facilitate or impede adherence.
Dauchy, Frédéric-Antoine; Lawson-Ayayi, Sylvie; de La Faille, Renaud; Bonnet, Fabrice; Rigothier, Claire; Mehsen, Nadia; Miremont-Salamé, Ghada; Cazanave, Charles; Greib, Carine; Dabis, Francois; Dupon, Michel
Abnormal kidney function is common in the course of human immunodeficiency virus (HIV) infection. Here, we performed a cross-sectional analysis using 399 patients within the Aquitaine cohort (a hospital-based cohort of HIV-1-infected patients receiving routine clinical management) to estimate the prevalence of proximal renal tubular dysfunction (PRTD) associated with HIV infection. These patients did not differ statistically by sociodemographics, median age, years since HIV diagnosis, AIDS stage, or median CD4 cell count from the entire 3080 patient cohort. Antiretroviral therapy was received by 352 patients, with 256 given tenofovir (TDF); 325 had undetectable HIV plasma viral load, and 26 were diagnosed with PRTD. In multivariate analysis, significant independent associations were found between PRTD and age (odds ratio (OR) 1.28 per 5-year increase), atazanavir (OR 1.28 per year of exposure), and TDF (OR 1.23 per year) treatment. Among patients having received TDF-containing regimens over a 5-year period, PRTD remained significantly associated with TDF exposure when treatment was ongoing (OR 5.22) or had been discontinued (OR 11.49). Thus, cumulative exposure to TDF and/or atazanavir was associated with an increased risk of PRTD, with concern about its reversibility in patients with HIV.
Talita Gabriela de Limas
Full Text Available Introduction Antiretroviral therapy (ART has been used to treat large numbers of patients living with human immunodeficiency virus (HIV infection. Lipid disorders are often observed in these patients, and include elevations in total cholesterol (TC and triglycerides (TG. Methods A cross-sectional study was performed using 333 patient records from the Regional Hospital of São José Doutor Homero de Miranda Gomes (HRSJHMG. The study population consisted of patients with HIV who were under medical follow up, either on or off drug treatment. The data were entered into Excel and exported to SPSS 16.0 for analysis using chi-square testing. We used prevalence ratios as the measure of association. Results Lipid abnormalities were observed in 78.9% of individuals who received ART. Of the 308 subjects on ART, 59.1%, 41.9%, and 33.1% had TG, TC and low-density lipoprotein (LDL abnormalities, respectively. The prevalence of LDL changes was 2.57-fold higher in individuals who had been using ART for more than 12 months, compared to those using ART for 6 to 12 months. Conclusions HIV patients showed a significant increase in the association between TC and TG levels and the use of ART. In particular, changes in TC, LDL and TG were greater in individuals who had received ART for over more than 12 months.
Culbert, Gabriel J; Bazazi, Alexander R; Waluyo, Agung; Murni, Astia; Muchransyah, Azalia P; Iriyanti, Mariska; Finnahari; Polonsky, Maxim; Levy, Judith; Altice, Frederick L
Negative attitudes toward HIV medications may restrict utilization of antiretroviral therapy (ART) in Indonesian prisons where many people living with HIV (PLH) are diagnosed and first offered ART. This mixed-method study examines the influence of medication attitudes on ART utilization among HIV-infected Indonesian prisoners. Randomly-selected HIV-infected male prisoners (n = 102) completed face-to-face in-depth interviews and structured surveys assessing ART attitudes. Results show that although half of participants utilized ART, a quarter of those meeting ART eligibility guidelines did not. Participants not utilizing ART endorsed greater concerns about ART efficacy, safety, and adverse effects, and more certainty that ART should be deferred in PLH who feel healthy. In multivariate analyses, ART utilization was independently associated with more positive ART attitudes (AOR = 1.09, 95 % CI 1.03-1.16, p = 0.002) and higher internalized HIV stigma (AOR = 1.03, 95 % CI 1.00-1.07, p = 0.016). Social marketing of ART is needed to counteract negative ART attitudes that limit ART utilization among Indonesian prisoners.
Full Text Available The World Health Organization (WHO currently recommends that HIV-positive adults start antiretroviral therapy (ART at CD4 counts <350 cells/μl. Several countries have changed their guidelines to recommend ART irrespective of CD4 count or at a threshold of 500 CD4 cells/μl. Consequently, WHO is currently revising its treatment guidelines and considering recommending ART initiation at CD4 counts <500 cells/μl. Such decisions are critically important, as WHO guidelines inform healthcare policies in developing countries and are used by activists in their advocacy work. Changing the CD4 initiation point from 350 to 500 cells/μl would, however, be premature and have profound cost implications on Global Fund, President’s Emergency Plan for AIDS Relief (PEPFAR and developing country health budgets. We should be willing to campaign for such a change in guidelines despite cost implications, if supported by evidence. However, the evidence remains outstanding. S Afr J HIV Med 2013;14(1:6-7. DOI:10.7196/SAJHIVMED.906
Patrick S Sullivan
Full Text Available BACKGROUND: Nonadherence to antiretroviral therapy (ARVT is an important behavioral determinant of the success of ARVT. Nonadherence may lead to virological failure, and increases the risk of development of drug resistance. Understanding the prevalence of nonadherence and associated factors is important to inform secondary HIV prevention efforts. METHODOLOGY/PRINCIPAL FINDINGS: We used data from a cross-sectional interview study of persons with HIV conducted in 18 U.S. states from 2000-2004. We calculated the proportion of nonadherent respondents (took or=4 medications; living in a shelter or on the street; and feeling "blue" >or=14 of the past 30 days. We found weaker associations with having both male-male sex and injection drug use risks for HIV acquisition; being prescribed ARVT for >or=21 months; and being prescribed a protease inhibitor (PI-based regimen not boosted with ritonavir. The median proportion of doses missed was 50%. The most common reasons for missing doses were forgetting and side effects. CONCLUSIONS/SIGNIFICANCE: Self-reported recent nonadherence was high in our study. Our data support increased emphasis on adherence in clinical settings, and additional research on how providers and patients can overcome barriers to adherence.
Morse, Caryn G.; Voss, Joachim G.; Rakocevic, Goran; McLaughlin, Mary; Vinton, Carol L.; Huber, Charles; Hu, Xiaojun; Yang, Jun; Huang, Da Wei; Logun, Carolea; Danner, Robert L.; Rangel, Zoila G.; Munson, Peter J.; Orenstein, Jan M.; Rushing, Elisabeth J.; Lempicki, Richard A.; Dalakas, Marinos C.; Kovacs, Joseph A.
Background. Although human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) affect mitochondrial DNA (mtDNA) content and function, comprehensive evaluations of their effects on mitochondria in muscle, adipose tissue, and blood cells are limited. Methods. Mitochondrial DNA quantification, mitochondrial genome sequencing, and gene expression analysis were performed on muscle, adipose tissue, and peripheral blood mononuclear cell (PBMC) samples from untreated HIV-positive patients, HIV-positive patients receiving nucleoside reverse transcriptase inhibitor (NRTI)–based ART, and HIV-negative controls. Results. The adipose tissue mtDNA/nuclear DNA (nDNA) ratio was increased in untreated HIV-infected patients (ratio, 353) and decreased in those receiving ART (ratio, 162) compared with controls (ratio, 255; P < .05 for both comparisons); the difference between the 2 HIV-infected groups was also significant (P = .002). In HIV-infected participants, mtDNA/nDNA in adipose tissue correlated with the level of activation (CD38+/HLA-DR+) for CD4+ and CD8+ lymphocytes. No significant differences in mtDNA content were noted in muscle or PMBCs among groups. Exploratory DNA microarray analysis identified differential gene expression between patient groups, including a subset of adipose tissue genes. Conclusions. HIV infection and ART have opposing effects on mtDNA content in adipose tissue; immune activation may mediate the effects of HIV, whereas NRTIs likely mediate the effects of ART. PMID:22476717
Souza, Déborah Teixeira; Rondó, Patrícia Helen Carvalho; Reis, Ligia Cardoso
The objective of this cross-sectional study was to assess the nutritional status of children and adolescents with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) receiving highly active antiretroviral therapy (HAART). One hundred and eighteen subjects aged 6-19 years attending an outpatient clinic in São Paulo city were involved in the study. The following anthropometric measurements were assessed: weight, height, waist circumference and triceps and subscapular skinfold thickness. One (0.9%) adolescent was diagnosed with abdominal obesity based on waist circumference measurement; three (2.5%) adolescents were obese based on subscapular skinfold thickness. According to the body mass index, the population studied was mainly eutrophic. The prevalence of fat redistribution, a characteristic of patients with HIV/AIDS under HAART, was low. We advise the development of further studies to assess the nutritional status of children and adolescents with HIV/AIDS using anthropometric measurements as well as computed tomography to detect fat redistribution.
Brewinski, Margaret; Megazzini, Karen; Hance, Laura Freimanis; Cruz, Miguel Cashat; Pavia-Ruz, Noris; Della Negra, Marinella; Ferreira, Flavia Gomes Faleiro; Marques, Heloisa; Hazra, Rohan
In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) = 2.7, 95% confidence interval (CI) 1.3-5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9-6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART.
Rizzardi, G. Paolo; Harari, Alexandre; Capiluppi, Brunella; Tambussi, Giuseppe; Ellefsen, Kim; Ciuffreda, Donatella; Champagne, Patrick; Bart, Pierre-Alexandre; Chave, Jean-Philippe; Lazzarin, Adriano; Pantaleo, Giuseppe
Primary HIV-1 infection causes extensive immune activation, during which CD4+ T cell activation supports massive HIV-1 production. We tested the safety and the immune-modulating effects of combining cyclosporin A (CsA) treatment with highly active antiretroviral therapy (HAART) during primary HIV-1 infection. Nine adults with primary HIV-1 infection were treated with CsA along with HAART. At week 8, all patients discontinued CsA but maintained HAART. Viral replication was suppressed to a comparable extent in the CsA + HAART cohort and in 29 control patients whose primary infection was treated with HAART alone. CsA restored normal CD4+ T cell levels, both in terms of percentage and absolute numbers. The increase in CD4+ T cells was apparent within a week and persisted throughout the study period. CsA was not detrimental to virus-specific CD8+ or CD4+ T cell responses. At week 48, the proportion of IFN-γ–secreting CD4+ and CD4+CCR7– T cells was significantly higher in the CsA + HAART cohort than in the HAART-alone cohort. In conclusion, rapid shutdown of T cell activation in the early phases of primary HIV-1 infection can have long-term beneficial effects and establish a more favorable immunologic set-point. Appropriate, immune-based therapeutic interventions may represent a valuable complement to HAART for treating HIV infection. PMID:11877476
Kjær, Andreas; Kristoffersen, U S; Kofoed, K;
OBJECTIVES: Antiretroviral therapy (ART) in HIV-infected patients is associated with increased cardiovascular risk. Circulating markers of endothelial dysfunction may be used to study early atherogenesis. The aim of our study was to investigate changes in such markers during initiation of ART....... METHODS: In 115 HIV-positive treatment-naïve patients, plasma lipids, E-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), tissue-type plasminogen activator inhibitor 1 (tPAI-1) and high-sensitivity C-reactive protein (hsCRP) were measured...... before and after 2 and 14 months of ART. A control group of 30 healthy subjects was included. Values are mean+/-standard error of the mean. RESULTS: Prior to treatment, HIV-infected patients had elevated levels of sICAM-1 (296+/-24 vs. 144+/-12 ng/mL), tPAI-1 (18 473+/-1399 vs. 5490+/-576 pg/mL) and hs...
Four million people of the global total of 35 million with HIV infection are from South-East Asia. ART is currently utilized by 15 million people and has led to a dramatic decline in the mortality rate, including those in low- and middle-income countries. A reduction in sexually transmitted HIV and in comorbidities including tuberculosis has also followed. Current recommendations for the initiation of antiretroviral therapy in people who are HIV+ are essentially to initiate ART irrespective of CD4 cell count and clinical stage. The frequency of HIV testing should be culturally specific and based on the HIV incidence in different key populations but phasing in viral load technology in LMIC is an urgent priority and this needs resources and capacity. With the availability of simplified potent ART regimens, persons with HIV now live longer. The recent WHO treatment guidelines recommending routine HIV testing and earlier initiation of treatment should be the stepping stone for ending the AIDS epidemic and to meet the UNAIDS mission of 90*90*90.
Ntusi, N B A; Taylor, D; Naidoo, N G; Mendelson, M
Cardiovascular abnormalities were appreciated early in the epidemic of the acquired immunodeficiency syndrome (AIDS), even before the aetiological agent, human immunodeficiency virus (HIV) was isolated and characterised. The aetiology and pathogenesis of cardiovascular disease in HIV infection is still the subject of intense speculation, and is likely multi-factorial. HIV affects every aspect of the cardiac axis, causing pericarditis, myocarditis, cardiomyopathy, coronary artery disease and microvascular dysfunction, valvular heart disease, pulmonary vascular disease and pulmonary hypertension, stroke and peripheral vascular disease. HIV-associated vasculopathy is an increasingly recognised clinical entity, causing high morbidity and increasing mortality in southern Africa, particularly from stroke and cardiovascular disease. HIV causes disease of the vascular tree, either by a direct effect on vascular or perivascular tissue, or indirectly via immune complex-mediated mechanisms, associated opportunistic infections and malignancies. As a result, highly active antiretroviral therapy (HAART) may have an important role in controlling disease progression. We report a case of histologically defined primary HIV vasculopathy in which the chance to start HAART was initially missed and in which the patient progressed to require bilateral amputations, but obtained disease quiescence upon commencement of HAART.
Martinez, Homero; Palar, Kartika; Linnemayr, Sebastian; Smith, Alexandria; Derose, Kathryn Pitkin; Ramírez, Blanca; Farías, Hugo; Wagner, Glenn
Food insecurity and malnutrition negatively affect adherence to antiretroviral therapy (ART) and are associated with poor HIV clinical outcomes. We examined the effect of providing household food assistance and nutrition education on ART adherence. A 12-month prospective clinical trial compared the effect of a monthly household food basket (FB) plus nutrition education (NE) versus NE alone on ART adherence on 400 HIV patients at four clinics in Honduras. Participants had been receiving ART for an average of 3.7 years and were selected because they had suboptimal adherence. Primary outcome measures were missed clinic appointments, delayed prescription refills, and self-reported missed doses of ART. These three adherence measures improved for both groups over 12 months (p < 0.01), mostly within 6 months. On-time prescription refills improved for the FB plus NE group by 19.6 % more than the group receiving NE alone after 6 months (p < 0.01), with no further change at 12 months. Change in missed appointments and self-reported missed ART doses did not significantly differ by intervention group.
Fiore, P; Donelli, E; Boni, S; Pontali, E; Tramalloni, R; Bassetti, D
Maintaining linear growth and weight gain in HIV-infected children is often difficult. Nutritional evaluation and support are recognised as important factors to improve their quality of life. Combination antiretroviral therapy including protease inhibitors (HAART) reduces HIV-viral load and improves survival, quality of life and nutritional status. Our study aimed to determine changes in nutrional status based on body weight, height and nutritional habits, of HIV-infected children receiving HAART. Possible side effects of lipid metabolism were also studied. Twenty five children, 13 treated with HAART (group B) were followed up for 12 months. We did not observe statistically significant differences in nutritional status over that time or between groups A and B. Inadequate energy intake was more common in patients with advanced HIV-disease. Hyperlipidemia was found in 70% of children receiving ritonavir and in approximately 50% of children receiving nelfinavir. We observed an important although not statistically significative modification in the height of those in group B.
Daniella J. Itinoseki Kaio
Full Text Available HIV/AIDS patients are probably more predisposed to vitamin E deficiency, considering that they are more exposed to oxidative stress. Additionally, there are an extensive number of drugs in the highly active antiretroviral therapy (HAART regimens that may interfere with vitamin E concentrations. The objective of this study was to compare serum concentrations of alpha-tocopherol in 182 HIV/AIDS patients receiving different HAART regimens. The patients were divided into three groups according to regimen: nucleoside analog reverse-transcriptase inhibitors (NRTIs + non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs; NRTIs + protease inhibitors + ritonavir; NRTIs + other classes. Alpha-tocopherol was assessed by high-performance liquid chromatography. Multiple linear regression analysis was used to evaluate the effects of HAART regimen, time of use, and compliance with the regimen on alpha-tocopherol concentrations. Alpha-tocopherol concentrations were on average 4.12 μmol/L lower for the NRTIs + other classes regimen when compared to the NRTIs + NNRTIs regimen (p = 0.037. A positive association (p < 0.001 was observed between alpha-tocopherol and cholesterol concentrations, a finding due, in part, to the relationship between liposoluble vitamins and lipid profile. This study demonstrated differences in alpha-tocopherol concentrations between patients using different HAART regimens, especially regimens involving the use of new drugs. Long-term prospective cohort studies are needed to monitor vitamin E status in HIV/AIDS patients since the beginning of treatment.
Fatai A. Fehintola
Full Text Available Background. Nevirapine- (NVP- based antiretroviral therapy (ART and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity. We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics. Methods. We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n=10 and ART-naive controls (n=11. Artesunate-amodiaquine 200/600 mg was given daily for three days. Measurement of drug concentrations occurred between 0 and 96 hours after the final dose. Pharmacokinetic parameters were determined using noncompartmental analysis. Results. Comparing the NVP group to controls, clearance of artesunate was reduced 50% (1950 versus 2995 L/h; P=0.03, resulting in a 45% increase in the AUC0-96 (105 versus 69 ug∗hr/L; P=0.02. The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2 h; P=0.004, but other dihydroartemisinin pharmacokinetic parameters were unchanged. A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC0-96=5.6 versuss 8.5 in NVP and control groups, respectively, P=0.008. Conclusion. Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group.
Mujugira, Andrew; Celum, Connie; Coombs, Robert W.; Campbell, James D.; Ndase, Patrick; Ronald, Allan; Were, Edwin; Bukusi, Elizabeth A.; Mugo, Nelly; Kiarie, James; Baeten, Jared M.
Objective Combination antiretroviral therapy (ART) decreases the risk of sexual HIV transmission by suppressing blood and genital HIV RNA concentrations. We sought to determine HIV transmission risk prior to achieving complete viral suppression. Design Prospective cohort study. Methods Using data from the Partners PrEP Study, a prospective study of 4747 heterosexual HIV-serodiscordant couples in Kenya and Uganda, we examined multiple markers of HIV transmission risk during the first months after ART initiation: time to viral suppression in blood, persistence of HIV RNA in genital specimens, sexual risk behavior, pregnancy incidence, and HIV transmission using survival analysis and GEE logistic regression. Results The cumulative probabilities of achieving blood viral suppression (6 months of ART (0 infections; 167 person-years). Conclusions Residual HIV transmission risk persists during the first 6-months of ART, with incomplete viral suppression in blood and genital compartments. For HIV-serodiscordant couples in which the infected partner starts ART, other prevention options are needed, such as pre-exposure prophylaxis, until viral suppression is achieved. PMID:27070123
Kunisaki, Ken M; Niewoehner, Dennis E; Collins, Gary
BACKGROUND: Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV...... were not masked to the treatment group assignment; however, the assessors who reviewed the outcomes were masked to the treatment group. The primary outcome was the annual rate of decline in lung function, expressed as the FEV1 slope in mL/year; spirometry was done annually during follow-up for up to 5...... and 28% were current smokers. Median follow-up time was 2·0 years (IQR 1·9-3·0). We noted no differences in FEV1 slopes between the immediate and deferred ART groups either in smokers (difference of -3·3 mL/year, 95% CI -38·8 to 32·2; p=0·86) or in non-smokers (difference of -5·6 mL/year, -29·4 to 18...
Heaton, Robert K.; Franklin, Donald R.; Deutsch, Reena; Letendre, Scott; Ellis, Ronald J.; Casaletto, Kaitlin; Marquine, Maria J.; Woods, Steven P.; Vaida, Florin; Atkinson, J. Hampton; Marcotte, Thomas D.; McCutchan, J. Allen; Collier, Ann C.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin B.; Sacktor, Ned; Morgello, Susan; Simpson, David M.; Abramson, Ian; Gamst, Anthony C.; Fennema-Notestine, Christine; Smith, David M.; Grant, Igor; Grant, Igor; McCutchan, J. Allen; Ellis, Ronald J.; Marcotte, Thomas D.; Franklin, Donald; Ellis, Ronald J.; McCutchan, J. Allen; Alexander, Terry; Letendre, Scott; Capparelli, Edmund; Heaton, Robert K.; Atkinson, J. Hampton; Woods, Steven Paul; Dawson, Matthew; Smith, David M.; Fennema-Notestine, Christine; Taylor, Michael J.; Theilmann, Rebecca; Gamst, Anthony C.; Cushman, Clint; Abramson, Ian; Vaida, Florin; Marcotte, Thomas D.; Marquie-Beck, Jennifer; McArthur, Justin; Rogalski, Vincent; Morgello, Susan; Simpson, David; Mintz, Letty; McCutchan, J. Allen; Toperoff, Will; Collier, Ann; Marra, Christina; Jones, Trudy; Gelman, Benjamin; Head, Eleanor; Clifford, David; Al-Lozi, Muhammad; Teshome, Mengesha
Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16–72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions. PMID:25362201
Full Text Available Background: Healthcare workers are often reluctant to start combination antiretroviral therapy (ART in patients receiving tuberculosis (TB treatment because of the fear of high pill burden, immune reconstitution inflammatory syndrome, and side-effects.Object: To quantify changes in adherence to tuberculosis treatment following ART initiation.Design: A prospective observational cohort study of ART-naïve individuals with baseline CD4 count between 50 cells/mm3 and 350 cells/mm3 at start of TB treatment at a primary care clinic in Johannesburg, South Africa. Adherence to TB treatment was measured by pill count,self-report, and electronic Medication Event Monitoring System (eMEMS before and after initiation of ART.Results: ART tended to negatively affect adherence to TB treatment, with an 8% – 10% decrease in the proportion of patients adherent according to pill count and an 18% – 22% decrease in the proportion of patients adherent according to eMEMS in the first month following ART initiation, independent of the cut-off used to define adherence (90%, 95% or 100%. Reasons for non-adherence were multi factorial, and employment was the only predictor for optimal adherence (adjusted odds ratio 4.11, 95% confidence interval 1.06–16.0.Conclusion: Adherence support in the period immediately following ART initiation could optimise treatment outcomes for people living with TB and HIV.
Cama, Elena; Brener, Loren; Slavin, Sean; de Wit, John
HIV-related stigma has been linked to avoidance of health care services and suboptimal adherence to antiretroviral therapy (ART). However, less is known about concerns of stigma related specifically to the taking of ART in uptake of treatment. This study examines experiences of HIV treatment-related stigma and assesses if these experiences are associated with ART uptake, independent of general HIV-related stigma. People living with HIV (PLHIV; n = 697) were targeted to complete an online questionnaire measuring perceived HIV- and treatment-related stigma, social support, self-esteem, resilience, psychological distress, health satisfaction and quality of life. Findings suggest that experiences of general and treatment-related stigma were common, and that participants appear to experience greater stigma related to taking HIV treatment than general stigma associated with HIV. Neither general nor treatment-related stigma uniquely impacted HIV treatment uptake. Instead, treatment uptake was associated with being older (adjusted OR 1.05; 95% CIs: 1.03, 1.08), greater duration of HIV infection (adjusted OR 1.07; 95% CIs: 1.03-1.11) and having greater health satisfaction (adjusted OR 1.28; 95% CIs: 1.03, 1.59). Findings highlight that concerns around taking HIV treatment can be an added source of stigma for PLHIV, however other factors may be greater contributors to the likelihood of taking HIV treatment.
Buchacz, Kate; Farrior, Jennifer; Beauchamp, Geetha; McKinstry, Laura; Kurth, Ann E; Zingman, Barry S; Gordin, Fred M; Donnell, Deborah; Mayer, Kenneth H; El-Sadr, Wafaa M; Branson, Bernard
As part of the HPTN 065 study in the Bronx, New York and Washington, the authors, we surveyed clinicians to assess for shifts in their practices and attitudes around HIV treatment and prevention. Antiretroviral therapy (ART)-prescribing clinicians at 39 HIV care sites were offered an anonymous Web-based survey at baseline (2010-2011) and at follow-up (2013). The 165 respondents at baseline and 141 respondents at follow-up had similar characteristics-almost 60% were female, median age was 47 years, two-thirds were physicians, and nearly 80% were HIV specialists. The percentage who reported recommending ART irrespective of CD4 count was higher at follow-up (15% versus 68%), as was the percentage who would initiate ART earlier for patients having unprotected sex with partners of unknown HIV status (64% versus 82%), and for those in HIV-discordant partnerships (75% versus 87%). In line with changing HIV treatment guidelines during 2010 to 2013, clinicians increasingly supported early ART for treatment and prevention.
Full Text Available Abstract Objective To evaluate the feasibility of a large immediate versus deferred antiretroviral therapy (ART study in children. Methods We conducted an open-label pilot randomized clinical trial study in 43 Thai children with CD4 15 to 24% of starting generic AZT/3TC/NVP immediately (Arm 1 or deferring until CD4 Results Recruitment took 15 months. Twenty-six of 69 (37.7% were not eligible due mainly to low CD4%. Twenty four and 19 were randomized to arms 1 and 2 respectively. All accepted the randomized arm; however, 3 in arm 1 stopped ART and 1 in arm 2 refused to start ART. Ten/19 (53% in arm 2 started ART. At baseline, median age was 4.8 yrs, CDC A:B were 36:7, median CD4 was 19% and viral load was 4.8 log. All in arm 1 and 17/19 in arm 2 completed the study (median of 134 weeks. No one had AIDS or death. Four in immediate arm had tuberculosis. Once started on ART, deferred arm children achieved similar CD4 and viral load response as the immediate arm. Adverse events were similar between arms. The deferred arm had a 26% ART saving. Conclusion Almost 40% of children were not eligible due mainly to low CD4% but adherence to randomized treatment and retention in trial were excellent. A larger study to evaluate when to start ART is feasible.
Magidson, Jessica F; Seitz-Brown, C J; Listhaus, Alyson; Lindberg, Briana; Anderson, Katelyn E; Daughters, Stacey B
Despite recent clinical guidelines recommending early initiation and widespread use of antiretroviral therapy (ART), many HIV-infected individuals are not receiving ART-in particular low-income, minority substance users. Few studies have examined psychological, as opposed to structural, factors related to not receiving ART in this population. Perceived capacity to tolerate physical and psychological distress, known as distress tolerance (DT), may be a particularly relevant yet understudied factor. The current study tested the relationship between self-reported physical and psychological DT and ART receipt among predominantly low-income, minority HIV-infected substance users (n=77). Psychiatric disorders, biological indicators of health status, ART use, structural barriers to health care, and self-reported physical and psychological DT were assessed. 61% of participants were receiving ART. The only factors that distinguished individuals not on ART were greater avoidance of physical discomfort, higher psychological DT, and higher CD4 count. Both DT measures remained associated with ART use after controlling for CD4 count and were associated with almost a two-fold decrease in likelihood of ART receipt. Current findings suggest higher perceived capacity to tolerate psychological distress and greater avoidance of physical discomfort are important factors associated with lower ART use among substance users and may be important intervention targets.
Full Text Available The provision of antiretroviral therapy (ART in low and middle-income countries is a chronic disease intervention of unprecedented magnitude and is the dominant health systems challenge for high-burden countries, many of which rank among the poorest in the world. Substantial external investment, together with the requirement for service evolution to adapt to changing needs, including the constant shift to earlier ART initiation, makes outcome monitoring and reporting particularly important. However, there is growing concern at the inability of many high-burden countries to report on the outcomes of patients who have been in care for various durations, or even the number of patients in care at a particular point in time. In many instances, countries can only report on the number of patients ever started on ART. Despite paper register systems coming under increasing strain, the evolution from paper directly to complex electronic medical record solutions is not viable in many contexts. Implementing a bridging solution, such as a simple offline electronic version of the paper register, can be a pragmatic alternative. This paper describes and recommends a three-tiered monitoring approach in low- and middle-income countries based on the experience implementing such a system in the Western Cape province of South Africa. A three-tier approach allows Ministries of Health to strategically implement one of the tiers in each facility offering ART services. Each tier produces the same nationally required monthly enrolment and quarterly cohort reports so that outputs from the three tiers can be aggregated into a single database at any level of the health system. The choice of tier is based on context and resources at the time of implementation. As resources and infrastructure improve, more facilities will transition to the next highest and more technologically sophisticated tier. Implementing a three-tier monitoring system at country level for pre-antiretroviral
Full Text Available Wondu Teshome,1 Mihretu Belayneh,1 Mathewos Moges,1 Misganu Endriyas,2 Emebet Mekonnen,2 Sinafiksh Ayele,2 Tebeje Misganaw,2 Mekonnen Shiferaw,2 Palanivel Chinnakali,3 Sven Gudmund Hinderaker,4 Ajay MV Kumar5 1School of Public and Environmental Health, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia; 2Research Technology Transfer Process Unit, SNNP Regional Health Bureau, Hawassa, Ethiopia; 3Department of Preventive and Social Medicine, Jawaharlal Institute of Post-graduate Medical Education and Research, Puducherry, India; 4Centre for International Health, University of Bergen, Bergen, Norway; 5The International Union Against Tuberculosis and Lung Disease, South-East Asia Regional Office, New Delhi, India Background: Treatment adherence is critical for the success of antiretroviral therapy (ART for people living with HIV. There is limited representative information on ART drug adherence and its associated factors from Southern Ethiopia. We aimed at estimating the level of adherence to ART among people living with HIV and factors associated with it in 20 randomly selected ART clinics of Southern Ethiopia.Methods: In this cross-sectional study, we interviewed consecutive HIV patients on first-line antiretroviral regimen attending the clinics in June 2014 using a pretested and structured questionnaire. For measuring adherence, we used 4-day recall method based on “The AIDS Clinical Trial Group adherence assessment tool”. Patients were classified as “Incomplete adherence” if they missed any of the doses in the last 4 days. Data were singly entered using EpiData and descriptive analysis, and unadjusted odds ratios were calculated using EpiDataStat software. Multivariate logistic regression analysis was performed using Stata v12.0.Results: Of 974 patients interviewed, 539 (56% were females, and mean age was 35 years. The proportion of patients with incomplete adherence was 13% (95% confidence interval: 11%–15
Full Text Available Introduction: In response to the increasing burden of HIV, the Ugandan government has employed different service delivery models since 2004 that aim to reduce costs and remove barriers to accessing HIV care. These models include community-based approaches to delivering antiretroviral therapy (ART and delegating tasks to lower-level health workers. This study aimed to provide data on annual ART cost per client among three different service delivery models in Uganda. Methods: Costing data for the entire year 2012 were retrospectively collected as part of a larger task-shifting study conducted in three organizations in Uganda: Kitovu Mobile (KM, the AIDS Support Organisation (TASO and Uganda Cares (UC. A standard cost data capture tool was developed and used to retrospectively collect cost information regarding antiretroviral (ARV drugs and non-ARV drugs, ART-related lab tests, personnel and administrative costs. A random sample of four TASO centres (out of 11, four UC clinics (out of 29 and all KM outreach units were selected for the study. Results: Cost varied across sites within each organization as well as across the three organizations. In addition, the number of annual ART visits was more frequent in rural areas and through KM (the community distribution model, which played a major part in the overall annual ART cost. The annual cost per client (in USD was $404 for KM, $332 for TASO and $257 for UC. These estimates were lower than previous analyses in Uganda or the region compared to data from 2001 to 2009, but comparable with recent estimates using data from 2010 to 2013. ARVs accounted for the majority of the total cost, followed by personnel and operational costs. Conclusions: The study provides updated data on annual cost per ART visit for three service delivery models in Uganda. These data will be vital for in-country budgetary efforts to ensure that universal access to ART, as called for in the 2015 World Health Organization (WHO
Full Text Available Objective: To describe the degree of HIV disease progression in infants initiating antiretroviral therapy (ART by three months of age in a programmatic setting in South Africa. Design: This was a programmatic cohort study. Methods: Electronic and manual data extraction from databases and antiretroviral registers in 20 public clinics in Cape Town and electronic data extraction from a large ART service at Chris Hani Baragwanath Hospital in Soweto were performed. Records of all infants initiated on ART by three months of age between June 2007 and September 2010 were extracted. Demographics, immunological and clinical stage at ART initiation were analyzed descriptively by chi-square, two-sample t-test and Kaplan–Meier methods. Results: A total of 403 records were identified: 88 in Cape Town and 315 in Soweto. Median age at ART initiation was 8.4 [interquartile range (IQR: 7.2–9.7] weeks. At ART initiation, 250 infants (62% had advanced HIV disease (CD4% <25% or absolute CD4<1500 cells/mm3 or WHO clinical Stage 3 or 4. Median age at ART initiation by site was 10.3 (IQR: 8.2–11.9 weeks in Cape Town and 8.6 (IQR: 7.7–10.0 weeks in Soweto infants (p<0.0001. In Cape Town, 73 infants (83% had advanced HIV disease at ART initiation, compared to 177 infants (56% in Soweto (p<0.0001. On logistic regression, each month increase in age at ART initiation lowered the odds of initiating ART in an optimal state (OR: 0.56, CI: 0.36–0.94 and increased the odds of advanced HIV disease at ART initiation (OR: 1.69, CI: 1.05–2.71. Conclusions: ART initiation by three months of age may not adequately prevent disease progression. New emphasis on early diagnosis and rapid initiation of ART in the first weeks of life are essential to further reduce infant mortality.
