Dose response for starting and stopping HIV preexposure prophylaxis for men who have sex with men.
BACKGROUND
This study estimated the number of daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) doses required to achieve and maintain (after discontinuation) intracellular drug concentrations that protect against human immunodeficiency virus (HIV) infection for men who have sex with men (MSM).


METHODS
Tenofovir diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs) and rectal mononuclear cells from an intensive pharmacokinetic study ("Cell-PrEP" [preexposure prophylaxis]) of 30 days of daily TDF/FTC followed by 30 days off drug were evaluated. A regression formula for HIV risk reduction derived from PBMCs collected in the preexposure prophylaxis initiative study was used to calculate inferred risk reduction. The time required to reach steady state for TFV-DP in rectal mononuclear cells was also determined.


RESULTS
Twenty-one HIV-uninfected adults participated in Cell-PrEP. The inferred HIV risk reduction, based on PBMC TFV-DP concentration, reached 99% (95% confidence interval [CI], 69%-100%) after 5 daily doses, and remained >90% for 7 days after stopping drug from steady-state conditions. The proportion of participants reaching the 90% effective concentration (EC90) was 77% after 5 doses and 89% after 7 doses. The percentage of steady state for natural log [TFV-DP] in rectal mononuclear cells was 88% (95% CI, 66%-94%) after 5 doses and 94% (95% CI, 78%-98%) after 7 doses.


CONCLUSIONS
High PrEP activity for MSM was achieved by approximately 1 week of daily dosing. Although effective intracellular drug concentrations persist for several days after stopping PrEP, a reasonable recommendation is to continue PrEP dosing for 4 weeks after the last potential HIV exposure, similar to recommendations for postexposure prophylaxis.
['Seifert|Sharon M|SM|', 'Glidden|David V|DV|', 'Meditz|Amie L|AL|', 'Castillo-Mancilla|Jose R|JR|', 'Gardner|Edward M|EM|', 'Predhomme|Julie A|JA|', 'Rower|Caitlin|C|', 'Klein|Brandon|B|', 'Kerr|Becky J|BJ|', 'Guida|L Anthony|LA|', 'Zheng|Jia-Hua|JH|', 'Bushman|Lane R|LR|', 'Anderson|Peter L|PL|']
D000293:Adolescent D000328:Adult D019380:Anti-HIV Agents D001774:Blood Chemical Analysis D018562:Disease Transmission, Infectious D000068679:Emtricitabine D015658:HIV Infections D018451:Homosexuality, Male D006801:Humans D007963:Leukocytes, Mononuclear D008297:Male D008875:Middle Aged D065129:Pre-Exposure Prophylaxis D011446:Prospective Studies D012007:Rectum D000068698:Tenofovir D013997:Time Factors D055815:Young Adult
HIV preexposure prophylaxis tenofovir MSM pharmacokinetics