Adherence to drug-refill is a useful early warning indicator of virologic and immunologic failure among HIV patients on first-line ART in South Africa.

Ziad El-Khatib,Gaetano Marrone,Fatima Laher,Max Petzold,Lerato Mohapi,Lynn Morris,Anna Mia Ekström,David Katzenstein,Gary Maartens

doi:10.1371/journal.pone.0017518

Abstract

BackgroundAffordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa.MethodsIn 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12–99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO).ResultsAfter a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2–6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2–3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02).ConclusionOne in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure.

Highlights

Antiretroviral treatment (ART) has saved millions of lives by transforming HIV infection from a fatal into a chronic disease [1] and the vast majority (97%) of patients in sub-Saharan Africa receive a non-nucleoside reverse transcriptase (NNRTI) based regimen as first-line treatment [2]
Given the costs associated with second-line protease inhibitors, the long-term sustainability of antiretroviral therapy (ART) in many of low- and some middle-income countries depends on finding feasible ways for early detection of treatment failure to maintain patients on first-line regimens [3,4]
Since viral load (VL) monitoring is not currently accessible in most resource-limited high-endemic contexts [2,5], patients are often continued on first-line ART until the emergence of clinical symptoms or until any of the World Health Organization (WHO) criteria for immunologic failure are met

Summary

Introduction

Antiretroviral treatment (ART) has saved millions of lives by transforming HIV infection from a fatal into a chronic disease [1] and the vast majority (97%) of patients in sub-Saharan Africa receive a non-nucleoside reverse transcriptase (NNRTI) based regimen as first-line treatment [2]. To routinely assess the effectiveness of ART at HIV treatment clinics and to minimize preventable HIV drug resistance (HIVDR), WHO recommends using available site-based data from medical and pharmacy records, e.g. on-time adherence to monthly ART drug pick-up and clinic appointment-keeping [9,10], as an early warning indicator (EWI) of inconsistent drug exposure. We examined the association between adherence to drugrefill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa

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