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Sample records for antiretroviral therapy contributes

  1. Antiretroviral therapy: Shifting sands

    PubMed Central

    Sashindran, V.K.; Chauhan, Rajeev

    2016-01-01

    HIV/AIDS has been an extremely difficult pandemic to control. However, with the advent of antiretroviral therapy (ART), HIV has now been transformed into a chronic illness in patients who have continued treatment access and excellent long-term adherence. Existing indications for ART initiation in asymptomatic patients were based on CD4 levels; however, recent evidence has broken the shackles of CD4 levels. Early initiation of ART in HIV patients irrespective of CD4 counts can have profound positive impact on morbidity and mortality. Early initiation of ART has been found not only beneficial for patients but also to community as it reduces the risk of transmission. There have been few financial concerns about providing ART to all HIV-positive people but various studies have proven that early initiation of ART not only proves to be cost-effective but also contributes to economic and social growth of community. A novel multidisciplinary approach with early initiation and availability of ART at its heart can turn the tide in our favor in future. Effective preexposure prophylaxis and postexposure prophylaxis can also lower transmission risk of HIV in community. New understanding of HIV pathogenesis is opening new vistas to cure and prevention. Various promising candidate vaccines and drugs are undergoing aggressive clinical trials, raising optimism for an ever-elusive cure for HIV. This review describes various facets of tectonic shift in management of HIV. PMID:26900224

  2. Cardiovascular risks of antiretroviral therapies.

    PubMed

    Mondy, Kristin; Tebas, Pablo

    2007-01-01

    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.

  3. The latest in antiretroviral therapy.

    PubMed

    Temesgen, Zelalem

    2006-10-01

    The XVI International AIDS Conference (AIDS 2006), organized by the International AIDS Society (IAS), took place August 12-18 in Toronto, Canada. It was attended by over 26,000 participants from more than 170 countries and featured more than 4,500 abstracts as well as an array of community and cultural activities. The theme of the meeting was "Time to deliver", emphasizing the continued need and urgency in bringing effective HIV prevention and treatment strategies to those living with and affected by HIV/AIDS. The meeting's agenda was broad and included policy and programmatic topics as well as scientific research. This report focuses on reports presented at the conference that directly deal with antiretroviral therapy. This is primarily because of the nature of the venue where it is intended to be published (Drug News & Perspectives) as well as the expertise of the author. It is not a lack of recognition of the other equally important topics and discussions that took place at AIDS 2006. The author is solely responsible for the selection of topics and presentations to be included in this report.

  4. CROI 2015: Advances in Antiretroviral Therapy.

    PubMed

    Olender, Susan A; Taylor, Barbara S; Wong, Marcia; Wilkin, Timothy J

    2015-01-01

    The 2015 Conference on Retroviruses and Opportunistic Infections included new and exciting advances in the realm of antiretroviral therapy. The Temprano trial demonstrated benefits from early antiretroviral therapy and isoniazid preventive therapy. Important data on investigational antiretroviral drugs were presented, including tenofovir alafenamide fumarate and BMS-955176, an HIV-1 maturation inhibitor. Novel data on the HIV care continuum from resource-rich and -limited settings highlighted persistent sex- and race-related disparities in care engagement, and the crucial need to bring HIV testing and care into the community to improve engagement across the care continuum. Life expectancy data from resource-limited settings reveal dramatic improvements across sub-Saharan Africa, although people with HIV still live 5 years to 10 years less than those without HIV, and new cost-effectiveness research revealed that the price of antiretroviral therapy itself remains a key driver of cost and cost-effectiveness calculations. Results from the PROMISE trial showed reduced rates of mother-to-child transmission among women who received antiretroviral therapy with 3 drugs compared with women who received zidovudine monotherapy, supporting current World Health Organization guidelines.

  5. Persistent HIV-1 replication during antiretroviral therapy

    PubMed Central

    Martinez-Picado, Javier; Deeks, Steven G.

    2016-01-01

    Purpose of review The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART). Recent findings Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on efficiently targeting these three aspects. The degree to which HIV replicates during ART remains controversial. Most studies have failed to find any evidence of HIV evolution in blood, even with samples collected over many years, although a recent very intensive study of three individuals suggested that the virus population does shift, at least during the first few months of therapy. Stronger but still not definitive evidence for replication comes from a series of studies in which standard regimens were intensified with an integration inhibitor, resulting in changes in episomal DNA (blood) and cell-associated RNA (tissue). Limited drug penetration within tissues and the presence of immune sanctuaries have been argued as potential mechanisms allowing HIV to spread during ART. Mathematical models suggest that HIV replication and evolution is possible even without the selection of fully drug-resistant variants. As persistent HIV replication could have clinical consequences and might limit the efficacy of curative interventions, determining if HIV replicates during ART and why, should remain a key focus of the HIV research community. Summary Residual viral replication likely persists in lymphoid tissues, at least in a subset of individuals. Abnormal levels of immune activation might contribute to sustain virus replication. PMID:27078619

  6. Individualization of antiretroviral therapy - Pharmacogenomic aspect

    PubMed Central

    Dalal, Bhavik; Shankarkumar, Aruna; Ghosh, K.

    2015-01-01

    Combination therapy with three drug regimens for human immunodeficiency virus (HIV) infection significantly suppresses the viral replication. However, this therapeutic impact is restricted by adverse drug events and response in terms of short and long term efficacy. There are multiple factors involved in different responses to antiretrovirals (ARVs) such as age, body weight, disease status, diet and heredity. Pharmacogenomics deals with individual genetic make-up and its role in drug efficacy and toxicity. In depth genetic research has provided evidence to predict the risk of developing certain toxicities for which personalized screening and surveillance protocols may be developed to prevent side effects. Here we describe the use of pharmacogenomics for optimal use of HAART (highly active antiretroviral therapy). PMID:26831415

  7. Guidelines for antiretroviral therapy for HIV infection

    PubMed Central

    Rachlis, A R; Zarowny, D P

    1998-01-01

    OBJECTIVE: To develop guidelines for health care providers and their HIV-positive patients on the clinical use of antiretroviral agents for HIV infection. OPTIONS: Recommendations published in 1996 by an international panel. OUTCOMES: Improvement in clinical outcomes or in surrogate markers of disease activity. EVIDENCE AND VALUES: The Canadian HIV Trials Network held a workshop on Oct. 19-20, 1996, to develop Canadian guidelines that incorporate information from recent basic and clinical research. RECOMMENDATIONS: Recommendations for the use of antiretroviral drugs in HIV infection are provided for initial therapy, continuing therapy, primary infection, vertical transmission, pediatric therapy and postexposure prophylaxis. VALIDATION: The guidelines are based on consensus of the participants attending the workshop: Canadian investigators, clinicians and invited representatives from the community, government and the pharmaceutical industry. They are subject to review and updating as new information on clinical benefits is published. SPONSORS: The workshop was organized by the National Centre of the Canadian HIV Trials Network. Unrestricted educational grants were provided by 8 pharmaceutical companies. Additional support was provided from the National AIDS Strategy of Health Canada. PMID:9627563

  8. [Pilot study of antiretroviral therapy in Djibouti].

    PubMed

    Ahmed, A A; Latoundji, S

    2007-01-01

    A cross-sectional survey was conducted among 112 HIV positive patients who had received antiretroviral therapy for >3 months to assess the efficacy of treatment (viral load <400 copies/mL). The median age at enrolment was 36 years, 90% of patients were at the AIDS stage and median CD4 rate was 118/mm3. Patients received a combined treatment of 2 NRTI +1 NNRTI (51%), 3 NRTI (45%) and 2 NRTI+1 PI (4%). Virological efficacy was seen in 74% of the patients, irrespective of the prescribed protocol and the initial clinical and immunological profile. Mean improvements measured were 20% on the Karnofsky index (KI), 2.1 kg/m2 in body mass index and 82 cells/mm in CD4. The prevalence of side effects was 84%. The predictors for treatment success were quality of care and KI > 70%.

  9. Increased Regulatory T-Cell Percentage Contributes to Poor CD4(+) Lymphocytes Recovery: A 2-Year Prospective Study After Introduction of Antiretroviral Therapy.

    PubMed

    Saison, Julien; Maucort Boulch, Delphine; Chidiac, Christian; Demaret, Julie; Malcus, Christophe; Cotte, Laurent; Poitevin-Later, Francoise; Miailhes, Patrick; Venet, Fabienne; Trabaud, Mary Anne; Monneret, Guillaume; Ferry, Tristan

    2015-04-01

    Background.  The primary aim of this study was to determine the impact of regulatory T cells (Tregs) percentage on immune recovery in human immunodeficiency virus (HIV)-infected patients after antiretroviral therapy introduction. Methods.  A 2-year prospective study was conducted in HIV-1 chronically infected naive patients with CD4 count <500 cells/mm(3). Regulatory T cells were identified as CD4(+)CD25(high)CD127(low) cells among CD4(+) lymphocytes. Effect of Treg percentage at inclusion on CD4 evolution overtime was analyzed using a mixed-effect Poisson regression for count data. Results.  Fifty-eight patients were included (median CD4 = 293/mm(3), median Treg percentage = 6.1%). Percentage of Treg at baseline and CD4 nadir were independently related to the evolution of CD4 absolute value according to time: (1) at any given nadir CD4 count, 1% increase of initial Treg was associated with a 1.9% lower CD4 absolute value at month 24; (2) at any given Treg percentage at baseline, 10 cell/mm(3) increase of CD4 nadir was associated with a 2.4% increase of CD4 at month 24; and (3) both effects did not attenuate with time. The effect of Treg at baseline on CD4 evolution was as low as the CD4 nadir was high. Conclusions.  Regulatory T-cell percentage at baseline is a strong independent prognostic factor of immune recovery, particularly among patients with low CD4 nadir.

  10. Men and antiretroviral therapy in Africa: our blind spot.

    PubMed

    Cornell, Morna; McIntyre, James; Myer, Landon

    2011-07-01

    Most antiretroviral therapy (ART)-related policies remain blind to men's treatment needs. Global and national programmes need to address this blindness urgently, to ensure equitable access to ART in Africa.

  11. Immune restoration disease after antiretroviral therapy.

    PubMed

    French, Martyn A; Price, Patricia; Stone, Shelley F

    2004-08-20

    Suppression of HIV replication by highly active antiretroviral therapy (HAART) often restores protective pathogen-specific immune responses, but in some patients the restored immune response is immunopathological and causes disease [immune restoration disease (IRD)]. Infections by mycobacteria, cryptococci, herpesviruses, hepatitis B and C virus, and JC virus are the most common pathogens associated with infectious IRD. Sarcoid IRD and autoimmune IRD occur less commonly. Infectious IRD presenting during the first 3 months of therapy appears to reflect an immune response against an active (often quiescent) infection by opportunistic pathogens whereas late IRD may result from an immune response against the antigens of non-viable pathogens. Data on the immunopathogenesis of IRD is limited but it suggests that immunopathogenic mechanisms are determined by the pathogen. For example, mycobacterial IRD is associated with delayed-type hypersensitivity responses to mycobacterial antigens whereas there is evidence of a CD8 T-cell response in herpesvirus IRD. Furthermore, the association of different cytokine gene polymorphisms with mycobacterial or herpesvirus IRD provides evidence of different pathogenic mechanisms as well as indicating a genetic susceptibility to IRD. Differentiation of IRD from an opportunistic infection is important because IRD indicates a successful, albeit undesirable, effect of HAART. It is also important to differentiate IRD from drug toxicity to avoid unnecessary cessation of HAART. The management of IRD often requires the use of anti-microbial and/or anti-inflammatory therapy. Investigation of strategies to prevent IRD is a priority, particularly in developing countries, and requires the development of risk assessment methods and diagnostic criteria.

  12. Investigational protease inhibitors as antiretroviral therapies

    PubMed Central

    Midde, Narasimha M.; Patters, Benjamin J.; Rao, PSS; Cory, Theodore J.; Kumar, Santosh

    2017-01-01

    Introduction Highly Active Antiretroviral Therapy (HAART) has tremendously improved the life expectancy of the HIV-infected population over the past three decades. Protease inhibitors have been one of the major classes of drugs in HAART regimens that are effective in treating HIV. However, the emergence of resistance and cross-resistance against protease inhibitors encourages researchers to develop new PIs with broad-spectrum activity, as well as novel means of enhancing the efficacy of existing PIs. Areas covered In this article we discuss recent advances in HIV protease inhibitor (PI) development, focusing on both investigational and experimental agents. We also include a section on pharmacokinetic booster drugs for improved bioavailability of protease inhibitors. Further, we discuss novel drug delivery systems using a variety of nanocarriers for the delivery of PIs across the blood-brain barrier to treat the HIV in the brain. Expert opinion We discuss our opinion on the promises and challenges on the development of novel investigational and experimental PIs that are less toxic and more effective in combating drug-resistance. Further, we discuss the future of novel nanocarriers that have been developed to deliver PIs to the brain cells. Although these are promising findings, many challenges need to be overcome prior to making them a viable option. PMID:27415449

  13. Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

    PubMed

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

    2015-06-01

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

  14. Incident Tuberculosis during Antiretroviral Therapy Contributes to Suboptimal Immune Reconstitution in a Large Urban HIV Clinic in Sub-Saharan Africa

    PubMed Central

    Hermans, Sabine M.; Kiragga, Agnes N.; Schaefer, Petra; Kambugu, Andrew; Hoepelman, Andy I. M.; Manabe, Yukari C.

    2010-01-01

    Background Antiretroviral therapy (ART) effectively decreases tuberculosis (TB) incidence long-term, but is associated with high TB incidence rates in the first 6 months. We sought to determine the incidence and the long-term effects of TB during ART on HIV treatment outcome, and the risk factors for incident TB during ART in a large urban HIV clinic in Uganda. Methodology/Principal Findings Routinely collected longitudinal clinical data from all patients initiated on first-line ART was retrospectively analysed. 5,982 patients were included with a median baseline CD4+ T cell count (CD4 count) of 117 cells/mm3 (interquartile range [IQR]; 42, 182). In the first 2 years, there were 336 (5.6%) incident TB events in 10,710 person-years (py) of follow-up (3.14 cases/100pyar [95% CI 2.82–3.49]); incidence rates at 0–3, 3–6, 6–12 and 12–24 months were 11.25 (9.58–13.21), 6.27 (4.99–7.87), 2.47 (1.87–3.36) and 1.02 (0.80–1.31), respectively. Incident TB during ART was independently associated with baseline CD4 count of <50 cells/mm3 (hazard ratio [HR] 1.84 [1.25–2.70], P = 0.002) and male gender (HR 1.68 [1.34–2.11], P<0.001). After two years on ART, the patients who had developed TB in the first 12 months had a significantly lower median CD4 count increase (184 cells/mm3 [IQR; 107, 258, n = 118] vs 209 cells/mm3 [124, 309, n = 2166], P = 0.01), a larger proportion of suboptimal immune reconstitution according to two definitions (increase in CD4 count <200 cells/mm3: 57.4% vs 46.9%, P = 0.03, and absolute CD4 count <200 cells/mm3: 30.4 vs 19.9%, P = 0.006), and a higher percentage of immunological failure according to the WHO criteria (13.6% vs 6.5%, P = 0.003). Incident TB during ART was independently associated with poor CD4 count recovery and fulfilling WHO immunogical failure definitions. Conclusions/Significance Incident TB during ART occurs most often within 3 months and in patients with CD4 counts less than 50 cells

  15. Abnormal contingent negative variation in HIV patients receiving antiretroviral therapy

    PubMed Central

    Chao, Linda L.; Cardenas, Valerie A.; Meyerhoff, Dieter J.; Rothlind, Johannes C.; Flenniken, Derek L.; Lindgren, Joselyn A.; Weiner, Michael W.

    2009-01-01

    The contingent negative variation, an event-related potential related to neural activity in the frontal lobe and basal ganglia, neuropsychological tests and structural MRI were used to examine CNS function and structure in HIV-positive patients receiving antiretroviral therapy. Relative to controls, HIV patients had smaller thalamic volume and reduced late contingent negative variation amplitude that correlated with caudal atrophy. Behaviorally, viremic patients were more impaired than virally suppressed patients and controls on neuropsychological measures of psychomotor speed, selective attention and mental flexibility. These results suggest that antiretroviral therapy may not be effective in protecting cortical and subcortical structures against HIV-related neuropathology, regardless of immune function. However, the benefits of antiretroviral therapy on immune function appear to facilitate neurocognitive performance. PMID:14600507

  16. Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC).

    PubMed

    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

    2014-06-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. Potential drug interactions in patients given antiretroviral therapy

    PubMed Central

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

    2016-01-01

    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. PMID:27878224

  19. Forgiveness of non-adherence to HIV-1 antiretroviral therapy.

    PubMed

    Shuter, Jonathan

    2008-04-01

    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.

  20. Antiretroviral Therapy for HIV Infection: When to Initiate Therapy, Which Regimen to Use, and How to Monitor Patients on Therapy.

    PubMed

    Johnson, Steven C

    Antiretroviral therapy is recommended for all patients with HIV infection. The benefit of immediate antiretroviral therapy was confirmed by results from the START (Strategic Timing of Antiretroviral Treatment) trial, which showed a 57% reduction in risk for the composite end point of AIDS-related events, serious non-AIDS-related events, or death from any cause with immediate treatment in antiretroviral therapy-naive participants with CD4+ cell counts above 500/µL. Other changes in HIV care include the widespread adoption of integrase strand transfer inhibitor-based regimens. Considerations regarding when to initiate antiretroviral therapy, which initial regimens to use, and appropriate monitoring of individuals taking antiretroviral therapy are discussed. This article summarizes an IAS-USA continuing education webinar presented by Steven C. Johnson, MD, in July 2015.

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

    PubMed Central

    Ramos-Sanchez, Eduardo Milton; Goto, Hiro; Rivero, Dolores Helena Rodriguez Ferreira; Mauad, Thais; de Souza, Fernando Nogueira; Monteiro, Andrea Moreira; Gidlund, Magnus

    2014-01-01

    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. PMID:25075786

  2. Antiretroviral Therapy for HIV-2 Infection: Recommendations for Management in Low-Resource Settings

    PubMed Central

    Peterson, Kevin; Jallow, Sabelle; Rowland-Jones, Sarah L.; de Silva, Thushan I.

    2011-01-01

    HIV-2 contributes approximately a third to the prevalence of HIV in West Africa and is present in significant amounts in several low-income countries outside of West Africa with historical ties to Portugal. It complicates HIV diagnosis, requiring more expensive and technically demanding testing algorithms. Natural polymorphisms and patterns in the development of resistance to antiretrovirals are reviewed, along with their implications for antiretroviral therapy. Nonnucleoside reverse transcriptase inhibitors, crucial in standard first-line regimens for HIV-1 in many low-income settings, have no effect on HIV-2. Nucleoside analogues alone are not sufficiently potent enough to achieve durable virologic control. Some protease inhibitors, in particular those without ritonavir boosting, are not sufficiently effective against HIV-2. Following review of the available evidence and taking the structure and challenges of antiretroviral care in West Africa into consideration, the authors make recommendations and highlight the needs of special populations. PMID:21490779

  3. Antiretroviral therapy reduces neurodegeneration in human immunodeficiency virus infection

    PubMed Central

    Bryant, Alex K.; Ellis, Ronald J.; Umlauf, Anya; Gouaux, Ben; Soontornniyomkij, Virawudh; Letendre, Scott L.; Achim, Cristian L.; Masliah, Eliezer; Grant, Igor; Moore, David J.

    2015-01-01

    Objective To determine the effect of virally-suppressive antiretroviral therapy on cortical neurodegeneration and associated neurocognitive impairment. Design Retrospective, postmortem observational study. Methods Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 human immunodeficiency virus-infected volunteers from the general community who had never undergone antiretroviral therapy (n=7, “naïve”) or who had undergone antiretroviral therapy and whose plasma viral load was detectable (n = 64 “unsuppressed”) or undetectable (n = 19, “suppressed”) at the last clinical visit prior to death. Subjects were predominately male (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections. Results The suppressed group had higher SYP density than the naïve group (p = 0.007) and higher MAP2 density than the unsuppressed group (p = 0.04). The suppressed group had lower odds of human immunodeficiency virus-associated neurocognitive disorders than naïve (OR 0.07, p = 0.03). Higher SYP was associated with lower likelihood of human immunodeficiency virus-associated neurocognitive disorders in univariable (OR 0.8, p=0.03) and multivariable models after controlling for antiretroviral treatment and brain human immunodeficiency virus p24 protein levels (OR 0.72, p=0.01). Conclusions We conclude that virally suppressive antiretroviral treatment protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes. PMID:25686681

  4. Clinically Relevant Pharmacokinetic Herb-drug Interactions in Antiretroviral Therapy.

    PubMed

    Fasinu, Pius S; Gurley, Bill J; Walker, Larry A

    2015-01-01

    For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In this review, the bases for potential interaction of medicinal herbs with specific antiretroviral drugs are presented, and several botanicals are discussed for which clinically relevant interactions in humans are established. Such studies have provided, in most cases, sufficient ground to warrant the avoidance of concurrent administration of antiretroviral (ARVs) drugs with St John's wort (Hypericum perforatum), black pepper (Piper species) and grapefruit juice. Other botanicals that require caution in the use with antiretrovirals include African potato (Hypoxis hemerocallidea), ginkgo (Ginkgo biloba), ginseng (Panax species), garlic (Allium sativum), goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum). The knowledge of clinically significant herb-drug interaction will be important in order to avoid herb-induced risk of sub-therapeutic exposure to ARVs (which can lead to viral resistance) or the precipitation of toxicity (which may lead to poor compliance and/or discontinuation of antiretroviral therapy).

  5. Effect of Antiretroviral Therapy on HIV Reservoirs in Elite Controllers

    PubMed Central

    Chun, Tae-Wook; Shawn Justement, J.; Murray, Danielle; Kim, Connie J.; Blazkova, Jana; Hallahan, Claire W.; Benko, Erika; Costiniuk, Cecilia T.; Kandel, Gabor; Ostrowski, Mario; Kaul, Rupert; Moir, Susan; Casazza, Joseph P.; Koup, Richard A.; Kovacs, Colin; Fauci, Anthony S.

    2013-01-01

    Elite controllers suppress human immunodeficiency virus (HIV) viremia to below the limit of detection in the absence of antiretroviral therapy (ART). However, precise frequencies of CD4+ T cells carrying replication-competent HIV and/or the dynamics of the infectious viral reservoirs in response to initiation and discontinuation of ART in elite controllers are unknown. We show that the size of the pool of CD4+ T cells harboring infectious HIV diminished significantly after initiation of ART and rebounded to baseline upon cessation of therapy. Our data provide compelling evidence that persistent viral replication occurs in untreated elite controllers even in the absence of detectable plasma viremia. PMID:23847057

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

    PubMed Central

    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.

    2016-01-01

    Objectives To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996–1999 and survived for more than ten years. Methods We used data from 18 European and North American HIV cohort studies contributing to the 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

  7. Adverse effects of antiretroviral therapy for HIV infection.

    PubMed

    Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G

    2004-01-20

    Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.

  8. Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

    PubMed

    Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia

    2015-08-01

    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.

  9. Antiretroviral therapy adherence among transgender women living with HIV.

    PubMed

    Sevelius, Jae M; Carrico, Adam; Johnson, Mallory O

    2010-01-01

    Despite disproportionate rates of HIV among transgender women and evidence that medication adherence is necessary for treatment success and increased likelihood of survival, there has been little investigation into antiretroviral therapy (ART) adherence issues among transgender women. This study examined rates of self-reported ART adherence among transgender women on ART (n = 35) and well-established correlates of nonadherence, including depression, adherence self-efficacy, patient perceptions of interactions with their providers, and perceived adverse side effects of ART compared to other respondents (n = 2,770). Transgender women on ART were less likely to report 90% adherence rates or higher and reported less confidence in their abilities to integrate treatment regimens into their daily lives. When transgender women were compared to other respondents, regardless of the current medication regimen, they reported significantly fewer positive interactions with their health care providers. Training for providers and integration of hormone therapy into HIV care is recommended.

  10. The future of antiretroviral therapy: challenges and needs.

    PubMed

    Moreno, Santiago; López Aldeguer, Jose; Arribas, José Ramón; Domingo, Pere; Iribarren, Jose Antonio; Ribera, Esteban; Rivero, Antonio; Pulido, Federico

    2010-05-01

    The introduction of combination antiretroviral therapy (cART) has substantially modified the natural history of HIV infection. At the beginning of the cART era the objective was focused on HIV-1-associated mortality and morbidity, but as this objective was accomplished other issues emerged, including toxicity, resistance and compliance with treatment. Moreover, the participation of other disease mechanisms, such as proinflammatory activity, in the so-called non-AIDS events is becoming increasingly important. To overcome these issues, therapeutic options have dramatically expanded, which has made the management of HIV-1-infected patients increasingly complex. The intense changes seen raise the question of what will be the future of HIV infection and its treatment. A projection into the future may help to reflect on current limitations, needs and research priorities, to optimize patient care. To debate on this topic a group of 38 experts has initiated The HIV 2020 Project, with the aim of reflecting on the future of HIV infection and identifying the needs that should be the attention of research in different areas. This document summarizes the group's conclusions on the future of antiretroviral treatment, presented as 20 relevant questions. Each question includes the current status of the topic and our vision for the future.

  11. What Time is it? Adherence to Antiretroviral Therapy in Ethiopia

    PubMed Central

    Tiruneh, Yordanos M.; Wilson, Ira B.

    2016-01-01

    This study assessed adherence to antiretroviral therapy (ART) among people living with HIV/AIDS in Ethiopia and explored the sociocultural context in which they relate to their regimen requirements. Data were collected through semi-structured in-depth interviews with 105 patients on ART and observations held at the study clinic. We analyzed data using both qualitative and quantitative methods. Our findings indicate that study participants are highly adherent to dose but less adherent to dose schedule. Strict dose time instructions were reported as stressful and unrealistic. The discrepancy between adherence to dose and dose schedule could be explained by time perception, difficulty with the strictness of medication regimens, or beliefs about dose timing adherence. Care providers should acknowledge the complexities of medication practices and engage in shared decision-making to incorporate patients’ perspectives and identify effective interventions. PMID:26873491

  12. Collaboration between health professionals in the era of antiretroviral therapy.

    PubMed

    Chetty, Verusia; Maharaj, Sonil S

    2013-01-01

    After antiretroviral therapy (ART) became available in South Africa, persons living with HIV (PLWH) began to survive, but they often experienced disability as a result of their illness and treatments. Management of HIV is more often successful with a holistic approach including medicine, rehabilitation, and social care. There is limited literature on collaborations between nurses and allied health professionals in the rehabilitation of PLWH, with no documentation of partnerships between nurses and physiotherapists in high-HIV burdened countries. We investigated the collaboration between nurses and physiotherapists in the rehabilitation of PLWH. We conducted two focus groups with experienced nurses at two residential facilities for PLWH in KwaZulu-Natal, South Africa, using Van Manen's pedagogy on interpretive phenomenology as the conceptual framework. Three barriers to collaboration were found: role governance, environmental structure, and organizational variance. Education and in-service programs and workshops were suggested to curb the divide.

  13. Early Combination Antiretroviral Therapy Limits HIV-1 Persistence in Children.

    PubMed

    Luzuriaga, Katherine

    2016-01-01

    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.

  14. Literacy, education and adherence to antiretroviral therapy in The Gambia.

    PubMed

    Hegazi, A; Bailey, R L; Ahadzie, B; Alabi, A; Peterson, K

    2010-11-01

    We examined the relationship of patients' literacy and education to antiretroviral therapy (ART) adherence in an urban treatment centre in The Gambia. Information on education and literacy systematically collected before ART initiation was compared against selected adherence outcomes. Formally educated patients were significantly more likely to achieve virological suppression at both six and 12 months (87% vs. 67%, OR=3.13, P=0.03; 88% vs. 63%, OR=4.49, P=0.007, respectively). Literate patients had similar benefit at 12 months (OR=3.39 P=0.03), with improved virological outcomes associated with degree of literacy (P=0.003). A trend towards similar results was seen at 6 months for Koranically educated patients; however, this was no longer apparent at 12 months. No significant correlation was seen between socio-demographic characteristics and missed appointments. Our study suggests that literacy, formal education and possibly Koranic education may impact favourably on adherence to ART.

  15. Use of Third Line Antiretroviral Therapy in Latin America

    PubMed Central

    Cesar, Carina; Shepherd, Bryan E.; Jenkins, Cathy A.; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdiléa Gonçalves; Cortes, Claudia P.; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine C.; Cahn, Pedro

    2014-01-01

    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. PMID:25221931

  16. Immune reconstitution syndromes in human immuno-deficiency virus infection following effective antiretroviral therapy.

    PubMed

    Behrens, G M; Meyer, D; Stoll, M; Schmidt, R E

    2000-08-01

    Effective antiretroviral therapy leads to rapid decrease in plasma HIV-1 RNA, frequently followed by an increase in CD4 T-helper cell counts. The improvement of immune function during highly active antiretroviral therapy has important impact on natural history of AIDS-related opportunistic disorders. Here we describe cases of unusual clinical inflammatory syndromes in CMV retinitis, hepatitis C, and atypical mycobacteriosis in HIV-1 infected patients associated with the initiation of antiretroviral therapy. Pathogenetic implications and therapeutic management of these new immunopathologic syndromes are discussed.

  17. Crofelemer for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on anti-retroviral therapy.

    PubMed

    Castro, Jose G; Chin-Beckford, Nafeesa

    2015-01-01

    Chronic diarrhea remains a common condition that affects people infected with human immunodeficiency virus (HIV) despite the widespread use of potent antiretroviral therapy. It is important that providers control this condition, as the persistence of diarrhea affects the quality of life of patients and may contribute to decreased adherence to antiretroviral therapy. Strategies to control diarrhea in patients with HIV infection include switching to a new antiretroviral regimen and/or the use of specific medications to control the diarrhea. This review aims to provide a concise evaluation of a newly approved medication (crofelemer) that has a novel mechanism of action and has received approval for the symptomatic relief of non-infectious diarrhea in adult patients with HIV on anti-retroviral therapy.

  18. Antiretroviral Therapy as Prevention of … Pneumococcal Infections?

    PubMed Central

    Leporrier, Jérémie; Delbos, Valérie; Unal, Guillemette; Honoré, Patricia; Etienne, Manuel; Bouchaud, Olivier; Caron, François

    2016-01-01

    Background. Despite antiretroviral therapy, it is generally believed that the risk for pneumococcal infections (PnIs) is high among patients infected with human immunodeficiency virus (HIV). However, most studies in this field have been conducted before 2010, and the proportion of virologically suppressed patients has drastically increased in these latter years thanks to larger indications and more effective antiretroviral regimens. This study aimed to re-evaluate the current risk of PnI among adult patients infected with HIV. Methods. The incidence of PnI was evaluated between 1996 and 2014 in 2 French regional hospitals. The 80 most recent cases of PnI (2000–2014) were retrospectively compared with 160 controls (HIV patients without PnI) to analyze the residual risk factors of PnI. Results. Among a mean annual follow-up cohort of 1616 patients, 116 PnIs were observed over 18 years. The risk factors of PnI among patients infected with HIV were an uncontrolled HIV infection or “classic” risk factors of PnI shared by the general population such as addiction, renal or respiratory insufficiency, or hepatitis B or C coinfection. Pneumococcal vaccination coverage was low and poorly targeted, because only 5% of the cases had been previously vaccinated. The incidence of invasive PnIs among HIV patients with a nonvirologically suppressed infection or comorbidities was 12 times higher than that reported in the general population at the country level (107 vs 9/100000 patients), whereas the incidence among virologically suppressed HIV patients without comorbidities was lower (7.6/100000 patients). Conclusions. Human immunodeficiency virus infection no longer per se seems to be a significant risk factor for PnI, suggesting a step-down from a systematic to an “at-risk patient” targeted pneumococcal vaccination strategy. PMID:28018929

  19. Predicting virological decay in patients starting combination antiretroviral therapy

    PubMed Central

    2016-01-01

    Objective: Model trajectories of viral load measurements from time of starting combination antiretroviral therapy (cART), and use the model to predict whether patients will achieve suppressed viral load (≤200 copies/ml) within 6-months of starting cART. Design: Prospective cohort study including HIV-positive adults (UK Collaborative HIV Cohort Study). Methods: Eligible patients were antiretroviral naive and started cART after 1997. Random effects models were used to estimate viral load trends. Patients were randomly selected to form a validation dataset with those remaining used to fit the model. We evaluated predictions of suppression using indices of diagnostic test performance. Results: Of 9562 eligible patients 6435 were used to fit the model and 3127 for validation. Mean log10 viral load trajectories declined rapidly during the first 2 weeks post-cART, moderately between 2 weeks and 3 months, and more slowly thereafter. Higher pretreatment viral load predicted steeper declines, whereas older age, white ethnicity, and boosted protease inhibitor/non-nucleoside reverse transcriptase inhibitors based cART-regimen predicted a steeper decline from 3 months onwards. Specificity of predictions and the diagnostic odds ratio substantially improved when predictions were based on viral load measurements up to the 4-month visit compared with the 2 or 3-month visits. Diagnostic performance improved when suppression was defined by two consecutive suppressed viral loads compared with one. Conclusions: Viral load measurements can be used to predict if a patient will be suppressed by 6-month post-cART. Graphical presentations of this information could help clinicians decide the optimum time to switch treatment regimen during the first months of cART. PMID:27124894

  20. Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

    PubMed

    Peluso, Michael J; Spudich, Serena

    2014-09-01

    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.

  1. Once-daily antiretroviral therapy in a cohort of HIV-infected children and adolescents.

    PubMed

    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

    2014-10-01

    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.

  2. Broadening the use of antiretroviral therapy: the case for feline leukemia virus

    PubMed Central

    Greggs, Willie M; Clouser, Christine L; Patterson, Steven E; Mansky, Louis M

    2011-01-01

    Antiretroviral drugs have saved and extended the lives of millions of individuals infected with HIV. The major classes of anti-HIV drugs include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry/fusion inhibitors. While antiretroviral drug regimens are not commonly used to treat other types of retroviral infections, there are instances where there is a perceived need for re-evaluation of the benefits of antiretroviral therapy. One case in point is that of feline leukemia virus (FeLV), an infection of companion felines. While vaccines exist to prevent FeLV infection and spread, they have not eliminated FeLV infection. For FeLV-infected felines and their human companions, antiretroviral therapy would be desirable and of practical importance if good options were available. Here, we discuss FeLV biology and current treatment options, and propose that there is a need for antiretroviral treatment options for FeLV infection. The comparative use and analysis of antiretroviral therapy can provide new insights into the mechanism of antiretroviral drug action. PMID:21479142

  3. Development of HIV Reservoir Targeted Long Acting Nanoformulated Antiretroviral Therapies

    PubMed Central

    Edagwa, Benson J; Zhou, Tian; McMillan, JoEllyn M; Liu, Xin-Ming; Gendelman, Howard E

    2014-01-01

    Human immunodeficiency virus (HIV) infection commonly results in a myriad of comorbid conditions secondary to immune deficiency. Infection also affects broad organ system function. Although current antiretroviral therapy (ART) reduces disease morbidity and mortality through effective control of peripheral viral load, restricted infection in HIV reservoirs including gut, lymphoid and central nervous system tissues, is not eliminated. What underlies these events is, in part, poor ART penetrance into each organ across tissue barriers, viral mutation and the longevity of infected cells. We posit that one means to improve these disease outcomes is through nanotechnology. To this end, this review discusses a broad range of cutting-edge nanomedicines and nanomedicine platforms that are or can be used to improve ART delivery. Discussion points include how polymer-drug conjugates, dendrimers, micelles, liposomes, solid lipid nanoparticles and polymeric nanoparticles can be harnessed to best yield cell-based delivery systems. When completely developed, such nanomedicine platforms have the potential to clear reservoirs of viral infection. PMID:25174930

  4. The Impact of Antiretroviral Therapy on Lung Immunology.

    PubMed

    Cribbs, Sushma K; Fontenot, Andrew P

    2016-04-01

    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.

  5. The first decade of antiretroviral therapy in Africa

    PubMed Central

    2011-01-01

    The past decade has seen remarkable progress in increasing access to antiretroviral therapy in resource-limited settings. Early concerns about the cost and complexity of treatment were overcome thanks to the efforts of a global coalition of health providers, activists, academics, and people living with HIV/AIDS, who argued that every effort must be made to ensure access to essential care when millions of lives depended on it. The high cost of treatment was reduced through advocacy to promote access to generic drugs; care provision was simplified through a public health approach to treatment provision; the lack of human resources was overcome through task-shifting to support the provision of care by non-physicians; and access was expanded through the development of models of care that could work at the primary care level. The challenge for the next decade is to further increase access to treatment and support sustained care for those on treatment, while at the same time ensuring that the package of care is continuously improved such that all patients can benefit from the latest improvements in drug development, clinical science, and public health. PMID:21958478

  6. Antiretroviral Therapy for the Prevention of HIV-1 Transmission

    PubMed Central

    Cohen, Myron S.; Chen, Ying Q.; McCauley, Marybeth; Gamble, Theresa; Hosseinipour, Mina C.; Kumarasamy, Nagalingeswaran; Hakim, James G.; Kumwenda, Johnstone; Grinsztejn, Beatriz; Pilotto, Jose H.S.; Godbole, Sheela V.; Chariyalertsak, Suwat; Santos, Breno R.; Mayer, Kenneth H.; Hoffman, Irving F.; Eshleman, Susan H.; Piwowar-Manning, Estelle; Cottle, Leslie; Zhang, Xinyi C.; Makhema, Joseph; Mills, Lisa A.; Panchia, Ravindre; Faesen, Sharlaa; Eron, Joseph; Gallant, Joel; Havlir, Diane; Swindells, Susan; Elharrar, Vanessa; Burns, David; Taha, Taha E.; Nielsen-Saines, Karin; Celentano, David D.; Essex, Max; Hudelson, Sarah E.; Redd, Andrew D.; Fleming, Thomas R.

    2016-01-01

    BACKGROUND An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1– negative partner in an intention-to-treat analysis. RESULTS Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS The early initiation of ART led to a sustained

  7. Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral therapy in Malawi.

    PubMed Central

    Libamba, Edwin; Makombe, Simon; Mhango, Eustice; de Ascurra Teck, Olga; Limbambala, Eddie; Schouten, Erik J.; Harries, Anthony D.

    2006-01-01

    OBJECTIVE: To describe the supervision, monitoring and evaluation strategies used to assess the delivery of antiretroviral therapy during nationwide scale-up of treatment in Malawi. METHODS: In the first quarter of 2005, the HIV Unit of the Ministry of Health and its partners (the Lighthouse Clinic; Médecins Sans Frontières-Belgium, Thyolo district; and WHO's Country Office) undertook structured supervision and monitoring of all public sector health facilities in Malawi delivering antiretroviral therapy. FINDINGS: Data monitoring showed that by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%) adults) who had ever started antiretroviral therapy. Of patients who had ever started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8% (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1% (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side effects; and, based on pill counts, 96% (6824/7114) had taken their treatment correctly. Mistakes in the registration and monitoring of patients were identified and corrected. Drug stocks were checked, and one potential drug stock-out was averted. As a result of the supervisory visits, by the end of March 2005 recruitment of patients to facilities scheduled to start delivering antiretroviral therapy had increased. CONCLUSION: This report demonstrates the importance of early supervision for sites that are starting to deliver antiretroviral therapy, and it shows the value of combining data collection with supervision. Making regular supervisory and monitoring visits to delivery sites are essential for tracking the national scale-up of delivery of antiretrovirals. PMID:16628306

  8. Alcohol use disorders and antiretroviral therapy among prisoners in Argentina

    PubMed Central

    Alpert, Michael; Wickersham, Jeffrey A.; Vázquez, Mariana; Altice, Frederick L.

    2013-01-01

    Purpose While Argentina has significantly improved access to HIV care and antiretroviral therapy (ART) for both the general population and prisoners, the prevalence of alcohol use disorders (AUDs) among HIV-infected prisoners and their relationship to accessing ART in Argentina is currently unknown. This study aims to characterize the substance abuse patterns of HIV-infected prisoners in Argentina and to assess the independent correlates of receipt of pre-incarceration ART. Design/methodology/approach An anonymous, cross-sectional survey of 100 HIV-infected federal prisoners was conducted in the Buenos Aires municipality from July–December 2010. AUDs were assessed using the AUDIT scale. Findings A majority (63 per cent) of participants met criteria for AUDs, 45 per cent of subjects were diagnosed with HIV in prison and one-quarter had initiated ART during the current incarceration. In addition, over one-third (35 per cent) of participants did not receive ART during the pre-incarceration period despite receiving it upon incarceration. This correlated significantly with the presence of having an AUD (AOR 0.20, 95 per cent CI 0.06–0.74, p = 0.016). Practical implications AUDs are prevalent among HIV-infected prisoners in Argentina and are significantly related to negative secondary HIV prevention and treatment outcomes. While Argentina has provided an exemplary model of HIV-related health care reform within its prisons, future efforts to provide screening and treatment for AUDs are needed to improve the health of the nation’s incarcerated population. Originality/value This paper is the first to describe pre-incarceration drug and alcohol use disorders and issues related to access to ART among prisoners in Argentina. PMID:24772187

  9. Acceptability of Early Antiretroviral Therapy Among South African Women.

    PubMed

    Garrett, Nigel; Norman, Emily; Leask, Kerry; Naicker, Nivashnee; Asari, Villeshni; Majola, Nelisile; Karim, Quarraisha Abdool; Karim, Salim S Abdool

    2017-02-21

    WHO guidelines recommend immediate initiation of antiretroviral therapy (ART) for all individuals at HIV diagnosis regardless of CD4 count, but concerns remain about potential low uptake or poor adherence among healthy patients with high CD4 counts, especially in resource-limited settings. This study assessed the acceptability of earlier treatment among HIV-positive South African women, median age at enrollment 25 (IQR 22-30), in a 10 year prospective cohort study by (i) describing temporal CD4 count trends at initiation in relation to WHO guidance, (ii) virological suppression rates post-ART initiation at different CD4 count thresholds, and (iii) administration of a standardized questionnaire. 158/232 (68.1%) participants initiated ART between 2006 and 2015. Mean CD4 count at initiation was 217 cells/µl (range 135-372) before 2010, and increased to 531 cells/µl (range 272-1095) by 2015 (p < 0.001). Median viral load at ART initiation decreased over this period from 5.2 (IQR 4.6-5.6) to 4.1 (IQR 3.4-4.6) log copies/ml (p = 0.004). Virological suppression rates at 3, 6, 12 and 18 months were consistently above 85% with no statistically significant differences for participants starting ART at different CD4 count thresholds. A questionnaire assessing uptake of early ART amongst ART-naïve women, median age 28 (IQR 24-33), revealed that 40/51 (78.4%) were willing to start ART at CD4 ≥500. Of those unwilling, 6/11 (54.5%) started ART within 6 months of questionnaire administration. Temporal increases in CD4 counts, comparable virological suppression rates, and positive patient perceptions confirm high acceptability of earlier ART initiation for the majority of patients.

  10. A qualitative assessment of barriers to antiretroviral therapy adherence among adolescents in western Kenya

    PubMed Central

    Kunapareddy, Catherine June; Nyandiko, Winstone; Inui, Thomas; Ayaya, Samwel; Marrero, David G.; Vreeman, Rachel

    2015-01-01

    Antiretroviral therapy (ART) requires nearly perfect adherence to be effective. This study aims to identify key factors identified by HIV-infected adolescents on ART as contributing to medication adherence in western Kenya. Using a qualitative study design, three adolescent focus groups discussions were conducted at an urban and rural clinic site in western Kenya. The study population included HIV-infected adolescents receiving ART through the USAID-AMPATH HIV care system. A trained facilitator conducted groups in Kiswahili using a semi-structured interview guide probing multiple aspects of experience of taking medicines. Transcribed focus group dialogues were analyzed using constant comparison, progressive coding, and triangulation. The adolescents described a context of negative societal beliefs about HIV, necessitating a lifestyle of secrecy and minimizing the information shared about HIV or ART. Assessing and addressing adolescents’ fears and behaviors regarding medication secrecy and disclosure may enable more accurate monitoring of adherence and development of intervention strategies. PMID:28367106

  11. Neurocognitive Function in HIV Infected Patients on Antiretroviral Therapy

    PubMed Central

    Winston, Alan; Arenas-Pinto, Alejandro; Stöhr, Wolfgang; Fisher, Martin; Orkin, Chloe M.; Aderogba, Kazeem; De Burgh-Thomas, Andrew; O'Farrell, Nigel; Lacey, Charles JN.; Leen, Clifford; Dunn, David; Paton, Nicholas I.

    2013-01-01

    Objective To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. Design We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. Main outcome measure NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. Results Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was −0.5 (−1.2/−0) overall, and −0.3 (−0.7/0.1) and −1.4 (−2/−0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). Conclusions In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. Trial registry ClinicalTrials.gov, NCT01230580 PMID:23646111

  12. When to Start Antiretroviral Therapy in Resource-limited Settings

    PubMed Central

    Walensky, Rochelle P.; Wolf, Lindsey L.; Wood, Robin; Fofana, Mariam O.; Freedberg, Kenneth A.; Martinson, Neil A.; Paltiel, A. David; Anglaret, Xavier; Weinstein, Milton C.; Losina, Elena

    2011-01-01

    Background Results of international clinical trials assessing when to initiate antiretroviral therapy (ART) will not be available for several years. Objective To inform HIV treatment decisions over the short- and long-term regarding the optimal CD4 threshold at which to initiate ART in South Africa, while awaiting “when to start” trial results. Design Cost-effectiveness analysis using a computer simulation model of HIV disease. Data Sources Published data from randomized trials and observational cohorts in South Africa. Target Population HIV-infected patients in South Africa. Time Horizon Five-year and lifetime. Perspective Modified societal. Interventions No treatment, initiate ART at CD4<250/μl, and initiate ART at CD4<350/μl. Outcome Measures Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness. Results of Base-Case Analysis If 10-100% of HIV-infected patients are diagnosed and linked to care, initiating ART at CD4<350/μl would reduce severe opportunistic diseases by 22,000-221,000 and deaths by 25,000-253,000 during the next 5 years, compared to initiating ART at CD4<250/μl; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART strategy increased long-term survival by at least 7.9 years, with a mean per person life expectancy of 3.8 years for no ART and 12.5 years for ART at <350/μl. Compared to initiating ART at <250/μl, initiating ART at <350/μl had an incremental cost-effectiveness ratio of $1,200/year of life saved. Results of Sensitivity Analysis Initiating ART at CD4<350/μl remained cost-effective over the next 5 years even if the probability that the trial would demonstrate superiority to earlier therapy is as low as 17%. Limitations This model does not consider the possible benefits of ART initiation at CD4>350/μl nor reduced HIV transmission. Conclusions Earlier ART initiation in South Africa will likely reduce morbidity and mortality, improve long-term survival, and be very cost

  13. Highly active antiretroviral therapy and tuberculosis control in Africa: synergies and potential.

    PubMed Central

    Harries, Anthony D.; Hargreaves, Nicola J.; Chimzizi, Rehab; Salaniponi, Felix M.

    2002-01-01

    HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) and TB (tuberculosis) are two of the world's major pandemics, the brunt of which falls on sub-Saharan Africa. Efforts aimed at controlling HIV/AIDS have largely focused on prevention, little attention having been paid to care. Work on TB control has concentrated on case detection and treatment. HIV infection has complicated the control of tuberculosis. There is unlikely to be a decline in the number of cases of TB unless additional strategies are developed to control both this disease and HIV simultaneously. Such strategies would include active case-finding in situations where TB transmission is high, the provision of a package of care for HIV-related illness, and the application of highly active antiretroviral therapy. The latter is likely to have the greatest impact, but for this therapy to become more accessible in Africa the drugs would have to be made available through international support and a programme structure would have to be developed for its administration. It could be delivered by means of a structure based on the five-point strategy called DOTS, which has been adopted for TB control. However, it may be unrealistic to give TB control programmes the responsibility for running such a programme. A better approach might be to deliver highly active antiretroviral therapy within a comprehensive HIV/AIDS management strategy complementing the preventive work already being undertaken by AIDS control programmes. TB programmes could contribute towards the development and implementation of this strategy. PMID:12132003

  14. Acquired immunodeficiency syndrome-related malignancies in the era of highly active antiretroviral therapy.

    PubMed

    Bernstein, Wendy B; Little, Richard F; Wilson, Wyndham H; Yarchoan, Robert

    2006-07-01

    Since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic, malignancies have been an important feature of this disease. Several cancers, including Kaposi sarcoma (KS), certain aggressive B-cell lymphomas, and cervical cancer, are considered AIDS-defining when they occur in patients infected with human immunodeficiency virus. Most AIDS-defining tumors are associated with one of 3 DNA viruses: KS-associated herpesvirus, Epstein-Barr virus, or human papillomavirus. With the introduction of highly active antiretroviral therapy (HAART), the incidence of KS and certain lymphomas has decreased, whereas that of other tumors, such as cervical cancer, has undergone little change. Several new drugs and therapies have been developed for KS and AIDS-related lymphomas, and these treatments, plus the development of HAART, have contributed to improvements in morbidity and mortality. At the same time, the improved overall survival of patients with HAART has contributed to an increase in the number of patients living with AIDS in developed countries such as the United States. With the development of HAART and improved prevention and treatment of opportunistic infections, an increasing percentage of the deaths in AIDS patients have been from malignancies. Strategies for prevention, screening, and therapy remain important areas of research in this developing field.

  15. Antiretroviral Therapy as HIV Prevention: Status and Prospects

    PubMed Central

    Venkatesh, Kartik K.

    2010-01-01

    As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined. PMID:20724682

  16. Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy.

    PubMed

    Stein, James H; Komarow, Lauren; Cotter, Bruno R; Currier, Judith S; Dubé, Michael P; Fichtenbaum, Carl J; Gerschenson, Mariana; Mitchell, Carol K C; Murphy, Robert L; Squires, Kathleen; Parker, Robert A; Torriani, Francesca J

    2008-12-01

    BACKGROUND: Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. OBJECTIVE: To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins. METHODS: This was a substudy of a prospective, multicenter study treatment-naïve HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy. RESULTS: Among the 82 participants, total and small low-density lipoprotein concentrations increased (median, interquartile range) by 152 (-49 - +407, p<0.01) and 130 (-98 - +417, p<0.01) nmol/L, respectively, especially in the arms containing lopinavir/ritonavir (p(KW)<0.04). Very low-density lipoproteins also increased (p<0.01), with a larger increase in the arms that contained lopinavir/ritonavir (p=0.022). High-density lipoproteins increased by 6.0 nmol/L (2.8 - 10.4, p<0.01), but differences between arms were not significant (p(KW)=0.069). Changes were not related to changes in markers of insulin/glucose metabolism. CONCLUSIONS: Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir.

  17. Contribution of substance use disorders on HIV treatment outcomes and antiretroviral medication adherence among HIV-infected persons entering jail.

    PubMed

    Chitsaz, Ehsan; Meyer, Jaimie P; Krishnan, Archana; Springer, Sandra A; Marcus, Ruthanne; Zaller, Nick; Jordan, Alison O; Lincoln, Thomas; Flanigan, Timothy P; Porterfield, Jeff; Altice, Frederick L

    2013-10-01

    HIV and substance use are inextricably intertwined. One-sixth of people living with HIV/AIDS (PLWHA) transition through the correctional system annually. There is paucity of evidence on the impact of substance use disorders on HIV treatment engagement among jail detainees. We examined correlates of HIV treatment in the largest sample of PLWHA transitioning through jail in 10 US sites from 2007 to 2011. Cocaine, alcohol, cannabis, and heroin were the most commonly used substances. Drug use severity was negatively and independently correlated with three outcomes just before incarceration: (1) having an HIV care provider (AOR = 0.28; 95 % CI 0.09-0.89); (2) being prescribed antiretroviral therapy (AOR = 0.12; 95 % CI 0.04-0.35) and (3) high levels (>95 %) of antiretroviral medication adherence (AOR = 0.18; 95 % CI 0.05-0.62). Demographic, medical and psychiatric comorbidity, and social factors also contributed to poor outcomes. Evidence-based drug treatments that include multi-faceted interventions, including medication-assisted therapies, are urgently needed to effectively engage this vulnerable population.

  18. Central Nervous System Strongyloidiasis and Cryptococcosis in an HIV-Infected Patient Starting Antiretroviral Therapy

    PubMed Central

    Rodríguez, Mónica; Flores, Paúl; Ahumada, Víctor; Vázquez-Vázquez, Lorena; Alvarado-de la Barrera, Claudia; Reyes-Terán, Gustavo

    2012-01-01

    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. PMID:22924046

  19. Is early antiretroviral therapy initiation useful in HIV(+) adults without co-infections?

    PubMed

    Chauriye, Verónica; Monsalve, Ximena

    2015-12-02

    HIV infection is a worldwide epidemic. Antiretroviral therapy has dramatically changed the outcome of the disease but there is still controversy about the best time to initiate it, especially in patients with CD4 counts over 350 cells/µL. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including four pertinent randomized controlled trials overall. We concluded early initiation of antiretroviral therapy probably reduces mortality, risk of opportunistic infections and tuberculosis, but increases the risk of important adverse effects.

  20. [Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy].

    PubMed

    Cifuentes M, Daniel; Blanco L, Sergio; Ramírez F, Camila

    2016-06-01

    High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results.

  1. AIDS in Brazilian children: history, surveillance, antiretroviral therapy, and epidemiologic transition, 1984-2008.

    PubMed

    Ramos, Alberto Novaes; Matida, Luiza Harunari; Hearst, Norman; Heukelbach, Jorg

    2011-04-01

    We present a systematic review of historical, political, and epidemiologic aspects of AIDS in Brazilian children. Over 25 years, Brazil has developed different strategies to control AIDS in children. Three revisions of criteria for defining AIDS cases in children and nine national guidelines on antiretroviral therapy administration for management of HIV infection were published. These guidelines represent important progress, including aspects of HIV/AIDS surveillance, antiretroviral treatment, opportunistic conditions, prophylaxis, and laboratory testing. Brazil has significantly expanded access to free therapy with different classes of antiretroviral drugs. Initially focusing on treatment for HIV and opportunistic conditions, the scope of treatment guidelines gradually expanded to comprehensive health care for children and adolescents. From 1996 to 2008, the number of AIDS cases and deaths in children has been reduced by 67% and 65%, respectively, as a result of different strategies to prevent mother-to-child transmission of HIV and highly active antiretroviral therapy administration to infected children. Improved morbidity, mortality, and survival of Brazilian children with AIDS demonstrate clear benefits of adopting a policy of free and universal access to antiretroviral drugs associated with comprehensive care. However, important issues remain to be resolved, mainly concerning social, operational, and regional inequalities in coverage and quality of care, and epidemiological surveillance in different regions of the country. This broad review shows that the overall situation of pediatric AIDS in Brazil represents an incomplete process of epidemiologic and demographic transition, with the coexistence of old and new clinical and epidemiologic challenges.

  2. Brief Exposure to Cognitive Behavioral Therapy Reduces Side-Effect Symptoms in Patients on Antiretroviral Therapy.

    PubMed

    Doerfler, R Eric; Goodfellow, Linda

    2016-01-01

    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 < .05). Brief CBT training may reduce fatigue and nausea in patients with HIV undergoing ART.

