Herbeck, J T; Müller, V; Maust, B S; Ledergerber, B; Torti, C; Di Giambenedetto, S; Gras, L; Günthard, H F; Jacobson, L P; Mullins, J I; Gottlieb, G S (2012). Is the virulence of HIV changing? A meta-analysis of trends in prognostic markers of HIV disease progression and transmission. AIDS, 26(2):193-205.
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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 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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases|
|DDC:||610 Medicine & health|
|Deposited On:||29 Mar 2012 08:51|
|Last Modified:||23 Nov 2012 15:47|
|Publisher:||Lippincott Wiliams & Wilkins|
|WoS Citation Count:||7|
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