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

Michael A. Eller, Marc S. Opollo, Michelle Liu, Andrew D. Redd, Leigh Anne Eller, Cissy Kityo, Joshua Kayiwa, Oliver Laeyendecker, Maria J. Wawer, Mark Milazzo, Noah Kiwanuka, Ronald H. Gray, David Serwadda, Nelson K. Sewankambo, Thomas C. Quinn, Nelson L. Michael, Fred Wabwire-Mangen, Johan K. Sandberg, Merlin L. Robb

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1574-1584
Number of pages11
JournalJournal of Infectious Diseases
Volume211
Issue number10
DOIs
StatePublished - May 15 2015
Externally publishedYes

Keywords

  • AIDS
  • HIV-1
  • Immune activation
  • PD-1
  • Subtype D
  • Viral load

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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