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Open Access Highly Accessed Research article

Mortality in members of HIV-1 serodiscordant couples in Africa and implications for antiretroviral therapy initiation: Results of analyses from a multicenter randomized trial

Guy de Bruyn18*, Amalia Magaret27, Jared M Baeten345, Jairam R Lingappa456, Patrick Ndase4, Connie Celum345, Anna Wald235 and for the Partners in Prevention HSV/HIV Transmission Study Team

Author Affiliations

1 Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa

2 Departments of Laboratory Medicine, University of Washington, Seattle, WA, USA

3 Departments of Epidemiology, University of Washington, Seattle, WA, USA

4 Departments of Global Health, University of Washington, Seattle, WA, USA

5 Departments of Medicine, University of Washington, Seattle, WA, USA

6 Departments of Paediatrics, University of Washington, Seattle, WA, USA

7 Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

8 Present address: Sanofi Pasteur, Discovery Drive, Swiftwater, PA, USA

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BMC Infectious Diseases 2012, 12:277  doi:10.1186/1471-2334-12-277

Published: 30 October 2012

Abstract

Background

The risk of HIV-1 related mortality is strongly related to CD4 count. Guidance on optimal timing for initiation of antiretroviral therapy (ART) is still evolving, but the contribution of HIV-1 infection to excess mortality at CD4 cell counts above thresholds for HIV-1 treatment has not been fully described, especially in resource-poor settings. To compare mortality among HIV-1 infected and uninfected members of HIV-1 serodiscordant couples followed for up to 24 months, we conducted a secondary data analysis examining mortality among HIV-1 serodiscordant couples participating in a multicenter, randomized controlled trial at 14 sites in seven sub-Saharan African countries.

Methods

Predictors of death were examined using Cox regression and excess mortality by CD4 count and plasma HIV-1 RNA was computed using Poisson regression for correlated data.

Results

Among 3295 HIV serodiscordant couples, we observed 109 deaths from any cause (74 deaths among HIV-1 infected and 25 among HIV-1 uninfected persons). Among HIV-1 infected persons, the risk of death increased with lower CD4 count and higher plasma viral levels. HIV-1 infected persons had excess mortality due to medical causes of 15.2 deaths/1000 person years at CD4 counts of 250 – 349 cells/μl and 8.9 deaths at CD4 counts of 350 – 499 cells/μl. Above a CD4 count of 500 cells/μl, mortality was comparable among HIV-1 infected and uninfected persons.

Conclusions

Among African serodiscordant couples, there is a high rate of mortality attributable to HIV-1 infection at CD4 counts above the current threshold (200 – 350 cells/μl) for ART initiation in many African countries. These data indicate that earlier initiation of treatment is likely to provide clinical benefit if further expansion of ART access can be achieved.

Trial Registration

Clinicaltrials.gov (NCT00194519)