期刊
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
卷 78, 期 2, 页码 175-182出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0000000000001655
关键词
pharmacokinetics; tenofovir gel; rectal; vaginal; microbicides; PrEP
资金
- Centers for Innovative Research to Control AIDS, Mailman School of Public Health, Columbia University [5UM1A1069466]
- National Institute of Allergy and Infectious Diseases [UM1AI068633, UM1AI068615, UM1AI106707]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institute of Mental Health
- U.S. National Institutes of Health
Background: Evidence is lacking regarding whether vaginal preexposure prophylaxis with topical tenofovir (TFV) reduces the risk of rectal HIV acquisition. Setting: Bronx, NY. Methods: MTN-014 was a phase 1, cross-over, randomized sequence trial comparing the cross-compartment pharmacokinetics and pharmacodynamics of daily TFV reduced-glycerin 1% gel after 14 days each of rectal and vaginal application, with directly observed dosing and a 6-week washout period between phases. Results: Fourteen HIV-uninfected women enrolled; 91% of doses were observed and 13 women completed all study procedures. TFV and TFV diphosphate (TFV-DP) were detected in most samples collected from the dosing compartment. After vaginal dosing, TFV was detected in 10/14 samples of rectal fluid (RF) (median 4.4 ng/sponge) and 1/13 rectal tissue samples (0.2 ng/mg); TFV-DP was detected in 2/13 rectal tissue samples at 59.8 and 76.5 fmol/mg. After rectal dosing, TFV was detected in 9/14 samples of vaginal fluid (median 1.1 ng/swab) and in 6/ 14 vaginal tissue samples (median below limit of quantification); TFVDP was detected in 3/14 vaginal tissue samples at 17.3, 87.6, and 77.1 fmol/mg. Neither cervicovaginal lavage fluid nor RF collected 24 hours after rectal or vaginal dosing resulted in a statistically significant suppression of viral replication. Conclusions: In this study of 14 days each of vaginal and rectal application of TFV reduced-glycerin 1% gel, we found only a small degree of cross-compartment distribution of TFV in RF and vaginal fluids and no pharmacodynamic activity in ex vivo testing. Although high TFV concentrations in the dosing compartment may be protective, low cross-compartment tissue concentrations are not likely to be protective.
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