title: Is the virulence of HIV changing? A meta-analysis of trends in prognostic markers of HIV disease progression and transmission.
abstract: OBJECTIVE
  The potential for changing HIV-1 virulence has significant implications for the AIDS epidemic, including changing HIV transmission rates, rapidity of disease progression, and timing of ART. Published data to date have provided conflicting results.
  
  
  METHODS
  We conducted a meta-analysis of changes in baseline CD4(+) T-cell counts and set point plasma viral RNA load over time in order to establish whether summary trends are consistent with changing HIV-1 virulence.
  
  
  METHODS
  We searched PubMed for studies of trends in HIV-1 prognostic markers of disease progression and supplemented findings with publications referenced in epidemiological or virulence studies. We identified 12 studies of trends in baseline CD4(+) T-cell counts (21, 052 total individuals), and eight studies of trends in set point viral loads (10 ,785 total individuals), spanning the years 1984-2010. Using random-effects meta-analysis, we estimated summary effect sizes for trends in HIV-1 plasma viral loads and CD4(+) T-cell counts.
  
  
  RESULTS
  Baseline CD4(+) T-cell counts showed a summary trend of decreasing cell counts [effect = -4.93  cells/μl per year, 95% confidence interval (CI) -6.53 to -3.3]. Set point viral loads showed a summary trend of increasing plasma viral RNA loads (effect = 0.013  log(10)  copies/ml per year, 95% CI -0.001 to 0.03). The trend rates decelerated in recent years for both prognostic markers.
  
  
  CONCLUSIONS
  Our results are consistent with increased virulence of HIV-1 over the course of the epidemic. Extrapolating over the 30 years since the first description of AIDS, this represents a CD4(+) T cells loss of approximately 148  cells/μl and a gain of 0.39  log(10)  copies/ml of viral RNA measured during early infection. These effect sizes would predict increasing rates of disease progression, and need for ART as well as increasing transmission risk.
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, Washington, USA. herbeck@uw.edu
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Herbeck
authors.forename: Viktor
authors.initials: V
authors.lastname: Müller
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Maust
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.forename: Luuk
authors.initials: L
authors.lastname: Gras
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Gottlieb
mesh_terms: D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count / Q000379:methods; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000453:epidemiology / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load; D014774:Virulence
chemical_list: D015415:Biomarkers; D012367:RNA, Viral
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