This research was supported by grants from the National Institutes of Health, P30 AI027763, R01 MH054907 and U01 AI069911, and U01 CA066529. Maya Petersen was supported by a Doris Duke Clinical Scientist Development Award. Steven Deeks was supported by K24 AI069994. David Bangsberg was supported by K24 MH87227 Elvin Geng was supported by K23 AI084544. S.J.R. was supported in part by the Division of Intramural Research, NIAID, NIH.
Antiretroviral therapy, HIV infections -- Treatment -- Uganda, HIV infections -- Treatment -- South Africa, AIDS (Disease) -- Patients -- Effect of virologic failure on, Pharmacoepidemiology -- Statistical methods
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.
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.
Wolters Kluwer Health
257. Petersen ML, Tran L, Geng EH, Reynolds SJ, Kambugu A, Wood R, Bangsberg DR, Yiannoutsos CT, Deeks SG, Martin JN. Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa. AIDS. 2014 Jun 28. [Epub ahead of print] PubMed PMID: 24977440