The effect of depot medroxyprogesterone acetate on tenofovir alafenamide in rhesus macaques.

The effect of depot medroxyprogesterone acetate on tenofovir alafenamide in rhesus macaques. Antiviral Res. 2020 Dec 29;:105001 Authors: Daly MB, Sterling M, Holder A, Dinh C, Nishiura K, Khalil G, García-Lerma JG, Dobard C Abstract Prevention of HIV infection and unintended pregnancies are public health priorities. In sub-Saharan Africa, where HIV prevalence is highest, depot-medroxyprogesterone acetate (DMPA) is widely used as contraception. Therefore, understanding potential interactions between DMPA and antiretrovirals is critical. Here, we use a macaque model to investigate the effect of DMPA on the pharmacology of the antiretroviral tenofovir alafenamide (TAF). Female rhesus macaques received 30 mg of DMPA (n=9) or were untreated (n=9). Macaques received a human equivalent dose of TAF (1.5 mg/kg) orally by gavage. Tenofovir (TFV) and TFV-diphosphate (TFV-DP) were measured in blood, secretions, and tissues over 72 hours. The median area under the curve (AUC0-72h) values for TFV-DP in peripheral blood mononuclear cells were similar in DMPA-treated (6,991 fmol*h/106 cells) and untreated controls (5,256 fmol*h/106 cells) (P=0.174). Rectal tissue TFV-DP concentrations from DMPA+ animals [median: 20.23 fmol/mg of tissue (range: 4.94-107.95)] were higher than the DMPA-group [median: below the limit of quantification (BLOQ-11.92)], (P=0.019). TFV-DP was not detectable in vaginal tissue from either group. A high-dose DMPA treatment in ...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research