  3. Outcome of pregnancy in HIV-positive women planned for vaginal delivery under effective antiretroviral therapy.

    PubMed

    Islam, S; Oon, V; Thomas, P

    2010-01-01

    This retrospective cohort study was conducted at Newham University Hospital, London to investigate maternal outcome of planned vaginal delivery as well as rate of maternal-to-child transmission. Between June 2004 and June 2006, 23 (16%) women of 144 HIV-infected pregnant women opted for planned vaginal delivery. Offer of vaginal delivery was based on maternal HIV RNA count <50 cells/ml around 36 weeks' gestation. All women received antiretroviral therapy. Fifteen (65%) women achieved vaginal delivery. Babies were followed up over 18 months. All babies had antiretroviral prophylaxis. No babies were breast-fed. There was no report of maternal-to-child transmission in any of these babies. Our study suggests that planned vaginal delivery could be safe with antiretroviral therapy in pregnancy, optimal intrapartum care, viral load of <1000 copies/ml at delivery, retroviral prophylaxis for babies and avoidance of breast-feeding.

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

    PubMed

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

    2016-11-01

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

  5. miR-34a is a common link in both HIV- and antiretroviral therapy-induced vascular aging

    PubMed Central

    Lu, Lili; Hu, Xiamin; Zhou, Jun; Sun, Yeying; Yang, Jian; Liu, Ying; Wang, Zunzhe; Tan, Ning; Chen, Jiyan; Zhang, Chunxiang

    2016-01-01

    Both HIV and antiretroviral therapy could induce vascular aging with unclear mechanisms. In this study, via microarray analysis, we identified, for the first time, that miR-34a expression was significantly increased in both HIV-infected, and antiretroviral agents-treated vessels and vascular endothelial cells (ECs) from these vessels. In cultured ECs, miR-34a expression was significantly increased by HIV-Tat protein and by the antiretroviral agents, lopinavir/ritonavir. Both HIV-Tat protein and antiretroviral agents could induce EC senescence, which was inhibited by miR-34a inhibition. In contrast, EC senescence was exacerbated by miR-34a overexpression. In addition, the vascular ECs isolated from miR-34a knockout mice were resistant to HIV and antiretroviral agents-mediated senescence. In vivo, miR-34a expression in mouse vascular walls and their ECs was increased by antiretroviral therapy and by HIV-1 Tat transgenic approach. miR-34a inhibition could effectively inhibit both HIV-Tat protein and antiretroviral therapy-induced vascular aging in mice. The increased miR-34a was induced via p53, whereas Sirt1 was a downstream target gene of miR-34a in both HIV-Tat protein and antiretroviral agents-treated ECs and vessels. The study has demonstrated that miR-34a is a common link in both HIV and antiretroviral therapy-mediated vascular aging. PMID:27889708

  6. Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.

    PubMed

    Fowler, Mary G; Qin, Min; Fiscus, Susan A; Currier, Judith S; Flynn, Patricia M; Chipato, Tsungai; McIntyre, James; Gnanashanmugam, Devasena; Siberry, George K; Coletti, Anne S; Taha, Taha E; Klingman, Karin L; Martinson, Francis E; Owor, Maxensia; Violari, Avy; Moodley, Dhayendre; Theron, Gerhard B; Bhosale, Ramesh; Bobat, Raziya; Chi, Benjamin H; Strehlau, Renate; Mlay, Pendo; Loftis, Amy J; Browning, Renee; Fenton, Terence; Purdue, Lynette; Basar, Michael; Shapiro, David E; Mofenson, Lynne M

    2016-11-03

    Background Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. Methods We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. Results The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated

  7. HIV rebound after discontinuation of antiretroviral therapy increases and expands HIV-specific CD8+ responses but has no impact on its functionality.

    PubMed

    López, Mariola; Rallón, Norma; Soriano, Vincent; Rodríguez, Isabel; Valencia, Eulalia; Labarga, Pablo; Moreno, Victoria; Vispo, Eugenia; Roncal, Fernando; González-Lahoz, Juan; Benito, José M

    2008-09-01

    A higher functionality of CD8(+) T cells might contribute to low-level HIV replication in long-term nonprogressors (LTNPs). However, the contrary could also be true, being the function of CD8(+) T cells modulated by HIV replication. We tested whether enhanced HIV replication following antiretroviral therapy interruption could modify the functional profile of HIV-specific CD8(+) responses. Production of MIP-1beta, IL-2, TNF-alpha, and CD107 expression by CD8(+) T cells in response to Gag and Nef optimal peptide pools was analyzed using polychromatic flow cytometry in nine HIV-infected individuals followed for 12 months after discontinuation of antiretroviral therapy. At baseline, CD8(+) T cell subsets with the greatest contribution to response were MIP-beta(+)TNF-alpha(-)IL-2(-)CD107(+) and MIP-beta(+)TNF-alpha(-)IL-2(-)CD107. Most responses were mediated by subsets expressing only one or two molecules. After 12 months of discontinuing antiretroviral therapy, no significant differences were observed in the functional profile of Gag- and Nef-specific CD8(+) responses. However, viral rebound induced a significant increase in the heterogeneity of Gag-specific CD8(+) responses. In summary, viral replication following discontinuation of antiretroviral therapy has no significant impact on qualitative aspects of HIV-specific CD8(+) responses. Thus, a higher functionality of CD8(+) responses does not seem to be the consequence of low-level virus replication.

  8. Prevention strategies for blood‐borne viruses—in the Era of vaccines, direct acting antivirals and antiretroviral therapy

    PubMed Central

    Pfaender, Stephanie; von Hahn, Thomas; Steinmann, Joerg; Ciesek, Sandra

    2016-01-01

    Summary Blood‐borne viruses, such as hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and the facultative blood‐borne hepatitis E virus, are considered a major public health problem given that they are accountable for millions of deaths each year. Treatment options, including effective vaccine design, development of antiviral strategies and the implementation of antiretroviral therapy have improved substantially over the last couple of years and contribute to successful treatment and prevention of these infectious diseases. In this review, we summarise the current knowledge and concepts in prevention of transmission of these blood‐borne viruses. PMID:27185010

  9. Antiretroviral concentrations in breast-feeding infants of mothers receiving highly active antiretroviral therapy.

    PubMed

    Mirochnick, Mark; Thomas, Timothy; Capparelli, Edmund; Zeh, Clement; Holland, Diane; Masaba, Rose; Odhiambo, Prisca; Fowler, Mary Glenn; Weidle, Paul J; Thigpen, Michael C

    2009-03-01

    There are limited data describing the concentrations of zidovudine, lamivudine, and nevirapine in nursing infants as a result of transfer via breast milk. The Kisumu Breastfeeding Study is a phase IIb open-label trial of prenatal, intrapartum, and postpartum maternal treatment with zidovudine, lamivudine, and nevirapine from 34 weeks of gestation to 6 months postpartum. In a pharmacokinetic substudy, maternal plasma, breast milk, and infant dried blood spots were collected for drug assay on the day of delivery and at 2, 6, 14, and 24 weeks after delivery. Sixty-seven mother-infant pairs were enrolled. The median concentrations in breast milk of zidovudine, lamivudine, and nevirapine during the study period were 14 ng/ml, 1,214 ng/ml, and 4,546 ng/ml, respectively. Zidovudine was not detectable in any infant plasma samples obtained after the day of delivery, while the median concentrations in infant plasma samples from postpartum weeks 2, 6, and 14 were 67 ng/ml, 32 ng/ml, and 24 ng/ml for lamivudine and 987 ng/ml, 1,032 ng/ml, and 734 ng/ml for nevirapine, respectively. Therefore, lamivudine and nevirapine, but not zidovudine, are transferred to infants via breast milk in biologically significant concentrations. The extent and effect of infant drug exposure via breast milk must be well understood in order to evaluate the benefits and risks of maternal antiretroviral use during lactation.

  10. Outcomes of infants starting antiretroviral therapy in Southern Africa, 2004-2012

    PubMed Central

    Porter, Mireille; Davies, Mary-Ann; Mapani, Muntanga K.; Rabie, Helena; Phiri, Sam; Nuttall, James; Fairlie, Lee; Technau, Karl-Günter; Stinson, Kathryn; Wood, Robin; Wellington, Maureen; Haas, Andreas D.; Giddy, Janet; Tanser, Frank; Eley, Brian

    2015-01-01

    Background There is limited published data on the outcomes of infants starting antiretroviral therapy (ART) in routine care in Southern Africa. This study aimed to examine the baseline characteristics and outcomes of infants initiating ART. Methods We analysed prospectively collected cohort data from routine ART initiation in infants from 11 cohorts contributing to the International Epidemiologic Database to Evaluate AIDS in Southern Africa. We included ART naïve HIV-infected infants <12 months of age initiating ≥ three antiretroviral drugs between 2004 and 2012. Kaplan-Meier estimates were calculated for mortality, loss to follow-up (LTFU), transfer out and virological suppression. We used Cox Proportional Hazards models stratified by cohort to determine baseline characteristics associated with outcomes mortality and virological suppression. Results The median (interquartile range) age at ART initiation of 4945 infants was 5.9 months (3.7-8.7) with follow-up of 11.2 months (2.8-20.0). At ART initiation 77% had WHO clinical stage 3 or 4 disease and 87% were severely immunosuppressed. Three-year mortality probability was 16% and LTFU 29%. Severe immunosuppression, WHO stage 3 or 4, anaemia, being severely underweight and initiation of treatment before 2010 were associated with higher mortality. At 12 months after ART initiation 17% of infants were severely immunosuppressed and the probability of attaining virological suppression was 56%. Conclusion Most infants initiating ART in Southern Africa had severe disease with high probability of LTFU and mortality on ART. Although the majority of infants remaining in care showed immune recovery and virological suppression, these responses were suboptimal. PMID:26167620

  11. HIV persists in CCR6+CD4+ T cells from colon and blood during antiretroviral therapy

    PubMed Central

    Gosselin, Annie; Wiche Salinas, Tomas Raul; Planas, Delphine; Wacleche, Vanessa S.; Zhang, Yuwei; Fromentin, Rémi; Chomont, Nicolas; Cohen, Éric A.; Shacklett, Barbara; Mehraj, Vikram; Ghali, Maged P.; Routy, Jean-Pierre; Ancuta, Petronela

    2017-01-01

    Objectives: The objective of this article is to investigate the contribution of colon and blood CD4+ T-cell subsets expressing the chemokine receptor CCR6 to HIV persistence during antiretroviral therapy. Design: Matched sigmoid biopsies and blood samples (n = 13) as well as leukapheresis (n = 20) were collected from chronically HIV-infected individuals receiving antiretroviral therapy. Subsets of CD4+ T cells with distinct differentiation/polarization profiles were identified using surface markers as follows: memory (TM, CD45RA−), central memory (TCM; CD45RA−CCR7+), effector (TEM/TM; CD45RA−CCR7−), Th17 (CCR6+CCR4+), Th1Th17 (CCR6+CXCR3+), Th1 (CCR6−CXCR3+), and Th2 (CCR6−CCR4+). Methods: We used polychromatic flow cytometry for cell sorting, nested real-time PCR for HIV DNA quantification, ELISA and flow cytometry for HIV p24 quantification. HIV reactivation was induced by TCR triggering in the presence/absence of all-trans retinoic acid. Results: Compared with blood, the frequency of CCR6+ TM was higher in the colon. In both colon and blood compartments, CCR6+ TM were significantly enriched in HIV DNA when compared with their CCR6− counterparts (n = 13). In blood, integrated HIV DNA levels were significantly enriched in CCR6+ versus CCR6− TCM of four of five individuals and CCR6+ versus CCR6− TEM of three of five individuals. Among blood TCM, Th17 and Th1Th17 contributed the most to the pool of cells harboring integrated HIV DNA despite their reduced frequency compared with Th2, which were infected the least. HIV reactivation was induced by TCR triggering and/or retinoic acid exposure at higher levels in CCR6+ versus CCR6− TM, TCM, and TEM. Conclusion: CCR6 is a marker for colon and blood CD4+ T cells enriched for replication-competent HIV DNA. Novel eradication strategies should target HIV persistence in CCR6+CD4+ T cells from various anatomic sites. PMID:27835617

  12. Prevalence and predictors of anaemia in patients with HIV infection at the initiation of combined antiretroviral therapy in Xinjiang, China.

    PubMed

    Mijiti, Peierdun; Yuexin, Zhang; Min, Liu; Wubuli, Maimaitili; Kejun, Pan; Upur, Halmurat

    2015-03-01

    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.

  13. Esophageal ulcer caused by cytomegalovirus: resolution during combination antiretroviral therapy for acquired immunodeficiency syndrome.

    PubMed

    Mönkemüller, K E; Wilcox, C M

    2000-08-01

    A 36-year-old man with a 5-year history of untreated human immunodeficiency virus (HIV) infection had odynophagia for 14 days. Fifteen days earlier, he had begun taking trimethoprim-sulphamethoxazole and combination antiretroviral therapy that included lamivudine, zidovudine, and nelfinavir. He had no history of opportunistic infection. The CD4 lymphocyte count was 67/microL and HIV-RNA level was 359,396 copies/mL. Esophagogastroduodenoscopy revealed a large, well-circumscribed esophageal ulceration 31 cm from the incisors. Histopathologic examination of esophageal biopsy specimens showed cytopathic changes diagnostic of cytomegalovirus (CMV). In situ DNA hybridization was positive for CMV. While combination antiretroviral therapy was continued, the esophageal symptoms resolved within 4 days of endoscopy without specific therapy for CMV. Follow-up endoscopy 4 weeks later revealed a normal-appearing esophagus, and the patient has remained symptom-free for 10 months.

  14. [Antiretroviral therapy: useful from prevention to HIV treatment].

    PubMed

    Tshikung, Olivier Nawej; Calmy, Alexandra

    2016-01-13

    In 2015, the publication of important studies allowed the development of new guidelines, notably by WHO and the European AIDS ClinicalSociety (EACS), for HIV preventive treatment (pre-exposure prophylaxis), as well as for the start of antiretroviral treatment. The START and TEMPRANO studies have extended the treatment to all HIV-infected patients, irrespective of the level of immunosuppression and therefore the CD4 count. In addition, innovative screening methods, such as self-tests, are now available in all French pharmacies since 15 September 2015. The latest developments in 2015 concerning the prevention, screening, and treatment of HIV are discussed in this article and will certainly have an impact on the care of patients in Switzerland.

  15. Current strategies for improving access and adherence to antiretroviral therapies in resource-limited settings

    PubMed Central

    Scanlon, Michael L; Vreeman, Rachel C

    2013-01-01

    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 compelling case for more data to guide strategies to improve access and adherence to treatment in resource-limited settings. PMID:23326204

  16. Current strategies for improving access and adherence to antiretroviral therapies in resource-limited settings.

    PubMed

    Scanlon, Michael L; Vreeman, Rachel C

    2013-01-01

    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 compelling case for more data to guide strategies to improve access and adherence to treatment in resource-limited settings.

  17. Integrating antiretroviral therapy in methadone maintenance therapy clinics: Service provider perceptions

    PubMed Central

    Lin, Chunqing; Cao, Xiaobin; Li, Li

    2014-01-01

    Background Using methadone maintenance therapy (MMT) clinics to deliver antiretroviral therapy (ART) is an effective strategy to promote treatment initiation and adherence for HIV-positive drug users. This paper describes the implementation barriers perceived by service providers for an intervention pilot designed to integrate ART services in MMT clinics. Methods The study was conducted in six MMT clinics in Sichuan province, China. Two service providers selected from each of the six clinics underwent training in administering ART. The trained providers delivered ART-related services in their clinics. A focus group was conducted among the service providers to assess their experiences and perceived challenges in delivering integrated services. Results Barriers at policy, institutional, provider, and client levels were identified. Policy level barriers included household registration restrictions and a lack of insurance coverage for testing expenses. Inefficient coordination between treatment sites and MMT clinics was an obstacle at the institutional level. Insufficient training and added workload were barriers at the provider level. Finally, conflict with daily dosing habits was identified as the primary reason that clients did not accept ART. Conclusion Although integrating ART into MMT clinics is beneficial, multilevel barriers to implementation need to be addressed. This study documents the need for treatment transferability and insurance coverage, protection of client confidentiality, proper provider training, coordination with treatment sites, and individualized ART service for MMT clients. PMID:24939555

  18. Predicting adherence to antiretroviral therapy among pregnant women in Guyana: Utility of the Health Belief Model.

    PubMed

    Vitalis, Deborah

    2016-08-29

    Barriers to antiretroviral therapy (ART) adherence among pregnant women are varied and complex. This study explored the constructs of a theoretical model, the Health Belief Model (HBM) to understand and predict ART adherence among pregnant women in Guyana. A cross-sectional study surveyed 108 pregnant women attending 11 primary care clinics. ART adherence ranging from the past weekend to three months was assessed through self-reports, and health beliefs with the Adherence Determinants Questionnaire (ADQ). Constructs with sufficient variation in responses were tested for association with the level of adherence using Spearman's rank correlation coefficient and test. Sixty-seven per cent (72) of the women reported being always adherent. Although there was positive endorsement of ART treatment and adherence, the HBM did not help in understanding or predicting ART adherence in this population. Only one item from the perceived susceptibility construct was significantly associated (p = 0.009) with adherence. Interventions are warranted to address ART adherence in this population, as 19% of the women were recently non-adherent. Although the ADQ did not contribute to a deeper understanding or provide insight into pathways that can be targeted for intervention, theoretical models can play a key role in identifying these pathways.

  19. How does the timing of antiretroviral therapy initiation in acute infection affect HIV reservoirs?

    PubMed Central

    Ananworanich, Jintanat; Dubé, Karine; Chomont, Nicolas

    2014-01-01

    Purpose of review The long-lived viral reservoir is a major obstacle to achieving a cure for HIV. Therapeutic strategies, such as early antiretroviral therapy (ART), may be a prerequisite to achieving long-term control of viral replication upon ART withdrawal. Recent findings HIV persistence is established early in acute HIV infection (AHI) with infection in long-lived memory CD4+ T cells. Studies conducted in nonhuman primates have suggested that this could occur as early as 3 days postinfection; however, the timing in humans is uncertain. ART during AHI significantly restricts the HIV reservoirs as compared with later treatment. Early ART, particularly prior to the detection of HIV immunoglobulin M, may also reduce the contribution of the long-lived central memory CD4+ T cells to the total HIV reservoir, a profile observed in individuals who naturally control HIV without ART. Summary It is clear that early ART has a greater impact in limiting the HIV reservoirs than later treatment. However, latently infected long-lived memory CD4+ T cells persist in most early treated individuals. Therefore, additional interventions will likely be required to eliminate all cells capable of producing replication-competent virus but treatment in AHI may be the critical first step in containing the HIV reservoirs. PMID:25415421

  20. Effect of antiretroviral therapy on HIV-1 genetic evolution during acute infection.

    PubMed

    Chamberland, A; Sylla, M; Boulassel, M R; Baril, J-G; Côté, P; Thomas, R; Trottier, B; Rouleau, D; Routy, J-P; Tremblay, C

    2011-03-01

    The rapid evolution of HIV-1 is a major obstacle to viral eradication. Early antiretroviral therapy (ART) during primary HIV-1 infection could limit viral diversity. Eighteen patients recently infected with HIV-1 were selected. Nine initiated ART soon after enrolment and nine remained untreated. Replication-competent (RC) viruses were quantified at baseline and after one year of follow-up. Viral diversity in the C2V5 envelope region was evaluated from plasma, peripheral blood mononuclear cells (PBMCs), and cell culture at both time points. The amount of RC virus in the treated group declined (median -5.42 infectious units per million [IUPM]) while it remained stable or increased in the untreated group (median +0.87 IUPM). At one year post infection, we observed a significant increase in diversity for the C2V5 (+0.150%) region, specifically in the hypervariable loops V4 (+0.73%) and V5 (+0.77%), in the untreated group. More importantly, viral diversity did not significantly increase in treated individuals during the first year post infection. Genetic diversity during primary infection remains low through the first year of infection. Early treatment could contribute to a decrease in RC viruses from PBMCs and to limitation of viral diversification in the viral reservoir. These findings may have relevance for the rational design of specific immunotherapeutic strategies.

  1. Clinical outcomes and antiretroviral therapy in 'elite' controllers: a review of the literature.

    PubMed

    Crowell, Trevor A; Hatano, Hiroyu

    2015-04-01

    Elite controllers naturally suppress HIV viraemia below the level of detection using standard methods, but demonstrate persistent inflammation and low-level viraemia that is detectable via ultrasensitive assays. These factors may contribute to an increased risk of non-AIDS-related morbidity and mortality among elite controllers. Data suggest that cardiovascular disease may be of particular concern in elite controllers, as evidenced by an increased burden of subclinical cardiovascular disease upon radiographic screening and an elevated rate of hospitalisations for cardiovascular disease as compared to non-controllers who are treated with antiretroviral therapy (ART). Widespread use of ART among non-controllers has led to significant declines in morbidity and mortality, but guidelines are generally silent on the role of ART in the care of elite controllers. Multiple small studies have demonstrated that laboratory markers of inflammation, immune activation and HIV burden improve after initiation of ART in elite controllers. Clinicians must consider these potential benefits of ART when deciding whether to initiate treatment in asymptomatic elite controllers.

  2. Antiretroviral Therapy in Relation to Birth Outcomes among HIV-infected Women: A Cohort Study.

    PubMed

    Li, Nan; Sando, Mary Mwanyika; Spiegelman, Donna; Hertzmark, Ellen; Liu, Enju; Sando, David; Machumi, Lameck; Chalamilla, Guerino; Fawzi, Wafaie

    2016-04-01

    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.

  3. Establishing a workplace antiretroviral therapy programme in South Africa.

    PubMed

    Charalambous, S; Grant, A D; Day, J H; Pemba, L; Chaisson, R E; Kruger, P; Martin, D; Wood, R; Brink, B; Churchyard, G J

    2007-01-01

    Ways to expand access to antiretroviral treatment (ART) in low income settings are being sought. We describe an HIV care programme including ART in an industrial setting in South Africa. The programme uses guidelines derived from local and international best practice. The training component aims to build capacity among health care staff. Nurses and doctors are supported by experienced HIV clinicians through telephone consultation and site visits. Patients undergo a three-stage counselling procedure prior to starting ART. Drug regimens and monitoring are standardised and prophylaxis against opportunistic infections (isoniazid and cotrimoxazole) is offered routinely. Laboratory and pharmacy services, using named-patient dispensing, are centralized. The programme is designed to ensure that data on clinical and economic outcomes will be available for programme evaluation. Between November 2002-December 2004, ART delivery has been established at 70 ART workplace ART sites. The sites range from 200 to 12000 employees, and from small occupational health clinics and general practitioner rooms to larger hospital clinics. During this period, 2456 patients began ART. Of those on treatment for at least three months, 1728 (78%) have been retained on the programme and only 38 (1.7%) patients have failed the first-line ART regimen. This model for delivery of ART is feasible and successful in an industrial setting. The model may be generalizable to other employment health services in settings of high HIV prevalence, and as a model for implementing ART in other types of health-care settings.

  4. Genital HSV Shedding among Kenyan Women Initiating Antiretroviral Therapy

    PubMed Central

    Manguro, Griffins O.; Masese, Linnet N.; Deya, Ruth W.; Magaret, Amalia; Wald, Anna; McClelland, R. Scott; Graham, Susan M.

    2016-01-01

    Objectives Genital ulcer disease (GUD) prevalence increases in the first month of antiretroviral treatment (ART), followed by a return to baseline prevalence by month 3. Since most GUD is caused by herpes simplex virus type 2 (HSV-2), we hypothesized that genital HSV detection would follow a similar pattern after treatment initiation. Methods We conducted a prospective cohort study of 122 HSV-2 and HIV-1 co-infected women with advanced HIV disease who initiated ART and were followed closely with collection of genital swab specimens for the first three months of treatment. Results At baseline, the HSV detection rate was 32%, without significant increase in genital HSV detection noted during the first month or the third month of ART. HIV-1 shedding declined during this period; no association was also noted between HSV and HIV-1 shedding during this period. Conclusion Because other studies have reported increased HSV detection in women initiating ART and we have previously reported an increase in GUD during early ART, it may be prudent to counsel HIV-1 infected women initiating ART that HSV shedding in the genital tract may continue after ART initiation. PMID:27683204

  5. Response of Human Immunodeficiency Virus-Associated Cerebral Angiitis to the Combined Antiretroviral Therapy

    PubMed Central

    Cheron, Julian; Wyndham-Thomas, Chloé; Sadeghi, Niloufar; Naeije, Gilles

    2017-01-01

    When secondary causes are excluded, mechanisms underlying central nervous system angiitis (ACNS) in human immunodeficiency virus (HIV)-infected patients are still not understood and optimal treatment remains undefined. We report here a patient with an untreated HIV infection who presented multiple ischemic strokes probably due to HIV-ACNS. ACNS signs on vessel-wall imaging magnetic resonance monitoring retracted with combined antiretroviral therapy without adjunct immunosuppressive drugs. PMID:28348548

  6. Decreasing incidence of cryptococcal meningitis in West Africa in the era of highly active antiretroviral therapy.

    PubMed

    Bamba, Sanata; Lortholary, Olivier; Sawadogo, Adrien; Millogo, Athanase; Guiguemdé, Robert T; Bretagne, Stéphane

    2012-05-15

    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.

  7. Anemia is associated with monocyte activation in HIV-infected adults on antiretroviral therapy

    PubMed Central

    Lipshultz, Hannah M; Hileman, Corrilynn O; Ahuja, Sanjay; Funderburg, Nicholas T; McComsey, Grace A

    2015-01-01

    Background Anemia has been linked with mortality in HIV infection. The mechanism of anemia in the era of contemporary antiretroviral therapy is not understood. The aim of this study was to describe the association between anemia and markers of immune activation and inflammation in a cohort of HIV-infected adults on stable antiretroviral therapy. Methods We performed a cross-sectional study of HIV-infected adults on antiretroviral therapy with HIV-1 RNA < 1000 copies/ml. Soluble and cellular markers of inflammation and immune activation were measured. Relationships between hemoglobin levels, anemia (hemoglobin <13 g/dL for men and <12 g/dL for women) and mild anemia (hemoglobin <14 g/dL for men and <13 g/dL for women) and these markers were explored using multivariable linear regression. Results Among the 147 participants, median age was 46 years, 78% were men, 68% were African American and 29% were Caucasian. Median BMI was 26.7 kg/m2, nadir and current CD4+ T cell counts were 179 and 613 cells/mm3, respectively, and 78% had HIV-1 RNA <50 copies/ml (range 20–600 copies/ml). Median (IQR) hemoglobin was 14.3 (13.1–15.1) g/dl; 14% were anemic and 33% had at least mild anemia. In multivariable analyses, mild anemia was independently associated with female sex, older age, shorter duration of ART, lower WBC count, higher platelet count, higher sCD14 and a greater number of CD14dimCD16+ cells or “patrolling” monocytes, which remained significant after further adjusting for race and BMI. Conclusions Having hemoglobin <14 g/dL for men and <13 g/dL for women was independently associated with monocyte activation (sCD14 and CD14dimCD16+ cells) in HIV-infected adults on stable antiretroviral therapy. PMID:25668820

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

    PubMed Central

    Mocroft, A; Wyatt, C; Szczech, L; Neuhaus, J; El-Sadr, W; Tracy, R; Kuller, L; Shlipak, M; Angus, B; Klinker, H; Ross, M

    2009-01-01

    Background Cystatin C has been proposed as an alternative marker of renal function. We sought to determine if participants randomized to episodic use of antiretroviral therapy guided by CD4+ count (drug conservation; DC) had altered cystatin C levels compared to those randomised to continuous antiretroviral therapy (viral suppression; VS) in the Strategies for Management of Antiretroviral Therapy Trial, and to identify factors associated with increased cystatin C. Methods Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the DC and VS groups respectively. Logistic regression was used to model the odds of ≥ 0.15 mg/dl increase in cystatin C (1 standard deviation [SD]) in the first month after randomisation, adjusting for demographic and clinical characteristics. Results At randomisation, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the DC and VS arms respectively (p=0.29). In the first month after randomisation, 21.8% and 10.6% had ≥0.15 mg/dl increase in cystatin C in the DC and VS arm respectively (p=0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomisation. After adjustment, participants in the VS arm had significantly reduced odds of ≥0.15 mg/dl increase in cystatin C in the first month (OR 0.42; 95% CI 0.23–0.74, p=0.0023). Conclusions These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function. PMID:19050388

  9. HIV-Associated Nephropathy: Clinical Presentation, Pathology, and Epidemiology in the Era of Antiretroviral Therapy

    PubMed Central

    Wyatt, Christina M.; Klotman, Paul E.; D’Agati, Vivette D.

    2008-01-01

    The classic kidney disease of Human Immunodeficiency Virus (HIV) infection, HIV-associated nephropathy, is characterized by progressive acute renal failure, often accompanied by proteinuria and ultrasound findings of enlarged, echogenic kidneys. Definitive diagnosis requires kidney biopsy, which demonstrates collapsing focal segmental glomerulosclerosis with associated microcystic tubular dilatation and interstitial inflammation. Podocyte proliferation is a hallmark of HIV-associated nephropathy, although this classic pathology is observed less frequently in antiretroviral-treated patients. The pathogenesis of HIV-associated nephropathy involves direct HIV infection of renal epithelial cells, and the widespread introduction of combination antiretroviral therapy has had a significant impact on the natural history and epidemiology of this unique disease. These observations have established antiretroviral therapy as the cornerstone of treatment for HIV-associated nephropathy, in the absence of prospective clinical trials. Adjunctive therapy for HIV-associated nephropathy includes ACE inhibitors or angiotensin receptor blockers, as well as corticosteroids in selected patients with significant interstitial inflammation or rapid progression. PMID:19013322

  10. Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

    PubMed Central

    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

    2012-01-01

    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

  11. Population-level associations between antiretroviral therapy scale-up and all-cause mortality in South Africa.

    PubMed

    Larson, Elysia; Bendavid, Eran; Tuoane-Nkhasi, Maletela; Mbengashe, Thobile; Goldman, Thurma; Wilson, Melinda; Klausner, Jeffrey D

    2014-08-01

    Our aim was to describe the association between increasing access to antiretroviral therapy and all-cause mortality in South Africa from 2005 to 2009. We undertook a longitudinal, population-level study, using antiretroviral monitoring data reported by PEPFAR implementing partners and province-level and national all-cause mortality records from Statistics South Africa (provider of official South African government statistics) to analyse the association between antiretroviral therapy and mortality. Using mixed effects models with a random intercept for province, we estimated the contemporaneous and lagging association between antiretroviral therapy and all-cause mortality in South Africa. We also conducted subgroup analyses and estimated the number of deaths averted. For each 100 HIV-infected individuals on antiretroviral therapy reported by PEPFAR implementing partners in South African treatment programmes, there was an associated 2.9 fewer deaths that year (95% CI: 1.5, 4.2) and 6.3 fewer deaths the following year (95% CI: 4.6, 8.0). The associated decrease in mortality the year after treatment reporting was seen in both adults and children, and men and women. Treatment provided from 2005 to 2008 was associated with 28,305 deaths averted from 2006 to 2009. The scale-up of antiretroviral therapy in South Africa was associated with a significant reduction in national all-cause mortality.

  12. Maximizing the benefits of antiretroviral therapy for key affected populations

    PubMed Central

    Grubb, Ian R; Beckham, Sarah W; Kazatchkine, Michel; Thomas, Ruth M; Albers, Eliot R; Cabral, Mauro; Lange, Joep; Vella, Stefano; Kurian, Manoj; Beyrer, Chris

    2014-01-01

    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 comprehensive harm

  13. The spectrum of kidney disease in patients with AIDS in the era of antiretroviral therapy

    PubMed Central

    Wyatt, Christina M.; Morgello, Susan; Katz-Malamed, Rebecca; Wei, Catherine; Klotman, Mary E.; Klotman, Paul E.; D’Agati, Vivette D.

    2009-01-01

    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

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

    PubMed Central

    Hosseini, Zahra; Eftkhar, Hasan; Nedjat, Saharnaz; Ebadi, Abbas; Abbasian, Ladan; Zamani, Fereshte; Aghamollaei, Teamur; Shojaeizade, Davood

    2016-01-01

    Background: The introduction of antiretroviral therapy has caused a remarkable decrease in the occurrence of diseases and mortality among HIV-positive patients, while this success has not been achieved among injection addicts due to a low adherence to antiretroviral medicine. This study aims at clarifying the important factors affecting adherence to treatment in addicts suffering from HIV. Materials and Methods: In this qualitative research, data were gathered through in-depth interviews and field notes, and were interpreted through content analysis in the form of constant comparison. The participants were 16 drug addicts living with HIV/AIDS. Most of them had records of imprisonment and were receiving Highly Active Antiretroviral Therapy (HAART) drug treatments in the AIDS center of Imam Khomeini Hospital complex, affiliated to Tehran University of Medical Sciences. Sampling was started in a purposive method and was continued until data were saturated. Results: Four main categories including psychological reactions, contradictory beliefs, perceived support, and individual and environmental barriers were extracted from the data, each having some sub-categories. Conclusions: The obtained results indicated that adherence to the treatment of HIV is not constant and mono-dimensional, but is a function of different factors. Hence, an individual having feeble adherence in a specific time and under specific circumstances may show desirable adherence under a different circumstance. Thus, treatment of addicts living with HIV/AIDS requires physical, psychological, and social attention along with drug treatments. PMID:26985220

  15. Hybrid data capture for monitoring patients on highly active antiretroviral therapy (HAART) in urban Botswana.

    PubMed Central

    Bussmann, Hermann; Wester, C. William; Ndwapi, Ndwapi; Vanderwarker, Chris; Gaolathe, Tendani; Tirelo, Geoffrey; Avalos, Ava; Moffat, Howard; Marlink, Richard G.

    2006-01-01

    Individual patient care and programme evaluation are pivotal for the success of antiretroviral treatment programmes in resource-limited countries. While computer-aided documentation and data storage are indispensable for any large programme, several important issues need to be addressed including which data are to be collected, who collects it and how it is entered into an electronic database. We describe a patient-monitoring approach, which uses patient encounter forms (in hybrid paper + electronic format) based on optical character recognition, piloted at Princess Marina Hospital in Gaborone, Botswana's first public highly active antiretroviral therapy (HAART) outpatient clinic. Our novel data capture approach collects "key" data for tracking patient and programme outcomes. It saves physician time and does not detract from clinical care. PMID:16501730

  16. [Antiretroviral therapy in inmates: between guidelines and reality of Italian correctional facilities].

    PubMed

    Ranieri, Roberto; Sommella, Jvana; D'Angelo, Cinzia; Nigro, Francesco; Poccobelli, Michelangelo; Lari, Cesare; Di Benedetto, Domenica; D'Arminio Monforte, Antonella

    2015-06-01

    In HIV-positive patients detention often represents a unique opportunity for health care. HIV-positive inmates enjoy the same rights as non-restricted people, as established under national and international legislation, declarations and guidelines. Antiretroviral therapy in restricted men shows some peculiarities such as the voluntary non-taking of drugs to worsen the health status or obtain legal benefits and the high frequency of concomitant psychiatric treatment. On the other hand, patient compliance may be considerably improved by adopting DOT strategy. Aiming to define the choices of first and subsequent lines of therapy with respect to the patient's epidemiological characteristics and other ongoing treatments in two major correctional facilities in Milan (Opera and San Vittore, harbouring about 2500 inmates), we collected punctual data (March 6, 2014) drawn from the single patient forms of therapy. Our results show the same prevalence of HIV infection in both facilities (3%), AIDS and viral hepatitis coinfection cases being more frequent in Opera. Both in Opera and San Vittore we found a high adherence to antiretroviral therapy (high CD4 count average and high percentage of HIV-RNA suppressed). The first and subsequent choice of main lines was TDF+FTC+RTV+ATV. The choice of efavirenz (EFV) as the third drug was often excluded due to its neuropsychiatric implications. The most common cause of drug change was toxicity followed by simplification and then by virological failure. Finally we showed a high frequency of concomitant psychiatric therapy (77% in Opera, 67% in San Vittore), noting the hypothetical interactions with antiretroviral drugs.

  17. Anaemia and zidovudine-containing antiretroviral therapy in paediatric antiretroviral programmes in the IeDEA Paediatric West African Database to evaluate AIDS

    PubMed Central

    Renner, Lorna A; Dicko, Fatoumata; Kouéta, Fla; Malateste, Karen; Gueye, Ramatoulaye D; Aka, Edmond; Eboua, Tanoh K; Azondékon, Alain; Okomo, Uduok; Touré, Pety; Ekouévi, Didier; Leroy, Valeriane

    2013-01-01

    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 severe

  18. Acne vulgaris and acne rosacea as part of immune reconstitution disease in HIV-1 infected patients starting antiretroviral therapy.

    PubMed

    Scott, Christopher; Staughton, Richard C D; Bunker, Christopher J; Asboe, David

    2008-07-01

    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.

  19. Novel Codon Insert in HIV Type 1 Clade B Reverse Transcriptase Associated with Low-Level Viremia During Antiretroviral Therapy

    PubMed Central

    Gianella, Sara; Vazquez, Homero; Ignacio, Caroline; Zweig, Adam C.; Richman, Douglas D.; Smith, Davey M.

    2014-01-01

    Abstract 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. PMID:24020934

  20. Novel codon insert in HIV type 1 clade B reverse transcriptase associated with low-level viremia during antiretroviral therapy.

    PubMed

    Chaillon, Antoine; Gianella, Sara; Vazquez, Homero; Ignacio, Caroline; Zweig, Adam C; Richman, Douglas D; Smith, Davey M

    2014-02-01

    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.

  1. Indian contribution to behavior therapy

    PubMed Central

    Kuruvilla, K.

    2010-01-01

    Publication of papers related to psycho-social interventions in general and Behavior Therapy, in particular, in Indian Journal of Psychiatry has been limited. Though the first paper related to Behavior Therapy was published in 1952, a manual search of all available issues of the journal from 1949 showed that only 42 papers related to Behavior Therapy have been published till 2009. Among them 10 are case reports. Methodological limitations abound even in the papers on larger groups of patients. Studies using operant conditioning have been very few. Aversion therapy and progressive muscle relaxation have been very frequently used. The published articles are reviewed under the various diagnostic categories. Publications in the recent years have been mostly on Cognitive Behavior Therapy. Even after 57 years of co-existence, the relationship between Behavior Therapy and Indian Psychiatry remains a tenuous one. PMID:21836708

  2. CD4+ T cell counts in initiation of antiretroviral therapy in HIV infected asymptomatic individuals; controversies and inconsistencies.

    PubMed

    Maina, E K; Bonney, E Y; Bukusi, E A; Sedegah, M; Lartey, M; Ampofo, W K

    2015-12-01

    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.

  3. Select Host Restriction Factors Are Associated with HIV Persistence During Antiretroviral Therapy

    PubMed Central

    ABDEL-MOHSEN, Mohamed; WANG, Charlene; STRAIN, Matthew C.; LADA, Steven M.; DENG, Xutao; COCKERHAM, Leslie R.; PILCHER, Christopher D.; HECHT, Frederick M.; LIEGLER, Teri; RICHMAN, Douglas D.; DEEKS, Steven G.; PILLAI, Satish K.

    2015-01-01

    Objective The eradication of HIV necessitates elimination of the HIV latent reservoir. Identifying host determinants governing latency and reservoir size in the setting of antiretroviral therapy (ART) is an important step in developing strategies to cure HIV infection. We sought to determine the impact of cell-intrinsic immunity on the HIV latent reservoir. Design We investigated the relevance of a comprehensive panel of established anti-HIV-1 host restriction factors to multiple established virologic and immunologic measures of viral persistence in HIV-1-infected, ART-suppressed individuals. Methods We measured the mRNA expression of 42 anti-HIV-1 host restriction factors, levels of cell-associated HIV-1 RNA, levels of total pol and 2-LTR circle HIV-1 DNA, and immunophenotypes of CD4+ T cells in 72 HIV-1-infected subjects on suppressive ART (23 subjects initiated ART <1 year post-infection, and 49 subjects initiated ART >1 year post-infection). Correlations were analyzed using non-parametric tests. Results The enhanced expression of a few select host restriction factors, p21, schlafen 11, and PAF1, was strongly associated with reduced CD4+ T cell-associated HIV RNA during ART (p<0.001). In addition, our data suggested that ART perturbs the regulatory relationship between CD4+ T cell activation and restriction factor expression. Lastly, cell-intrinsic immune responses were significantly enhanced in subjects who initiated ART during early versus chronic infection, and may contribute to the reduced reservoir size observed in these individuals. Conclusions Intrinsic immune responses modulate HIV persistence during suppressive ART, and may be manipulated to enhance the efficacy of ART and promote viral eradication through reversal of latency in vivo. PMID:25602681

  4. Incidence of pregnancy following antiretroviral therapy initiation and associated factors in eight West African countries

    PubMed Central

    Burgos-Soto, Juan; Balestre, Eric; Minga, Albert; Ajayi, Samuel; Sawadogo, Adrien; Zannou, Marcel D.; Leroy, Valériane; Ekouevi, Didier K.; Dabis, François; Becquet, Renaud

    2014-01-01

    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

  5. Survival benefits of antiretroviral therapy in Brazil: a model-based analysis

    PubMed Central

    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

    2016-01-01

    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

  6. Dynamics of the HIV infection under antiretroviral therapy: A cellular automata approach

    NASA Astrophysics Data System (ADS)

    González, Ramón E. R.; Coutinho, Sérgio; Zorzenon dos Santos, Rita Maria; de Figueirêdo, Pedro Hugo

    2013-10-01

    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.

  7. Management of HIV/AIDS in older patients–drug/drug interactions and adherence to antiretroviral therapy

    PubMed Central

    Burgess, Mary J; Zeuli, John D; Kasten, Mary J

    2015-01-01

    Patients with human immunodeficiency virus (HIV) are living longer with their disease, as HIV has become a chronic illness managed with combination antiretroviral therapy (cART). This has led to an increasing number of patients greater than 50 years old living successfully with HIV. As the number of older adults with HIV has increased, there are special considerations for the management of HIV. Older adults with HIV must be monitored for drug side effects and toxicities. Their other non-HIV comorbidities should also be considered when choosing a cART regimen. Older adults with HIV have unique issues related to medication compliance. They are more likely than the younger HIV patients to have vision loss, cognitive impairment, and polypharmacy. They may have lower expectations of their overall health status. Depression and financial concerns, especially if they are on a fixed income, may also contribute to noncompliance in the aging HIV population. PMID:26604826

  8. Impact of Opioid Substitution Therapy on Antiretroviral Therapy Outcomes: A Systematic Review and Meta-Analysis

    PubMed Central

    Low, Andrea J.; Mburu, Gitau; Welton, Nicky J.; May, Margaret T.; Davies, Charlotte F.; French, Clare; Turner, Katy M.; Looker, Katharine J.; Christensen, Hannah; McLean, Susie; Rhodes, Tim; Platt, Lucy; Hickman, Matthew; Guise, Andy; Vickerman, Peter

    2016-01-01

    Background. Human immunodeficiency virus (HIV)–infected people who inject drugs (PWID) frequently encounter barriers accessing and remaining on antiretroviral therapy (ART). Some studies have suggested that opioid substitution therapy (OST) could facilitate PWID's engagement with HIV services. We conducted a systematic review and meta-analysis to evaluate the impact of concurrent OST use on ART-related outcomes among HIV-infected PWID. Methods. We searched Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases for studies between 1996 to November 2014 documenting the impact of OST, compared to no OST, on ART outcomes. Outcomes considered were coverage and recruitment onto ART, adherence, viral suppression, attrition from ART, and mortality. Meta-analyses were conducted using random-effects modeling, and heterogeneity assessed using Cochran Q test and I2 statistic. Results. We identified 4685 articles, and 32 studies conducted in North America, Europe, Indonesia, and China were included. OST was associated with a 69% increase in recruitment onto ART (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.32–2.15), a 54% increase in ART coverage (odds ratio [OR], 1.54; 95% CI, 1.17–2.03), a 2-fold increase in adherence (OR, 2.14; 95% CI, 1.41–3.26), and a 23% decrease in the odds of attrition (OR, 0.77; 95% CI, .63–.95). OST was associated with a 45% increase in odds of viral suppression (OR, 1.45; 95% CI, 1.21–1.73), but there was limited evidence from 6 studies for OST decreasing mortality for PWID on ART (HR, 0.91; 95% CI, .65–1.25). Conclusions. These findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum among HIV-infected PWID. PMID:27343545

  9. CD4 responses in the setting or suboptimal virological responses to antiretroviral therapy: features, outcomes, and associated factors.

    PubMed

    Collazos, Julio; Asensi, Víctor; Cartón, José Antonio

    2009-07-01

    The factors associated with discordant viroimmunological responses following antiretroviral therapy are unclear. We studied 1380 patients who initiated a protease inhibitor (PI)-based antiretroviral regimen and who fulfilled the criteria for inclusion. Of them, 255 (18.5%) had CD4 increases > or =100 cells/microl after 1 year of therapy despite detectable viral load (immunological responders); they were compared with 669 patients (48.5%) who had CD4 increases <100 cells/microl regardless of their final viral load (immunological nonresponders). Immunological responders had higher rates of sexual acquisition of HIV (p = 0.03), lower rates of clinical progression (p = 0.02), higher probabilities of being naive to antiretroviral therapy (p = 0.006) or to PI if antiretroviral experienced (p = 0.03), higher rates of receiving only nucleoside reverse transcriptase inhibitors in addition to the PI (p = 0.04), and lower baseline CD4 counts (p = 0.007) and higher viral loads (p = 0.009), as compared with nonresponders. Multivariate analysis revealed that sexual transmission of HIV (homosexual p = 0.004, heterosexual p = 0.03), no prior PI experience (p = 0.005), absence of clinical progression (p = 0.02), and lower baseline CD4 counts (p = 0.03) were independently associated with immunological response. However, these factors differed according to the patients' prior antiretroviral status, as higher baseline viral load was also associated with immunological response in antiretroviral-experienced patients (p = 0.02), whereas baseline CD4 count (p = 0.007) was the only predictive parameter in antiretroviral-naive patients. We conclude that immunological responses despite suboptimal viral suppression are common. Prior PI experience, HIV transmission category, baseline CD4 counts, and clinical progression were independently predictive of this condition, although the associated factors were different depending on the patient's prior antiretroviral history.

  10. Long-term outcome of patients after a single interruption of antiretroviral therapy: a cohort study

    PubMed Central

    2012-01-01

    Background To describe the long term outcome of patients who interrupted highly active antiretroviral therapy (HAART) once, identify the variables associated with earlier need to re-start HAART, and the response when therapy was resumed. A retrospective observational cohort of 66 adult patients with HIV-1 infection who interrupted HAART with a CD4+cell count ≥350 cells/μL and undetectable viral load (VL) was performed. The pre-established CD4+ cell count for restarting therapy was 300cells/μL. Cox regression was used to analyse the variables associated with earlier HAART reinitiation. Results The median follow-up was 209 weeks (range, 64–395). Rates of HIV-related or possible HIV-related events were 0.37 (one case of acute retroviral syndrome) and 1.49 per 100 patient-years, respectively. Two patients died after re-starting therapy and having reached undetectable VL. Three patients suffered a sexually transmitted disease while off therapy. Fifty patients (76%) resumed therapy after a median of 97 weeks (range, 17–267). Age, a nadir of CD4+ <250 cells/μL, and a mean VL during interruption of >10,000 copies/ml were independent predictors for earlier re-start. The intention-to-treat success rate of the first HAART resumed regimen was 85.4%. There were no differences by regimen used, nor between regimens that were the same as or different from the one that had been interrupted. Conclusions Our data suggest highly active antiretroviral therapy may be interrupted in selected patients because in these patients, when the HAART is restarted, the viral and clinical response may be achieved. PMID:23095460

  11. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy

    PubMed Central

    Heaton, R.K.; Clifford, D.B.; Franklin, D.R.; Woods, S.P.; Ake, C.; Vaida, F.; Ellis, R.J.; Letendre, S.L.; Marcotte, T.D.; Atkinson, J.H.; Rivera-Mindt, M.; Vigil, O.R.; Taylor, M.J.; Collier, A.C.; Marra, C.M.; Gelman, B.B.; McArthur, J.C.; Morgello, S.; Simpson, D.M.; McCutchan, J.A.; Abramson, I.; Gamst, A.; Fennema-Notestine, C.; Jernigan, T.L.; Wong, J.; Grant, I.

    2010-01-01

    Objectives: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). Methods: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). Results: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm3 (30% vs 47% in remaining subgroups). Conclusions: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes. GLOSSARY ANI = asymptomatic neurocognitive impairment; CART = combination antiretroviral therapy; CHARTER = CNS HIV Antiretroviral Therapy Effects Research; CIDI = Composite International Diagnostic Interview; CLIA = Clinical Laboratory Improvement Amendments; CPE = CNS penetration effectiveness; HAD = HIV-associated dementia; HAND = HIV

  12. Administrative interventions associated with increased initiation on antiretroviral therapy in Irkutsk, Siberia

    PubMed Central

    Ogarkov, O. B.; Ebers, A.; Zhdanova, S.; Moiseeva, E.; Koshcheyev, M. E.; Zorkaltseva, E.; Shugaeva, S.; Vitko, S.; Lyles, G.; Houpt, E. R.

    2016-01-01

    A bundle of initiatives to integrate human immunodeficiency virus (HIV) and tuberculosis (TB) services was assessed for the impact on antiretroviral therapy (ART) initiation at a TB referral hospital in Irkutsk, Russian Federation, from February 2014 to December 2015. The ART initiation rates in 166 ART-naïve patients undergoing anti-tuberculosis treatment (34.1% with multidrug or extensively drug-resistant TB) increased significantly from 14 (17%) pre-intervention to 44 (54%) post-intervention (P < 0.001). A survey of TB hospital staff identified administrative prioritisation as the most important initiative for increasing ART initiation. PMID:28123963

  13. Early development of immune reconstitution inflammatory syndrome related to Pneumocystis pneumonia after antiretroviral therapy.

    PubMed

    Mok, Hoi Ping; Hart, Elizabeth; Venkatesan, Pradhib

    2014-04-01

    Immune reconstitution inflammatory syndrome is a recognized complication after the initiation of combination antiretroviral therapy (cART). We report a patient who developed life-threatening pulmonary immune reconstitution inflammatory syndrome (IRIS) three days after initiation of cART. We reviewed published cases of IRIS after Pneumocystis pneumonia (PCP), in particular the time from initiation of cART to IRIS event. The median duration from the initiation of cART to the onset of IRIS was 15 days in the 33 patients reviewed. This report alerts clinicians to the rapidity of the development of pulmonary IRIS following PCP after the initiation of cART.

  14. Electromagnetic detection of HIV DNA in the blood of AIDS patients treated by antiretroviral therapy.

    PubMed

    Montagnier, Luc; Aïssa, Jamal; Lavallée, Claude; Mbamy, Mireille; Varon, Joseph; Chenal, Henri

    2009-12-01

    Electromagnetic signals of low frequency have been shown to be durably produced in aqueous dilutions of the Human Imunodeficiency Virus DNA. In vivo, HIV DNA signals are detected only in patients previously treated by antiretroviral therapy and having no detectable viral RNA copies in their blood. We suggest that the treatment of AIDS patients pushes the virus towards a new mode of replication implying only DNA, thus forming a reservoir insensitive to retroviral inhibitors. Implications for new approaches aimed at eradicating HIV infection are discussed.

  15. Administrative interventions associated with increased initiation on antiretroviral therapy in Irkutsk, Siberia.

    PubMed

    Ogarkov, O B; Ebers, A; Zhdanova, S; Moiseeva, E; Koshcheyev, M E; Zorkaltseva, E; Shugaeva, S; Vitko, S; Lyles, G; Houpt, E R; Heysell, S K

    2016-12-21

    A bundle of initiatives to integrate human immunodeficiency virus (HIV) and tuberculosis (TB) services was assessed for the impact on antiretroviral therapy (ART) initiation at a TB referral hospital in Irkutsk, Russian Federation, from February 2014 to December 2015. The ART initiation rates in 166 ART-naïve patients undergoing anti-tuberculosis treatment (34.1% with multidrug or extensively drug-resistant TB) increased significantly from 14 (17%) pre-intervention to 44 (54%) post-intervention (P < 0.001). A survey of TB hospital staff identified administrative prioritisation as the most important initiative for increasing ART initiation.

  16. Monitoring antiretroviral therapy in resource-limited settings: balancing clinical care, technology, and human resources.

    PubMed

    Hosseinipour, Mina C; Schechter, Mauro

    2010-08-01

    Due to the rapid expansion of first-line antiretroviral therapy in resource-limited settings (RLS), increasing numbers of people are living with HIV for prolonged periods of time. Treatment programs must now decide how to balance monitoring costs necessary to maximize health benefits for those already on treatment with the continued demand to initiate more patients on first-line treatment. We review currently available evidence related to monitoring strategies in RLS and discuss their implications on timing of switching to second-line treatment, development of HIV resistance, and clinical outcome.

  17. Immediate access to antiretroviral therapy is important in children living with HIV

    PubMed Central

    Bhattacharya, Sangeeta Das; Arya, Bikas K.

    2016-01-01

    This article reviews a case of a child with perinatal HIV followed for 30 months during a prospective cohort study on pneumonia prevention in HIV-infected children. The point of this case report is to illustrate how delayed access to antiretroviral therapy (ART) in HIV-infected children impacts immunization response and growth. Given the WHO's early release guideline changes on ART recommendations and the expected full revised guidelines coming out this year, this article is a timely discussion on the need for access to ART for HIV infected Indian children regardless of CD4 count.

  18. Progressive HIV-associated Cholangiopathy in an HIV Patient Treated with Combination Antiretroviral Therapy

    PubMed Central

    Imai, Kazuo; Misawa, Kazuhisa; Matsumura, Takahiro; Fujikura, Yuji; Mikita, Kei; Tokoro, Masaharu; Maeda, Takuya; Kawana, Akihiko

    2016-01-01

    We herein describe a case of progressive human immunodeficiency virus (HIV)-associated cholangiopathy despite normalization of laboratory parameters, which had indicated liver dysfunction, after the initiation of combined anti-retroviral therapy (cART). HIV-associated cholangiopathy remains important as a differential diagnosis of bile duct disorders, although it is considered to be a rare disease in the era of cART. Magnetic resonance cholangiopancreatography could thus be a powerful tool for the diagnosis and follow-up of this disease. PMID:27725553

  19. Artemether-Lumefantrine Exposure in HIV-Infected Nigerian Subjects on Nevirapine-Containing Antiretroviral Therapy.

    PubMed

    Parikh, Sunil; Fehintola, Fatai; Huang, Liusheng; Olson, Alexander; Adedeji, Waheed A; Darin, Kristin M; Morse, Gene D; Murphy, Robert L; Taiwo, Babafemi O; Akinyinka, Olusegun O; Adewole, Isaac F; Aweeka, Francesca T; Scarsi, Kimberly K

    2015-12-01

    Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we compared the results with those for 16 HIV-negative adult historical controls. Exposure to artemether and lumefantrine was significantly lower and dihydroartemisinin exposure was unchanged in subjects receiving nevirapine-based ART, compared with controls. Nevirapine exposure was unchanged before and after artemether-lumefantrine administration.

  20. [Pneumocystis jiroveci pneumonia characteristics in adults with AIDS with or without antiretroviral therapy].

