Increasing clinical virulence in two decades of the Italian HIV epidemic.

The recent origin and great evolutionary potential of HIV imply that the virulence of the virus might still be changing, which could greatly affect the future of the pandemic. However, previous studies of time trends of HIV virulence have yielded conflicting results. Here we used an established methodology to assess time trends in the severity (virulence) of untreated HIV infections in a large Italian cohort. We characterized clinical virulence by the decline slope of the CD4 count (n = 1423 patients) and the viral setpoint (n = 785 patients) in untreated patients with sufficient data points. We used linear regression models to detect correlations between the date of diagnosis (ranging 1984-2006) and the virulence markers, controlling for gender, exposure category, age, and CD4 count at entry. The decline slope of the CD4 count and the viral setpoint displayed highly significant correlation with the date of diagnosis pointing in the direction of increasing virulence. A detailed analysis of riskgroups revealed that the epidemics of intravenous drug users started with an apparently less virulent virus, but experienced the strongest trend towards steeper CD4 decline among the major exposure categories. While our study did not allow us to exclude the effect of potential time trends in host factors, our findings are consistent with the hypothesis of increasing HIV virulence. Importantly, the use of an established methodology allowed for a comparison with earlier results, which confirmed that genuine differences exist in the time trends of HIV virulence between different epidemics. We thus conclude that there is not a single global trend of HIV virulence, and results obtained in one epidemic cannot be extrapolated to others. Comparison of discordant patterns between riskgroups and epidemics hints at a converging trend, which might indicate that an optimal level of virulence might exist for the virus.