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Transgender persons have an increased vulnerability to HIV infection yet have not been well-represented in past clinical trials for pre-exposure prophylaxis (PrEP). Because of this, there are few data available to understand whether gender-affirming hormone concentrations are influenced by PrEP agents in transgender men (TM) and transgender women (TW). The objective of this study was to compare gender-affirming hormone concentrations with versus without emtricitabine (F, FTC)-tenofovir disoproxil fumarate (TDF). TM and TW without HIV, aged 15-24 years, were enrolled for 1 month of directly observed daily F/TDF. Participants were required to be receiving a stable hormone dose (estradiol or testosterone) for at least 1 month or three consecutive doses, whichever was longer, before enrollment and willing to continue the same dose. Intensive pharmacokinetic (PK) sampling for gender-affirming hormones was collected before and 2-3 weeks after daily F/TDF. Serum estradiol and total testosterone were determined by liquid chromatography-tandem mass spectrometry; free testosterone by equilibrium dialysis. Maximum concentrations (Cmax) and area under the curve (AUClast) were log-transformed and compared between baseline and on F/TDF using geometric mean ratios (GMRs) with 95% confidence intervals (CIs). Twenty-five TW and 24 TM were enrolled (median age: 20 and 21 years, respectively). In TW, estradiol Cmax (GMR [95% CI]: 0.85 [0.65-1.11]) and AUClast (GMR [95% CI]: 0.87 [0.73-1.03]) were comparable on F/TDF versus baseline. In TM, similar comparability was observed for PrEP versus baseline including total testosterone Cmax (GMR [95% CI]: 0.91 [0.80-1.03]) and AUClast (GMR [95% CI]: 0.91 [0.81-1.04]) and free testosterone Cmax (GMR [95% CI]: 0.89 [0.74-1.07]) and AUClast (GMR [95% CI]: 0.88 [0.74-1.03]). Estradiol and testosterone exposures in young TW and TM did not significantly differ on F/TDF versus baseline. These findings should reassure patients and providers that F/TDF can be used as PrEP without concern for altering gender-affirming hormone PK. ClinicalTrials.gov (NCT03652623).

The transgender community has expressed concerns regarding drug-drug interactions between HIV-pre-exposure prophylaxis (PrEP) and gender-affirming hormones. In this study, we evaluated emtricitabine (F, FTC)/tenofovir (TFV) disoporoxil fumarate (TDF) pharmacokinetics (PK) among adolescent and young adult transgender persons receiving gender-affirming hormone therapy (GAHT). This was a prospective, observational study among transgender women (TW) and men (TM) without HIV, 15-24 years of age, receiving GAHT (estradiol with/without spironolactone, or testosterone). Participants received 1 month of directly observed daily F/TDF. Weekly convenience blood samples were collected for plasma TFV and FTC, and intracellular TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) in peripheral blood mononuclear cells (PBMC) and dried blood spots (DBS). After 2-3 weeks of F/TDF dosing, intensive PK sampling was conducted. PK parameters were estimated using noncompartmental methods. Data were log-transformed and compared between TM and TW, and to historical data among cisgender adults. Plasma TFV exposures were similar between TM and TW [geometric mean ratio (GMR); confidence interval (95% CI): 1.06 (0.89-1.28)], whereas FTC plasma exposures were 21% higher in TM versus TW (95% CI: 1.07-1.38). TFV-DP in PBMC and DBS and FTC-TP in DBS did not differ between TM versus TW after controlling for creatinine clearance (CrCl), but FTC-TP in PBMC remained 46% (95% CI: 1.15-1.86) higher in TM versus TW. All PK exposures were within expected ranges based on historical studies. TM had higher FTC exposures compared with TW, but overall plasma and intracellular exposures for both drugs were within the range of historical studies, suggesting high PrEP efficacy will be retained in adolescent and young adult transgender persons. Registered at ClinicalTrials.gov (NCT03652623).