    PubMed

    Bahamondes M, Laura; Villar Z, M José; Orellana C, Carolina; González R, Jimena; Montenegro U, Cristian

    2006-09-01

    Highly active antiretroviral therapy (HAART) has changed the epidemiology of Pneumocystis jiroveci pneumonia (PCP) in AIDS patients. Global incidence of PCP has decreased and now it is prevalent in AIDS patients who do not receive HAART or are unsuccessfully treated with persistent immune depression. Moreover, the immunologic response to HAART has caused a PCP form which is included in the immune restoration inflammatory syndrome (IRIS). As of late 2004, 75.5% of patients cared for at Dr. Lucio Córdova Infectious Diseases Hospital were receiving HAART. This study compares PCP clinical characteristics in patients under the effect of HAART (n: 6) with those without antiretroviral therapy (n: 12). Among those with HAART, 83.3% (5/6) were without immunologic responses and 16.7% with virologic response. The median CD4 counts were low in both groups: 20 cells/mm(3) without HAART and 51 cells/mm(3) with HAART. There were no differences in most of PCP characteristics, and no IRIS cases were observed. HAART-receiving group had less severe disease and lower frequency of both, complications and steroidal therapy prescription (P 0.023).

  1. Poor functional immune recovery in aged HIV-1-infected patients following successfully treatment with antiretroviral therapy.

    PubMed

    Kasahara, Taissa M; Hygino, Joana; Andrade, Regis M; Monteiro, Clarice; Sacramento, Priscila M; Andrade, Arnaldo F B; Bento, Cleonice A M

    2015-10-01

    Aging is now a well-recognized characteristic of the HIV-infected population and both AIDS and aging are characterized by a deficiency of the T-cell compartment. The objective of the present study was to evaluate the impact of antiretroviral (ARV) therapy in recovering functional response of T cells to both HIV-1-specific ENV peptides (ENV) and tetanus toxoid (TT), in young and aged AIDS patients who responded to ARV therapy by controlling virus replication and elevating CD4(+) T cell counts. Here, we observed that proliferative response of T-cells to either HIV-1-specific Env peptides or tetanus toxoid (TT) was significantly lower in older antiretroviral (ARV)-treated patients. With regard to cytokine profile, lower levels of IFN-γ, IL-17 and IL-21, associated with elevated IL-10 release, were produced by Env- or TT-stimulated T-cells from older patients. The IL-10 neutralization by anti-IL-10 mAb did not elevate IFN-γ and IL-21 release in older patients. Finally, even after a booster dose of TT, reduced anti-TT IgG titers were quantified in older AIDS patients and it was related to both lower IL-21 and IFN-γ production and reduced frequency of central memory T-cells. Our results reveal that ARV therapy, despite the adequate recovery of CD4(+) T cell counts and suppression of viremia, was less efficient in recovering adequate immune response in older AIDS patients.

  2. Adjunctive and Long-Acting Nanoformulated Antiretroviral Therapies for HIV-associated neurocognitive disorders

    PubMed Central

    Gendelman, Howard E.; Gelbard, Harris A.

    2014-01-01

    Purpose of review This review focuses on current and future strategies to modulate neuroinflammation while reducing residual viral burden in the central nervous system (CNS). This has been realized by targeted long acting antiretroviral nano- and adjunctive therapies being developed for HIV infected people. Our ultimate goal is to eliminate virus from its CNS reservoirs and, in so doing, reverse the cognitive and motor dysfunctions seen in HIV-associated neurocognitive disorders (HAND). Recent findings Herein, we highlight our laboratories development of adjunctive and nanomedicine therapies for HAND. An emphasis is placed on drug-drug interactions that target both the viral life cycle and secretory pro-inflammatory neurotoxic factors and signaling pathways. Summary Antiretroviral therapy (ART) has improved the quality and duration of life for people living with HIV-1. A significant long-term comorbid illness is HAND. Symptoms, while reduced in severity, are common. Disease occurs, in part, through continued low-level viral replication inducing secondary glial neuroinflammatory activities. Our recent works and those of others have seen disease attenuated in animal models through the use of adjunctive and long-acting reservoir targeted nanoformulated ART. The translation of these inventions from animals to humans is the focus of this review. PMID:25226025

  3. Unmasking histoplasmosis immune reconstitution inflammatory syndrome in a patient recently started on antiretroviral therapy

    PubMed Central

    Nabeta, Henry W; Okia, Richard; Rhein, Joshua; Lukande, Robert

    2016-01-01

    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

  4. Late Antiretroviral Therapy (ART) Initiation Is Associated with Long-Term Persistence of Systemic Inflammation and Metabolic Abnormalities

    PubMed Central

    Ghislain, Mathilde; Bastard, Jean-Philippe; Meyer, Laurence; Capeau, Jacqueline; Fellahi, Soraya; Gérard, Laurence; May, Thierry; Simon, Anne; Vigouroux, Corinne; Goujard, Cécile

    2015-01-01

    Objectives 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. Methods 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). Results 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). Conclusion 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. PMID:26636578

  5. [Antiretroviral therapy in HIV-infected children and adolescents: lessons learned in 30 years of the epidemic].

    PubMed

    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

    2014-04-01

    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.

  6. Immunological profile in persons under antiretroviral therapy in a rural Nigerian hospital

    PubMed Central

    Musa, Baba Maiyaki; Gebi, Usman; Etiebet, Mary-Ann; Omuh, Helen; Ekedegwa, Patrick; Dakum, Patrick; Blattner, William

    2010-01-01

    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 age

  7. Macrophage Folate Receptor-Targeted Antiretroviral Therapy Facilitates Drug Entry, Retention, Antiretroviral Activities and Biodistribution for Reduction of Human Immunodeficiency Virus Infections

    PubMed Central

    Puligujja, Pavan; McMillan, JoEllyn; Kendrick, Lindsey; Li, Tianyuzi; Balkundi, Shantanu; Smith, Nathan; Veerubhotla, Ram S.; Edagwa, Benson J.; Kabanov, Alexander V.; Bronich, Tatiana; Gendelman, Howard E.; Liu, Xin-Ming

    2013-01-01

    Macrophages serve as vehicles for the carriage and delivery of polymer-coated nanoformulated antiretroviral therapy (nanoART). Although superior to native drug, high drug concentrations are required for viral inhibition. Herein, folate-modified atazanavir/ritonavir (ATV/r)-encased polymers facilitated macrophage receptor targeting for optimizing drug dosing. Folate coating of nanoART ATV/r significantly enhanced cell uptake, retention and antiretroviral activities without altering cell viability. Enhanced retentions of folate-coated nanoART within recycling endosomes provided a stable subcellular drug depot. Importantly, five-fold enhanced plasma and tissue drug levels followed folate-coated formulation injection in mice. Folate polymer encased ATV/r improves nanoART pharmacokinetics bringing the technology one step closer to human use. PMID:23680933

  8. Comparative efficacy versus effectiveness of initial antiretroviral therapy in clinical trials versus routine care

    PubMed Central

    Routman, Justin S.; Willig, James H.; Westfall, Andrew O.; Abroms, Sarah R.; Varshney, Mohit; Adusumilli, Sunil; Allison, Jeroan J.; Savage, Karen G.; Saag, Michael S.; Mugavero, Michael J.

    2009-01-01

    Summary The generalizability of clinical trial findings (efficacy) to routine care (effectiveness) may be limited. The present study found similar first year virologic and CD4 outcomes among antiretroviral-naïve patients treated through routine care vs. those participating in clinical trials. Background The generalizability of clinical trial findings (efficacy) to routine care (effectiveness) may be limited due to study eligibility criteria and volunteer bias. While well chronicled in many conditions, the efficacy vs. effectiveness of antiretroviral therapy (ART) remains understudied. Methods A retrospective study of the UAB 1917 Clinic Cohort evaluated naïve patients starting ART between 1/1/00–12/31/06. Patients received ART through clinical trials or routine care. Multivariable logistic and linear regression models were fit to evaluate factors associated with virologic failure (VF=VL>50 copies/mL) and change from baseline CD4 count 6 and 12 months after ART initiation. Sensitivity analyses evaluated the impact of missing data on outcomes. Results Among 570 patients starting ART during the study period, 121 (21%) enrolled in clinical trials vs. 449 (79%) receiving ART via routine care. ART receipt through routine care was not associated with VF at either 6 (OR=1.00;95%CI=0.54–1.86) or 12 (OR=1.56;95%CI=0.80–3.05) months in primary analyses. No significant differences in CD4 count responses at 6 and 12 months were observed. Conclusions Though marked differences in efficacy vs. effectiveness have been observed in the therapeutic outcomes of other conditions, our analyses found no evidence of such divergence among our patients initiating antiretroviral therapy for HIV. PMID:20067423

  9. Infant peripheral blood repetitive element hypomethylation associated with antiretroviral therapy in utero.

    PubMed

    Marsit, Carmen J; Brummel, Sean S; Kacanek, Deborah; Seage, George R; Spector, Stephen A; Armstrong, David A; Lester, Barry M; Rich, Kenneth

    2015-01-01

    The use of combination antiretroviral therapy (cART) to prevent HIV mother-to-child transmission during pregnancy and delivery is generally considered safe. However, vigilant assessment of potential risks of these agents remains warranted. Epigenetic changes including DNA methylation are considered potential mechanisms linking the in utero environment with long-term health outcomes. Few studies have examined the epigenetic effects of prenatal exposure to pharmaceutical agents, including antiretroviral therapies, on children. In this study, we examined the methylation status of the LINE-1 and ALU-Yb8 repetitive elements as markers of global DNA methylation alteration in peripheral blood mononuclear cells obtained from newborns participating in the Pediatric HIV/AIDS Cohort Study SMARTT cohort of HIV-exposed, cART-exposed uninfected infants compared to a historical cohort of HIV-exposed, antiretroviral-unexposed infants from the Women and Infants Transmission Study Cohort. In linear regression models controlling for potential confounders, we found the adjusted mean difference of AluYb8 methylation of the cART-exposed compared to the -unexposed was -0.568 (95% CI: -1.023, -0.149) and for LINE-1 methylation was -1.359 (95% CI: -1.860, -0.857). Among those exposed to cART, subjects treated with atazanavir (ATV), compared to those on other treatments, had less AluYb8 methylation (-0.524, 95% CI: -0.025, -1.024). Overall, these results suggest a small but statistically significant reduction in the methylation of these repetitive elements in an HIV-exposed, cART-exposed cohort compared to an HIV-exposed, cART-unexposed historic cohort. The potential long-term implications of these differences are worthy of further examination.

  10. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

    PubMed Central

    2011-01-01

    Summary Background Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy. Methods The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude death rates were also calculated. Findings 18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, respectively. 2056 (4·7%) deaths were observed during the study period, with crude death rates decreasing from 16·3 deaths per 1000 person-years in 1996–99 to 10·0 deaths per 1000 person-years in 2003–05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36·1 (SE 0·6) years to 49·4 (0·5) years. Women had higher life expectancies than men. Patients with presumed transmission via injecting drug use had lower life expectancies than those from other transmission groups (32·6 [1·1] years vs 44·7 [0·3] years in 2003–05). Life expectancy was lower in patients with lower baseline CD4 counts than in those with higher baseline counts

  11. Understanding and mitigating HIV-related resource-based stigma in the era of antiretroviral therapy.

    PubMed

    Holmes, Kathleen; Winskell, Kate

    2013-01-01

    The perception in low-resource settings that investment of resources in people living with HIV (PLHIV) is wasted because AIDS is both an incurable and deadly disease is known as resource-based stigma. In this paper, we draw on in-depth interviews (IDI), focus group discussions (FGD), and key informant interviews (KII) with 77 HIV-positive microfinance participants and nongovernmental organization leaders to examine resource-based stigma in the context of increased access to antiretroviral therapy (ART) at an individual, household, and community level in Côte d'Ivoire. The purpose of this exploratory paper is to examine: (1) resource-based stigmatization in the era of ART and (2) the relationship among microfinance, a poverty-reduction intervention, and HIV stigmatization. The frequency with which resource-based stigma was discussed by respondents suggests that it is an important component of HIV-related stigma in this setting. It affected PLHIV's access to material as well as social resources, leading to economic discrimination and social devaluation. Participation in village savings and loans groups, however, mitigated resource-based HIV stigma, suggesting that in the era of increased access to antiretroviral therapy, economic programs should be considered as one possible HIV stigma-reduction intervention.

  12. Influence of the First Consultation on Adherence to Antiretroviral Therapy for HIV-infected Patients

    PubMed Central

    Peyre, Marion; Gauchet, Aurélie; Roustit, Matthieu; Leclercq, Pascale; Epaulard, Olivier

    2016-01-01

    Background: Physician attitude influences the way patients cope with diagnosis and therapy in chronic severe diseases such as cancer. Previous studies showed that such an effect exists in HIV care; it is likely that it begins with the first contact with a physician. Objective: We aimed to explore in HIV-infected persons their perception of the first consultation they had with an HIV specialist (PFC-H), and whether this perception correlates with adherence to antiretroviral therapy. Method: The study was conducted in Grenoble University Hospital, France, a tertiary care center. Every antiretroviral-experienced patient was asked to freely complete a self-reported, anonymous questionnaire concerning retrospective PFC-H, present adherence (Morisky scale), and present perceptions and beliefs about medicine (BMQ scale). Results: One hundred and fifty-one questionnaires were available for evaluation. PFC-H score and adherence were correlated, independently from age, gender, and numbers of pill(s) and of pill intake(s) per day. BMQ score also correlated with adherence; structural equation analysis suggested that the effect of PFC-H on adherence is mediated by positive beliefs. Conclusion: These results suggest that for HIV-infected persons, the perceptions remaining from the first consultation with an HIV specialist physician influence important issues such as adherence and perception about medicine. Physicians must be aware of this potentially long-lasting effect. PMID:27708747

  13. Adherence to highly active antiretroviral therapy in Hyderabad, India: barriers, facilitators and identification of target groups.

    PubMed

    Dworkin, Mark S; Douglas, G W; Sabitha Rani, G P; Chakraborty, Apurba

    2016-03-01

    We assessed the barriers and facilitators to highly active antiretroviral therapy adherence and determined their prevalence among HIV/AIDS patients in Hyderabad, India. We conducted a cross-sectional study among HIV-infected adults prescribed highly active antiretroviral therapy and receiving care from nine clinics. Depression was screened using Patient Health Questionnaire 9 and facilitators of HIV medication adherence were assessed using an 11-item scale which yielded a total positive attitude to disease score. Prevalence ratios of non-adherence between different categories of potential risk factors were calculated. We compared mean 'facilitators to adherence' scores between the adherent and non-adherent population. Multivariable Poisson regression with robust variance was used to identify independent risk factors. Among the 211 respondents, nearly 20% were non-adherent, approximately 8% had either moderately severe or severe depression and mean score for combined facilitators to medication adherence was 33.35 (±7.88) out of a possible 44 points. Factors significantly associated with non-adherence included older age, female sex worker, moderate-to-severe depression and the combined facilitators to medication adherence score. These data from a broad range of clinical settings in Hyderabad reveal that key groups to focus on for adherence intervention are female sex workers, older persons and those with depression.

  14. Modulation of HCV replication after combination antiretroviral therapy in HCV/HIV co-infected patients.

    PubMed

    Sherman, Kenneth E; Guedj, Jeremie; Shata, Mohamed Tarek; Blackard, Jason T; Rouster, Susan D; Castro, Mario; Feinberg, Judith; Sterling, Richard K; Goodman, Zachary; Aronow, Bruce J; Perelson, Alan S

    2014-07-23

    The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients co-infected with HIV. Co-infection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV co-infected patients into a cART initiation trial and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in increased HCV replication and increased alanine aminotransferase (ALT) in a subset of patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in co-infected patients who underwent successful cART. The effective suppression of HIV by cART initiated a cascade of early and late events in treated patients. Early events involving down-regulation of interferon-stimulated genes may have led to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declined to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV co-infection.

  15. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.

    PubMed

    Archin, N M; Liberty, A L; Kashuba, A D; Choudhary, S K; Kuruc, J D; Crooks, A M; Parker, D C; Anderson, E M; Kearney, M F; Strain, M C; Richman, D D; Hudgens, M G; Bosch, R J; Coffin, J M; Eron, J J; Hazuda, D J; Margolis, D M

    2012-07-25

    Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.

  16. Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas

    PubMed Central

    Firnhaber, Cynthia; Smeaton, Laura; Saukila, Nasinuku; Flanigan, Timothy; Gangakhedkar, Raman; Kumwenda, Johnstone; La Rosa, Alberto; Kumarasamy, Nagalingeswaran; De Gruttola, Victor; Hakim, James Gita; Campbell, Thomas B.

    2010-01-01

    Summary Background Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease. Methods This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition. Results The frequencies of neutropenia (absolute neutrophil count ≤ 1.3 × 109/l), anemia (hemoglobin ≤ 10 g/dl), and thrombocytopenia (platelets ≤ 125 × 109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p < 0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection. Conclusions Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings. PMID:20961784

  17. Direct observation therapy-highly active antiretroviral therapy in a resource-limited setting: the use of community treatment support can be effective.

    PubMed

    Idoko, J A; Agbaji, O; Agaba, P; Akolo, C; Inuwa, B; Hassan, Zuweira; Akintunde, L; Badung, B; Muazu, M; Danang, M; Imade, G; Sankale, J Louis; Kanki, Phyllis

    2007-11-01

    This study examines the use of various direct observation therapy-HAART treatment support modalities in Jos, Nigeria. A 12-month observational study enrolling 175 antiretroviral naïve patients into four arms of direct observation therapy-HAART (highly active antiretroviral therapy); daily observed therapy (DOT), twice weekly observed therapy (TWOT), weekly observed therapy (WOT) and self-administered therapy (SAT), examined community treatment support using family and community members. Treatment outcomes were much better in the treatment-supported groups compared with the control self-therapy group. CD4 cell increases were 218/microL (DOT), 267/microL (TWOT), 205/microL (WOT) versus 224/microL (SAT), whereas plasma HIV-1 RNA reached undetectable levels (<400 copies/mL) in 91%, 88%, 84% versus 79% of patients in the DOT, TWOT, WOT versus SAT groups, respectively, at 48 weeks. We, therefore, strongly support the use of treatment support in our settings.

  18. The Complexity of HIV Persistence and Pathogenesis in the Lung Under Antiretroviral Therapy: Challenges Beyond AIDS

    PubMed Central

    2014-01-01

    Abstract Antiretroviral therapy (ART) represents a significant milestone in the battle against AIDS. However, we continue learning about HIV and confronting challenges 30 years after its discovery. HIV has cleverly tricked both the host immune system and ART. First, the many HIV subtypes and recombinant forms have different susceptibilities to antiretroviral drugs, which may represent an issue in countries where ART is just being introduced. Second, even under the suppressive pressures of ART, HIV still increases inflammatory mediators, deregulates apoptosis and proliferation, and induces oxidative stress in the host. Third, the preference of HIV for CXCR4 as a co-receptor may also have noxious outcomes, including potential malignancies. Furthermore, HIV still replicates cryptically in anatomical reservoirs, including the lung. HIV impairs bronchoalveolar T-lymphocyte and macrophage immune responses, rendering the lung susceptible to comorbidities. In addition, HIV-infected individuals are significantly more susceptible to long-term HIV-associated complications. This review focuses on chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension, and lung cancer. Almost two decades after the advent of highly active ART, we now know that HIV-infected individuals on ART live as long as the uninfected population. Fortunately, its availability is rapidly increasing in low- and middle-income countries. Nevertheless, ART is not risk-free: the developed world is facing issues with antiretroviral drug toxicity, resistance, and drug–drug interactions, while developing countries are confronting issues with immune reconstitution inflammatory syndrome. Several aspects of the complexity of HIV persistence and challenges with ART are discussed, as well as suggestions for new avenues of research. PMID:24797368

  19. Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy

    PubMed Central

    Lacombe, Jean-Marc; Boue, François; Grabar, Sophie; Viget, Nathalie; Gazaignes, Sandrine; Lascaux-Cametz, Anne-Sophie; Pacanowski, Jérome; Partisani, Marialuisa; Launay, Odile; Matheron, Sophie; Rosenthal, Eric; Rouveix, Elisabeth; Tattevin, Pierre; de Truchis, Pierre; Costagliola, Dominique; Goedert, James J

    2013-01-01

    Objective Determine if incident AIDS-defining Kaposi sarcoma (KS) or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation. Design Compare risk for KS and PJP by time on cART and CD4 reconstitution. Methods In the FHDH-ANRS CO4 cohort (N=66,369), KS (N=1811) and PJP (N=1718) incidence rates were computed by demographic and HIV strata. Crude and adjusted relative risk (RR) with 95% confidence intervals (CI) following cART initiation were calculated by Poisson regression with untreated patients during 1996–2009 as reference. CD4 counts were compared by Wilcoxon rank sum tests. Results KS risk was very high during months 1–3 on cART (N=160, RRCrude 3.94, CI 3.26–4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 count (RRAdj 1.25, CI 1.02–1.53). Corresponding PJP risk was minimally elevated (N=84, RRCrude 1.80, CI 1.42–2.30) and markedly reduced with adjustment on the same variables and PJP prophylaxis (RRAdj 0.52, CI 0.41–0.67). HIV load had no added effect. Median CD4 cell count at cART initiation was much lower in patients with incident KS (82/mm3) or PJP (61/mm3) within 3 months compared with those without (>250/mm3). Notably, median CD4 change was +44 cells/month with incident KS within 3 months of cART initiation versus 0 cells/month with incident PJP (P=0.0003). Conclusions Failure of CD4 reconstitution during months 1–3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional KS cases per 1000 person-years during months 1–3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining KS. PMID:23196937

  20. Gender differences in diet and nutrition among adults initiating antiretroviral therapy in Dar es Salaam, Tanzania.

    PubMed

    Abioye, Ajibola I; Isanaka, Sheila; Liu, Enju; Mwiru, Ramadhani S; Noor, Ramadhani A; Spiegelman, Donna; Mugusi, Ferdinand; Fawzi, Wafaie

    2015-01-01

    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.

  1. Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy).

    PubMed Central

    Farmer, P.; Léandre, F.; Mukherjee, J.; Gupta, R.; Tarter, L.; Kim, J. Y.

    2001-01-01

    In 2000, acquired immunodeficiency syndrome (AIDS) overtook tuberculosis (TB) as the world's leading infectious cause of adult deaths. In affluent countries, however, AIDS mortality has dropped sharply, largely because of the use of highly active antiretroviral therapy (HAART). Antiretroviral agents are not yet considered essential medications by international public health experts and are not widely used in the poor countries where human immunodeficiency virus (HIV) takes its greatest toll. Arguments against the use of HAART have mainly been based on the high cost of medications and the lack of the infrastructure necessary for using them wisely. We re- examine these arguments in the setting of rising AIDS mortality in developing countries and falling drug prices, and describe a small community-based treatment programme based on lessons gained in TB control. With the collaboration of Haitian community health workers experienced in the delivery of home-based and directly observed treatment for TB, an AIDS-prevention project was expanded to deliver HAART to a subset of HIV patients deemed most likely to benefit. The inclusion criteria and preliminary results are presented. We conclude that directly observed therapy (DOT) with HAART, "DOT-HAART", can be delivered effectively in poor settings if there is an uninterrupted supply of high-quality drugs. PMID:11799447

  2. Adherence to antiretroviral therapy and its determinants among persons living with HIV/AIDS in Bayelsa state, Nigeria

    PubMed Central

    Suleiman, Ismail A.; Momo, Andrew

    2015-01-01

    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 which calls

  3. The Effect of Continuous Versus Pericycle Antiretroviral Therapy on IL-2 Responsiveness

    PubMed Central

    Healey, Letha M.; Hahn, Barbara K.; Rehm, Catherine A.; Adelsberger, Joseph; Qin, Jing; Follmann, Dean A.; Tavel, Jorge; Kovacs, Joseph A.; Sereti, Irini

    2008-01-01

    Background Intermittent administration of interleukin-2 (IL-2) to human immunodeficiency virus (HlV)-infected patients on antiretroviral therapy (ART) is capable of inducing significant increases in CD4 T cell counts as a result of increased T cell survival and decreased cell turnover. However, its role in the setting of ART interruptions (STI) is less well characterized. We sought to compare the effect of continuous (C) versus intermittent (P) ART on CD4 responses in patients undergoing IL-2 therapy. Methods CD4 cell responses were compared in 25 patients who underwent IL-2 therapy during periods of continuous ART (n = 90 cycles) as well as during STI (n = 45 cycles). During STI, patients resumed ART for only 10 days surrounding each IL-2 cycle. Results C cycles resulted in a significantly greater CD4 gain than P cycles (Δ156 cells/μL, 95% CI = 68–243). In multivariate analyses, baseline CD4/CD25 expression and treatment arm remained strong predictors of CD4 gain while CD8/CD38+, CD8/DR+, and CD4 Ki67+ phenotype were not predictive. Conclusions Continuous ART was associated with a statistically significantly greater CD4 cell response to IL-2 therapy than was intermittent ART. These observations may have important implications for the appropriate integration of IL-2 therapy into STI strategies. PMID:18597618

  4. Role of inosine triphosphate pyrophosphatase gene variant on fever incidence during zidovudine antiretroviral therapy.

    PubMed

    Coelho, A V C; Silva, S P S; Zandonà, L; Stocco, G; Decorti, G; Crovella, S

    2017-01-23

    Zidovudine, the antiretroviral drug used to treat HIV infection, commonly causes adverse effects, such as systemic fever and gastrointestinal alterations. In the present study, the potential role of inosine triphosphate pyrophosphatase (ITPA) gene variant on the incidence of adverse events during antiretroviral therapy (ART) of HIV with zidovudine was discussed. Individuals from Northeastern Brazil (N = 204) receiving treatment for HIV-1 infection were recruited. Zidovudine-related adverse effects developed during the treatment were registered. The rs1127354 polymorphism in the ITPA gene was genotyped using real-time PCR to assess whether this single nucleotide polymorphism was associated with the occurrence of zidovudine-related adverse effects. We observed a significant association between the ITPA variant genotype and the reported systemic fever (odds ratio = 7.17, 95% confidence interval = 1.19-43.15; P = 0.032). Zidovudine use could indirectly lead to an increase in the levels of inosine monophosphate in an antimetabolite-like manner, which is converted to inosine triphosphate (ITP). The rs1127354 variant caused a decrease in ITPA activity, thereby leading to ITP accumulation. This in turn resulted in cytotoxicity, which was manifested by neutropenia and fever. Therefore, we hypothesized a pharmacogenetic model involving the ITPA variant genotype in multifactorial components that act together to determine the onset of zidovudine-related adverse effects.

  5. Sequencing paediatric antiretroviral therapy in the context of a public health approach

    PubMed Central

    Boerma, Ragna S; Boender, T Sonia; van Hensbroek, Michael Boele; Rinke de Wit, Tobias F; Sigaloff, Kim CE

    2015-01-01

    Introduction As access to prevention of mother-to-child transmission (PMTCT) efforts has increased, the total number of children being born with HIV has significantly decreased. However, those children who do become infected after PMTCT failure are at particular risk of HIV drug resistance, selected by exposure to maternal or paediatric antiretroviral drugs used before, during or after birth. As a consequence, the response to antiretroviral therapy (ART) in these children may be compromised, particularly when non-nucleoside reverse transcriptase inhibitors (NNRTIs) are used as part of the first-line regimen. We review evidence guiding choices of first- and second-line ART. Discussion Children generally respond relatively well to ART. Clinical trials show the superiority of protease inhibitor (PI)- over NNRTI-based treatment in young children, but observational reports of NNRTI-containing regimens are usually favourable as well. This is reassuring as national guidelines often still recommend the use of NNRTI-based treatment for PMTCT-unexposed young children, due to the higher costs of PIs. After failure of NNRTI-based, first-line treatment, the rate of acquired drug resistance is high, but HIV may well be suppressed by PIs in second-line ART. By contrast, there are currently no adequate alternatives in resource-limited settings (RLS) for children failing either first- or second-line, PI-containing regimens. Conclusions Affordable salvage treatment options for children in RLS are urgently needed. PMID:26639116

  6. Adherence to antiretroviral therapy, virological response, and time to resistance in the Dakar cohort

    PubMed Central

    Tournoud, M.; Etard, J. F.; Ecochard, R.; DeGruttola, V.

    2012-01-01

    In 1998, with the launch of the Senegalese Initiative for Antiretroviral Access (ISAARV), Senegal became one of the first African countries to propose an antiretroviral access program. Our objective in this paper is to study the time to any first drug resistance, as well as predictors of the time to resistance. We propose a joint model to study the effect of adherence to the HAART therapy, and virological response on the time to resistance mutations. A logistic mixed model is used to model the time-dependent adherence process; and a Markov model is used to study the virological response. Given the presence of missing data in the adherence process and in the virological response, the latent adherence and virological states are then included in the linear predictor of the time to resistance model. The proposed time to resistance model takes into account interval-censored data as well as null hazard periods, during which the viral replication is very low. A Bayesian approach is used for accommodating with missing data and for prediction. We also propose model checking tools to study model adequacy. PMID:19941299

  7. Persistent Peripheral Nervous System Damage in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.

    PubMed

    Dorsey, Jamie L; Mangus, Lisa M; Hauer, Peter; Ebenezer, Gigi J; Queen, Suzanne E; Laast, Victoria A; Adams, Robert J; Mankowski, Joseph L

    2015-11-01

    Human immunodeficiency virus (HIV)-induced peripheral neuropathy is the most common neurologic complication associated with HIV infection. In addition to virus-mediated injury of the peripheral nervous system (PNS), treatment of HIV infection with combination antiretroviral therapy (cART) may induce toxic neuropathy as a side effect. Antiretroviral toxic neuropathy is clinically indistinguishable from the sensory neuropathy induced by HIV; in some patients, these 2 processes are likely superimposed. To study these intercurrent PNS disease processes, we first established a simian immunodeficiency virus (SIV)/pigtailed macaque model in which more than 90% of animals developed PNS changes closely resembling those seen in HIV-infected individuals with distal sensory neuropathy. To determine whether cART alters the progression of SIV-induced PNS damage, dorsal root ganglia and epidermal nerve fibers were evaluated in SIV-infected macaques after long-term suppressive cART. Although cART effectively suppressed SIV replication and reduced macrophage activation in the dorsal root ganglia, PGP 9.5 immunostaining and measurements of epidermal nerve fibers in the plantar surface of the feet of treated SIV-infected macaques clearly showed that cART did not normalize epidermal nerve fiber density. These findings illustrate that significant PNS damage persists in SIV-infected macaques on suppressive cART.

  8. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy.

    PubMed

    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

    2009-06-09

    In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is 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.

  9. HIV-1 and bacterial pneumonia in the era of antiretroviral therapy.

    PubMed

    Segal, Leopoldo N; Methé, Barbara A; Nolan, Anna; Hoshino, Yoshihiko; Rom, William N; Dawson, Rod; Bateman, Eric; Weiden, Michael D

    2011-06-01

    Community-acquired pneumonia affects approximately 4 million people in the United States, with 40,000 deaths per year. The incidence is increased about 35-fold in HIV-infected individuals, and this rate has decreased since the antiretroviral era has begun. Bacterial pneumonia has decreased from 5 to 20 cases per 100 person-years to less than 1 to 5 cases per 100 person-years in the era of antiretroviral therapy. HIV-1 infection impairs the function of neutrophils in the lung and infects CD4⁺ cells and alveolar macrophages. Opportunistic infections dramatically increase local HIV replication in the lung cells, especially alveolar macrophages and CD4⁺ cells. This enhanced replication increases viral mutations and provides opportunities for viral escape from latent reservoirs. Mortality is increased with more comorbidities in this highly susceptible population. Immunization with vaccines is recommended, especially pneumococcal vaccines, although the vaccine itself may stimulate viral replication. Recent studies show that the lower respiratory tract is a microbial reservoir in HIV-infected individuals rather than being a sterile environment, as originally thought. This may provide new opportunities for preventing opportunistic infections in HIV-infected subjects. Bacterial pneumonia presents an ongoing challenge in these high-risk individuals, particularly in studying the functions of the innate and acquired immune response.

  10. Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue.

    PubMed Central

    Cohen, O J; Pantaleo, G; Holodniy, M; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, G N; Lalezari, J; Bartlett, J A; Steigbigel, R T

    1995-01-01

    Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue. Images Fig. 1 Fig. 2 Fig. 3 PMID:7597072

  11. Low bone mass in behaviorally HIV-infected young men on antiretroviral therapy: adolescent trials network (ATN) study 021B

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peak bone mass is achieved in adolescence/early adulthood and is the key determinant of bone mass in adulthood. We evaluated the association of bone mass with HIV infection and antiretroviral therapy (ART) during this critical period among behaviorally HIV infected young men and seronegative control...

  12. The other genome: a systematic review of studies of mitochondrial DNA haplogroups and outcomes of HIV infection and antiretroviral therapy.

    PubMed

    Hart, Anna B; Samuels, David C; Hulgan, Todd

    2013-01-01

    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.

  13. Long-Term Outcomes on Antiretroviral Therapy in a Large Scale-Up Program in Nigeria

    PubMed Central

    Meloni, Seema T.; Chang, Charlotte A.; Eisen, Geoffrey; Jolayemi, Toyin; Banigbe, Bolanle; Okonkwo, Prosper I.; Kanki, Phyllis J.

    2016-01-01

    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

  14. Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy

    PubMed Central

    Freedberg, Kenneth A.; Kumarasamy, Nagalingeswaran; Losina, Elena; Cecelia, Anitha J.; Scott, Callie A.; Divi, Nomita; Flanigan, Timothy P.; Lu, Zhigang; Weinstein, Milton C.; Wang, Bingxia; Ganesh, Aylur K.; Bender, Melissa A.; Mayer, Kenneth H.; Walensky, Rochelle P.

    2008-01-01

    Background India has more than 5.7 million people infected with human immunodeficiency virus (HIV). In 2004, the Indian government began providing antiretroviral therapy (ART), and there are now an estimated 56 500 people receiving ART. Objective To project the life expectancy, cost, and cost-effectiveness associated with different strategies for using ART in India, to inform treatment programs. Methods We utilized an HIV disease simulation model, incorporating data on natural history, treatment efficacy, and costs of care from India. Input parameters for the simulated cohort included mean age 32.6 years and mean CD4 count 318 cells/μl (SD 291 cells/μl). We examined different criteria for starting and stopping ART with a first-line regimen of stavudine/lamivudine/nevirapine, and the impact of a second-line protease-inhibitor-based regimen. Cost-effectiveness in US dollars per year of life saved (US$/YLS) was compared incrementally among alternative starting, sequencing, and stopping criteria. Results Discounted (undiscounted) mean survival ranged from 34.5 (37.5) months with no ART to 64.7 (73.6) months with one line of therapy initiated at CD4 < 350 cells/μl, to 88.9 (106.5) months with two lines of therapy initiated at CD4 < 350 cells/μl. Lifetime medical costs ranged from US$530 (no ART) to US$5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US$430/YLS to US$550/YLS as the CD4 starting criterion was increased from CD4 < 250 cells/μl to < 350 cells/μl. Use of two lines of therapy had an incremental cost-effectiveness ratio of US$1880/YLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. Conclusions In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival

  15. The Continuing Evolution of HIV-1 Therapy: Identification and Development of Novel Antiretroviral Agents Targeting Viral and Cellular Targets

    PubMed Central

    Hartman, Tracy L.; Buckheit, Robert W.

    2012-01-01

    During the past three decades, over thirty-five anti-HIV-1 therapies have been developed for use in humans and the progression from monotherapeutic treatment regimens to today's highly active combination antiretroviral therapies has had a dramatic impact on disease progression in HIV-1-infected individuals. In spite of the success of AIDS therapies and the existence of inhibitors of HIV-1 reverse transcriptase, protease, entry and fusion, and integrase, HIV-1 therapies still have a variety of problems which require continued development efforts to improve efficacy and reduce toxicity, while making drugs that can be used throughout both the developed and developing world, in pediatric populations, and in pregnant women. Highly active antiretroviral therapies (HAARTs) have significantly delayed the progression to AIDS, and in the developed world HIV-1-infected individuals might be expected to live normal life spans while on lifelong therapies. However, the difficult treatment regimens, the presence of class-specific drug toxicities, and the emergence of drug-resistant virus isolates highlight the fact that improvements in our therapeutic regimens and the identification of new and novel viral and cellular targets for therapy are still necessary. Antiretroviral therapeutic strategies and targets continue to be explored, and the development of increasingly potent molecules within existing classes of drugs and the development of novel strategies are ongoing. PMID:22848825

  16. Socioeconomic Predictors of Adherence Behavior Among HIV-Positive Patients Receiving Antiretroviral Therapy in Selangor, Malaysia.

    PubMed

    Abdulrahman, Surajudeen Abiola; Rampal, Lekhraj; Othman, Norlijah; Ibrahim, Faisal; Kadir Shahar, Hayati; Radhakrishnan, Anuradha P

    2017-04-01

    Medication adherence remains a critical link between the prescribed ART regimen and treatment outcome. Several factors may influence adherence behavior. This cross-sectional study aimed to highlight socioeconomic predictors of adherence behavior among a cohort of 242 adult Malaysian patients receiving antiretroviral therapy in Hospital Sungai Buloh, Malaysia, where they were enrolled in a parent study (single-blinded randomized controlled trial) between January and December 2014. Statistical analysis of secondary data on adherence behavior and sociodemographic characteristics of the patients revealed mean age of 33.4 years and ranged from 18 to 64 years; 88.8% were males. A total of 224 (93%) patients who completed 6 months' adherence assessment were included in the model. Of these, 135 (60.3%) achieved optimal adherence. Multivariate binary logistic regression analysis revealed that patient's income and ethnicity were significant predictors of adherence behavior. This may be valuable for targeted programmatic interventions to further enhance successful treatment outcomes among the target population.

  17. HIV infection and arterial stiffness among older-adults taking antiretroviral therapy in rural Uganda

    PubMed Central

    Siedner, Mark J.; Kim, June-Ho; Nakku, Ruth Sentongo; Hemphill, Linda; Triant, Virginia A.; Haberer, Jessica E.; Martin, Jeffrey N.; Boum, Yap; Kwon, Douglas S.; Tsai, Alexander C.; Hunt, Peter W.; Okello, Samson; Bangsberg, David R.

    2015-01-01

    HIV infection is associated with arterial stiffness, but no studies have assessed this relationship in sub-Saharan Africa. We enrolled 205 participants over 40 years old in Uganda: 105 on antiretroviral therapy for a median of 7 years, and a random sample of 100 age and gender-matched HIV-uninfected controls from the clinic catchment area. The prevalence of arterial stiffness (ABI>1.2) was 33%, 18%, 19% and 2% in HIV+ men, HIV- men, HIV+ women, and HIV- women. In multivariable models adjusted for cardiovascular risk factors, HIV+ individuals had over double the prevalence of arterial stiffness (APR 2.86, 95%CI 1.41–5.79, P=0.003). PMID:26636926

  18. HIV-induced alteration in gut microbiota: driving factors, consequences, and effects of antiretroviral therapy.

    PubMed

    Lozupone, Catherine A; Rhodes, Matthew E; Neff, Charles P; Fontenot, Andrew P; Campbell, Thomas B; Palmer, Brent E

    2014-07-01

    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.

  19. Decreased HIV Type 1 Transcription in CCR5-Δ32 Heterozygotes During Suppressive Antiretroviral Therapy

    PubMed Central

    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.

    2014-01-01

    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. PMID:24935955

  20. Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy.

    PubMed

    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

    2014-12-01

    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.

  1. [MEDICO-SOCIAL CHARACTERISTIC OF HIV-INFECTED PATIENTS RECEIVING ANTIRETROVIRAL THERAPY].

    PubMed

    Rostova, N B; Ivanova, E S; Ivanova, Yu N

    2015-01-01

    The aim of the study was medico-social characteristic of HIV-infected patients receiving antiretroviral therapy in 2006-2012 based on the logical and comparative analysis of medical cards with the use of systemic informational approach. The study yielded the medico-social characteristic of HIV-infected patients suggesting the presence of concomitant disorders requiring prescription of several medications to be used either simultaneously or alternatively (in case of poor efficiency or side effects of primary treatment). The data obtained indicate the necessity of optimization of the choice and prescription of pharmacotherapy taking account of its effects and safety based on the analysis of the potential and cost-effectiveness of different therapeutic modalities. The results of the study can be used to develop organizational measures for the improvement of public drug supply.

  2. Decline in national tuberculosis notifications with national scale-up of antiretroviral therapy in Malawi.

    PubMed

    Kanyerere, H; Mganga, A; Harries, A D; Tayler-Smith, K; Jahn, A; Chimbwandira, F M; Mpunga, J

    2014-06-21

    From 2000 to 2012, Malawi scaled up antiretroviral therapy (ART) from <3000 to 404 905 persons living with HIV/AIDS (human immunodeficiency virus/acquired immune-deficiency syndrome), representing an ART coverage of 40.6% among those living with HIV. During this time, annual tuberculosis (TB) notifications declined by 28%, from 28 234 to 20 463. Percentage declines in annual TB case notifications were as follows: new TB (26%), recurrent TB (40%), new smear-positive pulmonary TB (19%), new smear-negative pulmonary TB (42%), extra-pulmonary TB (19%), HIV-positive TB (30%) and HIV-negative TB (10%). The decline in TB notifications is associated with ART scale-up, supporting its value in controlling TB in high HIV prevalence areas in sub-Saharan Africa.

  3. A case study of the provision of antiretroviral therapy for refugees in Tanzania.

    PubMed

    Stephen, Hobokela; Roberts, Bayard

    2009-01-01

    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.

  4. [Disorders of lipid and glucose metabolism. Long-term adverse effects of antiretroviral therapy].

    PubMed

    Landauer, N; Goebel, F D

    2002-04-09

    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.

  5. Adherence to antiretroviral therapy among HIV-infected adults in the United States.

    PubMed

    Beer, Linda; Skarbinski, Jacek

    2014-12-01

    National estimates of antiretroviral therapy (ART) adherence and adherence support services utilization are needed to inform efforts to improve the health of HIV-infected persons in the United States. In a nationally representative sample of HIV-infected adults receiving medical care, 86% self-reported taking all ART doses in the past 72 hours. Overall, 20% reported using adherence support services and 2% reported an unmet need for services. If all nonadherent persons not receiving adherence support and all persons with a self-perceived unmet need for adherence support accessed services, resources to support ∼42,673 additional persons would be needed. Factors associated with lower adherence included younger age, female gender, depression, stimulant use, binge alcohol use, greater than once-daily dosing, longer time since HIV diagnosis, and patient beliefs. Predictors of adherence are multifactorial so multiple targeted strategies to improve adherence are warranted. Providing adherence support services to all those in need may require additional resources.

  6. The Indirect Impact of Antiretroviral Therapy: Mortality Risk, Mental Health, and HIV-Negative Labor Supply

    PubMed Central

    Baranov, Victoria; Bennett, Daniel; Kohler, Hans-Peter

    2015-01-01

    To reduce the burden of the HIV/AIDS epidemic, international donors recently began providing free antiretroviral therapy (ART) in parts of Sub-Saharan Africa. ART dramatically prolongs life and reduces infectiousness for people with HIV. This paper shows that ART availability increases work time for HIV-negative people without caretaker obligations, who do not directly benefit from the medicine. A difference-in-difference design compares people living near and far from ART, before and after treatment becomes available. Next we explore the possible reasons for this pattern. Although we cannot pinpoint the mechanism, we find that ART availability substantially reduces subjective mortality risk and improves mental health. These results show an undocumented economic consequence of the HIV/AIDS epidemic and an important externality of medical innovation. They also provide the first evidence of a link between the disease environment and mental health. PMID:26516983

  7. Effect of antiretroviral HIV therapy on hepatitis B virus replication and pathogenicity.

    PubMed

    Gürtler, Lutz G

    2014-01-01

    Coinfections with hepatitis B virus (HBV) and HIV are very frequent. Although HBV is a DNA virus, it replicates via reverse transcription like HIV. Structural similarities between the enzymatic pocket of the HBV DNA polymerase and HIV-1 reverse transcriptase are the basis that certain drugs inhibit both enzymes and thus the replication of both viruses. HBV components increase the pathogenic action of HIV and vice versa directly by certain proteins like HBsAg in the case of HBV and HIV-encoded Tat and Vpr and by disturbing the cytokine balance in affected cells. Antiretroviral therapy is highly beneficial for HIV/HBV-coinfected patients, but carries the risk of drug-induced resistance development and hepatotoxicity. Even with restoration of the immune capacity, signs of hepatic inflammation may develop even after 10 years of treatment.

  8. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    PubMed

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    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.

  9. Antiretroviral Therapy and Nutrition in Southern Africa: Citizenship and the Grammar of Hunger.

    PubMed

    Cousins, Thomas

    2016-01-01

    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.

  10. The indirect impact of antiretroviral therapy: Mortality risk, mental health, and HIV-negative labor supply.

    PubMed

    Baranov, Victoria; Bennett, Daniel; Kohler, Hans-Peter

    2015-12-01

    To reduce the burden of the HIV/AIDS epidemic, international donors recently began providing free antiretroviral therapy (ART) in parts of Sub-Saharan Africa. ART dramatically prolongs life and reduces infectiousness for people with HIV. This paper shows that ART availability increases work time for HIV-negative people without caretaker obligations, who do not directly benefit from the medicine. A difference-in-difference design compares people living near and far from ART, before and after treatment becomes available. Next we explore the possible reasons for this pattern. Although we cannot pinpoint the mechanism, we find that ART availability substantially reduces subjective mortality risk and improves mental health. These results show an undocumented economic consequence of the HIV/AIDS epidemic and an important externality of medical innovation. They also provide the first evidence of a link between the disease environment and mental health.

  11. [Failure of first-line antiretroviral therapy in HIV-infected children in Ouagadougou, Burkina Faso].

    PubMed

    Kouéta, F; Yé, D; Zoungrana, A; Sacko, A; Ouédraogo-Traoré, R; Kafando, E; Ouédraogo, S

    2010-12-01

    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.

  12. The Evaluation of Carotid Atherosclerosis in Patients with the HIV-1 Infection: The Role of the Antiretroviral Therapy

    PubMed Central

    P.N., Suparna; Achappa, Basavaprabhu; B., Unnikrishnan; Madi, Deepak; Chowta, Mukta N.; Ramapuram, John T; Rao, Satish; Mahalingam, Soundarya

    2013-01-01

    Background and Objective: The recognition and the assessment of the carotid intimal thickness helps in predicting the risk of the cardiovascular events in Human Immunodeficiency Virus (HIV) infected patients who are on Antiretroviral Therapy (ART). The objective of this study was to assess and compare the carotid intimal thickness in HIV positive individuals who were on antiretroviral therapy with HIV positive individuals who were not on anti-retroviral therapy. Subjects and Methods: All the HIV positive individuals who were 20 years old and above, who had been diagnosed by the National AIDS Control Organization (NACO) guidelines were included in the study. The HIV positive individuals who were diagnosed with diabetes mellitus and hypertension were excluded from the study. The study subjects were divided into 2 groups i.e. HIV patients who were on anti-retroviral therapy and HIV patients who were not on anti-retroviral therapy. The patients had to be on anti-retroviral therapy for a minimum of 6 months for them to be included in the first group. The data was collected by using a semi structured, pre-tested proforma, which included the demographic details, the duration of the HIV infection, details of the antiretroviral treatment, a history of smoking/ alcohol consumption and details on the assessments of the metabolic syndrome. Results: A total of 42 patients were included in the study. Among them, 28 were males (66.7%) and 14 were females (33.3%). Twenty six patients were on ART and the remaining patients were treatment naive. There were significant differences with regards to their age and the duration of the HIV infection, which was longer in the patients who were on ART (p= 0.049, p=0.003 respectively). The Body Mass Index (BMI), the waist: hip ratio, the mid-arm circumference, the waist circumference, the skin fold thickness and the carotid intimal-media thickness were higher in the HIV patients who were on ART as compared to those in the treatment naive

  13. Modulation of HCV Replication After Combination Antiretroviral Therapy in HCV/HIV Coinfected Patients

    PubMed Central

    Sherman, Kenneth E.; Guedj, Jeremie; Shata, Mohamed Tarek; Blackard, Jason T.; Rouster, Susan D.; Castro, Mario; Feinberg, Judith; Sterling, Richard K.; Goodman, Zachary; Aronow, Bruce J.; Perelson, Alan S.

    2015-01-01

    The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients coinfected with human immunodeficiency virus (HIV). Coinfection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV coinfected patients into a cART initiation trial, and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in HCV flare and alanine aminotransferase (ALT) increase (2× or more increase from baseline) in a subset of treated patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in patients who underwent successful cART, particularly with respect to downregulation of genes with known antiviral roles. Our findings suggest that the effective suppression of HIV by cART initiates a cascade of early and late events in treated patients with HCV. Early events involving downregulation of interferon-stimulated genes may lead to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declines to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV coinfection. PMID:25101888

  14. Discordant Treatment Responses to Combination Antiretroviral Therapy in Rwanda: A Prospective Cohort Study

    PubMed Central

    Kayigamba, Felix R.; Franke, Molly F.; Bakker, Mirjam I.; Rodriguez, Carly A.; Bagiruwigize, Emmanuel; Wit, Ferdinand WNM; Rich, Michael L.; Schim van der Loeff, Maarten F.

    2016-01-01

    Introduction Some antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort. Methods A discordant immunological cART response was defined as an increase of <100 CD4 cells/mm3 at 12 months compared to baseline despite virological suppression (viral load [VL] <40 copies/mL). A discordant virological cART response was defined as detectable VL at 12 months with an increase in CD4 count ≥100 cells/mm3. The prevalence of, and independent predictors for these two types of discordant responses were analysed in two cohorts nested in a 12-month prospective study of cART-naïve HIV patients treated at nine rural health facilities in two regions in Rwanda. Results Among 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of <100 cells/mm3. Age ≥35 years and longer travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not. Conclusions Discordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes. PMID:27438000

  15. Antiretroviral Therapy and Reproductive Life Projects: Mitigating the Stigma of AIDS in Nigeria

    PubMed Central

    Mbakwem, Benjamin C

    2010-01-01

    As millions of people infected with HIV in Africa are increasingly able to live longer and healthier lives because of access to antiretroviral therapy, concerns have emerged that people might eschew protective practices after their health improves. Extending beyond the notion of sexual “disinhibition,” researchers have begun to analyze the sexual behavior of people in treatment through the perspective of their marital and childbearing aspirations. This article explores the reproductive life projects of HIV-positive men and women in southeastern Nigeria, showing how actions that contradict medical advice are understandable in the context of patients’ socially normative desires for marriage and children. Based on in-depth interviews and observations (June–December 2004; June–July 2006; June–July 2007) of people enrolled in the region’s oldest treatment program, we argue that broadly held social expectations with regard to reproduction are experienced even more acutely by HIV-positive people. This is because in Nigeria the stigma associated with AIDS is closely tied to widespread perceptions of social and moral crisis, such that AIDS itself is seen as both a cause and a symptom of anxiety-producing forms of social change. Specifically, in an era of rapid societal transformation, Nigerians see sexual promiscuity and the alienation of young people from traditional obligations to kin and community as indicative of threatened social reproduction. For people who are HIV-positive, marrying and having children offer not only the opportunity to lead normal lives, but also a means to mitigate the stigma associated with the disease. Four ethnographic case studies are provided to exemplify how and why social and personal life projects can trump or complicate medical and public health priorities. These examples suggest that treatment programs must openly address and proactively support the life projects of people on antiretroviral therapy if the full benefits of

  16. Facilitators and barriers to antiretroviral therapy adherence among adolescents in Ghana

    PubMed Central

    Ankrah, Daniel NA; Koster, Ellen S; Mantel-Teeuwisse, Aukje K; Arhinful, Daniel K; Agyepong, Irene A; Lartey, Margaret

    2016-01-01

    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 stigmatization after disclosure were the most frequently mentioned barriers. Self-motivation (knowledge induced) to adhere to treatment was a specific facilitator among older adolescents. Conclusion Continuous information provision in addition to unflinching support from health care workers and parents or guardians may improve adherence among adolescents. Also, interventions to reduce patient forgetfulness may be beneficial. A multi-sectorial approach would be needed to address adolescent disclosure of HIV/AIDS status. PMID:27042024

  17. The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic

    PubMed Central

    Broder, Samuel

    2010-01-01

    In the last 25 years, HIV-1, the retrovirus responsible for the Acquired Immunodeficiency Syndrome (AIDS), has gone from being an “inherently untreatable” infectious agent to one eminently susceptible to a range of approved therapies. During a five-year period, starting in the mid-1980s, my group at the National Cancer Institute played a role in the discovery and development of the first generation of antiretroviral agents, starting in 1985 with Retrovir® (zidovudine, AZT) in a collaboration with scientists at the Burroughs-Wellcome Company (now GlaxoSmithKline). We focused on AZT and related congeners in the dideoxynucleoside family of nucleoside reverse transcriptase inhibitors (NRTIs), taking them from the laboratory to the clinic in response to the pandemic of AIDS, then a terrifying and lethal disease. These drugs proved, above all else, that HIV-1 infection is treatable, and such proof provided momentum for new therapies from many sources, directed at a range of viral targets, at a pace that has rarely if ever been matched in modern drug development. Antiretroviral therapy has brought about a substantial decrease in the death rate due to HIV-1 infection, changing it from a rapidly lethal disease into a chronic manageable condition, compatible with very long survival. This has special implications within the classic boundaries of public health around the world, but at the same time in certain regions may also affect a cycle of economic and civil instability in which HIV-1/AIDS is both cause and consequence. Many challenges remain, including 1.) the life-long duration of therapy; 2.) the ultimate role of pre-exposure prophylaxis (PrEP); 3.) the cardiometabolic side effects or other toxicities of long-term therapy; 4.) the emergence of drug-resistance and viral genetic diversity (non-B subtypes); 5.) the specter of new cross-species transmissions from established retroviral reservoirs in apes and Old World monkeys; and 6.) the continued pace of new HIV-1

  18. Challenges faced by elderly guardians in sustaining the adherence to antiretroviral therapy in HIV-infected children in Zimbabwe.

    PubMed

    Skovdal, M; Campbell, C; Madanhire, C; Nyamukapa, C; Gregson, S

    2011-08-01

    Grandparents throughout sub-Saharan Africa have shown immense courage and fortitude in providing care and support for AIDS-affected children. However, growing old comes with a number of challenges which can compromise the quality of care and support they are able to provide, particularly for children infected by HIV and enrolled on antiretroviral therapy (ART) programmes. For ART to be effective, and for infected children not to develop drug-resistance, a complex treatment regimen must be followed. Drawing on the perspectives of 25 nurses and eight grandparents of HIV-infected children in Manicaland, eastern Zimbabwe, we explore some of the challenges faced by grandparents in sustaining children's adherence to ART. These challenges, serving as barriers to paediatric ART, are poverty, immobility, deteriorating memory and poor comprehension of complex treatments. Although older HIV-infected children were found to play an active role in sustaining the adherence to their programme of treatment by contributing to income and food generating activities and reminding their guardians about check-ups and drug administration, such contribution was not available from younger children. There is therefore an urgent need to develop ART services that both take into consideration the needs of elderly guardians and acknowledge and enhance the agency of older children as active and responsible contributors to ART adherence.

  19. Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy.

