Injectable Contraceptives Differentially Affect Select CD4+ HIV-1 Target Cells in the Genital Tract but Not Systemically: Implications for HIV-1 Acquisition.

PROBLEM

Observational data suggest lower HIV susceptibility in women using the injectable contraceptive norethisterone enanthate (NET-EN) versus intramuscular depo medroxyprogesterone acetate (DMPA-IM). Clinical data investigating the effects of injectables on HIV target cells are inconsistent or limited. No data on HIV target cells are available from head-to-head randomized trials comparing DMPA-IM and NET-EN, nor at peak progestin concentrations.

METHOD OF STUDY

The women's health, injectable contraception, and HIV (WHICH) trial randomized women to DMPA-IM or NET-EN at two South African sites (2018-2019). Cells from blood and cytobrushes from women at one site, taken at baseline and 1 week post the 24-week injection (at peak progestin levels), were analyzed by flow cytometry for select HIV-1 target cells (CD4 cells expressing HIV-1 co-receptors, an integrin and/or activation markers).

RESULTS

Systemically, DMPA-IM and NET-EN similarly reduced the frequency and number of some CD4 cells and expression of some CD4 cell surface markers. In contrast, female genital tract (FGT) results showed significantly different cell numbers between contraceptives for most cell populations; DMPA-IM tended to increase, but NET-EN tended to decrease cell numbers. Excluding for non-study progestin use revealed significant increases in frequency and/or number of several FGT cell populations from baseline to 25 weeks, within the DMPA-IM arm.

CONCLUSIONS

Both contraceptives exert minimal effects on systemic CD4 cells but have differential effects in the FGT. The changes in frequency and numbers of HIV-1 target cells investigated, particularly after exclusion for non-study progestin use, suggest that DMPA-IM use may increase HIV-1 acquisition in the FGT compared to NET-EN use.