Daley, M J; Oldham, E R
A recombinant bactericidal protein, recombinant lysostaphin (r-lysostaphin), that may be useful as an intramammary therapeutic for Staphylococcus aureus mastitis in dairy cattle, was evaluated for immunogenicity to various hosts. Although immunogenicity could be demonstrated in a variety of other species when administered parenterally, oral administration failed to elicit a significant immunological response. Similarly, intramammary infusion of r-lysostaphin failed to elicit significant serum titers in the bovine until 18-21 infusions were administered (total administered dose of 2-3 g of protein). Antibody titers from dairy cattle which did develop an immune response were predominantly of the IgG1 subclass. Dairy cattle with significant anti-lysostaphin titers showed no deleterious symptoms (anaphylaxis, etc.) upon subsequent infusion, and these titers did not effect the in vitro bacteriostatic activity of r-lysostaphin. Intramammary infusion of r-lysostaphin does not elicit any observable effects on the host animal or on the potential efficacy of the recombinant molecule. Intramammary recombinant proteins may be suitable effective and safe infusion products that provide an alternative to classical antibiotic therapy.
Full Text Available Purpose and Aim: Multi-drug resistance in treatment-experienced human immune deficiency virus (HIV patients has been a major cause to first line antiretroviral therapy (ART failure, necessitating a switch to second line therapy. In India, the second line treatment program is still relatively new with little experience and unclear outcomes. It is therefore, critical to assess the clinical, virological and immunological effectiveness and treatment outcome over the 1 st year of follow-up in the patients′ switched to the second line ART at public sector tertiary care center. Materials and Methods: A prospective, observational study was carried out on HIV positive patients switched on second line ART from January 2010 to December 2010 at ART Centre, Civil Hospital, Ahmedabad. Demographic details, symptoms, adverse drug reactions (ADRs, second line ART regimens, CD4 count, and plasma viral load (PVL were recorded in a case record form. Patients were followed-up monthly for 12 months. The data was analyzed by t-test, z-test, and Fisher-exact test. Results: Out of 126 patients, 82 received regimen V [zidovudine (ZDV + lamivudine (3TC + tenofovir (TDF + boosted lopinavir (LPV/r] and 44 received regimen Va [3TC + TDF + LPV/r]. A significant ( P < 0.0001 increase in mean body weight and marked reduction in number of patients (7 categorized as WHO stage III/IV was observed at 12 months of second line ART. Moreover, a significant immune reconstitution with increase in mean CD4 count and viral suppression (PVL < 400 copies/ml in 103 (82% patients ( P < 0.0001 was also observed. A total of 83 ADRs were observed in 69 (55% patients, the most common being dyslipidemia (57 followed by anemia (9. Conclusion: Early treatment outcome with second line ART was good with 82% success rate in treatment experienced HIV patients. Dyslipidemia and anemia were the common ADRs observed.
Peterson, Kevin; Togun, Toyin; Klis, Sandor; Menten, Joris; Colebunders, Robert
Mood disorders are more frequent among people with HIV infection than among non-HIV-infected individuals of the same age, socioeconomic status, and HIV risks. They have been associated with worse adherence and clinical outcomes, yet remain underdiagnosed and undertreated in sub-Saharan Africa. We explored the relationship between mood disorders using the 10-item depression scale of the Centers for Epidemiological Studies (CES-D10) and the 22-item Impact of Events Scale-Revised (IES-R) for posttraumatic stress disorder, and a range of demographic and HIV-related variables among 252 consecutive subjects on antiretroviral therapy (ART). The study was conducted in the Genito-Urinary Medicine Clinic of the Medical Research Council's Gambia Unit. These screening tests were positive in 7% and 30%, respectively, of the patients, with higher scores (more depression or more post-traumatic stress) associated with female gender, more advanced WHO clinical stage, and lower Karnofsky Perfomance Scale rating. Higher CES-D10 scores were also seen among those on their second ART regimen. No relationship was seen with age, time on ART, viral load, or CD4 cell count. Compared to an earlier study at the same site in subjects prior to starting ART, the prevalence of depression in those stabilized on ART was dramatically reduced (by 34%, from 41%) while that of PTSD dropped less (by 13%, from 43%). Integrating the CES-D10 or a similar instrument into patient preparation for ART is recommended in order to identify those who may benefit from further mental health investigations, specific therapy, or closer follow-up during early ART.
Fortuny, Clàudia; Deyà-Martínez, Ángela; Chiappini, Elena; Galli, Luisa; de Martino, Maurizio; Noguera-Julian, Antoni
Worldwide, the benefits of combined antiretroviral (ARV) therapy in morbidity and mortality due to perinatally acquired human immunodeficiency virus infection are beyond question and outweigh the toxicity these drugs have been associated with in HIV-infected children and adolescents to date. In puberty, abnormal body fat distribution is stigmatizating and leads to low adherence to ARV treatment. The other metabolic comorbidities (mitochondrial toxicity, dyslipidemias, insulin resistance and low bone mineral density) and renal toxicity, albeit nonsymptomatic in most children, are increasingly being reported and potentially put this population at risk for early cardiovascular or cerebrovascular atherosclerotic disease, diabetes, pathologic fractures or premature renal failure in the third and fourth decades of life. Evidence from available studies is limited because of methodological limitations and also because of several HIV-unrelated factors influencing, to some degree, the development of these conditions. Current recommendations for the prevention, diagnosis, monitoring and treatment of metabolic and renal adverse effects in HIV-children and adolescents are based on adult studies, observational pediatric studies and experts' consensus. Healthy lifestyle habits (regarding diet, exercise and refraining from toxic substances) and wise use of ARV options are the only preventive tools for the majority of patients. Should abnormal findings arise, switches in one or more ARV drugs have proved useful. Specific therapies are also available for some of these comorbidities, although the experience in the pediatric age is still very scarce. We aim to summarize the epidemiological, clinical and therapeutic aspects of metabolic and renal adverse effects in vertically HIV-infected children and adolescents.
Mosoko Jembia J
Full Text Available Abstract Background In 2002, Cameroon initiated scale up of antiretroviral therapy (ART; on 1 October 2004, a substantial reduction in ART cost occurred. We assessed the impact of this event and other factors on enrolment and retention in care among HIV-infected patients initiating ART from February 2002 to December 2005 at the single ART clinic serving the Southwest Region in Limbe, Cameroon. Methods We retrospectively analyzed clinical and pharmacy payment records of HIV-infected patients initiating ART according to national guidelines. We compared two cohorts of patients, enrolled before and after 1 October 2004, to determine if price reduction was associated with enhanced enrolment. We assessed factors associated with retention and survival by Cox proportional hazards models. Retention in care implied patients who had contact with the healthcare system as of 31 December 2005 (including those who were transferred to continue care in other ART centres, although these patients may have interrupted therapy at some time. A patient who was not retained in care may have dropped out (lost to follow up or died. Results Mean enrolment rates for 2920 patients who initiated ART before and after the price reduction were 46.5 and 95.5 persons/month, respectively (p Conclusions Reducing the cost of ART increased enrolment of clients in the programme, but did not change retention in care. In a system where most clients pay for ART, an accessible clinic location may be more important than the cost of medication for retention in care. Decentralizing ART clinics might improve retention and survival among patients on ART.
Puttkammer, Nancy H.; Zeliadt, Steven B.; Baseman, Janet G.; Destiné, Rodney; Domerçant, Jean Wysler; Coq, Nancy Rachel Labbé; Raphael, Nernst Atwood; Sherr, Kenneth; Tegger, Mary; Yuhas, Krista; Barnhart, Scott
Objective To identify factors associated with antiretroviral therapy (ART) attrition among patients initiating therapy in 2005–2011 at two large, public-sector department-level hospitals, and to inform interventions to improve ART retention. Methods This retrospective cohort study used data from the iSanté electronic medical record (EMR) system. The study characterized ART attrition levels and explored the patient demographic, clinical, temporal, and service utilization factors associated with ART attrition, using time-to-event analysis methods. Results Among the 2 023 patients in the study, ART attrition on average was 17.0 per 100 person-years (95% confidence interval (CI): 15.8–18.3). In adjusted analyses, risk of ART attrition was up to 89% higher for patients living in distant communes compared to patients living in the same commune as the hospital (hazard ratio: 1.89, 95%CI: 1.54–2.33; P < 0.001). Hospital site, earlier year of ART start, spending less time enrolled in HIV care prior to ART initiation, receiving a non-standard ART regimen, lacking counseling prior to ART initiation, and having a higher body mass index were also associated with attrition risk. Conclusions The findings suggest quality improvement interventions at the two hospitals, including: enhanced retention support and transportation subsidies for patients accessing care from remote areas; counseling for all patients prior to ART initiation; timely outreach to patients who miss ART pick-ups; “bridging services” for patients transferring care to alternative facilities; routine screening for anticipated interruptions in future ART pick-ups; and medical case review for patients placed on non-standard ART regimens. The findings are also relevant for policymaking on decentralization of ART services in Haiti. PMID:25563149
Lodwick, Rebecca; Costagliola, Dominique; Reiss, Peter;
the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI...... 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...
van Wijk, Jeroen P. H.; Cabezas, Manuel Castro
The use of combination antiretroviral therapy (CART) in HIV-infected patients has resulted in a dramatic decline in AIDS-related mortality. However, mortality due to non-AIDS conditions, particularly cardiovascular disease (CVD) seems to increase in this population. CART has been associated with several metabolic risk factors, including insulin resistance, low HDL-cholesterol, hypertriglyceridemia and postprandial hyperlipidemia. In addition, HIV itself, as well as specific antiretroviral agents, may further increase cardiovascular risk by interfering with endothelial function. As the HIV population is aging, CVD may become an increasingly growing health problem in the future. Therefore, early diagnosis and treatment of cardiovascular risk factors is warranted in this population. This paper reviews the contribution of both, HIV infection and CART, to insulin resistance, postprandial hyperlipidemia and cardiovascular risk in HIV-infected patients. Strategies to reduce cardiovascular risk are also discussed. PMID:21876813
Full Text Available In the HPTN 052 study, transmission between HIV-discordant couples was reduced by 96% when the HIV-infected partner received suppressive antiretroviral therapy (ART. We examined two transmission events where the newly infected partner was diagnosed after the HIV-infected partner (index initiated therapy. We evaluated the sequence complexity of the viral populations and antibody reactivity in the newly infected partner to estimate the dates of transmission to the newly infected partners. In both cases, transmission most likely occurred significantly before HIV-1 diagnosis of the newly infected partner, and either just before the initiation of therapy or before viral replication was adequately suppressed by therapy of the index. This study further strengthens the conclusion about the efficacy of blocking transmission by treating the infected partner of discordant couples. However, this study does not rule out the potential for HIV-1 transmission to occur shortly after initiation of ART, and this should be recognized when antiretroviral therapy is used for HIV-1 prevention.
Desmonde, Sophie; Eboua, François T; Malateste, Karen;
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 IeDEA clin...... 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....
Newcomb, Michael E; Bedoya, C Andres; Blashill, Aaron J; Lerner, Jonathan A; O'Cleirigh, Conall; Pinkston, Megan M; Safren, Steven A
There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depression in adult populations, and CBT for adherence and depression (CBT-AD) is an effective treatment for improving depressive symptoms and medication adherence in the context of various chronic health conditions, including diabetes and HIV-infection. This paper provides a description of the CBT-AD approach to treat depression and ART adherence in HIV-infected adults, which we have developed and tested in our clinic, and for which detailed therapist and client guides exist. To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment, including Life-Steps for medication adherence, orientation to CBT-AD and psychoeducation, and suggestions for adaptation of core CBT modules for HIV-infected adults. Discussion of video demonstrations highlights differences in patient presentations and course of treatment between HIV-infected adults receiving CBT-AD and HIV-uninfected adults receiving traditional CBT for depression. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting.
Full Text Available BACKGROUND: Little information exists on the impact of highly active antiretroviral therapy (HAART on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices. METHODS AND FINDINGS: Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3 and 27 with AIDS (WHO stage 4 receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group. Costs of service provision (January 2004 prices, USD 1 = 7.6 Rand included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of $730 per patient-year (PPY, whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97-1.19 for the HAART group versus 3.73 (95% CI: 3.55-3.97 for the No-ART group, and 8.71 (95% CI: 8.40-9.03 versus 4.35 (95% CI: 4.12-5.61, respectively, for mean number of outpatient visits PPY. Average service provision PPY was $950 for the No-ART group versus $1,342 and $793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG was $1,622 for scenario 1 and $675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63-2.52 for the HAART versus 15.36 (95% CI: 13.97-16.85 for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81-8.49 compared with 6.60 (95% CI: 5.69-7.62 respectively. Average service provision PPY was $3,520 for the No-ART group versus $1,513 and $964
Gutierrez, Mavel; Ludwig, David A.; Khan, Safia S.; Chaparro, Aida A.; Rivera, Delia M.; Cotter, Amanda M.; Scott, Gwendolyn B.
Background. Since the introduction of highly active antiretroviral therapy (HAART) for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in pregnancy in the United States, the time of seroreversion in infants born to HIV-infected mothers has not been documented. The objective of this study was to determine the timing of clearance of HIV antibodies and to identify any associated biological and clinical factors. Methods. A retrospective analysis of infants who remained uninfected after perinatal HIV exposure was performed. Infant and maternal medical records from January 2000 to December 2007 were reviewed and the time of seroreversion was estimated using methods for censored survival data. Results. In total, 744 infants were included in the study, with prenatal data available for 551 mothers. The median age of seroreversion was 13.9 months, and 14% of infants remained seropositive after 18 months, 4.3% after 21 months, and 1.2% after 24 months. Earlier age of seroreversion was associated with higher immunoglobulin G (IgG) levels at 3–7 months of age (P = .0029) and a higher rate of IgG change over the next 6 months of life (P = .003). Infants born by vaginal delivery were more likely to serorevert at a younger age (P = .0052), and maternal exposure to protease inhibitors was associated with a later age of seroreversion (P = .026). Conclusions. Clearance of HIV antibodies in uninfected infants was found to occur at a later age than has been previously reported. Fourteen percent of the infants had persistence of HIV antibodies at or beyond 18 months of age. PMID:22851494
Kasirye, Ronnie P.; Grosskurth, Heiner; Munderi, Paula; Levin, Jonathan; Anywaine, Zacchaeus; Nunn, Andrew; Kamali, Anatoli; Baisley, Kathy
Introduction: Using the data of a trial on cotrimoxazole (CTX) cessation, we investigated the effect of different antiretroviral therapy (ART) regimens on the incidence of clinical malaria. Methods: During the cotrimoxazole cessation trial (ISRCTN44723643), HIV-infected Ugandan adults with CD4+ at least 250 cells/μl were randomized to receive either CTX prophylaxis or placebo and were followed for a median of 2.5 years. Blood slides for malaria microscopy were examined at scheduled visits and at unscheduled visits when the participant felt unwell. CD4+ cell counts were done 6-monthly. Malaria was defined as fever with a positive blood slide. ART regimens were categorized as nucleoside reverse transcriptase inhibitor (NRTI) only, non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing or protease inhibitor containing. Malaria incidence was calculated using random effects Poisson regression to account for clustering of events. Results: Malaria incidence in the three ART regimen groups was 9.9 (3.6-27.4), 9.3 (8.3-10.4), and 3.5 (1.6-7.6) per 100 person-years, respectively. Incidence on protease inhibitors was lower than that on the other regimens with the results just reaching significance (adjusted rate ratio 0.4, 95% confidence interval = 0.2–1.0, comparing with NNRTI regimens). Stratification by CTX/placebo use gave similar results, without evidence of an interaction between the effects of CTX/placebo use and ART regimen. There was no evidence of an interaction between ART regimen and CD4+ cell count. Conclusion: There was some evidence that protease inhibitor-containing ART regimens may be associated with a lower clinical malaria incidence compared with other regimens. This effect was not modified by CTX use or CD4+ cell count. The antimalarial properties of protease inhibitors may have clinical and public health importance. PMID:28121670
Jessie K Edwards
Full Text Available Missing outcome data due to loss to follow-up occurs frequently in clinical cohort studies of HIV-infected patients. Censoring patients when they become lost can produce inaccurate results if the risk of the outcome among the censored patients differs from the risk of the outcome among patients remaining under observation. We examine whether patients who are considered lost to follow up are at increased risk of mortality compared to those who remain under observation. Patients from the US Centers for AIDS Research Network of Integrated Clinical Systems (CNICS who newly initiated combination antiretroviral therapy between January 1, 1998 and December 31, 2009 and survived for at least one year were included in the study. Mortality information was available for all participants regardless of continued observation in the CNICS. We compare mortality between patients retained in the cohort and those lost-to-clinic, as commonly defined by a 12-month gap in care. Patients who were considered lost-to-clinic had modestly elevated mortality compared to patients who remained under observation after 5 years (risk ratio (RR: 1.2; 95% CI: 0.9, 1.5. Results were similar after redefining loss-to-clinic as 6 months (RR: 1.0; 95% CI: 0.8, 1.3 or 18 months (RR: 1.2; 95% CI: 0.8, 1.6 without a documented clinic visit. The small increase in mortality associated with becoming lost to clinic suggests that these patients were not lost to care, rather they likely transitioned to care at a facility outside the study. The modestly higher mortality among patients who were lost-to-clinic implies that when we necessarily censor these patients in studies of time-varying exposures, we are likely to incur at most a modest selection bias.
Full Text Available Identifying follow-up (FU visit patterns, and exploring which factors influence them are likely to be useful in determining which patients on antiretroviral therapy (ART may become Lost to Follow-Up (LTFU. Using an operation and implementation research approach, we sought 1 to describe the timing of FU visits amongst patients who have been on ART for shorter and longer periods of time; and 2 to determine the median time to late visits, and 3 to identify specific factors that may be associated with these patterns in Zomba, Malawi.Using routinely collected programme monitoring data from Zomba District, we performed descriptive analyses on all ART visits among patients who initiated ART between Jan. 1, 2007-June 30, 2010. Based on an expected FU date, each FU visit was classified as early (≥4 day before an expected FU date, on time (3 days before an expected FU date/up to 6 days after an expected FU date, or late (≥7 days after an expected FU date. In total, 7,815 patients with 76417 FU visits were included. Ninety-two percent of patients had ≥2 FU visits. At the majority of visits, patients were either on time or late. The median time to a first late visit among those with 2 or more visits was 216 days (IQR: 128-359. Various patient- and visit-level factors differed significantly across Early, On Time, and Late visit groups including ART adherence and frequency of, and type of side effects.The majority of patients do not demonstrate consistent FU visit patterns. Individuals were generally on ART for at least 6 months before experiencing their first late visit. Our findings have implications for the development of effective interventions that meet patient needs when they present early and can reduce patient losses to follow-up when they are late. In particular, time-varying visit characteristics need further research.
Full Text Available BACKGROUND: Despite prolonged treatment with highly active antiretroviral therapy (HAART, the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS levels did not reveal any significant changes in the same treatment period. CONCLUSIONS/SIGNIFICANCE: Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART.
Claire L Risley
Full Text Available BACKGROUND: We set out to estimate, for the three geographical regions with the highest HIV prevalence, (sub-Saharan Africa [SSA], the Caribbean and the Greater Mekong sub-region of East Asia, the human resource and economic impact of HIV on the supply of education from 2008 to 2015, the target date for the achievement of Education For All (EFA, contrasting the continuation of access to care, support and Antiretroviral therapy (ART to the scenario of universal access. METHODOLOGY/PRINCIPAL FINDINGS: A costed mathematical model of the impact of HIV and ART on teacher recruitment, mortality and absenteeism (Ed-SIDA was run using best available data for 58 countries, and results aggregated by region. It was estimated that (1 The impact of HIV on teacher supply is sufficient to derail efforts to achieve EFA in several countries and universal access can mitigate this. (2 In SSA, the 2008 costs to education of HIV were about half of those estimated in 2002. Providing universal access for teachers in SSA is cost-effective on education returns alone and provides a return of $3.99 on the dollar. (3 The impacts on education in the hyperendemic countries in Southern Africa will continue to increase to 2015 from its 2008 level, already the highest in the world. (4 If treatment roll-out is successful, numbers of HIV positive teachers are set to increase in all the regions studied. CONCLUSIONS/SIGNIFICANCE: The return on investing in care and support is also greater in those areas with highest impact. SSA requires increased investment in teacher support, testing and particularly ART if it is to achieve EFA. The situation for teachers in the Caribbean and East Asia is similar but on a smaller scale proportionate to the lower levels of infection and greater existing access to care and support.
Russell, Steve; Martin, Faith; Zalwango, Flavia; Namukwaya, Stella; Nalugya, Ruth; Muhumuza, Richard; Katongole, Joseph; Seeley, Janet
The health of people living with HIV (PLWH) and the sustained success of antiretroviral therapy (ART) programmes depends on PLWH's motivation and ability to self-manage the condition over the long term, including adherence to drugs on a daily basis. PLWH's self-management of HIV and their wellbeing are likely to be interrelated. Successful self-management sustains wellbeing, and wellbeing is likely to motivate continued self-management. Detailed research is lacking on PLWH's self-management processes on ART in resource-limited settings. This paper presents findings from a study of PLWH's self-management and wellbeing in Wakiso District, Uganda. Thirty-eight PLWH (20 women, 18 men) were purposefully selected at ART facilities run by the government and by The AIDS Support Organisation in and around Entebbe. Two in-depth interviews were completed with each participant over three or four visits. Many were struggling economically, however the recovery of health and hope on ART had enhanced wellbeing and motivated self-management. The majority were managing their condition well across three broad domains of self-management. First, they had mobilised resources, notably through good relationships with health workers. Advice and counselling had helped them to reconceptualise their condition and situation more positively and see hope for the future, motivating their work to self-manage. Many had also developed a new network of support through contacts they had developed at the ART clinic. Second, they had acquired knowledge and skills to manage their health, a useful framework to manage their condition and to live their life. Third, participants were psychologically adjusting to their condition and their new 'self': they saw HIV as a normal disease, were coping with stigma and had regained self-esteem, and were finding meaning in life. Our study demonstrates the centrality of social relationships and other non-medical aspects of wellbeing for self-management which ART
FolefackKaze, Francois; Kengne, Andre-Pascal; Pefura Yone, Eric Walter; NdamFemben, Nelly Sandra; Ashuntantang, Gloria
As per guidelines and recommendations, screening for renal diseases should be performed at the time of diagnosis of human immuno-deficiency virus (HIV) infection; however, this remains largely unimplemented in many settings across Sub-Saharan Africa. We evaluated the renal function, urinalysis abnormalities and their correlates in HIV-infected individuals who were naïve to highly active antiretroviral therapy (HAART). This was a cross-sectional study of 2 months' duration involving 104 HIV-infected outpatients naive to HAART (71 women, 68%) attending the HIV clinic of the Yaoundé General Hospital in Cameroon. Renal and urinalysis parameters were measured and the Student t-test and Fischer exact test were used to compare the groups of participants. The mean age and CD4 count were, respectively, 35 ± 10.7 years and 305 ± 202/mL. Fifty-six (54%) patients presented with stages 3 and 4 of HIV infection. Forty-three (41%) patients had urinalysis abnormalities, including proteinuria (36%), leukocyturia (13%) and hematuria (12%). Proteinuria was associated with increased age, advanced stage of HIV infection, decreased CD4 count, hematuria and renal failure (P HIV infection, respectively (P = 0.04). The mean estimated glomerular filtration (eGFR) rate was 100.2 ± 32.7 mL/min; three (3%) patients had renal failure (eGFR patients had reduced kidney function 60 ≤eGFR ≤90 mL/min. There was a high prevalence of decreased kidney function and proteinuria among Cameroonian HIV-infected patients naïve to HAART. Indicators of the severity of HIV infection, including advanced stage and low CD4 count, were associated with urinalysis abnormalities.
Full Text Available To identify the prevalence and predictors of abnormal renal function among HIV-positive Chinese patients prior to antiretroviral therapy (ART initiation and to evaluate subsequent changes in renal function after ART exposure.We conducted a nationwide cohort study of subjects who enrolled in the national Chinese ART program from January 1, 2012 to December 31, 2012. We estimated the glomerular filtration rate (eGFR of subjects prior to and after initiating ART. Risk factors for abnormal renal function, as defined by eGFR 6.1 mmol/L (AOR = 1.46, 95% CI: 1.25-1.72, and hepatitis C co-infection (AOR = 1.36, 95% CI: 1.06-1.73. Among subjects with baseline eGFR >90 ml/min/1.73m2, the incidence of the eGFR falling to <60 ml/min/1.73m2 was 0.92/100 person-years after a median of 15.0 months of ART. Being on a tenofovir with lopinavir/ritonavir regimen (Adjusted hazard ratio [AHR] = 3.02, 95% CI: 1.96-4.66 and having an unsuppressed viral load (AHR = 2.70, 95% CI: 1.80-4.03 were independent predictors for eGFR <60 ml/min/1.73m2 after ART initiation as well as older age, female, and hemoglobin <120 g/L.A high proportion of HIV-positive subjects in China presented with abnormal renal function prior to ART initiation. But the incidence of the eGFR decrease after ART was low. Patient renal function should be regularly monitored by eGFR before initiating and during ART.
Muessig, Kathryn E; Panter, Abigail T; Mouw, Mary S; Amola, Kemi; Stein, Kathryn E; Murphy, Joseph S; Maiese, Eric M; Wohl, David A
Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) is crucial for health, but patients face numerous challenges achieving sustained lifetime adherence. We conducted six focus groups with 56 PLWH regarding ART adherence barriers and collected sociodemographics and ART histories. Participants were recruited through clinics and AIDS service organizations in North Carolina. Dedoose software was used to support thematic analysis. Participants were 59% male, 77% black, aged 23-67 years, and living with HIV 4-20 years. Discussions reflected the fluid, complex nature of ART adherence. Maintaining adherence required participants to indefinitely assert consistent control across multiple areas including: their HIV disease, their own bodies, health care providers, and social systems (e.g., criminal justice, hospitals, drug assistance programs). Participants described limited control over treatment options, ART's impact on their body, and inconsistent access to ART and subsequent inability to take ART as prescribed. When participants felt they had more decision-making power, intentionally choosing whether and how to take ART was not exclusively a decision about best treating HIV. Instead, through these decisions, participants tried to regain some amount of power and control in their lives. Supportive provider relationships assuaged these struggles, while perceived side-effects and multiple co-morbidities further complicated adherence. Adherence interventions need to better convey adherence as a continuous, changing process, not a fixed state. A perspective shift among care providers could also help address negative consequences of the perceived power struggles and pressures that may drive patients to exert control via intentional medication taking practices.