    PubMed

    Imamichi, Hiromi; Dewar, Robin L; Adelsberger, Joseph W; Rehm, Catherine A; O'Doherty, Una; Paxinos, Ellen E; Fauci, Anthony S; Lane, H Clifford

    2016-08-02

    Despite years of plasma HIV-RNA levels <40 copies per milliliter during combination antiretroviral therapy (cART), the majority of HIV-infected patients exhibit persistent seropositivity to HIV-1 and evidence of immune activation. These patients also show persistence of proviruses of HIV-1 in circulating peripheral blood mononuclear cells. Many of these proviruses have been characterized as defective and thus thought to contribute little to HIV-1 pathogenesis. By combining 5'LTR-to-3'LTR single-genome amplification and direct amplicon sequencing, we have identified the presence of "defective" proviruses capable of transcribing novel unspliced HIV-RNA (usHIV-RNA) species in patients at all stages of HIV-1 infection. Although these novel usHIV-RNA transcripts had exon structures that were different from those of the known spliced HIV-RNA variants, they maintained translationally competent ORFs, involving elements of gag, pol, env, rev, and nef to encode a series of novel HIV-1 chimeric proteins. These novel usHIV-RNAs were detected in five of five patients, including four of four patients with prolonged viral suppression of HIV-RNA levels <40 copies per milliliter for more than 6 y. Our findings suggest that the persistent defective proviruses of HIV-1 are not "silent," but rather may contribute to HIV-1 pathogenesis by stimulating host-defense pathways that target foreign nucleic acids and proteins.

  20. Mathematical Modeling of HIV Dynamics After Antiretroviral Therapy Initiation: A Review.

    PubMed

    Rivadeneira, Pablo S; Moog, Claude H; Stan, Guy-Bart; Brunet, Cecile; Raffi, François; Ferré, Virginie; Costanza, Vicente; Mhawej, Marie J; Biafore, Federico; Ouattara, Djomangan A; Ernst, Damien; Fonteneau, Raphael; Xia, Xiaohua

    2014-10-01

    This review shows the potential ground-breaking impact that mathematical tools may have in the analysis and the understanding of the HIV dynamics. In the first part, early diagnosis of immunological failure is inferred from the estimation of certain parameters of a mathematical model of the HIV infection dynamics. This method is supported by clinical research results from an original clinical trial: data just after 1 month following therapy initiation are used to carry out the model identification. The diagnosis is shown to be consistent with results from monitoring of the patients after 6 months. In the second part of this review, prospective research results are given for the design of individual anti-HIV treatments optimizing the recovery of the immune system and minimizing side effects. In this respect, two methods are discussed. The first one combines HIV population dynamics with pharmacokinetics and pharmacodynamics models to generate drug treatments using impulsive control systems. The second one is based on optimal control theory and uses a recently published differential equation to model the side effects produced by highly active antiretroviral therapy therapies. The main advantage of these revisited methods is that the drug treatment is computed directly in amounts of drugs, which is easier to interpret by physicians and patients.

  1. Mathematical Modeling of HIV Dynamics After Antiretroviral Therapy Initiation: A Review

    PubMed Central

    Moog, Claude H.; Stan, Guy-Bart; Brunet, Cecile; Raffi, François; Ferré, Virginie; Costanza, Vicente; Mhawej, Marie J.; Biafore, Federico; Ouattara, Djomangan A.; Ernst, Damien; Fonteneau, Raphael; Xia, Xiaohua

    2014-01-01

    Abstract This review shows the potential ground-breaking impact that mathematical tools may have in the analysis and the understanding of the HIV dynamics. In the first part, early diagnosis of immunological failure is inferred from the estimation of certain parameters of a mathematical model of the HIV infection dynamics. This method is supported by clinical research results from an original clinical trial: data just after 1 month following therapy initiation are used to carry out the model identification. The diagnosis is shown to be consistent with results from monitoring of the patients after 6 months. In the second part of this review, prospective research results are given for the design of individual anti-HIV treatments optimizing the recovery of the immune system and minimizing side effects. In this respect, two methods are discussed. The first one combines HIV population dynamics with pharmacokinetics and pharmacodynamics models to generate drug treatments using impulsive control systems. The second one is based on optimal control theory and uses a recently published differential equation to model the side effects produced by highly active antiretroviral therapy therapies. The main advantage of these revisited methods is that the drug treatment is computed directly in amounts of drugs, which is easier to interpret by physicians and patients. PMID:25371860

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

    PubMed

    Krentz, Hartmut B; Gill, M John

    2016-01-01

    Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p < 0.01); 32.1% stopped or switched ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p < 0.01). Non-continuous 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.

  3. Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy

    PubMed Central

    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.

    2014-01-01

    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

  4. Video observations of treatment administration to children on antiretroviral therapy in rural KwaZulu-Natal

    PubMed Central

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2016-01-01

    ABSTRACT For children younger than five years, caregivers are responsible for the measurement and administration of antiretroviral medication doses to children. Failure to adhere to the regimen as prescribed may lead to high viral loads (VLs), immune suppression and ultimately drug resistance. In the content of this study, adherence refers to adequate dosing of the medication by a caregiver. Acquired drug resistance to antiretroviral therapy (ART) is prevalent amongst children in South Africa, and poor adherence to the dosing regimen by caregivers may be associated with this problem. In this qualitative study, we purposively recruited 33 caregiver–child dyads from the Hlabisa HIV Treatment and Care Programme database. Children were divided into three groups based on their VL at the time of recruitment. Children with a VL ≥ 400 cps/ml were grouped as unsuppressed (n = 11); children with a VL ≤ 400 cps/ml were grouped as suppressed (n = 12); and children with no VL data were grouped as newly initiated (n = 10). Caregiver–child dyads were visited at their households twice to document, by means of video recording, how treatment was administered to the child. Observational notes and video recordings were entered into ATLAS.ti v 7 and analysed thematically. Results were interpreted through the lens of Ecological Systems Theory and the information–motivation–behavioural skills model was used to understand and reflect on several of the factors influencing adherence within the child’s immediate environment as identified in this study. Thematic video analysis indicated context- and medication-related factors influencing ART adherence. Although the majority of children in this sample took their medicine successfully, caregivers experienced several challenges with the preparation and administration of the medications. In the context of emerging drug resistance, efforts are needed to carefully monitor caregiver knowledge of treatment

  5. Impact of antiretroviral therapy on clinical outcomes in HIV + kidney transplant recipients: Review of 58 cases

    PubMed Central

    Lorio, Marco A.; Morris, Michele I.; Abbo, Lilian M.; Simkins, Jacques; Guerra, Giselle; Roth, David; Kupin, Warren L.; Mattiazzi, Adela; Ciancio, Gaetano; Chen, Linda J.; Burke, George W.; Figueiro, Jose M.; Ruiz, Phillip; Camargo, Jose F.

    2016-01-01

    Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients.  We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients.  Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation.  The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant.  Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02).  Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01).  Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients. PMID:28299182

  6. Formative evaluation of antiretroviral therapy scale-up efficiency in sub-Saharan Africa.

    PubMed

    Wagner, Glenn; Ryan, Gery; Taylor, Stephanie

    2007-11-01

    With millions in need of HIV antiretroviral therapy (ART) in the developing world, and scarce human and fiscal resources available, we conducted a formative evaluation of scale-up operations at clinics associated with AIDS Healthcare Foundation in Africa to identify lessons learned for improving scale-up efficiency. Site visits were made to six selected clinics in Uganda, Zambia, and South Africa, during which semistructured interviews with key stake-holders and observation of client flows and clinic operations were performed. This evaluation revealed the following lessons related to factors that are critical to efficient ART scale-up: (1) to ensure steady ART uptake, it is important to involve the community and community leaders in outreach, HIV education, and program decision-making; (2) minimizing bottlenecks to smooth patient flow requires efficient staff allocation to appropriate clinical duties, streamlined clinic visit schedule protocols, and tapping clients and the HIV community as a key source of labor; (3) to minimize clients dropping out of care, structures should be developed that enable clients to provide support and a "safety net" for helping each other remain in care; (4) computerized record management systems are essential for accurate antiretroviral inventory and dispensing records, quality assurance monitoring, and client enrollment records and visit scheduling; (5) effective organizational management and human resource policies are essential to maintain high job performance and satisfaction and limit burnout; (6) to maximize impact on social and economic health, it is important for ART programs to develop effective mechanisms for coordinating and referring clients to support service organizations.

  7. Endosomal Trafficking of Nanoformulated Antiretroviral Therapy Facilitates Drug Particle Carriage and HIV Clearance

    PubMed Central

    Guo, Dongwei; Zhang, Gang; Wysocki, Tadeusz A.; Wysocki, Beata J.; Gelbard, Harris A.; Liu, Xin-Ming; McMillan, JoEllyn M.

    2014-01-01

    ABSTRACT Limitations of antiretroviral therapy (ART) include poor patient adherence, drug toxicities, viral resistance, and failure to penetrate viral reservoirs. Recent developments in nanoformulated ART (nanoART) could overcome such limitations. To this end, we now report a novel effect of nanoART that facilitates drug depots within intracellular compartments at or adjacent to the sites of the viral replication cycle. Poloxamer 407-coated nanocrystals containing the protease inhibitor atazanavir (ATV) were prepared by high-pressure homogenization. These drug particles readily accumulated in human monocyte-derived macrophages (MDM). NanoATV concentrations were ∼1,000 times higher in cells than those that could be achieved by the native drug. ATV particles in late and recycling endosome compartments were seen following pulldown by immunoaffinity chromatography with Rab-specific antibodies conjugated to magnetic beads. Confocal microscopy provided cross validation by immunofluorescent staining of the compartments. Mathematical modeling validated drug-endosomal interactions. Measures of reverse transcriptase activity and HIV-1 p24 levels in culture media and cells showed that such endosomal drug concentrations enhanced antiviral responses up to 1,000-fold. We conclude that late and recycling endosomes can serve as depots for nanoATV. The colocalization of nanoATV at endosomal sites of viral assembly and its slow release sped antiretroviral activities. Long-acting nanoART can serve as a drug carrier in both cells and subcellular compartments and, as such, can facilitate viral clearance. IMPORTANCE The need for long-acting ART is significant and highlighted by limitations in drug access, toxicity, adherence, and reservoir penetrance. We propose that targeting nanoformulated drugs to infected tissues, cells, and subcellular sites of viral replication may improve clinical outcomes. Endosomes are sites for human immunodeficiency virus assembly, and increasing ART

  8. Risk of Cancer among Commercially Insured HIV-Infected Adults on Antiretroviral Therapy

    PubMed Central

    Dhakal, Ishwori; Casper, Corey; Noy, Ariela; Palefsky, Joel M.; Haigentz, Missak; Krown, Susan E.; Ambinder, Richard F.; Mitsuyasu, Ronald T.

    2016-01-01

    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 (<30, 30–39, 40–49, 50–59, and >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. PMID:27882054

  9. Effect of Pregnancy on Response to Antiretroviral Therapy in HIV-Infected African Women

    PubMed Central

    Wiener, Jeffrey; King, Caroline C.; Heffron, Renee; Mugo, Nelly R.; Nanda, Kavita; Pyra, Maria; Donnell, Deborah; Celum, Connie; Lingappa, Jairam R.; Baeten, Jared M.

    2017-01-01

    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

  10. Romidepsin-induced HIV-1 viremia during effective antiretroviral therapy contains identical viral sequences with few deleterious mutations

    PubMed Central

    Winckelmann, Anni; Barton, Kirston; Hiener, Bonnie; Schlub, Timothy E.; Shao, Wei; Rasmussen, Thomas A.; Østergaard, Lars; Søgaard, Ole S.; Tolstrup, Martin; Palmer, Sarah

    2017-01-01

    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

  11. Effectiveness of highly active antiretroviral therapy among HIV-1 infected women

    PubMed Central

    Gange, S; Barron, Y; Greenblatt, R; Anastos, K; Minkoff, H; Young, M; Kovacs, A; Cohen, M; Meyer, W; Munoz, A

    2002-01-01

    Design: Data collected from the Women's Interagency HIV Study, a prospective cohort study that enrolled women between October 1994 and November 1995. Setting: Six clinical consortia based in five cities in the United States (New York, NY; Washington, DC; Los Angeles, CA; San Francisco, CA; and Chicago, IL). Participants: A total of 1691 HIV seropositive women with a study visit after April 1996. Main results: Beginning in April 1996, the self reported use of HAART increased over time, with more than 50% of the cohort reporting HAART use in 1999. There was a 23% decline per semester in the incidence of AIDS from April 1996 (95% confidence intervals (CI) -29% to -16%). Furthermore, there was a 21% decline of the semiannual mortality rates among those with AIDS at baseline (95% CI -27% to -14%) and an 11% decline among those AIDS free at baseline (95% CI -3% to -18%). CD4+ lymphocyte counts either increased (women with baseline AIDS) or stabilised (women without baseline AIDS) after April 1996, and HIV RNA levels dramatically declined in both groups, although the percentage of women with HIV RNA above 4000 cps/ml remained stable at approximately 40% since mid-1997. Conclusions: Despite concerns regarding the use of antiretroviral therapies in this population, the use of therapies led to improved immunological function, suppressed HIV disease activity, and dramatic declines in morbidity and mortality. PMID:11812817

  12. Disseminated rhodococcus equi infection in HIV infection despite highly active antiretroviral therapy

    PubMed Central

    2011-01-01

    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. PMID:22168333

  13. Association of First-Line and Second-Line Antiretroviral Therapy Adherence

    PubMed Central

    Ramadhani, Habib O.; Bartlett, John A.; Thielman, Nathan M.; Pence, Brian W.; Kimani, Stephen M.; Maro, Venance P.; Mwako, Mtumwa S.; Masaki, Lazaro J.; Mmbando, Calvin E.; Minja, Mary G.; Lirhunde, Eileen S.; Miller, William C.

    2014-01-01

    Background  Adherence to first-line antiretroviral therapy (ART) may be an important indicator of adherence to second-line ART. Evaluating this relationship may be critical to identify patients at high risk for second-line failure, thereby exhausting their treatment options, and to intervene and improve patient outcomes. Methods  Adolescents and adults (n = 436) receiving second-line ART were administered standardized questionnaires that captured demographic characteristics and assessed adherence. Optimal and suboptimal cumulative adherence were defined as percentage adherence of ≥90% and <90%, respectively. Bivariable and multivariable binomial regression models were used to assess the prevalence of suboptimal adherence percentage by preswitch adherence status. Results  A total of 134 of 436 (30.7%) participants reported suboptimal adherence to second-line ART. Among 322 participants who had suboptimal adherence to first-line ART, 117 (36.3%) had suboptimal adherence to second-line ART compared with 17 of 114 (14.9%) who had optimal adherence to first-line ART. Participants who had suboptimal adherence to first-line ART were more likely to have suboptimal adherence to second-line ART (adjusted prevalence ratio, 2.4; 95% confidence interval, 1.5–3.9). Conclusions  Adherence to first-line ART is an important predictor of adherence to second-line ART. Targeted interventions should be evaluated in patients with suboptimal adherence before switching into second-line therapy to improve their outcomes. PMID:25734147

  14. Disease-modifying therapeutic concepts for HIV in the era of highly active antiretroviral therapy.

    PubMed

    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

    2011-11-01

    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.

  15. Transient Viremia, Plasma Viral Load, and Reservoir Replenishment in HIV-Infected Patients on Antiretroviral Therapy

    PubMed Central

    Jones, Laura E.; Perelson, Alan S.

    2008-01-01

    Summary When antiretroviral therapy (ART) is administered for long periods to HIV-1–infected patients, most achieve viral loads that are “undetectable” by standard assay methods (ie, HIV-1 RNA <50 copies/mL). Despite sustaining viral loads lower than the level of detection, a number of patients experience unexplained episodes of transient viremia or viral “blips.” We propose that transient activation of the immune system by infectious agents may explain these episodes of viremia. Using 2 different mathematical models, one in which blips arise because of target cell activation and subsequent infection and another in which latent cell activation generates blips, we establish a nonlinear (power law) relationship between blip amplitude and viral load (under ART) that suggest blips should be of lower amplitude, and thus harder to detect, as increasingly potent therapy is used. This effect can be more profound than is predicted by simply lowering the baseline viral load from which blips originate. Finally, we suggest that sporadic immune activation may elevate the level of chronically infected cells and replenish viral reservoirs, including the latent cell reservoir, providing a mechanism for recurrent viral blips and low levels of viremia under ART. PMID:17496565

  16. Relationship between depressive symptoms, alcohol use, and antiretroviral therapy adherence among HIV-infected, clinic-attending patients in South Africa.

    PubMed

    Magidson, Jessica F; Saal, Wylene; Nel, Adriaan; Remmert, Jocelyn E; Kagee, Ashraf

    2016-02-15

    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.

  17. START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection

    PubMed Central

    Siedner, Mark J.

    2016-01-01

    The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed. PMID:26989755

  18. HIV Cure Strategies: How Good Must They Be to Improve on Current Antiretroviral Therapy?

    PubMed Central

    Sax, Paul E.; Sypek, Alexis; Berkowitz, Bethany K.; Morris, Bethany L.; Losina, Elena; Paltiel, A. David; Kelly, Kathleen A.; Seage, George R.; Walensky, Rochelle P.; Weinstein, Milton C.; Eron, Joseph; Freedberg, Kenneth A.

    2014-01-01

    Background We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). Methods We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY. Results For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. Conclusions Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV. PMID:25397616

  19. Barriers and facilitators to paediatric adherence to antiretroviral therapy in rural South Africa: a multi-stakeholder perspective

    PubMed Central

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2015-01-01

    Poor adherence to antiretroviral therapy (ART) contributes to the development of drug resistance. HIV-infected children, especially those 5 years and under, are dependent on a caregiver to adhere to ART. However, characteristics of the caregiver, child, regimen, clinic and social context affect clinic attendance and medication-taking, both of which constitute adherent behaviour. We conducted nine interviews and three focus groups to determine how doctors, nurses, counsellors, traditional healers and caregivers understood the barriers and facilitators to ART adherence among children residing in rural South Africa. The data were transcribed, translated into English from isiZulu where necessary, and coded using Atlas.ti version 7. Results were interpreted through the lens of Bronfenbrenner's Ecological Systems Theory. We found that at the micro-level, palatability of medication and large volumes of medication were problematic for young children. Characteristics of the caregiver including absent mothers, grandmothers as caregivers and denial of HIV amongst fathers were themes related to the micro-system. Language barriers and inconsistent attendance of caregivers to monthly clinic visits were factors affecting adherence in the meso-system. Adherence counselling and training were the most problematic features in the exo-system. In the macro-system, the effects of food insecurity and the controversy surrounding the use of traditional medicines were most salient. Increased supervision and regular training amongst lay adherence counsellors are needed, as well as regular monitoring of the persons attending the clinic on the child's behalf. PMID:25355176

  20. Barriers and facilitators to paediatric adherence to antiretroviral therapy in rural South Africa: a multi-stakeholder perspective.

    PubMed

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2015-01-01

    Poor adherence to antiretroviral therapy (ART) contributes to the development of drug resistance. HIV-infected children, especially those 5 years and under, are dependent on a caregiver to adhere to ART. However, characteristics of the caregiver, child, regimen, clinic and social context affect clinic attendance and medication-taking, both of which constitute adherent behaviour. We conducted nine interviews and three focus groups to determine how doctors, nurses, counsellors, traditional healers and caregivers understood the barriers and facilitators to ART adherence among children residing in rural South Africa. The data were transcribed, translated into English from isiZulu where necessary, and coded using Atlas.ti version 7. Results were interpreted through the lens of Bronfenbrenner's Ecological Systems Theory. We found that at the micro-level, palatability of medication and large volumes of medication were problematic for young children. Characteristics of the caregiver including absent mothers, grandmothers as caregivers and denial of HIV amongst fathers were themes related to the micro-system. Language barriers and inconsistent attendance of caregivers to monthly clinic visits were factors affecting adherence in the meso-system. Adherence counselling and training were the most problematic features in the exo-system. In the macro-system, the effects of food insecurity and the controversy surrounding the use of traditional medicines were most salient. Increased supervision and regular training amongst lay adherence counsellors are needed, as well as regular monitoring of the persons attending the clinic on the child's behalf.

  1. Anemia and Red Blood Cell Indices Predict HIV-Associated Neurocognitive Impairment in the Highly Active Antiretroviral Therapy Era

    PubMed Central

    Kallianpur, Asha R.; Wang, Quan; Jia, Peilin; Hulgan, Todd; Zhao, Zhongming; Letendre, Scott L.; Ellis, Ronald J.; Heaton, Robert K.; Franklin, Donald R.; Barnholtz-Sloan, Jill; Collier, Ann C.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin B.; McArthur, Justin C.; Morgello, Susan; Simpson, David M.; McCutchan, J. A.; Grant, Igor

    2016-01-01

    Background. Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. Methods. We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4+ T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. Results. HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). Conclusions. Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons. PMID:26690344

  2. CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States

    PubMed Central

    Fairlie, Lee; Karalius, Brad; Patel, Kunjal; van Dyke, Russell B.; Hazra, Rohan; Hernán, Miguel A.; Siberry, George K.; Seage, George R.; Agwu, Allison; Wiznia, Andrew

    2015-01-01

    Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) −1.01 to 2.19], not different than those who continued failing cART (71%) (−0.64 percentage points, P = 0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P = 0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline −3.18 percentage points (95% CI −5.25 to −1.11) compared with those initiating new cART (P = 0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log10VL by 12 months, the new cART group having the largest drop (−1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring. PMID:26182197

  3. Focal epithelial hyperplasia (Heck disease) related to highly active antiretroviral therapy in an HIV-seropositive child. A report of a case, and a review of the literature.

    PubMed

    Feller, L; Khammissa, R A G; Wood, N H; Malema, V; Meyerov, R; Lemmer, J

    2010-05-01

    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.

  4. A method to manage and share anti-retroviral (ARV) therapy information of human immunodeficiency virus (HIV) patients in Vietnam.

    PubMed

    Nguyen, Phung Anh; Syed-Abdul, Shabbir; Minamareddy, Priti; Lee, Peisan; Ngo, Thuy Dieu; Iqbal, Usman; Nguyen, Phuong Hoang; Jian, Wen-Shan; Li, Yu-Chuan Jack

    2013-08-01

    Management of antiretroviral (ARV) drug and HIV patients data is an important component of Vietnam Administration of HIV/AIDS Control (VAAC) Department and hospitals/health care units when people often travel in other places of Vietnam; therefore, it would lead to a number of medical errors in treatment as well as patients do not adhere to ARV therapy. In this paper, we describe a system that manages and shares antiretroviral therapy information of 4438 HIV patients in three healthcare centers in Hanoi capital of Vietnam. The overall design considerations, architecture and the integration of centralized database and decentralized management for the system are also presented. The findings from this study can serve as a guide to consider in the implementation model of health care to manage and share information of patients not only in HIV infection, but also in the other chronic and non-communicable diseases.

  5. Cellular automata approach for the dynamics of HIV infection under antiretroviral therapies: The role of the virus diffusion

    NASA Astrophysics Data System (ADS)

    González, Ramón E. R.; de Figueirêdo, Pedro Hugo; Coutinho, Sérgio

    2013-10-01

    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.

  6. Antiretroviral Therapy in Simian Immunodeficiency Virus-Infected Sooty Mangabeys: Implications for AIDS Pathogenesis

    PubMed Central

    Calascibetta, Francesca; Micci, Luca; Carnathan, Diane; Lawson, Benton; Vanderford, Thomas H.; Bosinger, Steven E.; Easley, Kirk; Chahroudi, Ann; Mackel, Joseph; Keele, Brandon F.; Long, Samuel; Lifson, Jeffrey; Paiardini, Mirko

    2016-01-01

    ABSTRACT Simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) do not develop AIDS despite high levels of viremia. Key factors involved in the benign course of SIV infection in SMs are the absence of chronic immune activation and low levels of infection of CD4+ central memory (TCM) and stem cell memory (TSCM) T cells. To better understand the role of virus replication in determining the main features of SIV infection in SMs, we treated 12 SMs with a potent antiretroviral therapy (ART) regimen for 2 to 12 months. We observed that ART suppressed viremia to <60 copies/ml of plasma in 10 of 12 animals and induced a variable decrease in the level of cell-associated SIV DNA in peripheral blood (average changes of 0.9-, 1.1-, 1.5-, and 3.7-fold for CD4+ transitional memory [TTM], TCM, effector memory [TEM], and TSCM cells, respectively). ART-treated SIV-infected SMs showed (i) increased percentages of circulating CD4+ TCM cells, (ii) increased levels of CD4+ T cells in the rectal mucosa, and (iii) significant declines in the frequencies of HLA-DR+ CD8+ T cells in the blood and rectal mucosa. In addition, we observed that ART interruption resulted in rapid viral rebound in all SIV-infected SMs, indicating that the virus reservoir persists for at least a year under ART despite lower infection levels of CD4+ TCM and TSCM cells than those seen in pathogenic SIV infections of macaques. Overall, these data indicate that ART induces specific immunological changes in SIV-infected SMs, thus suggesting that virus replication affects immune function even in the context of this clinically benign infection. IMPORTANCE Studies of natural, nonpathogenic simian immunodeficiency virus (SIV) infection of African monkeys have provided important insights into the mechanisms responsible for the progression to AIDS during pathogenic human immunodeficiency virus (HIV) infection of humans and SIV infection of Asian macaques. In this study, for the first time, we treated SIV

  7. The Indigenous Red Ribbon Storytelling Study: What does it mean for Indigenous peoples living with HIV and a substance use disorder to access antiretroviral therapy in Saskatchewan?

    PubMed

    Nowgesic, Earl; Meili, Ryan; Stack, Sandra; Myers, Ted

    2015-01-01

    Indigenous peoples living with HIV are less likely than non-Indigenous peoples living with HIV to access antiretroviral therapy; however, there is not enough contextual information surrounding this issue. The Indigenous Red Ribbon Storytelling Study was conducted in part to examine how Indigenous peoples living with HIV construct and understand their experiences accessing antiretroviral therapy. Our study design was critical Indigenous qualitative research, using the Behavioral Model of Health Services Use and community-based participatory research approaches. The study was conducted in partnership with Indigenous and non-Indigenous organizations. Study participants were adults from two Canadian cities. The study methods included 20 individual and two Indigenous sharing circle interviews, six participant observation sessions, a short survey and thematic analysis. Accessing antiretroviral therapy within the context of living with a substance use disorder was an overarching theme. Indigenous peoples living with HIV felt they had to choose between living with their active substance use disorder and accessing antiretroviral therapy. They felt misunderstood as a person living with a substance use disorder and often felt coerced into using antiretroviral therapy. Despite these challenges, they persevered as Indigenous peoples living with HIV and a substance use disorder. Further research on antiretroviral therapy access among Indigenous peoples living with HIV and a substance use disorder, particularly from the perspective of health service providers, is needed.

  8. Pericardial effusion of HIV-infected patients - results of a prospective multicenter cohort study in the era of antiretroviral therapy

    PubMed Central

    2011-01-01

    Background Patients with human immunodeficiency virus (HIV) infection have an increased risk of cardiovascular diseases. Previous publications described pericardial effusion as one of the most common HlV-associated cardiac affiliations. The aim of the current study was to investigate if pericardial effusion still has a relevant meaning of HIV-infected patients in the era of antiretroviral therapy. Methods The HIV-HEART (HIV-infection and HEART disease) study is a cardiology driven, prospective and multicenter cohort study. Outpatients with a known HIV-infection were recruited during a 20 month period in a consecutive manner from September 2004 to May 2006. The study comprehends classic parameters of HIV-infection, comprising CD4-cell count (cluster of differentiation) and virus load, as well as non-invasive tests of cardiac diseases, including a thorough transthoracic echocardiography. Results 802 HIV-infected patients (female: 16.6%) with a mean age of 44.2 ± 10.3 years, were included. Duration of HIV-infection since initial diagnosis was 7.6 ± 5.8 years. Of all participants, 85.2% received antiretroviral therapy. Virus load was detectable in 34.4% and CD4 - cell count was in 12.4% less than 200 cells/μL. Pericardial effusions were present in only two patients of the analysed population. None of the participants had signs of a relevant cardiovascular impairment by pericardial effusion. Conclusions Our results demonstrate that the era of antiretroviral therapy goes along with low rates of pericardial effusions in HIV-infected outpatients. Our findings are in contrast to the results of publications, performed before the common use of antiretroviral therapy. PMID:22027640

  9. Impaired Lipoprotein Processing in HIV Patients on Antiretroviral Therapy: Aberrant HDL Lipids, Stability, and Function

    PubMed Central

    Gillard, Baiba K.; Raya, Joe L.; Ruiz-Esponda, Raul; Iyer, Dinakar; Coraza, Ivonne; Balasubramanyam, Ashok; Pownall, Henry J.

    2014-01-01

    Objective HIV patients on antiretroviral therapy (HIV/ART) exhibit a unique atherogenic dyslipidemic profile with hypertriglyceridemia (HTG) and low plasma concentrations of high density lipoprotein-cholesterol (HDL-C). In the Heart Positive Study of HIV/ART patients, a hypolipidemic therapy of fenofibrate, niacin, diet, and exercise reduced HTG and plasma non-HDL-C concentrations and raised plasma HDL-C and adiponectin concentrations. We tested the hypothesis that HIV/ART HDL have abnormal structures and properties and are dysfunctional. Approach and Results Hypolipidemic therapy reduced the TG contents of LDL and HDL. At baseline, HIV/ART low density lipoproteins (LDL) were more triglyceride (TG)-rich and HDL were more TG- and cholesteryl ester (CE)-rich than the corresponding lipoproteins from normolipidemic (NL) subjects. Very low density lipoproteins, LDL and HDL were larger than the corresponding lipoproteins from NL subjects; HIV/ART HDL were less stable than NL HDL. HDL-[3H]CE uptake by Huh7 hepatocytes was used to assess HDL functionality. HIV/ART plasma were found to contain significantly less competitive inhibition activity for hepatocyte HDL-CE uptake than did NL plasma (p<0.001). Conclusion Compared to NL subjects, lipoproteins from HIV/ART patients are larger and more neutral lipid-rich, and their HDL are less stable and less receptor-competent. Based on this work and previous studies of lipase activity in HIV, we present a model in which plasma lipolytic activities and/or hepatic CE uptake are impaired in HIV/ART patients. These findings provide a rationale to determine whether the distinctive lipoprotein structure, properties and function of HIV/ART HDL predict atherosclerosis as assessed by carotid artery intimal medial thickness. PMID:23640486

  10. Neurocognitive Impairment in Patients Treated with Protease Inhibitor Monotherapy or Triple Drug Antiretroviral Therapy

    PubMed Central

    Pérez-Valero, Ignacio; González-Baeza, Alicia; Estébanez, Miriam; Montes-Ramírez, María L.; Bayón, Carmen; Pulido, Federico; Bernardino, José I.; Zamora, Francisco X.; Monge, Susana; Gaya, Francisco; Lagarde, María; Rubio, Rafael; Hernando, Asunción; Arnalich, Francisco; Arribas, José R.

    2013-01-01

    Background In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment. Methods In this observational, cross-sectional study we included patients with plasma virological suppression (≥1 year) without concomitant major neurocognitive confounders, currently receiving for ≥1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed. Results Of the 191 included patients - triple therapy: 96, 1–2 years of monotherapy: 40 and >2 years of monotherapy: 55 - proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9–33.6); triple therapy, 31.6% (22.1–41.0); short-term monotherapy, 25.0% (11.3–38.7); long-term monotherapy: 21.4% (10.5–32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29–2.50) and for long-term monotherapy 0.40 (0.14–1.15). Conclusions Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART. PMID:23936029

  11. Managing potential drug-drug interactions between gastric acid-reducing agents and antiretroviral therapy: experience from a large HIV-positive cohort.

    PubMed

    Lewis, J M; Stott, K E; Monnery, D; Seden, K; Beeching, N J; Chaponda, M; Khoo, S; Beadsworth, M B J

    2016-02-01

    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.

  12. Opportunistic Diseases in HIV-Infected Patients in Gabon following the Administration of Highly Active Antiretroviral Therapy: A Retrospective Study

    PubMed Central

    Okome-Nkoumou, Madeleine; Guiyedi, Vincent; Ondounda, Magloire; Efire, Nora; Clevenbergh, Philippe; Dibo, Mireille; Dzeing-Ella, Arnaud

    2014-01-01

    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. PMID:24323514

  13. Long-term immunologic response to antiretroviral therapy in low-income countries: Collaborative analysis of prospective studies

    PubMed Central

    Nash, Denis; Katyal, Monica; Brinkhof, Martin W.G.; Keiser, Olivia; May, Margaret; Hughes, Rachael; Dabis, Francois; Wood, Robin; Sprinz, Eduardo; Schechter, Mauro; Egger, Matthias

    2009-01-01

    Background Few data are available on the long-term immunologic response to ART in resource-limited settings, where antiretroviral therapy (ART) is being scaled up using a public health approach, with a limited repertoire of drugs. Objectives To describe immunologic response to ART in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. Study population/methods Treatment-naïve patients aged 15 and older from 27 treatment programs were eligible. Multi-level, linear mixed models were used to assess associations between predictor variables and CD4 count trajectories following ART initiation. Results Of 29,175 patients initiating ART, 8,933 patients (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19,967 patients contributed 39,200 person-years on ART and 71,067 CD4 measurements. The median baseline CD4 count was 114 cells/μL, with 35%<100 cells μL and substantial inter-site variation (range: 61-181 cells/μL). Females had higher median baseline CD4 counts than males (121 vs. 104 cells/μL). The median CD4 count increased from 114 cells/μL at ART initiation to 230 (IQR:144-338) at 6 months, 263 (IQR:175-376) at 1 year, 336 (IQR:224-472) at 2 years, 372 (IQR:242-537) at 3 years, 377 (IQR:221-561) at 4 years, and 395 (IQR:240-592) at 5 years. In multivariable models, baseline CD4 count was the most important determinant of subsequent CD4 count trajectories. Conclusions These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings. PMID:18981768

  14. Examining the interplay between depression, motivation, and antiretroviral therapy adherence: a social cognitive approach.

    PubMed

    Tatum, A K; Houston, E

    2017-03-01

    A large body of research identifies depressive symptoms as a barrier to optimal antiretroviral therapy (ART) adherence, whereas treatment motivation has been characterized as a facilitator. There is evidence, however, that these patterns may not hold for some ART patients despite the widespread use of motivational techniques aimed at promoting adherence. Little is known about how the interplay between different levels of depressive symptoms and variations in the types and levels of motivation may influence ART adherence. The purpose of this study was to examine the relationship between depressive symptoms, two types of motivation, and adherence, with self-efficacy as a mediator. The sample consisted of 121 ART patients who reported various levels of depressive symptoms (mean age = 41 years; 84% African-American; and 68% female). Path analysis revealed that self-efficacy fully mediated the relationship between the three predictor variables (depressive symptoms, intrinsic motivation, and extrinsic motivation) and adherence, χ(2)(3, N = 121) = .78, RMSEA = .00, SRMR = .02, CFI = 1.00, NNFI = 1.06. Findings suggest that interventions using motivational techniques to build adherence among patients with varying levels of depressive symptoms should address the role of treatment self-efficacy to improve their effectiveness.

  15. Correlates of Antiretroviral Therapy Adherence among HIV-Infected Older Adults

    PubMed Central

    McCoy, Katryna; Waldrop-Valverde, Drenna; Balderson, Benjamin H.; Mahoney, Christine; Catz, Sheryl

    2016-01-01

    Background Despite the success of antiretroviral therapy (ART), HIV-infected older African Americans experience higher mortality rates compared to their white counterparts. This disparity may be partly attributable to the differences in ART adherence by different racial and gender groups. The purpose of this study was to describe demographic, psychosocial, and HIV disease-related factors that influence ART adherence and to determine whether race and gender impact ART adherence among HIV-infected adults aged 50 years and older. Methods This descriptive study involved a secondary analysis of baseline data from 426 participants in “PRIME,” a telephone-based ART adherence and quality-of-life intervention trial. Logistic regression was used to examine the association between independent variables and ART adherence. Results Higher annual income and increased self-efficacy were associated with being ≥95% ART adherent. Race and gender were not associated with ART adherence. Conclusion These findings indicated that improvements in self-efficacy for taking ART may be an effective strategy to improve adherence regardless of race or gender. PMID:27071744

  16. Neurobehavioral Effects in HIV-Positive Individuals Receiving Highly Active Antiretroviral Therapy (HAART) in Gaborone, Botswana

    PubMed Central

    Lawler, Kathy; Jeremiah, Kealeboga; Mosepele, Mosepele; Ratcliffe, Sarah J.; Cherry, Catherine; Seloilwe, Esther; Steenhoff, Andrew P.

    2011-01-01

    Objective To explore the prevalence and features of HIV-associated neurocognitive disorders (HANDS) in Botswana, a sub-Saharan country at the center of the HIV epidemic. Design and Methods A cross sectional study of 60 HIV-positive individuals, all receiving highly active antiretroviral therapy (HAART), and 80 demographically matched HIV-seronegative control subjects. We administered a comprehensive neuropsychological test battery and structured psychiatric interview. The lowest 10th percentile of results achieved by control subjects was used to define the lower limit of normal performance on cognitive measures. Subjects who scored abnormal on three or more measures were classified as cognitively impaired. To determine the clinical significance of any cognitive impairment, we assessed medication adherence, employment, and independence in activities of daily living (ADL). Results HIV+ subjects were impaired for all cognitive-motor ability areas compared with matched, uninfected control subjects. Thirty seven percent of HIV+ patients met criteria for cognitive impairment. Conclusion These findings indicate that neurocognitive impairment is likely to be an important feature of HIV infection in resource-limited countries; underscoring the need to develop effective treatments for subjects with, or at risk of developing, cognitive impairment. PMID:21365002

  17. Adherence and Risk Behaviour in Patients with HIV Infection Receiving Antiretroviral Therapy in Bangkok.

    PubMed

    Clarke, Amanda; Kerr, Stephen; Honeybrook, Adam; Cooper, David A; Avihingsanon, Anchalee; Duncombe, Chris; Phanuphak, Praphan; Ruxrungtham, Kiat; Ananworanich, Jintanat; Kaldor, John

    2012-01-01

    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.

  18. Retention in care and medication adherence: current challenges to antiretroviral therapy success.

    PubMed

    Holtzman, Carol W; Brady, Kathleen A; Yehia, Baligh R

    2015-04-01

    Health behaviors such as retention in HIV medical care and adherence to antiretroviral therapy (ART) pose major challenges to reducing new HIV infections, addressing health disparities, and improving health outcomes. Andersen's Behavioral Model of Health Service Use provides a conceptual framework for understanding how patient and environmental factors affect health behaviors and outcomes, which can inform the design of intervention strategies. Factors affecting retention and adherence among persons with HIV include patient predisposing factors (e.g., mental illness, substance abuse), patient-enabling factors (e.g., social support, reminder strategies, medication characteristics, transportation, housing, insurance), and healthcare environment factors (e.g., pharmacy services, clinic experiences, provider characteristics). Evidence-based recommendations for improving retention and adherence include (1) systematic monitoring of clinic attendance and ART adherence; (2) use of peer or paraprofessional navigators to re-engage patients in care and help them remain in care; (3) optimization of ART regimens and pharmaceutical supply chain management systems; (4) provision of reminder devices and tools; (5) general education and counseling; (6) engagement of peer, family, and community support groups; (7) case management; and (8) targeting patients with substance abuse and mental illness. Further research is needed on effective monitoring strategies and interventions that focus on improving retention and adherence, with specific attention to the healthcare environment.

  19. Factors associated with timely initiation of antiretroviral therapy in two HIV clinics in Lilongwe, Malawi.

    PubMed

    Johnson, D C; Feldacker, C; Tweya, H; Phiri, S; Hosseinipour, M C

    2013-01-01

    The World Health Organization (WHO) estimates that only 30% of eligible, HIV-infected individuals start antiretroviral therapy (ART). This study seeks to explore the geographic and individual factors associated with starting ART on time. This retrospective study includes 15,734 HIV-positive adults initiating ART at two HIV clinics in Lilongwe, Malawi. The outcome was starting ART within two weeks of meeting ART eligibility as defined by the Malawi ART guidelines. Euclidean distance from patient neighbourhood to their clinic was calculated using Google Earth. Logistic regression models assessed factors influencing starting ART on time. Of 15,734 adults initiating ART, 8178 were from Lighthouse (LH) and 7556 were from Martin Preuss Center (MPC). Combined, 68.7% started treatment on time. Patients who were eligible for ART based on a CD4 cell count <250 cells/mm(3) versus WHO stage were less likely to begin ART on time at both LH (odds ratio [OR] 0.16; 95% CI 0.13-0.19) and MPC (OR 0.24; 95% CI 0.21-0.28). Likelihood of starting on time decreased with each kilometer further from clinic location among LH patients (OR 0.97; 95% CI 0.94-0.99); distance was not significant at MPC. In conclusion, predictors differed by clinic. Distance to clinic and type of eligibility for ART significantly influence starting ART on time.

  20. Lipodystrophy among patients with HIV infection on antiretroviral therapy: a systematic review protocol

    PubMed Central

    Lana, Lorena Gomes Cunha; Junqueira, Daniela Rezende Garcia; Perini, Edson; Menezes de Pádua, Cristiane

    2014-01-01

    Introduction Lipodystrophy is a frequent and disfiguring adverse effect of antiretroviral therapy (ART) in patients with HIV. It affects the quality of life of the patient and adherence to treatment, and generates new needs for comprehensive healthcare services. The aim of this study will be to conduct a systematic review of the literature from observational studies and describe lipodystrophy among patients with HIV infection during current or previous use of ART. Methods and analysis A systematic review of observational studies published in MEDLINE, CINAHL, LILACS, EMBASE and International Pharmaceutical Abstracts will be carried out. Citations of included studies will be checked to identify additional studies not identified in the electronic searches. It will include any observational study that considered lipodystrophy as the primary or secondary outcome and that had enrolled adolescent and adult patients with HIV infection who were on current or previous ART for at least 6 months. Data extraction and analysis will be performed independently by two reviewers. The extracted data will be discussed, decisions documented and, where necessary, the authors of the studies will be contacted for clarification. Measures of frequency, prevalence and incidence of lipodystrophy will be stratified according to definition, method of diagnosis and risk factors of the outcome. Ethics and dissemination Ethics is not required given this is a protocol for a systematic review. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations. Updates of the review will be conducted to inform and guide healthcare practice. Protocol registration PROSPERO—42013005450. PMID:24625638

  1. Tailored nutrition education and food assistance improve adherence to HIV antiretroviral therapy: evidence from Honduras.

    PubMed

    Martinez, Homero; Palar, Kartika; Linnemayr, Sebastian; Smith, Alexandria; Derose, Kathryn Pitkin; Ramírez, Blanca; Farías, Hugo; Wagner, Glenn

    2014-10-01

    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.

  2. Early initiation of highly active antiretroviral therapies for AIDS: dynamic choice with endogenous and exogenous learning.

    PubMed

    Lasserre, Pierre; Moatti, Jean-Paul; Soubeyran, Antoine

    2006-05-01

    Criteria for initiation of highly active antiretroviral treatments (HAART) in HIV-infected patients remain a matter of debate world-wide because short-term benefits have to be balanced with costs of these therapies, and restrictions placed on future treatment options if resistant viral strains develop. On the other hand, postponing the introduction of HAART may involve a therapeutic opportunity cost if a patient's health is allowed to deteriorate to such an extent of becoming unable to benefit from new treatments currently under development when they become available. We introduce a two period model where period one treatment adoption is an irreversible act with future, but uncertain, consequences. New information, both endogenous and exogenous, arises over time and shapes the conditions surrounding the second period therapeutic decision. A surprising result is that, under conditions that appear close to those surrounding the HAART debate, the magnitude of the feared resistance effect has no effect on leaves the optimal treatment decision as far as it is high enough.

  3. Changing Clinician Practices and Attitudes Regarding the Use of Antiretroviral Therapy for HIV Treatment and Prevention.

    PubMed

    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.

  4. The impact of HIV treatment-related stigma on uptake of antiretroviral therapy.

    PubMed

    Cama, Elena; Brener, Loren; Slavin, Sean; de Wit, John

    2015-01-01

    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.

  5. Evidence for ongoing brain injury in human immunodeficiency virus–positive patients treated with antiretroviral therapy

    PubMed Central

    Cardenas, VA; Meyerhoff, DJ; Studholme, C; Kornak, J; Rothlind, J; Lampiris, H; Neuhaus, J; Grant, RM; Chao, LL; Truran, D; Weiner, MW

    2009-01-01

    Treatment with antiretroviral therapy (ART) has greatly reduced the incidence of dementia. The goal of this longitudinal study was to determine if there are ongoing macrostructural brain changes in human immunodeficiency virus–positive (HIV+) individuals treated with ART. To quantify brain structure, three-dimensional T1-weighted magnetic resonance imaging (MRI) scans were performed at baseline and again after 24 months in 39 HIV+ patients on ART and 30 HIV− controls. Longitudinal changes in brain volume were measured using tissue segmentation within regions of interest and deformation morphometry. Measured by tissue segmentation, HIV+ patients on ART had significantly (all P < .05) greater rates of white matter volume loss than HIV− control individuals. Compared with controls, the subgroup of HIV+ individuals on ART with viral suppression also had significantly greater rates of white matter volume loss. Deformation morphometry confirmed these results with more specific spatial localization. Deformation morphometry also detected greater rates of gray matter and white matter loss in the subgroup of HIV+ individuals with detectable viral loads. These results provide evidence of ongoing brain volume loss in HIV+ individuals on stable ART, possibly suggesting ongoing cerebral injury. The presence of continuing injury raises the possibility that HIV+ individuals—even in the presence of viral suppression in the periphery—are at greater risk for future cognitive impairments and dementia and possibly faster cognitive decline. Therefore, HIV+ individuals on ART should be monitored for cognitive decline, and treatments that reduce ongoing neurological injury should be considered. PMID:19499454

  6. Cerebrovascular disease in HIV-infected individuals in the era of highly active antiretroviral therapy.

    PubMed

    Cruse, Belinda; Cysique, Lucette A; Markus, Romesh; Brew, Bruce J

    2012-08-01

    The widespread use of highly active antiretroviral therapy (HAART) in HIV-infected individuals mostly in developed countries has dramatically improved their prognosis. In such advantaged regions of the world, therefore, many patients are now transitioning from middle into older age, with altered patterns of disease. While previously a rare complication of HIV infection, cerebrovascular disease (particularly that associated with atherosclerosis) is becoming relatively more important in this treated group of individuals. This review summarises the evidence regarding the shifting epidemiology of cerebrovascular diseases affecting HIV-infected individuals. While outlining the association between HIV infection and AIDS and cerebrovascular disease, as well as opportunistic diseases and HIV-associated vasculopathies, the current evidence supporting an increase in atherosclerotic disease in treated HIV-infected individuals is emphasised and a management approach to ischaemic stroke in HIV-infected individuals is presented. Evidence supporting the important role of HAART and HIV infection itself in the pathogenesis of atherosclerotic disease is discussed, together with preventative approaches to this increasingly important disease process as the population ages. Finally, a discussion regarding the significant association between cerebrovascular disease and HIV-associated neurocognitive disorder is presented, together with possible mechanisms behind this relationship.

  7. Progressive human immunodeficiency virus-associated vasculopathy: time to revise antiretroviral therapy guidelines?

    PubMed

    Ntusi, N B A; Taylor, D; Naidoo, N G; Mendelson, M

    2011-01-01

    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.

  8. Assessing treatment motivation among patients receiving antiretroviral therapy: a multidimensional approach.

    PubMed

    Houston, Eric; McKirnan, David J; Cervone, Daniel; Johnson, Matthew S; Sandfort, Theo G M

    2012-01-01

    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.

  9. Dyslipidemia in a cohort of HIV-infected Latin American children receiving highly active antiretroviral therapy.

    PubMed

    Brewinski, Margaret; Megazzini, Karen; Hance, Laura Freimanis; Cruz, Miguel Cashat; Pavia-Ruz, Noris; Della Negra, Marinella; Ferreira, Flavia Gomes Faleiro; Marques, Heloisa; Hazra, Rohan

    2011-10-01

    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.

  10. The Influence of Medication Attitudes on Utilization of Antiretroviral Therapy (ART) in Indonesian Prisons.

    PubMed

    Culbert, Gabriel J; Bazazi, Alexander R; Waluyo, Agung; Murni, Astia; Muchransyah, Azalia P; Iriyanti, Mariska; Finnahari; Polonsky, Maxim; Levy, Judith; Altice, Frederick L

    2016-05-01

    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.

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

    PubMed Central

    Langs-Barlow, Allison; Paintsil, Elijah

    2014-01-01

    Worldwide circulating HIV-1 genomes show extensive variation represented by different subtypes, polymorphisms and drug-resistant strains. Reports on the impact of sequence variation on antiretroviral therapy (ART) outcomes are mixed. In this review, we summarize relevant published data from both resource-rich and resource-limited countries in the last 10 years on the impact of HIV-1 sequence diversity on treatment outcomes. The prevalence of transmission of drug resistant mutations (DRMs) varies considerably, ranging from 0% to 27% worldwide. Factors such as geographic location, access and availability to ART, duration since inception of treatment programs, quality of care, risk-taking behaviors, mode of transmission, and viral subtype all dictate the prevalence in a particular geographical region. Although HIV-1 subtype may not be a good predictor of treatment outcome, review of emerging evidence supports the fact that HIV-1 genome sequence-resulting from natural polymorphisms or drug-associated mutations-matters when it comes to treatment outcomes. Therefore, continued surveillance of drug resistant variants in both treatment-naïve and treatment-experienced populations is needed to reduce the transmission of DRMs and to optimize the efficacy of the current ART armamentarium. PMID:25333465

  12. Barriers to and Facilitators of Antiretroviral Therapy Adherence in Nepal: A Qualitative Study

    PubMed Central

    Simkhada, Padam; Randall, Julian; Freeman, Jennifer V; van Teijlingen, Edwin

    2012-01-01

    Patient's adherence is crucial to get the best out of antiretroviral therapy (ART). This study explores in-depth the barriers to and facilitators of ART adherence among Nepalese patients and service providers prescribing ART. Face-to-face semi-structured interviews were conducted with 34 participants. Interviews were audio-taped, transcribed, and translated into English before being analyzed thematically. ART-prescribed patients described a range of barriers for failing to adhere to ART. Financial difficulties, access to healthcare services, frequent transport blockades, religious/ritual obstacles, stigma and discrimination, and side-effects were the most-frequently discussed barriers whereas trustworthy health workers, perceived health benefits, and family support were the most-reported facilitators. Understanding barriers and facilitators can help in the design of an appropriate and targeted intervention. Healthcare providers should address some of the practical and cultural issues around ART whilst policy-makers should develop appropriate social policy to promote adherence among ART-prescribed patients. PMID:23304907

  13. Reasons for non-adherence to antiretroviral therapy: patients' perspectives provide evidence of multiple causes.

    PubMed

    Walsh, J C; Horne, R; Dalton, M; Burgess, A P; Gazzard, B G

    2001-12-01

    The objective of the study was to define common reasons for non-adherence (NA) to highly active antiretroviral therapy (HAART) and the number of reasons reported by non-adherent individuals. A confidential questionnaire was administered to HIV-seropositive patients taking proteinase inhibitor based HAART. Median self-reported adherence was 95% (n = 178, range = 60-100%). The most frequent reasons for at least 'sometimes' missing a dose were eating a meal at the wrong time (38.2%), oversleeping (36.3%), forgetting (35.0%) and being in a social situation (30.5%). The mean number of reasons occurring at least 'sometimes' was 3.2; 20% of patients gave six or more reasons; those reporting the lowest adherence reported a significantly greater numbers of reasons (rho = - 0.59; p < 0.001). Three factors were derived from the data by principal component analysis reflecting 'negative experiences of HAART', 'having a low priority for taking medication' and 'unintentionally missing doses', accounting for 53.8% of the variance. On multivariate analysis only the latter two factors were significantly related to NA (odds ratios 0.845 and 0.849, respectively). There was a wide spectrum of reasons for NA in our population. The number of reasons in an individual increased as adherence became less. A variety of modalities individualized for each patient are required to support patients with the lowest adherence.

  14. Neurocognitive Change in the Era of HIV Combination Antiretroviral Therapy: The Longitudinal CHARTER Study

    PubMed Central

    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

    2015-01-01

    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

  15. Declining tuberculosis case notification rates with the scale-up of antiretroviral therapy in Zimbabwe

    PubMed Central

    Harries, A. D.; Sandy, C.; Mutasa-Apollo, T.; Zishiri, C.

    2016-01-01

    Setting: Zimbabwe has a human immunodeficiency virus (HIV) driven tuberculosis (TB) epidemic, with antiretroviral therapy (ART) scaled up in the public sector since 2004. Objective: To determine whether national ART scale-up was associated with annual national TB case notification rates (CNR), stratified by disease type and category, between 2000 and 2013. Design: This was a retrospective study using aggregate data from global reports. Results: The number of people living with HIV and retained on ART from 2004 to 2013 increased from 8400 to 665 299, with ART coverage increasing from <0.5% to 48%. TB CNRs, all types and categories, increased from 2000 to 2003, and declined thereafter from 2004 to 2013. The decreases in annual TB notifications between the highest rates (before 2004) and lowest rates (2013) were all forms of TB (56%), new TB (60%), previously treated TB (53%), new smear-positive pulmonary TB (PTB) (40%), new smear-negative/smear-unknown PTB (58%) and extra-pulmonary TB (58%). Conclusion: Significant declines in TB CNRs were observed during ART scale-up, especially for smear-negative PTB and extra-pulmonary TB. These encouraging national trends support the continued scale-up of ART for people living with HIV as a way of tackling the twin epidemics of HIV/acquired immune-deficiency syndrome and TB in Zimbabwe. PMID:27695678

  16. The impact of antiretroviral therapy in resource-limited settings and current HIV therapeutics.

    PubMed

    Kumarasamy, N

    2016-04-01

    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.

  17. Effect of highly active antiretroviral therapy on incident AIDS using calendar period as an instrumental variable.

    PubMed

    Cain, Lauren E; Cole, Stephen R; Greenland, Sander; Brown, Todd T; Chmiel, Joan S; Kingsley, Lawrence; Detels, Roger

    2009-05-01

    Human immunodeficiency virus (HIV) researchers often use calendar periods as an imperfect proxy for highly active antiretroviral therapy (HAART) when estimating the effect of HAART on HIV disease progression. The authors report on 614 HIV-positive homosexual men followed from 1984 to 2007 in 4 US cities. During 5,321 person-years, 268 of 614 men incurred acquired immunodeficiency syndrome, 49 died, and 90 were lost to follow-up. Comparing the pre-HAART calendar period (<1996) with the HAART calendar period (>or=1996) resulted in a naive rate ratio of 3.62 (95% confidence limits: 2.67, 4.92). However, this estimate is likely biased because of misclassification of HAART use by calendar period. Simple calendar period approaches may circumvent confounding by indication at the cost of inducing exposure misclassification. To correct this misclassification, the authors propose an instrumental-variable estimator analogous to ones previously used for noncompliance corrections in randomized clinical trials. When the pre-HAART calendar period was compared with the HAART calendar period, the instrumental-variable rate ratio was 5.02 (95% confidence limits: 3.45, 7.31), 39% higher than the naive result. Weighting by the inverse probability of calendar period given age at seroconversion, race/ethnicity, and time since seroconversion did not appreciably alter the results. These methods may help resolve discrepancies between observational and randomized evidence.

  18. Explaining Antiretroviral Therapy Adherence Success Among HIV-Infected Children in Rural Uganda: A Qualitative Study

    PubMed Central

    Olds, Peter K.; Kiwanuka, Julius P.; Ware, Norma C.; Tsai, Alexander C.

