Mortality in members of HIV-1 serodiscordant couples in Africa and implications for antiretroviral therapy initiation: Results of analyses from a multicenter randomized trial
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
BMC Infectious Diseases 2012, 12:277 doi:10.1186/1471-2334-12-277Published: 30 October 2012
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.
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.
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.
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.