Kanters, Steve; Park, Jay JH; Chan, Keith; Ford, Nathan; Forrest, Jamie; Thorlund, Kristian; Nachega, Jean B; Mills, Edward J
Introduction It is unclear whether using peers can improve adherence to antiretroviral therapy (ART). To construct the World Health Organization's global guidance on adherence interventions, we conducted a systematic review and network meta-analysis to determine the effectiveness of using peers for achieving adequate adherence and viral suppression. Methods We searched for randomized clinical trials of peer-based interventions to promote adherence to ART in HIV populations. We searched six electronic databases from inception to July 2015 and major conference abstracts within the last three years. We examined the outcomes of adherence and viral suppression among trials done worldwide and those specific to low- and middle-income countries (LMIC) using pairwise and network meta-analyses. Results and discussion Twenty-two trials met the inclusion criteria. We found similar results between pairwise and network meta-analyses, and between the global and LMIC settings. Peer supporter+Telephone was superior in improving adherence than standard-of-care in both the global network (odds-ratio [OR]=4.79, 95% credible intervals [CrI]: 1.02, 23.57) and the LMIC settings (OR=4.83, 95% CrI: 1.88, 13.55). Peer support alone, however, did not lead to improvement in ART adherence in both settings. For viral suppression, we found no difference of effects among interventions due to limited trials. Conclusions Our analysis showed that peer support leads to modest improvement in adherence. These modest effects may be due to the fact that in many settings, particularly in LMICs, programmes already include peer supporters, adherence clubs and family disclosures for treatment support. Rather than introducing new interventions, a focus on improving the quality in the delivery of existing services may be a more practical and effective way to improve adherence to ART. PMID:27914185
Full Text Available Introduction: Every year, approximately 260,000 children are infected with HIV in low- and middle-income countries. The timely initiation and high level of maintenance of antiretroviral therapy (ART are crucial to reducing the suffering of HIV-positive children. We need to develop a better understanding of the background of children's ART non-adherence because it is not well understood. The purpose of this study is to explore the background related to ART non-adherence, specifically in relation to the orphan status of children in Kigali, Rwanda. Methods: We conducted 19 focus group discussions with a total of 121 caregivers of HIV-positive children in Kigali. The primary data for analysis were verbatim transcripts and socio-demographic data. A content analysis was performed for qualitative data analysis and interpretation. Results: The study found several contextual factors that influenced non-adherence: among double orphans, there was psychological distance between the caregivers and children, whereas economic burden was the primary issue among paternal orphans. The factors promoting adherence also were unique to each orphan status, such as the positive attitude about disclosing serostatus to the child by double orphans’ caregivers, and feelings of guilt about the child's condition among non-orphaned caregivers. Conclusions: Knowledge of orphan status is essential to elucidate the factors influencing ART adherence among HIV-positive children. In this qualitative study, we identified the orphan-related contextual factors that influenced ART adherence. Understanding the social context is important in dealing with the challenges to ART adherence among HIV-positive children.
Full Text Available Introduction: This retrospective study aimed to investigate that if switch of combination antiretroviral therapy (cART would result in viral suppression (20 to 5 log10 (% (59.4% (61.3% (54.3% .480 CD4 at LLV, median (range, cells/uL (63–1092 (63–1092 (134–1010 .156 PVL at enrollment, copies/mL (21–999 (21–939 (21–999 .002 PVL of 20–199 (% (77.0% (84.0% (58.7% .001 PVL of 200–999 (% (23.0% (16.0% (41.3% .001 Duration of cART exposure, median (range, weeks (12–391 (15–321 (12–391 .062 Years of HIV diagnosed, median, (range, years (1–14 (1–14 (2–13 .356 Ever treatment failure (% /165 /119 /46 .111 Current cART NRTIs+nNRTI (23.6% (32.8% (0% <0.001 NRTIs+PI (18.8% (24.4% (4.3% .003 NRTIs+PI/r (51.5% (39.5% (82.6% <0.001 NRTIs+II (4.2% (3.3% (6.5% .967 II+PI/r (1.8% (0% (6.5% .021 Conclusions: According to the clinical guidelines of BHIVA, patients with low-level viremia who switched to cART consisting of 2 NRTIs plus boosted PI or newer mechanisms were more likely to re-establish viral suppression to <40 copies/mL at week 48.
Full Text Available Abstract Background As the resource implications of expanding anti-retroviral therapy (ART are likely to be large, there is a need to explore its cost-effectiveness. So far, there is no such information available from Ethiopia. Objective To assess the cost-effectiveness of ART for routine clinical practice in a district hospital setting in Ethiopia. Methods We estimated the unit cost of HIV-related care from the 2004/5 fiscal year expenditure of Arba Minch Hospital in southern Ethiopia. We estimated outpatient and inpatient service use from HIV-infected patients who received care and treatment at the hospital between January 2003 and March 2006. We measured the health effect as life years gained (LYG for patients receiving ART compared with those not receiving such treatment. The study adopted a health care provider perspective and included both direct and overhead costs. We used Markov model to estimate the lifetime costs, health benefits and cost-effectiveness of ART. Findings ART yielded an undiscounted 9.4 years expected survival, and resulted in 7.1 extra LYG compared to patients not receiving ART. The lifetime incremental cost is US$2,215 and the undiscounted incremental cost per LYG is US$314. When discounted at 3%, the additional LYG decreases to 5.5 years and the incremental cost per LYG increases to US$325. Conclusion The undiscounted and discounted incremental costs per LYG from introducing ART were less than the per capita GDP threshold at the base year. Thus, ART could be regarded as cost-effective in a district hospital setting in Ethiopia.
Burgos-Soto, Juan; Balestre, Eric; Minga, Albert; Ajayi, Samuel; Sawadogo, Adrien; Zannou, Marcel D.; Leroy, Valériane; Ekouevi, Didier K.; Dabis, François; Becquet, Renaud
Introduction This study aimed at estimating the incidence of pregnancy after antiretroviral therapy (ART) initiation in eight West African countries over a 10-year period. Methods A retrospective analysis was conducted within the international database of the IeDEA West Africa Collaboration. All HIV-infected women aged <50 years and starting ART for their own health between 1998 and 2011 were eligible. Pregnancy after ART initiation was the main outcome and was based on clinical reporting. Poisson regression analysis accounting for country heterogeneity was computed to estimate first pregnancy incidence post-ART and to identify its associated factors. Pregnancy incidence rate ratios were adjusted on country, baseline CD4 count and clinical stage, haemoglobin, age, first ART regimen and calendar year. Results Overall 29,425 HIV-infected women aged 33 years in median [Inter Quartile Range: 28–38] contributed for 84,870 women-years of follow-up to this analysis. The crude incidence of first pregnancy (2,304 events) was 2.9 per 100 women-years [95% confidence interval [CI]: 2.7–3.0], the highest rate being reported among women aged 25–29 years: 4.7 per 100 women-years; 95% CI: 4.3–5.1. The overall Kaplan-Meier probability of pregnancy occurrence by the fourth year on ART was 10.9% (95% CI: 10.4–11.4) and as high as 28.4% (95% CI: 26.3–30.6) among women aged 20–29 years at ART initiation. Conclusion The rate of pregnancy occurrence after ART initiation among HIV-infected women living in the West Africa region was high. Family planning services tailored to procreation needs should be provided to all HIV-infected women initiating ART and health consequences carefully monitored in this part of the world. PMID:25216079
Full Text Available BACKGROUND: Little is known about the impact of pregnancy on response to highly active antiretroviral therapy (HAART in sub-Saharan Africa. We examined the effect of incident pregnancy after HAART initiation on clinical response to HAART. METHODS: We evaluated a prospective clinical cohort of adult women initiating HAART in Johannesburg, South Africa between 1 April 2004 and 31 March 2011, and followed up until an event, transfer, drop-out, or administrative end of follow-up on 30 September 2011. Women over age 45 and women who were pregnant at HAART initiation were excluded from the study. Main exposure was having experienced pregnancy after HAART initiation; main outcome was death and (separately death or new AIDS event. We calculated adjusted hazard ratios (HRs and 95% confidence limits (CL using marginal structural Cox proportional hazards models. RESULTS: The study included 7,534 women, and 20,813 person-years of follow-up; 918 women had at least one recognized pregnancy during follow-up. For death alone, the weighted (adjusted HR was 0.84 (95% CL 0.44, 1.60. Sensitivity analyses confirmed main results, and results were similar for analysis of death or new AIDS event. Incident pregnancy was associated with a substantially reduced hazard of drop-out (HR = 0.62, 95% CL 0.51, 0.75. CONCLUSIONS: Recognized incident pregnancy after HAART initiation was not associated with increases in hazard of clinical events, but was associated with a decreased hazard of drop-out. High rates of pregnancy after initiation of HAART may point to a need to better integrate family planning services into clinical care for HIV-infected women.
Ana Cecília Montes Gil
Full Text Available CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART. We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6, A (29, B (78 and C (39. Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN, grade 2 (5.0-9.9 times ULN, grade 3 (10.0-15.0 times ULN and grade 4 (> 15.0 times ULN. To assess hepatotoxicity risk factors, odds ratios (OR and adjusted odds ratios (aOR for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152 patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI, 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85 and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25. No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.
Full Text Available Abstract Introduction The global scale-up of antiretroviral therapy (ART for HIV patients has led to concerns regarding inequities in utilization of ART services in resource-limited contexts. In this paper, we describe regional and sex differentials in the distribution of ART among adult HIV patients in Ghana. We highlight the need for interventions to address the gender-based and geographic inequities related to the utilization of ART services in Ghana. Methods We reviewed National AIDS/STIs Control Program’s ART service provision records from January 2003 through December 2010, extracting data on adults aged 15+ who initiated ART in Ghana over a period of eight years. Data on the number of patients on treatment, year of enrollment, sex, and region were obtained and compared. Results The number of HIV patients receiving ART in Ghana increased more than 200-fold from 197 in 2003, to over 45,000 in 2010. However, for each of six continuous years (2005-2010 males comprised approximately one-third of adults newly enrolled on ART. As ART coverage has expanded in Ghana, the proportion of males receiving ART declined from 41.7% in 2004 to 30.1% in 2008 and to 27.6% in 2010. Also, there is disproportionate regional ART utilization across the country. Some regions report ART enrollment lower than their percent share of number of HIV infected persons in the country. Conclusions Attention to the comparatively fewer males initiating ART, as well as disproportionate regional ART utilization is urgently needed. All forms of gender-based inequities in relation to HIV care must be addressed in order for Ghana to realize successful outcomes at the population level. Policy makers in Ghana and elsewhere need to understand how gender-based health inequities in relation to HIV care affect both men and women and begin to design appropriate interventions.
Matthews, Lynn T.; Ashaba, Scholastic; Tsai, Alexander C.; Kanters, Steve; Robak, Magdalena; Psaros, Christina; Kabakyenga, Jerome; Boum, Yap; Haberer, Jessica E.; Martin, Jeffrey N.; Hunt, Peter W.; Bangsberg, David R.
Background: Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown. Methods: We analyzed prospective data from 447 HIV-infected women (18–49 years) initiating ART in rural Uganda (2005–2012). Participants completed blood work and comprehensive questionnaires quarterly. Pregnancy status was assessed by self-report. Analysis time periods were defined as currently pregnant, postpartum (0–12 months post-pregnancy outcome), or non–pregnancy-related. Depression symptom severity was measured using a modified Hopkins Symptom Checklist 15, with scores ranging from 1 to 4. Probable depression was defined as >1.75. Linear regression with generalized estimating equations was used to compare mean depression scores over the 3 periods. Results: At enrollment, median age was 32 years (interquartile range: 27–37), median CD4 count was 160 cells per cubic millimeter (interquartile range: 95–245), and mean depression score was 1.75 (s = 0.58) (39% with probable depression). Over 4.1 median years of follow-up, 104 women experienced 151 pregnancies. Mean depression scores did not differ across the time periods (P = 0.75). Multivariable models yielded similar findings. Increasing time on ART, viral suppression, better physical health, and “never married” were independently associated with lower mean depression scores. Findings were consistent when assessing probable depression. Conclusions: Although the lack of association between depression and perinatal periods is reassuring, high depression prevalence at treatment initiation and continued incidence across pregnancy and non–pregnancy-related periods of follow-up highlight the critical need for mental health services for HIV-infected women to optimize both maternal and perinatal health. PMID:25436816
So-Ngern, Apichot; Montakantikul, Preecha; Manosuthi, Weerawat
We conducted a cross sectional study of the outpatient medical records of 1000 HIV-infected patients receiving antiretroviral therapy (ART) in 2011 to determine the incidence of clinically significant drug interactions (CSDI). The severities of the CSDI were graded following the Micromedex" 2.0 database and the Department of Health and Human Services (DHHS) 2012 HIV treatment guidelines. Three hundred thirty-five patients (34%) had 554 episodes of CSDI. Of which 337 episodes (61%), 163 episodes (29%) and 54 episodes (10%) had grades 2, 3 and 4 severity CSDI, respectively. The CSDI were caused by protease inhibitor (PI)-based drug regimens in 79%, by efavirenz-based regimens in 34% and by nevirapine-based regimens in 10% (p5 items prescribed at a time (OR 1.80; 95% CI: 1.23-2.63), seeing a doctor >4 times a year (OR 1.72; 95% CI: 1.20-2.46), having hypertension (OR 0.60; 95% CI: 0.37-0.98), having a duration of receiving ART of >5 years (OR 0.46; 95% CI: 0.28-0.77) and having a CD4 count of >200 cells/mm3 (OR 0.46; 95%CI: 0.26-0.84). CSDI were common among HIV-infected patients receiving ARV in our outpatient clinic. Patients having a low CD, count, having dyslipidemia, receiving PI-based ART, having a frequent number of visits per year and having a large number of items prescribed at each visit had a greater chance of a CSDI.
Felix F. Widjaja
Full Text Available Background: Highly active antiretroviral therapy (HAART can reduce morbidity and mortality of HIV-infected patients. However, it depends upon adherence to medication. The objective of this study was to examine the adherence to HAART and to evaluate individual patient characteristics i.e. self-efficacy, depression level, and social support and to finally determine HAART adherence in selected regions in Indonesia.Methods: This cross-sectional study was conducted in Jakarta, Malang, Bandung, Makasar and Banda Aceh. The subject of the study was HIV-infected patients who were older than 13 years old and had taken HAART for at least a month. They were recruited consecutively then asked how many pills they had missed during the previous month. Poor adherence can be stated if the percentage of adherence rate is below 95%. HIV treatment adherence self-efficacy scale (HIVASES, Beck Depression Inventory (BDI-II and Interpersonal Support Evaluation List (ISEL was adapted to assess self-efficacy, depression level and social support, respectively.Results: We found that 96% (n=53 of the subjects adhered to HAART. There were no associations between adherence with self-efficacy, depression level, and social support. The main cause of non-adherence in this study was ‘simply forget’.Conclusion: Adherence to HAART was found to be high and not associated with self-efficacy, depression level and social support in some central regions in Indonesia. (Med J Indones 2011; 20:50-5Keywords: adherence, depression, HAART, HIV, self-efficacy, social support
Carlson, Renee Donahue; Rolfes, Melissa A; Birkenkamp, Kate E; Nakasujja, Noeline; Rajasingham, Radha; Meya, David B; Boulware, David R
Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n = 100). Comparison was made with an HIV-infected, non-meningitis cohort (n = 110). Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/μL (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P = 0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores meningitis severity. Paradoxically, persons with sterile CSF cultures after 14 days of induction amphotericin therapy had worse neurocognitive outcomes than those still culture-positive at 14 days (P = 0.002). Cryptococcal meningitis survivors have significant short-term neurocognitive impairment with marked improvement over the first 12 months. Few characteristics related to severity of cryptococcosis, including Cryptococcus burden, were associated with neurocognitive outcome.
Full Text Available The health of people living with HIV (PLWH and the sustained success of antiretroviral therapy (ART programmes depends on PLWH's motivation and ability to self-manage the condition over the long term, including adherence to drugs on a daily basis. PLWH's self-management of HIV and their wellbeing are likely to be interrelated. Successful self-management sustains wellbeing, and wellbeing is likely to motivate continued self-management. Detailed research is lacking on PLWH's self-management processes on ART in resource-limited settings. This paper presents findings from a study of PLWH's self-management and wellbeing in Wakiso District, Uganda. Thirty-eight PLWH (20 women, 18 men were purposefully selected at ART facilities run by the government and by The AIDS Support Organisation in and around Entebbe. Two in-depth interviews were completed with each participant over three or four visits. Many were struggling economically, however the recovery of health and hope on ART had enhanced wellbeing and motivated self-management. The majority were managing their condition well across three broad domains of self-management. First, they had mobilised resources, notably through good relationships with health workers. Advice and counselling had helped them to reconceptualise their condition and situation more positively and see hope for the future, motivating their work to self-manage. Many had also developed a new network of support through contacts they had developed at the ART clinic. Second, they had acquired knowledge and skills to manage their health, a useful framework to manage their condition and to live their life. Third, participants were psychologically adjusting to their condition and their new 'self': they saw HIV as a normal disease, were coping with stigma and had regained self-esteem, and were finding meaning in life. Our study demonstrates the centrality of social relationships and other non-medical aspects of wellbeing for self
Kagee, Ashraf; Nel, Adriaan; Saal, Wylene
Considerable evidence suggests that mood disturbance is common among patients living with HIV and may be an important barrier to anti-retroviral therapy (ART) adherence. Thus the assessment of depressed mood is an important and necessary aspect of the experience of persons living with HIV as it may impact the health status of individuals directly and indirectly. We sought to determine the factor structure of the Beck Depression Inventory (BDI) among a sample of 185 South Africans living with HIV and receiving ART. The mean BDI score was 16.5 (SD 12.15) with a range from 0-50 (out of a possible 63), indicating on average moderate levels of depression. Cronbach's alpha for the total scale was 0.90. Although the four factors had eigenvalues that were technically above 1.0, only three factors could logically be extracted, the combination of which accounted for 47.29% of the variance. These three factors were Cognitive, Affective and Somatic. The results indicate that the BDI-II is a reliable measure of symptoms of depression among persons living with HIV. The factor structure among South Africans receiving ART is similar to that of other samples, although surprisingly, the item assessing appetite disturbance did not load on any factor. The results of the study suggest that the BDI-II is a useful measure among South Africans living with HIV. In the context of the need to rapidly identify depressed mood among persons receiving ART in public health clinics, the BDI may be a useful instrument. We end the paper with certain cautions associated with routine screening.
Full Text Available BACKGROUND: Recent studies suggest certain antiretroviral therapy (ART drugs are associated with increases in cardiovascular disease. PURPOSE: We performed a systematic review and meta-analysis to summarize the available evidence, with the goal of elucidating whether specific ART drugs are associated with an increased risk of myocardial infarction (MI. DATA SOURCES: We searched Medline, Web of Science, the Cochrane Library, and abstract archives from the Conference on Retroviruses and Opportunistic Infections and International AIDS Society up to June 2011 to identify published articles and abstracts. STUDY SELECTION: Eligible studies were comparative and included MI, strokes, or other cardiovascular events as outcomes. DATA EXTRACTION: Eligibility screening, data extraction, and quality assessment were performed independently by two investigators. DATA SYNTHESIS: Random effects methods and Fisher's combined probability test were used to summarize evidence. FINDINGS: Twenty-seven studies met inclusion criteria, with 8 contributing to a formal meta-analysis. Findings based on two observational studies indicated an increase in risk of MI for patients recently exposed (usually defined as within last 6 months to abacavir (RR 1.92, 95% CI 1.51-2.42 and protease inhibitors (PI (RR 2.13, 95% CI 1.06-4.28. Our analysis also suggested an increased risk associated with each additional year of exposure to indinavir (RR 1.11, 95% CI 1.05-1.17 and lopinavir (RR 1.22, 95% CI 1.01-1.47. Our findings of increased cardiovascular risk from abacavir and PIs were in contrast to four published meta-analyses based on secondary analyses of randomized controlled trials, which found no increased risk from cardiovascular disease. CONCLUSION: Although observational studies implicated specific drugs, the evidence is mixed. Further, meta-analyses of randomized trials did not find increased risk from abacavir and PIs. Our findings that implicate specific ARTs in the
Luz, Paula M; Girouard, Michael P; Grinsztejn, Beatriz; Freedberg, Kenneth A; Veloso, Valdilea G; Losina, Elena; Struchiner, Claudio J; MacLean, Rachel L; Parker, Robert A; Paltiel, A David; Walensky, Rochelle P
Objective In Brazil, universal provision of antiretroviral therapy (ART) has been guaranteed free of charge to eligible HIV-positive patients since December 1996. We sought to quantify the survival benefits of ART attributable to this programme. Methods We used a previously published microsimulation model of HIV disease and treatment (CEPAC-International) and data from Brazil to estimate life expectancy increase for HIV-positive patients initiating ART in Brazil. We divided the period of 1997 to 2014 into six eras reflecting increased drug regimen efficacy, regimen availability and era-specific mean CD4 count at ART initiation. Patients were simulated first without ART and then with ART. The 2014-censored and lifetime survival benefits attributable to ART in each era were calculated as the product of the number of patients initiating ART in a given era and the increase in life expectancy attributable to ART in that era. Results In total, we estimated that 598,741 individuals initiated ART. Projected life expectancy increased from 2.7, 3.3, 4.1, 4.9, 5.5 and 7.1 years without ART to 11.0, 17.5, 20.7, 23.0, 25.3, and 27.0 years with ART in Eras 1 through 6, respectively. Of the total projected lifetime survival benefit of 9.3 million life-years, 16% (or 1.5 million life-years) has been realized as of December 2014. Conclusions Provision of ART through a national programme has led to dramatic survival benefits in Brazil, the majority of which are still to be realized. Improvements in initial and subsequent ART regimens and higher CD4 counts at ART initiation have contributed to these increasing benefits. PMID:27029828
Dagli-Hernandez, Carolina; Lucchetta, Rosa Camila; de Nadai, Tales Rubens; Galduróz, José Carlos Fernandez; Mastroianni, Patricia de Carvalho
Objectives To evaluate which indirect method for assessing adherence best reflects highly active antiretroviral therapy (HAART) effectiveness and the factors related to adherence. Method 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. Results 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. Conclusion 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. PMID:27695297
Ai-xia Wang; Tai-sheng Li; Yun-zhen Cao; Yang Han; Zhi-feng Qiu; Jing Xie
Objective To investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy (HAART).Methods From October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients were selected to participate in this opened and randomised study, we purposely chose those with CD4+ T cell counts ＜ 100/mm3. All of them had one or two opportunistic infections and none had been treated with anti-HIV drugs. All patients were tested with CD4+(naive CD4+ T cell defined by CD45RA+ and CD62L+, memory CD4+ T cell defined by CD45RA-), CD8+ T cell,plasma HIV viral load, and clinical manifestations on before, during, and after HAART (5 different regimes) on 1, 3, 6, 9,and 12 months.Results Before HAART mean CD4+ T cell counts were 32 ± 31 (range 2-91)/mm3, and plasma HIV viral load were 5.07±0.85(range 2.04-5.70) log copies/mL. In 1 month's time patients treated with HAART had mean CD4+ and CD8T cell counts increasing rapidly. After 1 month the increasing speed turned to slow down, but HIV viral load decreased predominantly within the first 3 months. The major part of increasing CD4+ T cells were memory CD4+ T cells, as for naive CD4+ T cells increasing low and slow. Clinical symptoms and signs improved, and opportunistic infections reduced. The quality of life will be far much better than before. Each patient was followed for 12 months, and had finished 12 months' HAART.Conclusion This is the first report in China that late stage Chinese AIDS patients after HAART could have their immune reconstitution. The regular pattern is similar to what had been reported in Western countries and also in China. So it is worth to treat late stage Chinese AIDS patients with HAART.
Subiela, José D; Dapena, Elida
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.
Akanbi, Maxwell O; Achenbach, Chad J; Feinglass, Joe; Taiwo, Babafemi; Onu, Adamu; Pho, Mai T; Agbaji, Oche; Kanki, Phyllis; Murphy, Robert L
Our objective was to determine tuberculosis (TB) incidence and evaluate TB risk in adults after one or more years of use of combination antiretroviral therapy (cART) through a retrospective cohort study in Jos, Nigeria. We studied a cohort of HIV-infected adults treated with ART for at least 1 year. Based on immunologic and virologic responses to ART, patients were categorized into four groups: CD4 T cell count ≥350 cells/mm(3) and HIV-1 RNA level ≤400 copies/ml (group 1), CD4 T cell count ≥350 cells/mm(3) and HIV-1 RNA level >400 copies/ml (group 2), CD4 T cell count 400 copies/ml (group 4). Time to incident TB for the four groups was analyzed using the Kaplan-Meier method. Cox regression models were used to evaluate predictors of incident TB. In this cohort of 5,093 HIV-infected adults, of which 68.4% were female, with a mean age 35.1 years (standard deviation 9.1 years), we observed 98 cases of incident TB during 4 years and 3 months of follow-up. The overall TB incidence rate was 8.7 cases/1,000 patient-years of follow-up. Adjusted hazards for incident TB were 2.11 (95% CI 0.97-4.61), 2.05 (95% CI 1.10-3.79), and 3.65 (95% CI 1.15-5.06) in group 2, 3, and 4 patients, respectively, compared to group 1. Tuberculosis incidence in patients on ART is driven by poor immunologic and/or virologic response. Optimization of HIV treatment should be prioritized to reduce the burden of TB in this high-risk population.
Full Text Available South Africa bears the greatest burden of HIV infection globally with the most infected people living in KwaZulu-Natal (KZN. Decentralised medical care for HIV positive patients and antiretroviral therapy (ART delivery to primary health care facilities were proposed nationally to achieve adequate ART coverage for patients in need of treatment. This study described the HIV positive patients who accessed medical care and were initiated on ART at two existing government Primary Health Care (PHC clinics with no added donor support, in Ilembe, KZN. This was an observational descriptive study of ART initiation from 01 April 2008 to 30 April 2009. Data were collected from clinical records kept on site. HIV Testing and the pre-ART programmes which consisted of medical care prior to ART initiation are briefly described. Socio-economic, demographic and clinical characteristics of patients who were initiated on ART were sampled and described. A minority (2.95% of the study population tested for HIV of which 36.0%tested positive. Majority (60.0% of patients who joined the pre-ART programme care did not return. The ART sample consisted of 375 patients of whom 65.0%were women, 85.9%were unmarried, 61.6%were unemployed and 50.4%had a secondary level of education. Tuberculosis (TB prevalence and incidence at ART initiation were 22.1%and 14.7%respectively. The prevalence of Syphilis and Hepatitis B co-infections were 13.1%and 8.6 %respectively. Two thirds of female patients (66.4% received a Pap smear result of which the majority (62.3% were abnormal. Uptake for HIV testing followed by relevant CD4 testing was poor. High TB, Hepatitis B and Syphilis co-infection was noted amongst patients initiated on ART. Cervical cancer screening must be intensified. Although ART initiation with no added external resources was successful, record keeping was suboptimal.
Full Text Available OBJECTIVE: To evaluate the prevalence of and the associated factors for metabolic syndrome (MS among Latin American HIV-infected patients receiving antiretroviral therapy (ART using baseline data from the RAPID II study. METHODS: A longitudinal study to evaluate the metabolic profile, cardiovascular disease (CVD risk and associated treatment practices to reduce this risk has been conducted in seven Latin American countries (the RAPID II study. Adult HIV patients with at least six months of RT were enrolled. MS was defined following ATP-III criteria. Demographic and anthropometric data, serum biochemical and clinical parameters were compared in patients with and without MS using bivariate and multivariate analysis. RESULTS: A total of 4,010 patients were enrolled, 2,963 (74% were males. Mean age (SD was 41.9 (10.0 years. The prevalence of MS was 20.2%. Females had higher prevalence of MS than males (22.7% vs. 19.4%, p = 0.02. MS was driven by high triglycerides, low HDL-cholesterol and high blood pressure (HBP. Patients with MS had higher 10year CVD risk: 22.2% vs. 7.4%, p < 0.001. Age (OR: 1.05 per year, female gender (OR: 1.29, family history of CVD (OR: 1.28, CD4 cell count (OR: 1.09 per 100 cell increase, and protease inhibitor based-ART (OR: 1.33 correlated with MS in the multivariate analysis. CONCLUSIONS: Prevalence of MS in this setting was similar to that reported from developed countries. MS was driven by high triglycerides, low-HDL and HBP, and it was associated with higher risk of CVD. Traditional risk factors, female gender, immune reconstitution, and protease inhibitor based-ART correlated with MS.
