@article{3163760,
    title = "Temporal trends in prognostic markers of HIV-1 virulence and
transmissibility: an observational cohort study",
    author = "Pantazis, Nikos and Porter, Kholoud and Costagliola, Dominique and De and Luca, Andrea and Ghosn, Jade and Guiguet, Marguerite and Johnson, Anne and M. and Kelleher, Anthony D. and Morrison, Charles and Thiebaut, Rodolphe and and Wittkop, Linda and Touloumi, Giota and CASCADE Collaboration and EuroCoord",
    journal = "The Lancet HIV",
    year = "2014",
    volume = "1",
    number = "3",
    pages = "E119-E126",
    publisher = "HANLEY & BELFUS-ELSEVIER INC",
    issn = "2352-3018",
    doi = "10.1016/S2352-3018(14)00002-2",
    abstract = "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."
}