Disease progression and evolution of the HIV-1 env gene in 24 infected infants.

We have studied the relationship between disease progression and HIV-1 evolution in 24 infants classified as rapid or non-rapid progressors, during nearly the entire disease progression cycle from infection to AIDS. Specifically, we examined the temporal relationship between clinical status and changes in genetic diversity, divergence, selection and recombination at the C2V3C3 region of the env gene during a period of 3 years. Statistical analyses were performed using linear mixed models that are particularly well-suited for longitudinal studies in which repeated measures are taken from the same patients. We did not observe significant differences in genetic diversity or overall substitution rates between clinical categories. However, the nonsynonymous substitution rate per nonsynonymous site (dN) evolved differently between groups. Changes in dN explained the evolutionary slowdown of the dN/dS ratio in the rapid progressors, while in non-rapid progressors the dN/dS ratio continuously increased through time. The number of positively selected sites had limited power for predicting disease progression. Recombination rate estimates were different among groups, although not significantly in the linear mixed models analysis. They showed some power predicting clinical categories and, interestingly, they were significantly correlated with the frequency of positively selected sites. Overall, the results obtained confirm that viral adaptation in the C2V3C3 region of the env gene is related to disease progression, although the statistical characterization of such pattern seems rather difficult.