    2014-01-01

    High adherence is critical for achieving clinical benefits of HIV antiretroviral therapy (ART) and particularly challenging for children. We conducted 35 qualitative interviews with caregivers of HIV-infected Ugandan children who were followed in a longitudinal study of real-time ART adherence monitoring; 18 participants had undetectable HIV RNA, while 17 had detectable virus. Interviews blinded to viral suppression status elicited information on adherence experiences, barriers and facilitators to adherence, and social support. Using an inductive content analytic approach, we identified ‘lack of resources,’ ‘Lazarus effect,’ ‘caregiver's sense of obligation and commitment,’ and ‘child's personal responsibility’ as categories of influence on adherence, and defined types of caregiver social support. Among children with viral suppression, high hopes for the child's future and ready access to private instrumental support appeared particularly important. These findings suggest clinical counseling should explore caregivers' views of their children's futures and ability to access support in overcoming adherence barriers. PMID:25323679

  19. Declining tuberculosis case notification rates with the scale-up of antiretroviral therapy in Zimbabwe.

    PubMed

    Takarinda, K C; Harries, A D; Sandy, C; Mutasa-Apollo, T; Zishiri, C

    2016-09-01

    Setting: Zimbabwe has a human immunodeficiency virus (HIV) driven tuberculosis (TB) epidemic, with antiretroviral therapy (ART) scaled up in the public sector since 2004. Objective: To determine whether national ART scale-up was associated with annual national TB case notification rates (CNR), stratified by disease type and category, between 2000 and 2013. Design: This was a retrospective study using aggregate data from global reports. Results: The number of people living with HIV and retained on ART from 2004 to 2013 increased from 8400 to 665 299, with ART coverage increasing from <0.5% to 48%. TB CNRs, all types and categories, increased from 2000 to 2003, and declined thereafter from 2004 to 2013. The decreases in annual TB notifications between the highest rates (before 2004) and lowest rates (2013) were all forms of TB (56%), new TB (60%), previously treated TB (53%), new smear-positive pulmonary TB (PTB) (40%), new smear-negative/smear-unknown PTB (58%) and extra-pulmonary TB (58%). Conclusion: Significant declines in TB CNRs were observed during ART scale-up, especially for smear-negative PTB and extra-pulmonary TB. These encouraging national trends support the continued scale-up of ART for people living with HIV as a way of tackling the twin epidemics of HIV/acquired immune-deficiency syndrome and TB in Zimbabwe.

  20. A Qualitative Study of Patient Motivation to Adhere to Combination Antiretroviral Therapy in South Africa

    PubMed Central

    Gray, Debra; Gengiah, Santhanalakshmi; Kunene, Pinky; Gengiah, Tanuja N.; Naidoo, Kogieleum; Grant, Alison D.

    2015-01-01

    Abstract Taken as prescribed, that is, with high adherence, combination antiretroviral therapy (ART) has changed HIV infection and disease from being a sure predictor of death to a manageable chronic illness. Adherence, however, is difficult to achieve and maintain. The CAPRISA 058 study was conducted between 2007 and 2009 to test the efficacy of individualized motivational counselling to enhance ART adherence in South Africa. As part of the overall trial, a qualitative sub-study was conducted, including 30 individual interviews and four focus group discussions with patients in the first 9 months of ART initiation. Data were inductively analyzed, using thematic analysis, to identify themes central to ART adherence in this context. Four themes emerged that characterize the participants' experiences and high motivation to adhere to ART. Participants in this study were highly motivated to adhere, as they acknowledged that ART was ‘life-giving’, in the face of a large amount of morbidity and mortality. They were further supported by techniques of routine remembering, and highlighted the importance of good social support and access to supportive healthcare workers, to their continued success in negotiating their treatment. Participants in the current study told us that their adherence motivation is enhanced by free accessible care, approachable and supportive healthcare workers, broad social acceptance of ART, and past first-hand experiences with AIDS-related co-morbidity and mortality. Programs that include specific attention to these aspects of care will likely be successful in the long term. PMID:25692575

  1. Nutritional status changes in HIV-infected children receiving combined antiretroviral therapy including protease inhibitors.

    PubMed

    Fiore, P; Donelli, E; Boni, S; Pontali, E; Tramalloni, R; Bassetti, D

    2000-11-01

    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.

  2. Body mass index changes during highly active antiretroviral therapy in Nigeria.

    PubMed

    Denue, B A; Ikunaiye, P N Y; Denue, C B A

    2014-01-09

    Wasting remains an important condition in HIV-infected patients receiving highly active antiretroviral therapy (HAART). In this study, 120 patients with newly diagnosed HIV infection were prospectively evaluated to determine the effect of HAART on body mass index (BMI). Eighty-nine (83.1%) patients gained weight, 5 (4.7%) had no weight change, and 13 (12.2%) lost weight. There was a significant increase in overweight and obese patients. On multivariate analysis, time-updated CD4 count and higher baseline BMI were associated with a greater increase in BMI. Anaemia at diagnosis was associated with a significant increase in BMI. There were no significant effects of age, sex, disease severity, viral load or educational status on BMI changes. About 27% of the HIV patients presented with weight loss, which emphasizes that weight loss and wasting remain important AIDS-defining conditions, despite the advent of HAART. A linear association was observed between time-updated CD4 count and increase in BMI. The association between time-updated CD4 count and greater increase in BMI suggests that BMI could be a surrogate for CD4 count in monitoring treatment response in resource-limited settings.

  3. Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy

    PubMed Central

    Lee, Kuan-Yeh; Tsai, Mao-Song; Kuo, Kuang-Che; Tsai, Jen-Chih; Sun, Hsin-Yun; Cheng, Aristine C; Chang, Sui-Yuan; Lee, Chen-Hsiang; Hung, Chien-Ching

    2014-01-01

    HIV-infected patients remain at higher risk for pneumococcal disease than the general population despite immune reconstitution and suppression of HIV replication with combination antiretroviral therapy. Vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) composed of T-cell-independent antigens has been recommended to reduce the risk of pneumococcal disease in HIV-infected adults. However, given the heterogeneity of study design, execution and subjects enrolled, studies examining serological responses to PPV23 yielded conflicting results and observational studies of clinical effectiveness only provided moderate evidence to support the routine use of PPV23 in HIV-infected adults. Pneumococcal conjugate vaccine (PCV), with conjugation of the capsular polysaccharide to a protein carrier, is more immunogenic than PPV23 and has been demonstrated to protect against pneumococcal disease in HIV-infected children and recurrent invasive pneumococcal disease in HIV-infected adolescents and adults. Guidelines have recently been revised to recommend that HIV-infected patients aged 19 y or older receive one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by a booster vaccination with PPV23. In this paper, we review the studies using different vaccination strategies to improve immunogenicity among HIV-infected adult patients. PMID:25483681

  4. Monitoring the scale-up of antiretroviral therapy programmes: methods to estimate coverage.

    PubMed Central

    Boerma, J. Ties; Stanecki, Karen A.; Newell, Marie-Louise; Luo, Chewe; Beusenberg, Michel; Garnett, Geoff P.; Little, Kirsty; Calleja, Jesus Garcia; Crowley, Siobhan; Kim, Jim Yong; Zaniewski, Elizabeth; Walker, Neff; Stover, John; Ghys, Peter D.

    2006-01-01

    This paper reviews the data sources and methods used to estimate the number of people on, and coverage of, antiretroviral therapy (ART) programmes in low- and middle-income countries and to monitor the progress towards the "3 by 5" target set by WHO and UNAIDS. We include a review of the data sources used to estimate the coverage of ART programmes as well as the efforts made to avoid double counting and over-reporting. The methods used to estimate the number of people in need of ART are described and expanded with estimates of treatment needs for children, both for ART and for cotrimoxazole prophylaxis. An estimated 6.5 million people were in need of treatment in low- and middle-income countries by the end of 2004, including 660,000 children under age 15 years. The mid-2005 estimate of 970,000 people receiving ART in low- and middle-income countries (with an uncertainty range 840,000-1,100,000) corresponds to a coverage of 15% of people in need of treatment. PMID:16501733

  5. Does Food Insecurity Undermine Adherence to Antiretroviral Therapy? A Systematic Review.

    PubMed

    Singer, Amanda W; Weiser, Sheri D; McCoy, Sandra I

    2015-08-01

    A growing body of research has identified food insecurity as a barrier to antiretroviral therapy (ART) adherence. We systematically reviewed and summarized the quantitative literature on food insecurity or food assistance and ART adherence. We identified nineteen analyses from eighteen distinct studies examining food insecurity and ART adherence. Of the thirteen studies that presented an adjusted effect estimate for the relationship between food insecurity and ART adherence, nine found a statistically significant association between food insecurity and sub-optimal ART adherence. Four studies examined the association between food assistance and ART adherence, and three found that ART adherence was significantly better among food assistance recipients than non-recipients. Across diverse populations, food insecurity is an important barrier to ART adherence, and food assistance appears to be a promising intervention strategy to improve ART adherence among persons living with HIV. Additional research is needed to determine the effectiveness and cost-effectiveness of food assistance in improving ART adherence and other clinical outcomes among people living with HIV in the era of widespread and long-term treatment.

  6. Does antiretroviral therapy improve HIV-associated cognitive impairment? A quantitative review of the literature.

    PubMed

    Al-Khindi, Timour; Zakzanis, Konstantine K; van Gorp, Wilfred G

    2011-11-01

    The development of antiretroviral therapy (ART) has dramatically improved survival for those living with human immunodeficiency virus (HIV), but whether ART improves cognitive functioning remains unclear. The aim of the present review was to examine systematically the extent to which ART improves cognition among individuals with HIV using meta-analytic methods. Twenty-three studies were included in the quantitative review. ART was associated with modest improvements in attention (mean d = .17; p < .001; 95% confidence interval [CI], .09/.25), executive function (mean d = .18; p < .001; 95% CI, .10/.26), and motor function (mean d = .24; p < .001; 95% CI, .16/.32). ART did not improve language, verbal memory, visual memory or visuospatial function. The extent to which cognition improved was correlated with the change in CD4 cell count following ART, suggesting a link between cognitive outcome and immune system integrity. Together, the present findings indicate that the neuropsychological test performance of most HIV patients taking ART is comparable to those not taking ART. Development of pharmaceutical treatments and rehabilitation strategies that target the cognitive effects of HIV infection is needed.

  7. The nutritional status of children and adolescents with HIV/AIDS on antiretroviral therapy.

    PubMed

    Souza, Déborah Teixeira; Rondó, Patrícia Helen Carvalho; Reis, Ligia Cardoso

    2011-02-01

    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.

  8. The impact of antiretroviral therapy on population-level virulence evolution of HIV-1.

    PubMed

    Roberts, Hannah E; Goulder, Philip J R; McLean, Angela R

    2015-12-06

    In HIV-infected patients, an individual's set point viral load (SPVL) strongly predicts disease progression. Some think that SPVL is evolving, indicating that the virulence of the virus may be changing, but the data are not consistent. In addition, the widespread use of antiretroviral therapy (ART) has the potential to drive virulence evolution. We develop a simple deterministic model designed to answer the following questions: what are the expected patterns of virulence change in the initial decades of an epidemic? Could administration of ART drive changes in virulence evolution and, what is the potential size and direction of this effect? We find that even without ART we would not expect monotonic changes in average virulence. Transient decreases in virulence following the peak of an epidemic are not necessarily indicative of eventual evolution to avirulence. In the short term, we would expect widespread ART to cause limited downward pressure on virulence. In the long term, the direction of the effect is determined by a threshold condition, which we define. We conclude that, given the surpassing benefits of ART to the individual and in reducing onward transmission, virulence evolution considerations need have little bearing on how we treat.

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

    PubMed Central

    Rao, PSS; Earla, Ravindra; Kumar, Anil

    2015-01-01

    Introduction Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. Areas covered This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. Expert opinion We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse. PMID:25539046

  10. Current Scenario of HIV/AIDS, Treatment Options, and Major Challenges with Compliance to Antiretroviral Therapy

    PubMed Central

    Usman, Muhammad; Kandi, Venkataramana

    2016-01-01

    The discovery of the human immunodeficiency virus (HIV) as the causative organism of acquired immunodeficiency syndrome (AIDS) and the inability of modern medicine to find a cure for it has placed HIV as one of the most dreaded pathogens of the 21st century. With millions of people infected with HIV, it was once thought to result in “medical apocalypse”. However, with the advent of antiretroviral therapy (ART), it is now possible to control HIV. Adherence to ART helps to keep the viral load under control and prolong the time of progression to AIDS, resulting in near normal life expectancy. Even with the introduction of ART, a substantial number of patients fail to adhere due to a variety of reasons, including adverse side effects, drug abuse, mental disorders, socioeconomic status, literacy, and social stigma. With the availability of so many options for HIV treatment at each stage of the disease progression, physicians can switch between the treatment regimens to avoid and/or minimize the adverse effects of drugs. Close monitoring, major social reforms, and adequate counselling should also be implemented to circumvent other challenges. PMID:27054050

  11. FUNCTIONAL PROTEOME OF MACROPHAGE CARRIED NANOFORMULATED ANTIRETROVIRAL THERAPY DEMONSTRATES ENHANCED PARTICLE CARRYING CAPACITY

    PubMed Central

    Martinez-Skinner, Andrea L.; Veerubhotla, Ram S.; Liu, Han; Xiong, Huangui; Yu, Fang; McMillan, JoEllyn M.; Gendelman, Howard E.

    2013-01-01

    Our laboratory has pioneered the development of long-acting nanoformulations of antiretroviral therapy (nanoART). NanoART serves to improve drug compliance, toxicities, and access to viral reservoirs. These all function to improve treatment of human immunodeficiency virus (HIV) infection. Formulations are designed to harness the carrying capacities of mononuclear phagocytes (MP; monocytes and macrophages) and to use these cells as Trojan horses for drug delivery. Such a drug distribution system limits ART metabolism and excretion while facilitating access to viral reservoirs. Our prior works demonstrated a high degree of nanoART sequestration in macrophage recycling endosomes with broad and sustained drug tissue biodistribution and depots with limited untoward systemic toxicities. Despite such benefits, the effects of particle carriage on the cells’ functional capacities remained poorly understood. Thus, we employed pulsed stable isotope labeling of amino acids in cell culture to elucidate the macrophage proteome and assess any alterations in cellular functions that would affect cell-drug carriage and release kinetics. NanoART-MP interactions resulted in the induction of a broad range of activation-related proteins that can enhance phagocytosis, secretory functions, and cell migration. Notably, we now demonstrate that particle-cell interactions serve to enhance drug loading while facilitating drug tissue depots and transportation. PMID:23544708

  12. Suboptimal antiretroviral therapy adherence among HIV-infected adults in Guangzhou, China.

    PubMed

    Muessig, Kathryn E; McLaughlin, Megan M; Nie, Jing Min; Cai, Weiping; Zheng, Heping; Yang, Ligang; Tucker, Joseph D

    2014-01-01

    Despite China's free antiretroviral therapy (ART) program, there are high rates of treatment failure, large sociodemographic disparities in care outcomes and emerging medication resistance. Understanding patient medication adherence behaviors and challenges could inform adherence interventions to maximize the individual and prevention benefits of ART. This study assessed recent nonadherence and treatment interruption among 813 HIV-infected adult outpatients in Guangzhou, China. Participants completed a behavioral survey, underwent chart review, and were tested for syphilis, gonorrhea, and chlamydia. Factors associated with suboptimal adherence were identified using univariate and multivariate logistic regression. Among 721 HIV-infected adults receiving ART, 18.9% reported recent nonadherence (any missed ART in the past four weeks) and 6.8% reported treatment interruption (four or more weeks of missed ART in the past year). Lower education, living alone, alcohol use, and being on ART one to three years were associated with recent nonadherence. Male gender, lower education, and being on ART one to three years were associated with treatment interruption. ART medication adherence interventions are needed in China that include individualized, long-term adherence plans sensitive to patients' educational and economic situations. These interventions should also consider possible gender disparities in treatment outcomes and address the use of alcohol during ART. Successful ART medication adherence interventions in China can inform other international settings that face similar adherence challenges and disparities.

  13. Assessment of the effect of antiretroviral therapy on renal and liver functions among HIV-infected patients: a retrospective study

    PubMed Central

    Wondifraw Baynes, Habtamu; Tegene, Birhanemeskel; Gebremichael, Mikiyas; Birhane, Gebrehawaria; Kedir, Wabe; Biadgo, Belete

    2017-01-01

    Background The emergence of highly active antiretroviral therapy (HAART) has dramatically improved quality of life in prolonging survival of human immunodeficiency virus (HIV)-infected patients on treatment in developed as well as developing countries. However, the main shortcoming of HAART in long-term use is its potential to cause liver and kidney derangements that may be life threatening. The drugs are actively accumulated in the proximal renal tubule resulting in functional disturbance with mitochondrial injury being one of the most important targets recognized. Therefore, the aim of this study was to assess the adverse effects of HAART on kidney and liver functions among HIV-infected patients presenting to the University of Gondar Hospital, Ethiopia. Materials and methods An institution-based retrospective study was conducted from 2010 to 2015 on a subset of HIV-infected patients. Data were collected from the registration book of the University of Gondar Hospital antiretroviral clinic laboratory after checking the completeness of age, gender, creatinine, blood urea nitrogen, and alanine aminotransferase level. Data were entered and analyzed using SPSS version 20. Descriptive statistics, chi-square test, one-way analysis of variance, and logistic regression were done to determine associations. A P-value <0.05 was considered statistically significant. Results A total of 275 study subjects were included in the study. Of these, 62.2% were females, and the overall prevalence of chronic kidney disease (CKD) before and after treatment was 3.6% and 11.7%, respectively. A majority of the CKD patients were in stage 3 for patients after treatment. The overall prevalence of hepatotoxicity was 6.5% and 16.7% before and after treatment, respectively. A majority of the patients developed Grade 2 hepatotoxicity 66.7% and 65.2% before and after treatment, respectively. Binary and multiple logistic regression analysis indicated that the female gender was a risk factor for CKD

  14. Impact of Randomized Antiretroviral Therapy Initiation on Glucose Metabolism: AIDS Clinical Trials Group Study A5224s

    PubMed Central

    ERLANDSON, Kristine Mace; KITCH, Douglas; TIERNEY, Camlin; SAX, Paul E.; DAAR, Eric S.; MELBOURNE, Kathleen M.; HA, Belinda; MCCOMSEY, Grace A.

    2014-01-01

    Objective Prior studies have found that early HIV protease inhibitors (PIs) contribute to glucose dysregulation. Few randomized trials have evaluated glucose indices in antiretroviral-naïve subjects on newer antiretroviral therapy (ART). Methods A5224s was a substudy of A5202, a prospective trial of 1857 ART-naïve participants randomized to blinded abacavir-lamivudine (ABC/3TC) or tenofovir DF-emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV/r). Analyses used 2-sample t-tests, Spearman correlation coefficients and linear regression. Results A5224s included 269 non-diabetic subjects: 85% male, 47% white non-Hispanic, baseline median age 38 years, HIV-1 RNA 4.6 log10 copies/mL and CD4 233 cells/μL. Overall, significant 96-week increases occurred in fasting glucose, insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR), p≤0.004. Assignment to EFV (vs ATV/r) resulted in significantly greater glucose increase (mean difference 4.4; 95% CI 1.3, 7.5 mg/dL; p=0.006) but not insulin or HOMA-IR (p≥0.72). Glucose indices were not significantly different between ABC/3TC or TDF/FTC arms, p≥0.18. Significant correlations were detected between changes in glucose indices and changes in body mass index; all r≥0.23, p≤0.001. In multivariable analyses, in addition to the EFV effect, higher baseline HIV-1 RNA, and greater BMI change were significant independent factors associated with greater glucose increase. Conclusions Changes in glucose metabolism were not significantly different between TDF/FTC- and ABC/3TC-based regimens. A small but significantly greater increase in glucose was observed in those assigned to EFV. As glucose dysregulation may increase with time on ART, longer term studies will be needed to further clarify the clinical significance of these findings. PMID:24637543

  15. A three-tier framework for monitoring antiretroviral therapy in high HIV burden settings

    PubMed Central

    Osler, Meg; Hilderbrand, Katherine; Hennessey, Claudine; Arendse, Juanita; Goemaere, Eric; Ford, Nathan; Boulle, Andrew

    2014-01-01

    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 wellness, ART

  16. A three-tier framework for monitoring antiretroviral therapy in high HIV burden settings.

    PubMed

    Osler, Meg; Hilderbrand, Katherine; Hennessey, Claudine; Arendse, Juanita; Goemaere, Eric; Ford, Nathan; Boulle, Andrew

    2014-01-01

    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 wellness, ART

  17. Research as a path to wide-scale implementation of antiretroviral therapy in Africa.

    PubMed

    Sanne, Ian; van der Horst, Charles

    2004-09-01

    Although some would deny the importance of research in resource-poor countries, the benefits of research to implementation of treatment for HIV infection are innumerable. These benefits include the development of infrastructure, training of staff, creation and validation of algorithms appropriate for the setting, and answering questions necessary for a safe and effective roll-out of therapy. This was true in the USA in 1986, 1 year after the antibody test for HIV was developed, and is true in Africa today. Shortly after the development of the HIV antibody test and before any antiretroviral therapy, few physicians or centres were willing to provide care for HIV patients and fewer had adequate facilities to do so. At that time it was not known how to make an adequate diagnosis of many of the opportunistic infections nor was there a clear idea of how to treat the patients. No-one knew either the best or most cost-effective method to prevent infections. Even as roll-out of therapy proceeded in early 1987 with the approval of zidovudine by the US Food and Drug Administration, physicians were clueless as to when to start treatment. With the addition of other medications in the armamentarium, clinicians began to make mistakes in their ignorance, adding on medications one at a time as they were approved, which led to accumulation of resistance mutations for a generation of patients. These mutations were transmitted to partners and children. What single-handedly helped advance treatment in the USA and Europe in the 1980s was the willingness of respective governing authorities to create clinical research groups not only to develop new drugs but to help create cost-effective ways to use them. All the current treatment guidelines were developed from that research. Over the years these research groups provided care, including medications, laboratory tests and physician and nurse time, for thousands of patients. Medical centres, where these indigent patients were receiving their

  18. Provider-Focused Intervention Increases Adherence-Related Dialogue, But Does Not Improve Antiretroviral Therapy Adherence in Persons with HIV

    PubMed Central

    Wilson, Ira B.; Laws, M. Barton; Safren, Steven A.; Lee, Yoojin; Lu, Minyi; Coady, William; Skolnik, Paul R.; Rogers, William H.

    2010-01-01

    Background Physicians' limited knowledge of patients' antiretroviral adherence may reduce their ability to perform effective adherence counseling. Methods We conducted a randomized, cross-over study of an intervention to improve physicians' knowledge of patients' antiretroviral adherence. The intervention was a report given to the physician prior to a routine office visit that included data on: MEMS and self-reported data on antiretroviral adherence, patients' beliefs about antiretroviral therapy, reasons for missed doses, alcohol and drug use, and depression. We audio-recorded one intervention and one control visit for each patient to analyze differences in adherence related dialogue. Results 156 patients were randomized, and 106 completed all 5 study visits. Paired audio-recorded visits were available for 58 patients. Using a linear regression model that adjusted for site and baseline MEMS adherence, adherence following intervention visits did not differ significantly from control visits (2.0% higher, p=0.31, 95% CI -1.95% – 5.9%). There was a trend toward more total adherence-related utterances (median of 76 vs. 49.5, p=0.07) and a significant increase in utterances about the current regimen (median of 51.5 vs. 32.5, p=0.0002) in intervention compared with control visits. However less than 10% of adherence-related utterances were classified as “problem solving” in content, and one third of physicians' problem solving utterances were directive in nature. Conclusions Receipt of a detailed report prior to clinic visits containing data about adherence and other factors did not improve patients' antiretroviral adherence. Analyses of patient-provide dialogue suggests that providers who care for persons with HIV may benefit from training in adherence counseling techniques. PMID:20048680

  19. Plasma and cerebrospinal fluid biomarkers predict cerebral injury in HIV-infected individuals on stable combination antiretroviral therapy

    PubMed Central

    Anderson, Albert M.; Harezlak, Jaroslaw; Bharti, Ajay; Mi, Deming; Taylor, Michael J.; Daar, Eric S.; Schifitto, Giovanni; Zhong, Jianhui; Alger, Jeffry R.; Brown, Mark S.; Singer, Elyse J.; Campbell, Thomas B.; McMahon, Deborah D.; Buchthal, Steven; Cohen, Ronald; Yiannoutsos, Constantin; Letendre, Scott L.; Navia, Bradford A.

    2015-01-01

    Objectives HIV-associated brain injury persists despite antiretroviral therapy (cART), but contributing factors remain poorly understood. We postulated that inflammation-associated biomarkers will be associated with cerebral injury on proton magnetic resonance spectroscopy (MRS) in chronically HIV-infected subjects. Methods Five biomarkers were measured in 197 HIV-infected subjects: soluble CD14, MCP-1, IP-10, MIP-1β, and fractalkine. Levels of N-acetyl aspartate (NAA), Choline (Cho), Myoinositol (MI), Glutamate+Glutamine (Glx), and Creatine (Cr) were acquired in the midfrontal cortex (MFC), frontal white matter (FWM), and basal ganglia (BG). Predictive models were built via linear regression and the best models were chosen using the Akaike Information Criterion. Results Increases in plasma or CSF MCP-1 were associated with lower NAA/Cr in the MFC and BG while metabolite changes in the FWM for NAA/Cr, GlxCr and Cho/Cr were explained almost exclusively by a single factor, sCD14. Plasma and CSF levels of this factor were also significantly associated with Glx/Cr in MFC and BG. Higher CSF FKN was associated with higher NAA/Cr in BG. Best predictors for higher Cho/Cr in BG and MFC were CSF sCD14 and CSF MIP-1β. Plasma and CSF IP-10 were only associated with Cho/Cr in MFC. Of the three models that simultaneously accounted for both plasma and CSF, there were more associations between CSF biomarkers and MRS metabolites. Conclusions Markers of inflammation and immune activation, in particular MCP-1 and sCD14, predominantly reflecting CNS sources, contribute to the persistence of brain injury in a metabolite and region dependent manner in chronically HIV-infected patients on stable cART. PMID:25622053

  20. Patient attrition from the HIV antiretroviral therapy program at two hospitals in Haiti

    PubMed Central

    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

    2016-01-01

    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

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

    PubMed

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

    2015-05-01

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

  2. Effect of 24 Weeks of Statin Therapy on Systemic and Vascular Inflammation in HIV-Infected Subjects Receiving Antiretroviral Therapy

    PubMed Central

    Eckard, Allison Ross; Jiang, Ying; Debanne, Sara M.; Funderburg, Nicholas T.; McComsey, Grace A.

    2014-01-01

    Background. Human immunodeficiency virus (HIV)–infected individuals are at increased risk of cardiovascular disease (CVD) due in part to inflammation. Statins decrease inflammation in the general population, but their effect during HIV infection is largely unknown. Methods. This is an ongoing randomized, double-blinded, placebo-controlled trial to evaluate the effect of statin therapy on inflammatory markers during HIV infection. Subjects received rosuvastatin 10 mg daily or placebo for 24 weeks. Subjects were receiving stable (>12 weeks) antiretroviral therapy and had a low-density lipoprotein (LDL) cholesterol level of ≤130 mg/dL and evidence of heightened immune activation or inflammation. This was a prespecified interim analysis. Results. A total of 147 subjects were enrolled (78% were male, 70% were black, and the median age was 47 years). By 24 weeks, LDL cholesterol levels had decreased in the statin group, compared with an increase in the placebo group (−28% vs +3.8%; P < .01). A 10% reduction in the lipoprotein-associated phospholipase A2 (Lp-PLA2) level was seen in the statin group, compared with a 2% reduction in the placebo group (P < .01). In multivariable regression, receipt of statin treatment and having a nadir CD4+ T-cell count of ≤100 cell/µL were the only statistically significant predictors of a decrease in Lp-PLA2 level. Markers of systemic inflammation did not change significantly between groups. Conclusions. Twenty-four weeks of rosuvastatin therapy significantly decreased the level of Lp-PLA2, a vascular-specific, inflammatory enzyme that predicts cardiovascular events in the general population. Statins may hold promise as a means of attenuating CVD risk in HIV-infected individuals by decreasing Lp-PLA2 levels. PMID:24415784

  3. Adherence to antiretroviral therapy and its associated factors among children at South Wollo Zone Hospitals, Northeast Ethiopia: a cross-sectional study

    PubMed Central

    2014-01-01

    Background Poor adherence to antiretroviral therapy negatively affects the suppression of viral replication. It increases risks of drug resistance, treatment failure, Acquired Immuno Deficiency Syndrome (AIDS)-related morbidity and mortality among children. This study assessed the level of adherence to antiretroviral therapy and its associated factors among children at hospitals in South Wollo Zone, Northeast Ethiopia. Methods An institution-based cross-sectional study was conducted among Human Immunodeficiency Virus (HIV)-infected children in April 2013. A total of 464 children who were taking Antiretroviral Therapy (ART) in the hospitals were included. Data were collected using pretested and structured questionnaires using a face-to-face interview method. Descriptive and summary statistics were employed. Bivariate and multiple logistic regressions were computed. Odds ratios and their 95% confidence intervals were computed to determine the level of significance. Results Of the 464 study samples, 440 children with their caregivers were included in the final analysis. A total of 78.6% of the caregivers reported that their children were adherent to antiretroviral therapy in the month prior to the interview. Caregivers' knowledge about antiretroviral treatment [AOR = 2.72(95% CI: 1.82, 5.39)], no current substance use of the caregivers [Adjusted Odds Ratio (AOR) = 2.21(95% Confidence Interval (CI): 1.34, 7.13)], proximity to the health care facility [AOR = 2.31(95% CI: 1.94, 4.63)], if the child knows HIV-positive status [AOR = 3.47(95% CI: 2.10, 6.81)] and caregiver’s educational status [AOR = 0.59(95% CI: 0.21, 0.82)] were significantly and independently associated with adherence of children to antiretroviral therapy. Conclusion Adherence of antiretroviral therapy in this study was comparable to other studies conducted in developing countries. Caregiver’s knowledge about antiretroviral therapy, no current use of substances, close proximity to

  4. Initiating Antiretroviral Therapy for HIV at a Patient’s First Clinic Visit: The RapIT Randomized Controlled Trial

    PubMed Central

    Rosen, Sydney; Maskew, Mhairi; Fox, Matthew P.; Nyoni, Cynthia; Mongwenyana, Constance; Sanne, Ian; Sauls, Celeste; Long, Lawrence

    2016-01-01

    Background High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit. Methods and Findings RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study (“rapid arm”) received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study (“standard arm”) followed standard clinic procedures (three to five additional clinic visits over 2–4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis

  5. HIV-1 Transmission during Early Antiretroviral Therapy: Evaluation of Two HIV-1 Transmission Events in the HPTN 052 Prevention Study

    PubMed Central

    Rodrigo, Allen G.; Hudelson, Sarah E.; Piwowar-Manning, Estelle; Wang, Lei; Eshleman, Susan H.; Cohen, Myron S.; Swanstrom, Ronald

    2013-01-01

    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. PMID:24086252

  6. DOSE-RESPONSE RELATIONSHIP BETWEEN METHADONE DOSE AND ADHERENCE TO ANTIRETROVIRAL THERAPY AMONG HIV-POSITIVE PERSONS WHO USE ILLICIT OPIOIDS

    PubMed Central

    Lappalainen, Leslie; Nolan, Seonaid; Dobrer, Sabina; Puscas, Cathy; Montaner, Julio; Ahamad, Keith; Dong, Huiru; Kerr, Thomas; Wood, Evan; Milloy, M-J

    2015-01-01

    Background and Aims For HIV-positive individuals who use illicit opioids, engagement in methadone maintenance therapy (MMT) can contribute to improved HIV treatment outcomes. However, to our knowledge, the role of methadone dosing in adherence to antiretroviral therapy (ART) has not yet been investigated. We sought to examine the relationship between methadone dose and ART adherence among a cohort of persons who use illicit opioids. Design and Setting We used data from the ACCESS study, an ongoing prospective observational cohort of HIV-positive persons who use illicit drugs in Vancouver, Canada, confidentially linked to comprehensive HIV treatment data in a setting of universal no-cost medical care including medications. We evaluated the longitudinal relationship between methadone dose and the likelihood of ≥ 95% adherence to ART among ART-exposed participants during periods of engagement in MMT. Participants 297 ART-exposed individuals on MMT were recruited between December 2005 and May 2013 and followed for a median of 42.1 months. Measurements We measured methadone dose at ≥ 100 vs < 100 mg/day and the likelihood of ≥ 95% adherence to ART. Findings In adjusted generalized estimating equation (GEE) analyses, MMT dose ≥ 100 mg/day was independently associated with optimal adherence to ART (adjusted odds ratio [AOR] = 1.38; 95% confidence interval [CI]: 1.08 – 1.77, p = 0.010). In a sub-analysis, we observed a dose-response relationship between increasing MMT dose and ART adherence (AOR = 1.06 per 20 mg/day increase, 95% CI: 1.00 – 1.12, p = 0.041). Conclusion Among HIV-positive individuals in methadone maintenance therapy, those receiving higher doses of methadone (≥ 100 mg/day) are more likely to achieve ≥ 95% adherence to antiretroviral therapy than those receiving lower doses. PMID:25940906

  7. Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy

    PubMed Central

    Lankowski, Alexander J.; Tsai, Alexander C.; Kanyesigye, Michael; Bwana, Mwebesa; Haberer, Jessica E.; Wenger, Megan; Martin, Jeffrey N.; Bangsberg, David R.; Hunt, Peter W.; Siedner, Mark J.

    2014-01-01

    Background There is conflicting evidence on the immunologic benefit of treating helminth co-infections (“deworming”) in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART. Methodology/Principal Findings To estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (β = 42.8; 95% CI, −2.1 to 87.7) or after the first year of ART (β = −9.9; 95% CI, −24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (β = 63.0; 95% CI, 6.0 to 120.1) in females. Conclusions/Significance Empiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART

  8. Recent trends in early stage response to combination antiretroviral therapy in Australia

    PubMed Central

    McManus, Hamish; Hoy, Jennifer F; Woolley, Ian; Boyd, Mark A; Kelly, Mark D; Mulhall, Brian; Roth, Norman J; Petoumenos, Kathy; Law, Matthew G

    2014-01-01

    Background There have been improvements in combination antiretroviral therapy (cART) over the last 15 years. The aim of this analysis was to assess whether improvements in ART have resulted in improvements in surrogates of HIV outcome. Methods Patients in the Australian HIV Observational Database who initiated treatment using mono/duo therapy prior to 1996, or using cART from 1996 onwards, were included in the analysis. Patients were stratified by era of ART initiation. Median changes in CD4+ and the proportion of patients with detectable HIV viral load (>400 copies/ml) were calculated over the first 4 years of treatment. Probabilities of treatment switch were estimated using the Kaplan-Meier method. Results 2,753 patients were included in the analysis: 28% initiated treatment <1996 using mono/duo therapy; and 72% initiated treatment ≥1996 using cART (30% 1996–99; 12% 2000–03; 11% 2004–07; and 19% ≥2008). Overall CD4 response improved by later era of initiation (p<0.001), although 2000–03 CD4 response was less than that for 1996–99 (p=0.007). The average proportion with detectable viral load from 2 to 4 years post treatment commencement by era was: <1996 mono/duo 0.69 (0.67–0.71); 1996–99 cART 0.29 (0.28–0.30); 2000–03 cART 0.22 (0.20–0.24); 2004–07 cART 0.09 (0.07–0.10); ≥2008 cART 0.04 (0.03–0.05). Probability of treatment switch at 4 years after initiation decreased from 53% in 1996–99 to 29% after 2008 (p<0.001). Conclusions Across the five time-periods examined, there have been incremental improvements for patients initiated on cART, as measured by overall response (viral load and CD4 count), and also increased durability of first-line ART regimens. PMID:24704818

  9. Description and Demonstration of Cognitive Behavioral Therapy to Enhance Antiretroviral Therapy Adherence and Treat Depression in HIV-Infected Adults.

    PubMed

    Newcomb, Michael E; Bedoya, C Andres; Blashill, Aaron J; Lerner, Jonathan A; O'Cleirigh, Conall; Pinkston, Megan M; Safren, Steven A

    2015-11-01

    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.

  10. Description and Demonstration of Cognitive Behavioral Therapy to Enhance Antiretroviral Therapy Adherence and Treat Depression in HIV-Infected Adults

    PubMed Central

    Newcomb, Michael E.; Bedoya, C. Andres; Blashill, Aaron J.; Lerner, Jonathan A.; O’Cleirigh, Conall; Pinkston, Megan M.; Safren, Steven A.

    2015-01-01

    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. PMID:26688659

  11. Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples

    PubMed Central

    Anglemyer, Andrew; Rutherford, George W; Horvath, Tara; Baggaley, Rachel C; Egger, Matthias; Siegfried, Nandi

    2014-01-01

    Background Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). Objectives To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples. Search methods We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. Selection criteria Randomised controlled trials (RCT), cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART Data collection and analysis Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 3,833 references and examined 87 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. Main results One RCT and nine observational studies were included in the review. These ten studies identified 2,112 episodes of HIV transmission, 1,016 among treated couples and 1,096 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350–550 cells/µL. Similarly, the summary rate ratio for the nine observational studies was 0.58 [95% CI 0.35, 0.96], with substantial heterogeneity (I2=64%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.36 [95%CI 0.17, 0.75] with substantial heterogeneity (I2=62%). We also performed

  12. Persistent Immune Activation and Carotid Atherosclerosis in HIV-Infected Ugandans Receiving Antiretroviral Therapy

    PubMed Central

    Siedner, Mark J.; Kim, June-Ho; Nakku, Ruth Sentongo; Bibangambah, Prossy; Hemphill, Linda; Triant, Virginia A.; Haberer, Jessica E.; Martin, Jeffrey N.; Mocello, A. Rain; Boum, Yap; Kwon, Douglas S.; Tracy, Russell P.; Burdo, Tricia; Huang, Yong; Cao, Huyen; Okello, Samson; Bangsberg, David R.; Hunt, Peter W.

    2016-01-01

    Background. Human immunodeficiency virus (HIV) infection and associated immune activation predict the risk of cardiovascular disease in resource-rich areas. Less is known about these relationships in sub-Saharan Africa. Methods. Beginning in 2005, we enrolled subjects in southwestern Uganda into a cohort at the time of antiretroviral therapy (ART) initiation. Multiple immune activation measures were assessed before and 6 months after ART initiation. Beginning in 2013, participants aged >40 years underwent metabolic profiling, including measurement of hemoglobin A1c and lipid levels and carotid ultrasonography. We fit regression models to identify traditional and HIV-specific correlates of common carotid intima media thickness (CCIMT). Results. A total of 105 participants completed carotid ultrasonography, with a median completion time of 7 years following ART initiation. Age, low-density lipoprotein cholesterol level, and pre-ART HIV load were correlated with CCIMT. No association was found between CCIMT and any pre-ART biomarkers of immune activation. However, in multivariable models adjusted for cardiovascular disease risk factors, lower absolute levels of soluble CD14 and interleukin 6 and greater declines in the CD14 level and kynurenine-tryptophan ratio after 6 months of ART predicted a lower CCIMT years later (P < .01). Conclusions. Persistent immune activation despite ART-mediated viral suppression predicts the future atherosclerotic burden among HIV-infected Ugandans. Future work should focus on clinical correlates of these relationships, to elucidate the long-term health priorities for HIV-infected people in the region. PMID:26347573

  13. Neuronal-glia markers by Magnetic Resonance Spectroscopy in HIV Before and After Combination Antiretroviral Therapy

    PubMed Central

    Sailasuta, Napapon; Ananworanich, Jintanat; Lerdlum, Sukalaya; Sithinamsuwan, Pasiri; Fletcher, James LK; Tipsuk, Somporn; Pothisri, Mantana; Jadwattanakul, Tanate; Jirajariyavej, Supunnee; Chalermchai, Thep; Catella, Stephanie; Busovaca, Edgar; Desai, Akash; Paul, Robert; Valcour, Victor

    2015-01-01

    Objective Combination antiretroviral therapy (cART) can suppress plasma HIV RNA to undetectable levels; yet reports indicate persistent HIV-associated neurocognitive disorders (HAND) among treated individuals. We sought to investigate imaging correlates of incomplete cognitive recovery among individuals with chronic HIV. Methods We used single voxel proton magnetic resonance spectroscopy (MRS) in four brain regions to measure changes in neuronal and glia biomarkers in cART-naïve subjects before (n=59, 27 with HAND) and after 12 months of cART. Results At baseline we observed elevated total choline (CHO) in the basal ganglia (BG, p=0.002) and in the posterior cingulate gyrus (PCG, p=0.022) associated with HIV-infection. Myo-inositol (MI) was elevated in the frontal white matter (FWM, p=0.040). N-acetylaspartate (NAA) was elevated in the BG (p=0.047). Using a mixed model approach among all HIV-infected individuals at 6 months, we observed decreased NAA in FWM (p =0.031), decreased creatine (CR) in PCG (p=0.026) and increased MI in FGM (p=0.023). At 12 months, we observed an increase in BG MI (p=0.038) and in FGM (p=0.021). Compared to those with normal cognition, HAND cases had higher FGM MI (p=0.014) at baseline. At 12 months, individuals that remained cognitively impaired compared to those without HAND exhibited elevated CHO in the PCG (p=0.018) and decreased GLU in both FWM (p=0.027) and BG (p=0.013). Conclusions cART started during chronic HIV is associated with reduced neuronal-glia and inflammatory markers. Alterations in CHO are noted among individuals who remain impaired after 12 months of cART. PMID:26258565

  14. Violence and the perceived risks of taking antiretroviral therapy in US jails and prisons

    PubMed Central

    Culbert, Gabriel J.

    2014-01-01

    Purpose About one in five men living with HIV in the USA passes through a correctional center annually. Jails and prisons are seen therefore as key intervention sites to promote HIV treatment as prevention. Almost no research, however, has examined inmates' perspectives on HIV treatment or their strategies for retaining access to antiretroviral therapy (ART) during incarceration. The purpose of this paper is to describe the results of an exploratory study examining men's perceptions of and experiences with HIV care and ART during incarceration. Design/methodology/approach Semi-structured, in-depth interviews were conducted with 42 HIV positive male and male-to-female transgendered persons recently released from male correctional centers in Illinois, USA. Findings Interpersonal violence, a lack of safety, and perceived threats to privacy were frequently cited barriers to one's willingness and ability to access and adhere to treatment. Over 60 percent of study participants reported missed doses or sustained treatment interruption (greater than two weeks) because of failure to disclose their HIV status, delayed prescribing, intermittent dosing and out-of-stock medications, confiscation of medications, and medication strikes. Research limitations/implications Substantial improvements in ART access and adherence are likely to follow organizational changes that make incarcerated men feel safer, facilitate HIV status disclosure, and better protect the confidentiality of inmates receiving ART. Originality/value This study identified novel causes of ART non-adherence among prisoners and provides first-hand information about how violence, stigma, and the pursuit of social support influence prisoner's decisions to disclose their HIV status or accept ART during incarceration. PMID:25764073

  15. Antiretroviral Therapy Reduces HIV Transmission in Discordant Couples in Rural Yunnan, China

    PubMed Central

    He, Na; Duan, Song; Ding, Yingying; Rou, Keming; McGoogan, Jennifer M.; Jia, Manhong; Yang, Yuecheng; Wang, Jibao; Montaner, Julio S. G.; Wu, Zunyou

    2013-01-01

    Background Although HIV treatment as prevention (TasP) via early antiretroviral therapy (ART) has proven to reduce transmissions among HIV-serodiscordant couples, its full implementation in developing countries remains a challenge. In this study, we determine whether China's current HIV treatment program prevents new HIV infections among discordant couples in rural China. Methods A prospective, longitudinal cohort study was conducted from June 2009 to March 2011, in rural Yunnan. A total of 1,618 HIV-discordant couples were eligible, 1,101 were enrolled, and 813 were followed for an average of 1.4 person-years (PY). Routine ART was prescribed to HIV-positive spouses according to eligibility (CD4<350 cells/µl). Seroconversion was used to determine HIV incidence. Results A total of 17 seroconversions were documented within 1,127 PY of follow-up, for an overall incidence of 1.5 per 100 PY. Epidemiological and genetic evidence confirmed that all 17 seroconverters were infected via marital secondary sexual transmission. Having an ART-experienced HIV-positive partner was associated with a lower rate of seroconvertion compared with having an ART-naïve HIV-positive partner (0.8 per 100 PY vs. 2.4 per 100 PY, HR = 0.34, 95%CI = 0.12–0.97, p = 0.0436). While we found that ART successfully suppressed plasma viral load to <400 copies/ml in the majority of cases (85.0% vs. 19.5%, p<0.0001 at baseline), we did document five seroconversions among ART-experienced subgroup. Conclusions ART is associated with a 66% reduction in HIV incidence among discordant couples in our sample, demonstrating the effectiveness of China's HIV treatment program at preventing new infections, and providing support for earlier ART initiation and TasP implementation in this region. PMID:24236010

  16. Initiation of antiretroviral therapy in HIV-infected adults with skin complaints in northern Tanzania

    PubMed Central

    Mavura, Daudi R.; Masenga, E. John; Minja, Eli; Grossmann, Henning; Crump, John A.; Bartlett, John A.

    2015-01-01

    Abnormal skin findings are identified in over 90% of human immunodeficiency virus (HIV)-infected persons globally. A prospective cohort study of HIV-infected patients with skin complaints commencing antiretroviral therapy (ART) in northern Tanzania was undertaken. Consecutive HIV-infected subjects presenting with skin complaints, who met criteria for ART initiation, were recruited at a Tanzanian Regional Dermatology Training Center. A single dermatologist evaluated all subjects; baseline skin biopsies were performed, and CD4+ cell counts and plasma HIV RNA levels were measured. All subjects received a fixed-dose combination of stavudine, lamivudine, and nevirapine. A total of 100 subjects were enrolled; 86 subjects completed six months of follow-up. Median baseline CD4+ cell counts and plasma HIV RNA levels were 120 cells/μl and 5.2 log10 copies/ml. The most common dermatologic condition was papular pruritic eruption (47%). The median baseline score on the Burn Scale was 38%. After six months, 10 subjects had achieved the complete resolution of skin abnormalities. In those without complete resolution, the median Burn Scale score improved to 7%. Five patients developed new eruptions by month 3, which in two cases were attributed to drug reactions. In the 86 subjects remaining on ART after six months, the median CD4+ cell count had increased to 474 cells/μl, and plasma HIV RNA levels were <400 copies/ml in 85 (99%) subjects. Patients with HIV infection with skin complaints experienced marked clinical improvements following ART initiation. PMID:25256912

  17. Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study.

    PubMed

    Carlson, Renee Donahue; Rolfes, Melissa A; Birkenkamp, Kate E; Nakasujja, Noeline; Rajasingham, Radha; Meya, David B; Boulware, David R

    2014-06-01

    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 < -1), only in domains of motor speed, gross motor and executive function at 12 months. There was no evidence that neurocognitive outcome was associated with initial demographics, HIV parameters, or 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.

  18. Immunodeficiency at the start of combination antiretroviral therapy in low-, middle- and high-income countries

    PubMed Central

    2013-01-01

    Objectives To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC) and high-income (HIC) countries. Methods Patients aged ≥16 years starting cART in a clinic participating in a multi-cohort collaboration spanning six continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multi-level linear regression models were adjusted for age, gender and calendar year; missing CD4 counts were imputed. Findings 379,865 patients from nine LIC, four LMIC, four UMIC and six HIC were included. In LIC the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/μl between 2002 and 2009. Corresponding increases in LMIC, UMIC and HIC were from 87 to 155 cells/μl (76% increase), 88 to 135 cells/μl (53%) and 209 to 274 cells/μl (31%). In 2009, compared to LIC, median counts were 13 cells/μl (95% CI -56 to +30) lower in LMIC, 22 cells/μl (-62 to +18) lower in UMIC and 112 /μl (+75 to +149) higher in HIC. They were 23 cells/μl (95% CI +18 to +28) higher in women than men. Median counts were 88 cells/μl (95% CI +35 to +141) higher in countries with an estimated national cART coverage >80%, compared to countries with <40% coverage. Conclusions Median CD4 cell counts at start of cART increased 2000-2009 but remained below 200 cells/μl in LIC and MIC and below 300 cells/μl in HIC. Earlier start of cART will require substantial efforts and resources globally. PMID:24419071

  19. Depression During Pregnancy and the Postpartum Among HIV-Infected Women on Antiretroviral Therapy in Uganda

    PubMed Central

    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.

    2014-01-01

    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

  20. Effectiveness of Hormonal Contraception in HIV-Infected Women using Antiretroviral Therapy: A Prospective Study

    PubMed Central

    Pyra, Maria; Heffron, Renee; Mugo, Nelly R.; Nanda, Kavita; Thomas, Katherine K.; Celum, Connie; Kourtis, Athena P.; Were, Edwin; Rees, Helen; Bukusi, Elizabeth; Baeten, Jared M.

    2015-01-01

    Objective To assess whether antiretroviral therapy (ART) may diminish the effectiveness of hormonal contraceptive methods. Methods Using data from 5,153 HIV-infected women followed prospectively one to three years in three HIV prevention studies in Africa, we compared incident pregnancy rates by contraceptive method (implant, injectable, oral, or none) and ART use. Multivariable Cox regression models were used to determine adjusted hazard ratios (aHR) and test interactions between each method and ART use. Results During follow-up, 9% of women ever used implants, 40% used injectables, and 14% used oral contraceptives; 31% of women ever used ART, mostly nevirapine (75% of ART users) or efavirenz-based (15%). Among women not using contraception, pregnancy rates were 13.2 and 22.5 per 100 women-years for those on and not on ART, respectively. Implants greatly reduced the incidence of pregnancy among both women on ART (aHR 0.06, 95% CI 0.01-0.45) and not on ART (aHR 0.05, 95% CI 0.02-0.11). Injectables (aHR 0.18 on ART and aHR 0.20 not on ART) and oral contraceptives (aHR 0.37 on ART and aHR 0.36 not on ART) also reduced pregnancy risk, though by lesser degrees. ART use did not significantly diminish contraceptive effectiveness, although all methods showed non-statistically significant reduced effectiveness when concurrently using efavirenz. Conclusion Hormonal contraceptive methods are highly effective in reducing pregnancy risk in HIV-infected women, including those concurrently using ART. Studies of potential interactions between ART and contraceptives should evaluate real-world effectiveness of contraceptive methods; in this study, implants were the most effective method to prevent pregnancy, even during ART use. PMID:26544706

  1. Medication-Taking Practices of Patients on Antiretroviral HIV Therapy: Control, Power, and Intentionality

    PubMed Central

    Panter, Abigail T.; Mouw, Mary S.; Amola, Kemi; Stein, Kathryn E.; Murphy, Joseph S.; Maiese, Eric M.; Wohl, David A.

    2015-01-01

    Abstract 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. PMID:26505969

  2. Neuropsychological impairment in acute HIV and the effect of immediate antiretroviral therapy

    PubMed Central

    Kore, Idil; Ananworanich, Jintanat; Valcour, Victor; Fletcher, James LK; Chalermchai, Thep; Paul, Robert; Reynolds, Jesse; Tipsuk, Somporn; Ubolyam, Sasiwimol; Rattanamanee, Somprartthana; Jagodzinski, Linda; Kim, Jerome; Spudich, Serena

    2015-01-01

    OBJECTIVE To investigate neuropsychological performance (NP) during acute HIV infection (AHI) before and after combination antiretroviral therapy (cART). DESIGN Prospective study of Thai AHI participants examined at 3 and 6 months following initiation of cART. METHODS 36 AHI participants were evaluated pre-cART at median 19 days since HIV exposure and 3 and 6 months after cART with the Grooved Pegboard test (GP), Color Trails 1 & 2 (CT1, CT2), and Trail Making Test A (TM). Raw scores were standardized to 251 age-and-education-matched HIV-uninfected Thais. To account for learning effects, change in NP performance was compared to that of controls at 6 months. Analyses included multivariable regression, non-parametric repeated measures ANOVA, and Mann-Whitney U test. RESULTS Baseline NP scores for the AHI group were within normal range (Z scores range: −0.26 to −0.13). NP performance improved on CT1, CT2, and TM in the initial 3 months (ps <0.01) with no significant change during the last 3 months. Only improvement in CT1 was greater than that seen in controls at 6 months (p=0.018). Participants that performed >1 standard deviation below normative means on >2 tests (n=8) exhibited higher baseline cerebrospinal fluid (CSF) HIV RNA (p=0.047) and had no improvement after cART. CONCLUSIONS Most AHI individuals had normal NP performance and early cART slightly improved their psychomotor function. However, approximately 25% had impaired NP performance which correlated with higher CSF HIV RNA, and these abnormalities were not reversed by early cART possibly indicating limited reversibility of cognitive impairment in a subset of AHI individuals. PMID:26509933

  3. Randomized Controlled Trial of a Personalized Cellular Phone Reminder System to Enhance Adherence to Antiretroviral Therapy

    PubMed Central

    Kumar, Vikram; Doros, Gheorghe; Farmer, Eric; Drainoni, Mari-Lynn; Rybin, Denis; Myung, Dan; Jackson, Jonathan; Backman, Elke; Stanic, Anela; Skolnik, Paul R.

    2011-01-01

    Abstract Adherence to antiretroviral therapy (ART) represents one of the strongest predictors of progression to AIDS, yet it is difficult for most patients to sustain high levels of adherence. This study compares the efficacy of a personalized cell phone reminder system (ARemind) in enhancing adherence to ART versus a beeper. Twenty-three HIV-infected subjects on ART with self-reported adherence less than 85% were randomized to a cellular phone (CP) or beeper (BP). CP subjects received personalized text messages daily; in contrast, BP subjects received a reminder beep at the time of dosing. Interviews were scheduled at weeks 3 and 6. Adherence to ART was measured by self-report (SR, 7-day recall), pill count (PC, past 30 days at baseline, then past 3 weeks), Medication Event Monitoring System (MEMS; cumulatively at 3 and 6 weeks), and via a composite adherence score constructed by combining MEMS, pill count, and self report. A mixed effects model adjusting for baseline adherence was used to compare adherence rates between the intervention groups at 3 and 6 weeks. Nineteen subjects completed all visits, 10 men and 9 females. The mean age was 42.7 ± 6.5 years, 37% of subjects were Caucasian and 89% acquired HIV heterosexually. The average adherence to ART was 79% by SR and 65% by PC at baseline in both arms; over 6 weeks adherence increased and remained significantly higher in the ARemind group using multiple measures of adherence. A larger and longer prospective study is needed to confirm these findings and to better understand optimal reminder messages and user fatigue. PMID:21323532

  4. Nevirapine Resistance in Previously Nevirapine-Unexposed HIV-1-Infected Kenyan Infants Initiating Early Antiretroviral Therapy.

    PubMed

    Chohan, Bhavna H; Tapia, Kenneth; Benki-Nugent, Sarah; Khasimwa, Brian; Ngayo, Musa; Maleche-Obimbo, Elizabeth; Wamalwa, Dalton; Overbaugh, Julie; John-Stewart, Grace

    2015-08-01

    Nevirapine (NVP) resistance occurs frequently in infants following NVP use in prevention of mother-to-child transmission (PMTCT) regimens. However, among previously NVP-unexposed infants treated with NVP-antiretroviral therapy (ART), the development and impact of NVP resistance have not been well characterized. In a prospective clinical trial providing early ART to HIV-infected infants <5 months of age in Kenya (OPH03 study), we followed NVP-unexposed infants who initiated NVP-ART for 12 months. Viral loads were assessed and resistance determined using a population-based genotypic resistance assay. Of 99 infants screened, 33 had no prior NVP exposure, 22 of whom were initiated on NVP-ART. Among 19 infants with follow-up, seven (37%) infants developed resistance: one at 3 months and six at 6 months after ART initiation. The cumulative probability of NVP resistance was 5.9% at 3 months and 43.5% at 6 months. Baseline HIV RNA levels (p=0.7) and other characteristics were not associated with developing resistance. Post-ART, higher virus levels at visits preceding the detection of resistance were significantly associated with increased detection of resistance (p=0.004). Virus levels after 6 and 12 months of ART were significantly higher in infants with resistance than those without (p=0.007, p=0.030, respectively). Among infants without previous NVP exposure, development of NVP resistance was frequent and was associated with virologic failure during the first year of ART. Earlier development of NVP resistance in infants than in adults initiating NVP-ART may be due to longer viremia following ART or inadequate NVP levels resulting from NVP lead-in dosing. The development of NVP resistance may, in part, explain the superiority of protease inhibitor-based ART in infants.

