Medroxyprogesterone Acetate (MPA) Enhances HIV-1 Accumulation and Release in Primary Cervical Epithelial Cells by Inhibiting Lysosomal Activity

Abstract

Medroxyprogesterone acetate (MPA) is one of the most widely used contraceptives in the world. Epidemiologic studies have uncovered a possible link between the use of MPA and an increased risk of HIV-1 transmission. However, the understanding of the mechanism is still limited. Our previous publication demonstrated that the lysosomal activity in human vaginal epithelial cells attenuated the trafficking of viral particles during HIV-1 transcytosis. In this study, we show that treating human primary cervical epithelial cells with MPA led to a reduction in lysosomal activity. This reduction caused an increase in the intracellular HIV-1 accumulation and, consequently, an increase in viral release. Our study uncovers a novel mechanism by which MPA enhances HIV-1 release in primary cervical epithelial cells, thus providing vital information for HIV intervention and prevention.

Female Sex Hormones Upregulate the Replication Activity of HIV-1 Sub-Subtype A6 and CRF02_AG but Not HIV-1 Subtype B

“…The methods of hormonal contraception such as intramuscular DMPA injections, copper intrauterine spirals, and levonorgestrel implants were considered safe. However, despite the updated WHO guidelines, the use of DMPA remains controversial and raises questions among specialists, since extensive clinical and laboratory data indicate that this contraceptive can still increase the risk of HIV infection [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. A number of epidemiological studies indicate that women living with HIV-1 who use hormonal contraception, compared with HIV-positive women who do not, have a significantly higher viral load, simultaneous infection with several HIV-1 genotypes, and more accelerated CD4+T cell loss, which correlates with increased mortality among this cohort [ 14 , 31 , 32 , 33 , 34 ].…”