Early Mortality and AIDS Progression Despite High Initial Antiretroviral Therapy Adherence and Virologic Suppression in Botswana

Katherine T Steele,Jean B Nachega,Craig W Newcomb,Scarlett L Bellamy,Tumelo Rantleru,Rudo Nthobatsang,Gloria Lesetedi,Andrew P Steenhoff,Robert Gross,Gregory P Bisson,Nitika Pant Pai

doi:10.1371/journal.pone.0020010

Abstract

BackgroundAdverse outcomes occurring early after antiretroviral therapy (ART) initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana.MethodsThis prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence <0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs) and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%).ResultsSuboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1–4.8) and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4–4.7). However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively.ConclusionsSuboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on understanding early adverse outcomes that occur despite optimal adherence.

Highlights

Death in the initial months after initiating combination antiretroviral therapy (ART), often termed ‘‘early mortality,’’ accounts for the majority of all first-year deaths in adult HIV treatment programs in resource-limited settings [1,2,3].published data indicate that ART adherence is high in the very settings most affected by high rates of early mortality [4]
This suggests that classic mechanisms of HIV treatment failure, whereby suboptimal ART adherence leads to AIDS progression and death, may not predominate as a cause of early events
We evaluated the relationship between the earliest routinely available objective measure of early ART adherence and risk of early adverse outcomes after ART initiation in a sub-Saharan African setting

Summary

Introduction

Published data indicate that ART adherence is high in the very settings most affected by high rates of early mortality [4] This suggests that classic mechanisms of HIV treatment failure, whereby suboptimal ART adherence leads to AIDS progression and death, may not predominate as a cause of early events. Adherence as well as virologic and immunologic responses to ART among patients who suffer early mortality after ART initiation remains largely uncharacterized, in part because many events occur before these measures can be obtained. Landmark studies documenting the importance of initial ART response to subsequent survival have usually measured initial response several months after ART initiation, after the majority of very early deaths occur, and do not inform the relationship between virological and immunological response to ART and early mortality [10,11].

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Conclusion