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

• Published in: The Journal of infectious diseases Vol. 211; no. 10; pp. 1574 - 1584
• Main Authors: Eller, Michael A., Opollo, Marc S., Liu, Michelle, Redd, Andrew D., Eller, Leigh Anne, Kityo, Cissy, Kayiwa, Joshua, Laeyendecker, Oliver, Wawer, Maria J., Milazzo, Mark, Kiwanuka, Noah, Gray, Ronald H., Serwadda, David, Sewankambo, Nelson K., Quinn, Thomas, Michael, Nelson L., Wabwire-Mangen, Fred, Sandberg, Johan K., Robb, Merlin L.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.05.2015
• Subjects: Adolescent; Adult; Disease Progression; Female; Genotype; HIV Infections - epidemiology; HIV Infections - immunology; HIV Infections - mortality; HIV Infections - virology; HIV-1 - classification; HIV-1 - genetics; HIV-1 - isolation & purification; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Lymphocyte Activation; Major and Brief Reports; Male; Medicin och hälsovetenskap; Rural Population; Survival Analysis; T-Lymphocytes - immunology; Uganda - epidemiology; Viral Load; Young Adult; Uganda; HIV-1; AIDS; viral load; PD-1; immune activation; subtype D
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiu646

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.