The contraceptive medroxyprogesterone acetate, unlike norethisterone, directly increases R5 HIV-1 infection in human cervical explant tissue at physiologically relevant concentrations.

ABSTRACT: The intramuscular progestin-only injectable contraceptive, depo-medroxyprogesterone acetate (DMPA-IM), is more widely used in Sub-Saharan Africa than another injectable contraceptive, norethisterone enanthate (NET-EN). Epidemiological data show a significant 1.4-fold increased risk of HIV-1 acquisition for DMPA-IM usage, while no such association is shown from limited data for NET-EN. We show that MPA, unlike NET, significantly increases R5-tropic but not X4-tropic HIV-1 replication ex vivo in human endocervical and ectocervical explant tissue from pre-menopausal donors, at physiologically relevant doses. Results support a mechanism whereby MPA, unlike NET, acts via the glucocorticoid receptor (GR) to increase HIV-1 replication in cervical tissue by increasing the relative frequency of CD4

SUBMITTER: Ray RM 

PROVIDER: S-EPMC6416361 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature