Sex-associated differences in pre-antiretroviral therapy plasma HIV-1 RNA in diverse areas of the world vary by CD4(+) T-cell count

Background: Sex differences in the natural history of HIV infection may vary between resource-rich and resource-limited settings. Methods: Baseline characteristics from a randomized clinical trial of treatment-naive subjects conducted at sites in Africa, Asia, the Caribbean, and North and South America were analysed to determine if there were significant differences by sex. Results: Of the 1,571 participants, 740 (47.1%) were women. Women had higher mean screening CD4(+) T-cell counts (mean 15 cells higher; P<0.001), lower mean haemoglobin and creatinine clearance, a lower mean baseline HIV-1 viral load (4.85 log(10) versus 5.05 log(10) copies/ml; P<0.001) and were less likely to have a prior AIDS diagnosis than men. The sex difference in viral load was related to CD4(+) T-cell count; however, it was independent of country and persisted within the strata with CD4(+) T-cell count <200 cells/mm(3). Conclusions: Women in resource-limited settings have lower levels of plasma HIV-1 RNA and appear to present for enrolment into clinical trials at an earlier stage of disease than men. The biological basis for lower viral load in women compared to men remains unexplained. It will be important to determine if the sex differences observed at baseline impact clinical outcomes once the PEARLS clinical trial is completed.