TY - JOUR
TI - Temporal trends in prognostic markers of HIV-1 virulence and
transmissibility: an observational cohort study
AU - Pantazis, Nikos
AU - Porter, Kholoud
AU - Costagliola, Dominique
AU - De
AU - Luca, Andrea
AU - Ghosn, Jade
AU - Guiguet, Marguerite
AU - Johnson, Anne
AU - M.
AU - Kelleher, Anthony D.
AU - Morrison, Charles
AU - Thiebaut, Rodolphe
AU - and Wittkop, Linda
AU - Touloumi, Giota
AU - CASCADE Collaboration
AU - EuroCoord
JO - The Lancet HIV
PY - 2014
VL - 1
TODO - 3
SP - E119-E126
PB - HANLEY & BELFUS-ELSEVIER INC
SN - 2352-3018
TODO - 10.1016/S2352-3018(14)00002-2
TODO - null
TODO - 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.
ER -