Effect of HIV-1 Subtypes on Disease Progression in Rural Uganda: A Prospective Clinical Cohort Study |
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Authors: | Deogratius Ssemwanga Rebecca N Nsubuga Billy N Mayanja Frederick Lyagoba Brian Magambo Dave Yirrell Lieve Van der Paal Heiner Grosskurth Pontiano Kaleebu |
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Institution: | 1. Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe, Uganda.; 2. Department of Medical Microbiology, Ninewells Hospital, Dundee, United Kingdom.; 3. International Rescue Committee, Dar es Salaam, Tanzania.; 4. London School of Hygiene and Tropical Medicine, London, United Kingdom.; The University of Hong Kong, China, |
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Abstract: | ObjectiveWe examined the association of HIV-1 subtypes with disease progression based on three viral gene regions.DesignA prospective HIV-1 clinical cohort study in rural Uganda.MethodsPartial gag, env and pol genes were sequenced. Cox proportional hazard regression modelling was used to estimate adjusted hazard ratios (aHRs) of progression to: CD4≤250, AIDS onset and death, adjusted for sex, age and CD4 count at enrolment.ResultsBetween 1990 and 2010, 292 incident cases were subtyped: 25% had subtype A, 45% had D, 26% had A/D recombinants, 1% had C and 4% were other recombinant forms. Of the 278 incident cases included in the disease progression analysis, 62% progressed to CD4≤250, 32% to AIDS, and 34% died with a higher proportion being among subtype D cases. The proportions of individuals progressing to the three endpoints were significantly higher among individuals infected with subtype D. Throughout the study period, individuals infected with subtype D progressed faster to CD4≤250, adjusted HR (aHR), (95% CI) = 1.72 (1.16–2.54), but this was mainly due to events in the period before antiretroviral therapy (ART) introduction, when individuals infected with subtype D significantly progressed faster to CD4≤250 than subtype A cases; aHR (95% CI) = 1.78 (1.01–3.14).ConclusionsIn this population, HIV-1 subtype D was the most prevalent and was associated with faster HIV-1 disease progression than subtype A. Further studies are needed to examine the effect of HIV-1 subtypes on disease progression in the ART period and their effect on the virological and immunological ART outcomes. |
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