Background
New HIV-1 infections are increasing in older American women largely through heterosexual transmission. Activated CD4+ T-cells and CCR5 expression are linked to HIV-1 susceptibility, but whether these parameters are altered in the cervix of older women is unknown.
Methods
Whole blood and in some instances endocervical brush samples were collected from healthy premenopausal (n=22) and postmenopausal women (n=24). Percentages of HLA-DR(DR)+CD38(38)+CD4+ T-cells, and HIV-1 chemokine coreceptor expression were determined by flow cytometry.
Results
Percentages of DR+38+CD4+ T-cells were 6-times greater in cervix (median, 6.4%) than blood (median, 1.1%; p<0.001), but did not differ within each compartment between premenopausal and postmenopausal women (p=0.2). Postmenopausal women had greater percentages of CCR5+CD4+ and CCR5+DR+38+CD4+ T-cells compared to premenopausal women in cervix (median, 70% vs. 42%, p=0.005; and 80% vs. 57%; p<0.05, respectively) and blood (medians, 22% vs. 13%, and 76% vs. 62%, respectively; p<0.001). Postmenopausal women had more CCR5 molecules on cervical DR+38+CD4+ T-cells (median, 3,176) than premenopausal women (median, 1,776; p=0.02). Age and percent CCR5+CD4+ and CCR5+DR+38+CD4+-cells were linearly related in cervix (r2=0.47, p<0.001 and r2=0.25, p=0.01, respectively) and blood (r2=0.20, p=0.001 and r2=0.31, respectively; p<0.001), but confounding of age with menopause could not be excluded. Cervical CXCR4 expression did not differ substantially between premenopausal and postmenopausal women.
Conclusions
Elevated cervical CCR5 expression in postmenopausal women may increase their risk for HIV-1 acquisition. Studies are needed to confirm whether elevated CCR5 expression confers increased HIV-1 susceptibility in postmenopausal women, and if it is related to hormonal or nonhormonal effects of aging.