Long-term Virological Outcomes of First-Line Antiretroviral Therapy for HIV-1 in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis

Boender, T. Sonia; Sigaloff, Kim C.E.; McMahon, James; Kiertiburanakul, Sasisopin; Jordan, Michael R.; Barcarolo, Jhoney; Ford, Nathan; Wit, Tobias F. Rinke de; Bertagnolio, Silvia

doi:10.1093/cid/civ556

Cited by 137 publications

(122 citation statements)

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“…Subsequent sustenance of long-term and successful treatment outcomes depends primarily on achieving sustained viral suppression, supported by optimum life-long adherence [2]. Remarkably high levels of adherence have been reported in sub-Saharan Africa in comparison to western countries [3], but these findings contrast with those from other studies reporting increasing levels of patients with treatment failure [4,5], low retention [6] and high mortality rates [7]. Fewer studies have assessed adherence in long-term treated patients, despite the growing numbers as ART programs mature in the region [8–10].…”

Section: Introductionmentioning

confidence: 99%

Long-Term Antiretroviral Treatment Adherence in HIV-Infected Adolescents and Adults in Uganda: A Qualitative Study

Inzaule¹,

Hamers²,

Kityo³

et al. 2016

PLoS ONE

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BackgroundLong-term success of HIV antiretroviral therapy requires near-perfect adherence, maintained throughout one’s lifetime. However, perceptions towards ART and patterns of adherence may change during the life course. We assessed challenges to long-term adherence in adolescents and adults in three regional HIV treatment centers in Uganda.MethodsWe conducted 24 in-depth interviews and 2 focus group discussions with a total of 33 health-care providers and expert clients (HIV patients on long-term ART who assist with adherence support of fellow patients). Interview topics included experiences with patients on long-term treatment with either declining adherence or persistent poor adherence. Transcribed texts were coded and analyzed based on the social-ecological framework highlighting differences and commonalities between adolescents and adults.ResultsThe overarching themes in adolescents were unstructured treatment holidays, delays in disclosure of HIV status by caretakers, stigma, which was mainly experienced in boarding schools, and diminishing or lack of clinical support. In particular, there was minimal support for early and gradual disclosure for caretakers to the infected children, diminishing clinical support for young adults during transition to adult-based care and declining peer-to-peer support group activities. The predominating theme in adults was challenges with treatment access among temporary economic migrants. Common themes to adults and adolescents were challenges with disclosure in intimate relationships, treatment related factors including side effects, supply of single tablets in place of fixed-dose combined drugs, supply of drug brands with unfavorable taste and missed opportunities for counseling due to shortage of staff.ConclusionAdherence counseling and support should be adapted differently for adolescents and adults and to the emerging life course challenges in long-term treated patients. Programs should also address constraints experienced by temporary economic migrants to ensure continuity of treatment within the host country.

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Section: Introductionmentioning

confidence: 99%

Long-Term Antiretroviral Treatment Adherence in HIV-Infected Adolescents and Adults in Uganda: A Qualitative Study

Inzaule¹,

Hamers²,

Kityo³

et al. 2016

PLoS ONE

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“…[6–7] As WHO targets were not available for Viral load suppression at 6 months , Namibia used WHO’s 12-month targets as international literature reflected similar viral load suppression rates at 6 and 12 months. [18] The targets utilize three performance classifications: red (poor performance, below desired level), amber (fair performance, not yet at desired level), and green (excellent performance, achieving desired level). The targets also allow for a “grey” classification if a site does not have data available to monitor a specific EWI.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2016

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

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“…This is of importance, since although most ART regimens applied in the developed world do not include NRTIs, the great majority of HIV-infected patients are treated in the developing world (such as Africa) with regimens in which NRTIs are part of most first line therapies for ART 64,65. Interestingly, a recent study suggested that exposure to didanosine (even if later replaced) is a risk factor for liver fibrosis in HIV, although the mechanisms behind this effect are unclear 66.…”

Section: Mitochondrial Dysfunction and Toxicitymentioning

confidence: 99%

Mechanisms of Accelerated Liver Fibrosis Progression during HIV Infection

Debes

Bohjanen

Boonstra

2016

JCTH

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With the introduction of antiretroviral therapy (ART), a dramatic reduction in HIV-related morbidity and mortality has been observed. However, it is now becoming increasingly clear that liver-related complications, particularly rapid fibrosis development from ART as well as from the chronic HIV infection itself, are of serious concern to HIV patients. The pathophysiology of liver fibrosis in patients with HIV is a multifactorial process whereby persistent viral replication, and bacterial translocation lead to chronic immune activation and inflammation, which ART is unable to fully suppress, promoting production of fibrinogenic mediators and fibrosis. In addition, mitochondrial toxicity, triggered by both ART and HIV, contributes to intrahepatic damage, which is even more severe in patients co-infected with viral hepatitis. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV has been obtained, and these are detailed and discussed in this review.

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Long-term Virological Outcomes of First-Line Antiretroviral Therapy for HIV-1 in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis

Abstract: Among individuals retained on ART, virological suppression rates during the first 5 years of ART were high (>80%) and stable. Suppression rates in ITT analysis declined during 4 years.

Cited by 137 publications

References 13 publications

Long-Term Antiretroviral Treatment Adherence in HIV-Infected Adolescents and Adults in Uganda: A Qualitative Study

Long-Term Antiretroviral Treatment Adherence in HIV-Infected Adolescents and Adults in Uganda: A Qualitative Study

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

Mechanisms of Accelerated Liver Fibrosis Progression during HIV Infection

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