  5. Finding Meaning: HIV Self-Management and Wellbeing among People Taking Antiretroviral Therapy in Uganda.

    PubMed

    Russell, Steve; Martin, Faith; Zalwango, Flavia; Namukwaya, Stella; Nalugya, Ruth; Muhumuza, Richard; Katongole, Joseph; Seeley, Janet

    2016-01-01

    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

  6. Early antiretroviral therapy initiation: access and equity of viral load testing for HIV treatment monitoring.

    PubMed

    Peter, Trevor; Ellenberger, Dennis; Kim, Andrea A; Boeras, Debrah; Messele, Tsehaynesh; Roberts, Teri; Stevens, Wendy; Jani, Ilesh; Abimiku, Alash'le; Ford, Nathan; Katz, Zachary; Nkengasong, John N

    2017-01-01

    Scaling up access to HIV viral load testing for individuals undergoing antiretroviral therapy in low-resource settings is a global health priority, as emphasised by research showing the benefits of suppressed viral load for the individual and the whole population. Historically, large-scale diagnostic test implementation has been slow and incomplete because of service delivery and other challenges. Building on lessons from the past, in this Personal View we propose a new framework to accelerate viral load scale-up and ensure equitable access to this essential test. The framework includes the following steps: (1) ensuring adequate financial investment in scaling up this test; (2) achieving pricing agreements and consolidating procurement to lower prices of the test; (3) strengthening functional tiered laboratory networks and systems to expand access to reliable, high-quality testing across countries; (4) strengthening national leadership, with prioritisation of laboratory services; and (5) demand creation and uptake of test results by clinicians, nurses, and patients, which will be vital in ensuring viral load tests are appropriately used to improve the quality of care. The use of dried blood spots to stabilise and ship samples from clinics to laboratories, and the use of point-of-care diagnostic tests, will also be important for ensuring access, especially in settings with reduced laboratory capacity. For countries that have just started to scale up viral load testing, lessons can be learnt from countries such as Botswana, Brazil, South Africa, and Thailand, which have already established viral load programmes. This framework might be useful for guiding the implementation of viral load with the aim of achieving the new global HIV 90-90-90 goals by 2020.

  7. Has Highly Active Antiretroviral Therapy Increased the Time to Seroreversion in HIV Exposed but Uninfected Children?

    PubMed Central

    Gutierrez, Mavel; Ludwig, David A.; Khan, Safia S.; Chaparro, Aida A.; Rivera, Delia M.; Cotter, Amanda M.; Scott, Gwendolyn B.

    2012-01-01

    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

  8. Determinants of non-adherence to antiretroviral therapy in adult hospitalized patients, Northwest Ethiopia

    PubMed Central

    Tsega, Bayew; Srikanth, Bhagavathula Akshaya; Shewamene, Zewdneh

    2015-01-01

    Aim The aim of this study was to assess the rate of antiretroviral therapy (ART) adherence and to identify any determinants among adult patients. Methods A cross-sectional study was conducted on 351 ART patients in the ART clinic of the University of Gondar referral hospital. Data were collected by a pretested interviewer-administered structured questionnaire from May to June 2014. Multivariate logistic regression was used to determine factors significantly associated with adherence. Results Of 351 study subjects, women were more predominant than men (64.4% versus 35.6%). Three hundred and forty (96.9%) patients agreed and strongly agreed that the use of ART is essential in their life, and approximately 327 (93.2%) disclosed their sero-status to family. Seventy-nine (22.5%) participants were active substance users. The level of adherence was 284 (80.9%). Three hundred forty-one (97.2%) respondents had good or fair adherence. Among the reasons for missing doses were forgetfulness (29 [43.3%]), missing appointments (14 [20.9%]), running out of medicine (9 [13.4%]), depression, anger, or hopelessness (4 [6.0%]), side effects of the medicine used (2 [3.0%]), and nonbelief in the ART (2 [3.0%]). The variables found significantly associated with non-adherence were age (P-value 0.017), employment (P-value 0.02), HIV disclosure (P-value 0.04), and comfortability to take ART in the presence of others (P-value 0.02). Conclusion From this study, it was determined that forgetfulness (43.3%) was the most common reason for missing doses. Also, employment and acceptance in using ART in the presence of others are significant issues observed for non-adherence. Hence, the ART counselor needs to place more emphasis on the provision and use of memory aids. PMID:25784793

  9. Alcohol use and immune reconstitution among HIV-infected patients on antiretroviral therapy in Nairobi, Kenya.

    PubMed

    Cagle, Anthony; McGrath, Christine; Richardson, Barbra A; Donovan, Dennis; Sakr, Sameh; Yatich, Nelly; Ngomoa, Richard; Chepngeno Langat, Agnes; John-Stewart, Grace; Chung, Michael H

    2017-01-29

    Studies on the effects of alcohol use on HIV disease progression have been contradictory, with at least one study finding a positive effect of low alcohol consumption on CD4 count. In addition, most such studies have taken place in the developed West. We investigated the association between alcohol use and immune reconstitution through CD4 count response among HIV-infected individuals on antiretroviral therapy (ART) at an urban sub-Saharan African clinic. This was a retrospective cohort study of treatment-naïve HIV-infected adults initiating ART in Nairobi, Kenya and followed for 12 months between January 2009 and December 2012. At enrollment, a standardized questionnaire was used to collect data on sociodemographic variables and alcohol consumption. CD4 count was measured every six months. Linear regression models assessed the association between CD4 count and alcohol consumption, categorized as abstinent, moderate, or hazardous. Overall, 854 participants were included, 522 of which were women, with 85 (25.6%) men and 50 (9.6%) women reporting any alcohol use, and 8 (2.4%) men and 7 (1.3%) women reporting hazardous drinking. At baseline, alcohol use was associated with higher education and socioeconomic status. Median CD4 count was higher among alcohol users compared to those who abstained at baseline and at 6 and 12 months post-ART initiation, although this was only significant at 6 months. There were no differences in adherence between abstainers and drinkers. While overall alcohol use was significantly associated with higher CD4 counts, moderate and hazardous use treated separately were not. We conclude that, while alcohol use was associated with higher CD4 counts at 12 months post-ART, the mechanism for this association is unclear but may reflect unmeasured socioeconomic or nutritional differences. Additional research is required on the specific drinking patterns of this population and the types of alcoholic beverages consumed to clarify this relationship.

  10. Antiretroviral Therapy and Pregnancy Outcomes in Developing Countries: A Systematic Review

    PubMed Central

    Alemu, Fekadu Mazengia; Yalew, Alemayehu Worku; Fantahun, Mesganaw; Ashu, Eta Ebasi

    2015-01-01

    Background: Despite significant efforts to understand adverse pregnancy outcome in women receiving Antiretroviral Therapy (ART), ART-related adverse birth outcomes are still poorly understood. We systematically review ART-related adverse birth outcomes among HIV-infected pregnant women; we also review the covariates associated with adverse birth outcomes in the aforementioned group. Methods: The main source for our systematic review was electronic bibliographic databases. Databases such as MEDLINE, PubMed, EMBASE and AIDSLINE were searched. Furthermore, search engines such as Google and Google Scholar were specifically searched for gray literature. Methodological quality of available literature was assessed using the Newcastle - Ottawa Quality Assessment Scale & M. Hewitt guideline. We examined a total of 1,124 papers and reviewed the studies using the PICOT criteria which stands for Patient (population), Intervention (or “Exposure”), Comparison, Outcome and Type of study. Finally, 32 methodologically fit studies were retained and included in our review. Results: Frequently observed adverse birth outcomes included low birth weight (LBW), Preterm Birth (PB), Small for Gestational Age (SGA), while still birth and congenital anomalies were infrequent. Type of regimen such as Protease Inhibitor (PI) based regimens and timing of initiation of ART are some of the factors associated with adverse pregnancy outcomes. Covariates principally included malnutrition and other co-morbidities such as malaria and HIV. Conclusions and Public Health Implications: There is growing evidence in published literature suggesting that ART might be causing adverse birth outcomes among pregnant women in developing countries. There is a need to consider regimen types for HIV-infected pregnant women. There is need to design large cohort studies. PMID:27621984

  11. Rapamycin with Antiretroviral Therapy in AIDS-Associated Kaposi Sarcoma: An AIDS Malignancy Consortium Study

    PubMed Central

    Krown, Susan E.; Roy, Debasmita; Lee, Jeannette Y.; Dezube, Bruce J.; Reid, Erin G.; Venkataramanan, Raman; Han, Kelong; Cesarman, Ethel; Dittmer, Dirk P.

    2011-01-01

    Purpose The mammalian target of rapamycin (mTOR) is activated in Kaposi sarcoma (KS) and its inhibitor, rapamycin, has induced KS regression in transplant-associated KS. This study aimed to evaluate rapamycin's safety and toxicity in HIV-infected individuals with KS receiving antiretroviral therapy (ART), investigate rapamycin interactions with both protease inhibitor (PI)-containing and non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing ART regimens, and assess clinical and biological endpoints including KS response and mTOR-dependent signaling. Methods Seven participants, 4 on PI-based and 3 on NNRTI-based ART, had rapamycin titrated to achieve trough concentrations of 5-10 ng/mL. Patients were monitored for safety and KS response. KS biopsies were evaluated for changes in phospho-Ribosomal S6 protein (pRPS6), and phospho-Akt expression. Interleukin-6 and vascular endothelial growth factor levels, HIV and KS-associated herpesvirus viral loads, and CD4 counts were monitored. Results Despite pharmacokinetic interactions resulting in >200-fold differences in cumulative weekly rapamycin doses between participants on PI-containing and NNRTI-containing regimens, treatment was well tolerated. There were no significant changes in viral loads or cytokine levels; modest initial decreases in CD4 counts occurred in some patients. Three participants, all on PI-containing regimens and with higher rapamycin exposure, showed partial KS responses. Three of four subjects whose biopsies were studied at ≥day 50 showed decreased pRPS6 staining. Conclusions Rapamycin appears safe in HIV-infected individuals with KS and can, in some cases, induce tumor regression and affect its molecular targets. Significant pharmacokinetic interactions require careful titration to achieve target drug trough concentrations, but may be exploited to achieve therapeutic benefit. PMID:22067664

  12. Effect of antiretroviral therapy on malaria incidence in HIV-infected Ugandan adults

    PubMed Central

    Kasirye, Ronnie P.; Grosskurth, Heiner; Munderi, Paula; Levin, Jonathan; Anywaine, Zacchaeus; Nunn, Andrew; Kamali, Anatoli; Baisley, Kathy

    2017-01-01

    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

  13. Using CD4 Percentage and Age to Optimize Pediatric Antiretroviral Therapy Initiation

    PubMed Central

    Warshaw, Meredith G.; Miller, William C.; Castro, Hannah; Fiscus, Susan A.; Harper, Lynda M.; Harrison, Linda J.; Klein, Nigel J.; Lewis, Joanna; Melvin, Ann J.; Tudor-Williams, Gareth; McKinney, Ross E.

    2014-01-01

    BACKGROUND: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation. METHODS: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization “mild” immunosuppression and CD4% <10th percentile, were analyzed for improvement to a normal CD4% (≥10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years. RESULTS: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with “severe” immunosuppression, more children with “mild” immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or “advanced” immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with “mild” immunosuppression at any age or “advanced” immunosuppression at age <3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%). CONCLUSIONS: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks. PMID:25266426

  14. Loss to Clinic and Five-Year Mortality among HIV-Infected Antiretroviral Therapy Initiators

    PubMed Central

    Edwards, Jessie K.; Cole, Stephen R.; Westreich, Daniel; Moore, Richard; Mathews, Christopher; Geng, Elvin; Eron, Joseph J.; Mugavero, Michael J.

    2014-01-01

    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. PMID:25010739

  15. Medication-Taking Practices of Patients on Antiretroviral HIV Therapy: Control, Power, and Intentionality.

    PubMed

    Muessig, Kathryn E; Panter, Abigail T; Mouw, Mary S; Amola, Kemi; Stein, Kathryn E; Murphy, Joseph S; Maiese, Eric M; Wohl, David A

    2015-11-01

    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.

  16. Effect of Different Types of Exercise in HIV + Mozambican Women Using Antiretroviral Therapy

    PubMed Central

    Mangona, Lucília; Daca, Timóteo; Tchonga, Francisco; Bule, Odete; Bhatt, Nilesh; Jani, Ilesh; Damasceno, Albertino; Prista, António

    2015-01-01

    The aim of this study was to evaluate and compare the effect of two types of exercises interventions on the regularity and health-related physical fitness in HIV-infected individuals who use antiretroviral therapy (ART). A total of 53 HIV+ African women (mean age=39.5±8.4 years) on ART participated in the study. Subjects were randomly divided into 3 groups, namely, formal exercise (FEG), playful exercise (PEG) and control (CG). During 12 weeks, the exercise groups underwent a program of 1-hour duration with a frequency of 3 times a week. The FEG performed a protocol that included 20 minutes of exercise, cycling at 60 % of V̇O2peak, increasing to 75 % and 85 % in the 4th and 8th weeks, respectively, and a muscular endurance circuit consisted of 6 exercises at 15 repetitions per minute (RM). The PEG followed a program consisting of active games. Before and after the intervention the participants were submitted to a clinical evaluation including immunological parameters (CD4+), cardiovascular risk factors, physical fitness and anthropometry. Comparison of somatic variables before and after the program showed no exercise effect. Immunological and cardiovascular variables were also independent of the exercise group. The main effect was found in cardiorespiratory fitness: exercise groups increased significantly in V̇O2peak (FEG=14.7 %; PEG=11.1 %) with no significant differences in CG. The percentage of high attendance was identical between the two groups. It was concluded that there is no contraindication for exercise in this type of population and the beneficial effect was mainly in cardiorespiratory fitness, regardless of the type of exercise performed. PMID:26587077

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

    PubMed Central

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

    2016-01-01

    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

  18. Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy

    PubMed Central

    2012-01-01

    Background The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods We analyzed data on 20,379 treatment-naive HIV-1–infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count <25 cells/µL had persistently higher progression rates than individuals with a baseline CD4 count >350 cells/µL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART. PMID:18043315

  19. HIV Transmission Risk Persists During the First 6 Months of Antiretroviral Therapy

    PubMed Central

    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.

    2016-01-01

    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 (<80 copies/ml) 3, 6 and 9-months after ART initiation were 65.3%, 84.8% and 89.1%, respectively. Endocervical and seminal HIV RNA were detectable in 12% and 21% of samples obtained within 6-months of ART. Pregnancy incidence was 8.8 per 100 person-years during the first 6-months of ART, and sex unprotected by condoms was reported at 10.5% of visits. Among initially uninfected partners, HIV incidence before ART was 2.08 per 100 person-years (55 infections; 2644 person-years), 1.79 for 0–6 months after ART initiation (3 infections; 168 person-years), and 0.00 with >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

  20. Unhealthy Alcohol Use is Associated with Monocyte Activation Prior to Starting Anti-Retroviral Therapy

    PubMed Central

    Carrico, Adam W.; Hunt, Peter W.; Emenyonu, Nneka I.; Muyindike, Winnie; Ngabirano, Christine; Cheng, Debbie M.; Winter, Michael R.; Samet, Jeffrey H.; Hahn, Judith A.

    2015-01-01

    Background Alcohol use may accelerate HIV disease progression, but the plausible biological mechanisms have not been clearly elucidated. Methods HIV-positive persons who were not on anti-retroviral therapy (ART) completed the baseline assessment for a longitudinal study examining the association of alcohol use with HIV disease markers. Oversampling drinkers, baseline samples were tested for markers of monocyte activation (sCD14), inflammation (IL-6), and coagulation (D-dimer). We defined “unhealthy alcohol use” as testing positive using the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C; ≥ 3 for women and ≥ 4 for men) in the past 3 months or testing positive using a biomarker of heavy drinking, phophatidylethanol (PEth; ≥ 50 ng/ml). Multiple linear regression was used to examine the associations of unhealthy alcohol use with sCD14, Log10 IL-6, and D-dimer. Results Compared to those who were abstinent from alcohol, unhealthy drinkers had significantly higher sCD14 levels (mean = 1,676 vs. 1,387 ng/ml; mean difference (95% CI) = 289 (83, 495), p < 0.01). In analyses adjusted for demographic factors, current cigarette smoking, and HIV disease markers, unhealthy drinkers continued to display significantly higher sCD14 levels compared to those who were abstinent from alcohol (adjusted mean = 1,670 vs. 1,406 ng/ml; adjusted mean difference (95% CI) = 264 (47, 480), p = 0.02). Unhealthy alcohol use was not significantly associated with IL-6 or D-dimer levels. Conclusions unhealthy alcohol use was independently associated with a marker of monocyte activation (i.e., higher sCD14) that predicts mortality in treated HIV infection. Longitudinal research should examine if unhealthy alcohol use predicts changes in sCD14 prior to and following ART initiation. PMID:26509359

  1. Use of peers to improve adherence to antiretroviral therapy: a global network meta-analysis

    PubMed Central

    Kanters, Steve; Park, Jay JH; Chan, Keith; Ford, Nathan; Forrest, Jamie; Thorlund, Kristian; Nachega, Jean B; Mills, Edward J

    2016-01-01

    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

  2. Polyomavirus JCV excretion and genotype analysis in HIV-infected patients receiving highly active antiretroviral therapy

    NASA Technical Reports Server (NTRS)

    Lednicky, John A.; Vilchez, Regis A.; Keitel, Wendy A.; Visnegarwala, Fehmida; White, Zoe S.; Kozinetz, Claudia A.; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    OBJECTIVE: To assess the frequency of shedding of polyomavirus JC virus (JCV) genotypes in urine of HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Single samples of urine and blood were collected prospectively from 70 adult HIV-infected patients and 68 uninfected volunteers. Inclusion criteria for HIV-infected patients included an HIV RNA viral load < 1000 copies, CD4 cell count of 200-700 x 106 cells/l, and stable HAART regimen. PCR assays and sequence analysis were carried out using JCV-specific primers against different regions of the virus genome. RESULTS: JCV excretion in urine was more common in HIV-positive patients but not significantly different from that of the HIV-negative group [22/70 (31%) versus 13/68 (19%); P = 0.09]. HIV-positive patients lost the age-related pattern of JCV shedding (P = 0.13) displayed by uninfected subjects (P = 0.01). Among HIV-infected patients significant differences in JCV shedding were related to CD4 cell counts (P = 0.03). Sequence analysis of the JCV regulatory region from both HIV-infected patients and uninfected volunteers revealed all to be JCV archetypal strains. JCV genotypes 1 (36%) and 4 (36%) were the most common among HIV-infected patients, whereas type 2 (77%) was the most frequently detected among HIV-uninfected volunteers. CONCLUSION: These results suggest that JCV shedding is enhanced by modest depressions in immune function during HIV infection. JCV shedding occurred in younger HIV-positive persons than in the healthy controls. As the common types of JCV excreted varied among ethnic groups, JCV genotypes associated with progressive multifocal leukoencephalopathy may reflect demographics of those infected patient populations.

  3. Pubertal development in HIV-infected African children on first-line antiretroviral therapy

    PubMed Central

    Szubert, Alexander J.; Musiime, Victor; Bwakura-Dangarembizi, Mutsawashe; Nahirya-Ntege, Patricia; Kekitiinwa, Adeodata; Gibb, Diana M.; Nathoo, Kusum; Prendergast, Andrew J.; Walker, A. Sarah

    2015-01-01

    Objectives: To estimate age at attaining Tanner stages in Ugandan/Zimbabwean HIV-infected children initiating antiretroviral therapy (ART) in older childhood and investigate predictors of delayed puberty, particularly age at ART initiation. Design: Observational analysis within a randomized trial. Methods: Tanner staging was assessed every 24 weeks from 10 years of age, menarche every 12 weeks and height every 4–6 weeks. Age at attaining different Tanner stages was estimated using normal interval regression, considering predictors using multivariable regression. Growth was estimated using multilevel models with child-specific intercepts and trajectories. Results: Median age at ART initiation was 9.4 years (inter-quartile range 7.8, 11.3) (n = 582). At the first assessment, the majority (80.2%) were in Tanner stage 1; median follow-up with staging was 2.8 years. There was a strong delaying effect of older age at ART initiation on age at attaining all Tanner stages (P < 0.05) and menarche (P = 0.02); in boys the delaying effect generally weakened with older age. There were additional significant delays associated with greater impairments in pre-ART height-for-age Z-score (P < 0.05) in both sexes and pre-ART BMI-for-age in girls (P < 0.05). There was no evidence that pre-ART immuno-suppression independently delayed puberty or menarche. However, older children/adolescents had significant growth spurts in intermediate Tanner stages, and were still significantly increasing their height when in Tanner stage 5 (P < 0.01). Conclusion: Delaying ART initiation until older childhood substantially delays pubertal development and menarche, independently of immuno-suppression. This highlights that factors other than CD4+, such as pubertal development, need consideration when making decisions about timing of ART initiation in older children. PMID:25710288

  4. Nevirapine Resistance in Previously Nevirapine-Unexposed HIV-1-Infected Kenyan Infants Initiating Early Antiretroviral Therapy

    PubMed Central

    Chohan, Bhavna H.; Tapia, Kenneth; Benki-Nugent, Sarah; Khasimwa, Brian; Ngayo, Musa; Maleche-Obimbo, Elizabeth; Wamalwa, Dalton; Overbaugh, Julie

    2015-01-01

    Abstract Nevirapine (NVP) resistance occurs frequently in infants following NVP use in prevention of mother-to-child transmission (PMTCT) regimens. However, among previously NVP-unexposed infants treated with NVP-antiretroviral therapy (ART), the development and impact of NVP resistance have not been well characterized. In a prospective clinical trial providing early ART to HIV-infected infants<5 months of age in Kenya (OPH03 study), we followed NVP-unexposed infants who initiated NVP-ART for 12 months. Viral loads were assessed and resistance determined using a population-based genotypic resistance assay. Of 99 infants screened, 33 had no prior NVP exposure, 22 of whom were initiated on NVP-ART. Among 19 infants with follow-up, seven (37%) infants developed resistance: one at 3 months and six at 6 months after ART initiation. The cumulative probability of NVP resistance was 5.9% at 3 months and 43.5% at 6 months. Baseline HIV RNA levels (p=0.7) and other characteristics were not associated with developing resistance. Post-ART, higher virus levels at visits preceding the detection of resistance were significantly associated with increased detection of resistance (p=0.004). Virus levels after 6 and 12 months of ART were significantly higher in infants with resistance than those without (p=0.007, p=0.030, respectively). Among infants without previous NVP exposure, development of NVP resistance was frequent and was associated with virologic failure during the first year of ART. Earlier development of NVP resistance in infants than in adults initiating NVP-ART may be due to longer viremia following ART or inadequate NVP levels resulting from NVP lead-in dosing. The development of NVP resistance may, in part, explain the superiority of protease inhibitor-based ART in infants. PMID:25819584

  5. Adherence and Viral Suppression among Infants and Young Children Initiating Protease Inhibitor-Based Antiretroviral Therapy

    PubMed Central

    Teasdale, Chloe A; Abrams, Elaine J; Coovadia, Ashraf; Strehlau, Renate; Martens, Leigh; Kuhn, Louise

    2012-01-01

    Background High levels of adherence to antiretroviral therapy (ART) are considered necessary to achieve viral suppression. We analyzed data from a cohort of HIV-infected children who were less than 2 years of age receiving protease inhibitor (PI)-based ART to investigate associations between viral suppression and adherence ascertained using different methods. Methods Data were from the pre-randomization phase of a clinical trial in South Africa of HIV-infected children initiating either ritonavir-boosted lopinavir (LPV/r)- or ritonavir-based ART. At scheduled visits during the first 24 weeks of enrollment, study pharmacists measured quantities of medications returned (MR) to the clinic. Caregivers answered questionnaires on missed doses and adherence barriers. Associations between adherence and viral suppression (HIV-1 RNA <400 copies/mL) were investigated by regimen. Results By 24 weeks, 197/269 (73%) children achieved viral suppression. There was no association between viral suppression and caregiver reported missed doses or adherence barriers. For children receiving the LPV/r-based regimen, MR adherence to each of the three drugs in the regimen (LPV/r, lamivudine or stavudine) individually or together was associated with viral suppression at different adherence thresholds. For example, <85% adherence to any of the three medications significantly increased odds of lack of viral suppression (Odds Ratio [OR] 2.30 [95% CI: 1.30–4.07], p=.004). In contrast, for children receiving the ritonavir-based regimen, there was no consistent pattern of association between MR and viral suppression. Conclusions Caregiver reports of missed doses did not predict virologic response to treatment. Pharmacist medication reconciliation correlated strongly with virologic response for children taking a LPV/r-based regimen and appears to be a valid method for measuring pediatric adherence. PMID:23249913

  6. Immunologic Risk Factors for Early Mortality After Starting Antiretroviral Therapy in HIV-Infected Zambian Children

    PubMed Central

    Rainwater-Lovett, Kaitlin; Nkamba, Hope C.; Mubiana-Mbewe, Mwangelwa; Moore, Carolyn Bolton

    2013-01-01

    Abstract To explore immunologic risk factors for death within 90 days of highly active antiretroviral therapy (HAART) initiation, CD4+ and CD8+ T cell subsets were measured by flow cytometry and characterized by logistic regression in 149 Zambian children between 9 months and 10 years of age enrolled in a prospective, observational study of the impact of HAART on measles immunity. Of 21 children who died during follow-up, 17 (81%) had known dates of death and 16 (76%) died within 90 days of initiating HAART. Young age and low weight-for-age z-scores were associated with increased risks of mortality within 90 days of starting HAART, whereas CD4+ T cell percentage was not associated with mortality. After adjusting for these factors, each 10% increase in CD8+ effector T cells increased the odds of overall mortality [OR=1.43 (95% CI: 1.08, 1.90)] and was marginally associated with early mortality [OR=1.29 (95% CI: 0.97, 1.72)]. Conversely, each 10% increase in CD4+ central memory T cells decreased the odds of overall [OR=0.06 (95% CI: 0.01, 0.59)] and early mortality [OR=0.09 (95% CI: 0.01, 0.97)]. Logistic regression prediction models demonstrated areas under the receiver-operator characteristic curves of ≥85% for early and overall mortality, with bootstrapped sensitivities of 82–85% upon validation, supporting the predictive accuracy of the models. CD4+ and CD8+ T cell subsets may be more accurate predictors of early mortality than CD4+ T cell percentages and could be used to identify children who would benefit from more frequent clinical monitoring after initiating HAART. PMID:23025633

  7. Incident Pregnancy and Time to Death or AIDS among HIV-Positive Women Receiving Antiretroviral Therapy

    PubMed Central

    Westreich, Daniel; Maskew, Mhairi; Evans, Denise; Firnhaber, Cindy; Majuba, Pappie; Sanne, Ian

    2013-01-01

    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. PMID:23520489

  8. Improving performance of Zambia Defence Force antiretroviral therapy providers: evaluation of a standards-based approach

    PubMed Central

    Kim, Young Mi; Banda, Joseph; Kanjipite, Webby; Sarkar, Supriya; Bazant, Eva; Hiner, Cyndi; Tholandi, Maya; Reinhardt, Stephanie; Njobvu, Panganani Dalisani; Kols, Adrienne; Benavides, Bruno

    2013-01-01

    ABSTRACT Background: The Zambia Defence Force (ZDF) has applied the Standards-Based Management and Recognition (SBM-R®) approach, which uses detailed performance standards, at some health facilities to improve HIV-related services offered to military personnel and surrounding civilian communities. This study examines the effectiveness of the SBM-R approach in improving facility readiness and provider performance at ZDF facilities. Methods: We collected data on facility readiness and provider performance before and after the 2010–2012 intervention at 4 intervention sites selected for their relatively poor performance and 4 comparison sites. Assessors observed whether each facility met 16 readiness standards and whether providers met 9 performance standards during consultations with 354 returning antiretroviral therapy (ART) clients. We then calculated the percentages of criteria achieved for each readiness and performance standard and conducted bivariate and multivariate analyses of provider performance data. Results: Facilities' ART readiness scores exceeded 80% before the intervention at both intervention and comparison sites. At endline, scores improved on 4 facility readiness standards in the intervention group but on only 1 standard in the comparison group. Multivariate analysis found that the overall provider performance score increased significantly in the intervention group (from 58% to 84%; P<.01) but not in the comparison group (from 62% to 70%). The before-and-after improvement in scores was significantly greater among intervention sites than among comparison sites for 2 standards—initial assessment of the client's condition and nutrition counseling. Conclusion: The standards-based approach, which involved intensive and mutually reinforcing intervention activities, showed modest improvements in some aspects of providers' performance during ART consultations. Further research is needed to determine whether improvements in provider performance affect

  9. Equity in adherence to antiretroviral therapy among economically vulnerable adolescents living with HIV in Uganda

    PubMed Central

    Bermudez, Laura Gauer; Jennings, Larissa; Ssewamala, Fred M.; Nabunya, Proscovia; Mellins, Claude; McKay, Mary

    2016-01-01

    ABSTRACT Studies from sub-Saharan Africa indicate that children made vulnerable by poverty have been disproportionately affected by HIV with many exposed via mother-to-child transmission. For youth living with HIV, adherence to life-saving treatment regimens are likely to be affected by the complex set of economic and social circumstances that challenge their families and also exacerbate health problems. Using baseline data from the National Institute of Child and Human Development (NICHD) funded Suubi+Adherence study, we examined the extent to which individual and composite measures of equity predict self-reported adherence among Ugandan adolescents aged 10–16 (n = 702) living with HIV. Results showed that greater asset ownership, specifically familial possession of seven or more tangible assets, was associated with greater odds of self-reported adherence (OR 1.69, 95% CI: 1.00–2.85). Our analyses also indicated that distance to the nearest health clinic impacts youth’s adherence to an ARV regimen. Youth who reported living nearest to a clinic were significantly more likely to report optimal adherence (OR 1.49, 95% CI: 0.92–2.40). Moreover, applying the composite equity scores, we found that adolescents with greater economic advantage in ownership of household assets, financial savings, and caregiver employment had higher odds of adherence by a factor of 1.70 (95% CI: 1.07–2.70). These findings suggest that interventions addressing economic and social inequities may be beneficial to increase antiretroviral therapy (ART) uptake among economically vulnerable youth, especially in sub-Saharan Africa. This is one of the first studies to address the question of equity in adherence to ART among economically vulnerable youth with HIV. PMID:27392003

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

    PubMed

    Subiela, José D; Dapena, Elida

    2016-03-01

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

  11. Outcomes of antiretroviral therapy among younger versus older adolescents and adults in an urban clinic, Zimbabwe

    PubMed Central

    Takarinda, K. C.; Owiti, P.; Mutasa-Apollo, T.; Mugurungi, O.; Buruwe, L.; Reid, A. J.

    2016-01-01

    Setting: A non-governmental organisation-supported clinic offering health services including antiretroviral therapy (ART). Objective: To compare ART retention between younger (age 10–14 years) vs. older (age 15–19 years) adolescents and younger (age 20–29 years) vs. older (age ⩾30 years) adults and determine adolescent- and adult-specific attrition-associated factors among those initiated on ART between 2010 and 2011. Design: Retrospective cohort study. Results: Of 110 (7%) adolescents and 1484 (93%) adults included in the study, no differences in retention were observed between younger vs. older adolescents at 6, 12 and 24 months. More younger adolescents were initiated with body mass index <16 kg/m2 compared with older adolescents (64% vs. 47%; P = 0.04). There were more females (74% vs. 52%, P < 0.001) and fewer patients initiating ART with CD4 count ⩽350 cells/mm3 (77% vs. 81%, P = 0.007) among younger vs. older adults. Younger adults demonstrated more attrition than older adults at all time-points. No attrition risk factors were observed among adolescents. Attrition-associated factors among adults included being younger, having a lower CD4 count and advanced human immunodeficiency virus disease at initiation, and initiation on a stavudine-based regimen. Conclusion: Younger adults demonstrated greater attrition and may require more attention. We were unable to demonstrate differences in attrition among younger vs. older adolescents. Loss to follow-up was the main reason for attrition across all age groups. Overall, earlier presentation for ART care appears important for improved ART retention among adults. PMID:27358802

  12. Prevalence of Depressive Symptoms Amongst Highly Active Antiretroviral Therapy (HAART) Patients in AIDSRelief Uganda

    PubMed Central

    Atukunda, Ruth; Imakit, Richard; Memiah, Peter

    2013-01-01

    There is limited data on the prevalence of depression in HIV and AIDS patients in Sub-Saharan Africa and little resources have been allocated to address this issue. Depression affects patient adherence to treatment and predisposes patients to resistance which poses a public health threat. It also affects quality of life and productivity of patients. From August 2008 to March 2009, 731 patient adherence surveys were administered to assess disease, treatment knowledge and services received. The primary variable of interest was patients’ level of depressive symptoms score, constructed using factor analysis from five survey questions relating to: sadness, need to be alone, hopelessness and confusion and was categorized as no depressive symptoms (score 0), low depressive symptoms (score 1-2), moderate depressive symptoms (score 3-4) and high depressive symptoms (score 5-10). Majority of the patients on highly active antiretroviral therapy (HAART) (59%) were found to have depressive symptoms and this was more among women than men (66% vs 43%). There was some association of depressive symptoms with non-disclosure (70% of those who had not disclosed had depressive symptoms compared to 53% among those who had disclosed). There is a high prevalence of depressive symptoms among adult patients on HAART. There is need for in-depth evaluation to find out the root causes of depressive symptoms among HAART patients in AIDSRelief clinics. There is need to integrate mental health management in HIV care and treatment as well as training the existing health workers on mental health management. PMID:28299108

  13. Quality of life, psychosocial health, and antiretroviral therapy among HIV-positive women in Zimbabwe.

    PubMed

    Patel, Rena; Kassaye, Seble; Gore-Felton, Cheryl; Wyshak, Grace; Kadzirange, Gerard; Woelk, Godfrey; Katzenstein, David

    2009-12-01

    Little is known about the psychosocial impact of antiretroviral therapy (ART) among women in sub-Saharan Africa. Therefore, we conducted a cross-sectional study in Zimbabwe to assess the impact of ART on HIV-positive women's health-related quality of life, using the Medical Outcomes Study-HIV Quality of Life (QOL) questionnaire. Additionally, we assessed socio-demographics, reproductive and sexual health, HIV-related history, disclosure, social stigma, self-esteem, and depression. Structured interviews were conducted with 200 HIV-positive women and categorized into three groups by treatment: (1) Group 1 (n=31) did not meet clinical or laboratory criteria to begin treatment; (2) Group 2 (n=73) was eligible to begin treatment but awaiting initiation of treatment; and (3) Group 3 (n=96) was on ART for a median of 13 months. The women had similar socio-demographic characteristics but varied significantly in clinical characteristics. Women on ART reported fewer AIDS-related symptoms in the last week and year and had higher current and lower baseline CD4 counts compared to women not on ART. On most QOL domains women on ART reported higher mean scores as compared to women not on ART (p<0.01). Additionally, women on ART reported less depression compared to women not on ART (p<0.001). Between the two groups of women not on ART, unexpectedly, there were no significant differences in their scores for QOL or depression. Thus, Zimbabwean women living with HIV experience better overall QOL and lower depression on ART. Altogether, our findings suggest that ART delivery in resource-poor communities can enhance overall QOL as well as psychosocial functioning, which has wide-ranging public health implications.

  14. High-intensity cannabis use and adherence to antiretroviral therapy among people who use illicit drugs in a Canadian setting.

    PubMed

    Slawson, Gregory; Milloy, M-J; Balneaves, Lynda; Simo, Annick; Guillemi, Silvia; Hogg, Robert; Montaner, Julio; Wood, Evan; Kerr, Thomas

    2015-01-01

    Cannabis is increasingly prescribed clinically and utilized by people living with HIV/AIDS (PLWHA) to address symptoms of HIV disease and to manage side effects of antiretroviral therapy (ART). In light of concerns about the possibly deleterious effect of psychoactive drug use on adherence to ART, we sought to determine the relationship between high-intensity cannabis use and adherence to ART among a community-recruited cohort of HIV-positive illicit drug users. We used data from the ACCESS study, an ongoing prospective cohort study of HIV-seropositive illicit drug users linked to comprehensive ART dispensation records in a setting of universal no-cost HIV care. We estimated the relationship between at least daily cannabis use in the last 6 months, measured longitudinally, and the likelihood of optimal adherence to ART during the same period, using a multivariate linear mixed-effects model accounting for relevant socio-demographic, behavioral, clinical and structural factors. From May 2005 to May 2012, 523 HIV-positive illicit drug users were recruited and contributed 2,430 interviews. At baseline, 121 (23.1 %) participants reported at least daily cannabis use. In bivariate and multivariate analyses we did not observe an association between using cannabis at least daily and optimal adherence to prescribed HAART (Adjusted Odds Ratio = 1.12, 95 % Confidence Interval [95 % CI]: 0.76-1.64, p value = 0.555.) High-intensity cannabis use was not associated with adherence to ART. These findings suggest cannabis may be utilized by PLWHA for medicinal and recreational purposes without compromising effective adherence to ART.

  15. Dose-response Effect of Incarceration Events on Nonadherence to HIV Antiretroviral Therapy Among Injection Drug Users

    PubMed Central

    Milloy, M. J.; Kerr, Thomas; Buxton, Jane; Rhodes, Tim; Guillemi, Silvia; Hogg, Robert; Montaner, Julio

    2011-01-01

    (See the editorial commentary by Flanigan and Beckwith, on pages 1201–3.) Background. Although some studies have identified impressive clinical gains for incarcerated HIV-seropositive injection drug users (IDUs) undergoing antiretroviral therapy (ART), the effect of incarceration on adherence to ART remains undetermined. Methods. We used data from a long-term community-recruited cohort of HIV-seropositive IDUs, including comprehensive ART dispensation records, in a setting where HIV care is free. We estimated the relationship between the cumulative burden of incarceration, measured longitudinally, and the odds of <95% adherence to ART, with use of multivariate modeling. Results. From 1996 through 2008, 490 IDUs were recruited and contributed 2220 person-years of follow-up; 271 participants (55.3%) experienced an incarceration episode, with the number of incarcerations totaling 1156. In a multivariate model, incarceration had a strong dose-dependent effect on the likelihood of nonadherence to ART: 1-2 incarceration events (adjusted odds ratio [AOR], 1.49; 95% confidence interval [95% CI], 1.03–2.05), 3–5 events (AOR, 2.48; 95% CI, 1.62–3.65), and > 5 events (AOR, 3.11; 95% CI, 1.86–4.95). Conclusions. Among HIV-seropositive IDUs receiving ART, an increasing burden of incarceration was associated with poorer adherence in a dose-dependent fashion. Our findings support improved adherence support for HIV-seropositive IDUs experiencing incarceration. PMID:21459814

  16. The Metabolic and Cardiovascular Consequences of Obesity in Persons with HIV on Long-term Antiretroviral Therapy

    PubMed Central

    Koethe, John R.; Grome, Heather; Jenkins, Cathy A.; Kalams, Spyros A.; Sterling, Timothy R.

    2015-01-01

    Objective This study assessed the effect of obesity on metabolic and cardiovascular disease risk factors in HIV-infected adults on antiretroviral therapy (ART) with sustained virologic suppression. Design Observational, comparative cohort study with three group-matched arms: 35 non-obese and 35 obese HIV-infected persons on efavirenz, tenofovir, and emtricitabine with plasma HIV-1 RNA <50 copies/ml for >2 years, and 30 obese HIV-uninfected controls. Subjects did not have diabetes or known cardiovascular disease. Methods We compared glucose tolerance, serum lipids, brachial artery flow mediated dilation (FMD), carotid intima-media thickness (cIMT), and soluble inflammatory and vascular adhesion markers between non-obese and obese HIV-infected subjects, and between obese HIV-infected and HIV-uninfected subjects, using Wilcoxon rank sum tests and multivariate linear regression. Results The cohort was 52% male and 48% non-white. Non-obese and obese HIV-infected subjects did not differ by clinical or demographic characteristics. HIV-uninfected obese controls were younger than obese HIV-infected subjects and less likely to smoke (p≤0.03 for both). Among HIV-infected subjects, obesity was associated with greater insulin release, lower insulin sensitivity, and higher serum hsCRP, IL-6, and TNF-α receptor 1 levels (p<0.001), but similar lipid profiles, sCD14, sCD163, ICAM-1 and VCAM-1, and cIMT and FMD. In contrast, HIV-infected subjects had adverse lipid changes, and greater circulating ICAM-1, VCAM-1 and sCD14, compared to HIV-uninfected controls after adjusting for age and other factors. Conclusions Obesity impairs glucose metabolism and contributes to circulating hsCRP, IL-6, and TNF-α receptor 1 levels, but has few additive effects on dyslipidemia and endothelial activation, in HIV-infected adults on long-term ART. PMID:26418084

  17. Weight status and associated factors among HIV-infected people on antiretroviral therapy in rural Dikgale, Limpopo, South Africa

    PubMed Central

    Alberts, Marianne

    2016-01-01

    Background Underweight in human immunodeficiency virus (HIV)-infected people on antiretroviral therapy (ART) complicates the management of HIV infection and contributes to mortality, whereas overweight increases the risk of cardiovascular disease (CVD). Aim The study determined weight status and associated factors in people with HIV infection receiving ART. Setting Rural primary health care clinics in Dikgale, Limpopo province, South Africa. Methods A cross-sectional study in which data were collected using the World Health Organization (WHO) stepwise approach to surveillance (STEPS) questionnaire and calculated using WHO analysis programmes guide. Weight and height were measured using standard WHO procedures, and body mass index was calculated as weight (kg)/height (m2). Data on ART duration were extracted from patients’ files. CD4 lymphocyte counts and viral load were determined using standard laboratory techniques. Results Of the 214 participants, 8.9%, 54.7% and 36.4% were underweight, normal weight and overweight, respectively. Physical activity (OR: 0.99, p = 0.001) and male gender (OR: 0.29, p = 0.04) were negatively associated with overweight. Men who used tobacco were more likely to be underweight than non-tobacco users (OR: 10.87, p = 0.02). Neither ART duration nor viral load or CD4 count was independently associated with underweight or overweight in multivariate analysis. Conclusion A high proportion of people on ART were overweight and a smaller proportion underweight. There is a need to simultaneously address the two extreme weight problems in this vulnerable population through educating them on benefits of avoiding tobacco, engaging in physical activity and raising awareness of CVD risk. PMID:28155318

  18. Before and after the earthquake: a case study of attrition from the HIV antiretroviral therapy program in Haiti

    PubMed Central

    Puttkammer, Nancy H.; Zeliadt, Steven B.; Balan, Jean Gabriel; Baseman, Janet G.; Destiné, Rodney; Domerçant, Jean Wysler; Duvilaire, Jean Marie; Raphael, Nernst Atwood; Sherr, Kenneth; Yuhas, Krista; Barnhart, Scott

    2014-01-01

    Background On January 12, 2010, a devastating 7.0 magnitude earthquake struck the West Department of Haiti, killing more than 200,000 people and injuring or displacing many more. This disaster threatened continuity of HIV care and treatment services. Objectives This case study examined the effect of the devastating 2010 earthquake in Haiti on attrition from the HIV antiretroviral therapy (ART) program. Design The study triangulated retrospective data from existing sources, including: 1) individual-level longitudinal patient data from an electronic medical record for ART patients at two large public sector departmental hospitals differently affected by the earthquake; and 2) aggregate data on the volume of HIV-related services delivered at the two hospitals before and after the earthquake. Methods The study compared ART attrition and service delivery in Jacmel, a site in the ‘very strong’ zone of earthquake impact, and in Jérémie, a site in the ‘light’ zone of earthquake impact. The analysis used time-to-event analysis methods for the individual-level patient data, and descriptive statistical methods for the aggregate service delivery data. Results Adjusted ART attrition risk was lower at the hospital in Jacmel after vs. before the earthquake (HR=0.51; p=0.03), and was lower in Jacmel vs. Jérémie both before (HR=0.55; p=0.01) and after the earthquake (HR=0.35; p=0.001). The number of new ART patient enrollments, new HIV patient registrations, and HIV clinical visits dropped notably in Jacmel immediately after the earthquake, but then rapidly rebounded. On average, there was no change in new ART enrollments per month after vs. before the earthquake at either site. Conclusion These findings underscore the resilience of Haitian ART providers and patients, and contribute evidence that it is possible to maintain continuity of ART services even in the context of a complex humanitarian crisis. PMID:25103146

  19. Low Baseline CD4+ Count Is Associated With Greater Bone Mineral Density Loss After Antiretroviral Therapy Initiation

    PubMed Central

    Grant, Philip M.; Kitch, Douglas; McComsey, Grace A.; Dube, Michael P.; Haubrich, Richard; Huang, Jeannie; Riddler, Sharon; Tebas, Pablo; Zolopa, Andrew R.; Collier, Ann C.; Brown, Todd T.

    2013-01-01

    Background. Bone mineral density (BMD) decreases 2%–6% in the 2 years after antiretroviral therapy (ART) initiation. Pre-ART immune deficiency and early immune recovery may contribute to this loss. Methods. We pooled data from 3 studies of ART initiation in treatment-naive patients in which serial whole-body dual-energy X-ray absorptiometry scans were performed. We used linear regression to evaluate effects of baseline CD4+ and 16-week CD4+ change (both absolute and relative) on 96-week total BMD change from baseline. We performed multivariable linear regression to assess associations between baseline variables of age, sex, race/ethnicity, body mass index (BMI), hepatitis C status, parent study, human immunodeficiency virus type 1 (HIV-1) RNA level, and assignment to a protease inhibitor (PI)– or tenofovir-containing regimen on 96-week total BMD change. Results. The included 796 subjects had mean 96-week total BMD loss of 2.0%. In multivariable analysis, baseline CD4+ cell count was significantly associated with 96-week BMD loss; individuals with baseline CD4+ <50 cells/µL lost significantly more BMD compared to those with CD4+ ≥500 cells/µL. A greater relative, but not absolute, 16-week increase in CD4+ count was significantly associated with greater declines in BMD, but not after controlling for baseline CD4+ count. In multivariable analysis, older age, female sex, lower BMI, higher HIV-1 RNA levels, and PI and tenofovir assignment were also associated with greater BMD decline. Conclusions. Low pretreatment CD4+ count, but not greater CD4+ count increase, is a strong and independent risk factor for bone loss after ART initiation. ART initiation at higher CD4+ counts may reduce the burden of osteoporosis and fragility fractures. PMID:23943825

  20. Effects of a switch from tenofovir- to abacavir-based antiretroviral therapy, with or without atazanavir, on renal function

    PubMed Central

    Guillemi, Silvia A; Ling, Sean H; Dahlby, Julia S; Yip, Benita; Zhang, Wendy; Hull, Mark W; Lima, Viviane Dias; Hogg, Robert S; Werb, Ronald; Montaner, Julio S; Harris, Marianne

    2016-01-01

    Introduction Tenofovir disoproxil fumarate (TDF)–associated renal dysfunction may abate when TDF is replaced with abacavir (ABC). The extent to which the third drug atazanavir contributes to renal dysfunction is unclear. Methods A retrospective analysis was conducted on adults who had plasma viral load (pVL)<200 copies/mL for≥six months while receiving TDF/lamivudine (3TC) – or TDF/emtricitabine (FTC)–based antiretroviral therapy (ART), then switched to ABC/3TC while retaining the third drug in the ART regimen. CD4, pVL, creatinine, estimated glomerular filtration rate (eGFR), serum phosphorus, urine albumin to creatinine ratio and serum lipids were compared between pre-switch baseline and 3, 6 and 12 months after the switch to ABC. Results A total of 286 patients switched from TDF to ABC between 2004 and 2014: 232 (81%) male, median age 48 years (interquartile range (IQR) 42, 56). The third drug was atazanavir (± ritonavir) in 141 (49%) cases. The pVL was<50 copies/mL in 93 to 96% at all time points. Median serum creatinine was 93 µmol/L (IQR 80–111) at baseline and decreased to 88 µmol/L (IQR 78–98) at 12 months after the switch to ABC. Median eGFR increased from 74 (IQR 60–88) mL/min at baseline to 80 mL/min (IQR 69–89) at 12 months. Results were not significantly different between patients on atazanavir versus those on another third drug. Conclusions Viral suppression was maintained among patients who switched from TDF/3TC or TDF/FTC to ABC/3TC. Serum creatinine and eGFR improved up to 12 months after switching to ABC/3TC, irrespective of whether or not patients were also receiving atazanavir±ritonavir. PMID:27624144

  1. Lipopolysaccharide, immune activation, and liver abnormalities in HIV/hepatitis B virus (HBV)-coinfected individuals receiving HBV-active combination antiretroviral therapy.

    PubMed

    Crane, Megan; Avihingsanon, Anchalee; Rajasuriar, Reena; Velayudham, Pushparaj; Iser, David; Solomon, Ajantha; Sebolao, Baotuti; Tran, Andrew; Spelman, Tim; Matthews, Gail; Cameron, Paul; Tangkijvanich, Pisit; Dore, Gregory J; Ruxrungtham, Kiat; Lewin, Sharon R

    2014-09-01

    We investigated the relationship between microbial translocation, immune activation, and liver disease in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection. Lipopolysaccharide (LPS), soluble CD14, CXCL10, and CCL-2 levels were elevated in patients with HIV/HBV coinfection. Levels of LPS, soluble CD14, and CCL-2 declined following receipt of HBV-active combination antiretroviral therapy (cART), but the CXCL10 level remained elevated. No markers were associated with liver disease severity on liver biopsy (n = 96), but CXCL10, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α, and interferon γ (IFN-γ) were all associated with elevated liver enzyme levels during receipt of HBV-active cART. Stimulation of hepatocyte cell lines in vitro with IFN-γ and LPS induced a profound synergistic increase in the production of CXCL10. LPS may contribute to liver disease via stimulating persistent production of CXCL10.

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

    PubMed Central

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

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. PMID:26082630

  3. Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India

    PubMed Central

    Khan, Samsuddin; Das, Mrinalini; Andries, Aristomo; Deshpande, Alaka; Mansoor, Homa; Saranchuk, Peter; Isaakidis, Petros

    2014-01-01

    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 monitoring and HIV

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

    PubMed

    Dossou-Yovo, Flore; Mamadou, Godefroy; Soudy, Imar Djibrine; Limas-Nzouzi, Nicolas; Miantezila, Joe; Desjeux, Jehan-François; Eto, Bruno

    2014-01-01

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

  5. Metronidazole or Cotrimoxazole Therapy Is Associated with a Decrease in Intestinal Bioavailability of Common Antiretroviral Drugs

    PubMed Central

    Dossou-Yovo, Flore; Mamadou, Godefroy; Soudy, Imar Djibrine; Limas-Nzouzi, Nicolas; Miantezila, Joe; Desjeux, Jehan-François; Eto, Bruno

    2014-01-01

    Metronidazole (MTZ) and Cotrimoxazole (CTX) are used in HIV/AIDS patients eligible for antiretroviral treatment. The objective of this animal study was to determine whether pre-treatment with antibiotics affects the intestinal bioavailability of Atazanavir (ATV) and Ritonavir (RTV). After oral administration of 1 mg MTZ and CTX for 7 days, the rat colonic mucosa were analyzed for mucus thickness or placed in Ussing chambers to measure ATV and RTV net transepithelial fluxes (Jnet). 1. In control rats, the mucus thickness was 43.3±7.6 µm and 40.7±6.9 µm, in proximal and distal colon, respectively. In proximal colon, the thickness was 57.2±8.8 and 58.2±6.9 µm after MTZ and CTX, respectively whereas in distal colon, the thickness was 121.1±38.4 and 170.5±35.0 µm (P<0.05) respectively. 2. Transepithelial conductance was reduced after MTZ or CTX in the proximal and distal colon. 3. In control, net ATV secretion was observed both in proximal (−0.36±0.02 µg.hr−1 cm−2) and distal colon (−0.30±0.08 µg.hr−1 cm−2). After MTZ and CTX, it was increased in the proximal colon by two 2 fold and 4 fold, respectively and in the distal colon by 3 fold and 5 fold, respectively. 4. In control, there was no net active RTV transport either in proximal (+0.01±0.01 µg.hr−1 cm−2) or distal colon (+0.04±0.01 µg.hr−1 cm−2). After MTZ and CTX, secretion was increased 5 fold and 10 fold, respectively, in the proximal colon and two fold and 5 fold, respectively in the distal colon (p<0.001). In conclusion, after MTZ and CTX therapy, the mucus layer was enlarged, passive permeability was decreased and ATV and RTV were actively secreted by the colonic epithelium suggesting that, in rat, the intestinal bioavailability of ATV and RTV is impaired after antibiotic therapy. PMID:24587140

  6. Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence.

    PubMed

    Oladele, Rita O; Akanmu, Alani S; Nwosu, Augustina O; Ogunsola, Folasade T; Richardson, Malcolm D; Denning, David W

    2016-03-01

    Background.  Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria. Methods.  Sera were collected from 214 consenting HIV-infected participants with CD4(+) counts <250 cells/mm(3), irrespective of their antiretroviral therapy (ART) status, between November 2014 and May 2015. A cryptococcal antigen (CrAg) lateral flow assay was used for testing. Pertinent clinical data were obtained from patients and their case notes. Results.  Of the 214 participants, females (124; 57.9%) outnumbered males. Mean age was 41.3 ± 9.4 (standard deviation) years. The majority (204; 95.3%) were ART experienced. The median CD4(+) cell count was 160 cells/mm(3) (interquartile range, 90-210). The overall seroprevalence of cryptococcal antigenemia was 8.9% (19 of 214); 6 of 61 (9.8%) in those with CD4(+) cell counts <100 cells/mm(3), 4 of 80 (5.0%) in the 100-200 group, and 9 of 73 (12.3%) in 200-250 cells/mm(3) group. Among ART-naive patients, 1 of 10 (10%) was CrAg positive. Twenty-seven of 214 (12.6%) had associated oral thrush. Potential baseline meningitis symptoms (3 of 214 [1.4%] experienced neck pain or stiffness and 21 of 214 [9.8%] experienced headache) were common in the study group, but the result was not statistically significant in relation to CrAg positivity. Two of 19 (10.5%) CrAg-positive patients died, 10 of 19 (52.6%) were lost to follow up, and 7 of 19 (36.8%) were alive. Empirical fluconazole was routinely given to those with low CD4 counts <100 cells/mm(3), which was unrelated to CrAg positivity (P = .018). Conclusions.  We report a prevalence of 8.9% cryptococcal antigenemia in a setting where first-line antifungals are not readily available. We

  7. Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence

    PubMed Central

    Oladele, Rita O.; Akanmu, Alani S.; Nwosu, Augustina O.; Ogunsola, Folasade T.; Richardson, Malcolm D.; Denning, David W.

