No evidence of a change in HIV-1 virulence since 1996 in France

Objective: We investigated temporal trends in the CD4 cell count and in plasma HIV RNA and total HIV DNA levels measured at the time of primary HIV infection, as proxies for HIV-1 virulence, taking changes in patient characteristics into account. Design: We studied 903 patients enrolled during primary HIV infection in the French multicenter ANRS PRIMO cohort from 1996 to 2007. Methods: Associations between the year of primary HIV infection and the values of the three markers were tested with regression models. The year of primary HIV infection was first introduced as a restricted cubic splines function in a regression model in order to explore the shape of the associations, and then as a continuous/categorical variable. The following confounders were considered in multiple regression analysis: time since infection and age (introduced as restricted cubic spline functions), sex, place of birth (Africa vs. others), symptomatic primary HIV infection, smoking, and virus-related factors (subtype B vs. non-B, and drug resistance mutations). Results: Multivariate analysis showed no temporal trends in the CD4 cell count (square-root) or in HIV-1 RNA and DNA levels (log 10 ) measured at the time of primary HIV infection. We observed the well described associations between the prognostic markers and the time since infection, sex, symptomatic primary HIV infection, and smoking. Conclusion: The CD4 cell count and HIV RNA and DNA levels measured at the time of primary HIV-1 infection remained stable across 12 consecutive years (1996-2007) in the ANRS PRIMO cohort, suggesting no major change in virulence, after taking into account changes in patient characteristics.