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Antiretroviral therapy, HIV infections -- Treatment -- Uganda, HIV infections -- Treatment -- South Africa, AIDS (Disease) -- Patients -- Effect of virologic failure on, Pharmacoepidemiology -- Statistical methods

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19 pages


Objective—Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa.

Design—A cohort.

Methods—We examined patients with confirmed virologic failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA.

Results—Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30% [95% confidence interval (CI) 27–33]. The majority of patients (74%) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95% CI 1.1 –4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95% CI 0.99–5.8) to that of the entire cohort, although of borderline statistical significance.

Conclusion—Among HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality.


David Bangsberg was affiliated with Mbarara University of Science and Technology and Harvard Medical School at the time of writing.

Published in final edited form as: AIDS. 2014 September 10; 28(14): 2097–2107. doi:10.1097/QAD.0000000000000349.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins



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Wolters Kluwer Health