    2016-01-01

    Background. Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria. Methods. Sera were collected from 214 consenting HIV-infected participants with CD4+ counts <250 cells/mm3, irrespective of their antiretroviral therapy (ART) status, between November 2014 and May 2015. A cryptococcal antigen (CrAg) lateral flow assay was used for testing. Pertinent clinical data were obtained from patients and their case notes. Results. Of the 214 participants, females (124; 57.9%) outnumbered males. Mean age was 41.3 ± 9.4 (standard deviation) years. The majority (204; 95.3%) were ART experienced. The median CD4+ cell count was 160 cells/mm3 (interquartile range, 90–210). The overall seroprevalence of cryptococcal antigenemia was 8.9% (19 of 214); 6 of 61 (9.8%) in those with CD4+ cell counts <100 cells/mm3, 4 of 80 (5.0%) in the 100–200 group, and 9 of 73 (12.3%) in 200–250 cells/mm3 group. Among ART-naive patients, 1 of 10 (10%) was CrAg positive. Twenty-seven of 214 (12.6%) had associated oral thrush. Potential baseline meningitis symptoms (3 of 214 [1.4%] experienced neck pain or stiffness and 21 of 214 [9.8%] experienced headache) were common in the study group, but the result was not statistically significant in relation to CrAg positivity. Two of 19 (10.5%) CrAg-positive patients died, 10 of 19 (52.6%) were lost to follow up, and 7 of 19 (36.8%) were alive. Empirical fluconazole was routinely given to those with low CD4 counts <100 cells/mm3, which was unrelated to CrAg positivity (P = .018). Conclusions. We report a prevalence of 8.9% cryptococcal antigenemia in a setting where first-line antifungals are not readily available. We recommend Cr

  8. Interaction between artemether-lumefantrine and nevirapine-based antiretroviral therapy in HIV-1-infected patients.

    PubMed

    Kredo, T; Mauff, K; Van der Walt, J S; Wiesner, L; Maartens, G; Cohen, K; Smith, P; Barnes, K I

    2011-12-01

    Artemether-lumefantrine and nevirapine-based antiretroviral therapy (ART) are the most commonly recommended first-line treatments for malaria and HIV, respectively, in Africa. Artemether, lumefantrine, and nevirapine are metabolized by the cytochrome P450 3A4 enzyme system, which nevirapine induces, creating potential for important drug interactions. In a parallel-design pharmacokinetic study, concentration-time profiles were obtained in two groups of HIV-infected patients: ART-naïve patients and those stable on nevirapine-based therapy. Both groups received the recommended artemether-lumefantrine dose. Patients were admitted for intense pharmacokinetic sampling (0 to 72 h) with outpatient sampling until 21 days. Concentrations of lumefantrine, artemether, dihydroartemisinin, and nevirapine were determined by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The primary outcome was observed day 7 lumefantrine concentrations, as these are associated with therapeutic response in malaria. We enrolled 36 patients (32 females). Median (range) day 7 lumefantrine concentrations were 622 ng/ml (185 to 2,040 ng/ml) and 336 ng/ml (29 to 934 ng/ml) in the nevirapine and ART-naïve groups, respectively (P = 0.0002). The median artemether area under the plasma concentration-time curve from 0 to 8 h [AUC((0-8 h))] (P < 0.0001) and dihydroartemisinin AUC((60-68 h)) (P = 0.01) were lower in the nevirapine group. Combined artemether and dihydroartemisinin exposure decreased over time only in the nevirapine group (geometric mean ratio [GMR], 0.76 [95% confidence interval {CI}, 0.65 to 0.90]; P < 0.0001) and increased with the weight-adjusted artemether dose (GMR, 2.12 [95% CI, 1.31 to 3.45]; P = 0.002). Adverse events were similar between groups, with no difference in electrocardiographic Fridericia corrected QT and P-R intervals at the expected time of maximum lumefantrine concentration (T(max)). Nevirapine-based ART decreased artemether and

  9. Emergence of HIV Drug Resistance During First- and Second-Line Antiretroviral Therapy in Resource-Limited Settings

    PubMed Central

    Hosseinipour, Mina C.; Gupta, Ravindra K; Van Zyl, Gert; Eron, Joseph J.; Nachega, Jean B.

    2013-01-01

    Introduction Antiretroviral therapy (ART) in resource-limited settings has expanded in the last decade, reaching >8 million individuals and reducing AIDS mortality and morbidity. Continued success of ART programs will require understanding the emergence of HIV drug resistance patterns among individuals in whom treatment has failed and managing ART from both an individual and public health perspective. We review data on the emergence of HIV drug resistance among individuals in whom first-line therapy has failed and clinical and resistance outcomes of those receiving second-line therapy in resource-limited settings. Results Resistance surveys among patients initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based therapy suggest that 76%–90% of living patients achieve HIV RNA suppression by 12 months after ART initiation. Among patients with detectable HIV RNA at 12 months, HIV drug resistance, primarily due to M184V and NNRTI mutations, has been identified in 60%–72%, although the antiretroviral activity of proposed second-line regimens has been preserved. Complex mutation patterns, including thymidine-analog mutations, K65R, and multinucleoside mutations, are prevalent among cases of treatment failure identified by clinical or immunologic methods. Approximately 22% of patients receiving second-line therapy do not achieve HIV RNA suppression by 6 months, with poor adherence, rather than HIV drug resistance, driving most failures. Major protease inhibitor resistance at the time of second-line failure ranges from 0% to 50%, but studies are limited. Conclusions Resistance of HIV to first-line therapy is predictable at 12 months when evaluated by means of HIV RNA monitoring and, when detected, largely preserves second-line therapy options. Optimizing adherence, performing resistance surveillance, and improving treatment monitoring are critical for long-term prevention of drug resistance. PMID:23687289

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

    PubMed Central

    López-Verdín, Sandra; Andrade-Villanueva, Jaime; Zamora-Perez, Ana Lourdes; Bologna-Molina, Ronell; Cervantes-Cabrera, José Justino

    2013-01-01

    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. PMID:24455222

  11. Altered natural history of AIDS-related opportunistic infections in the era of potent combination antiretroviral therapy.

    PubMed

    Jacobson, M A; French, M

    1998-01-01

    Since potent HIV protease inhibitor drugs became widely available in early 1996, many HIV clinical specialists have noted a marked decrease in the occurrence of AIDS-related opportunistic infections, and some specialists have reported unusual clinical presentations and manifestations of previously common opportunistic infections. In this article, we will review (1) the available data regarding recent trends in AIDS-related opportunistic infections incidence and manifestations, (2) clinical and immunologic evidence that potent combination antiretroviral therapy can alter the natural history of these opportunistic infections, and (3) the implications of these findings for current patient management practice and future clinical and immunologic research. As a preface to this review, however, it is important to acknowledge that any evaluation of the potential benefit of potent combination antiretroviral therapy in reducing the risk of serious opportunistic infections can be confounded by the concomitant use of prophylactic antimicrobial agents co-administered to prevent specific opportunistic infections. For example, it is standard clinical practice to administer trimethoprim-sulfamethoxazole (or another agent if trimethoprim-sulfamethoxazole cannot be tolerated) to patients with an absolute CD4 lymphocyte count < 200 cells/microliters, unexplained chronic fever or a history of oropharyngeal candidiasis. Similarly, specific antimicrobial prophylaxis to prevent disseminated Mycobacterium avium complex (MAC) infection in patients with absolute CD4 counts < 50 cells/microliters is also a widely recommended guideline. Although the relative efficacies of specific antimicrobial prophylaxis regimens in preventing the most common life- and sight-threatening opportunistic infectious complications of AIDS [Pneumocystis carinii pneumonia (PCP), disseminated MAC infection, and cytomegalovirus (CMV) retinitis] are now well established, these relative efficacies were established in

  12. Moresby food isn't good: food security, nutritional information and adherence to antiretroviral therapy in Papua New Guinea.

    PubMed

    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

    2011-01-01

    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.

  13. Epicardial Fat is Associated with Duration of Antiretroviral Therapy and Coronary Atherosclerosis: The Multicenter AIDS Cohort Study

    PubMed Central

    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

    2014-01-01

    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

  14. Assessing social preparedness for antiretroviral therapy in a generalized AIDS epidemic: a diffusion of innovations approach.

    PubMed

    Mitchell, Shannon K; Kelly, Kevin J; Potgieter, François E; Moon, Martha W

    2009-02-01

    Researchers conducted focus groups in the Eastern Cape Province of South Africa concerning AIDS and treatment options. Constituent groups included adults aged 25-45, HIV/AIDS caregivers, HIV-positive adults, nurses, rural elders, teenagers, and traditional healers. This pilot work aimed to gather early evidence on perceptions about the government's rollout of antiretroviral treatment (ART), identify potential barriers to success, and inform a subsequent pilot survey. Diffusion of innovations theory was used to interpret the data and helped identify potential obstacles to the ART rollout. AIDS stigma and a weakened healthcare system were negatively impacting the program. There was a lack of accurate knowledge about HIV/AIDS and antiretroviral treatment, with wide disparities among groups. Many people were not convinced that antiretroviral treatment is superior to other treatments, and a few people were afraid it was poisonous. There was no evidence that people were aware of the long-term difficulties of adherence to the regimen.

  15. Care of the HIV-positive patient in the emergency department in the era of highly active antiretroviral therapy.

    PubMed

    Venkat, Arvind; Piontkowsky, David M; Cooney, Robert R; Srivastava, Adarsh K; Suares, Gregory A; Heidelberger, Cory P

    2008-09-01

    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.

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

    PubMed

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

    2013-11-01

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

  17. Successful treatment of histiocytic sarcoma and concurrent HIV infection using a combination of CHOP and antiretroviral therapy.

    PubMed

    Narita, Kosuke; Noro, Rintaro; Seike, Masahiro; Matsumoto, Masaru; Fujita, Kazue; Matsumura, Jiro; Takahashi, Mikiko; Kawamoto, Masashi; Gemma, Akihiko

    2013-01-01

    Histiocytic sarcoma (HS) is a rare malignancy of soft tissues with an unknown etiology. The CHOP (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride and prednisolone) regimen is often adopted as first-line chemotherapy; however, its therapeutic efficacy against HS is usually low. We herein first present the case of a patient with HS who was infected with human immunodeficiency virus-1 (HIV) in whom treatment with a combination of CHOP and antiretroviral therapy (ART) was successful. The patient has been in complete remission for 12 months following the discontinuation of chemotherapy under continuous ART. This case report may help to promote further investigation of both HS and HIV-related malignancy.

  18. Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with HIV in Latin America

    PubMed Central

    Duarte, Horacio A.; Harris, D. Robert; Tassiopoulos, Katherine; Leister, Erin; Negrini, Silvia Fabiana Biason de Moura; Ferreira, Flavia Faleiro; Cruz, Maria Leticia Santos; Pinto, Jorge; Allison, Susannah; Hazra, Rohan

    2016-01-01

    Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of HIV-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with HIV viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load (<400 copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p=0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio=4.1, 95% confidence interval: 1.8–9.1; p<0.001), but not at enrollment or the 6-month visit (p>0.3). Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p<0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤0.005), but not at the 6-month visit (p=0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population. PMID:25743569

  19. Modulation of polyfunctional HIV-specific CD8 T cells in patients responding differently to antiretroviral therapy.

    PubMed

    Casetti, R; De Simone, G; Sacchi, A; Bordoni, V; Viola, D; Rinaldi, A; Agrati, C; Gioia, C; Martini, F

    2014-01-01

    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.

  20. Nevirapine versus efavirenz-based antiretroviral therapy regimens in antiretroviral-naive patients with HIV and tuberculosis infections in India: a pilot study

    PubMed Central

    2013-01-01

    Background Administration of rifampicin along with nevirapine reduces the plasma concentration of nevirapine in human immunodeficiency virus positive individuals with concomitant tuberculosis (HIV-TB patients). Nevirapine is a much cheaper drug than its alternative efavirenz, and might be beneficial in resource constrained settings. Methods A randomised open label trial was conducted at All India Institute of Medical Sciences, New Delhi, India. During the regimen of an antiretroviral therapy (ART), naive HIV-TB patients were randomly assigned to receive either nevirapine or efavirenz based ART with concomitant rifampicin based anti-tubercular therapy (ATT). Participants were followed for 24 months after starting ART. The end points were virological, immunological and clinical responses, and progression of HIV disease marked by failure of ART. Results Of the 135 HIV-TB patients, who were receiving rifampicin based ATT, 68 were selected randomly to receive efavirenz based ART and 67 to receive nevirapine based ART. The virological failure rates in the overall population, and the nevirapine and efavirenz groups were 14.1% (19/135); 14.9% (10/67) and 13.2% (9/68), respectively (p = 0.94). No significant difference was found between the groups in the rate of clinical, immunological or virological failures. The overall mortality was 17% with no significant difference between the two groups. Except for the lead in period on day 14, the mean nevirapine concentration remained above 3 mg/L. No association was found between plasma levels of nevirapine and incidence of unfavourable outcomes in this group. Conclusions Outcome of ART in HIV-TB patients on rifampicin based ATT showed no significant difference, irrespective of whether efavirenz or nevirapine was used. Therefore, nevirapine based ART could be an alternative in the resource limited settings in patients with HIV and tuberculosis co-infection. Trial registration NCT No. 01805258. PMID:24134449

  1. Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV

    PubMed Central

    Rosenbloom, Daniel I. S.; Goldstein, Edward; Hanhauser, Emily; Kuritzkes, Daniel R.

    2016-01-01

    Monitoring the efficacy of novel reservoir-reducing treatments for HIV is challenging. The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART) interruption studies are generally required. Here we introduce a set of mathematical and statistical modeling tools to aid in the design and interpretation of ART-interruption trials. We show how the likely size of the remaining reservoir can be updated in real-time as patients continue off treatment, by combining the output of laboratory assays with insights from models of reservoir dynamics and rebound. We design an optimal schedule for viral load sampling during interruption, whereby the frequency of follow-up can be decreased as patients continue off ART without rebound. While this scheme can minimize costs when the chance of rebound between visits is low, we find that the reservoir will be almost completely reseeded before rebound is detected unless sampling occurs at least every two weeks and the most sensitive viral load assays are used. We use simulated data to predict the clinical trial size needed to estimate treatment effects in the face of highly variable patient outcomes and imperfect reservoir assays. Our findings suggest that large numbers of patients—between 40 and 150—will be necessary to reliably estimate the reservoir-reducing potential of a new therapy and to compare this across interventions. As an example, we apply these methods to the two “Boston patients”, recipients of allogeneic hematopoietic stem cell transplants who experienced large reductions in latent infection and underwent ART-interruption. We argue that the timing of viral rebound was not particularly surprising given the information available before treatment cessation. Additionally, we show how other clinical data can be used to estimate the relative contribution that remaining HIV+ cells in the recipient versus newly infected cells from the donor made to the residual reservoir

  2. Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV.

    PubMed

    Hill, Alison L; Rosenbloom, Daniel I S; Goldstein, Edward; Hanhauser, Emily; Kuritzkes, Daniel R; Siliciano, Robert F; Henrich, Timothy J

    2016-04-01

    Monitoring the efficacy of novel reservoir-reducing treatments for HIV is challenging. The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART) interruption studies are generally required. Here we introduce a set of mathematical and statistical modeling tools to aid in the design and interpretation of ART-interruption trials. We show how the likely size of the remaining reservoir can be updated in real-time as patients continue off treatment, by combining the output of laboratory assays with insights from models of reservoir dynamics and rebound. We design an optimal schedule for viral load sampling during interruption, whereby the frequency of follow-up can be decreased as patients continue off ART without rebound. While this scheme can minimize costs when the chance of rebound between visits is low, we find that the reservoir will be almost completely reseeded before rebound is detected unless sampling occurs at least every two weeks and the most sensitive viral load assays are used. We use simulated data to predict the clinical trial size needed to estimate treatment effects in the face of highly variable patient outcomes and imperfect reservoir assays. Our findings suggest that large numbers of patients-between 40 and 150-will be necessary to reliably estimate the reservoir-reducing potential of a new therapy and to compare this across interventions. As an example, we apply these methods to the two "Boston patients", recipients of allogeneic hematopoietic stem cell transplants who experienced large reductions in latent infection and underwent ART-interruption. We argue that the timing of viral rebound was not particularly surprising given the information available before treatment cessation. Additionally, we show how other clinical data can be used to estimate the relative contribution that remaining HIV+ cells in the recipient versus newly infected cells from the donor made to the residual reservoir that

  3. Developing a predictive risk model for first-line antiretroviral therapy failure in South Africa

    PubMed Central

    Rohr, Julia K; Ive, Prudence; Horsburgh, C Robert; Berhanu, Rebecca; Shearer, Kate; Maskew, Mhairi; Long, Lawrence; Sanne, Ian; Bassett, Jean; Ebrahim, Osman; Fox, Matthew P

    2016-01-01

    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 to experience

  4. Clinically significant drug interactions among HIV-infected patients receiving antiretroviral therapy.

    PubMed

    So-Ngern, Apichot; Montakantikul, Preecha; Manosuthi, Weerawat

    2014-09-01

    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% (p<0.001). The three most common grade 4 CSDI were: a PI with simvastatin (n=24), simvastatin with gemfibrozil (n=24) and didanosine with allopurinol (n=2). The three most common grade 3 CSDI were: a PI with a statin drug except simvastatin (n=56), fenofibrate with a statin drug (n=28) and amlodipine with simvastatin (n=14). On multivariate analysis, risk factors associated with CSDI were: receiving a PI-based regimen (OR 14.44; 95% CI: 9.10-22.88), having dyslipidemia (OR 3.94; 95% CI: 1.89-8.21), having >5 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.

  5. Finding Meaning: HIV Self-Management and Wellbeing among People Taking Antiretroviral Therapy in Uganda

    PubMed Central

    Russell, Steve; Martin, Faith; Zalwango, Flavia; Namukwaya, Stella; Nalugya, Ruth; Muhumuza, Richard; Katongole, Joseph; Seeley, Janet

    2016-01-01

    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

  6. Kinetics of Microbial Translocation Markers in Patients on Efavirenz or Lopinavir/r Based Antiretroviral Therapy

    PubMed Central

    Vesterbacka, Jan; Nowak, Piotr; Barqasho, Babilonia; Abdurahman, Samir; Nyström, Jessica; Nilsson, Staffan; Funaoka, Hiroyuki; Kanda, Tatsuo; Andersson, Lars-Magnus; Gisslèn, Magnus; Sönnerborg, Anders

    2013-01-01

    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

  7. Incidence of Severe Neutropenia in HIV-Infected People Starting Antiretroviral Therapy in West Africa

    PubMed Central

    Leroi, Charline; Balestre, Eric; Messou, Eugene; Minga, Albert; Sawadogo, Adrien; Drabo, Joseph; Maiga, Moussa; Zannou, Marcel; Seydi, Moussa; Dabis, Francois; Jaquet, Antoine

    2017-01-01

    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

  8. Co-calibration of two self-reported measures of adherence to antiretroviral therapy.

    PubMed

    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

    2017-04-01

    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

  9. Chronic lung disease in HIV-infected children established on antiretroviral therapy

    PubMed Central

    Rylance, Jamie; Mchugh, Grace; Metcalfe, John; Mujuru, Hilda; Nathoo, Kusum; Wilmore, Stephanie; Rowland-Jones, Sarah; Majonga, Edith; Kranzer, Katharina; Ferrand, Rashida A

    2016-01-01

    Objective: Respiratory disease is a major cause of morbidity and mortality in HIV-infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function and exercise capacity among older children established on ART and an age-matched HIV-uninfected group. Design: A cross-sectional study in Zimbabwe of HIV-infected children aged 6–16 years receiving ART for over 6 months and HIV-uninfected children attending primary health clinics from the same area. Methods: Standardized questionnaire, spirometry, incremental shuttle walk testing, CD4+ cell count, HIV viral load and sputum culture for tuberculosis were performed. Results: A total of 202 HIV-infected and 150 uninfected participants (median age 11.1 years in each group) were recruited. Median age at HIV diagnosis and ART initiation was 5.5 (interquartile range 2.8–7.5) and 6.1 (interquartile range 3.6–8.4) years, respectively. Median CD4+ cell count was 726 cells/μl, and 79% had HIV viral load less than 400 copies/ml. Chronic respiratory symptoms were rare in HIV-uninfected children [n = 1 (0.7%)], but common in HIV-infected participants [51 (25%)], especially cough [30 (15%)] and dyspnoea [30 (15%)]. HIV-infected participants were more commonly previously treated for tuberculosis [76 (38%) vs 1 (0.7%), P < 0.001], had lower exercise capacity (mean incremental shuttle walk testing distance 771 vs 889 m, respectively, P < 0.001) and more frequently abnormal spirometry [43 (24.3%) vs 15 (11.5%), P = 0.003] compared with HIV-uninfected participants. HIV diagnosis at an older age was associated with lung function abnormality (P = 0.025). No participant tested positive for Mycobacterium tuberculosis. Conclusion: In children, despite ART, HIV is associated with significant respiratory symptoms and functional impairment. Understanding pathogenesis is key, as new treatment strategies are urgently required. PMID:27662546

  10. Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy

    PubMed Central

    Lee, Sulggi A.; Bacchetti, Peter; Chomont, Nicolas; Fromentin, Remi; Lewin, Sharon R.; O’Doherty, Una; Palmer, Sarah; Richman, Douglas D.; Siliciano, Janet D.; Yukl, Steven A.; Deeks, Steven G.; Burbelo, Peter D.

    2016-01-01

    Background A major challenge to HIV eradication strategies is the lack of an accurate measurement of the total burden of replication-competent HIV (the “reservoir”). We assessed the association of anti-HIV antibody responses and the estimated size of the reservoir during antiretroviral therapy (ART). Methods We evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems (LIPS) assay in relation to several blood-based HIV reservoir measures: total and 2-LTR DNA (rtPCR or droplet digital PCR); integrated DNA (Alu PCR); unspliced RNA (rtPCR), multiply-spliced RNA (TILDA), residual plasma HIV RNA (single copy PCR), and replication-competent virus (outgrowth assay). We also assessed total HIV DNA and RNA in gut-associated lymphoid tissue (rtPCR). Spearman correlations and linear regressions were performed using log-transformed blood- or tissue-based reservoir measurements as predictors and log-transformed antibody levels as outcome variables. Results Among 51 chronically HIV-infected ART-suppressed participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9 years), the most statistically significant associations were between antibody responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold-increase per two-fold RNA increase, P = 0.004) and between antibody responses to matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two-fold DNA increase, P = 0.003). However, these associations were not statistically significant after a stringent Bonferroni-adjustment of P<0.00045. Multivariate models including age and duration of ART did not markedly alter results. Conclusions Our findings suggest that anti-HIV antibody responses may reflect the size of the HIV reservoir during chronic treated HIV disease, possibly via antigen recognition in reservoir sites. Larger, prospective studies are needed to validate the utility of antibody levels as a measure of the total body burden of HIV

  11. High-Dose Vitamin D and Calcium Attenuates Bone Loss with Antiretroviral Therapy Initiation

    PubMed Central

    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.

    2015-01-01

    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

  12. Predictors of New Onset Distal Neuropathic Pain in HIV-infected Individuals in the Era of Combination Antiretroviral Therapy

    PubMed Central

    Malvar, Jemily; Vaida, Florin; Sanders, Chelsea Fitzsimons; Atkinson, J. Hampton; Bohannon, William; Keltner, John; Robinson-Papp, Jessica; Simpson, David M.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin; Fan, Juanjuan; Grant, Igor; Ellis, Ronald J.

    2015-01-01

    Despite modern combination antiretroviral therapy (CART), distal neuropathic pain (DNP) continues to affect many individuals with HIV infection. We evaluated risk factors for new onset DNP in the CNS Antiretroviral Therapy Effects Research (CHARTER) study, an observational cohort. Standardized, semi-annual clinical evaluations were administered at six U.S. sites. DNP was defined by using a clinician-administered instrument standardized across sites. All participants analyzed were free of DNP at study entry. New onset DNP was recorded at the first follow-up visit at which it was reported. Mixed effects logistic regression was used to evaluate potential predictors including HIV disease and treatment factors, demographics, medical comorbidities and neuropsychiatric factors. Among 493 participants, 131 (27%) reported new DNP over 2,306 visits during a median follow-up of 24 months [interquartile range (IQR) 12-42]. In multivariable regression, after adjusting for other covariates, significant entry predictors of new DNP were older age, female sex, current and past antiretroviral treatment, lack of virologic suppression, and lifetime history of opioid use disorder. During follow-up, more severe depression symptoms conferred a significantly elevated risk. The associations with opioid use disorders and depression reinforce the view that the clinical expression of neuropathic pain with peripheral nerve disease is strongly influenced by neuropsychiatric factors. Delineating such risk factors might help target emerging preventive strategies, for example, to individuals with a prior history of opioid use disorder, or might lead to new treatment approaches such as the use of tools to ameliorate depressed mood. PMID:25659067

  13. [Correction of anaemia in HIV-positive pregnant women receiving antiretroviral therapy].

    PubMed

    Krugova, L V; Vartanov, V Ia; Khutorskaia, N N; Lapteva, I V; Shifman, E M

    2012-01-01

    The analysis of 162 surgical deliveries cases in HIV-infected pregnant women was carried out. Anaemia type identification was based on blood analysis data and erythrocytes morphology. Ways of disease correction were defined. Recommendations for anemia prevention and treatment in HIV-infected patients receiving anti-retroviral drugs are presented.

  14. Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada

    PubMed Central

    Jenkins, Cathy A.; Lau, Bryan; Shepherd, Bryan E.; Justice, Amy C.; Tate, Janet P.; Buchacz, Kate; Napravnik, Sonia; Mayor, Angel M.; Horberg, Michael A.; Blashill, Aaron J.; Willig, Amanda; Wester, C. William; Silverberg, Michael J.; Gill, John; Thorne, Jennifer E.; Klein, Marina; Eron, Joseph J.; Kitahata, Mari M.; Sterling, Timothy R.; Moore, Richard D.

    2016-01-01

    Abstract The proportion of overweight and obese adults in the United States and Canada has increased over the past decade, but temporal trends in body mass index (BMI) and weight gain on antiretroviral therapy (ART) among HIV-infected adults have not been well characterized. We conducted a cohort study comparing HIV-infected adults in the North America AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to United States National Health and Nutrition Examination Survey (NHANES) controls matched by sex, race, and age over the period 1998 to 2010. Multivariable linear regression assessed the relationship between BMI and year of ART initiation, adjusting for sex, race, age, and baseline CD4+ count. Temporal trends in weight on ART were assessed using a generalized least-squares model further adjusted for HIV-1 RNA and first ART regimen class. A total of 14,084 patients from 17 cohorts contributed data; 83% were male, 57% were nonwhite, and the median age was 40 years. Median BMI at ART initiation increased from 23.8 to 24.8 kg/m2 between 1998 and 2010 in NA-ACCORD, but the percentage of those obese (BMI ≥30 kg/m2) at ART initiation increased from 9% to 18%. After 3 years of ART, 22% of individuals with a normal BMI (18.5–24.9 kg/m2) at baseline had become overweight (BMI 25.0–29.9 kg/m2), and 18% of those overweight at baseline had become obese. HIV-infected white women had a higher BMI after 3 years of ART as compared to age-matched white women in NHANES (p = 0.02), while no difference in BMI after 3 years of ART was observed for HIV-infected men or non-white women compared to controls. The high prevalence of obesity we observed among ART-exposed HIV-infected adults in North America may contribute to health complications in the future. PMID:26352511

  15. Generation of Neutralizing Antibodies and Divergence of SIVmac239 in Cynomolgus Macaques Following Short-Term Early Antiretroviral Therapy

    PubMed Central

    Parker, Joe; Uchtenhagen, Hannes; Sheik-Khalil, Enas; Taylor, Stephen; Pybus, Oliver G.; Mäkitalo, Barbro; Walther-Jallow, Lilian; Spångberg, Mats; Thorstensson, Rigmor; Achour, Adnane; Fenyö, Eva Maria; Stewart-Jones, Guillaume B. E.; Spetz, Anna-Lena

    2010-01-01

    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 104 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. However, early broad

  16. Baseline Cellular HIV DNA Load Predicts HIV DNA Decline and Residual HIV Plasma Levels during Effective Antiretroviral Therapy

    PubMed Central

    Andreis, Samantha; Mengoli, Carlo; Scaggiante, Renzo; Ferretto, Roberto; Manfrin, Vinicio; Cruciani, Mario; Giobbia, Mario; Boldrin, Caterina; Basso, Monica; Andreoni, Massimo; Palù, Giorgio; Sarmati, Loredana

    2012-01-01

    Cellular human immunodeficiency virus type 1 (HIV-1) DNA may be considered a marker of disease progression with significant predictive power, but published data on its correlation with plasma HIV RNA levels and CD4 counts in acute and chronic patients are not conclusive. We evaluated a cohort of 180 patients naïve for antiretroviral therapy before the beginning of treatment and after a virological response in order to define the indicators correlated with HIV DNA load decrease until undetectability. The following variables were evaluated as continuous variables: age, CD4 cell count and log10 HIV DNA level at baseline and follow-up, and baseline log10 HIV RNA level. Primary HIV infection at the start of therapy, an HIV RNA level at follow-up of <2.5 copies/ml, origin, gender, and transmission risk were evaluated as binary variables. The decline of HIV DNA values during effective therapy was directly related to baseline HIV DNA and HIV RNA values, to an increase in the number of CD4 cells, and to the achievement of an HIV RNA load of <2.5 copies/ml. An undetectable cellular HIV DNA load was achieved by 21.6% of patients at the follow-up time point and correlated significantly with lower baseline cellular HIV DNA values and with being in the primary stage of infection when therapy started. In conclusion, early treatment facilitated the achievement of undetectable levels of plasma viremia and cellular HIV DNA and a better recovery of CD4 lymphocytes. HIV DNA levels before and during highly active antiretroviral therapy may be used as a new tool for monitoring treatment efficacy. PMID:22135262

  17. Access to antiretroviral therapy among HIV/AIDS patients in Chiang Mai province, Thailand

    PubMed Central

    Himakalasa, Woraluck; Grisurapong, Siriwan; Phuangsaichai, Sasipen

    2013-01-01

    The objective of this study is to investigate the access to antiretroviral treatment among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Chiang Mai province, Thailand. Access to antiretroviral treatment is defined in terms of availability, affordability, and acceptability. The data for the study were collected during the period of April 1, 2012–May 31, 2012 from a sample of 380 HIV/AIDS patients in eight hospitals who had received antiretroviral treatment for more than 6 months at the time of data collection. The results of the study show that for most patients, the average traveling time to access health care was acceptable, but the nearly half day waiting time caused them to be absent from their work. In particular, it took longer for patients in the rural and lower income groups to access the treatment than the other groups. Their travel times and food costs relating to the treatment were found to be relatively high and therefore these patients had a higher tendency to borrow or seek financial assistance from their relatives. However, due to improvements in the access to treatment, most patients were satisfied with the services they received. The results imply that policy should be implemented to raise the potential of subdistrict hospitals where access to antiretroviral treatment is available, with participating HIV/AIDS patients acting as volunteers in providing services and other forms of health promotion to new patients. Privacy issues could be reduced if the antiretroviral treatment was isolated from other health services. Additionally, efforts to educate HIV/AIDS patients and society at large should be made. PMID:23986652

  18. Adherence to antiretroviral therapy in Nigeria: an overview of research studies and implications for policy and practice.

    PubMed

    Monjok, Emmanuel; Smesny, Andrea; Okokon, Ita B; Mgbere, Osaro; Essien, E James

    2010-01-01

    Both Human Immunodeficiency Virus (HIV) infection and AIDS remain major public health crises in Nigeria, a country which harbors more people living with HIV/AIDS than any country in the world, with the exception of South Africa and India. In response to the HIV pandemic, global and international health initiatives have targeted several countries, including Nigeria, for the expansion of antiretroviral therapy (ART) programs for the increasing number of affected patients. The success of these expanded ART initiatives depends on the treated individual's continual adherence to antiretroviral (ARV) drugs. Thirteen peer-reviewed studies concerning adherence to ART in Nigeria were reviewed with very few pediatric and adolescent studies being found. Methodologies of adherence measurement were analyzed and reasons for nonadherence were identified in the geopolitical zones in the federal republic of Nigeria. The results of the literature review indicate that adherence to ART is mixed (both high and low adherence) with patient self-recall identified as the common method of assessment. The most common reasons identified for patient nonadherence include the cost of therapy (even when the drugs are heavily subsidized), medication side effects, nonavailability of ARV drugs, and the stigma of taking the drugs. This manuscript highlights the policy and practice implications from these studies and provides recommendations for future ART program management.

  19. Food Insecurity, Dietary Diversity, and Body Mass Index of HIV-Infected Individuals on Antiretroviral Therapy in Rural Haiti.

    PubMed

    Rebick, Gabriel W; Franke, Molly F; Teng, Jessica E; Gregory Jerome, J; Ivers, Louise C

    2016-05-01

    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 < 0.001). Compared with those with little to no 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.

  20. Discordance between genotypic resistance and pseudovirus phenotypic resistance in AIDS patients after long-term antiretroviral therapy and virological failure.

    PubMed

    Yang, Jing; Geng, Wenqing; Zhang, Min; Han, Xiaoxu; Shang, Hong

    2014-10-01

    Sixteen original recombinant pseudoviruses were generated by cloning the reverse transcriptase and protease genes of human immunodeficiency virus (HIV)-1 from patients into a plasmid vector (pNL4-3-ΔE-EGFP). By site-directed mutagenesis two restriction endonuclease sites, ApaI and AgeI, were inserted into pNL4-3-ΔE-EGFP. Phenotypic susceptibility of recombinant pseudoviruses to five different classes of antiretroviral drugs was determined using a luciferase reporter assay system. The results were subjected to comparative analyses to detect genotype-phenotype associations. Among 16 strains tested, 12 strains had a discordant genotype-phenotype resistance pattern to at least one drug. In five strains resistance to two, in two strains to three, and in one strain resistance to four drugs was detected. HIV resistance genotyping could predict the phenotype for nevirapine and azidothymidine. For lamivudine, 2'-3'-didehydro-2'-3'dideoxythymidine and didanosine, phenotypic resistance testing was necessary. The study showed that in patients who experienced long-term highly active antiretroviral therapy and virological failure, there is some discordance between genotypic and phenotypic HIV drug resistance. To address the issue of limited resources in China, genotypic and phenotypic resistance testing should be done for different drugs in order to guide clinical therapy more effectively.

  1. [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].

    PubMed

    Moshkovich, G F; Minaeva, S V; Varlova, L W; Goryaeva, M P; Gulyaeva, S S; Tichonova, E V

    2016-01-01

    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.

  2. Marked sex differences in all-cause mortality on antiretroviral therapy in low- and middle-income countries: a systematic review and meta-analysis

    PubMed Central

    Beckham, Sarah W; Beyrer, Chris; Luckow, Peter; Doherty, Meg; Negussie, Eyerusalem K; Baral, Stefan D

    2016-01-01

    Introduction While women and girls are disproportionately at risk of HIV acquisition, particularly in low- and middle-income countries (LMIC), globally men and women comprise similar proportions of people living with HIV who are eligible for antiretroviral therapy. However, men represent only approximately 41% of those receiving antiretroviral therapy globally. There has been limited study of men’s outcomes in treatment programmes, despite data suggesting that men living with HIV and engaged in treatment programmes have higher mortality rates. This systematic review (SR) and meta-analysis (MA) aims to assess differential all-cause mortality between men and women living with HIV and on antiretroviral therapy in LMIC. Methods A SR was conducted through searching PubMed, Ovid Global Health and EMBASE for peer-reviewed, published observational studies reporting differential outcomes by sex of adults (≥15 years) living with HIV, in treatment programmes and on antiretroviral medications in LMIC. For studies reporting hazard ratios (HRs) of mortality by sex, quality assessment using Newcastle–Ottawa Scale (cohort studies) and an MA using a random-effects model (Stata 14.0) were conducted. Results A total of 11,889 records were screened, and 6726 full-text articles were assessed for eligibility. There were 31 included studies in the final MA reporting 42 HRs, with a total sample size of 86,233 men and 117,719 women, and total time on antiretroviral therapy of 1555 months. The pooled hazard ratio (pHR) showed a 46% increased hazard of death for men while on antiretroviral treatment (1.35–1.59). Increased hazard was significant across geographic regions (sub-Saharan Africa: pHR 1.41 (1.28–1.56); Asia: 1.77 (1.42–2.21)) and persisted over time on treatment (≤12 months: 1.42 (1.21–1.67); 13–35 months: 1.48 (1.23–1.78); 36–59 months: 1.50 (1.18–1.91); 61 to 108 months: 1.49 (1.29–1.71)). Conclusions Men living with HIV have consistently and

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

    PubMed Central

    Melikian, George; van Dyk, Gisela; Thomas, Winifred; du Plessis, Nicolette M.; Avenant, Theunis

    2015-01-01

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

  4. Etiology and pharmacologic management of noninfectious diarrhea in HIV-infected individuals in the highly active antiretroviral therapy era.

    PubMed

    MacArthur, Rodger D; DuPont, Herbert L

    2012-09-01

    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.

  5. Early Antiretroviral Therapy at High CD4 Counts Does Not Improve Arterial Elasticity: A Substudy of the Strategic Timing of AntiRetroviral Treatment (START) Trial

    PubMed Central

    Hullsiek, Katherine Huppler; Engen, Nicole Wyman; Nelson, Ray; Chetchotisakd, Ploenchan; Gerstoft, Jan; Jessen, Heiko; Losso, Marcelo; Markowitz, Norman; Munderi, Paula; Papadopoulos, Antonios; Shuter, Jonathan; Rappoport, Claire; Pearson, Mary T.; Finley, Elizabeth; Babiker, Abdel; Emery, Sean; Duprez, Daniel

    2016-01-01

    Background. Both human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Vascular function assessments can be used to study CVD pathogenesis. We compared the effect of immediate versus deferred ART initiation at CD4 counts >500 cells/mm3 on small arterial elasticity (SAE) and large artery elasticity (LAE). Methods. Radial artery blood pressure waveforms were recorded noninvasively. Small arterial elasticity and LAE were derived from analysis of the diastolic pulse waveform. Randomized treatment groups were compared with linear models at each visit and longitudinal mixed models. Results. Study visits involved 332 participants in 8 countries: mean (standard deviation [SD]) age 35 (10), 70% male, 66% nonwhite, 30% smokers, and median CD4 count 625 cells/mm3 and 10-year Framingham risk score for CVD 1.7%. Mean (SD) SAE and LAE values at baseline were 7.3 (2.9) mL/mmHg × 100 and 16.6 (4.1) mL/mmHg × 10, respectively. Median time on ART was 47 and 12 months in the immediate and deferred ART groups, respectively. The treatment groups did not demonstrate significant within-person changes in SAE or LAE during the follow-up period, and there was no difference in mean change from baseline between treatment groups. The lack of significant differences persisted after adjustment, when restricted to early or late changes, after censoring participants in deferred group who started ART, and among subgroups defined by CVD and HIV risk factors. Conclusions. Among a diverse global population of HIV-positive persons with high CD4 counts, these randomized data suggest that ART treatment does not have a substantial influence on vascular function among younger HIV-positive individuals with preserved immunity. PMID:27942541

  6. Determinants of survival in adult HIV patients on antiretroviral therapy in Eastern Uttar Pradesh: A prospective study

    PubMed Central

    Chakravarty, Jaya; Tiwary, Narendra K.; Prasad, Shashi Ranjan; Shukla, Saurabh; Tiwari, Anurag; Mishra, Rabindra Nath; Sundar, Shyam

    2014-01-01

    Background & objectives: The National AIDS Control Organization (NACO) of India has been providing free ARV (antiretroviral) drugs since 2004. By 2012, 486,173 patients had received treatment through the antiretroviral therapy (ART) centres. The objective of this observational study was to assess the factors determining survival of patients on ART under routine programme conditions in an ART centre in north India five years after its inception. Methods: Treatment naive HIV positive patients who were enrolled in the ART centre between May 2009 and May 2010 and started on ART as per the Revised NACO guidelines 2009, were included in the study and outcome was assessed after two years of follow up. Results: A total of 1689 patients were included in the analysis, of whom 272 (16.10%) expired, 205 (12.13%) were lost to follow up (LFU), 526 (31.14%) were transferred out to other facilities and 686 (40.63%) were alive at the end of two years. Majority (92%) of the deaths occurred in the first six months of therapy. Age >30 yr, male gender, poor functional status, haemoglobin level <11 g/dl, body weight <45 kg and CD4 count <100/μl at baseline had significantly higher relative hazard of death. Most LFU also occurred in the first six months and these patients had significantly low CD4 count, weight, haemoglobin level and higher number of patients in Stages III and IV as compared to those who survived. Interpretation & conclusions: The study findings revealed poor survival in the first six months of therapy especially in those with severe immunosuppression. This emphasizes the need for early enrolment into the programme. The high LFU occurring early after initiation of therapy suggests the urgent need to build an efficient patient retrieval system in the programme. PMID:25488442

  7. HIV-associated Neurocognitive Disorders and Antiretroviral Therapy: Current Concepts and Controversies.

    PubMed

    Etherton, Mark R; Lyons, Jennifer L; Ard, Kevin L

    2015-06-01

    Antiretroviral drugs may help prevent neurological decline in individuals with HIV infection by suppressing viral replication and associated chronic immune activation in the central nervous system. However, HIV control in the brain may come at the price of drug-induced neurotoxicity. Herein, we review recent advances in the balance between adequate viral suppression in the nervous system and adverse effects of the medications used in HIV treatment.

  8. Patient-Reported Barriers to Adherence to Antiretroviral Therapy: A Systematic Review and Meta-Analysis

    PubMed Central

    Mills, Edward J.; Nachega, Jean B.; Nsanzimana, Sabin; Penazzato, Martina; Appolo, Tsitsi; Ford, Nathan

    2016-01-01

    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

  9. Risk factors for mortality during antiretroviral therapy in older populations in resource-limited settings

    PubMed Central

    O'Brien, Daniel; Spelman, Tim; Greig, Jane; McMahon, James; Ssonko, Charles; Casas, Esther; Mesic, Anita; Du Cros, Philipp; Ford, Nathan

    2016-01-01

    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)], p<0.0001. Higher CD4 levels at baseline were associated with significantly reduced mortality rates in the 15 to 50 age group but this association was not seen in the >50 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

  10. [Successful treatment of HIV-associated chronic inflammatory demyelinating polyneuropathy by early initiation of highly active anti-retroviral therapy].

    PubMed

    Kume, Kodai; Ikeda, Kazuyo; Kamada, Masaki; Touge, Tetsuo; Deguchi, Kazushi; Masaki, Tsutomu

    2013-01-01

    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.

  11. HIV-positive patients’ perceptions of care received at a selected antiretroviral therapy clinic in Vhembe district, South Africa

    PubMed Central

    Ndou, Tshifhiwa V.; Risenga, Patrone R.

    2016-01-01

    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. PMID:27380841

  12. Impact of Extended Combination Antiretroviral Therapy on the Decline of HIV Prevalence in Pregnant Women in Malawi.

    PubMed

    Liotta, Giuseppe; Chimbwandira, Frank; Wouters, Kristien; Nielsen-Saines, Karin; Jere, Haswell; Mancinelli, Sandro; Ceffa, Susanna; Erba, Fulvio; Palombi, Leonardo; Marazzi, Maria Cristina

    2016-01-01

    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.

  13. Cervical Shedding of HIV-1 RNA Among Women With Low Levels of Viremia While Receiving Highly Active Antiretroviral Therapy

    PubMed Central

    Neely, Michael N.; Benning, Lorie; Xu, Jiaao; Strickler, Howard D.; Greenblatt, Ruth M.; Minkoff, Howard; Young, Mary; Bremer, James; Levine, Alexandra M.; Kovacs, Andrea

    2011-01-01

    Background Among women with low o r undetectable quantities of HIV-1 RNA in plasma, factors associated with genital HIV-1 RNA shedding, including choice of treatment regimen, are poorly characterized. Methods We measured HIV-1 RNA in cervical swab specimens obtained from participants in the Women’s Interagency HIV Study who had concurrent plasma viral RNA levels <500 copies/mL, and we assessed factors associated with genital HIV shedding. The study was powered to determine the relative effects of antiretroviral protease inhibitors (PIs) versus nonnucleoside reverse transcriptase inhibitors (NNRTIs) on viral RNA shedding. Results Overall, 44 (15%) of 290 women had detectable HIV-1 RNA in cervical specimens. In the final multivariate model, shedding was independently associated with NNRTI (vs. PI) use (odds ratio [OR], 95% confidence interval [CI]: 2.24, 1.13 to 4.45) and illicit drug use (OR, 95% CI: 2.41, 0.96 to 5.69). Conclusions This is the largest study to define risks for genital HIV-1 RNA shedding in women with low/undetectable plasma virus. Shedding in this population was common, and NNRTI-based highly active antiretroviral therapy (HAART) (vs. PI-based HAART) was associated with genital HIV shedding. Further study is required to determine the impact of these findings on transmission of HIV from mother to child or to sexual partners. PMID:17106279

  14. Influence of antiretroviral therapy on programmed death-1 (CD279) expression on T cells in lymph nodes of human immunodeficiency virus-infected individuals.

    PubMed

    Ehrhard, Simone; Wernli, Marion; Dürmüller, Ursula; Battegay, Manuel; Gudat, Fred; Erb, Peter

    2009-10-01

    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.

  15. Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Although some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) Cmin and Cmax values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations. Methods HIV-positive women with virologic suppression (viral load < 50copies/mL) on their first antiretroviral regimen were enrolled. Timed blood samples for Cmin and Cmax were drawn weekly for 3 weeks. The ratio of each individual’s median Cmin and Cmax to the published population mean values for their PI or NNRTI was calculated and assessed using Wilcoxon sign-rank. Intra- and inter-patient variability of antiretroviral drug levels was assessed using coefficient of variation and intra-class correlation. Linear regression was used to identify correlates of the square root-transformed Cmin and Cmax ratios. Results Data from 82 women were analyzed. Their median age was 41 years (IQR=36-48) and duration of antiretrovirals was 20 months (IQR=9-45). Median antiretroviral Cmin and Cmax ratios were 1.21 (IQR=0.72-1.89, p=0.003) (highest ratios for nevirapine and lopinavir) and 0.82 (IQR=0.59-1.14, p=0.004), respectively. Nevirapine and efavirenz showed the least and unboosted atazanavir showed the most intra- and inter-patient variability. Higher CD4+ count correlated with higher Cmin. No significant correlates for Cmax were found. Conclusions Compared to historical control data, Cmin in the women enrolled was significantly higher whereas Cmax was significantly lower. Antiretroviral Cmin ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations. Trial registration NCT00433979 PMID:23732043

  16. Cognitive and Behavioural Correlates of Non-Adherence to HIV Anti-Retroviral Therapy: Theoretical and Practical Insight for Clinical Psychology and Health Psychology

    ERIC Educational Resources Information Center

    Begley, Kim; McLaws, Mary-Louise; Ross, Michael W.; Gold, Julian

    2008-01-01

    This cross-sectional study identified variables associated with protease inhibitor (PI) non-adherence in 179 patients taking anti-retroviral therapy. Univariate analyses identified 11 variables associated with PI non-adherence. Multiple logistic regression modelling identified three predictors of PI non-adherence: low adherence self-efficacy and…

  17. Immunoglobulin G(κ) [IgG(κ)] and IgG(λ) Paraproteinemia in a Child with AIDS and Response to Highly Active Antiretroviral Therapy

    PubMed Central

    Seeborg, Filiz Odabasi; Gay, Hannah; Schmiege, Lorenz M.; Bernard, David; Shearer, William T.

    2005-01-01

    We report an 8-year-old boy with AIDS, extremely elevated serum immunoglobulin G (IgG) concentration and IgG kappa [IgG(κ)] and IgG lambda [IgG(λ)] paraproteinemia. This paraproteinemia partially responded to highly active antiretroviral therapy. This case emphasizes the importance of controlling B-cell activation. PMID:16275950

  18. Rehabilitation Program for the Quality of Life for Individuals on Highly Active Antiretroviral Therapy in KwaZulu-Natal, South Africa: A Short Report

    ERIC Educational Resources Information Center

    Maharaj, Sonill S.; Chetty, Verusia

    2011-01-01

    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…

  19. Cumulative Viral Load and Virologic Decay Patterns After Antiretroviral Therapy in HIV-Infected Subjects Influence CD4 Recovery and AIDS

    DTIC Science & Technology

    2011-05-20

    Cohorte Agence Nationale de Recherches sur le SIDA EP 11 study. J Infect Dis 186: 710–714. 8. Hermankova M, Ray SC, Ruff C, Powell-Davis M, Ingersoll R, et...malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine

  20. CROI 2014: Viral hepatitis and complications of HIV disease and antiretroviral therapy.

    PubMed

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

    2014-05-01

    The remarkable advances in interferon-sparing, all-oral hepatitis C virus (HCV) treatment were a highlight of the 2014 Conference on Retroviruses and Opportunistic Infections (CROI). The backbone of the nucleotide inhibitor sofosbuvir and the nonstructural protein 5A (NS5A) inhibitor ledipasvir with an additional third agent (HCV protease inhibitor or HCV nonnucleoside reverse transcriptase inhibitor) led to a sustained virologic response (SVR) rate 12 weeks after cessation of treatment of 95% to 100% after only 6 weeks of treatment. These results demonstrate the potential of combination directacting antiviral (DAA) therapy for abbreviated, well-tolerated, and highly effective HCV treatment. Two triple-drug regimens that comprised 12 weeks of an NS5A inhibitor, an HCV protease inhibitor, and a nonnucleoside inhibitor also resulted in SVRs of more than 90% in patients with HCV genotype 1. HIV coinfection does not appear to negatively impact response to DAA-based HCV therapy, as evidenced by similar response rates in HIV/HCV-coinfected patients compared with HCV-monoinfected patients receiving interferonsparing or -containing regimens. There was continued emphasis at CROI 2014 on non-AIDS complications of HIV infection, specifically cardiovascular disease, renal insufficiency, and bone and endocrine disorders that persist among patients with treated HIV disease and contribute to morbidity and mortality. Finally, new data on novel drugs and combinations for treatment of tuberculosis (TB), patient outcomes using new rapid TB diagnostics, and a short-course TB prevention strategy were presented.

  1. Factors associated with adherence to antiretroviral therapy for the treatment of HIV-infected women attending an urban care facility.

    PubMed

    Aspeling, Heila E; van Wyk, Neltjie C

    2008-02-01

    Adherence to antiretroviral therapy (ART) is often jeopardized by factors misapprehended by health-care providers. As South Africa is severely affected by HIV and AIDS, identifying factors that influence adherence in this specific context becomes essential. An exploratory and descriptive case study design was used to further explore this subject and to identify factors that could influence adherence to ART. A significant correlation with international data was found. Most participants indicated that their traditional beliefs and customs did not interfere with their adherence to ART, although the lack of HIV education might facilitate reversion to traditional customs. Adequate treatment preparation, comprehensive HIV education and a supportive patient-provider relationship seemed to impact adherence significantly.

  2. Hepatitis B virus infection is associated with impaired immunological recovery during antiretroviral therapy in the Swiss HIV cohort study.

    PubMed

    Wandeler, Gilles; Gsponer, Thomas; Bihl, Florian; Bernasconi, Enos; Cavassini, Matthias; Kovari, Helen; Schmid, Patrick; Battegay, Manuel; Calmy, Alexandra; Egger, Matthias; Furrer, Hansjakob; Rauch, Andri

    2013-11-01

    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.

  3. Challenges in using mobile phones for collection of antiretroviral therapy adherence data in a resource-limited setting.

    PubMed

    Haberer, Jessica E; Kiwanuka, Julius; Nansera, Denis; Wilson, Ira B; Bangsberg, David R

    2010-12-01

    Frequent antiretroviral therapy adherence monitoring could detect incomplete adherence before viral rebound develops and thus potentially prevent treatment failure. Mobile phone technologies make frequent, brief adherence interviews possible in resource-limited settings; however, feasibility and acceptability are unknown. Interactive voice response (IVR) and short message service (SMS) text messaging were used to collect adherence data from 19 caregivers of HIV-infected children in Uganda. IVR calls or SMS quantifying missed doses were sent in the local language once weekly for 3-4 weeks. Qualitative interviews were conducted to assess participant impressions of the technologies. Participant interest and participation rates were high; however, weekly completion rates for adherence queries were low (0-33%), most commonly due to misunderstanding of personal identification numbers. Despite near ubiquity of mobile phone technology in resource-limited settings, individual level collection of healthcare data presents challenges. Further research is needed for effective training and incentive methods.

  4. Expanding Access to Antiretroviral Therapy in Sub-Saharan Africa: Avoiding the Pitfalls and Dangers, Capitalizing on the Opportunities

    PubMed Central

    McCoy, David; Chopra, Mickey; Loewenson, Rene; Aitken, Jean-Marion; Ngulube, Thabale; Muula, Adamson; Ray, Sunanda; Kureyi, Tendayi; Ijumba, Petrida; Rowson, Mike

    2005-01-01

    We describe a number of pitfalls that may occur with the push to rapidly expand access to antiretroviral therapy in sub-Saharan Africa. These include undesirable opportunity costs, the fragmentation of health systems, worsening health care inequities, and poor and unsustained treatment outcomes. On the other hand, AIDS “treatment activism” provides an opportunity to catalyze comprehensive health systems development and reduce health care inequities. However, these positive benefits will only happen if we explicitly set out to achieve them. We call for a greater commitment toward health activism that tackles the broader political and economic constraints to human and health systems development in Africa, as well as toward the resuscitation of inclusive and equitable public health systems. PMID:15623853

  5. Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs.

    PubMed

    da Cunha, Joel; Maselli, Luciana Morganti Ferreira; Stern, Ana Carolina Bassi; Spada, Celso; Bydlowski, Sérgio Paulo

    2015-05-12

    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.

  6. Monotherapy with darunavir/ritonavir or lopinavir/ritonavir versus standard antiretroviral therapy: a randomized clinical trial (2pm Study).

    PubMed

    Gianotti, Nicola; Galli, Laura; Maserati, Renato; Sighinolfi, Laura; Ripamonti, Diego; Palvarini, Loredana; Lo Caputo, Sergio; Focà, Emanuele; Celesia, Benedetto Maurizio; Baldelli, Franco; Sterrantino, Gaetana; Lazzarin, Adriano

    2016-10-01

    In a multicentre, open-label, clinical trial, 43 patients virologically suppressed while receiving a standard triple antiretroviral therapy were randomized (1:1:1) to switch to monotherapy with darunavir/ritonavir (DRV/r-MT arm), monotherapy with lopinavir/ritonavir (LPV/r-MT arm) or to continue on the ongoing regimen (cART arm). The proportion (95% CI) of patients with virological success (Snapshot analysis) at week 48 was 73% (48%-90%) in the DRV/r-MT arm, 69% (42%-88%) in the LPV/r-MT arm and 87% (61%-98%) in the cART arm. Virological failure was detected in only one patient receiving LPV/r-MT. The LPV/r-MT arm showed a modest worsening in lipid profile.

  7. Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs

    PubMed Central

    da Cunha, Joel; Maselli, Luciana Morganti Ferreira; Stern, Ana Carolina Bassi; Spada, Celso; Bydlowski, Sérgio Paulo

    2015-01-01

    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. PMID:25964872

  8. Religiosity and adherence to antiretroviral therapy among patients attending a public hospital-based HIV/AIDS clinic in Uganda.

