"Medroxyprogesterone Acetate has

Minimal Impact on HIV-1 Replication

in Ectocervical Tissue Ex Vivo"

Abstract:  The link between depomedroxyprogesterone acetate use and risk of HIV-1 acquisition has been demonstrated in epidemiologic studies. Peak medroxyprogesterone-17-acetate (MPA) levels occur 4 days post-injection with serum progestin levels of 2 nM. Our hypothesis is physiologic concentrations of MPA will not affect HIV replication in ectocervical tissue ex vivo.

Ectocervical tissue was processed into polarized explants. Explants were cultured alone (control) or with MPA in the basolateral compartment at physiological (0.05nM, 0.5nM, 1nM, 5nM) (n=17) or higher concentrations (500nM, 5µM, 500µM) (n=10) for 48 h, infected with either 5x102  or 5x103 TCID50  HIV-1BaL apically for 24 h, and then washed. Basolateral supernatants were collected and replenished with fresh medium containing MPA every 3-4 days up to 21 days. Supernatant collections at the 48 h time point (pre-infection) were tested for cytokine expression while all following supernatant collections post-infection were analyzed for viral p24gag (pg/ml).

Viral growth over 21 days for supraphysiologic concentrations indicated suppression, while that for physiologic concentrations was not significantly different from the control. Cytokine   marker   evaluation   indicated   a   hormone   dose-dependent   relationship   between decreasing MPA concentrations (500µM-5nM) and increasing expression of pro-inflammatory cytokines approaching levels of the control, significant for IL-12 (p40), IL6, and IL-8.

MPA does not significantly impact HIV-1 replication at physiologic concentrations but has   an   overall suppressive effect on replication at supraphysiologic concentrations in ectocervical tissue in cervical tissue ex vivo.

The public health significance of DMPA continuation requires balancing unintended pregnancy while diminishing HIV acquisition risk, especially when the risks of infection do not outweigh the contraceptive benefits.