The effect of depot medroxyprogesterone acetate on tenofovir alafenamide in rhesus macaques.
Antiviral Res
; 186: 105001, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33385420
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 h. The median area under the curve (AUC0-72h) values for TFV-DP in peripheral blood mononuclear cells were similar in DMPA-treated (6991 fmol*h/106 cells) and untreated controls (5256 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 macaques was associated with increased rectal TFV-DP levels, indicating a potential tissue-specific drug-drug interaction. The lack of detectable TFV-DP in the vaginal tissue warrants further investigation of PrEP efficacy with single-agent TAF products. DMPA did not affect systemic TAF metabolism, with similar PBMC TFV-DP in both groups, suggesting that DMPA use should not alter the antiviral activity of TAF.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
2_ODS3
Problema de saúde:
2_enfermedades_transmissibles
Assunto principal:
Acetato de Medroxiprogesterona
/
Anticoncepcionais Femininos
/
Fármacos Anti-HIV
/
Tenofovir
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Antiviral Res
Ano de publicação:
2021
Tipo de documento:
Article