Katherine T Steele
Full Text Available BACKGROUND: Adverse outcomes occurring early after antiretroviral therapy (ART initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana. METHODS: This prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence <0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%. RESULTS: Suboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1-4.8 and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4-4.7. However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively. CONCLUSIONS: Suboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on
Jeffrey K Hom
Full Text Available OBJECTIVE: 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. DESIGN: Cross-sectional cohort study. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Alfred C Banda
Full Text Available BACKGROUND: HIV/AIDS affects all sectors of the population and the defence forces are not exempt. A national survey was conducted in all public and private sectors in Malawi that provide antiretroviral therapy (ART to determine the uptake of ART by army personnel, their outcomes while on treatment, and the impact of ART on mortality in the Malawi Defence Force. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort analysis was carried out, collecting data on access and retention on treatment from all 103 public and 38 private sector ART clinics in Malawi, using standardised patient master cards and clinic registers. Observations were censored on December 31(st 2006. Independent data on mortality trends in army personnel from all causes between 2002 and 2006 were available from army records. By December 31(st 2006, there were 85,168 patients ever started on ART in both public and private sectors, of whom 547 (0.7% were army personnel. Of these, 22% started ART in WHO clinical stage 1 or 2 with a CD4-lymphocyte count of
Lorna A Renner
Full Text Available Introduction: There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART containing zidovudine (ZDV recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. Methods: Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ≥18 months followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7g/dL per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. Results: As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was−2.7; and 1772 (60.4% had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p≤0.01: the prevalence of severe anaemia was 3.0% (n=38 in the ZDV group versus 10.2% (n=89 in those without (p<0. 01. Over the first-line follow-up, 58.9% of the children had ≥1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45. Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p≤0.01. Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ≤−3 was a strong predictor associated with a 5.59 times risk of
Gülşen Ozkaya Sahin
Full Text Available Neutralizing antibodies (NAb able to react to heterologous viruses are generated during natural HIV-1 infection in some individuals. Further knowledge is required in order to understand the factors contributing to induction of cross-reactive NAb responses. Here a well-established model of experimental pathogenic infection in cynomolgus macaques, which reproduces long-lasting HIV-1 infection, was used to study the NAb response as well as the viral evolution of the highly neutralization-resistant SIVmac239. Twelve animals were infected intravenously with SIVmac239. Antiretroviral therapy (ART was initiated ten days post-inoculation and administered daily for four months. Viral load, CD4(+ T-cell counts, total IgG levels, and breadth as well as strength of NAb in plasma were compared simultaneously over 14 months. In addition, envs from plasma samples were sequenced at three time points in all animals in order to assess viral evolution. We report here that seven of the 12 animals controlled viremia to below 10(4 copies/ml of plasma after discontinuation of ART and that this control was associated with a low level of evolutionary divergence. Macaques that controlled viral load developed broader NAb responses early on. Furthermore, escape mutations, such as V67M and R751G, were identified in virus sequenced from all animals with uncontrolled viremia. Bayesian estimation of ancestral population genetic diversity (PGD showed an increase in this value in non-controlling or transient-controlling animals during the first 5.5 months of infection, in contrast to virus-controlling animals. Similarly, non- or transient controllers displayed more positively-selected amino-acid substitutions. An early increase in PGD, resulting in the generation of positively-selected amino-acid substitutions, greater divergence and relative high viral load after ART withdrawal, may have contributed to the generation of potent NAb in several animals after SIVmac239 infection
Madi, Deepak; Gupta, Parul; Bhaskaran, Unnikrishnan; Ramapuram, John T.; Rao, Satish; Mahalingam, Soundarya
Introduction As patients with HIV live longer due to Combination Anti-Retroviral Therapy (cART) serostatus disclosure becomes an important issue. Disclosure can have both positive and negative outcomes. Disclosure of HIV status has been associated with better adherence to medication and reduction in levels of psychological distress. Stigma and disruption of family relationships are barriers for disclosure. Most studies regarding disclosure status have been conducted in West. There are many cultural differences in Indian society when compared to west. There is a dearth of research in the field of disclosure of HIV infection in India. Aim To determine the prevalence of HIV status disclosure among people living with HIV (PLHIV) in South India. Materials and Methods This descriptive cross-sectional study was done in the hospital attached to Kasturba Medical College (KMC), Mangalore, India from May–June 2013. PLHIV of age more than 18 years were included. During the study period 111 consecutive patients who consented for the study were enrolled. Statistical Analysis Data was collected using a pre-tested interviewer administered semi structured questionnaire. Data collected was analysed using SPSS Version 11.5 statistical software. Descriptive statistics were done and the results are presented as proportions and mean. Results The mean age of the study population was 44.86 ± 10.8 years. Majority of the study subjects were men 76 (68.4%). Out of 111 study subjects, 102 (91.9%) had disclosed their HIV status to at least one person while 9 (8.1%) had not disclosed their HIV status to anyone. Disclosure on doctor’s advice was the main reason for 56 (54.9%) participants to disclose their HIV status. The main reason for non-disclosure was fear of shame in family. Conclusion Disclosure rate was high in our study in the era of cART. Society must stop discriminating against PLHIV so that they can disclose their serostatus and gain access to care and treatment services without
Tshifhiwa V. Ndou
Full Text Available Background: Patients’ experiences are a reflection of what has happened during the care process and, therefore, provide information about the performance of health care professional workers. They refer to the process of care provision at the antiretroviral therapy (ART sites.Aim and setting: This article explored the perceptions of HIV-positive patients of care received at the Gateway Clinic of the regional hospital that provides antiretroviral treatment in the Vhembe district.Methods: A qualitative, explorative and descriptive design was used. A non-probability, convenient sampling method was used to select 20 HIV-positive patients who were above 18 years of age. In-depth individual interviews were used to collect data. Data were analysed through Tech’s open coding method.Results: One theme and two sub-themes emerged, namely positive experiences related to the environment and attitudes of health professionals, and negative experiences concerning the practices by health care providers.Conclusion: Patients’ perceptions of quality of, and satisfaction with, health care may affect health outcomes. Recommendations are made to consider, practice and strengthen the protocols, the standard operating procedures and the principles of infection control in the health facilities.Keywords: Human Immunodeficiecy Virus, Antiretroviral Treatment, HIV positive, Limpopo
Full Text Available Objective: To evaluate whether or not highly active antiretroviral therapy is associated with carotid artery stiffness in human immunodeficiency virus-positive patients in Henan Province, China. Method: Fifty human immunodeficiency virus-positive patients with at least a 5-year history of highly active antiretroviral therapy use and 50 human immunodeficiency virus-positive patients without a history of highly active antiretroviral therapy use were enrolled in this study. Carotid artery intima-media thickness and stiffness were determined by quantitative inter-media thickness and quantitative artery stiffness, respectively. Results: No statistically significant difference in carotid artery intima-media thickness and stiffness was observed between groups. A significant association between human immunodeficiency virus infection time and carotid artery stiffness was observed, but no significant association between human immunodeficiency virus infection time and intima-media thickness was found. No significant association between intima-media thickness, stiffness, and CD4+ and CD8+ T-cell counts were observed. Conclusion: The first-line highly active antiretroviral therapy currently used in China is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients with good highly active antiretroviral therapy compliance. Human immunodeficiency virus may play a role in the development of atherosclerosis.
Full Text Available Background: There are limited data on the failure of second-line antiretroviral therapy (ART and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care. Objective: To describe the experiences and programmatic challenges during management of suspected second-line ART failure and third-line ART therapy for patients living with HIV, including the use of HIV viral load (VL testing. Design: This was a retrospective, observational cohort study of patients with suspected second-line ART treatment failure, who were followed for at least 12 months between January 2011 and March 2014. Results: A total of 47 patients with suspected second-line failure met the inclusion criteria during the study period. Twenty-nine of them (62% responded to enhanced adherence support, had a subsequent undetectable VL after a median duration of 3 months and remained on second-line ART. The other 18 patients had to be initiated on a third-line ART regimen, which consisted of darunavir–ritonavir, raltegravir, and one or more appropriate nucleoside or nucleotide reverse transcriptase inhibitors, based on the results of HIV genotype testing. Of the 13 patients for whom follow-up VL results were available, 11 achieved virological suppression after a median duration of 3 months on third-line ART (interquartile range: 2.5–3.0. No serious treatment-related adverse events were recorded. Conclusions: With intensive counselling and adherence support in those suspected of failing second-line ART, unnecessary switching to more expensive third-line ART can be averted in the majority of cases. However, there is an increasing need for access to third-line ART medications such as darunavir and raltegravir, for which national ART programmes should be prepared. The cost of such medications and inadequate access to VL
Full Text Available BACKGROUND: Combination antiretroviral treatment (cART has been very successful, especially among selected patients in clinical trials. The aim of this study was to describe outcomes of cART on the population level in a large national cohort. METHODS: Characteristics of participants of the Swiss HIV Cohort Study on stable cART at two semiannual visits in 2007 were analyzed with respect to era of treatment initiation, number of previous virologically failed regimens and self reported adherence. Starting ART in the mono/dual era before HIV-1 RNA assays became available was counted as one failed regimen. Logistic regression was used to identify risk factors for virological failure between the two consecutive visits. RESULTS: Of 4541 patients 31.2% and 68.8% had initiated therapy in the mono/dual and cART era, respectively, and been on treatment for a median of 11.7 vs. 5.7 years. At visit 1 in 2007, the mean number of previous failed regimens was 3.2 vs. 0.5 and the viral load was undetectable (4 previous failures compared to 1 were 0.9 (95% CI 0.4-1.7, 0.8 (0.4-1.6, 1.6 (0.8-3.2, 3.3 (1.7-6.6 respectively, and 2.3 (1.1-4.8 for >2 missed cART doses during the last month, compared to perfect adherence. From the cART era, odds ratios with a history of 1, 2 and >2 previous failures compared to none were 1.8 (95% CI 1.3-2.5, 2.8 (1.7-4.5 and 7.8 (4.5-13.5, respectively, and 2.8 (1.6-4.8 for >2 missed cART doses during the last month, compared to perfect adherence. CONCLUSIONS: A higher number of previous virologically failed regimens, and imperfect adherence to therapy were independent predictors of imminent virological failure.
Baba Maiyaki Musa
Full Text Available Human immunodeficiency virus (HIV contributes significantly to morbidity and mortality in sub-Saharan Africa, with Nigeria having the third highest burden of HIV infection globally; efforts are made to increases access to HIV/AIDS care and treatment. This has currently reached rural areas with limited manpower and laboratory evaluation capacity. This review is necessitated by the paucity of interim report on treatment profile in Nigerian rural areas. We report on the immunological profile of patients on antiretroviral therapy (ART in Otukpo General Hospital, a rural Nigerian hospital. This is a retrospective cohort study of patients receiving ART treatment and care, on April 2009, when 2347 patients were under ART therapy. Out of these, 96 patients were selected by simple random sampling from hospital register, with their data abstracted from standardized Ministry of Health registers and facility documents kept at the hospital, and analyzed for descriptive and biometric measures. Ninty-six patients (29% males with a median age of 35 years, median baseline CD4 lymphocyte count 221 cells/mL, median one year CD4 lymphocyte count of 356 cells/mL and median one year CD4 lymphocyte increment of 124 cells/mL were studied. There is no statistically significant difference in baseline CD4 lymphocyte count when data is disaggregated by type of drug regimen (AZT, D4T and TDF. Fourty-four percent, 23% and 33% of patients were on TDF, D4T & AZT based regimen, respectively (P=0.66. Increment of >100 cells/mL was seen in 64.58% of the reviewed patients. There was a higher CD4 lymphocyte count increment in patients on TDF & D4T compared with those in AZT based regimens (ANOVA; P<0.0003. Multivariate linear regression model showed one year CD4 lymphocyte count, one year increment in CD4 lymphocyte count, WBC count, and absolute neutrophil count to be significant correlates of baseline CD4 lymphocyte count (P<0.0001. Equally, multivariate logistic regression found
Mastroianni Claudio M
Full Text Available Abstract Introduction The availability of raltegravir plus atazanavir provides an alternative antiretroviral strategy that may be equally efficacious and less toxic than those currently recommended in HIV treatment guidelines. In fact, this new combination antiretroviral therapy attracts the attention of the scientific community because both drugs have a good safety profile coupled with potent antiviral activity, and their combined use would avert nucleoside- and ritonavir-related toxicities. Case presentation We describe the case of a 47-year-old, Caucasian woman treated for HIV-1 infection who developed Buffalo Hump during antiretroviral therapy, including raltegravir and unboosted atazanavir. Clinical evaluation and an ultrasonography scan of the cervical region showed a new progressive increase of lipohypertrophy and the results of DEXA confirmed these data. In our patient the worsening of the Buffalo Hump cannot be attributed to hypercortisolism; insulin-resistance, diabetes, dyslipidemia, hyperlactatemia and metabolic syndrome were not present. Moreover, she was not in therapy with antiretroviral drugs that are described as the cause of Buffalo Hump; on the other hand she developed this side effect three months after the switch of the antiretroviral therapy to raltegravir plus unboosted atazanavir. Conclusion Current data indicate that the etiology of HIV-associated Buffalo Hump remains elusive but is likely multifactorial; a possible contributing cause, but not the main cause, could be exposure to antiretroviral drugs. To the best of our knowledge, this is the first report on development of Buffalo Hump in the course of antiretroviral therapy, including the use of these drugs. On the basis of our data we can formulate the hypothesis of a pharmacological pathogenesis that underlies the development of this case of Buffalo Hump in the absence of other risk factors.
Allen, Patrick B
BACKGROUND: Infliximab is usually administered by two monthly intravenous (iv) infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc) injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn\\'s Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration.The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD) patients for two currently available anti-TNF agents and the reasons for their choices. METHODS: An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK) between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous) were available, which drug route of administration would they choose. RESULTS: One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response). The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent) preferred infliximab and 19 patients (24 percent) preferred adalimumab (p = 0.07). Twenty-six patients (33 percent) did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv) was: "I do not like the idea of self-injecting," (67 percent). For those patients who preferred adalimumab (sc) the commonest reason cited was: "I prefer the convenience of injecting at home," (79 percent). Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab) six patients stated that they would prefer infliximab if given the choice
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.
Kelly, A; Mek, A; Frankland, A; Akunai, F; Kepa, B; Kupul, M; Nosi, S; Cangah, B; Walizopa, L; Pirpir, L; Emori, R; Worth, H; Siba, P M; Man, W Y N
The relationship between HIV (human immunodeficiency virus), food security and nutrition has become increasingly important to practitioners, policy makers and people living with HIV. In this paper we describe for the first time the connection between HIV and antiretroviral therapies, the extent of nutritional counselling for HIV-positive people and food security in Papua New Guinea (PNG). A total of 374 HIV-positive people who were over the age of 16 and who had been on antiretroviral therapy (ART) for more than two weeks were recruited from six provinces, using a non-probability, convenience sampling methodology. A subsample of 36 participants also completed an in-depth qualitative interview. Participants received nutritional advice when beginning ART which focused on three main domains, of which the first two were the most frequently mentioned: what foods to avoid; what foods to eat; and how frequently to eat. 72% of the sample reported that they had experienced an increase in their appetite. Of those who reported that their appetite had increased on ART 33% reported that they did not have enough food to satisfy hunger. People who lived in the capital city, Port Moresby, within the Southern Region of PNG, had significantly more difficulty with food security than those who lived in other regions of the country. Not having enough food was the third most commonly recorded reason for non-adherence to ART. Responses to the HIV epidemic in Papua New Guinea must also begin to address the phenomenon of food insecurity for people with HIV, in particular those who are receiving antiretroviral therapies and who live in the urban areas.
CHAN Chi-wai; CHENG Lai-sim; CHAN Wai-kit; WONG Ka-hing
Background Morbidity and mortality of advanced human immunodeficiency virus infection (HIV) have declined in Western industrialized countries since the availability of highly active antiretroviral therapy (HAART). It is unclear if this has also happened in Hong Kong.Methods We studied a retrospective cohort of patients with advanced HIV disease in Hong Kong, China. First, the mortality of advanced HIV disease per year was calculated for the decade 1993 to 2002, both annually and according to patient observation before and after 1997. Second, the event rates were estimated for the clinical end points of acquired immune deficiency syndrome (AIDS) and death. Univariate and multivariate analyses were then performed to identify associated factors. Results The crude mortality of advanced HIV disease declined from 10.8-30.4 per 100 patients during 1993-1996, to 0.8-6.9 per 100 patients during 1997-2002. A rate ratio of 4.04 (95% CI, 2.52-6.47) was evident for those observed in 1993-1996, compared to those in 1997-2002. In a multivariate analysis where calendar period was adjusted, use of highly active antiretroviral therapy was associated with rate ratios of 0.13 (95% CI, 0.05-0.33) for death after AIDS, 0.08 (95% CI, 0.04-0.19) for AIDS after a CD4 cell count <200/μl, and 0.21 (95% CI, 0.07-0.67) for death after CD4 cell count <200/μl. In the same analysis, calendar period ceased to be a significant factor after adjustment for use of HAART.Conclusions The mortality and morbidity of advanced human immunodeficiency virus disease have declined in Hong Kong. This improved prognosis was attributable to the use of highly active antiretroviral therapy.
Brener, Michael; Ketlogetswe, Kerunne; Budoff, Matthew; Jacobson, Lisa P.; Li, Xiuhong; Rezaeian, Panteha; Razipour, Aryabod; Palella, Frank J; Kingsley, Lawrence; Witt, Mallory D; George, Richard T; Post, Wendy S
Objective Cytokines released by epicardial fat are implicated in the pathogenesis of atherosclerosis. HIV infection and anti-retroviral therapy have been associated with changes in body fat distribution and coronary artery disease. We sought to determine if HIV infection is associated with greater epicardial fat and if epicardial fat is associated with subclinical coronary atherosclerosis. Design We studied 579 HIV-infected and 353 HIV-uninfected men age 40 to 70 years with non-contrast computed tomography (CT) to measure epicardial adipose tissue volume (EAT) and coronary artery calcium (CAC). Total plaque score (TPS), and plaque subtypes (non-calcified, calcified and mixed) were measured by coronary CT angiography in 706 men. Methods We evaluated the association between EAT and HIV serostatus, and the association of EAT with subclinical atherosclerosis, adjusting for age, race and serostatus and with additional cardiovascular (CV) risk factors and tested for modifying effects of HIV serostatus. Results HIV-infected men had greater EAT than HIV-uninfected men (p=0.001). EAT was positively associated with duration of antiretroviral therapy (p=0.02), specifically AZT (p<0.05). EAT was associated with presence of any coronary artery plaque (p=0.006) and non-calcified plaque (p=0.001), adjusting for age, race, serostatus and CV risk factors. Among men with CAC, EAT was associated with CAC extent (p=0.006). HIV serostatus did not modify associations between EAT and either CAC extent or presence of plaque. Conclusions Greater epicardial fat volume in HIV-infected men and its association with coronary plaque and antiretroviral therapy duration suggest potential mechanisms that might lead to increased risk for cardiovascular disease in HIV. PMID:24809732
Full Text Available Abstract Background Women infected with human immunodeficiency virus (HIV may be at higher risk of developing cervical cancer than non infected women. In a pilot study, we assessed the relationships among cervical cytology abnormalities associated to Human Papillomavirus (HPV, HIV infection and Highly Active Antiretroviral Therapy (HAART on the development of Squamous Intraepithelial lesions (SILs. Out of the 70 HIV infected women from Douala -Cameroon (Central Africa that we included in the study, half (35 were under HAART. After obtaining information related to their lifestyle and sexual behaviour, cervicovaginal samples for Pap smears and venous blood for CD4 count were collected and further divided into two groups based upon the presence or absence of cervical cytology abnormalities i.e. those with normal cervical cytology and those with low and high Squamous Intraepithelial lesions (LSIL, HSIL. Results Assessment was done according to current antiretroviral regimens available nationwide and CD4 count. It was revealed that 44.3% of HIV-infected women had normal cytology. The overall prevalence of LSIL and HSIL associated to HPV in the studied groups was 24.3% (17/70 and 31.4% (22/70 respectively. Among the 22 HSIL-positive women, 63.6% (14/22 were not on antiretroviral therapy, while 36.4% (8/22 were under HAART. HIV infected women under HAART with positive HSIL, showed a median CD4+ T cell count of 253.7 +/- 31.7 higher than those without therapy (164.7 +/- 26.1. The incidence of HSIL related to HPV infection within the study group independently of HAART initiation was high. Conclusion These results suggest the need for extension and expansion of the current study in order to evaluate the incidence of HPV infection and cervical cancer among HIV-infected and non HIV- infected women in Cameroon.
Full Text Available Abstract Background For antiretroviral therapy (ART naive human immunodeficiency virus (HIV infected adults suffering from tuberculosis (TB, there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART after starting antituberculosis treatment (ATT, in order to minimize mortality, HIV disease progression, and adverse events. Methods In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. Findings A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART and 62 after 8-12 weeks (delayed ART of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045. Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05. Rates of adverse events were similar. Interpretation Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. Trial registration CTRI/2011/12/002260
Donoghoe, Martin C; Bollerup, Annemarie R; Lazarus, Jeff
Providing equitable access to highly active antiretroviral treatment (HAART) to injecting drug users (IDUs) is both feasible and desirable. Given the evidence that IDUs can adhere to HAART as well as non-IDUs and the imperative to provide universal and equitable access to HIV/AIDS treatment for all...... the injecting status of those initiating HAART and the use of opioid substitution therapy among HAART patients, and discuss how HAART might be better delivered to injecting drug users. Our data adds to the evidence that IDUs in Europe have poor and inequitable access to HAART, with only a relatively small...
Venkat, Arvind; Piontkowsky, David M; Cooney, Robert R; Srivastava, Adarsh K; Suares, Gregory A; Heidelberger, Cory P
More than 1 million individuals in the United States are HIV positive, with greater than 40,000 new patients being diagnosed per year. With the advent of highly active antiretroviral therapy (HAART), HIV-infected patients in the United States are living longer. HIV-infected patients receiving HAART now more commonly have noninfectious and nonopportunistic complications of their disease. This review article will discuss the assessment and treatment of HIV-positive patients in the era of HAART, with an emphasis on the noninfectious and changing infectious complications that require emergency care.
Nguyen, Nam Thi Thu; Rasch, Vibeke; Bygbjerg, Ib Christian;
There is a need to understand how social and cultural expectations of being a woman shape the challenges women face when trying to access antiretroviral therapy (ART) and to continue the treatment over time. Based on a 7-month prospective study of 15 HIV-infected women, the particular challenges...... met by these women in northern Vietnam are discussed in this article. We argued that, by taking ART to maintain their health and to fulfill their responsibilities to family and community, the women managed to reclaim the "moral worth" they had lost as a result of having HIV infection. At the same time...
Elise Arrivé; Fatoumata Dicko; Hind Amghar; Addi Edmond Aka; Hélène Dior; Belinda Bouah; Mariam Traoré; Patricia Ogbo; Hortense Aka Dago-Akribi; Tanoh Kassi F Eboua; Kouadio Kouakou; Haby Signate Sy; Ahmadou Alioum; François Dabis; Didier Koumavi Ekouévi
OBJECTIVE: We assessed the effect of HIV status disclosure on retention in care from initiation of antiretroviral therapy (ART) among HIV-infected children aged 10 years or more in Cote d'Ivoire, Mali and Sénégal. METHODS: Multi-centre cohort study within five paediatric clinics participating in the IeDEA West Africa collaboration. HIV-infected patients were included in this study if they met the following inclusion criteria: aged 10-21 years while on ART; having initiated ART ≥ 200 days befo...
Salimo, Anna T.; Ledwaba, Johanna; Coovadia, Ashraf; Abrams, Elaine J.; Technau, Karl-Günter; Kuhn, Louise; Morris, Lynn; Hunt, Gillian M.
Paired plasma and dried blood spots (DBS) from 232 South African HIV-infected children initiating antiretroviral therapy (ART) were genotyped for drug resistance mutations, most of who had prior exposure to ART for prevention-of-mother-to-child-transmission. Non-nucleoside reverse transcriptase inhibitor mutations were most commonly detected in both specimen types, particularly Y181C/I and K103N/S. Resistance interpretation concordance was achieved in 97% of pairs with 7 children having mutations detected in DBS only. These results validate the preferential use of DBS specimens for HIVDR genotyping in this patient group. PMID:26192603
Data on the effectiveness of second-line combination antiretroviral therapy (cART) are limited. We evaluated virologic outcomes of second cART in a multicenter cohort collaboration. The study population initiated first and second modern cART between 1996 and 2010. The second cART required a switch in at least the anchor agent of first cART. We evaluated time to virologic failure of second cART and factors associated with greater risk of failure using multivariable Cox proportional hazards mod...
McNairy, Margaret L; Deryabina, Anna; Hoos, David; El-Sadr, Wafaa M
Interest in the use of antiretroviral therapy (ART) for prevention stems from mounting evidence from research studies demonstrating that ART is associated with a decrease in sexual HIV transmission among serodiscordant couples and, perhaps, in other populations at risk. There is paucity of data on the efficacy of ART for prevention in key populations, including persons who inject drugs (PWID). In this paper, we examine the current status of HIV services for PWID in Central Asia, the use of ART by this population and explore ART for prevention for PWID in this context. We also discuss research and implementation questions with relevance to such a strategy in the region.
Rasmussen, Dlama; da Silva Te, David; Rodkjær, Lotte Ørneborg;
Adherence is a decisive factor in achieving a successful response to antiretroviral therapy (ART) for HIV infection. No previous studies have been conducted regarding HIV treatment adherence in Guinea-Bissau. In this study we assessed barriers and facilitators to patient ART adherence. Semi......-structured interviews were conducted with 20 adult, HIV infected individuals receiving ART at a HIV treatment centre in Bissau, Guinea-Bissau. The grounded theory method was used to gather and analyse data. Results indicated that HIV-related knowledge was a determining factor for optimal adherence. The facilitators...
Srinivasa Rao Nanyam; Ravala Siddeswari; Budithi Sudarsi; Barla Suryanarayana; Challagali Prabhu Kumar; Thatikala Abhilash
The present study aims serial four year assessment of CD4 cell response after initiation of anti-retroviral therapy (ART) in patients with HIV/AIDS attending Osmania General Hospital, Hyderabad. It was a retrospective hospital based observational study. We included 110 HIV/AIDS who were on ART. Data was collected over a period of 04 years from 2005 to 2008 in the ART Centre, Upgraded Department of General Medicine, Osmania General Hospital. Data regarding CD4 cell count over 4 years was asse...
Casetti, R; De Simone, G; Sacchi, A; Bordoni, V; Viola, D; Rinaldi, A; Agrati, C; Gioia, C; Martini, F
Antiretroviral therapy allows a restoration of immune cell homeostasis associated with a normal immune competence. Our goal was to analyze the modulation of polyfunctional HIV-specific CD8+ T-cell responses during antiretroviral therapy. HIV-infected individuals were divided into four groups according to CD4+ cell count and viral load at the moment of recruitment. Whole blood was stimulated with a pool of CD8-specific HIV-antigens to assess cytokine/chemokine production and cytotoxicity activity by using flow cytometry. The groups show different modulation in HIV-specific CD8+ T-cell responses. In particular, immunological failure showed different distributions of polyfunctional HIVspecific CD8+ responses, mainly due to an increase of cells producing CD107alpha/IFNgamma/IL-2/MIP-1beta. Our results indicate that this particular 4+ functional subset is a possible correlate of immunological failure. Considering the complexity of interactions among HAART, immune system and HIV, work is in progress to find correlates of therapy efficacy.
Full Text Available Abstract Background HIV-infected patients on long-term highly active antiretroviral therapy often present peculiar patterns of fat redistribution, referred to as lipodystrophy. In spite of recent investigations, it is not known whether and to what extent the main features of lipodystrophy – that is lipoatrophy of peripheral fat at face, limbs and buttocks, as well as fat accumulation at breasts, abdomen and the dorso-cervical region – can be reversible once clinically manifest. Case presentation A 35 year old Caucasian HIV infected female developed severe diffuse lipodystrophy while on highly active antiretroviral therapy. A remarkable increase of breast size, fat accumulation at waist, and a fat pad on her lumbar spine were paralleled by progressive and disfiguring lipoatrophy of face, limbs and buttocks. The patient decided to interrupt her therapy after 20 months, with a stably suppressed viremia and a CD4 lymphocyte count >500/μL. She could carry on a safe treatment interruption for longer than 4 years. Most sites of fat accumulation switched to nearly normal appearance, whereas lipoatrophy was substantially unchanged at all affected sites. Conclusion our observation provides pictorial evidence that lipoatrophy may not be reversible even under ideal circumstances. Therefore, strategies to prevent lipoatrophy should be considered when defining therapeutic regimens for HIV infected patients, especially those at high risk.
Bracher, Linda; Valerius, Niels Henrik; Rosenfeldt, Vibeke;
The long-term impact of highly active antiretroviral therapy (HAART) on HIV-1 infected children is not well known. The Danish Paediatric HIV Cohort Study includes all patients HIV-1 infection in Denmark. We report the complete follow-up from 1996 to 2005 of 49 perinatally infected...... characteristics were median CD4 percentage 14% and HIV-RNA viral load 4.9 log(10). Within the first 12 weeks of therapy approximately 60% achieved HIV-RNA viral load ... children treated with HAART. Initial HAART included 2 nucleoside reverse-transcriptase inhibitors in combination with either a protease inhibitor (n =38) or a non-nucleoside reverse-transcriptase inhibitor (n =12). 19 (39%) patients were previously treated with mono- or dual therapy. Baseline...
Full Text Available Importance: With increasing number of persons living with Human Immunodeficiency Virus (HIV in major cities there is a need to have a comprehensive strategy to reduce the number of drop outs from the anti-retroviral (ART therapy. This can be done effectively only when we study the reasons why patients are lost to follow up. This study has brought to light novel causes of non-adherence to ART, like migration, discordance and resort to alternative therapies. DESIGN: This is a qualitative study conducted at ART Center, Byramjee Jeejeebhoy Medical College (BJMC and Sassoon General Hospital (SGH, Pune, a tertiary referral center in India. We included all those patients who were initiated antiretroviral therapy and lost to follow-up (LFU any time during the entire month after three months during which the appointment was scheduled. All these patients were interviewed during restart of ART, in ART center, BJMC and SGH. MAIN OUTCOMES AND MEASURES: All socio-demographic and clinical factors associated with antiretroviral therapy adherence. RESULTS: Out of a total 51patients lost to follow-up, patients above thirty five years of age and male sex were associated with a higher chance of being lost to LFU. Illiteracy rate was high in age group above 35 years (64.1% and in females. Male drivers were lost to follow-up at a greater extent [14(24.75%]. Out of 24(47.06% married patients, 12(50% male patients were sero-discordant. The chance of defaulting from therapy was high in the first three months and one year later from the initiation of therapy. Migration led to drop out of 13(25.49% patients. Other important factors leading to loss to follow up were: death in family, side effects of drugs and family disturbance. Alcoholism was the cause in 23(45.10% male patients. CONCLUSION AND RELEVANCE: Migration, illiteracy, alcoholism, discordant couples, death in family, low socio-economic status, resorting to alternative therapies were the prominent factors which
Maria Rosa Ceccato Colombrini
que contribuyen a la construcción y ejercicio de la ciudadanía.The non-adherence to the highly active antiretroviral therapy (HAART is considered one of the most threatening risks for the effectiveness of the treatment of the person with HIV/AIDS on the individual plan and for the resistance-virus dissemination on the collective plan. The objective of this study was to analyze, through a literature review, the predicting factors of non-adherence to the HAART, as well as to assemble and relate them to the person in treatment, the disease, the treatment and the health and social support service. The literature points to the need for studies that evaluate social-cultural aspects, beliefs, quality of the service and the relationship of the patient with the multi-professional team, as well as others related to race and to the side effects of the antiretroviral agents. These studies aim at favoring the creation of strategies that im-prove the adherence of patients to the HAART, contributing at the same time for the development and the exercise of citizenship.
Bannister, Wendy P; Cozzi-Lepri, Alessandro; Clotet, Bonaventura;
OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients...... with detection of TDR, with virological (viral loador=50% increase) to combination antiretroviral therapy at months 6-12. RESULTS: The overall prevalence of TDR was 11.4%, which was stable over 1996-2004. There were no significant differences in virological suppression......-naive patients was found to be in line with other European studies. No significant differences were found in virological and CD4 count response after initiation of first-line combination antiretroviral therapy between resistant and susceptible patients, possibly due to the small number of patients...