    PubMed

    Kisenyi, Rita N; Muliira, Joshua K; Ayebare, Elizabeth

    2013-03-01

    In Uganda, the prevalence of non-adherence to antiretroviral therapy (ART) by HIV/AIDS patients remains high and sometimes this is blamed on patients' religious behavior. A descriptive design was used to examine the relationship between religiosity and ART adherence in a sample of 220 patients attending a HIV/AIDS clinic in a Ugandan public hospital. Participants who self-identified as Pentecostal and Muslim had the highest percentage of members with high religiosity scores and ART adherence. Among Muslim participants (34), 82% reported high religiosity scores and high levels of ART adherence. Of the fifty Pentecostals participants, 96% reported high religiosity scores and 80% reported high levels of ART adherence. Correlation analysis showed a significant relationship between ART adherence and religiosity (r = 0.618, P ≤ 0.01). Therefore, collaboration between religious leaders and HIV/AIDS healthcare providers should be encouraged as one of the strategies for enhancing ART adherence.

  9. Monitoring Antiretroviral Therapy in HIV-Infected Children in Resource-Limited Countries: A Tale of Two Epidemics

    PubMed Central

    Paintsil, Elijah

    2011-01-01

    Twenty-nine years into the HIV epidemic, several advances have been made; however, there remain several challenges particularly with pediatric HIV in resource-limited countries. The obstacles facing pediatric antiretroviral therapy (ART) delivery in resource-limited countries are multifaceted: lack of health care infrastructure, limited availability of pediatric drug formulations, lack of early HIV diagnostic and monitoring techniques, limited manpower with expertise in pediatric HIV care, limited donor funding, and competing public health priorities with limited health care budget. In this paper, the challenges with various ART monitoring tools in resource-limited countries are discussed. Noninvasive (e.g., patient, clinical events outcome, and adherence) and invasive (e.g., immunologic and virologic) monitoring tools are discussed. Several cheap and technically less complex laboratory tests for monitoring are becoming available. Funding agencies and country programs should invest in validating the use of current technologies to optimize pediatric HIV care in resource-limited countries. PMID:21490777

  10. Antiretroviral Therapy Fails to Restore Levels of HIV-1 Restriction miRNAs in PBMCs of HIV-1-infected MSM

    PubMed Central

    Liu, Man-Qing; Zhao, Min; Kong, Wen-Hua; Peng, Jin-Song; Wang, Fang; Qiu, Hong-Yan; Zhu, Ze-Rong; Tang, Li; Sang, Ming; Wu, Jian-Guo; Ho, Wen-Zhe; Zhou, Wang

    2015-01-01

    Abstract A number of cellular microRNAs (miRNAs) have been identified to have the ability to inhibit HIV-1 replication. In this study, we examined the impact of combination antiretroviral therapy (cART) on the expression of HIV-1 restriction miRNAs in peripheral blood mononuclear cells of HIV-1–infected men who have sex with men (MSM). Compared with male healthy donors, HIV-infected MSM had significantly lower levels of 9 HIV-1 restriction miRNAs. The treatment of HIV-1–infected MSM with cART, however, failed to restore the levels of these miRNAs in peripheral blood mononuclear cells. These observations suggest that the suppression of the cellular restriction miRNAs by HIV-1 may attribute to the virus latency during cART. PMID:26579828

  11. Antiretroviral Therapy Fails to Restore Levels of HIV-1 Restriction miRNAs in PBMCs of HIV-1-infected MSM.

    PubMed

    Liu, Man-Qing; Zhao, Min; Kong, Wen-Hua; Peng, Jin-Song; Wang, Fang; Qiu, Hong-Yan; Zhu, Ze-Rong; Tang, Li; Sang, Ming; Wu, Jian-Guo; Ho, Wen-Zhe; Zhou, Wang

    2015-11-01

    A number of cellular microRNAs (miRNAs) have been identified to have the ability to inhibit HIV-1 replication. In this study, we examined the impact of combination antiretroviral therapy (cART) on the expression of HIV-1 restriction miRNAs in peripheral blood mononuclear cells of HIV-1-infected men who have sex with men (MSM). Compared with male healthy donors, HIV-infected MSM had significantly lower levels of 9 HIV-1 restriction miRNAs. The treatment of HIV-1-infected MSM with cART, however, failed to restore the levels of these miRNAs in peripheral blood mononuclear cells. These observations suggest that the suppression of the cellular restriction miRNAs by HIV-1 may attribute to the virus latency during cART.

  12. Associations between alcohol use, other psychosocial factors, structural factors and antiretroviral therapy (ART) adherence among South African ART recipients.

    PubMed

    Morojele, Neo K; Kekwaletswe, Connie T; Nkosi, Sebenzile

    2014-03-01

    We examined whether alcohol use is associated with antiretroviral therapy (ART) adherence independently of structural and psychosocial factors among 304 male and female ART recipients in ART sites in Tshwane, South Africa. ART adherence was assessed by the CASE Adherence Index. Independent variables were demographic, structural, psycho-social, and alcohol use (AUDIT score) factors. In hierarchical multiple regression, demographic variables (Step 1) explained 4 % of variance in ART adherence (p ≤ 0.01). Variance explained increased to 16 % (p ≤ 0.001) after entering structural variables (Step 2); 19 % (p ≤ 0.001) after entering psychosocial variables (Step 3); and 24 % (p ≤ 0.001) after entering AUDIT score (Step 4). Alcohol use is independently associated with ART adherence.

  13. The influence of age, smoking, antiretroviral therapy, and esophagitis on the local immunity of the esophagus in patients with AIDS.

    PubMed

    Cavellani, Camila Lourencini; Gomes, Nayara Cândida; de Melo e Silva, Ana Teresa; Silva, Renata Beatriz; Ferraz, Mara Lúcia Fonseca; Faria, Humberto Aparecido; Corrêa, Rosana Rosa Miranda; Teixeira, Vicente de Paula Antunes; Rocha, Laura Penna

    2013-01-01

    Studies have shown immunological and morphological alterations in the esophagus during the course of AIDS. Esophageal postmortem samples of 22 men with AIDS autopsied in a teaching hospital between 1982 and 2009 were collected. We carried out revision of the autopsy reports and medical records, morphometric analysis (Image J and KS-300 Kontron-Zeiss), and immunohistochemical (anti-S100, anti-IgA, anti-IgG, and anti-IgM) analysis of the esophagus. In accordance with most of the parameters evaluated, age and the smoking habit harmed the esophageal local immunity, whereas the use of antiretroviral therapy improved the immune characteristics of this organ. Patients with esophagitis also presented immunological fragility of the esophagus. This leads to the conclusion that alterations in the esophageal epithelium of patients with AIDS are not only caused by direct action of HIV but also the clinical and behavioral characteristics of the patient.

  14. Pharmacy adherence measures to assess adherence to antiretroviral therapy: review of the literature and implications for treatment monitoring.

    PubMed

    McMahon, James H; Jordan, Michael R; Kelley, Karen; Bertagnolio, Silvia; Hong, Steven Y; Wanke, Christine A; Lewin, Sharon R; Elliott, Julian H

    2011-02-15

    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.

  15. Optimizing Antiretroviral Therapy (ART) for Maternal and Child Health (MCH): Rationale and Design of the MCH-ART Study

    PubMed Central

    Phillips, Tamsin K.; Zerbe, Allison; Ronan, Agnes; Hsiao, Nei-Yuan; Mellins, Claude A.; Remien, Robert H.; Le Roux, Stanzi M.; Brittain, Kirsty; Ciaranello, Andrea; Petro, Greg; McIntyre, James A.; Abrams, Elaine J.

    2016-01-01

    Background: Prevention of mother-to-child transmission of HIV implementation faces significant challenges globally, particularly in the context of universal lifelong antiretroviral therapy (ART) for all HIV-infected pregnant women. Methods: We describe the rationale and methods of the Maternal and Child Health-Antiretroviral Therapy (MCH-ART) study, an implementation science project examining strategies for providing HIV care and treatment to HIV-infected women who initiate ART during pregnancy and their HIV-exposed infants. Results: MCH-ART is composed of 3 interrelated study designs across the antenatal and postnatal periods. Phase 1 is a cross-sectional evaluation of consecutive HIV-infected pregnant women seeking antenatal care; phase 2 is an observational cohort of all women from phase 1 who are eligible for initiation of ART following local guidelines; and phase 3 is a randomized trial of strategies for delivering ART to breastfeeding women from phase 2 during the postpartum period. During each phase, a set of study measurement visits is carried out separately from antenatal care and ART services; a maximum of 9 visits takes place from the beginning of antenatal care through 12 months postpartum. In parallel, in-depth interviews are used to examine issues of ART adherence and retention qualitatively, and costs and cost-effectiveness of models of care are examined. Separate substudies examine health outcomes in HIV-uninfected women and their HIV-unexposed infants, and the role of the adherence club model for long-term adherence and retention. Discussion: Combining observational and experimental components, the MCH-ART study presents a novel approach to understand and optimize ART delivery for MCH. PMID:27355508

  16. Depressive and Anxiety Symptoms Predict Sustained Quality of Life Deficits in HIV-Positive Ugandan Adults Despite Antiretroviral Therapy

    PubMed Central

    Ezeamama, Amara E; Woolfork, Makhabele N; Guwatudde, David; Bagenda, Danstan; Manabe, Yukari C; Fawzi, Wafaie W; Smith Fawzi, Mary C

    2016-01-01

    Abstract The impact of psychosocial status at onset of antiretroviral therapy on changes in quality of life (QOL) and subjectively rated health (SRH) among adults on highly active antiretroviral therapy (HAART) in resource-limited settings is poorly understood. Therefore, we evaluate the association between stigma, anxiety, depression, and social support and change in QOL and SRH in HIV-infected Ugandan adults during an 18-month period. Psychosocial indicators were assessed at enrollment using structured questionnaires. QOL and SRH measures were assessed at months 0, 6, 12, and 18 using the Medical Outcomes Survey-HIV. Linear mixed models determined risk estimated differences in QOL and SRH in relation to quartiles of each psychosocial status indicator. Repeated measures generalized estimating equations modeling was implemented to assess differences in likelihood of improved versus nonimproved SRH during follow-up. QOL scores and SRH improved significantly for all participants over 18 months (P < 0.0001). The gain in QOL increased dose-dependently as baseline depressive symptoms (time∗depression P < 0.001) and anxiety levels (time∗anxiety P < 0.001) declined. Lower social support was associated with worse QOL at baseline (P = 0.0005) but QOL improvement during follow-up was not dependent on baseline level of social support (time∗social support P = 0.8943) or number of stigmatizing experiences (time∗stigma P = 0.8662). Psychosocial determinants did not predict changes in SRH in this study. High levels of depression and anxiety symptoms at HAART initiation predicts lower gains in QOL for HIV-positive patients for as long as 18 months. Long-term QOL improvements in HIV-infected adults may be enhanced by implementation of psychosocial interventions to reduce depression and anxiety in HIV-infected adults. PMID:26945347

  17. Bounded agency in humanitarian settings: a qualitative study of adherence to antiretroviral therapy among refugees situated in Kenya and Malaysia.

    PubMed

    Mendelsohn, Joshua B; Rhodes, Tim; Spiegel, Paul; Schilperoord, Marian; Burton, John Wagacha; Balasundaram, Susheela; Wong, Chunting; Ross, David A

    2014-11-01

    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

  18. Antiretroviral therapy suppressed participants with low CD4+ T-cell counts segregate according to opposite immunological phenotypes

    PubMed Central

    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

    2016-01-01

    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

  19. Failure of highly active antiretroviral therapy in reconstituting immune response to Clostridium tetani vaccine in aged AIDS patients.

    PubMed

    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

    2010-05-01

    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.

  20. Changes in Inflammatory and Coagulation Biomarkers: A Randomized Comparison of Immediate Versus Deferred Antiretroviral Therapy in Patients with HIV Infection

    PubMed Central

    Baker, Jason V; Neuhaus, Jacqueline; Duprez, Daniel; Kuller, Lewis H.; Tracy, Russell; Belloso, Waldo H.; De Wit, Stephane; Drummond, Fraser; Lane, H. Clifford; Ledergerber, Bruno; Lundgren, Jens; Nixon, Daniel E.; Paton, Nicholas I.; Neaton, James D.

    2010-01-01

    Ojectives 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) at study entry, risk of AIDS and serious non-AIDS events was increased for participants who deferred ART compared to those randomized to (re)initiate ART immediately. Our objective was to determine whether ART initiation in this group reduced markers of inflammation and coagulation that have been associated with increased mortality risk in SMART. Changes in these biomarkers have been described after stopping ART, but not after starting ART in SMART. Methods Stored specimens for 254 participants (126 DC and 128 VS) who were naïve to ART or off ART (≥6 months) were analyzed for interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP) and D-dimer at baseline and months 2 and 6. Results At month 6, 62% of VS group had HIV RNA <400copies/mL and median CD4 count was 190 cells/mm3 higher than for the DC group (590 vs. 400 cells/mm3). Compared with DC, the VS group had 32% (95%CI: 19 to 43%) lower D-dimer levels at month 6 (p<0.001); differences were not significant for hsCRP or IL-6 levels. Conclusions In this randomized comparison of immediate versus delayed ART initiation, D-dimer, but not IL-6 and hsCRP, declined significantly after starting ART. Further studies are needed to determine whether improvements in D-dimer are associated with reduced risk of clinical disease, and whether adjunct treatments used in combination with ART can reduce inflammation among individuals with HIV infection. PMID:20930640

  1. Evaluation of improvement of onychomycosis in HIV-infected patients after initiation of combined antiretroviral therapy without antifungal treatment.

    PubMed

    Ruíz-López, Patricia; Moreno-Coutiño, Gabriela; Fernández-Martínez, Ramón; Espinoza-Hernández, Jessica; Rodríguez-Zulueta, Patricia; Reyes-Terán, Gustavo

    2015-09-01

    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.

  2. Prevalence and factors associated with traditional herbal medicine use among patients on highly active antiretroviral therapy in Uganda

    PubMed Central

    2011-01-01

    Background In Africa, herbal medicines are often used as primary treatment for Human immunodeficiency virus (HIV) related problems. Concurrent use of traditional herbal medicines (THM) with antiretroviral drugs (ARVs) is widespread among HIV infected patients. However, the extent of THM use is not known in most settings in Sub-Saharan Africa. This study aimed at determining the prevalence and factors associated with THM use among HIV infected patients on highly active antiretroviral therapy (HAART) attending The AIDS Support Organization (TASO) in Uganda. TASO is a non-governmental organization devoted to offering HIV/AIDS care and treatment services in the population. Methods This was a cross-sectional study carried out in two TASO treatment centres in Uganda among 401 randomly selected eligible participants. We included participants who were 18 years and above, were enrolled on HAART, and consented to participate in the study. Data was collected using an interviewer-administered semi-structured questionnaire. THM use referred to someone who had ever used or was currently using herbal medicine while on highly active antiretroviral therapy (HAART) by the time of the study. Data was captured in Epi-data version 3.1 and exported to STATA version 9.0 for analysis. Results The prevalence of THM use was 33.7%. Patients on HAART for < 4 years were more likely to use THM (OR = 5.98, 95% CI 1.13 - 31.73) as well as those who experienced HAART side effects (OR = 3.66, 95% CI: 1.15 - 11.68). Older patients (≥39 years) were less likely to use THM (OR = 0.26 95% CI: 0.08 - 0.83). Participants with HAART adherence levels > 95% were less likely to use THM (OR = 0.09, 95% CI 0.01 - 0.65). Conclusion The prevalence of THM use among participants on HAART was high. This raises clinical and pharmacological concerns that need attention by the health care service providers. PMID:22074367

  3. Natural conception in HIV-serodiscordant couples with the infected partner in suppressive antiretroviral therapy

    PubMed Central

    Del Romero, Jorge; Baza, María Begoña; Río, Isabel; Jerónimo, Adrián; Vera, Mar; Hernando, Victoria; Rodríguez, Carmen; Castilla, Jesús

    2016-01-01

    Abstract The potential of antiretroviral treatment (ART) to prevent the sexual transmission of HIV has increased the number of serodiscordant couples who are considering natural conception. We aim to describe the results of a protocol for reproductive counseling aimed at HIV serodiscordant couples who desire natural conception, in which the infected partner, the index case, is receiving suppressive antiretroviral treatment. A prospective cohort included all HIV serodiscordant couples attended a counseling program in the period 2002 to 2013 who opted for natural conception and met the following criteria: index case on ART with persistent plasma viral suppression for at least the previous 6 months, ART compliance over 95%, preserved immune status, undetectable HIV viral and proviral load in semen in male index cases, and absence of genitourinary infections and fertility problems in both members of the couple. Of the 161 HIV serodiscordant couples included, 133 with male index cases, 66% achieved at least 1 pregnancy, 18% a second one, and 5% a third pregnancy. A total of 144 natural pregnancies occurred and 107 babies were born. The pregnancy rate was 1.9 for each 100 acts of vaginal intercourse, and the mean time to conception was 6.1 months, both independently of the sex of the index case. No case of sexual or vertical HIV transmission occurred. In the absence of fertility problems and under controlled conditions, natural conception might be a safe and effective reproductive method for those HIV serodiscordant couples who choose this reproductive option. PMID:27472733

  4. The impact of maternal anti-retroviral therapy on cytokine profile in the uninfected neonates.

    PubMed

    Kasahara, Taissa M; Hygino, Joana; Blanco, Bernardo; Xavier, Luciana; Araújo-Lima, Carlos Fernando; Guillermo, Landi V C; Bittencourt, Vera Carolina B; Guimarães, Vander; Andrade, Arnaldo F B; Bento, Cleonice A M

    2013-09-01

    The number of HIV-infected young women has been increasing since the beginning of the AIDS epidemic. The objective of the present study was to investigate the impact of anti-retroviral treatment (ART) of HIV-1-infected pregnant women (PW) on cytokine profile of uninfected neonates. Our results demonstrated that higher levels of IL-1β and TNF-α associated with lower IL-10 production were detected in the plasma obtained from neonates born from ART-treated PW. Furthermore, the production of TNF- α and IFN-γ was also significantly higher in polyclonally-activated T cells from those neonates. This elevated pro-inflammatory pattern detected by these activated-T cells was not associated to HIV-1 antigens sensitization. Finally, ART-exposed neonates showed to be born with lower weight, and it was inversely correlated with maternal peripheral TNF-a level. In summary, the data presented here suggest a significant disturbance in cytokine network of HIV-1-uninfected neonates exposed to potent anti-retroviral schemes during pregnancy.

  5. CD8(+) Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy.

    PubMed

    Cartwright, Emily K; Spicer, Lori; Smith, S Abigail; Lee, David; Fast, Randy; Paganini, Sara; Lawson, Benton O; Nega, Melon; Easley, Kirk; Schmitz, Joern E; Bosinger, Steven E; Paiardini, Mirko; Chahroudi, Ann; Vanderford, Thomas H; Estes, Jacob D; Lifson, Jeffrey D; Derdeyn, Cynthia A; Silvestri, Guido

    2016-09-20

    Infection with HIV persists despite suppressive antiretroviral therapy (ART), and treatment interruption results in rapid viral rebound. Antibody-mediated CD8(+) lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows that these cells contribute to viral control in untreated animals. However, the contribution of CD8(+) lymphocytes to maintaining viral suppression under ART remains unknown. Here, we have shown that in SIV-infected RMs treated with short-term (i.e., 8-32 week) ART, depletion of CD8(+) lymphocytes resulted in increased plasma viremia in all animals and that repopulation of CD8(+) T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4(+) T cells before depletion positively correlated with both the peak and area under the curve of viremia after depletion. These results suggest a role for CD8(+) T cells in controlling viral production during ART, thus providing a rationale for exploring immunotherapeutic approaches in ART-treated HIV-infected individuals.

  6. Cryptococcal antigen screening and preemptive therapy in patients initiating antiretroviral therapy in resource-limited settings: a proposed algorithm for clinical implementation.

    PubMed

    Jarvis, Joseph N; Govender, Nelesh; Chiller, Tom; Park, Benjamin J; Longley, Nicky; Meintjes, Graeme; Bekker, Linda-Gail; Wood, Robin; Lawn, Stephen D; Harrison, Thomas S

    2012-01-01

    HIV-associated cryptococcal meningitis (CM) is estimated to cause over half a million deaths annually in Africa. Many of these deaths are preventable. Screening patients for subclinical cryptococcal infection at the time of entry into antiretroviral therapy programs using cryptococcal antigen (CRAG) immunoassays is highly effective in identifying patients at risk of developing CM, allowing these patients to then be targeted with "preemptive" therapy to prevent the development of severe disease. Such CRAG screening programs are currently being implemented in a number of countries; however, a strong evidence base and clear guidance on how to manage patients with subclinical cryptococcal infection identified by screening are lacking. We review the available evidence and propose a treatment algorithm for the management of patients with asymptomatic cryptococcal antigenemia.

  7. Patients' characteristics and clinical implications of suboptimal CD4 T-cell gains after 1 year of successful antiretroviral therapy.

    PubMed

    Gutiérrez, Félix; Padilla, Sergio; Masiá, Mar; Iribarren, José A; Moreno, Santiago; Viciana, Pompeyo; Hernández-Quero, José; Alemán, Remedios; Vidal, Francesc; Salavert, Miguel; Blanco, José R; Leal, Manuel; Dronda, Fernando; Perez Hoyos, Santiago; del Amo, Julia

    2008-03-01

    To describe characteristics and prognosis of patients with suboptimal immunological response to combined antiretroviral therapy (CART). Using data from a multicenter cohort study, we selected patients who initiated CART and showed suboptimal CD4-T cell response (defined as <50 cells/L increase) after 1 year of therapy, despite sustained virological suppression. Characteristics of those patients were compared with subjects who showed optimal immunological response. Of 650 patients with virological suppression, 108 (16.6%) showed suboptimal CD4-T cell response. Independent predictors of suboptimal response were previous injection drug use (OR, 1.85; 95% CI, 1.12-2.98) and age at CART initiation (OR, 1.04 per year increase; 95%CI, 1.01-1.06). Hepatitis C virus coinfection was not associated with impaired immunological response. As compared with patients with optimal immunological response, those with suboptimal response had a higher mortality rate (3.22 versus 0.71 per 100 person-years; p=.001), but a similar rate of new AIDS-defining events. In patients with sustained virological suppression with CART, previous injection drug use, but not hepatitis C virus coinfection, and older age at initiation of therapy were associated with suboptimal CD4 T-cell responses. Patients with suboptimal response had a higher mortality over time, mainly due to diseases other than AIDS-defining events.

  8. Antiretroviral therapy provided to HIV-infected Malawian women in a randomized trial diminishes the positive effects of lipid-based nutrient supplements on breast-milk B vitamins123

    PubMed Central

    Allen, Lindsay H; Hampel, Daniela; Shahab-Ferdows, Setareh; York, Emily R; Adair, Linda S; Flax, Valerie L; Tegha, Gerald; Chasela, Charles S; Kamwendo, Debbie; Jamieson, Denise J; Bentley, Margaret E

    2015-01-01

    Background: Little information is available on B vitamin concentrations in human milk or on how they are affected by maternal B vitamin deficiencies, antiretroviral therapy, or maternal supplementation. Objective: The objective was to evaluate the effects of antiretroviral therapy and/or lipid-based nutrient supplements (LNSs) on B vitamin concentrations in breast milk from HIV-infected women in Malawi. Design: Breast milk was collected from 537 women recruited within the Breastfeeding, Antiretrovirals, and Nutrition study at 2 or 6 wk and 24 wk postpartum. Women were assigned to receive antiretrovirals and LNSs, antiretrovirals only, LNSs only, or a control. Antiretrovirals and LNSs were given to the mothers from weeks 0 to 28. The antiretrovirals were zidovudine/lamivudine and nelfinavir or lopinavir/ritonavir. LNSs provided 93–118% of the Recommended Dietary Allowances of thiamin, riboflavin, niacin, pyridoxine, and vitamin B-12. Infants were exclusively breastfed. Results: LNSs increased milk concentrations of all vitamins except thiamin, whereas antiretrovirals lowered concentrations of nicotinamide, pyridoxal, and vitamin B-12. Although antiretrovirals alone had no significant effect on riboflavin concentrations, they negatively affected the LNS-induced increase in this vitamin. Thiamin was not influenced by the study interventions. Concentrations of all B vitamins were much lower than usually accepted values. Conclusions: All B vitamins were low in milk, and all but thiamin were increased by maternal supplementation with LNSs. Antiretrovirals alone decreased concentrations of some B vitamins in milk. When LNS was given in addition to antiretrovirals, the negative effect of antiretrovirals offset the positive effect of LNSs for all vitamins except thiamin. This trial was registered at clinicaltrials.gov as NCT00164762. PMID:26537941

  9. Home-based caregivers' knowledge regarding anti-retroviral therapy in Namibia.

    PubMed

    Niikondo, H N; Hoque, M E; Ntuli-Ngcobo, B

    2011-03-01

    Lack of practical knowledge among home-based caregivers (HBCs) on HIV/AIDS, anti-retroviral treatment (ART) and poor individual adherence to treatment are among the root causes of ineffective ART service delivery in Namibia. The purpose of the study was to investigate the knowledge of HBCs in Namibia regarding ART. The study was a descriptive, cross-sectional study in which 89 participants completed self-administered questionnaires to assess their knowledge regarding ART. Knowledge of HBCs on ART was above average in some aspects, there was still lack of knowledge on necessity of post-test counseling. Training organizations should put emphasis on the necessity of post-test counseling, consequence of poor adherence and type of facilities that issue ART.

  10. Prevention of HIV-1 Infection with Early Antiretroviral Therapy: Treatment as -

    NASA Astrophysics Data System (ADS)

    Gilada, Ishwar; Gilada, T.

    2014-07-01

    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...

  11. HBV influence on Response to Antiretroviral Therapy in Horizontally HIV-HBV Coinfected Patient during Early Childhood

    PubMed Central

    Niculescu, Irina; Cupşa, A.M.; Stoian, Andreea Cristina; Dumitrescu, FLorentina; Giubelan, L.I.; Alexandru, D.O.

    2013-01-01

    Background: There are few studies on pediatric HIV-HBV coinfection, so evidences about relationships between the two viruses are scarce. Objectives: influence of HBV infection on virological and immunological response to antiretroviral therapy (ART) in antiretroviral-naïve horizontally HIV-HBV coinfected subjects during early childhood. Material and methods: observational study on 826 HIV+ subjects in evidence of Craiova Regional Centre (CRC); we analyzed the immunological and virological response at 6-12 months after starting first antiretroviral regimens compared in 2 groups: horizontally HIV-HBV coinfected subjects during early childhood (CoS) versus horizontally HIV infected subjects during early childhood without HBV infection (non-CoS). Results: Number of subjects: CoS-66 subjects, non-CoS-132 subjects. Demographic data: CoS-gender ratio F:M=0.886, the majority lived in rural area (57.58%), mean age on diagnosis-9.288±4.607 years, non-CoS-gender ratio F:M=0.859, the majority lived in urban area (53.79%), mean age on diagnosis-10.742±5.107 years. At baseline, HIV category was: CoS-A-1.52%, B-80.30%, C-18.18%, non-CoS-A-2.27%, B-70.45%, C-27.27% (p Chi2=0.332), the mean CD4+ cell count was: CoS-148.33±148.10 cells/ml, non-CoS-163.17±155.39 cells/ml (p Student=0.521) and the mean HIV viral load (HIV VL) was: CoS-5.06±0.80 lgcopies/ml (for 29 subjects), non-CoS-5.04±0.84 lgcopies/ml (for 61 subjects) (p Student=0.978). At the end of the studied period, the mean increase in CD4+ cell count was: CoS-177.068±141.676 cells/ml, non-CoS-176.015±191.751 cells/ml (p Student=0.969) and the mean decrease in HIV VL was: CoS-5.04±0.79 lgcopies/ml, non-COS-4.69±2.04 lgcopies/ml (p Student=0.911). Conclusions: The presence of HBV coinfection does not influence immunological or virological response to ART. PMID:24778861

  12. The vulnerability of men to virologic failure during antiretroviral therapy in a public routine clinic in Burkina Faso

    PubMed Central

    Penot, Pauline; Héma, Arsène; Bado, Guillaume; Kaboré, Firmin; Soré, Ibrahim; Sombié, Diamasso; Traoré, Jean-Richard; Guiard-Schmid, Jean-Baptiste; Fontanet, Arnaud; Slama, Laurence; Sawadogo, Adrien Bruno; Laurent, Christian

    2014-01-01

    Introduction Gender differences in antiretroviral therapy (ART) outcomes are critical in sub-Saharan Africa. We assessed the association between gender and virologic failure among adult patients treated in a public routine clinic (one of the largest in West Africa) in Burkina Faso. Methods We performed a case-control study between July and October 2012 among patients who had received ART at the Bobo Dioulasso Day Care Unit. Patients were eligible if they were 15 years or older, positive for HIV-1 or HIV-1+2, and on first-line ART for at least six months. Cases were all patients with two consecutive HIV loads >1000 copies/mL (Biocentric Generic or Abbott Real Time assays), or one HIV load >1000 copies/mL associated with immunologic or clinical failure criteria. Controls were all patients who only had HIV loads <300 copies/mL. The association between gender and virologic failure was assessed using a multivariate logistic regression, adjusted on age, level of education, baseline CD4+ T cell count, first and current antiretroviral regimens and time on ART. Results Of 2303 patients (74.2% women; median age: 40 years; median time on ART: 34 months), 172 had virologic failure and 2131 had virologic success. Among the former, 130 (75.6%) had confirmed virologic failure, 38 (22.1%) had viro-immunologic failure, and four (2.3%) had viro-clinical failure. The proportion of men was significantly higher among the cases than among the controls (37.2% vs. 24.9%; p<0.001). Compared to controls, cases were also younger, more immunodeficient at ART initiation, less likely to receive a protease inhibitor-based antiretroviral regimen and had spent a longer period of time on ART. After adjustment, male gender remained strongly associated with virologic failure (odds ratio 2.52, 95% CI: 1.77–3.60; p<0.001). Conclusions Men on ART appeared more vulnerable to virologic failure than women. Additional studies are needed to confirm the poorer prognosis of men in this setting and to

  13. Long-Term Efficacy of First Line Antiretroviral Therapy in Indian HIV-1 Infected Patients: A Longitudinal Cohort Study

    PubMed Central

    Neogi, Ujjwal; Heylen, Elsa; Shet, Anita; Chandy, Sara; Shamsunder, Ranjani; Sönnerborg, Anders; Ekstrand, Maria L.

    2013-01-01

    Background Short term efficacy of combination antiretroviral therapy (cART) in resource-constrained settings is comparable to that found in western studies. However, long term data are limited. India has the third largest HIV infected population in the world but the long-term outcome of first line therapy according to the national guidelines has not been evaluated yet. Therefore, we conducted a long-term longitudinal analysis of the efficacy of the national first-line therapy in India from an observational cohort of Indian patients in two different clinical settings. Methodology/Principal Findings A total 323 patients who had been on ART for a median of 23 months and achieved virological suppression <100 copies/ml by their study baseline visit, were included and followed for two years. Blood samples were collected every six months for viral load and CD4 count. Drug resistance genotyping was performed when the viral load was >2000 copies/mL. Adherence and treatment interruptions (>48 h) were assessed via self-report. In the studied patients, the median duration of viral suppression was 44 months; 15.8% of patients showed viral rebound, and 2.8% viral failure. Viral rebound or failure was significantly negatively related to perfect adherence (100% adherence and no treatment interruption >48 hrs). Virological re-suppression in the subsequent visit was observed in three patients without any change in therapy despite the presence of key mutations. Conclusion/Significance Our study reports for the first time, a good long-term response to the first line therapy for a median of nearly four years although a less than perfect adherence increases the risk for treatment failure and subsequent drug resistance development. The empirical findings in this study also indicate the overall success of the Indian ART program in two different settings which likely are representative of other clinics that operate under the national guidelines. PMID:23383185

  14. “Risk factors associated with virologic failure in HIV-infected patients receiving antiretroviral therapy at a public hospital in Peru”

    PubMed Central

    Jorge, Alave R; Jorge, Paz B; Elsa, Gonzalez L; Miguel, Campos S; Rodriguez, Martin; Willig, James; Juan, Echevarría Z

    2013-01-01

    OBJECTIVE To describe clinical and biological characteristics of subjects with virologic failure who participated in the sexually transmitted diseases HIV/AIDS National Program from a Peruvian public hospital. MATERIALS AND METHODS An exploratory descriptive study was performed with data from subjects older than 18 who started high activity antiretroviral therapy (HAART) between May 2004 and December 2009 and who had a viral load control after 24 weeks of HAART. Virologic failure was defined as a viral load value above 1000 copies/mL on follow up after 24 weeks on HAART. RESULTS Of 1 478 records of patients on HAART analized, the median age was 35 years [IQR, 29-41] and 69.6% were male. Also, virologic failure occurred in 24% and 3.7% died. Of subjects with virologic failure, 9.5% died. On multivariate analysis, age, history of antiretroviral use before starting HAART, change of antiretroviral therapy due to toxicity, opportunistic infections during HAART, level of CD4 + lymphocytes below 100 cells/ml at start of HAART, adherence and clinical stage were independently associated with virologic failure. In the group of patient with no history of antiretroviral use before starting HAART, age, opportunistic infections during HAART were associated with virologic failure. CONCLUSION This study identified factors associated with virologic failure. Further studies are needed to evaluate whether the use of these factors can help to identify prospectively patients at high risk of failure, and to design interventions aimed to reduce this risk. PMID:23450408

  15. A pharmacogenetic study of CD4 recovery in response to HIV antiretroviral therapy in two South African population groups.

    PubMed

    Parathyras, John; Gebhardt, Stefan; Hillermann-Rebello, Renate; Grobbelaar, Nelis; Venter, Mauritz; Warnich, Louise

    2009-05-01

    South Africa, like many other Southern African countries, has one of the highest HIV infection rates in the world and many individuals consequently receive antiretroviral therapy (ART). However, knowledge regarding (i) the prevalence of functional single nucleotide polymorphisms (SNPs) in pharmacologically relevant genes, and (ii) variance in pharmacotherapy both within and between different populations and ethnic groups is limited. The aim of this study was to determine whether selected polymorphisms in cytochrome P450 (CYP) genes (CYP2B6 and CYP3A4) and the multidrug-resistance 1 (ABCB1) gene underlie altered antiretroviral (ARV) drug response in two South African populations. DNA samples from 182 HIV-positive individuals of Mixed-Ancestry and Xhosa ethnicity on ART were genotyped for the A-392G SNP in CYP3A4, the G516T and A785G SNPs in CYP2B6, and the T-129C, C1236T, G2677T/A and C3435T SNPs in ABCB1. Univariate two-way analysis of variance (ANOVA) testing revealed no apparent effect of ethnicity on immune recovery (in terms of CD4-cell count) in response to ART. Univariate one-way ANOVA testing revealed a discernible effect of genotype on immune recovery in the cases of the T-129C (P=0.03) and G2677A (P<0.01) polymorphisms in the ABCB1 gene. This study serves as a basis for better understanding and possible prediction of pharmacogenetic risk profiles and drug response in individuals and ethnic groups in South Africa.

  16. Maternal Highly Active Antiretroviral Therapy Reduces Vertical Cytomegalovirus Transmission But Does Not Reduce Breast Milk Cytomegalovirus Levels.

    PubMed

    Slyker, Jennifer A; Richardson, Barbra; Chung, Michael H; Atkinson, Claire; Ásbjörnsdóttir, Kristjana H; Lehman, Dara A; Boeckh, Michael; Emery, Vincent; Kiarie, James; John-Stewart, Grace

    2017-04-01

    To evaluate the impact of highly active antiretroviral therapy (HAART) on CMV transmission and breast milk level in the context of maternal HIV. Specimens from a randomized trial conducted in Nairobi, Kenya between 2003-2005 were used to compare CMV transmission and breast milk levels between mother-infant pairs randomized to HAART versus short-course antenatal zidovudine plus single-dose nevirapine (ZDV/sdNVP) for prevention of mother-to-child HIV transmission (PMTCT). Fifty-one antiretroviral-naïve women ≤32 weeks gestation, and CD4 between 200-500 cells/mm(3) were randomized at 34 weeks to begin either antenatal ZDV/sdNVP, or HAART through 6 months postpartum. Mean breast milk CMV levels and transmission were compared between arms. Age, sociodemographics, CD4%, and HIV plasma RNA viral load were similar between arms at baseline. CMV viral loads were measured from 243 infant plasma and 185 breast milk specimens during the first year postpartum. The probability of infant CMV infection at 12 months was 19% lower in the HAART arm compared to ZDV/sdNVP (75% vs. 94%, p = .04). All women had CMV detected in breast milk, with 72%, 98%, and 97% testing positive during the first, second, and third weeks postpartum, respectively. There was a trend for early higher mean breast milk CMV level in the HAART arm at 1 week (p = .08), and there was significantly slower decline in breast milk CMV levels (area under the curve, p = .01). HAART started during the third trimester may decrease infant CMV infections, by mechanisms independent of breast milk CMV levels.

  17. Quality of life of people living with HIV/AIDS and on highly active antiretroviral therapy in Ethiopia.

    PubMed

    Abera, Kebede; Gedif, Teferi; Engidawork, Ephrem; Gebre-Mariam, Tsige

    2010-04-01

    The Amharic version of the Short Form-36 Health Survey (SF-36) was used to measure quality of life among patients on highly active antiretroviral therapy (HAART) at selected governmental hospitals in central and southern Ethiopia. The study was cross-sectional and used SF-36-specific software for automatic scoring of the form's scales and dimensions. Pearson bivariate correlations showed moderate correlation between the SF-36 scales, ranging from 0.2673 between 'general health' and 'vitality,' to 0.8583 between 'role physical' and 'role emotional.' Cronbach's-αwas >0.70 for six out of eight multi-item scales, with values ranging from 0.6500 to 0.8860 for all scales, thus indicating good internal reliability of the Amharic version of the SF-36. The independent variables shown to positively affect mean scores were: duration of treatment, CD4 cell count, and adherence to doses of antiretrovirals. Participants treated for >12 months had higher mean scores for all domains than those who had been treated for ≤12 months. Likewise, those with a CD4 cell count >200 cells/mm(3) had better mean scores for all scales except 'social functioning' and 'mental health' than those with counts ≤200. Participants adhering to treatment (in the last 15 days, according to self-report) had better mean scores for all scales except 'role physical,' 'bodily pain' and 'vitality' in comparison to those who were not adherent. The findings suggest that the Amharic version of the SF-36 is a valid and reliable health survey instrument for use in Ethiopia to assess the quality of life of people living with HIV/AIDS on HAART.

  18. Assessment of HIV antiretroviral therapy adherence by measuring drug concentrations in hair among children in rural Uganda

    PubMed Central

    Olds, Peter K.; Kiwanuka, Julius P.; Nansera, Denis; Huang, Yong; Bacchetti, Peter; Jin, Chengshi; Gandhi, Monica; Haberer, Jessica E.

    2014-01-01

    Current tools for measuring medication adherence have significant limitations, especially among pediatric populations. We conducted a prospective observational study to assess the use of antiretroviral (ARV) drug levels in hair for evaluating antiretroviral therapy (ART) adherence among HIV-infected children in rural Uganda. Three-day caregiver recall, 30-day visual analog scale (VAS), Medication Event Monitoring System (MEMS), and unannounced pill counts and liquid formulation weights (UPC) were collected monthly over a one-year period. Hair samples were collected quarterly and analyzed for nevirapine (NVP) levels, and plasma HIV RNA levels were collected every six months. Among children with at least one hair sample collected, we used univariable random intercept linear regression models to compare log transformed NVP concentrations with each adherence measure, and the child’s age, sex, and CD4 count percentage (CD4%). 121 children aged 2–10 years were enrolled in the study; 74 (61%) provided at least one hair sample, and the mean number of hair samples collected per child was 1.9 (standard deviation [SD] 1.0). Three-day caregiver recall, VAS, and MEMS were found to be positively associated with increasing NVP concentration in hair, although associations were not statistically significant. UPC was found to have a non-significant negative association with increasing hair NVP concentration. In conclusion, NVP drug concentrations in hair were found to have non-significant, although generally positive, associations with other adherence measures in a cohort of HIV-infected children in Uganda. Hair collection in this population proved challenging, suggesting the need for community education and buy-in with the introduction of novel methodologies. PMID:25483955

  19. Evaluation of the virological and metabolic effects of switching protease inhibitor combination antiretroviral therapy to nevirapine-based therapy for the treatment of HIV infection.

    PubMed

    Tebas, Pablo; Yarasheski, Kevin; Henry, Keith; Claxton, Sherri; Kane, E; Bordenave, B; Klebert, Michael; Powderly, William G

    2004-06-01

    In spite of indisputable benefits, the use of antiretroviral therapy is associated with multiple metabolic complications. Switching to simpler regimens might maintain viral suppression, improve metabolic side effects, and provide insight into the pathogenesis of these complications. Our objective was to carefully characterize the virological and metabolic effects of switching from a successful protease inhibitor (PI)-based antiretroviral regimen to a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with nevirapine (NVP). Forty patients, taking their first successful (less than 40 HIV RNA copies/ml) PI-based regimen, switched their PI to NVP. If patients did not tolerate NVP, substitution with efavirenz was allowed. The duration of the study was 48 weeks. At 12 weeks intervals subjects had multiple virological and metabolic parameters including glucose, insulin, C-peptide, glucagon, proinsulin, blood lipids, and lipoproteins. A subgroup of 18 patients also had body composition evaluations with DEXA scans and MRIs of the abdomen and the thighs as well as insulin tolerance tests. Ninety-five percent of the patients maintained viral suppression (95% CI 88-100%); only one patient failed and another developed hepatitis. There were improvements in glucose (decreased fasting glucose, insulin, and improved insulin tolerance) and lipid metabolism (decreased triglycerides and increased HDL), but no changes in body composition and bone mineral density. Our study supports a pathogenic role for PIs in the development of hypertriglyceridemia and insulin resistance, but a more limited role in the fat redistribution syndrome.

  20. Early Combination Antiretroviral Therapy Limits Exposure to HIV-1 Replication and Cell-Associated HIV-1 DNA Levels in Infants

    PubMed Central

    McManus, Margaret; Mick, Eric; Hudson, Richard; Mofenson, Lynne M.; Sullivan, John L.; Somasundaran, Mohan; Luzuriaga, Katherine

    2016-01-01

    The primary aim of this study was to measure HIV-1 persistence following combination antiretroviral therapy (cART) in infants and children. Peripheral blood mononuclear cell (PBMC) HIV-1 DNA was quantified prior to and after 1 year of cART in 30 children, stratified by time of initiation (early, age <3 months, ET; late, age >3 months-2 years, LT). Pre-therapy PBMC HIV-1 DNA levels correlated with pre-therapy plasma HIV-1 levels (r = 0.59, p<0.001), remaining statistically significant (p = 0.002) after adjustment for prior perinatal antiretroviral exposure and age at cART initiation. PBMC HIV-1 DNA declined significantly after 1 year of cART (Overall: -0.91±0.08 log10 copies per million PBMC, p<0.001; ET: -1.04±0.11 log10 DNA copies per million PBMC, p<0.001; LT: -0.74 ±0.13 log10 DNA copies per million PBMC, p<0.001) but rates of decline did not differ significantly between ET and LT. HIV-1 replication exposure over the first 12 months of cART, estimated as area-under-the-curve (AUC) of circulating plasma HIV-1 RNA levels, was significantly associated with PBMC HIV-1 DNA at one year (r = 0.51, p = 0.004). In 21 children with sustained virologic suppression after 1 year of cART, PBMC HIV-1 DNA levels continued to decline between years 1 and 4 (slope -0.21 log10 DNA copies per million PBMC per year); decline slopes did not differ significantly between ET and LT. PBMC HIV-1 DNA levels at 1 year and 4 years of cART correlated with age at cART initiation (1 year: p = 0.04; 4 years: p = 0.03) and age at virologic control (1 and 4 years, p = 0.02). Altogether, these data indicate that reducing exposure to HIV-1 replication and younger age at cART initiation are associated with lower HIV-1 DNA levels at and after one year of age, supporting the concept that HIV-1 diagnosis and cART initiation in infants should occur as early as possible. PMID:27104621

  1. Impact of chemotherapy for HIV-1 related lymphoma on residual viremia and cellular HIV-1 DNA in patients on suppressive antiretroviral therapy.

    PubMed

    Cillo, Anthony R; Krishnan, Supriya; McMahon, Deborah K; Mitsuyasu, Ronald T; Para, Michael F; Mellors, John W

    2014-01-01

    The first cure of HIV-1 infection was achieved through complex, multimodal therapy including myeloablative chemotherapy, total body irradiation, anti-thymocyte globulin, and allogeneic stem cell transplantation with a CCR5 delta32 homozygous donor. The contributions of each component of this therapy to HIV-1 eradication are unclear. To assess the impact of cytotoxic chemotherapy alone on HIV-1 persistence, we longitudinally evaluated low-level plasma viremia and HIV-1 DNA in PBMC from patients in the ACTG A5001/ALLRT cohort on suppressive antiretroviral therapy (ART) who underwent chemotherapy for HIV-1 related lymphoma without interrupting ART. Plasma HIV-1 RNA, total HIV-1 DNA and 2-LTR circles (2-LTRs) in PBMC were measured using sensitive qPCR assays. In the 9 patients who received moderately intensive chemotherapy for HIV-1 related lymphoma with uninterrupted ART, low-level plasma HIV-1 RNA did not change significantly with chemotherapy: median HIV-1 RNA was 1 copy/mL (interquartile range: 1.0 to 20) pre-chemotherapy versus 4 copies/mL (interquartile range: 1.0 to 7.0) post-chemotherapy. HIV-1 DNA levels also did not change significantly, with median pre-chemotherapy HIV-1 DNA of 355 copies/106 CD4+ cells versus 228 copies/106 CD4+ cells post-chemotherapy. 2-LTRs were detectable in 2 of 9 patients pre-chemotherapy and in 3 of 9 patients post-chemotherapy. In summary, moderately intensive chemotherapy for HIV-1 related lymphoma in the context of continuous ART did not have a prolonged impact on HIV-1 persistence. Clinical trials registration unique identifier: NCT00001137.

  2. Impact of Chemotherapy for HIV-1 Related Lymphoma on Residual Viremia and Cellular HIV-1 DNA in Patients on Suppressive Antiretroviral Therapy

    PubMed Central

    Cillo, Anthony R.; Krishnan, Supriya; McMahon, Deborah K.; Mitsuyasu, Ronald T.; Para, Michael F.; Mellors, John W.

    2014-01-01

    The first cure of HIV-1 infection was achieved through complex, multimodal therapy including myeloablative chemotherapy, total body irradiation, anti-thymocyte globulin, and allogeneic stem cell transplantation with a CCR5 delta32 homozygous donor. The contributions of each component of this therapy to HIV-1 eradication are unclear. To assess the impact of cytotoxic chemotherapy alone on HIV-1 persistence, we longitudinally evaluated low-level plasma viremia and HIV-1 DNA in PBMC from patients in the ACTG A5001/ALLRT cohort on suppressive antiretroviral therapy (ART) who underwent chemotherapy for HIV-1 related lymphoma without interrupting ART. Plasma HIV-1 RNA, total HIV-1 DNA and 2-LTR circles (2-LTRs) in PBMC were measured using sensitive qPCR assays. In the 9 patients who received moderately intensive chemotherapy for HIV-1 related lymphoma with uninterrupted ART, low-level plasma HIV-1 RNA did not change significantly with chemotherapy: median HIV-1 RNA was 1 copy/mL (interquartile range: 1.0 to 20) pre-chemotherapy versus 4 copies/mL (interquartile range: 1.0 to 7.0) post-chemotherapy. HIV-1 DNA levels also did not change significantly, with median pre-chemotherapy HIV-1 DNA of 355 copies/106 CD4+ cells versus 228 copies/106 CD4+ cells post-chemotherapy. 2-LTRs were detectable in 2 of 9 patients pre-chemotherapy and in 3 of 9 patients post-chemotherapy. In summary, moderately intensive chemotherapy for HIV-1 related lymphoma in the context of continuous ART did not have a prolonged impact on HIV-1 persistence. Clinical Trials Registration Unique Identifier: NCT00001137 PMID:24638072

  3. [Successful treatment with hyper-CVAD and highly active anti-retroviral therapy (HAART) for AIDS-related Burkitt lymphoma].

    PubMed

    Suzuki, Kazuhito; Nakazato, Tomonori; Sanada, Yukinari; Mihara, Ai; Tachikawa, Natsuo; Kurai, Hanako; Yoshimura, Yukihiro; Hayashi, Hiroyuki; Yoshida, Sachiko; Kakimoto, Tsunayuki

    2010-03-01

    A 38-year-old man was admitted to our hospital because of continuous fever and right facial palsy. He was diagnosed as HIV positive. Abdominal CT scan showed a large mass in the ascending colon. Gallium scintigraphy demonstrated increased uptake in the ascending colon. Colonoscopy was performed and histological examination of the colon tumor revealed Burkitt's lymphoma (BL). He received highly active anti-retroviral therapy (HAART) and his facial palsy improved. Because CD4 count was significantly low at 31/microl, he was treated with dose-adjusted EPOCH (DA-EPOCH) combined with HAART. Although the tumor was decreased in size by DA-EPOCH, we changed to the combination of hyper-CVAD/MTX-Ara-C alternating therapy with HAART in order to increase dose intensity. Six cycles of hyper-CVAD/MTX-Ara-C were performed and complete remission was obtained. In the HAART era, the survival of patients with AIDS-related diffuse large cell lymphoma (DLCL) improved dramatically, whereas the survival of similarly treated patients with AIDS-related BL remained poor. Our case suggests that intensive chemotherapy with hyper-CVAD/MTX-Ara-C combined with HAART may be well tolerated and effective in AIDS-related BL.

  4. Elevated Plasma Viral Loads in Romidepsin-Treated Simian Immunodeficiency Virus-Infected Rhesus Macaques on Suppressive Combination Antiretroviral Therapy

    PubMed Central

    Del Prete, Gregory Q.; Oswald, Kelli; Lara, Abigail; Shoemaker, Rebecca; Smedley, Jeremy; Macallister, Rhonda; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Li, Yuan; Fast, Randy; Kiser, Rebecca; Lu, Bing; Zheng, Jim; Alvord, W. Gregory; Trubey, Charles M.; Piatak, Michael; Deleage, Claire; Keele, Brandon F.; Estes, Jacob D.; Hesselgesser, Joseph; Geleziunas, Romas

    2015-01-01

    Replication-competent human immunodeficiency virus (HIV) persists in infected people despite suppressive combination antiretroviral therapy (cART), and it represents a major obstacle to HIV functional cure or eradication. We have developed a model of cART-mediated viral suppression in simian human immunodeficiency virus (SIV) mac239-infected Indian rhesus macaques and evaluated the impact of the histone deacetylase inhibitor (HDACi) romidepsin (RMD) on viremia in vivo. Eight macaques virologically suppressed to clinically relevant levels (<30 viral RNA copies/ml of plasma), using a three-class five-drug cART regimen, received multiple intravenous infusions of either RMD (n = 5) or saline (n = 3) starting 31 to 54 weeks after cART initiation. In vivo RMD treatment resulted in significant transient increases in acetylated histone levels in CD4+ T cells. RMD-treated animals demonstrated plasma viral load measurements for each 2-week treatment cycle that were significantly higher than those in saline control-treated animals during periods of treatment, suggestive of RMD-induced viral reactivation. However, plasma virus rebound was indistinguishable between RMD-treated and control-treated animals for a subset of animals released from cART. These findings suggest that HDACi drugs, such as RMD, can reactivate residual virus in the presence of suppressive antiviral therapy and may be a valuable component of a comprehensive HIV functional cure/eradication strategy. PMID:26711758

  5. Three different patterns of CD4 recovery in a cohort of Chinese HIV patients following antiretroviral therapy - a five-year observational study.

    PubMed

    Naftalin, Claire M; Wong, Ngai Sze; Chan, Denise P C; Wong, Ka Hing; Reidpath, Daniel D; Lee, Shui Shan

    2015-10-01

    To explore the heterogeneity of CD4 responses following highly active antiretroviral therapy, the patterns of CD4 recovery of HIV-1-infected Chinese patients who have been on their first antiretroviral regimen for ≥5 years were analysed. The CD4 trajectories were traced, smoothed and differentiated into three defined profiles. Half (56.3%) were 'satisfactory responders', with CD4 gain of >100 cells/μL and a peak of >350 cells/μL, plateauing before the end of Year 5. Thirty-three (24.4%) were 'continuing responders' whose CD4 rise persisted at Year 4-5. The remaining 26 (19.3%) were 'poor responders'. Presentation with AIDS before therapy was common not just among 'poor' but also paradoxically the 'continuing' responders. While a majority had responded well to antiretroviral therapy, older patients and those with AIDS diagnosis before initiation of therapy may never achieve a satisfactory level even with effective treatment. Categorization of HIV patients by their CD4 trajectory may support the prediction of immunological outcome over time, and ultimately inform treatment choices.

  6. Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa

    PubMed Central

    Petersen, Maya L.; Tran, Linh; Geng, Elvin H.; Reynolds, Steven J.; Kambugu, Andrew; Wood, Robin; Bangsberg, David R.; Yiannoutsos, Constantin T.; Deeks, Steven G.; Martin, Jeffrey N.

    2015-01-01

    Objective Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa. Design A cohort. Methods We examined patients with confirmed virologic failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA. Results Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30% [95% confidence interval (CI) 27–33]. The majority of patients (74%) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95% CI 1.1 –4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95% CI 0.99–5.8) to that of the entire cohort, although of borderline statistical significance. Conclusion Among HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality. PMID:24977440

  7. Variable Impact on Mortality of AIDS-Defining Events Diagnosed during Combination Antiretroviral Therapy: Not All AIDS-Defining Conditions Are Created Equal

    PubMed Central

    2011-01-01

    Background The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. Methods We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a “rare ADEs” category. Results During a median follow-up period of 43 months (interquartile range, 19–70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]). Conclusions In the combination antiretroviral therapy era, mortality rates

  8. Depression, Substance Use, Viral Load, and CD4+ Count among Patients who continued or left Antiretroviral Therapy for HIV in St. Petersburg, Russian Federation

    PubMed Central

    Pecoraro, Anna; Mimiaga, Matthew; O'Cleirigh, Conall; Safren, Steven A.; Blokhina, Elena; Verbitskaya, Elena; Yaroslavtseva, Tatiana; Ustinov, Andrey; Lioznov, Dmitry A.; Zvartau, Edwin; Krupitsky, Evgeny; Woody, George E.

    2014-01-01

    Antiretroviral therapy (ART) became more widely available in the Russian Federation in 2006 when the Global Fund made a contribution to purchase ART with a mandate to increase numbers of patients receiving it. Funds were distributed to AIDS Centers and selected hospitals, and numbers quickly increased. Though ART is highly effective for adherent patients, dropout has been a problem; thus understanding characteristics of patients who remain on ART vs. those who leave treatment may provide information to facilitate engagement. We retrospectively assessed depression, hopelessness, substance use, viral load, and CD4+ counts of 120 patients who dropped out of ART for >12 months (Lost-to-Care; LTCs) and 120 who continued for >12 months (Engaged-in-Care; EICs). As expected, LTCs had higher viral loads and depression, lower CD4+ counts, and more alcohol, heroin, and injection drug use in the past 30 days. A binary logistic regression with Center for Epidemiologic Studies Depression score, Beck Hopelessness score, whether drugs/alcohol had ever prevented them from taking ART, and past 30 days’ alcohol use [X2(4)=64.27, p=.0.000] correctly classified 74.5% of participants as LTC or EIC, suggesting that integrated treatment for substance use, ps