ImportanceAdolescents represent a key population for implementing preexposure prophylaxis (PrEP) interventions worldwide, yet tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for PrEP is only licensed for adults.ObjectiveTo examine the safety of and adherence to PrEP along with changes in sexual risk behavior among adolescent men who have sex with men (MSM).Design, setting, and participantsAdolescent Medicine Trials Network for HIV/AIDS Interventions 113 (Project PrEPare) was a PrEP demonstration project that evaluated the safety, tolerability, and acceptability of TDF/FTC and patterns of use, rates of adherence, and patterns of sexual risk behavior among healthy young MSM aged 15 to 17 years. Participants were recruited from adolescent medicine clinics and their community partners in 6 US cities, had negative test results for human immunodeficiency virus (HIV) but were at high risk for acquiring an infection, and were willing to participate in a behavioral intervention and accept TDF/FTC as PrEP.ExposuresAll participants completed an individualized evidence-based behavioral intervention and were provided with daily TDF/FTC as PrEP for 48 weeks.Main outcomes and measuresThe main objectives were to: (1) provide additional safety data regarding TDF/FTC use among young MSM who had negative test results for HIV; (2) examine the acceptability, patterns of use, rates of adherence, and measured levels of tenofovir diphosphate in dried blood spots; and (3) examine patterns of risk behavior when young MSM were provided with a behavioral intervention in conjunction with open-label TDF/FTC.ResultsAmong 2864 individuals screened (from August 2013 to September 2014), 260 were eligible and 78 were enrolled (mean [SD] age, 16.5 [0.73] years), of whom 2 (3%) were Asian/Pacific Islander, 23 (29%) were black/African American, 11 (14%) were white, 16 (21%) were white Hispanic, and 26 (33%) were other/mixed race/ethnicity. Over 48 weeks of PrEP use, 23 sexually transmitted infections were diagnosed in 12 participants. The HIV seroconversion rate was 6.4 (95% CI: 1.3-18.7) per 100 person-years. Tenofovir diphosphate levels consistent with a high degree of anti-HIV protection (>700 fmol/punch) were found in 42 (54%), 37 (47%), 38 (49%), 22 (28%), 13 (17%), and 17 (22%) participants at weeks 4, 8, 12, 24, 36, and 48, respectively.Conclusions and relevanceAdolescent Medicine Trials Network for HIV/AIDS Interventions 113 enrolled a diverse sample of adolescent MSM at risk for HIV who consented to study participation. Approximately half achieved protective drug levels during the monthly visits, but adherence decreased with quarterly visits. Youth may need additional contact with clinical staff members to maintain high adherence.Trial registrationclinicaltrials.gov Identifier: NCT01769456.

ImportanceAdolescents represent a key population for implementing preexposure prophylaxis (PrEP) interventions worldwide, yet tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for PrEP is only licensed for adults.ObjectiveTo examine the safety of and adherence to PrEP along with changes in sexual risk behavior among adolescent men who have sex with men (MSM).Design, setting, and participantsAdolescent Medicine Trials Network for HIV/AIDS Interventions 113 (Project PrEPare) was a PrEP demonstration project that evaluated the safety, tolerability, and acceptability of TDF/FTC and patterns of use, rates of adherence, and patterns of sexual risk behavior among healthy young MSM aged 15 to 17 years. Participants were recruited from adolescent medicine clinics and their community partners in 6 US cities, had negative test results for human immunodeficiency virus (HIV) but were at high risk for acquiring an infection, and were willing to participate in a behavioral intervention and accept TDF/FTC as PrEP.ExposuresAll participants completed an individualized evidence-based behavioral intervention and were provided with daily TDF/FTC as PrEP for 48 weeks.Main outcomes and measuresThe main objectives were to: (1) provide additional safety data regarding TDF/FTC use among young MSM who had negative test results for HIV; (2) examine the acceptability, patterns of use, rates of adherence, and measured levels of tenofovir diphosphate in dried blood spots; and (3) examine patterns of risk behavior when young MSM were provided with a behavioral intervention in conjunction with open-label TDF/FTC.ResultsAmong 2864 individuals screened (from August 2013 to September 2014), 260 were eligible and 78 were enrolled (mean [SD] age, 16.5 [0.73] years), of whom 2 (3%) were Asian/Pacific Islander, 23 (29%) were black/African American, 11 (14%) were white, 16 (21%) were white Hispanic, and 26 (33%) were other/mixed race/ethnicity. Over 48 weeks of PrEP use, 23 sexually transmitted infections were diagnosed in 12 participants. The HIV seroconversion rate was 6.4 (95% CI: 1.3-18.7) per 100 person-years. Tenofovir diphosphate levels consistent with a high degree of anti-HIV protection (>700 fmol/punch) were found in 42 (54%), 37 (47%), 38 (49%), 22 (28%), 13 (17%), and 17 (22%) participants at weeks 4, 8, 12, 24, 36, and 48, respectively.Conclusions and relevanceAdolescent Medicine Trials Network for HIV/AIDS Interventions 113 enrolled a diverse sample of adolescent MSM at risk for HIV who consented to study participation. Approximately half achieved protective drug levels during the monthly visits, but adherence decreased with quarterly visits. Youth may need additional contact with clinical staff members to maintain high adherence.Trial registrationclinicaltrials.gov Identifier: NCT01769456.

