A pharmacokinetic study presented at the Conference on Retroviruses and Opportunistic Infections in Boston in February evaluated concentrations of tenofovir (TFV) and TFV-diphosphate (DP) in genital and rectal tissue and in anogenital fluid samples after administration of oral tenofovir alafenamide (TAF). This is of interest because administration of TAF (25 mg orally) results in 90% lower plasma concentrations of the TFV and TFV-DP than TDF, and 7-fold higher levels of TFV in mononuclear cells. TFV exposure in mucosal tissues after administration of TAF had not been studied, but researchers postulated that it also would be substantially higher than after administration of TDF.
HIV-uninfected women were given a single dose of TAF 25 mg, and followed for 14 days; over this period of time, plasma, peripheral blood mononuclear cells (PBMCs), and cervicovaginal fluid samples were obtained, and biopsies (2 at each site) were taken from the cervix, vagina, and rectum. TFV and TDV-DP levels were determined and were compared with reference values for TDF collected by the same laboratory using the same techniques. Findings included:
Over the first 48 hours after TAF/FTC administration:
|Lower plasma but higher PBMC TFV exposure with TAF:
|In plasma, TFV exposure was 19-fold lower and in PBMCs TFV-DP exposure was 9-fold higher with TAF compared with TDF|
|Substantially lower TFV exposure in mucosal tissues with TAF:
|Genital tissue: 2-fold lower TFV exposure, 1-fold lower TFV-DP; TFV-DP was not detected in 75% of samples|
|Rectal tissue: TFV AUC was 10-fold lower with TAF vs TDF, TDF-DP AUC was 13-fold lower; TFV-DP was not detected in 63% of samples vs 0% of the TDF samples|
|Cervicovaginal fluid: TFV AUC was 11-fold lower with TAF vs TDF, and was not detected in twice as many samples|
Clinical Bottom Line
It is not clear whether (or to what degree) TFV in mucosal tissues and genital fluids (as opposed to lymphoid cells) contributes to preventing HIV infection in persons on preexposure prophylaxis (PrEP). However, we know from earlier research on TDF/FTC that TFV levels in the cervix and vagina are much lower than in the rectum, and there is some concern that this may play a role in the higher rates of PrEP failure in women than in men. This study, which showed that administration of TAF resulted in substantially lower levels of TFV in mucosal tissues and genital fluids compared with TDF, raises additional concern about the potential use of TAF in PrEP. Pending further study, TAF/FTC should not be used for PrEP.