Are gender-related differences in viral load present in infants and children?

Studies in HIV-infected adults comparing genders have reported lower HIV-1 RNA values in women compared to men [1]. The exact mechanism for this phenomenon is currently uncertain, although it is speculated that the cause could be the influence of sex steroid hormone. A report from Mofenson and colleagues evaluated whether similar gender-related differences may also be present in infants and children [2].

HIV-RNA levels were performed on stored specimens (using the NASBA assay) from 254 HIV-infected antiretroviral naive children and infants, age range 0.3 to 11 years, enrolled in the PACTG 045 trial (of intravenous IgG) during 1988 to 1991. These were retrieved and tested in late 1995/early 1996, the lower limit of the assay was 4,000 copies/ml and for the purpose of this analysis results less than 4,000 copies/ml were assigned a value of 2,000 copies/ml. HIV-1 RNA levels in boys and girls were compared by t-test and repeated measure analysis. CD4 and lymphocyte percent was used due to less variability in measurement and less age-related change in children.

At study entry analysis of HIV-1 RNA levels did not show significant differences by gender. 1,118 RNA values were measured in a group of 113 girls and 141 boys, age range 0.4-10 (mean age 3.4) and 0.3 – 11 (mean age 3.4) years respectively. Mean baseline HIV-1 RNA did not differ significantly between girls compared to boys (97,806 vs. 110,423 copies/ml) and the mean value overall was 104,625 copies/ml (range <4,000 – 32,000,000).

When RNA levels were stratified by age, levels were significantly higher in girls compared to boys at age 1-2 years (p=0.004) and lower in girls at >6 years (p=0.04). Repeated measures showed girls and boys similar at younger but diverging at older ages. In children £6 years baseline HIV-1 RNA in girls compared to boys was 13,261 (95% CI 4,905-35,847) vs. 53,680 (24,350-117,471; p=0.04). In subjects <9 years HIV-1 RNA in girls compared to boys was 71,105 (55,873-90,469) vs. 81,115 (64,938-101,321; p=0.43). And at >=9 years the values were 8,710 (3,311-23,442) vs. 30,902 (12,303-77,625) in boys and girls respectively (p=0.06).

Adjusting for age and CD4 percentage at study entry HIV-1 RNA levels were not significantly associated with gender in younger children < 6 years of age but were associated in those >= 6 years of age. The investigators reported that the difference between girls and boys in their study aged 9 years and above (-0.5 log) is similar to that from adult studies reporting gender differences in HIV-1 RNA (-0.3 to – 0.5 log). And that although after adjusting for age and CD4% they observed no significant differences in HIV-1 RNA according to gender in children less than 6 years old, this trend towards lower values in girls than boys was observed as the children approached puberty. They concluded that ‘gender-specific differences in HIV-1 RNA levels may be mediated by factors associated with sexual maturation including sex steroid hormone levels.’