Sex differences in HIV RNA level and CD4 cell percentage during childhood

HIV-infected women have lower HIV RNA levels and higher CD4-cell counts than do men. This observation has been attributed to the immunomodulatory effects of sex steroid hormones, such as estrogen and progesterone. Limited data exist regarding potential sex differences in HIV RNA level and CD4 parameters among prepubertal children with untreated HIV infection.

We examined the relationship of sex to HIV RNA level and CD4 parameters among 670 perinatally HIV-infected, antiretroviral therapy-naive African children aged <18 years (median age, 4.8 years) using multivariate linear regression. In a subset of 188 children, we used longitudinal data to compare changes in HIV RNA levels and CD4 percentage over time. Levels of CD4 and CD8 T-cell activation (CD38+HLA-DR+) were also compared between boys and girls.

Female children had lower HIV RNA levels (P = .0004) and higher CD4 percentages (P < .0001), compared to male children. Multivariate linear regression demonstrated an independent association of sex with both HIV RNA level and CD4 percentages after controlling for other covariates. Multilevel mixed-effects linear regression analysis of longitudinal HIV RNA level and CD4 parameter data showed that sex differences persisted across all observed ages. Levels of T-cell activation did not differ between the sexes.

Significant sex differences in HIV RNA levels and CD4 parameters are present in HIV-infected children before the onset of puberty. These data suggest that intrinsic genetic differences between male and female individuals, unrelated to sex steroid hormone levels, influence HIV RNA level and CD4 parameters in HIV-infected individuals.