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. 2011 Mar 9;6(3):e17518.
doi: 10.1371/journal.pone.0017518.

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  1 , David Katzenstein, Gaetano Marrone, Fatima Laher, Lerato Mohapi, Max Petzold, Lynn Morris, Anna Mia Ekström
Affiliations

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 et al. PLoS One. .

Abstract

Background: Affordable 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.

Methods: In 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).

Results: After 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).

Conclusion: One 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. (a) Kaplan-Meier survival analysis for time to virologic failure by level of cumulative adherence to drug refill visits.
(b) Cox regression analysis after adjustment for confounding by CD4 cell count, age and being exposed to sdNVP or any ART pre-ART initiation.
Figure 2
Figure 2. (a) Kaplan-Meier survival analysis for time to immunologic failure, by level of cumulative adherence to drug refill visits.
(b) Cox regression analysis, adjusted for confounding by virologic failure, CD4 cell count, age and being exposed to sdNVP or any ART pre-ART initiation
Figure 3
Figure 3. Median CD4 (IQR) for patients initiated on ART, by adherence < or ≥95% based on drug-refill visits.
Figure 4
Figure 4. Median CD4 (IQR) for patients initiated on ART, with CD4 ≤ or >100 cells/µl.
Figure 5
Figure 5. Median CD4 (IQR) for patients who showed virologic failure vs. those who remained suppressed.
Figure 6
Figure 6. Proportion of patients (%) with self-reported reasons for not taking any of their pills in general at study enrolment (N = 458).
See this image and copyright information in PMC

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