Vesterbacka, Jan; Nowak, Piotr; Barqasho, Babilonia; Abdurahman, Samir; Nyström, Jessica; Nilsson, Staffan; Funaoka, Hiroyuki; Kanda, Tatsuo; Andersson, Lars-Magnus; Gisslèn, Magnus; Sönnerborg, Anders
Objectives We investigated whether there are differences in the effects on microbial translocation (MT) and enterocyte damage by different antiretroviral therapy (ART) regimens after 1.5 years and whether antibiotic use has impact on MT. In a randomized clinical trial (NCT01445223) on first line ART, patients started either lopinavir/r (LPV/r) (n = 34) or efavirenz (EFV) containing ART (n = 37). Lipopolysaccharide (LPS), sCD14, anti-flagellin antibodies and intestinal fatty acid binding protein (I-FABP) levels were determined in plasma at baseline (BL) and week 72 (w72). Results The levels of LPS and sCD14 were reduced from BL to w72 (157.5 pg/ml vs. 140.0 pg/ml, p = 0.0003; 3.13 ug/ml vs. 2.85 ug/ml, p = 0.005, respectively). The levels of anti-flagellin antibodies had decreased at w72 (0.35 vs 0.31 [OD]; p<0.0004), although significantly only in the LPV/r arm. I-FABP levels increased at w72 (2.26 ng/ml vs 3.13 ng/ml; p<0.0001), although significantly in EFV treated patients only. Patients given antibiotics at BL had lower sCD14 levels at w72 as revealed by ANCOVA compared to those who did not receive (Δ = −0.47 µg/ml; p = 0.015). Conclusions Markers of MT and enterocyte damage are elevated in untreated HIV-1 infected patients. Long-term ART reduces the levels, except for I-FABP which role as a marker of MT is questionable in ART-experienced patients. Why the enterocyte damage seems to persist remains to be established. Also antibiotic usage may influence the kinetics of the markers of MT. Trial Registration ClinicalTrials.gov NCT01445223 PMID:23383047
Nance, Robin M; Delaney, J A Chris; Golin, Carol E; Wechsberg, Wendee M; Cunningham, Chinazo; Altice, Frederick; Christopoulos, Katerina; Knight, Kevin; Quan, Vu; Gordon, Michael S; Springer, Sandra; Young, Jeremy; Crane, Paul K; Mayer, Kenneth H; Mugavero, Michael J; Del Rio, Carlos; Kronmal, Richard A; Crane, Heidi M
Adherence to antiretroviral therapy (ART) is an important determinant of clinical success assessed in many HIV studies. Harmonizing adherence data from studies that use different measures is difficult without a co-calibration equation to convert between validated instruments. Our purpose was to co-calibrate two commonly used adherence measures: the AIDS Clinical Trials Group (ACTG) questionnaire and the Visual Analog Scale (VAS). We used robust linear regression to develop a co-calibration equation in a clinical care cohort. The outcome was the 30-day VAS percentage of ART taken and the predictors were ACTG questions. We evaluated the equation's goodness of fit in five STTR (Seek, Test, Treat, Retain) consortium studies where individuals completed both measures: 2 criminal justice; 2 international; and 1 other high-risk vulnerable population. We developed a three-phase decision rule to convert ACTG to VAS in 1045 participants. First, when the last missed dose on the ACTG was reported as >30 days ago, the VAS was set to 100% (N = 582). Second, if "doses missed" was zero for all items, VAS was 100% (N = 104). Third, among remaining participants (N = 359), VAS was estimated as 96.8% minus 2.9% times the number of missed doses ("doses per day" was non-significant). Correlation between predicted and reported VAS was r = 0.80 in the criminal justice group (N = 446), r = 0.46 in the international group (N = 311), r = 0.32 in the other vulnerable population (N = 63), and r = 0.66 overall. When outliers due to inversion of the VAS scale were excluded (n = 25), these correlations were 0.88, 0.78, 0.80, and 0.86, respectively. We concluded that a simple decision rule and equation allowed us to co-calibrate between two widely used adherence measures thus combining data from studies with different instruments. This study highlighted issues with VAS inversions and its limitations as a single item. Combining studies using different
Full Text Available Abstract Background Strengthened national health systems are necessary for effective and sustained expansion of antiretroviral therapy (ART. ART and its supply chain management in Uganda are largely based on parallel and externally supported efforts. The question arises whether systems are being strengthened to sustain access to ART. This study applies systems thinking to assess supply chain management, the role of external support and whether investments create the needed synergies to strengthen health systems. Methods This study uses the WHO health systems framework and examines the issues of governance, financing, information, human resources and service delivery in relation to supply chain management of medicines and the technologies. It looks at links and causal chains between supply chain management for ART and the national supply system for essential drugs. It combines data from the literature and key informant interviews with observations at health service delivery level in a study district. Results Current drug supply chain management in Uganda is characterized by parallel processes and information systems that result in poor quality and inefficiencies. Less than expected health system performance, stock outs and other shortages affect ART and primary care in general. Poor performance of supply chain management is amplified by weak conditions at all levels of the health system, including the areas of financing, governance, human resources and information. Governance issues include the lack to follow up initial policy intentions and a focus on narrow, short-term approaches. Conclusion The opportunity and need to use ART investments for an essential supply chain management and strengthened health system has not been exploited. By applying a systems perspective this work indicates the seriousness of missing system prerequisites. The findings suggest that root causes and capacities across the system have to be addressed synergistically to
Full Text Available Rajesh Shigdel,1 Elise Klouman,2 Anita Bhandari,2 Luai A Ahmed11Department of Health and Care Sciences, 2Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, NorwayPurpose: There are a high number of HIV-infected patients receiving antiretroviral therapy (ART in the Kathmandu District of Nepal, but information on adherence and factors influencing it are scarce in this population. The present study aimed to estimate ART adherence among HIV-infected patients in the Kathmandu District of Nepal, and to determine the factors associated with ART adherence.Patients and methods: This study included 316 HIV-infected patients attending three ART centers in the Kathmandu District. Information on sociodemographic characteristics, socioeconomic status, and ART use for the previous 7 days was collected via interview. Participants were considered adherent if they reported taking ≥95% of their ART as prescribed. The association between explanatory variables and ART adherence was measured using logistic regression and reported as odds ratios (OR with 95% confidence intervals (CI.Results: Male participants accounted for 64.6% (n=204. Overall ART adherence was 86.7%. ART adherence in men and women were 84.3% and 91.1%, respectively. Age (OR 1.04; 95% CI 1.00–1.09, travel time to ART centers (OR 1.38; 95% CI 1.12–1.71, history of illegal drug use (OR 3.98; 95% CI 1.71–9.24, and adverse effects (OR 4.88; 95% CI 1.09–21.8, were all independently and negatively associated with ART adherence. Use of reminder tools (OR 3.45; 95% CI 1.33–8.91 was independently and positively associated with ART adherence.Conclusion: The observed ART adherence in this study is encouraging. Travel time to ART centers, self-reported adverse effects, illegal drug use, and not using reminder tools were the major determinants of ART adherence. Interventions that take these factors into account could further improve ART
Full Text Available BACKGROUND: Antiretroviral therapy (ART has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART. METHODOLOGY: Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885 was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103 testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis. FINDINGS: Only 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1% and individuals testing on their own initiative (53.5% the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period. CONCLUSION: Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.
Full Text Available Candidia esophagitis (CE is an AIDS-defining condition, usually occurring in individuals with low CD4 counts of <200 cells/µL. Endoscopy is a valuable definitive diagnostic method for CE but may not be indicated for asymptomatic patients or for those with high CD4 counts or without oral candidiasis. This study assessed such patients to clarify the factors associated with CE and its severity on endoscopy in the highly active antiretroviral therapy (HAART era.A total of 733 HIV-infected patients who underwent upper gastrointestinal (GI endoscopy were analyzed. Sexual behavior, CD4(+ count, HIV-RNA viral load (VL, history of HAART, GI symptoms, GI diseases, and oral candidiasis were assessed. Endoscopic severity of CE was classified as mild (Kodsi's grade I/II or severe (grade III/IV. Of the 733 subjects, 62 (8.46% were diagnosed with CE (mild, n = 33; severe, n = 29. Of them, 56.5% (35/62 had no GI symptoms, 30.6% (19/62 had CD4 + ≥200 cells/μL, and 55.3% (21/38 had no oral candidiasis. Univariate analysis found lower CD4+ counts, higher HIV VL, and no history of HAART to be significantly associated with CE. With lower CD4(+ counts and higher HIV VL, CE occurrence increased significantly (P<0.01 for trend in odds. Multivariate analysis showed low CD4+ counts and high HIV VL to be independently associated with CE. Of the severe CE patients, 55.2% (16/29 had no GI symptoms and 44.4% (8/18 had no oral candidiasis. Median CD4(+ counts in severe cases were significantly lower than in mild cases (27 vs. 80; P = 0.04.Low CD4+ counts and high HIV VL were found to be factors associated with CE, and advanced immunosuppression was associated with the development of severity. Endoscopy is useful as it can detect CE, even severe CE, in patients without GI symptoms, those with high CD4 counts, and those without oral candidiasis.
Ekouevi, Didier K.; Balestre, Eric; Ba-Gomis, Franck-Olivier; Eholie, Serge Paul; Maiga, Moussa; Amani-Bosse, Clarisse; Minga, Albert; Messou, Eugène; Sow, Papa Salif; Lewden, Charlotte; Traoré, Hamar Allassane; Bissagnene, Emmanuel; Dabis, François
Summary Objective To study factors associated with the probability of retention in antiretroviral therapy (ART) programs in West Africa. Methods The International epidemiologic Databases to Evaluate AIDS (IeDEA) in West Africa is a prospective, operational, observational cohort study based on collaboration between 11 cohorts of HIV-infected adult patients in Benin, Côte d'Ivoire, Gambia, Mali and Senegal. All patients aged 16 and older at ART initiation, with documented gender and date of ART initiation, were included. For those with at least one day of follow-up, Kaplan-Meier method and Weibull regression model were used to estimate the 12-month probability of retention in care and the associated factors. Results 14,352 patients (61% female) on ART were included in this data merger. Median age was 37 years (IQR: 31-44 years) and median CD4 count at baseline was 131 cells/mm3 (IQR: 48-221 cells/mm3). The first line regimen was NNRTI-based for 78% of patients, protease-inhibitor based for 17%, and three NRTIs for 3%. The probability of retention was 0.90 (95% confidence interval [CI]: 0.89-0.90) at 3 months, 0.84 (95%CI: 0.83-0.85) at 6 months and 0.76 (95%CI: 0.75-0.77) at 12 months. The probability of retention in care was lower in patients with baseline CD4 count 200 cells/mm3, in men (aHR=1.17; 95%CI: 1.10-1.24; p=0.0002), in younger patients (<30 years) (aHR=1.10; 95%CI: 1.03-1.19; p=0.01) and in patients with low hemoglobinemia <8g/dL (aHR=1.33; 95%CI: 1.21-1.45; p<0.0001). Availability of funds for systematic tracing was associated with better retention (aHR=0.29; 95%CI: 0.16-0.55; p=0.001). Conclusions Close follow-up, promoting early access to care and ART and a decentralized system of care may improve the retention in care of HIV-patients on ART. PMID:20586958
Serena P Koenig
Full Text Available BACKGROUND: In a randomized clinical trial of early versus standard antiretroviral therapy (ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial. METHODS AND FINDINGS: Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS, including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART and US$979 (standard ART. Early ART patients had higher mean costs for ART (US$398 versus US$81 but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384. The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS-US$9,979/YLS including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS-US$5,537/YLS. CONCLUSIONS: Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita after a maximum of 3 years, after excluding research-related laboratory tests. TRIAL REGISTRATION: ClinicalTrials.gov NCT00120510.
Full Text Available Abstract Background Many national antiretroviral therapy (ART programmes encourage providers to identify and address baseline factors associated with poor treatment outcomes, including modifiable adherence-related behaviours, before initiating ART. However, evidence on such predictors is scarce, and providers judgement may often be inaccurate. To help address this evidence gap, this observational cohort study examined baseline factors potentially predictive of poor treatment outcomes in two ART programmes in South Africa, with a particular focus on determinants of adherence. Methods Treatment-naïve patients starting ART were enrolled from a community and a workplace ART programme. Potential baseline predictors associated with poor treatment outcomes (defined as viral load > 400 copies/ml or having discontinued treatment by six months were assessed using logistic regression. Exposure variables were organised for regression analysis using a hierarchical framework. Results 38/227 (17% of participants in the community had poor treatment outcomes compared to 47/117 (40% in the workplace. In the community, predictors of worse outcomes included: drinking more than 20 units of alcohol per week, having no prior experience of chronic medications, and consulting a traditional healer in the past year (adjusted odds ratio [aOR] 15.36, 95% CI 3.22-73.27; aOR 2.30, 95%CI 1.00-5.30; aOR 2.27, 95% CI 1.00-5.19 respectively. Being male and knowing someone on ART were associated with better outcomes (aOR 0.25, 95%CI 0.09-0.74; aOR 0.44, 95%CI 0.19-1.01 respectively. In the workplace, predictors of poor treatment outcomes included being uncertain about the health effects of ART and a traditional healer's ability to treat HIV (aOR 7.53, 95%CI 2.02-27.98; aOR 4.40, 95%CI 1.41-13.75 respectively. Longer pre-ART waiting time (2-12 weeks compared to Conclusion Baseline predictors of poor treatment outcomes were largely unique to each programme, likely reflecting
Full Text Available OBJECTIVES: We investigated whether there are differences in the effects on microbial translocation (MT and enterocyte damage by different antiretroviral therapy (ART regimens after 1.5 years and whether antibiotic use has impact on MT. In a randomized clinical trial (NCT01445223 on first line ART, patients started either lopinavir/r (LPV/r (n = 34 or efavirenz (EFV containing ART (n = 37. Lipopolysaccharide (LPS, sCD14, anti-flagellin antibodies and intestinal fatty acid binding protein (I-FABP levels were determined in plasma at baseline (BL and week 72 (w72. RESULTS: The levels of LPS and sCD14 were reduced from BL to w72 (157.5 pg/ml vs. 140.0 pg/ml, p = 0.0003; 3.13 ug/ml vs. 2.85 ug/ml, p = 0.005, respectively. The levels of anti-flagellin antibodies had decreased at w72 (0.35 vs 0.31 [OD]; p<0.0004, although significantly only in the LPV/r arm. I-FABP levels increased at w72 (2.26 ng/ml vs 3.13 ng/ml; p<0.0001, although significantly in EFV treated patients only. Patients given antibiotics at BL had lower sCD14 levels at w72 as revealed by ANCOVA compared to those who did not receive (Δ = -0.47 µg/ml; p = 0.015. CONCLUSIONS: Markers of MT and enterocyte damage are elevated in untreated HIV-1 infected patients. Long-term ART reduces the levels, except for I-FABP which role as a marker of MT is questionable in ART-experienced patients. Why the enterocyte damage seems to persist remains to be established. Also antibiotic usage may influence the kinetics of the markers of MT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01445223.
Rachel C Vreeman
Full Text Available Introduction: High levels of adherence to antiretroviral therapy (ART are central to HIV management. The objective of this study was to compare multiple measures of adherence and investigate factors associated with adherence among HIV-infected children in western Kenya. Methods: We evaluated ART adherence prospectively for six months among HIV-infected children aged ≤14 years attending a large outpatient HIV clinic in Kenya. Adherence was reported using caregiver report, plasma drug concentrations and Medication Event Monitoring Systems (MEMS®. Kappa statistics were used to compare adherence estimates with MEMS®. Logistic regression analyses were performed to assess the association between child, caregiver and household characteristics with dichotomized adherence (MEMS® adherence ≥90% vs. <90% and MEMS® treatment interruptions of ≥48 hours. Odds ratios (ORs and 95% confidence intervals (95% CIs were calculated. Results: Among 191 children, mean age at baseline was 8.2 years and 55% were female. Median adherence by MEMS® was 96.3% and improved over the course of follow-up (p<0.01, although 49.5% of children had at least one MEMS® treatment interruption of ≥48 hours. Adherence estimates were highest by caregiver report, and there was poor agreement between MEMS® and other adherence measures (Kappa statistics 0.04–0.37. In multivariable logistic regression, only caregiver-reported missed doses in the past 30 days (OR 1.25, 95% CI 1.14–1.39, late doses in the past seven days (OR 1.14, 95% CI 1.05–1.22 and caregiver-reported problems with getting the child to take ART (OR 1.10, 95% CI 1.01–1.20 were significantly associated with dichotomized MEMS® adherence. The caregivers reporting that ART made the child sick (OR 1.12, 95% CI 1.01–1.25 and reporting difficulties in the community that made giving ART more difficult (e.g. stigma (OR 1.14, 95% CI 1.02–1.27 were significantly associated with MEMS® treatment interruptions in
Full Text Available Abstract Background Ugandan national guidelines recommend initiation of combination antiretroviral therapy (cART at CD4+ T cell (CD4 count below 350 cell/μl, but the implementation of this is limited due to availability of medication. However, cART initiation at higher CD4 count increases survival, albeit at higher lifetime treatment cost. This analysis evaluates the cost-effectiveness of initiating cART at a CD4 count between 250–350 cell/μl (early versus Methods Life expectancy of cART-treated patients, conditional on baseline CD4 count, was modeled based on published literature. First-line cART costs $192 annually, with an additional $113 for patient monitoring. Delaying initiation of cART until the CD4 count falls below 250 cells/μl would incur the cost of the bi-annual CD4 count tests and routine maintenance care at $85 annually. We compared lifetime treatment costs and disability adjusted life-expectancy between early vs. delayed cART for ten baseline CD4 count ranges from 250-350 cell/μl. All costs and benefits were discounted at 3% annually. Results Treatment delay varied from 6–18 months. Early cART initiation increased life expectancy from 1.5-3.5 years and averted 1.33–3.10 disability adjusted life years (DALY’s per patient. Lifetime treatment costs were $4,300–$5,248 for early initiation and $3,940–$4,435 for delayed initiation. The cost/DALY averted of the early versus delayed start ranged from $260–$270. Conclusions In HIV-positive patients presenting with CD4 count between 250-350 cells/μl, immediate initiation of cART is a highly cost-effective strategy using the recommended one-time per capita GDP threshold of $490 reported for Uganda. This would constitute an efficient use of scarce health care funds.
Tumaini M. Nyamhanga
Full Text Available Background: This article presents part of the findings from a larger study that sought to assess the role that gender relations play in influencing equity regarding access and adherence to antiretroviral therapy (ART. Review of the literature has indicated that, in Southern and Eastern Africa, fewer men than women have been accessing ART, and the former start using ART late, after HIV has already been allowed to advance. The main causes for this gender gap have not yet been fully explained. Objective: To explore how masculinity norms limit men's access to ART in Dar es Salaam. Design: This article is based on a qualitative study that involved the use of focus group discussions (FGDs. The study employed a stratified purposive sampling technique to recruit respondents. The study also employed a thematic analysis approach. Results: Overall, the study's findings revealed that men's hesitation to visit the care and treatment clinics signifies the superiority norm of masculinity that requires men to avoid displaying weakness. Since men are the heads of families and have higher social status, they reported feeling embarrassed at having to visit the care and treatment clinics. Specifically, male respondents indicated that going to a care and treatment clinic may raise suspicion about their status of living with HIV, which in turn may compromise their leadership position and cause family instability. Because of this tendency towards ‘hiding’, the few men who register at the public care and treatment clinics do so late, when HIV-related signs and symptoms are already far advanced. Conclusion: This study suggests that the superiority norm of masculinity affects men's access to ART. Societal expectations of a ‘real man’ to be fearless, resilient, and emotionally stable are in direct conflict with expectations of the treatment programme that one has to demonstrate health-promoting behaviour, such as promptness in attending the care and treatment
Abioye, Ajibola I; Isanaka, Sheila; Liu, Enju; Mwiru, Ramadhani S; Noor, Ramadhani A; Spiegelman, Donna; Mugusi, Ferdinand; Fawzi, Wafaie
Human immunodeficiency virus (HIV)-infected males have poor treatment outcomes after initiation of antiretroviral therapy (ART) compared to HIV-infected women. Dietary factors might mediate the association between sex and disease progression. However, the gender difference in diet among HIV-infected individuals in sub-Saharan Africa is largely unknown. The objective of this study was to examine differences in dietary intake among HIV-infected men and women. We conducted a cross-sectional analysis of dietary questionnaire data from 2038 adults initiating ART in Dar es Salaam, Tanzania to assess whether nutrient adequacy differed by sex. We dichotomized participants' nutrient intakes by whether recommended dietary allowances (RDAs) were met and estimated the relative risk (RR) of meeting RDAs in males using binomial regression models. We also estimated the mean difference in intake of foods and food groups by gender. We found poorer dietary practices among men compared to women. Males were less likely to meet the RDAs for micronutrients critical for slowing disease progression among HIV patients: niacin (RR = 0.39, 95% confidence interval [CI]: 0.27 to 0.55), riboflavin (RR = 0.81, 95% CI: 0.73 to 0.91), vitamin C (RR = 0.94, 95% CI: 0.89 to 1.00), and zinc (RR = 0.06, 95% CI: 0.01 to 0.24). Intake of thiamine, pantothenate, vitamins B6, B12, and E did not vary by gender. Males were less likely to eat cereals (mean difference [servings per day] = -0.21, 95% CI: -0.44 to 0.001) and vegetables (mean difference = -0.47, 95% CI: -0.86 to -0.07) in their diet, but more likely to have meat (mean difference = 0.14, 95% CI: 0.06 to 0.21). We conclude that male HIV patients have poorer dietary practices than females, and this may contribute to faster progression of the disease in males.
Full Text Available Abstract Human Immunodeficiency Virus Type 1 (HIV-1 protease inhibitors (PIs are the most potent class of drugs in antiretroviral therapies. However, viral drug resistance to PIs could emerge rapidly thus reducing the effectiveness of those drugs. Of note, all current FDA-approved PIs are competitive inhibitors, i.e., inhibitors that compete with substrates for the active enzymatic site. This common inhibitory approach increases the likelihood of developing drug resistant HIV-1 strains that are resistant to many or all current PIs. Hence, new PIs that move away from the current target of the active enzymatic site are needed. Specifically, allosteric inhibitors, inhibitors that prohibit PR enzymatic activities through non-competitive binding to PR, should be sought. Another common feature of current PIs is they were all developed based on the structure-based design. Drugs derived from a structure-based strategy may generate target specific and potent inhibitors. However, this type of drug design can only target one site at a time and drugs discovered by this method are often associated with strong side effects such as cellular toxicity, limiting its number of target choices, efficacy, and applicability. In contrast, a cell-based system may provide a useful alternative strategy that can overcome many of the inherited shortcomings associated with structure-based drug designs. For example, allosteric PIs can be sought using a cell-based system without considering the site or mechanism of inhibition. In addition, a cell-based system can eliminate those PIs that have strong cytotoxic effect. Most importantly, a simple, economical, and easy-to-maintained eukaryotic cellular system such as yeast will allow us to search for potential PIs in a large-scaled high throughput screening (HTS system, thus increasing the chances of success. Based on our many years of experience in using fission yeast as a model system to study HIV-1 Vpr, we propose the use of
Full Text Available Introduction: Recent international guidelines call for expanded access to triple-drug antiretroviral therapy (ART in HIV-positive women during pregnancy and postpartum. However, high levels of non-adherence and/or disengagement from care may attenuate the benefits of ART for HIV transmission and maternal health. We examined the frequency and predictors of disengagement from care among women initiating ART during pregnancy in Cape Town, South Africa. Methods: We used routine medical records to follow-up pregnant women initiating ART within prevention of mother-to-child transmission of HIV services in Cape Town, South Africa. Outcomes assessed through six months postpartum were (1 disengagement (no attendance within 56 days of a scheduled visit and (2 missed visits (returning to care 14–56 days late for a scheduled visit. Results: A total of 358 women (median age, 28 years; median gestational age, 26 weeks initiated ART during pregnancy. By six months postpartum, 24% of women (n=86 had missed at least one visit and an additional 32% (n=115 had disengaged from care; together, 49% of women had either missed a visit or had disengaged by six months postpartum. Disengagement was more than twice as frequent postpartum compared to in the antenatal period (6.2 vs. 2.4 per 100 woman-months, respectively; p<0.0001. In a proportional hazards model, later gestational age at initiation (HR: 1.04; 95% CI: 1.00–1.07; p=0.030 and being newly diagnosed with HIV (HR: 1.57; 95% CI: 1.07–2.33; p=0.022 were significant predictors of disengagement after adjusting for patient age, starting CD4 cell count and site of ART initiation. Conclusions: These results demonstrate that missed visits and disengagement from care occur frequently, particularly post-delivery, among HIV-positive women initiating ART during pregnancy. Women who are newly diagnosed with HIV may be particularly vulnerable and there is an urgent need for interventions both to promote retention
Full Text Available Introduction: An increasing proportion of adult patients initiating antiretroviral therapy (ART in resource-limited settings are aged >50 years. Older populations on ART appear to have heightened risk of death, but little is known about factors influencing mortality in this population. Methods: We performed a retrospective observational multisite cohort study including all adult patients (≥15 years initiating ART between 2003 and 2013 in programmes supported by Médecins Sans Frontières across 12 countries in Asia, Africa and Europe. Patients were stratified into two age groups, >50 years and 15 to 50 years. A Cox proportional hazards model was used to explore factors associated with mortality. Results: The study included 41,088 patients: 2591 (6.3% were aged >50 years and 38,497 (93.7% were aged 15 to 50 years. The mortality rate was significantly higher in the age group >50 years [367 (14.2% deaths; mortality rate 7.67 deaths per 100 person-years (95% confidence interval, CI: 6.93 to 8.50] compared to the age group 15 to 50 years [3788 (9.8% deaths; mortality rate 4.18 deaths per 100 person-years (95% CI: 4.05 to 4.31], p50 age group. WHO Stage 4 conditions were more strongly associated with increased mortality rates in the 15 to 50 age group compared to populations >50 years. WHO Stage 3 conditions were associated with an increased mortality rate in the 15 to 50 age group but not in the >50 age group. Programme region did not affect mortality rates in the >50 age group; however being in an Asian programme was associated with a 36% reduced mortality rate in populations aged 15 to 50 years compared to being in an African programme. There was a higher overall incidence of Stage 3 WHO conditions in people >50 years (12.8/100 person-years compared to those 15 to 50 years (8.1/100 person-years (p50 age groups. Conclusions: Older patients on ART in resource-limited settings have increased mortality rates, but compared to younger populations this
Full Text Available Introduction: Patient preference to antiretroviral therapy (ART characteristics should be a key consideration in treatment decisions. ART options exist for people living with HIV (PLWH, however concerns remain related to PLWH satisfaction with current ARTs. The current study examines patient preferences and the strength of preferences for treatment characteristics associated with ART. Materials and Methods: Patients’ preferences to ART were explored using a discrete choice experiment (DCE. Seven defined treatment characteristics (each with three categories were identified from a literature review, input from experts, PLWH and physicians. A total of 1582 PLWH from France, Germany, Spain, Italy and the UK were recruited for the study. An adjusted odds ratio <1 signified lower odds of selecting a treatment with this characteristic category, compared to the reference category, independently of other characteristics. Results: The patient preference analyses showed that participants preferred treatments with a rapid reduction in viral load (OR=0.78; 95% CI 0.74–0.81 and CD4 count (OR=0.86; 95% CI=0.82–0.89. Participants had a strong preference for avoiding diarrhoea (Odds ratio, OR=0.36 95% CI=0.33–0.38 and long term health problems (OR=0.30, 95% CI=0.28–0.32. Convenience related issues related to restrictions on taking drugs because of food or drug interactions were important to avoid (OR=0.80, 95% CI=0.76–0.83 and OR=0.72 95% CI=0.69–0.76 respectively. Participants also had a strong preference to avoid drugs which limited the effectiveness of future treatments (OR=0.70, 95% CI=0.67–0.73. Conclusions: Avoidance of diarrhoea and long-term complications were the most important drivers of patient choice. This study, from a large sample of European patients, demonstrates the importance to patients when different aspects of HIV treatment are considered simultaneously.
Jan A C Hontelez
Full Text Available BACKGROUND: Expanded access to antiretroviral therapy (ART using universal test and treat (UTT has been suggested as a strategy to eliminate HIV in South Africa within 7 y based on an influential mathematical modeling study. However, the underlying deterministic model was criticized widely, and other modeling studies did not always confirm the study's finding. The objective of our study is to better understand the implications of different model structures and assumptions, so as to arrive at the best possible predictions of the long-term impact of UTT and the possibility of elimination of HIV. METHODS AND FINDINGS: We developed nine structurally different mathematical models of the South African HIV epidemic in a stepwise approach of increasing complexity and realism. The simplest model resembles the initial deterministic model, while the most comprehensive model is the stochastic microsimulation model STDSIM, which includes sexual networks and HIV stages with different degrees of infectiousness. We defined UTT as annual screening and immediate ART for all HIV-infected adults, starting at 13% in January 2012 and scaled up to 90% coverage by January 2019. All models predict elimination, yet those that capture more processes underlying the HIV transmission dynamics predict elimination at a later point in time, after 20 to 25 y. Importantly, the most comprehensive model predicts that the current strategy of ART at CD4 count ≤350 cells/µl will also lead to elimination, albeit 10 y later compared to UTT. Still, UTT remains cost-effective, as many additional life-years would be saved. The study's major limitations are that elimination was defined as incidence below 1/1,000 person-years rather than 0% prevalence, and drug resistance was not modeled. CONCLUSIONS: Our results confirm previous predictions that the HIV epidemic in South Africa can be eliminated through universal testing and immediate treatment at 90% coverage. However, more realistic
Leroi, Charline; Balestre, Eric; Messou, Eugene; Minga, Albert; Sawadogo, Adrien; Drabo, Joseph; Maiga, Moussa; Zannou, Marcel; Seydi, Moussa; Dabis, Francois; Jaquet, Antoine
Background In sub-Saharan Africa, antiretroviral therapy (ART) including drugs with potential toxicity such as Zidovudine (ZDV) are routinely prescribed. This study aimed at estimating the incidence of severe neutropenia and associated factors after ART initiation in five West African countries. Methods A retrospective cohort analysis was conducted within the international epidemiologic database to evaluate AIDS (IeDEA) collaboration in West Africa. All HIV-infected adults, initiating ART between 2002 and 2014, with a baseline and at least one follow-up absolute neutrophil count (ANC) measurement were eligible. Incidence of severe neutropenia (ANC <750 cells/mm3) was estimated with 95% confidence interval (CI) according to age, gender, HIV clinic, hemoglobin, CD4 count, clinical stage, and ART duration. A Cox proportional hazard model was used to identify factors associated with severe neutropenia, expressed with their adjusted hazard ratios (aHR). Results Between 2002 and 2014, 9,426 HIV-infected adults were enrolled. The crude incidence rate of a first severe neutropenia was 9.1 per 100 person-years (95% CI: 8.6–9.8). Factors associated with severe neutropenia were exposure to ZDV <6 months (aHR = 2.2; 95% CI: 1.8–2.6), ≥6–12 months (aHR = 2.1; 95% CI: 1.6–2.8) and ≥12 months (aHR = 1.6; 95% CI: 1.2–2.2) [Ref. no ZDV exposure], CD4 count <350 cells/mm3 (aHR = 1.3; 95% CI: 1.1–1.5) and advanced clinical stage at ART initiation (aHR = 1.2; 95% CI: 1.0–1.4). Conclusion The incidence of severe neutropenia after ART initiation in West Africa is high and associated with ZDV exposure and advanced HIV disease. In this context, efforts are needed to scale-up access to less toxic first-line ART drugs and to promote early ART initiation. PMID:28122041
Overton, Edgar Turner; Chan, Ellen S.; Brown, Todd T.; Tebas, Pablo; McComsey, Grace A.; Melbourne, Kathleen M.; Napoli, Andrew; Hardin, William Royce; Ribaudo, Heather J.; Yin, Michael T.
