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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa
AIDS, Volume 28, No. 14, Year 2014
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Description
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 nonnucleoside 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. © 2014 Wolters Kluwer Health.
Authors & Co-Authors
Petersen, Maya L.
United States, Berkeley
University of California, Berkeley
Tran, Linh
United States, Berkeley
University of California, Berkeley
Geng, Elvin H.
United States, San Francisco
University of California, San Francisco
Reynolds, Steven James
Uganda, Kalisizo
Rakai Health Sciences Program
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
United States, Baltimore
Johns Hopkins School of Medicine
Kambugu, Andrew Ddungu
Uganda, Kampala
Infectious Diseases Institute
Wood, Robin Y.
South Africa, Cape Town
University of Cape Town
Bangsberg, David R.
Uganda, Mbarara
Mbarara University of Science and Technology
United States, Boston
Harvard Medical School
Yiannoutsos, Constantin Theodore
United States, Indianapolis
Indiana University-purdue University Indianapolis
Deeks, Steven G.
United States, San Francisco
University of California, San Francisco
Martin, Jeffrey N.
United States, San Francisco
University of California, San Francisco
Statistics
Citations: 100
Authors: 10
Affiliations: 10
Identifiers
Doi:
10.1097/QAD.0000000000000349
e-ISSN:
14735571
Research Areas
Infectious Diseases
Study Design
Cohort Study
Case-Control Study
Study Locations
South Africa
Uganda