Abstract
BackgroundIn Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up.MethodsThis was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained.Results161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01).ConclusionsAfter viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0567-3) contains supplementary material, which is available to authorized users.
Highlights
In Tanzania, HIV-1 RNA testing is rarely available and not standard of care
After viral load testing in 2008-09 many participants switched to second-line therapy
Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of antiretroviral therapy (ART) and improve virologic outcomes among youth in resource-limited settings
Summary
In Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. Despite a continued antiretroviral therapy (ART) treatment gap for children in resource-limited settings, the number of HIV-infected children initiating ART is increasing [3]. This scale up Therapeutic monitoring poses an additional challenge as HIV-1 RNA (viral load) testing is frequently unavailable in resource-limited settings. Unsuppressed viremia leads to accumulation of resistance mutations and patients monitored by clinical or immunologic criteria tend to have increased durations of unsuppressed viremia compared to those monitored with viral load [5] Despite this limitation, a majority of adults in resource-limited settings have attained virologic suppression on second-line regimens, even in the context of clinical or immunologically driven monitoring strategies [6,7]. The utility and cost/benefit of obtaining viral load and/or resistance profiles in such settings is controversial [8,9,10]
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