Gender Differences in HIV RNA Levels: A Meta-Analysis of Published Studies

The concentration of circulating HIV RNA in plasma is an important prognostic marker for progression to AIDS, independent of CD4 count. The development of the use of this marker grew out of research conducted principally among male cohorts, and it has informed current US recommendations for the initiation of antiretroviral therapy (ART) in therapy-naive persons. Some recent studies have indicated that women have lower plasma HIV RNA levels than men, but other reports have not confirmed these observations. The present study seeks to offer research to assist the discussion over whether there is a need to revise downward the threshold for starting ART for treatment-naive women.

The authors conducted a quantitative meta-analysis of published studies to explore whether women have lower plasma HIV RNA levels than men. Separate analyses of gender comparisons were done with studies where HIV RNA levels were adjusted for CD4 counts, as well as of studies without that adjustment. Heterogeneity among the individual study CD4-adjusted estimates of gender differences in HIV RNA levels was investigated using formal statistical approaches. Sources of heterogeneity, differences in study design and differences in study subject characteristics were examined to see if these factors influenced the estimated gender difference in plasma HIV RNA copy number.

Fourteen published articles and one conference abstract met the authors' search criteria (see full study). The study subjects of most articles were subsets of participants enrolled in larger cohort studies or clinical trials. Results from 12 articles were available for the CD4-unadjusted analysis. Nine reports estimated a gender difference in average HIV RNA levels adjusted for CD4 counts and other covariates.

A gender difference in HIV RNA levels was observed in the CD4-unadjusted and -adjusted analyses. The authors of the articles reported CD4-adjusted HIV RNA gender comparisons in 10 patient groups. The summary estimate including only CD4-adjusted results with the lowest heterogeneity indicated that on average, women have 41 percent lower plasma HIV RNA levels than men (-.23 log10; 95 percent confidence interval [CI] -.16 to -.31 log10).

In 14 of the 15 available gender comparisons of CD4-unadjusted median or geometric mean (12) HIV RNA levels, women had lower values than men. The median female-to-male difference in HIV RNA was -.30 log10 (interquartile range, -.20 to -.42 log10, full range, .13 to -.80 log10), suggesting that women had, on average, half the CD4-unadjusted HIV RNA levels as men in these studies. With all studies included, the median or mean CD4 T cell counts were similar among men and women in the CD4-unadjusted studies. With all studies included, the median female-to-male difference in CD4 count levels was 11 cells/mm³ (interquartile range, 0 to 36; full range, -18 to 167; sign test, p=.1).

According to the researchers, because numerous studies have found similar HIV disease progression rates in men and women, adjusted for CD4 but not HIV RNA, the present study supports the use of lower HIV RNA thresholds in women than in men to guide initiation of ART. Given the patient characteristics in the articles for the meta-analysis, as well as evidence from this study and others that the gender difference in HIV RNA levels diminish at late stages of the disease, the results are most likely to apply to therapy-naive persons with CD4 counts greater than 200 cells/mm³, a subgroup for whom HIV RNA levels may strongly influence the decision to initiate therapy.

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