Background:  Previous studies of gender associations in HIV disease demonstrated that CD4⁺ lymphocyte count-adjusted plasma HIV-1 RNA is approximately 0.2 log₁₀ copies/mL greater in men compared to women. Existing data are limited because they come largely from persons in developed areas of the world. We compared the characteristics of men and women with advanced HIV infection in Africa, Asia, the Caribbean, and North and South America to assess whether gender-associated differences in viral load are constant in diverse HIV-infected populations.

Methods:  Cross-sectional evaluation of 1571 antiretroviral-naïve persons (831 men, 740 women) with CD4⁺ lymphocytes <300 mm^–3 from 8 resource-limited countries and the United States enrolled in a randomized clinical trial, prior to initiation of ART. Comparisons between genders used Pearson χ² tests for categorical variables and t-tests for continuous variables. Linear regression modeled baseline plasma HIV-1 RNA (viral load) with screening CD4⁺ cell count, gender, history of AIDS, race and country as co-variates.

Results:  Compared to women, men were older, had lower body mass index, platelet and CD4⁺ lymphocyte counts, but higher albumin, hemoglobin, and creatinine clearance (p <0.001 for each comparison). Controlling for screening CD4⁺ cell count and stratifying by country, men had greater odds of any prior AIDS diagnosis  (OR 2.1, 95%CI 1.4 to 3.3), Pneumocystis jiroveci pneumonia (OR 4.5, 95%CI 1.0 to 20.0), and herpes simplex ulcers (OR 3.0, 95%CI 1.1 to 7.7). Unadjusted mean viral load was 5.05 log₁₀ copies/mL in men compared to 4.85 log₁₀ copies/mL in women (p <0.001). Viral load gender differences were not associated with country (p = 0.9). The male/female difference in viral load varied by CD4⁺ lymphocyte count (p = 0.04) in a linear regression model (see the table) that adjusted for race, country, and prior or current AIDS-related infections or malignancies. Gender by country, race and AIDS interactions were not significant (all p >0.5).

Conclusions:  Our analyses suggest that gender-associated viral load differences are more likely to be associated with inherent biological differences in men and women than with factors linked to geographic location including race, co-infections, culture, or environment.