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
Title | 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 |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Eller, 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 |
Journal | J Infect Dis |
Volume | 211 |
Pagination | 1574-84 |
Date Published | May 15 |
ISBN Number | 1537-6613 (Electronic)0022-1899 (Linking) |
Accession Number | 25404522 |
Keywords | AIDS, 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 |