Is the virulence of HIV changing? A meta-analysis of trends in prognostic markers of HIV disease progression and transmission

Joshua T. Herbeck, Viktor Müller, Brandon S. Maust, Bruno Ledergerber, Carlo Tortie, Simona Di Giambenedetto, Luuk Gras, Huldrych F. Günthard, Lisa P. Jacobsonh, James I. Mullins, Geoffrey S. Gottlieb

Research output: Contribution to journalArticlepeer-review


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. Design: 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 + Tcell 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 metaanalysis, 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 log10 copies/ml per year, 95% CI -0.001 to 0.03). The trend rates decelerated in recent years for both prognostic markers. Conclusion: 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 log10 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.

Original languageEnglish (US)
Pages (from-to)193-205
Number of pages13
Issue number2
StatePublished - Jan 14 2012


  • CD4 lymphocyte count
  • Disease progression
  • HIV infections/epidemiology
  • HIV infections/virology
  • HIV pathogenicity
  • Viral load/trends
  • Virulence

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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