Background Antiretroviral therapy (ART) initiation for HIV-1 infection is associated with 2-6% loss in bone mineral density (BMD). Objective To evaluate vitamin D3 (4000 IU daily) plus calcium (1000 mg calcium carbonate daily) supplementation on bone loss associated with ART initiation. Design 48-week prospective, randomized, double-blind, placebo-controlled study. Setting Thirty nine AIDS Clinical Trials Network research units. Participants ART-naïve HIV-infected adults. Measurements BMD by dual-energy X-ray absorptiometry (DXA); 25-hydroxy vitamin D (25(OH)D) levels, parathyroid hormone (PTH), phosphate metabolism, markers of bone turnover and systemic inflammation. Results 165 eligible subjects were randomized (79 Vitamin D/calcium (VitD/Cal); 86 placebo); 142 subjects with evaluable DXA data were included in the primary analysis. The study arms were well-balanced at baseline: median age 33 years; 90% male; 33% non-Hispanic black; median CD4 count 341 cells/mm3; and median 25(OH)D 23 ng/mL (57 nmol/L). At 48 weeks, subjects receiving placebo had greater decline in total hip BMD than VitD/Cal: −3.19% median change (1st-3rd quartile (Q1, Q3) −5.12%, −1.02%) vs. (−1.46% −3.16%,−0.40%). respectively (p=0.001). Lumbar spine BMD loss for the two groups was similar: −2.91% (−4.84%, −1.06%) vs. −1.41% (−3.78%, 0.00%), (p=0.085). At week 48, 90% of participants achieved HIV-1 RNA <50 copies/mL. Levels of 25(OH)D3 increased in the VitD/Cal but not the placebo group: median change of 24.5 (14.6, 37.8) vs. 0.7 (−5.3, 4.3) ng/mL, respectively (p<0.001). Additionally, increases in markers of bone turnover were blunted in the VitD/Cal group. Limitations No international sites were included; only 48 weeks of follow up Conclusion Vitamin D/calcium supplementation mitigates the loss of BMD seen with initiation of efavirenz/emtricitabine/tenofovir, particularly at the total hip, which is the site of greatest concern for fragility fracture. Primary Funding
Full Text Available Initiation of HIV-positive patients on antiretroviral therapy (ART in Nigeria was restricted to secondary and tertiary level hospitals due to weak health systems in primary health centres (PHCs. Shell Petroleum Development Company (SDPC Nigeria and FHI 360 using a systems strengthening approach, piloted ART enrolment in a PHC in south-eastern Nigeria. This study sought to evaluate patients’ adherence and mortality on ART, and associated risk factors. We reviewed clinic records of adult patients initiating ART between January 2007 and December 2009. Adherence was calculated as the number of days of medication dispensed as a percentage of total number of days evaluated. Outcome measures were probability of being alive and retained in care at 12 and 24 months on ART. Competing risks regression models were used to assess potential predictors associated with mortality. Total of 196 patients (64.8% males were initiated on ART. Patients’ median age was 35 years (IQR 30–44; median CD4 at initiation was 132 cells/mm3 (IQR 82–212, Patients in WHO stage III and IV constituted 73 (37.6% and 83 (42.8% respectively. Majority (108 [55.1%] of patients had adherence rates >95%. Adherence levels ranged: 70–85%, 50–65% and <50% in 29 (14.8%, 30 (15.3% and 29 (14.8% of patients respectively. Nucleoside backbone use were AZT/3TC (69.4% d4T/3TC (28.6% and TDF/FTC (2%. At 12 months of follow up, 80.6% (158 were alive and on ART, mortality accounted for 12.8% (25, 11 (5.6% were LTFU and 2 (1.1% transferred out. At 24 months on ART survival decreased to 64.3% (126, 20.4% (40 died, 9.2% (18 were LTFU and 12 (6.1% transferred out. Competing risks regression models revealed that patients’ factors significantly associated with mortality include: bedridden patients (HR=3.6 [95% CI: 1.11–11.45], p=0.03, referent: working, <50% adherence levels (HR=27.7 [95% CI: 8.55–89.47], p<0.0001, referent: >95% adherence level. In conclusion, majority of attrition was
Full Text Available Abstract Background Lower-income countries face severe health worker shortages. Recent evidence suggests that this problem can be mitigated by task-shifting--delegation of aspects of health care to less specialized health workers. We estimated the potential impact of task-shifting on costs of antiretroviral therapy (ART and physician supply in Uganda. The study was performed at the Infectious Diseases Institute (IDI clinic, a large urban HIV clinic. Methods We built an aggregate cost-minimization model from societal and Ministry of Health (MOH perspectives. We compared physician-intensive follow-up (PF, the standard of care, with two methods of task-shifting: nurse-intensive follow-up (NF and pharmacy-worker intensive follow-up (PWF. We estimated personnel and patient time use using a time-motion survey. We obtained unit costs from IDI and the literature. We estimated physician personnel impact by calculating full time equivalent (FTE physicians saved. We made national projections for Uganda. Results Annual mean costs of follow-up per patient were $59.88 (societal and $31.68 (medical for PF, $44.58 (societal and $24.58 (medical for NF and $18.66 (societal and $10.5 (medical for PWF. Annual national societal ART follow-up expenditure was $5.92 million using PF, $4.41 million using NF and $1.85 million using PWF, potentially saving $1.51 million annually by using NF and $4.07 million annually by using PWF instead of PF. Annual national MOH expenditure was $3.14 million for PF, $2.43 million for NF and $1.04 for PWF, potentially saving $0.70 million by using NF and $2.10 million by using PWF instead of PF. Projected national physician personnel needs were 108 FTE doctors to implement PF and 18 FTE doctors to implement NF or PWF. Task-shifting from PF to NF or PWF would potentially save 90 FTE physicians, 4.1% of the national physician workforce or 0.3 FTE physicians per 100,000 population. Conclusion Task-shifting results in substantial cost and
Full Text Available Introduction: Morphological and metabolic complications in HIV patients on antiretroviral therapy remain a challenge. While new cases of lipoatrophy (LA disappear, irreducible central lipohypertrophy (LH and metabolic complications require highly specialized management. We described a day hospital dedicated to lipodystrophy (LD and metabolic disorders in HIV patients on treatment in Geneva, Switzerland, with a focus on LH. Materials and Methods: The “Groupe Lipo & Metabolism” is a multidisciplinary consultation where patients undergo a standard evaluation including questionnaire, physical examination, dual-energy x-ray absorptiometry (DEXA and L5-level CT scans, blood tests and consultations with various specialists. Based on prospectively maintained data, we describe clinical, biological and radiological characteristics of patients ≥18 years who attended the consultation between 2008 and 2013. We defined LH by CT scan, the gold standard method, as abdominal visceral adipose tissue (VAT ≥130 cm2, value associated with increased risk of cardiovascular event. Results: A total of 195 patients attended the consultation during study period. Reasons for referral included LH in 28.3%, LA in 25% and mixed syndrome in 15.5% of cases. Metabolic disorders accounted for 19% of referrals with or without LD features. Among patients with a CT scan performed (n=183, 46 (25% had LH with a VAT ≥130 cm2. In this population, mean age was 49.1 years and 53.6% were male. HIV viral load was 6% in 10.5% of patients. Vitamin-D level was <75 nmol/L in 70.7% of patients. Respectively 31.2% and 12.1% of patients had osteopenia and osteoporosis on the spine and 44.8% and 6.6% on the hip neck. Factors associated with a VAT≥130 cm2 included male gender (OR 3.7 [95% CI 1.7–8.2] p<0.001, triglycerides ≥2 mmol/L (OR 2.6 [95% CI 1.3–5.4] P<0.01 and increase in BMI category (OR 1.8 [95% CI 1.2–2.8] p<0.01. Conclusions: Lipohypertrophy is a prevalent feature of
Duc Bui Nguyen
Full Text Available OBJECTIVES: Vietnam has significantly scaled up its national antiretroviral therapy (ART program since 2005. With the aim of improving Vietnam's national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID. The results of this evaluation may have relevance for other national ART programs with significant PWID populations. DESIGN: Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART. METHODS: Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data. RESULTS: Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4-76.5, median age 30, interquartile range [IQR]: 26-34, 62.0% reported a history of intravenous drug use, CI: 58.6-65.3. Median baseline CD4 cell count was 78 cells/mm(3 (IQR: 30-162 and 30.4% (CI: 25.8-35.1 of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3% or d4T/3TC/EFV (18.6%. Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8-89.9, 84.0% (CI: 81.8-86.0, 78.8% (CI: 75.7-81.6, and 74.6% (CI: 69.6-79.0. Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45-153, 142 (IQR: 78-217, 213 (IQR: 120-329, and 254 (IQR: 135-391 cells/mm(3. Patients who were PWID showed significantly poorer retention. CONCLUSIONS: The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline.
Julia K Rohr
Full Text Available Introduction: A substantial number of patients with HIV in South Africa have failed first-line antiretroviral therapy (ART. Although individual predictors of first-line ART failure have been identified, few studies in resource-limited settings have been large enough for predictive modelling. Understanding the absolute risk of first-line failure is useful for patient monitoring and for effectively targeting limited resources for second-line ART. We developed a predictive model to identify patients at the greatest risk of virologic failure on first-line ART, and to estimate the proportion of patients needing second-line ART over five years on treatment. Methods: A cohort of patients aged ≥18 years from nine South African HIV clinics on first-line ART for at least six months were included. Viral load measurements and baseline predictors were obtained from medical records. We used stepwise selection of predictors in accelerated failure-time models to predict virologic failure on first-line ART (two consecutive viral load levels >1000 copies/mL. Multiple imputations were used to assign missing baseline variables. The final model was selected using internal-external cross-validation maximizing model calibration at five years on ART, and model discrimination, measured using Harrell's C-statistic. Model covariates were used to create a predictive score for risk group of ART failure. Results: A total of 72,181 patients were included in the analysis, with an average of 21.5 months (IQR: 8.8–41.5 of follow-up time on first-line ART. The final predictive model had a Weibull distribution and the final predictors of virologic failure were men of all ages, young women, nevirapine use in first-line regimen, low baseline CD4 count, high mean corpuscular volume, low haemoglobin, history of TB and missed visits during the first six months on ART. About 24.4% of patients in the highest quintile and 9.4% of patients in the lowest quintile of risk were predicted
Full Text Available BACKGROUND: The provision of antiretroviral therapy (ART to migrant populations raises particular challenges with respect to ensuring adequate treatment support, adherence, and retention in care. We assessed rates of loss to follow-up for migrant workers compared with non-migrant workers in a routine treatment programme in Morjia, Lesotho. DESIGN: All adult patients (≥18 years initiating ART between January 1, 2008, and December 31, 2008, and followed up until the end of 2009, were included in the study. We described rates of loss to follow-up according to migrant status by Kaplan-Meier estimates, and used Poisson regression to model associations between migrant status and loss to follow-up controlling for potential confounders identified a priori. RESULTS: Our cohort comprised 1185 people, among whom 12% (148 were migrant workers. Among the migrant workers, median age was 36.1 (29.6-45.9 and the majority (55% were male. We found no statistically significant differences between baseline characteristics and migrant status. Rates of lost to follow up were similar between migrants and non-migrants in the first 3 months but differences increased thereafter. Between 3 and 6 months after initiating antiretroviral therapy, migrants had a 2.78-fold increased rate of defaulting (95%CI 1.15-6.73; between 6 and 12 months the rate was 2.36 times greater (95%CI 1.18-4.73, whereas after 1 year the rate was 6.69 times greater (95%CI 3.18-14.09. CONCLUSIONS: Our study highlights the need for programme implementers to take into account the specific challenges that may influence continuity of antiretroviral treatment and care for migrant populations.
Full Text Available Abstract Background HIV and AIDS are significant and growing public health concerns in southern Africa. The majority of countries in the region have national adult HIV prevalence estimates exceeding 10 percent. The increasing availability of highly active antiretroviral therapy (HAART has potential to mitigate the situation. There is however concern that women may experience more barriers in accessing treatment programs than men. Methods A systematic review of the literature was carried out to describe the gender distribution of patients accessing highly active antiretroviral therapy (HAART in Southern Africa. Data on number of patients on treatment, their mean or median age and gender were obtained and compared across studies and reports. Results The median or mean age of patients in the studies ranged from 33 to 39 years. While female to male HIV infection prevalence ratios in the southern African countries ranged from 1.2:1 to 1.6:1, female to male ratios on HAART ranged from 0.8: 1 to 2.3: 1. The majority of the reports had female: male ratio in treatment exceeding 1.6. Overall, there were more females on HAART than there were males and this was not solely explained by the higher HIV prevalence among females compared to males. Conclusion In most Southern African countries, proportionally more females are on HIV antiretroviral treatment than men, even when the higher HIV infection prevalence in females is accounted for. There is need to identify the factors that are facilitating women's accessibility to HIV treatment. As more patients access HAART in the region, it will be important to continue assessing the gender distribution of patients on HAART.
Full Text Available Background: Antiretroviral therapy has transformed the HIV infection into a chronic manageably disease. Optimal adherence (≥ 95% has required to achieve treatment success; however, still non-adherence remains major problem among patients receiving antiretroviral therapy (ART. The aim of this study was to determine adherences rate and evaluate factors affecting adherence among patients on ART in Dessie Referral Hospital (DRH. Materials and Methods: A cross sectional study employing both qualitative and quantitative methods was used. A total of 130 people living with HIV/AIDS on ART were included. All patients who came to the hospital during study period were considered based on convenient sampling technique. Chi-Square test is used to examine the association of adherence with associated factors. Both data entry and analysis was done using SPSS version 16. Results: Of 130 respondents, 58(44.6% were males and 72(55.4% were females and 107 (82.3% had 100% adherences, 10(7.7% had 95 -100% and the rest, 13(10% had <95% adherences with overall adherence rate of 90% for last month prior to the study period. The main reasons for non-adherence were 12(37.5% forgetfulness, 7(21.8% being away from home and 4 (12.5% being extremely ill. Use of other medications in addition to antiretroviral drugs (p=0.01, treatment fit into daily routines (p=0.01, family disclosure (p=0.01, active substance use (p=0.04 and living condition (p=0.00 were significantly associated with adherence to ART. Conclusion: The self reported adherence rate to ART (90% was found to be relatively higher which needs inclusion of other methods to ensure consistency of this value. Forgetfulness, being away from home and being extremely ill were the foremost reasons for non-adherence. The patients should be encouraged to maintain this high level of adherence.
Michael, OG; Kirk, O; Mathiesen, Lars Reinhardt
Current antiretroviral therapy can induce considerable, sustained viral suppression followed by immunological recovery, in which naive CD4 + cells are important. Long-term immunological recovery was investigated during the first 3 y of highly active antiretroviral therapy (HAART) in 210 HIV-1...... was sustained. There was no association between plasma viral load and the increase in naive CD4 + cell count. Importantly, baseline naive CD4 + cell count was significantly associated with the change in naive CD4 + cell count, suggesting that the naive cell count at baseline does influence the immunological...
Balak, Dashika A; Bissell, Karen; Roseveare, Christine; Ram, Sharan; Devi, Rachel R; Graham, Stephen M
Introduction. An absolute lymphocyte count is commonly used as an alternative to a CD4 count to determine initiation of antiretroviral therapy for HIV-infected individuals in Fiji when a CD4 count is unavailable. Methods. We conducted a retrospective analysis of laboratory results of HIV-infected individuals registered at all HIV clinics in Fiji. Results. Paired absolute lymphocyte and CD4 counts were available for 101 HIV-infected individuals, and 96% had a CD4 count of ≤500 cells/mm(3). Correlation between the counts in individuals was poor (Spearman rank correlation r = 0.5). No absolute lymphocyte count could be determined in this population as a suitable surrogate for a CD4 count of either 350 cells/mm(3) or 500 cells/mm(3). The currently used absolute lymphocyte count of ≤2300 cells/μL had a positive predictive value of 87% but a negative predictive value of only 17% for a CD4 of ≤350 cells/mm(3) and if used as a surrogate for a CD4 of ≤500 cells/mm(3) it would result in all HIV-infected individuals receiving ART including those not yet eligible. Weight, CD4 count, and absolute lymphocyte count increased significantly at 3 months following ART initiation. Conclusions. Our findings do not support the use of absolute lymphocyte count to determine antiretroviral therapy initiation in Fiji.
Abdissa, Alemseged; Yilma, Daniel; Fonager, Jannik;
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......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...... resistance (HIVDR) was performed on patients exhibiting virological failure (>1000 copies/mL at 6 months) or slow virological response (>5000 copies/mL at 3 months and Virological failure...... was observed among 14 (5.3%) participants out of 265 patients. Twelve samples were genotyped and six had HIV drug resistance (HIVDR) mutations at baseline. Among virological failures, 9/11 (81.8%) harbored one or more HIVDR mutations at 6 months. The most frequent mutations were K103N and M184VI. CONCLUSIONS...
Rebick, Gabriel W; Franke, Molly F; Teng, Jessica E; Gregory Jerome, J; Ivers, Louise C
Food rations are increasingly offered as part of HIV programs in resource-poor settings, often targeted solely to those with under-nutrition by low body mass index (BMI). This practice does not consider food insecurity, another important risk factor for poor outcomes in people living with HIV/AIDS (PLWH). We analyzed factors associated with low BMI and severe food insecurity in 523 PLWH receiving antiretroviral therapy in rural Haiti using logistic regression. Food insecurity was present in 89 % of individuals. Among those with severe food insecurity, 86 % had a BMI ≥ 18.5 kg/m(2). Severe food insecurity was associated with illiteracy [adjusted odds ratio (AOR) 1.79, p = 0.005], having no income (AOR 1.58, p = 0.04), and poverty (p food insecurity, individuals with severe food insecurity had a less diverse diet. We found that food insecurity was highly prevalent in PLWH receiving antiretroviral therapy in rural Haiti. Using BMI as a sole criterion for food supplementation in HIV programs can exclude highly vulnerable individuals who may benefit from such support.
[CLINICAL AND PHARMACOECONOMIC RESULTS OF THE USAGE OF VARIOUS HIV REVERSE TRANSCRIPTASE INHIBITORS IN THE SCHEMES OF ANTIRETROVIRAL THERAPY OF PATIENT RECEIVING THERAPY FOR THE CHRONIC HEPATITIS C VIRUS].
Moshkovich, G F; Minaeva, S V; Varlova, L W; Goryaeva, M P; Gulyaeva, S S; Tichonova, E V
Efficacy, safety, and economical aspects of treatment with abacavir, zidovudine, stavudine, and phosphazide in the schemes of antiretroviral therapy of the HIV-infected patients receiving therapy for hepatitis C virus were tested. Clinical, immunological, and virologic efficacy of treatment and dynamics of hemoglobin, thrombocytes, and alanine aminotransferase as markers of common adverse events recorded at the start of the antiviral therapy of chronic hepatitis C and after 4, 8, 12, 24, 48 weeks of the treatment were evaluated. The usage of these drugs in the schemes of antiretroviral therapy exhibited efficacy, high tolerability and safety for all HIV reverse transcriptase inhibitors.
Bradley N Gaynes
Full Text Available Recent blue-ribbon panel reports have concluded that HIV treatment programs in less wealthy countries must integrate mental health identification and treatment into normal HIV clinical care and that research on mental health and HIV in these settings should be a high priority. We assessed the epidemiology of depression in HIV patients on antiretroviral therapy in a small urban setting in Cameroon by administering a structured interview for depression to 400 patients consecutively attending the Bamenda Regional Hospital AIDS Treatment Center. One in five participants met lifetime criteria for MDD, and 7% had MDD within the prior year. Only 33% had ever spoken with a health professional about depression, and 12% reported ever having received depression treatment that was helpful or effective. Over 2/3 with past-year MDD had severe or very severe episodes. The number of prior depressive episodes and the number of HIV symptoms were the strongest predictors of past-year MDD. The prevalence of MDD in Cameroon is as high as that of other HIV-associated conditions, such as tuberculosis and Hepatitis B virus, whose care is incorporated into World Health Organization guidelines. The management of depression needs to be incorporated in HIV-care guidelines in Cameroon and other similar settings.
Bere, Tarisai; Nyamayaro, Primrose; Magidson, Jessica F; Chibanda, Dixon; Chingono, Alfred; Munjoma, Ronald; Macpherson, Kirsty; Ndhlovu, Chiratidzo Ellen; O'Cleirigh, Conall; Kidia, Khameer; Safren, Steven A; Abas, Melanie
Few evidence-based interventions to improve adherence to antiretroviral therapy have been adapted for use in Africa. We selected, culturally adapted and tested the feasibility of a cognitive-behavioural intervention for adherence and for delivery in a clinic setting in Harare, Zimbabwe. The intervention consisted of a single, 50-minute problem-solving cognitive-behavioural intervention session with four skill-based booster sessions, delivered by four lay adherence counsellors in the context of HIV care. Adaptation followed a theoretically driven approach to intervention adaptation, Assessment-Decision-Administration-Production-Topical Experts-Integration-Training-Testing (ADAPT-ITT), and included modifications to language, session length, tailoring content for delivery by lay counsellors and inclusion of culturally competent probes. The feasibility of the intervention was evaluated using a mixed-methods assessment, including ratings of provider fidelity of intervention delivery, and qualitative assessments of feasibility using individual semi-structured interviews with counsellors (n = 4) and patients (n = 15). The intervention was feasible and acceptable when administered to 42 patients and resulted in improved self-reported adherence in a subset of 15 patients who were followed up after 6 months. Next steps from this study include conducting a randomised control trial to evaluate the adapted intervention compared to standard of care in a larger sample over a long-term follow-up.
Abdissa, Alemseged; Yilma, Daniel; Fonager, Jannik;
BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub......-Saharan Africa is sparse. METHODS: HIV viral load (VL) and resistance mutations pre-ART and after 6 months were determined in a prospective cohort study of ART-naïve HIV patients initiating first-line therapy in Jimma, Ethiopia. VL measurements were done at baseline and after 3 and 6 months. Genotypic HIV drug...... was observed among 14 (5.3%) participants out of 265 patients. Twelve samples were genotyped and six had HIV drug resistance (HIVDR) mutations at baseline. Among virological failures, 9/11 (81.8%) harbored one or more HIVDR mutations at 6 months. The most frequent mutations were K103N and M184VI. CONCLUSIONS...
MacArthur, Rodger D; DuPont, Herbert L
Diarrhea remains a common problem for patients with human immunodeficiency virus (HIV) infection despite highly active antiretroviral therapies (HAART) and can negatively affect patient quality of life and lead to discontinuation or switching of HAART regimens. In the era of HAART, diarrhea from opportunistic infections is uncommon, and HIV-associated diarrhea often has noninfectious causes, including HAART-related adverse events and HIV enteropathy. Diarrhea associated with HAART is typically caused by protease inhibitors (eg, ritonavir), which may damage the intestinal epithelial barrier (leaky-flux diarrhea) and/or alter chloride ion secretion (secretory diarrhea). HIV enteropathy may result from direct effects of HIV on gastrointestinal tract cells and on the gastrointestinal immune system and gut-associated lymphoid tissue, which may be active sites of HIV infection and ongoing inflammation and mucosal damage. New therapies targeting the pathogenic mechanisms of noninfectious diarrheas are needed.
A. V. Mordyk
Full Text Available Retrospective research of 381 clinical records is conducted to study HIV infection influence on stationary stage of tuberculosis treatment outcome in HIV-TB co-infected patients. All cases were divided depending on a hospitalization outcome on favorable and adverse. At most of patients tuberculosis of respiratory organs met. Immunological researches were conducted, the stage of HIV infection was registered and the issue of purpose of anti-retroviral therapy was resolved. Besides, as indirect signs of an immunodeficiency at the patients with a combination of tuberculosis and HIV infection who were on hospitalization the indicators received when carrying out clinical laboratory trials were analyzed: absolute and relative quantity of lymphocytes according to the general blood test, the contents the globulin fractions and circulating immune complexes concentration according to the clinical chemistry blood test. At an assessment of results in both groups of research more than at a half of patients existence of HIV infection at late stages that speaks about late identification and neglect of an immunodeficiency was revealed. At patients with tuberculosis of lungs in combination with HIV infection at a failure statistically significant decrease in an immunoregulatory index is revealed. It is interesting that the level of CD4 lymphocytes and a stage of HIV infection had no impact on the co-infection’s outcome. However, existence of virus loa ding more than 100 000 copies/ml reduced probability favorable an outcome of treatment of tuberculosis at the patient with HIV infection. Timely purpose of anti-retroviral therapy at patients with co-infection increased chances of treatment of tuberculosis at patients with an immunodeficiency. Frequency of adverse side effect of antiviral therapy met equally often at patients in both groups. Thus, patients at any stages of HIV infection with any forms of tuberculosis, including generalized, had a
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
Imaz, Arkaitz; Falcó, Vicenç; Ribera, Esteban
Drug resistance is one of the key problems in the management of long-term HIV-1-infected patients. Due to cross-resistance patterns within classes, broad resistance to the three original antiretroviral classes can develop in some patients, mainly those with extensive antiretroviral treatment experience and multiple treatment failures. Triple-class-resistant HIV-1 infection has been associated with a higher risk of clinical progression and death. Additionally, it increases the probability of transmission of multidrug-resistant HIV-1 strains. Over the last years, the availability of new antiretroviral agents against novel targets (integrase inhibitors and CCR5 antagonists), and new drugs within old classes (nonnucleoside reverse transcriptase inhibitors and protease inhibitors) has opened a range of new therapeutic options for patients with multiclass drug-resistant HIV-1 infection and scarce therapeutic options with previous drugs. In randomized clinical trials, each of these new drugs has shown exceptional efficacy results, especially in patients who received other fully active drugs in the regimen. Indeed, in nonrandomized trials and observational studies, unprecedented rates of virologic suppression similar to those obtained in naive patients have been achieved when three of the currently available new drugs were combined, even in heavily experienced patients who had no viable salvage options with the previous classes. Thus, the goal of suppression and maintenance (plasma HIV-1 RNA infection. Treatment failure can still occur, however, and the management of patients with multidrug-resistant HIV-1 infection remains a challenge. Clinicians are encouraged to optimize use of the new drugs to obtain better control of HIV infection while avoiding emergence of new resistance-associated mutations. The aim of this article is to summarize current knowledge on the management of salvage therapy for patients with multidrug-resistant HIV-1 infection by analyzing the evidence
Hsu, Ling Chin; Truong, Hong-Ha M; Vittinghoff, Eric; Zhi, Qi; Scheer, Susan; Schwarcz, Sandra
In 2010, the San Francisco Department of Public Health offered antiretroviral therapy (ART) to all its patients with human immunodeficiency virus (HIV) regardless of CD4 count. We assessed trends in time from diagnosis to ART initiation and factors associated with ART initiation among San Francisco residents living with HIV between 2007 and 2011. Time to ART initiation decreased among those diagnosed with higher CD4 count. ART initiation rate was significantly higher in recent years and lower among African Americans, men who have sex with men who also inject drugs, and persons aged ≥50 years. We found a trend toward early treatment. However, racial and social disparities persist.
Mills, Edward J.; Nachega, Jean B.; Nsanzimana, Sabin; Penazzato, Martina; Appolo, Tsitsi; Ford, Nathan
Background Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities. Methods and Findings We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%–45.4%; adolescents 63.1%, 95% CI 46.3%–80.0%; children/caregivers 29.2%, 95% CI 20.1%–38.4%), being away from home (adults 30.4%, 95% CI 25.5%–35.2%; adolescents 40.7%, 95% CI 25.7%–55.6%; children/caregivers 18.5%, 95% CI 10.3%–26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%–35.0%; adolescents 32.4%, 95% CI 0%–75.0%; children/caregivers 26.3%, 95% CI 15.3%–37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%–18.3%; adolescents 25.7%, 95% CI 17.7%–33.6%; children 15.1%, 95% CI 3.9%–26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%–16.1%) and adolescents (28.8%, 95% CI 11.8%–45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%–15.3%; children/caregivers 22.3%, 95% CI 10.2%–34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%–18.8%) was a more commonly cited barrier to
Full Text Available Introduction: Paediatric antiretroviral therapy (ART guidelines have been updated several times in recent years. We assessed implementation of ART guidelines among under-five children to inform the transition to universal paediatric ART in Tanzania. Methods: We conducted a retrospective cohort analysis of infants (0 to 11 months and children (12 to 59 months enrolled between 2010 and 2012 using routinely collected data. Infants and children were initiated on ART according to the 2008 World Health Organization (WHO recommendations/2009 Tanzania guidelines (universal ART for infants. Cumulative ART initiation incidence and correlates of ART initiation were examined using competing risk methods accounting for attrition (death or loss to follow-up. Kaplan-Meier methods and Cox regression models were used to examine attrition on ART and its correlates. Results: A total of 1679 children were enrolled at 69 clinics: 469 (28% infants and 1210 (74% children. Infant cumulative ART initiation incidence was 59.6, 71.3 and 78.0% at one, three and six months of follow-up. Infants were more likely to start ART if enrolled in 2012 [adjusted sub-hazard ratio (AsHR=2.2, 95% confidence interval (CI: 1.7 to 2.8] or 2011 (AsHR=1.8, 95% CI: 1.4 to 2.3 compared to 2010; they were more likely to start ART from prevention of mother-to-child HIV transmission (AsHR=1.6, 95% CI: 1.3 to 2.1 and inpatient wards (AsHR=1.5, 95% CI: 1.2 to 2.0 versus being enrolled from voluntary counselling and testing centres. Attrition at 12 months on ART was 33.9% and was more likely among infants with WHO Stage 4 [adjusted hazard ratio (AHR=3.1. 95% CI: 1.8 to 5.2] and severe malnutrition (AHR=1.4, 95% CI: 1.0 to 1.9.Among 599 children eligible for ART at enrolment, cumulative ART initiation incidence was 51.8, 68.6 and 76.1% at one, three, and six months. Children were more likely to start ART if enrolled in 2012 (AsHR=1.8, 95% CI: 1.4 to 2.3 or 2011 (AsHR=1.5, 95% CI: 1.2 to 1.8 compared
Wiener, Jeffrey; King, Caroline C.; Heffron, Renee; Mugo, Nelly R.; Nanda, Kavita; Pyra, Maria; Donnell, Deborah; Celum, Connie; Lingappa, Jairam R.; Baeten, Jared M.