BackgroundYoung men who have sex with men (YMSM) are a key population for implementation of preexposure prophylaxis (PrEP) interventions. This open-label study examined adherence to PrEP and assessed sexual behavior among a diverse sample of YMSM in 12 US cities.MethodsEligible participants were 18- to 22-year-old HIV-uninfected MSM who reported HIV transmission risk behavior in the previous 6 months. Participants were provided daily tenofovir disoproxil fumarate/emtricitabine (Truvada). Study visits occurred at baseline, monthly through week 12, and then quarterly through week 48. Dried blood spots were serially collected for the quantification of tenofovir diphosphate (TFV-DP).ResultsBetween March and September 2013, 2186 individuals were approached and 400 were found to be preliminarily eligible. Of those 400, 277 were scheduled for an in-person screening visit and 200 were enrolled (mean age = 20.2; 54.5% black, 26.5% Latino). Diagnosis of sexually transmitted infections, including urethral and rectal chlamydial/gonococcal infection and syphilis, at baseline was 22% and remained high across visits. At week 4, 56% of participants had TFV-DP levels consistent with ≥4 pills per week. By week 48, 34% of participants had TFV-DP levels consistent with ≥4 pills per week, with a noticeable drop-off occurring at week 24. Four HIV seroconversions occurred on study (3.29/100 person-years). Condomless sex was reported by >80% of participants, and condomless anal sex with last partner was associated with higher TFV-DP levels.ConclusionsAcceptability of PrEP was high, and most participants achieved protective drug levels during monthly visits. As visit frequency decreased, so did adherence. YMSM in the United States may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.

BackgroundYoung men who have sex with men (YMSM) are a key population for implementation of preexposure prophylaxis (PrEP) interventions. This open-label study examined adherence to PrEP and assessed sexual behavior among a diverse sample of YMSM in 12 US cities.MethodsEligible participants were 18- to 22-year-old HIV-uninfected MSM who reported HIV transmission risk behavior in the previous 6 months. Participants were provided daily tenofovir disoproxil fumarate/emtricitabine (Truvada). Study visits occurred at baseline, monthly through week 12, and then quarterly through week 48. Dried blood spots were serially collected for the quantification of tenofovir diphosphate (TFV-DP).ResultsBetween March and September 2013, 2186 individuals were approached and 400 were found to be preliminarily eligible. Of those 400, 277 were scheduled for an in-person screening visit and 200 were enrolled (mean age = 20.2; 54.5% black, 26.5% Latino). Diagnosis of sexually transmitted infections, including urethral and rectal chlamydial/gonococcal infection and syphilis, at baseline was 22% and remained high across visits. At week 4, 56% of participants had TFV-DP levels consistent with ≥4 pills per week. By week 48, 34% of participants had TFV-DP levels consistent with ≥4 pills per week, with a noticeable drop-off occurring at week 24. Four HIV seroconversions occurred on study (3.29/100 person-years). Condomless sex was reported by >80% of participants, and condomless anal sex with last partner was associated with higher TFV-DP levels.ConclusionsAcceptability of PrEP was high, and most participants achieved protective drug levels during monthly visits. As visit frequency decreased, so did adherence. YMSM in the United States may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.