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HIV Type 1 Disease Progression to AIDS and Death in a Rural Ugandan Cohort Is Primarily Dependent on Viral Load Despite Variable Subtype and T-Cell Immune Activation Levels

TitleHIV Type 1 Disease Progression to AIDS and Death in a Rural Ugandan Cohort Is Primarily Dependent on Viral Load Despite Variable Subtype and T-Cell Immune Activation Levels
Publication TypeJournal Article
Year of Publication2015
AuthorsEller, MA, Opollo, MS, Liu, M, Redd, AD, Eller, LA, Kityo, C, Kayiwa, J, Laeyendecker, O, Wawer, MJ, Milazzo, M, Kiwanuka, N, Gray, RH, Serwadda, D, Sewankambo, NK, Quinn, TC, Michael, NL, Wabwire-Mangen, F, Sandberg, JK, Robb, ML
JournalJ Infect Dis
Volume211
Pagination1574-84
Date PublishedMay 15
ISBN Number1537-6613 (Electronic)0022-1899 (Linking)
Accession Number25404522
KeywordsAIDS, HIV-1, immune activation, Pd-1, subtype D, Viral Load
Abstract

BACKGROUND: Untreated human immunodeficiency virus type 1 (HIV) infection is associated with persistent immune activation, which is an independent driver of disease progression in European and United States cohorts. In Uganda, HIV-1 subtypes A and D and recombinant AD viruses predominate and exhibit differential rates of disease progression. METHODS: HIV-1 seroconverters (n = 156) from rural Uganda were evaluated to assess the effects of T-cell activation, viral load, and viral subtype on disease progression during clinical follow-up. RESULTS: The frequency of activated T cells was increased in HIV-1-infected Ugandans, compared with community matched uninfected individuals, but did not differ significantly between viral subtypes. Higher HIV-1 load, subtype D, older age, and high T-cell activation levels were associated with faster disease progression to AIDS or death. In a multivariate Cox regression analysis, HIV-1 load was the strongest predictor of progression, with subtype also contributing. T-cell activation did not emerge an independent predictor of disease progression from this particular cohort. CONCLUSIONS: These findings suggest that the independent contribution of T-cell activation on morbidity and mortality observed in European and North American cohorts may not be directly translated to the HIV epidemic in East Africa. In this setting, HIV-1 load appears to be the primary determinant of disease progression.

PMCID

PMC4425824