Background: While most recent evidence does not support a role for pregnancy in accelerating HIV disease progression, very little information is available on the effects of incident pregnancy in response to antiretroviral therapy (ART). Hormonal, immune, and behavioral changes during pregnancy may influence response to ART. We sought to explore the effects of incident pregnancy (after ART initiation) on virologic, immunologic, and clinical response to ART. Methods: Data were collected from HIV-infected women participating in 3 prospective studies (Partners in Prevention Herpes simplex virus/HIV Transmission Study, Couples Observational Study, and Partners Preexposure Prophylaxis Study) from 7 countries in Africa from 2004 to 2012. Women were included in this analysis if they were ≤45 years of age, were started on ART during the study and were not pregnant at ART initiation. Pregnancy was treated as a time-dependent exposure variable covering the duration of pregnancy, including all pregnancies occurring after ART initiation. Virologic failure was defined as a viral load (VL) greater than 400 copies per milliliter ≥6 months after ART initiation and viral suppression was defined as VL ≤400 copies per milliliter. Multivariable Cox proportional hazards models were used to assess the association between pregnancy and time to viral suppression, virologic failure, World Health Organization clinical stage III/IV, and death. Linear mixed-effects models were used to assess the association between pregnancy and CD4+ count and VL. All analyses were adjusted for confounders, including pre-ART CD4+ count and plasma VL. Results: A total of 1041 women were followed, contributing 1196.1 person-years of follow-up. Median CD4+ count before ART initiation was 276 cells per cubic millimeter (interquartile range, 209–375); median pre-ART VL was 17,511 copies per milliliter (interquartile range, 2480–69,286). One hundred ten women became pregnant after ART initiation. Pregnancy
Full Text Available Introduction: Despite normalization of total CD4 counts, ongoing immune dysfunction is noted amongst those on antiretroviral therapy (ART. Low CD4/CD8 ratio is associated with a high risk of AIDS and non-AIDS events and may act as a marker of immune senescence . This ratio is improved by ART although normalization is uncommon (~7% . The probability of normalization of CD4 count is improved with immediate ART initiation in primary HIV infection (PHI . We examined whether CD4/CD8 ratio similarly normalized in immediate vs. deferred ART at PHI. Material and Methods: Using data from the SPARTAC trial and the UK Register of HIV Seroconverters, we examined the effect of ART with time (continuous from HIV seroconversion (SC on CD4/CD8 ratio (≥1 adjusted for sex, risk group, ethnicity, enrolment from an African site and both CD4 count and age at ART initiation. We also examined that effect by dichotomizing HIV duration at ART initiation (ART started within six months of SC: early ART; ART initiated>six months after SC: deferred. We also considered time to CD4 count normalization (≥900 cells/mm3. Results: In total, 353 initiated ART with median (IQR 97.9 (60.5, 384.5 days from estimated seroconversion; 253/353 early ART, 100 deferred ART. At one year after starting ART, 114/253 (45% early ART had normalized CD4/8 ratio, compared with 11/99 (11% in the deferred group, whilst 83/253 (33% of early ART had normalized CD4 counts, compared with 3/99 (3% in the deferred group. Individuals initiating within six months of PHI were significantly more likely to reach normal ratio than those initiating later (HR, 95% CI 2.96, 1.75 – 5.01, p<0.001. The longer after SC ART was initiated, the reduced likelihood of achieving normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.96 – 0.99 for each 30-day increase. CD4 count at ART initiation was also associated with normalization, as expected (HR 1.002, 95% CI 1.001 – 1.002, p<0.001. There was an
Full Text Available Purpose: Bone turnover markers (BTM - aminoterminal propeptide of type 1 collagen (P1NP and C-terminal telopeptide of type 1 collagen (β-CTX - are related to bone density and fracture risk. A high prevalence of osteopenia/osteoporosis and hypovitaminosis D has been reported in HIV patients, however there are few data about BTM in this population. Our aim was to analyse the prevalence of elevated serum levels of BTM in HIV patients before starting antiretroviral therapy (ART, and related factors. Methods: Cross-sectional study of a series of HIV-patients who started ART during June/11–June/12 in our hospital. Patients with presence of diseases or treatments known to affect bone metabolism were excluded. Epidemiological, clinical, and immunovirological data in addition to serum fasting levels of glucose, lipid profile, calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D3 (25OHD, parathyroid hormone (PTH, P1NP, and β-CTX were collected. Definitions: hypovitaminosis D if 25OHD<30 ng/ml, vitamin D deficiency if 25OHD<20 ng/ml; elevated levels of BTM if β-CTX (ng/ml >0.64 (men<70 years,>0.85 (men >70 years,>0.58 (pre-menopause women, >0.99 (post-menopause women, or P1NP (ng/mL>69.4 (men <60 years, >71.1 (men>60 years, >55.7 (pre-menopause women, >61.2 (post-menopause women. Results: 47 patients were included, 91.5% men, median age 37.1 years (30.0–44.3, and 93.6% sexual transmission of HIV (34 HMX, 10 HTX. Median time since the diagnosis of HIV was 3.4 months (1.4–31.7; there were 7 (14.9% Aids cases, median CD4 count was 277/mm3 (155–433, and HIV-VL 4.8 log10 (4.1–5.2. Median serum 25OHD was 29 µg/L (21.9–41.1, with a prevalence of hypovitaminosis of 52.2%, and deficiency of 17.4%. PTH was in range in all cases. Median serum P1NP was 33.3 ng/mL (24.5–52.5 and β-CTX 0.25 ng/mL (0.20–0.45; five (11.4% patients presented high levels of BTM: 4 men, median age 37.1 years, median CD4 count 247/mm3, median HIV-VL 5.18 log10
Maina, E K; Bonney, E Y; Bukusi, E A; Sedegah, M; Lartey, M; Ampofo, W K
The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART.
Jeannia J Fu
Full Text Available Throughout Asia, people who use drugs are confined in facilities referred to as compulsory drug detention and rehabilitation centers. The limited transparency and accessibility of these centers has posed a significant challenge to evaluating detainees and detention conditions directly. Despite HIV being highly prevalent in this type of confined setting, direct evaluation of detainees with HIV and their access to medical care has yet to be reported in the literature.We evaluated the health status of 100 adult male detainees with HIV and their access to medical care in the two largest Malaysian compulsory drug detention and rehabilitation centers holding HIV-infected individuals.Approximately 80% of all detainees with HIV were surveyed in each detention center. Most participants reported multiple untreated medical conditions. None reported being able to access antiretroviral therapy during detention and only 9% reported receiving any HIV-related clinical assessment or care. Nearly a quarter screened positive for symptoms indicative of active tuberculosis, yet none reported having been evaluated for tuberculosis. Although 95% of participants met criteria for opioid dependence prior to detention, none reported being able to access opioid substitution therapy during detention, with 86% reporting current cravings for opioids and 87% anticipating relapsing to drug use after release. Fourteen percent of participants reported suicidal ideation over the previous two weeks.We identified a lack of access to antiretroviral therapy in two of the six compulsory drug detention and rehabilitation centers in Malaysia designated to hold HIV-infected individuals and found significant, unmet health needs among detainees with HIV. Individuals confined under such conditions are placed at considerably high risk for morbidity and mortality. Our findings underscore the urgent need for evidence-based drug policies that respect the rights of people who use drugs and seek
Jin, Xia; Ramanathan, Murugappan; Barsoum, Shady; Deschenes, Geoffrey R; Ba, Lei; Binley, James; Schiller, Daryl; Bauer, Daniel E; Chen, Donald C; Hurley, Arlene; Gebuhrer, Lucette; El Habib, Raphaelle; Caudrelier, Pierre; Klein, Michel; Zhang, Linqi; Ho, David D; Markowitz, Martin
In order to boost immune responses in persons in whom highly active antiretroviral therapy (HAART) was initiated within 120 days of the onset of symptoms of newly acquired human immunodeficiency virus type 1 (HIV-1) infection, we administered vaccines containing a canarypox virus vector, vCP1452, with HIV-1 genes encoding multiple HIV-1 proteins, and recombinant gp160. Fifteen HIV-1-infected subjects who achieved sustained suppression of plasma viremia for at least 2 years were enrolled. While continuing antiretroviral therapy, each subject received at least four intramuscular injections of the vaccines on days 0, 30, 90, and 180. Adverse events were mild, with the most common being transient tenderness at the vCP1452 injection site. Of the 14 patients who completed vaccination, 13 had significant increases in anti-gp120 or anti-p24 antibody titers, and 9 had transient augmentation of their T-cell proliferation responses to gp160 and/or p24. HIV-1-specific CD8(+) T cells were quantified using an intracellular gamma interferon staining assay. Among 11 patients who had increased CD8(+) T-cell responses, seven had responses to more than one HIV-1 antigen. In summary, vaccination with vCP1452 and recombinant gp160 appears safe and immunogenic in newly HIV-1-infected patients on HAART.
Do, Natalie T; Phiri, Kelesitse; Bussmann, Hermann; Gaolathe, Tendani; Marlink, Richard G; Wester, C William
As increasing numbers of persons are placed on potentially life-saving combination antiretroviral therapy (cART) in sub-Saharan Africa, it is imperative to identify the psychosocial and social factors that may influence antiretroviral (ARV) medication adherence. Using an 87 question survey, the following data were collected from patients on cART in Botswana: demographics, performance (Karnofsky) score, perceived stigma and level of HIV disclosure, attitudes and beliefs concerning HIV/AIDS, substance and/or drug use, depression, and pharmacy and healthcare provider-related factors. Overall adherence rates were determined by patient self-report, institutional adherence, and a culturally modified Morisky scale. Three hundred adult patients were recruited between April and May 2005. The overall cART adherence rate was 81.3% based on 4 day and 1 month patient recall and on clinic attendance for ARV medication refills during the previous 3 months. Adults receiving cART for 1-6 months were the least adherent (77%) followed by those receiving cART for greater than 12 months (79%). Alcohol use, depression, and nondisclosure of positive HIV status to their partner were predictive of poor adherence rates (p value HIV disclosure to "at-risk" partners and provide ongoing counseling and education to help patients recognize and overcome HIV-associated stigma, alcohol abuse, and depression.
Liotta, Giuseppe; Chimbwandira, Frank; Wouters, Kristien; Nielsen-Saines, Karin; Jere, Haswell; Mancinelli, Sandro; Ceffa, Susanna; Erba, Fulvio; Palombi, Leonardo; Marazzi, Maria Cristina
Combination antiretroviral therapy has been shown to reduce HIV transmission and incident infections. In recent years, Malawi has significantly increased the number of individuals on combination antiretroviral drugs through more inclusive treatment policies. Using a retrospective observational cohort design, records with HIV test results were reviewed for pregnant women attending a referral hospital in Malawi over a 5-year period, with viral load measurements recorded. HIV prevalence over time was determined, and results correlated with population viral load. A total of 11 052 women were included in this analysis, with 440 (4.1%) HIV infections identified. HIV prevalence rates in pregnant women in Malawi halved from 6.4% to 3.0% over 5 years. Mean viral loads of adult patients decreased from 120 000 copies/mL to less than 20 000 copies/mL. Results suggest that community viral load has an effect on HIV incidence rates in the population, which in turn correlates with reduced HIV prevalence rates in pregnant women.
Kenneth Anene Agu
Full Text Available PURPOSE: 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. METHODS: 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. CONCLUSION: 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.
Okonkwo, Prosper; Sagay, Atiene S; Agaba, Patricia A; Yohanna, Stephen; Agbaji, Oche O; Imade, Godwin E; Banigbe, Bolanle; Adeola, Juliet; Oyebode, Tinuade A; Idoko, John A; Kanki, Phyllis J
Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care.
Kume, Kodai; Ikeda, Kazuyo; Kamada, Masaki; Touge, Tetsuo; Deguchi, Kazushi; Masaki, Tsutomu
A 47-year-old man with HIV infection presented with lower leg dominant dysesthesia, muscle weakness and sensory ataxia of 3 month's duration. Nerve conduction studies (NCS) showed demyelination change in the median and tibial nerves and sensory nerve action potential (SNAP) in the sural nerve was not evoked. Somatosensory evoked potential (SEP) showed the delayed N9 latency. Diagnose of HIV-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was made. Although the CD4 lymphocyte counts were relatively preserved (466/μl), highly active anti-retroviral therapy (HAART) was started according to a new guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommending early initiation of treatment. After six months, HIV1-RNA was not detected and the CD4 lymphocyte counts showed a recovering trend (585/μl). His symptoms had disappeared, except for dysesthesia in the tip of a toe. Repeated NCS demonstrated full recovery from the demyelination and appearance of SNAP in the sural nerve. The improvement of his symptoms and NCS findings has been maintained for two years. Although effectiveness of immunotherapies such as oral prednisone, high-dose immunoglobulins and plasmapheresis have been reported in HIV-associated CIDP, early initiation of HAART may be also important for favorable prognosis in HIV-associated CIDP.
Ehrhard, Simone; Wernli, Marion; Dürmüller, Ursula; Battegay, Manuel; Gudat, Fred; Erb, Peter
Human immunodeficiency virus infection leads to T-cell exhaustion and involution of lymphoid tissue. Recently, the programmed death-1 pathway was found to be crucial for virus-specific T-cell exhaustion during human immunodeficiency virus infection. Programmed death-1 expression was elevated on human immunodeficiency virus-specific peripheral blood CD8+ and CD4+ T cells and correlated with disease severity. During human immunodeficiency infection, lymphoid tissue acts as a major viral reservoir and is an important site for viral replication, but it is also essential for regulatory processes important for immune recovery. We compared programmed death-1 expression in 2 consecutive inguinal lymph nodes of 14 patients, excised before antiretroviral therapy (antiretroviral therapy as of 1997-1999) and 16 to 20 months under antiretroviral therapy. In analogy to lymph nodes of human immunodeficiency virus-negative individuals, in all treated patients, the germinal center area decreased, whereas the number of germinal centers did not significantly change. Programmed death-1 expression was mostly found in germinal centers. The absolute extent of programmed death 1 expression per section was not significantly altered after antiretroviral therapy resulting in a significant-relative increase of programmed death 1 per shrunken germinal center. In colocalization studies, CD45R0+ cells that include helper/inducer T cells strongly expressed programmed death-1 before and during therapy, whereas CD8+ T cells, fewer in numbers, showed a weak expression for programmed death-1. Thus, although antiretroviral therapy seems to reduce the number of programmed death-1-positive CD8+ T lymphocytes within germinal centers, it does not down-regulate programmed death-1 expression on the helper/inducer T-cell subset that may remain exhausted and therefore unable to trigger immune recovery.
Maharaj, Sonill S.; Chetty, Verusia
Patients on highly active antiretroviral therapy (HAART) spend less time on vigorous activities due to lower aerobic capacity with functional limitations that can be attributed to a detraining effect, resulting in a poor quality of life (QoL). The overall aims of rehabilitation are to restore, to maintain, and to enhance the QoL and this…
Calmy, A; Carey, D; Mallon, P W G
BACKGROUND: No biological marker has been identified that predicts the development of lipodystrophy (LD). We investigated whether metabolic and body composition parameters could predict the development of LD over 2 years in adults initiating antiretroviral therapy (ART). METHODS: We used stored p...
Musiime, V.; Cook, A.; Kayiwa, J.; Zangata, D.; Nansubuga, C.; Arach, B.; Kenny, J.; Wavamunno, P.; Komunyena, J.; Kabamba, D.; Asiimwe, A.R.; Mirembe, G.; Abongomera, G.; Mulenga, V.; Kekitiinwa, A.; Kityo, C.; Walker, S.A.; Klein, N.; Gibb, D.M.; Burger, D.M.; Fillekes, Q.
BACKGROUND: Few studies have investigated objective markers of lipodystrophy in African children. We compared body circumferences, skin-fold thickness (SFT) and lipids in antiretroviral therapy (ART)-naive and stavudine (d4T)-exposed children with HIV-uninfected controls. METHODS: In the CHAPAS-3 tr
Ekouevi, Didier K; Coffie, Patrick A; Messou, Eugene
HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework...
von Wyl, Viktor; Cambiano, Valentina; Jordan, Michael R;
The most recent World Health Organization (WHO) antiretroviral treatment guidelines recommend the inclusion of zidovudine (ZDV) or tenofovir (TDF) in first-line therapy. We conducted a cost-effectiveness analysis with emphasis on emerging patterns of drug resistance upon treatment failure and the...
Tirivayi, Nyasha; Koethe, John R; Groot, Wim
BACKGROUND: There has been limited research to date on the effects of food assistance provided to HIV-infected adults in resource-constrained settings with a high prevalence of malnutrition and chronic food insecurity. We compare antiretroviral therapy (ART) adherence, weight gain, and CD4+ lymphocy
Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C;
Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function...
Hartling, Hans Jakob; Thørner, Lise W; Erikstrup, Christian;
OBJECTIVES: To investigate single-nucleotide polymorphisms (SNPs) in the gene encoding interleukin-7 receptor α (IL7RA) as predictors for CD4⁺ T-cell change after initiation of combination antiretroviral therapy (cART) in HIV-infected whites. DESIGN: SNPs in IL7RA were determined in the Danish HIV...
Wittkop, Linda; Günthard, Huldrych F; de Wolf, Frank;
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....
Obel, Niels; Kirk, Ole
BACKGROUND: The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS: We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS...
Cohen, Sophie; Smit, Colette; van Rossum, Annemarie M. C.; Fraaij, Pieter L. A.; Wolfs, Tom F. W.; Geelen, Sibyl P. M.; Schölvinck, Elisabeth H.; Warris, Adilia; Scherpbier, Henriette J.; Pajkrt, Dasja
Objectives:To describe demographic and treatment characteristics of the Dutch vertically HIV-infected paediatric population from 1996 to 2012, and to investigate the long-term virological and immunological response to combination antiretroviral therapy (cART), with emphasis on the influence of age a
Cohen, Sophie; Innes, Steve; Geelen, SPM; Wells, Jonathan C. K.; Smit, Colette; Wolfs, Tom F. W.; van Eck-Smit, Berthe L. F.; Kuijpers, Taco W.; Reiss, Peter; Scherpbier, Henriette J.; Pajkrt, Dasja; Bunders, Madeleine J.
Objective Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected child
We examined specific causes of mortality in human immunodeficiency virus type 1 (HIV-1)-infected patients who initiated antiretroviral therapy (ART) in Europe and North America from 1996 through 2006, and we quantified associations of prognostic factors with cause-specific mortality....
Mocroft, Amanda; Sterne, Jonathan A C; Egger, Matthias; May, Margaret; Grabar, Sophie; Furrer, Hansjakob; Sabin, Caroline; Fatkenheuer, Gerd; Justice, Amy; Reiss, Peter; d'Arminio Monforte, Antonella; Gill, John; Hogg, Robert; Bonnet, Fabrice; Kitahata, Mari; Staszewski, Schlomo; Casabona, Jordi; Harris, Ross; Saag, Michael; Niesters, Bert
BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started co
Dunn, DT; Gibb, DM; Duong, T; Babiker, AG; Bulterys, M; Gabiano, C; Galli, L; Giaquinto, C; Harris, DR; Hughes, M; McKinney, R; Mofenson, L; Moye, J; Newell, ML; Pahwa, S; Palumbo, P; Rudin, C; Schluchter, M; Sharland, M; Shearer, W; Thompson, B; Tookey, P
Background Data on the short-term risk of disease progression in HIV-1-infected children are needed to address the question of when to begin combination antiretroviral therapy. We estimated 12-month risks of progression to AIDS and death, by age and most recent measurement of CD4 T-cell percentage (
Lundgren, Jens; Emery, Sean; Neuhaus, Jacqueline A;
BACKGROUND: The SMART study randomized 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral suppression [VS] group). In the DC group...
Rodger, Alison J; Cambiano, Valentina; Bruun, Tina
IMPORTANCE: A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. OBJECTIVE: To evaluate the rate...
Reduction in coronary and peripheral vasomotor function in patients with HIV after initiation of antiretroviral therapy: a longitudinal study with positron emission tomography and flow-mediated dilation
Kristoffersen, Ulrik Sloth; Wiinberg, Niels; Petersen, Claus Leth;
The mechanisms underlying the increased cardiovascular risk in patients with HIV on antiretroviral therapy (ART) are not known. Our aim was to study the endothelial function of the coronary arteries by cardiac perfusion positron emission tomography (PET) in patients with HIV initiating ART...
J.W. Eaton (Jeffrey); D. Menzies; J. Stover (John); V. Cambiano (Valentina); L. Chindelevitch (Leonid); A. Cori (Anne); J.A.C. Hontelez (Jan A.C.); S. Humair (Salal); C.C. Kerr (Cliff); D.J. Klein (David); S. Mishra (Sharmistha); K.M. Mitchell (Kate); B.E. Nichols (Brooke); K. Vickerman; R. Bakker (Roel); T. Bärnighausen (Till); A. Bershteyn (Anna); D.E. Bloom (David); M-C. Boily (Marie-Claude); S.T. Chang (Stewart); T. Cohen (Ted); P. Dodd (Peter); C. Fraser (Christophe); C. Gopalappa (Chaitra); J. Lundgren (Jens); N.K. Martin (Natasha); T.S. Mikkelsen; E. Mountain (Elisa); Q.D. Pham (Quang); T. Pickles (Tom); A. Phillips (Andrew); S. Platt; C. Pretorius (Carel); H.J. Prudden (Holly); J.A. Salomon (Joshua); D.A.M.C. van de Vijver (David); S.J. de Vlas (Sake); B.G. Wagner (Bradley); R.G. White (Richard); D.C. Wilson (David); L. Zhang (Lingling); J. Blandford (John); G. Meyer-Rath (Gesine); M. Remme (Michelle); P. Revill (Paul); N. Sangrujee (Nalinee); F. Terris-Prestholt (Fern); M.C. Doherty (Meg); N. Shaffer (Nathan); P.J. Easterbrook (Philippa); G. Hirnschall (Gottfried); T.B. Hallett (Timothy)
textabstractBackground: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretr
May, M; Sterne, J; Costagliola, D
BACKGROUND: Highly active antiretroviral therapy (HAART) for the treatment of HIV infection was introduced a decade ago. We aimed to examine trends in the characteristics of patients starting HAART in Europe and North America, and their treatment response and short-term prognosis. METHODS: We ana...
Dragsted, Ulrik Bak; Mocroft, Amanda; Vella, Stefano;
BACKGROUND: Factors that determine the immunological response to highly active antiretroviral therapy (HAART) are poorly defined. OBJECTIVE: Our aim was to investigate predictors of immunological failure after initial CD4(+) response. METHODS: Data were from EuroSIDA, a prospective, international...
Full Text Available HIV-induced immunodeficiency is associated with metabolic abnormalities and systemic inflammation. We investigated the effect of antiretroviral therapy (ART on restoration of insulin sensitivity, markers of immune activation and inflammation.Immunological, metabolic and inflammatory status was assessed at antiretroviral therapy initiation and three years later in 208 patients from the ANRS-COPANA cohort. Patients were compared according to their pre-ART CD4+ cell count (group 1: ≤ 200/mm3, n = 66 vs. group 2: > 200/mm3, n = 142.Median CD4+ cell count increased in both groups after 3 years of successful ART but remained significantly lower in group 1 than in group 2 (404 vs 572 cells/mm3. Triglyceride and insulin levels were higher or tended to be higher in group 1 than in group 2 at ART initiation (median: 1.32 vs 0.97 mmol/l, p = 0.04 and 7.6 vs 6.8 IU, p = 0.09, respectively and remained higher after three years of ART (1.42 vs 1.16 mmol/L, p = 0.0009 and 8.9 vs 7.2 IU, p = 0.01. After adjustment for individual characteristics and antiretroviral therapy regimens (protease inhibitor (PI, zidovudine, insulin levels remained significantly higher in patients with low baseline CD4+ cell count. Baseline IL-6, sCD14 and sTNFR2 levels were higher in group 1 than in group 2. Most biomarkers of immune activation/inflammation declined during ART, but IL-6 and hsCRP levels remained higher in patients with low baseline CD4+ cell count than in the other patients (median are respectively 1.4 vs 1.1 pg/ml, p = 0.03 and 2.1 vs 1.3 mg/ml, p = 0.07.After three years of successful ART, low pretreatment CD4+ T cell count remained associated with elevated insulin, triglyceride, IL-6 and hsCRP levels. These persistent metabolic and inflammatory abnormalities could contribute to an increased risk of cardiovascular and metabolic disease.
Full Text Available The management of multidrug-resistant human immunodeficiency virus (MDR HIV infections in children is particularly challenging due to the lack of experience with new drugs. Dolutegravir, combined with an optimized antiretroviral background therapy, is promising for the treatment of MDR HIV and has been approved recently for adults and adolescents. Data for children are extremely limited. We describe the efficacy, safety and plasmatic levels of a dolutegravir-based, complex active antiretroviral treatment regimen in a severely overweight 11-year-old child infected with an MDR HIV strain.
El desenvolupament de fàrmacs que inhibeixen el cicle de replicació del virus de la immunodeficiència humana tipus 1 (VIH-1), coneguts com teràpia antiretroviral combinada (TAR), va ser un dels majors èxits clínics del segle XX. Tanmateix, malgrat que el tractament suprimeix eficientment la replicació viral, millora la funció immunitària i disminueix la morbiditat y mortalitat associades a la síndrome de la immunodeficiència humana (SIDA), la TAR no és capaç de curar aquesta infecció i presen...
Dzangare, J; Gonese, E; Mugurungi, O; Shamu, T; Apollo, T; Bennett, D E; Kelley, K F; Jordan, M R; Chakanyuka, C; Cham, F; Banda, R M
Monitoring human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) can help national antiretroviral treatment (ART) programs to identify clinic factors associated with HIVDR emergence and provide evidence to support national program and clinic-level adjustments, if necessary. World Health Organization-recommended HIVDR EWIs were monitored in Zimbabwe using routinely available data at selected ART clinics between 2007 and 2009. As Zimbabwe's national ART coverage increases, improved ART information systems are required to strengthen routine national ART monitoring and evaluation and facilitate scale-up of HIVDR EWI monitoring. Attention should be paid to minimizing loss to follow-up, supporting adherence, and ensuring clinic-level drug supply continuity.
Wandeler, Gilles; Gsponer, Thomas; Bihl, Florian; Bernasconi, Enos; Cavassini, Matthias; Kovari, Helen; Schmid, Patrick; Battegay, Manuel; Calmy, Alexandra; Egger, Matthias; Furrer, Hansjakob; Rauch, Andri
Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients worldwide. It is unclear whether HIV-related outcomes are affected by HBV coinfection. We compared virological suppression and immunological recovery during antiretroviral therapy (ART) of patients of different HBV serological status in the Swiss HIV Cohort Study. CD4 cell recovery during ART was significantly impaired in hepatitis B surface antigen-positive patients and in those with anti-hepatitis B core antigen alone compared with HBV-uninfected patients, despite similar virological efficacy of ART. CD4 increase in patients with resolved HBV infection was similar to that in HBV-uninfected individuals.
Ramalho, L C de Barros; Gonçalves, E M; de Carvalho, W R G; Guerra-Junior, G; Centeville, M; Aoki, F H; Morcillo, A M; dos Santos Vilela, M M; da Silva, M T N
This cross-sectional study aimed to compare growth, nutritional status and body composition outcomes between a group of 94 HIV-infected children and adolescents on antiretroviral therapy (ART) and 364 healthy controls, and to evaluate their association with clinical and lifestyle variables within the HIV-infected group. When compared with the control group, HIV patients had higher risk of stunting (odds ratio [OR] 5.33, 95% confidence interval [CI]: 2.83-10.04) and thinness (OR 4.7, 95% CI: 2.44-9.06), higher waist-to-hip ratios (medians 0.89 versus 0.82 for boys and 0.90 versus 0.77 for girls, P HIV-infected children on ART showed significant nutritional status and body composition abnormalities, consistent with the severity of vertical HIV infection and the consequences of prolonged ART.
da Cunha, Joel; Maselli, Luciana Morganti Ferreira; Stern, Ana Carolina Bassi; Spada, Celso; Bydlowski, Sérgio Paulo
For human immunodeficiency virus (HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy (HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results.
Full Text Available Aripiprazole is the first medication approved by the FDA as an add-on treatment for MDD. The impact of aripiprazole on the response to HIV is unknown. The patient we report on was diagnosed HIV-positive in 1997 and has been treated with antiretroviral therapy since then. In 2008, we diagnosed resistant major depression, hypochondria, and panic disorder. On that occasion, blood tests showed a significantly reduced CD4 count and a positive viral load. We treated this patient with aripiprazole and citalopram. Mood, somatic symptoms, and occupational functioning progressively improved. The last blood examination showed an increase in the CD4 count and a negative viral load. On the basis of the present case study and the review of the literature concerning the effects of psychotropic agents on viral replication, we suggest that the use of aripiprazole in HIV-infected subjects warrants further research.
McMahon, James H; Jordan, Michael R; Kelley, Karen; Bertagnolio, Silvia; Hong, Steven Y; Wanke, Christine A; Lewin, Sharon R; Elliott, Julian H
Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤ 6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to ART.
Desmonde, Sophie; Dicko, Fatoumata; Koueta, Fla;
OBJECTIVE: We describe the association between age at antiretroviral therapy (ART) initiation and 24-month CD4 cell response in West African HIV-infected children. METHODS: All HIV-infected children from the IeDEA paediatric West African cohort, initiating ART, with at least two CD4 cell count...... measurements, including one at ART initiation (baseline) were included. CD4 cell gain on ART was estimated using a multivariable linear mixed model adjusted for baseline variables: age, CD4 cell count, sex, first-line ART regimen. Kaplan-Meier survival curves and a Cox proportional hazards regression model...... compared immune recovery for age within 24 months post-ART. RESULTS: Of the 4808 children initiated on ART, 3014 were enrolled at a median age of 5.6 years; 61.2% were immunodeficient. After 12 months, children at least 4 years at baseline had significantly lower CD4 cell gains compared with children less...
Full Text Available In South Africa, abacavir (ABC is currently recommended as part of first- and second-line antiretroviral therapy (ART for HIV-positive paediatric patients. Concerns about overprescribing of the drug, particularly to adults, led to an analysis of ABC use in public sector ART programmes. We investigated current prescription of the drug to adults and children accessing ART in 4 public sector programmes across Gauteng Province, South Africa. ABC was almost exclusively prescribed to children initiating ART and adults requiring regimen changes due to drug toxicities. Patterns of ABC use among HIV-positive paediatric patients followed national ART treatment guidelines on the application of the drug. Although ABC is commonly used in the private sector for adults, the current national ART treatment guidelines for adults and adolescents should include ABC as an alternative to standard first- or second-line ART.
