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

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(+) 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.

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  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.