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.
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.
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring Henry M. Jackson Foundation for the Advancement of Military Medicine.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Eller
authors.affiliation: Makerere University Walter Reed Project.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Opollo
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring Henry M. Jackson Foundation for the Advancement of Military Medicine.
authors.forename: Michelle
authors.initials: M
authors.lastname: Liu
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Redd
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring Henry M. Jackson Foundation for the Advancement of Military Medicine.
authors.forename: Leigh Anne
authors.initials: LA
authors.lastname: Eller
authors.affiliation: Joint Clinical Research Center.
authors.forename: Cissy
authors.initials: C
authors.lastname: Kityo
authors.affiliation: Joint Clinical Research Center.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kayiwa
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda School of Medicine.
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.affiliation: Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring Henry M. Jackson Foundation for the Advancement of Military Medicine.
authors.forename: Mark
authors.initials: M
authors.lastname: Milazzo
authors.affiliation: School of Public Health Rakai Health Sciences Program, Uganda Virus Research Institute, Entebbe.
authors.forename: Noah
authors.initials: N
authors.lastname: Kiwanuka
authors.affiliation: Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
authors.affiliation: School of Public Health Rakai Health Sciences Program, Uganda Virus Research Institute, Entebbe.
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.affiliation: Faculty of Medicine, Makerere University College of Health Sciences, Kampala Rakai Health Sciences Program, Uganda Virus Research Institute, Entebbe.
authors.forename: Nelson K
authors.initials: NK
authors.lastname: Sewankambo
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda School of Medicine.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: Makerere University Walter Reed Project School of Public Health.
authors.forename: Fred
authors.initials: F
authors.lastname: Wabwire-Mangen
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring Henry M. Jackson Foundation for the Advancement of Military Medicine.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
mesh_terms: D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology / Q000401:mortality* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D012424:Rural Population; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load; D055815:Young Adult
keywords: AIDS; HIV-1; PD-1; immune activation; subtype D; viral load