The Role of Gender in HIV Progression

Ross G. Hewitt, MD; Nader Parsa, PhD; Lawrence Gugino, MD

Disclosures

AIDS Read. 2001;11(1) 

In This Article

Surrogate Marker Differences

The absolute number of CD4 cells indicates the extent of immune system damage that has already occurred in an HIV-infected person.[28] The decline rate of CD4 T-lymphocyte count can vary but normally averages 40 to 80/µL a year in untreated homosexual men.[6] However, some patients may have relatively stable CD4 cell counts for years, while others may experience a rapid decline over a period of several months. In a cohort of Zambian (untreated) HIV-seropositive women, median annual CD4 cell decline was significantly higher than in Zambian men.[29]

The absolute CD4 cell count and percentage were significantly higher in HIV-seronegative women than in heterosexual, HIV-seronegative men.[19] At baseline evaluation, HIV-seropositive women have higher absolute CD4 cell counts and higher CD4:CD8 ratios than do men.[30] This difference may persist for up to 5 years after HIV infection.[31] Women also have higher CD4 cell counts at AIDS onset than men.[32] Therefore, for any given CD4 cell count, women may be at a higher risk for HIV progression than men.

In men, there is an inverse correlation between plasma HIV RNA level and CD4 cell counts.[33,34] However, at any CD4 cell count, plasma HIV RNA concentrations show wide interindividual variation.[33,34,35] Those who display higher steady-state concentrations of plasma HIV RNA are at greater risk for disease progression.[36]

Among HIV-infected children aged 6 years or older, baseline geometric mean HIV RNA level was 13,261 copies/mL for girls versus 53,680 copies/mL for boys (P = .04).[37] Among children aged 9 years and older, repeated measures analysis showed a trend toward lower geometric mean HIV RNA values for girls than for boys: 8710 copies/mL versus 30,902 copies/mL (P = .06). Yet, among children younger than 6 years, no gender difference in HIV RNA levels was observed. These results suggest that gender differences in HIV RNA levels may be mediated by factors associated with sexual maturation.

In a cohort of injection drug users in the pre-HAART era, HIV-seropositive women were found to have significantly lower HIV RNA levels both at baseline and at a later follow-up visit compared with men.[38] Median viral load values for women were approximately half of those values for men, a finding also seen in other studies.[39,40] The differences were consistent by branched chain assay, polymerase chain reaction assay, and quantitative microculture technique after controlling for CD4 cell count. HIV RNA levels were also consistently lower for women across various CD4 cell count strata (0 to 200, 201 to 499, and greater than 500/µL). Women with the same viral load values as men had a 1.6-fold higher risk of progression to AIDS.

A nested, case-control, longitudinal study of HIV-1 seroconverters also showed that women have an initial median viral load level that is much lower than that of men: 14,918 copies/mL versus 148,354 copies/mL (P = .001).[41] Women experienced a much greater viral load increase over time (0.24 log per year versus 0.003 log per year, P = .002), so that after 5 years, the median viral load values became equivalent. These results are corroborated by other studies that show women with lower HIV RNA values in early-stage disease[42,43,44,45] but equivalent HIV RNA values in advanced-stage disease.[46,47]

The increased magnitude of HIV RNA levels was associated with an increased likelihood of isolating high-risk, oncogenic human papillomavirus genotypes from cervical specimens.[48] The incidence of abnormal Papanicolaou test results was 81% in women with such isolates. This observation is similar to the increased risk of opportunistic infection in men with high viral loads.[49]

When used in concert with viral load determinations, enumeration of CD4 cells enhances the accuracy with which the risk of disease progression and death in men can be predicted.[38] CD4 cell count was highly predictive of survival in a cohort of HIV-infected women, even in the presence of a low viral load.[50] Both CD4 cell count and HIV RNA level were predictive of survival. While lower viral loads and higher CD4 cell counts were also seen in the Swiss HIV Cohort Study, there were no gender differences in disease progression when CD4 cell counts and HIV RNA levels were controlled in Cox regression analyses.[51]

Not all cohorts have observed gender differences in patients' CD4 cell counts and viral loads. Within the Johns Hopkins primary care inner-city population, women had the same CD4:HIV RNA ratio as did men.[52] Investigators from the Community Programs for Clinical Research on AIDS (CPCRA) who conducted community-based studies also found no significant gender differences in viral load among patients enrolled in 6 clinical trials.[53]

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