Temporal trends in prognostic markers of HIV-1 virulence and transmissibility: an observational cohort study

Background Measures of CD4 T-cell count and HIV-1 plasma viral load before antiretroviral therapy are proxies for virulence. Whether these proxies are changing over time has implications for prevention and treatment. The aim of this study was to investigate those trends. Methods Data were derived from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) collaboration of mainly European seroconverter cohorts. Longitudinal CD4 cell counts and plasma viral load measurements before the initiation of antiretroviral therapy or AIDS onset were analysed by use of linear or fractional polynomials mixed models adjusting for all available potential confounders. Calendar time effects were modelled through natural cubic splines. Findings 15 875 individuals seroconverting from 1979 to 2008 fulfilled the inclusion criteria; 3215 (20.3%) were women; median follow-up was 31 months (IQR 14-62); dropout before starting antiretroviral therapy or AIDS onset was 8.1%. Estimated CD4 counts at seroconversion for a typical individual declined from about 770 cells per mu L (95% CI 750-800) in the early 1980s to a plateau of about 570 cells per mu L (555-585) after 2002. CD4 cell rate of loss increased up to 2002. Estimated set-point plasma viral loads increased from 4 . 05 log 10 copies per mL (95% CI 3.98-4.12) in 1980 to 4.50 log 10 copies per mL (4.45-4.54) in 2002 with a tendency of returning to lower loads thereafter. Results were similar when we restricted analyses to various subsets, including adjusting for plasma viral load assay, censored follow-up at 3 years, or used variations of the main statistical approach. Interpretation Our results provide strong indications of increased HIV-1 virulence and transmissibility during the course of the epidemic and a potential plateau effect after about 2002.