Phillips, Andrew N; Cambiano, Valentina; Miners, Alec
BACKGROUND: Increased rates of testing, with early antiretroviral therapy (ART) initiation, represent a key potential HIV-prevention approach. Currently, in MSM in the United Kingdom, it is estimated that 36% are diagnosed by 1 year from infection, and the ART initiation threshold is at CD4 cell...... on HIV in MSM in the United Kingdom. Outcomes were projected according to future alternative HIV testing and ART initiation scenarios to 2030, considering also potential changes in levels of condomless sex. RESULTS: For ART use to result in an incidence of close to 1/1000 person-years requires...... the proportion of all HIV-positive MSM with viral suppression to increase from below 60% currently to 90%, assuming no rise in levels of condomless sex. Substantial increases in HIV testing, such that over 90% of men are diagnosed within a year of infection, would increase the proportion of HIV-positive men...
Filteau, Suzanne; PrayGod, George; Kasonka, Lackson
BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study...... was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) ... was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART...
Ostrowski, Sisse R; Katzenstein, Terese L; Piironen, Timo;
High blood levels of the soluble urokinase receptor (suPAR) strongly predict increased mortality in human immunodeficiency virus-1 (HIV-1)-infected patients. This study investigated the plasma concentration of suPAR in 29 treatment-naive HIV-1-infected patients during 5 years treatment with highly...... active antiretroviral therapy (HAART). Plasma suPAR decreased after introducing HAART, most pronounced during the first treatment year. The change in plasma suPAR was independent of changes in viral replication and CD4+ cells but it was strongly correlated with plasma levels of the soluble TNF receptor...... is linked to inflammation in untreated as well as HAART-treated HIV-1-infected patients....
Dhasmana, Devesh J; Dheda, Keertan; Ravn, Pernille;
The use of antiretroviral therapy (ART) to treat HIV infection, by restoring CD4+ cell count and immune function, is associated with significant reductions in morbidity and mortality. Soon after ART initiation, there is a rapid phase of restoration of pathogen-specific immunity. In certain patients...... to a heterogeneous range of clinical manifestations. The commonest forms of IRIS are associated with mycobacterial infections, fungi and herpes viruses. In most patients, ART should be continued and treatment for the associated condition optimized, and there is anecdotal evidence for the use of corticosteroids...... in patients who are severely affected. In this review, we discuss research relating to pathogenesis, the range of clinical manifestations, treatment options and prevention issues....
Tseng, Alice L; la Porte, Charles; Salit, Irving E
A 42-year-old, treatment-experienced woman, virologically suppressed on tenofovir/emtricitabine and boosted atazanavir, experienced virological breakthrough, drop in CD4(+) T-cell count and undetectable drug concentrations. Adherence to treatment was confirmed, but repeat testing yielded similar results. After 2 months, the patient stated that she had been taking activated charcoal to manage gastrointestinal symptoms associated with her combination antiretroviral therapy, but she had recently discontinued the charcoal. Atazanavir concentrations were therapeutic but the patient's viral load rebounded and genotype testing revealed new reverse transcriptase mutations. The patient was changed to zidovudine, lamivudine, and boosted darunavir and achieved viral suppression. At 1 year follow-up, her viral load remained activated charcoal and atazanavir/ritonavir leading to virological breakthrough and development of resistance.
Treskova, Marina; Kuhlmann, Alexander; Bogner, Johannes; Hower, Martin; Heiken, Hans; Stellbrink, Hans-Jürgen; Mahlich, Jörg; Schulenburg, Johann-Matthias Graf von der; Stoll, Matthias
To analyze contemporary costs of HIV health care and the cost distribution across lines of combination antiretroviral therapy (cART). To identify variations in expenditures with patient characteristics and to identify main cost determinants. To compute cost ratios between patients with varying characteristics.Empirical data on costs are collected in Germany within a 2-year prospective observational noninterventional multicenter study. The database contains information for 1154 HIV-infected patients from 8 medical centers.Means and standard deviations of the total costs are estimated for each cost fraction and across cART lines and regimens. The costs are regressed against various patient characteristics using a generalized linear model. Relative costs are calculated using the resultant coefficients.The average annual total costs (SD) per patient are &OV0556;22,231.03 (8786.13) with a maximum of &OV0556;83,970. cART medication is the major cost fraction (83.8%) with a mean of &OV0556;18,688.62 (5289.48). The major cost-driving factors are cART regimen, CD4-T cell count, cART drug resistance, and concomitant diseases. Viral load, pathology tests, and demographics have no significant impact. Standard non-nucleoside reverse transcriptase inhibitor-based regimens induce 28% lower total costs compared with standard PI/r regimens. Resistance to 3 or more antiretroviral classes induces a significant increase in costs.HIV treatment in Germany continues to be expensive. Majority of costs are attributable to cART. Main cost determinants are CD4-T cells count, comorbidity, genotypic antiviral resistance, and therapy regimen. Combinations of characteristics associated with higher expenditures enhance the increasing effect on the costs and induce high cost cases.
Pérez-Santiago, Josué; Ouchi, Dan; Urrea, Victor; Carrillo, Jorge; Cabrera, Cecilia; Villà-Freixa, Jordi; Puig, Jordi; Paredes, Roger; Negredo, Eugènia; Clotet, Bonaventura; Massanella, Marta; Blanco, Julià
Background: The failure to increase CD4+ T-cell counts in some antiretroviral therapy suppressed participants (immunodiscordance) has been related to perturbed CD4+ T-cell homeostasis and impacts clinical evolution. Methods: We evaluated different definitions of immunodiscordance based on CD4+ T-cell counts (cutoff) or CD4+ T-cell increases from nadir value (ΔCD4) using supervised random forest classification of 74 immunological and clinical variables from 196 antiretroviral therapy suppressed individuals. Unsupervised clustering was performed using relevant variables identified in the supervised approach from 191 individuals. Results: Cutoff definition of CD4+ cell count 400 cells/μl performed better than any other definition in segregating immunoconcordant and immunodiscordant individuals (85% accuracy), using markers of activation, nadir and death of CD4+ T cells. Unsupervised clustering of relevant variables using this definition revealed large heterogeneity between immunodiscordant individuals and segregated participants into three distinct subgroups with distinct production, programmed cell-death protein-1 (PD-1) expression, activation and death of T cells. Surprisingly, a nonnegligible number of immunodiscordant participants (22%) showed high frequency of recent thymic emigrants and low CD4+ T-cell activation and death, very similar to immunoconcordant participants. Notably, human leukocyte antigen - antigen D related (HLA-DR) PD-1 and CD45RA expression in CD4+ T cells allowed reproducing subgroup segregation (81.4% accuracy). Despite sharp immunological differences, similar and persistently low CD4+ values were maintained in these participants over time. Conclusion: A cutoff value of CD4+ T-cell count 400 cells/μl classified better immunodiscordant and immunoconcordant individuals than any ΔCD4 classification. Immunodiscordance may present several, even opposite, immunological patterns that are identified by a simple immunological follow-up. Subgroup
HABERLEN, Sabina A.; NAKIGOZI, Gertrude; GRAY, Ronald H.; BRAHMBHATT, Heena; SSEKASANVU, Joseph; SERWADDA, David; NALUGODA, Fred; KAGAAYI, Joseph; WAWER, Maria. J.
Background A decade after the rollout of antiretroviral therapy (ART) in sub-Saharan Africa, the effects of this structural change on social aspects of HIV such as rates of HIV disclosure to partners remain largely unmeasured. We evaluated whether the introduction of ART was associated with disclosure of HIV diagnosis to spouses in Rakai, Uganda, using longitudinal, population-based data. Methods We identified individuals in marital/cohabitating unions who were newly diagnosed with HIV in Rakai Community Cohort Study (RCCS) surveys between 2000 and 2008, where antiretroviral therapy (ART) was introduced in mid-2004. Using discrete-time survival analysis, we assessed the hazard of self-reported HIV disclosure to spouse after diagnosis pre- and post-ART rollout, adjusting for individual and union characteristics. Disclosure in the ART period was further stratified by ART initiation. Results The analysis included 557 married adults, 264 of whom were diagnosed with HIV before ART was available (2000-2004) and 293 diagnosed after ART was introduced (2005-2008). The cumulative incidence of self-reported disclosure was 75.2% in the post-ART period, compared to 58.3% before ART availability (p<0.001, adjusted hazard 1.46 [95% CI 1.16, 1.83]). In the post-ART period, observed disclosure rates were 39% (72/184) among those not in HIV care, 65% (82/126) among those in pre-ART care, and 85% (64/75) among persons on ART (p<0.001). Conclusions Treatment availability and use, especially ART initiation, was associated with increased self-disclosure of HIV diagnosis to partners. ART access may facilitate the prevention of transmission to uninfected partners and linkage to treatment for infected couples. PMID:26009833
Anne Cecile Zoung-Kanyi
Full Text Available Background:Retention in long-term antiretroviral therapy (ART program remains a major challenge for effective management of HIV infected people in sub-Saharan Africa. Highly Active Antiretroviral Therapy (ART discontinuation raises concerns about drug resistance and could negate much of the benefit sought by ART programs. Methods:Based on existing patient records, we assessed determinants of retention in HIV care among HIV patients enrolled in an urban ART at two urban hospitals in Cameroon. Extended Cox regression procedures were used to identify significant predictors of retention in HIV care. Results:Of 455 patients, 314 (69% were women, median (IQR age and baseline CD4 cell count were respectively 36 years (30 – 43 and 110 cells/µL (39 – 177. Forty patients (9% had active tuberculosis (TB at enrollment. After a median (IQR follow-up of 18 months (10–18, 346 (75% were still in care, 8 (2% were known dead, and 101 (22% were lost to follow-up (LFU. Severe immunosuppression (CD4 cell count ≤ 50 cells/µL at baseline (aHR 2.3; 95% CI 1.4 - 3.7 and active tuberculosis upon enrollment (aHR 1.8; 95% CI 1.0 - 3.6 were independent predictors of cohort losses to follow-up within the first 6 months after HAART initiation. Conclusion:These data suggest that three-quarter of HIV patients initiated on HAART remained in care and on HAART by 18 months; however, those with compromised immunologic status at treatment initiation, and those co-infected with TB were at increased risk for being lost to follow-up within the first 6 months on treatment.
Marina Hjertquist Tremeschin
Full Text Available INTRODUCTION: HIV-infected children and adolescents treated with highly active antiretroviral therapy (HAART regimens that include a protease inhibitor (PI can show significant improvements in clinical outcomes, nutritional status and quality of life. The study aimed to report nutritional and metabolic alterations for pediatric patients continuously exposed to HAART and for healthy controls for up to 1 year. METHODS: Clinical, anthropometric, lipid profile and food intake data were collected prospectively over approximately 12-months for each patient. RESULTS: Fifty-one individuals were studied, of these, 16 were healthy. After 12 months follow-up, HIV-positive individuals remained below the healthy control group parameters. No change was observed concerning food intake. Triglyceride serum levels were higher in patients using protease inhibitor at the onset of the study [PI groups: 114 (43 - 336, and 136 (63 - 271 versus control group: 54.5 (20 - 162; p = 0.003], but after twelve months follow-up, only the group using protease inhibitor for up to two months presented higher values [140 (73 - 273 versus 67.5 (33 - 117; p = 0.004]. HDL-cholesterol was lower in HIV-positive individuals [HIV-positive groups: 36 (27 - 58 and 36 (23 - 43; control 49.5 (34 - 69; p = 0.004]. CONCLUSIONS: HIV-infected children and adolescents treated with highly active antiretroviral therapy showed compromised nutritional parameters compared to a paired healthy control group. Individuals using protease inhibitor presented worse triglyceride serum levels compared to their healthy counterparts.
Ruíz-López, Patricia; Moreno-Coutiño, Gabriela; Fernández-Martínez, Ramón; Espinoza-Hernández, Jessica; Rodríguez-Zulueta, Patricia; Reyes-Terán, Gustavo
Onychomycosis in HIV-infected patients has a prevalence of 20-44% and is more frequently seen with CD4(+) T cell counts ≤450 cel μl(-1). There are case reports of improvement in onychomycosis after initiation of combined antiretroviral therapy (cART), but there are no prospective studies that prove the existence and frequency of this phenomenon. The aim of this study was to evaluate if HIV-infected patients with onychomycosis who begin cART improve and/or cure without antifungal treatment. We included HIV-infected patients with onychomycosis who had not started cART and nor received antifungal therapy during 6 months prior to the study. We evaluated affected the nails with the Onychomycosis Severity Index (OSI); nail scrapings were collected and direct microscopy with potassium hydroxide (KOH) as well as mycological culture were performed. We repeated these procedures at 3 and 6 months to assess changes. CD4 T cell counts and HIV viral load were obtained. A total of 16 patients were included, with male gender predominance (68.7%); distal and lateral subungual onychomycosis (DLSO) was the most common form (31.3%). Trichophyton rubrum was the most frequently isolated microorganism. OSI decreased 21.5% at 3 months and 40% at 6 months after initiation of antiretrovirals (P = 0.05). We found a non-significant tendency towards improvement with higher CD4(+) T cell counts and with viral loads <100 000 copies ml(-1). This could be due to the increase in CD4(+) T cells, decreased percentage of Treg (CD4(+)CD25(+)) among CD4(+) Tcells and/or a decreased viral load; further studies are necessary to prove these hypothesis.
Mendelsohn, Joshua B; Rhodes, Tim; Spiegel, Paul; Schilperoord, Marian; Burton, John Wagacha; Balasundaram, Susheela; Wong, Chunting; Ross, David A
HIV-positive refugees confront a variety of challenges in accessing and adhering to antiretroviral therapy (ART) and attaining durable viral suppression; however, there is little understanding of what these challenges are, how they are navigated, or how they may differ across humanitarian settings. We sought to document and examine accounts of the threats, barriers and facilitators experienced in relation to HIV treatment and care and to conduct comparisons across settings. We conducted semi-structured interviews among a purposive sample of 14 refugees attending a public, urban HIV clinic in Kuala Lumpur, Malaysia (July-September 2010), and 12 refugees attending a camp-based HIV clinic in Kakuma, Kenya (February-March 2011). We used framework methods and between-case comparison to analyze and interpret the data, identifying social and environmental factors that influenced adherence. The multiple issues that threatened adherence to antiretroviral therapy or precipitated actual adherence lapses clustered into three themes: "migration", "insecurity", and "resilience". The migration theme included issues related to crossing borders and integrating into treatment systems upon arrival in a host country. Challenges related to crossing borders were reported in both settings, but threats pertaining to integration into, and navigation of, a new health system were exclusive to the Malaysian setting. The insecurity theme included food insecurity, which was most commonly reported in the Kenyan setting; health systems insecurity, reported in both settings; and emotional insecurity, which was most common in the Kenyan setting. Resilient processes were reported in both settings. We drew on the concept of "bounded agency" to argue that, despite evidence of personal and community resilience, these processes were sometimes insufficient for overcoming social and environmental barriers to adherence. In general, interventions might aim to bolster individuals' range of action with
Full Text Available Abstract Background In resource limited settings, many People Living with HIV/AIDS (PLWHA lack access to sufficient quantities of nutritious foods, which poses additional challenges to the success of antiretroviral therapy (ART. Maintaining adequate food consumption and nutrient intake levels and meeting the special nutritional needs to cope up with the disease and the ART are critical for PLWHA to achieve the full benefit of such a treatment. Objective To determine the prevalence and correlates of food insecurity among HIV-infected individuals receiving highly active antiretroviral therapy in resource-limited settings. Methods A cross sectional study was carried out from January 1, 2009 to March 3, 2009 at ART clinic at Jimma University specialized hospital (JUSH in Ethiopia. We used multivariable logistic regression model to compare independent risk factors by food insecurity status among 319 adult PLWHA (≥18 years attending ART Clinic. Results A total of 319 adult PLWHA participated in the study giving a response rate of 100%. Out of 319 PLWHA the largest numbers of participants, 46.4% were in the age group of 25-34 years. The overall 201(63.0% PLWHA were food insecure. Educational status of elementary or lower [OR = 3.10 (95%CI; (1.68-5.71], average family monthly income Conclusion Food insecurity is a significant problem among PLWHA on HAART. Lower educational status and low family income were the predictors of food insecurity. Food security interventions should be an integral component of HIV/AIDS care and support programs. Special attention need to be given to patients who have lower educational status and are members of households with low income.
Full Text Available Background: An increase in tuberculosis (TB incidence has been associated with human immunodeficiency virus (HIV. Aims: To describe the clinical characteristics and treatment outcome of patients with HIV and miliary TB treated with short-course intermittent chemotherapy in the absence of access to highly active antiretroviral therapy (HAART. Settings and Design: Prospective study of HIV infected adults referred to a TB clinic between July 1999 and July 2004. Materials and Methods: On diagnosis of miliary TB, patients were treated with a standard regimen of two months of isoniazid, rifampicin, ethambutol and pyrazinamide followed by four months of isoniazid and rifampicin (2EHRZ 3 /4RH 3 thrice weekly and followed up for 24 months. Patients were reviewed clinically every month and two sputa were collected. Chest radiographs and blood investigations were done at two months, end of treatment and every six months thereafter. Results: Of 498 patients with HIV and tuberculosis, 31 (6% were diagnosed as miliary tuberculosis. At diagnosis, sputum smear was positive for acid-fast bacilli (AFB in 14 patients (45% and Mycobacterium tuberculosis was isolated in 21 (68%. The mean CD4 cell count was 129 ± 125 cells/mm 3 . Twenty-five patients were declared cured at the end of treatment (81% while one (3% died and five (16% failed. The recurrence rate was 19.4/100 person-years and the median survival was 17 months (95% CI 14 to 20. None of the patients received antiretroviral therapy. Conclusions: Miliary TB tends to occur among HIV infected patients with severe immunosuppression. Though the initial response to short-course chemotherapy was encouraging, a high recurrence rate and mortality was observed indicating poor prognosis in HIV.
Full Text Available BACKGROUND: FcRgamma is an immunoreceptor tyrosine-based activation motif (ITAM-signalling protein essential for immunoreceptor signaling and monocyte, macrophage and NK cell function. Previous study from our laboratory showed that FcRgamma is down-regulated in HIV-infected macrophages in vitro. FcRgamma expression in immune cells present in HIV-infected individuals is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We compared FcRgamma expression in peripheral blood mononuclear cells isolated from HIV-1-infected individuals receiving combination antiretroviral therapy and healthy, HIV-1-uninfected individuals. FcRgamma mRNA and protein levels were measured using quantitative real-time PCR and immunoblotting, respectively. CD56(+ CD94(+ lymphocytes isolated from blood of HIV-1 infected individuals had reduced FcRgamma protein expression compared to HIV-uninfected individuals (decrease = 76.8%, n = 18 and n = 12 respectively, p = 0.0036. In a second group of patients, highly purified NK cells had reduced FcRgamma protein expression compared to uninfected controls (decrease = 50.2%, n = 9 and n = 8 respectively, p = 0.021. Decreased FcRgamma expression in CD56+CD94+ lymphocytes was associated with reduced mRNA (51.7%, p = 0.021 but this was not observed for the smaller group of patients analysed for NK cell expression (p = 0.36. CONCLUSION/SIGNIFICANCE: These data suggest biochemical defects in ITAM-dependent signalling within NK cells in HIV-infected individuals which is present in the context of treatment with combination antiretroviral therapy.
Andrade, Regis M; Andrade, Arnaldo F B; Lazaro, Marta A; Vieira, Morgana M M; Barros, Priscila O; Borner, Alice R S; Silva-Filho, Renato G; Santos, Juliana O; Brindeiro, Rodrigo M; Tanuri, Amilcar; Bento, Cleonice A M
The purpose of this study was to evaluate the impact of age on tetanus-specific immune response in successfully highly active antiretroviral therapy-treated AIDS patients, using healthy age-matched individuals as controls. Whole Peripheral blood mononuclear cells or CD8(+) cell-depleted peripheral blood mononuclear cells from previously tetanus toxoid (TT)-immunized individuals were activated with TT plus IL-2, and cell proliferation, cytokine production, and in vitro HIV-1 replication were measured. The in vivo magnitude of the humoral immune response was also assessed by antibody measurements. Our results showed that, compared with other groups, both in vitro TT-specific lymphoproliferation and serum antibody concentration were lower in older AIDS patients. Although the IL-1beta and tumour necrosis factor alpha (TNF-alpha) production were higher in cultures from aged HIV-1-infected patients, a dramatic damage on the interferon gamma (IFN-gamma) release was observed, when compared with younger patients. CD8(+) T lymphocytes depletion reduced IL-1beta and TNF-alpha release in the older groups, however, it did not significantly alter their IFN-gamma production. Furthermore, the neutralization of endogenous IL-10 did not change the IFN-gamma deficiency in older AIDS patients. Finally, the lower cellular immune response in this patient group was not related to in vitro HIV-1 replication. The results suggest that successfully highly active antiretroviral therapy-treated aged AIDS patients do not reconstitute the immune response to TT, making them probably more susceptible to tetanus even after vaccination.
Full Text Available Pharmaceutical care (PC has been shown to improve the outcome of drug therapy in many disease conditions. HIV/AIDS is one of the disease conditions that are fraught with many problems that can benefit from this new emphasis of pharmacy practice also known as ‘pharmacists care’. Adverse drug reactions or effects are unintended and undesirable effects of drugs other than their known and expected actions which can be unpleasant and sometimes fatal. This study is designed to evaluate the impact of pharmaceutical care activities on the occurrence of side/adverse drug reactions in HIV/AIDS patients receiving antiretroviral drugs. The components of the American society of health-system pharmacists (ASHP guidelines on ‘standardized method for pharmaceutical care’ was used as a data collection instrument to evaluate, document and intervene in the antiretroviral therapy of about one thousand four hundred and seventy three (1,473 patients. The study identified about sixty (60 different types of side/adverse effects occurring among these patients through observation and patient complaints. The study also showed significant reduction in the incidence of side/adverse drug effects following the Pharmacist’s intervention activities, p ≥ 0.5. The study showed that pharmacists’ interventions in antiretroviral drug therapy through Pharmaceutical care can significantly reduce the incidence of side/adverse drug effects in HIV/AIDS patients receiving antiretroviral drugs.
Han, In-Kwon; Kim, Mi Young; Byun, Hyang-Min; Hwang, Tae Sun; Kim, Jung Mogg; Hwang, Kwang Woo; Park, Tae Gwan; Jung, Woon-Won; Chun, Taehoon; Jeong, Gil-Jae; Oh, Yu-Kyoung
Recently, nasal administration has been studied as a noninvasive route for delivery of plasmid DNA encoding therapeutic or antigenic genes. Here, we examined the brain targeting efficiency and transport pathways of intranasally administered plasmid DNA. Quantitative polymerase chain reaction (PCR) measurements of plasmid DNA in blood and brain tissues revealed that intranasally administered pCMVbeta (7.2 kb) and pN2/CMVbeta (14.1 kb) showed systemic absorption and brain distribution. Following intranasal administration, the beta-galactosidase protein encoded by these plasmids was significantly expressed in brain tissues. Kinetic studies showed that intranasally administered plasmid DNA reached the brain with a 2,595-fold higher efficiency than intravenously administered plasmid DNA did, 10 min post-dose. Over 1 h post-dose, the brain targeting efficiencies were consistently higher for intranasally administered plasmid DNA than for intravenously administered DNA. To examine how plasmid DNA enters the brain and moves to the various regions, we examined tissues from nine brain regions, at 5 and 10 min after intranasal or intravenous administration of plasmid DNA. Intravenously administered plasmid DNA displayed similar levels of plasmid DNA in the nine different regions, whereas, intranasally administered plasmid DNA exhibited different levels of distribution among the regions, with the highest plasmid DNA levels in the olfactory bulb. Moreover, plasmid DNA was mainly detected in the endothelial cells, but not in glial cells. Our results suggest that intranasally applied plasmid DNA may reach the brain through a direct route, possibly via the olfactory bulb, and that the nasal route might be an alternative method for efficiently delivering plasmid DNA to the brain.
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.
Full Text Available Connie T Kekwaletswe,1 Neo K Morojele1,21Alcohol and Drug Abuse Research Unit, Medical Research Council, Pretoria, 2School of Public Health, University of the Witwatersrand, Johannesburg, South AfricaBackground: The primary objectives of this study were to determine the association between alcohol and antiretroviral therapy (ART adherence and the perceived appropriateness and acceptability of elements of an adherence counseling program with a focus on alcohol-related ART nonadherence among a sample of ART recipients in human immunodeficiency virus (HIV clinics in Tshwane, South Africa.Methods: We conducted a cross-sectional study with purposive sampling. The sample comprised 304 male and female ART recipients at two President's Emergency Plan For AIDS Relief-supported HIV clinics. Using an interview schedule, we assessed patients' alcohol use (Alcohol Use Disorders Identification Test, other drug use, level of adherence to ART, and reasons for missing ART doses (AIDS Clinical Trials Group adherence instrument. Additionally, patients’ views were solicited on: the likely effectiveness of potential facilitators; the preferred quantity, duration, format, and setting of the sessions; the usefulness of having family members/friends attend sessions along with the patient; and potential skill sets to be imparted.Results: About half of the male drinkers’ and three quarters of the female drinkers’ Alcohol Use Disorders Identification Test scores were suggestive of hazardous or harmful drinking. Average self-reported ART adherence was 89.7%. There was a significant association between level of alcohol use and degree of ART adherence. Overall, participants perceived two clinic-based sessions, each of one hour’s duration, in a group format, and facilitated by a peer or adherence counselor, as most appropriate and acceptable. Participants also had a favorable attitude towards family and friends accompanying them to the sessions. They also favored an
Full Text Available The patient information leaflet (PIL is recognised as playing a key role in informing patients about their medicines. The objectives of this research were to evaluate the readability and understanding of a PIL for the first-line ARV (antiretroviral regimen available in the South African public health sector, and investigate its acceptability in the target Xhosa population. Opsomming Daar word algemeen aanvaar dat die pasiëntinligtingsblaadjie (PIB ‘n sleutelrol speel in die oordra van inligting ten opsigte van medikasie aan pasiënte. Die doelwitte van hierdie navorsing was om die leesbaarheid en begrip van ‘n PIB vir die eerste-linie antiretrovirale (ARV regimen wat in die Suid-Afrikaanse openbare gesondheidsektor beskikbaar is, te evalueer, en om die aanvaarbaarheid daarvan in ‘n teiken-Xhosabevolking te ondersoek. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.
Frederikke F Rönsholt
Full Text Available OBJECTIVE: The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART. METHODS: Inflammation and endothelial activation were assessed by measuring levels of immunoglobulins, β2-microglobulin, interleukin (IL 8, tumor necrosis factor α (TNFα, vascular cell adhesion molecule-1 (sVCAM-1, intercellular adhesion molecule-1 (sICAM-1, sE-Selectin, and sP-Selectin. RESULTS: HIV infected patients had higher levels of β2-microglobulin, IL-8, TNFα, and sICAM-1 than uninfected controls, and HIV infected patients lacked correlation between platelet counts and sP-Selectin levels found in uninfected controls. CONCLUSION: Discrete signs of systemic and vascular inflammation persist even after very long term cART.
Ballif, Marie; Renner, Lorna; Claude Dusingize, Jean;
BACKGROUND: The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge. METHODS: We describe TB diagnosis...... and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries...... participated in the study. RESULTS: Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART...
Gilada, Ishwar; Gilada, T.
There are 34.2 million living with HIV/AIDS globally according to the UNAIDS. The incidence is 2.5 million new infections every year. Out of the 24.8 million patients eligible for antiretroviral treatment, only 8 million are actually receiving it. Nearly 1.7 million people (4658 per day) die of the disease every year i.e., 4658/day, making HIV/AIDS a planetary emergency. The most disturbing fact is that more than 50% of the infected people do not reveal their HIV status to their sexual partners. The UN Sec-Gen Ban Ki-moon suggested "3 Zeros"--Zero Infection, Zero Stigma, Zero AIDS-deaths in 2008...
Full Text Available Abstract Background Several lines of evidence suggest that retinoids (retinol-ROL or vitamin A, and its active metabolites, retinoic acids-RAs play important pathogenic roles in HIV infection and combination antiretroviral therapy (cART-related events. We previously reported that antiretrovirals alter RAs synthesis in vitro. We hypothesised that in vivo serum retinoid concentrations are affected by both cART and HIV infection. This might explain several clinical and laboratory abnormalities reported in HIV-infected patients receiving cART. Methods The effects of optimal cART and chronic HIV on serum retinoids were firstly assessed longitudinally in 10 HIV-infected adults (group1 = G1: twice while on optimal cART (first, during long-term and second, during short term cART and twice during 2 cART interruptions when HIV viral load (VL was detectable. Retinoid concentrations during optimal long term cART in G1 were compared with cross-sectional results from 12 patients (G2 with suboptimal cART (detectable VL and from 28 healthy adults (G3. Serum retinoids were measured by HPLC with ultraviolet detection. Retinoid concentrations were correlated with VL, CD4+ T- cell count and percentages, CD8+38+ fluorescence, triglycerides, cholesterol and C-peptide serum levels. Results During optimal cART, G1 participants had drastically reduced RAs (0.5 ± 0.3 μg/dL; P + T- cell count, CD8+38+ fluorescence, VL. ROL correlated with triglycerides and cholesterol in G1 (rs = 0.8; P = 0.01. Conclusions Serum RAs levels are significantly diminished by cART, whereas ROL concentrations significantly decreased during uncontrolled HIV infection but augmented with optimal cART. These alterations in retinoid concentrations may affect the expression of retinoid-responsive genes involved in metabolic, hormonal and immune processes and be responsible for some adverse events observed in HIV-infected persons treated with antiretrovirals. Further studies should assess
Pomarico, Luciana; Ferraz Cerqueira, Daniella; de Araujo Soares, Rosangela Maria; Ribeiro de Souza, Ivete Pomarico; Barbosa de Araujo Castro, Gloria Fernanda; Socransky, Sigmund; Haffajee, Anne; Palmier Teles, Ricardo
Objectives To examine the impact of antiretroviral therapy on the prevalence of oral candidiasis, recovery of oral Candida species (spp) and salivary levels of total secretory immunoglobulin A (SIgA) and Candida-specific SIgA in human immunodeficiency virus (HIV)-infected children. Methods Sixty six HIV-positive and 40 HIV-negative children were cross-sectionally examined for the presence of oral lesions. Whole stimulated saliva samples were collected for the identification of Candida spp using culture and measurement of total and specific SIgA using enzyme-linked immunosorbent assay (ELISA). Results HIV-positive children