CCR5 expression is reduced in lymph nodes of HIV type 1-infected women, compared with men, but does not mediate sex-based differences in viral loads

Background. Human immunodeficiency virus type 1 (HIV-1)-infected women have lower viral loads than men but similar rates of disease progression. We hypothesized that sex-based differences in CCR5 expression mediate viral load differences.Methods. CCR5 was analyzed by flow cytometry in disaggregated lymph node cells from untreated HIV-1-infected women (n = 28) and men (n = 27). The frequencies of HIV-1 RNA-producing cells in the lymph node were determined by in situ hybridization. Linear and generalized linear regression models were used.Results. The percentage of CCR5⁺CD3⁺CD4⁺ cells was lower in women (mean, 12%) than men (mean, 16%; P =. 034). Neither the percentage of CCR5⁺CD3⁺CD4⁺ cells nor the CCR5 density predicted viral load or HIV-1 RNA-producing lymph node cells (P ≥. 24), after adjusting for CD4⁺ T-cell count, race, and age. Women had marginally fewer HIV-1 RNA-producing cells (mean, 0.21 cells/mm²) than men (mean, 0.44 cells/mm²; P =. 046). After adjusting for the frequency of HIV-1 RNA-producing cells and potential confounders, the viral load in women were 0.46 log₁₀ copies/mL lower than that in men (P =. 018).Conclusions. Reduced lymph node CCR5 expression in women did not account for the viral load difference between sexes. CCR5 expression did not predict viral load or frequencies of HIV-1 RNA-producing cells, indicating that physiologic levels of CCR5 do not limit HIV-1 replication in lymph node. Less plasma virus was associated with each HIV-1 RNA-producing cell in women as compared to men, suggesting that women may either produce fewer virions per productively infected cell or more effectively clear extracellular virus.