Daily Oral HIV Pre-exposure Prophylaxis Among Young Men Who Have Sex With Men in the United States: Cost-saving at Generic Drug Price.

BACKGROUND: Adherence and retention concerns raise questions about the effectiveness and cost-effectiveness of oral HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). METHODS: Using an adolescent-focused simulation model, we compared annual HIV screening alone with tenofovir disoproxil fumarate/emtricitabine-based oral PrEP with every 3-month HIV screening in YMSM (aged 15-24) at increased risk of HIV. Data derived from published sources included: age-stratified HIV incidence/100 person-years (PY) on- or off-PrEP (0.6-10.1 or 0.4-6.4), PrEP retention at 6 years (28%), transmissions by HIV RNA level (0.0-78.4/100PY) and annual costs of antiretroviral therapy ($32 000-69 000), HIV care ($3100-34 600), and PrEP program/generic drug ($900/360). Outcomes included transmissions (percent of cohort infected), quality-adjusted life-years (QALYs), costs ($), and incremental cost-effectiveness ratios ($/QALY). We explored the sensitivity of findings to variation in HIV incidence and drug prices. RESULTS: Compared with annual screening alone, PrEP would increase QALYs (9.58 to 9.67), reduce new infections (37% to 30%), and decrease costs (by $5000) over 10 years. PrEP would remain cost-saving for HIV incidence off-PrEP ≥5.1/100PY or annual PrEP price ≤$1200. Over a lifetime horizon, PrEP would be cost-saving for HIV incidence off-PrEP ≥1.0/100PY, across all retention assumptions examined. PrEP would not be cost-effective at HIV incidence ≤0.1/100PY, regardless of drug price, due to programmatic costs. CONCLUSIONS: In US YMSM at increased risk of HIV, generic oral PrEP and every-3-month screening would be cost-saving compared with annual screening alone, even with high discontinuation and low adherence, over a range of HIV incidences.

High study participation but diverging adherence levels: qualitatively unpacking PrEP use among adolescent girls and young women over two years in Eastern Cape, South Africa.

In Southern and Eastern Africa, initiation of daily oral pre-exposure prophylaxis (PrEP) for HIV prevention has been high among adolescent girls and young women (AGYW) offered PrEP. However, persistence and prevention-effective use of PrEP among this critical group continues to be a challenge. We conducted a qualitative sub-study of AGYW from the Community PrEP Study in Eastern Cape Province, South Africa who had high rates of pick up for monthly PrEP refills over two years, but differing levels of PrEP adherence based on tenofovir-diphosphate (TFV-DP) measurements in dried blood spots (DBS). Contrasting 22 AGYW with low versus high levels of TFV-DP in DBS, we qualitatively explored factors which influenced PrEP persistence vs. non-persistence, unique patterns of PrEP use (e.g., discarding or stockpiling), and participant recommendations for improving AGYW prevention-effective use of PrEP in the future. Results showed that PrEP misconceptions and mistrust among participants' social networks negatively influenced adherence. In comparison, supportive families and/or partners and personal trust that PrEP works positively influenced adherence. Those with low adherence described being motivated to come to the site for other study benefits (e.g., reimbursement money, snacks, sanitary pads) and discarding PrEP to avoid stigma associated with being seen with pills. Future PrEP implementation strategies should focus on involving families and partners in PrEP support for AGYW and minimizing PrEP stigma at a community level.Trial registration NCT03977181. Retrospectively registered on June 6, 2019.

Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial.

BACKGROUND: Oral pre-exposure prophylaxis has been introduced in more than 70 countries, including many in sub-Saharan Africa, but women experience considerable barriers to daily pill-taking, such as stigma, judgement, and the fear of violence. Safe and effective long-acting agents for HIV prevention are needed for women. We aimed to evaluate the safety and efficacy of injectable cabotegravir compared with daily oral tenofovir diphosphate plus emtricitabine (TDF-FTC) for HIV prevention in HIV-uninfected women. METHODS: HPTN 084 was a phase 3, randomised, double-blind, double-dummy, active-controlled, superiority trial in 20 clinical research sites in seven countries in sub-Saharan Africa. Participants were eligible for enrolment if they were assigned female sex at birth, were aged 18-45 years, reported at least two episodes of vaginal intercourse in the previous 30 days, were at risk of HIV infection based on an HIV risk score, and agreed to use a long-acting reversible contraceptive method. Participants were randomly assigned (1:1) to either active cabotegravir with TDF-FTC placebo (cabotegravir group) or active TDF-FTC with cabotegravir placebo (TDF-FTC group). Study staff and participants were masked to study group allocation, with the exception of the site pharmacist who was responsible for study product preparation. Participants were prescribed 5 weeks of daily oral product followed by intramuscular injections every 8 weeks after an initial 4-week interval load, alongside daily oral pills. Participants who discontinued injections were offered open-label daily TDF-FTC for 48 weeks. The primary endpoints of the study were incident HIV infection in the intention-to-treat population, and clinical and laboratory events that were grade 2 or higher in all women who had received at least one dose of study product. This study is registered with ClinicalTrials.gov, NCT03164564. FINDINGS: From Nov 27, 2017, to Nov 4, 2020, we enrolled 3224 participants (1614 in the cabotegravir group and 1610 in the TDF-FTC group). Median age was 25 years (IQR 22-30); 1755 (54·7%) of 3209 had two or more partners in the preceding month. 40 incident infections were observed over 3898 person-years (HIV incidence 1·0% [95% CI 0·73-1·40]); four in the cabotegravir group (HIV incidence 0·2 cases per 100 person-years [0·06-0·52]) and 36 in the TDF-FTC group (1·85 cases per 100 person-years [1·3-2·57]; hazard ratio 0·12 [0·05-0·31]; p<0·0001; risk difference -1·6% [-1·0% to -2·3%]. In a random subset of 405 TDF-FTC participants, 812 (42·1%) of 1929 plasma samples had tenofovir concentrations consistent with daily use. Injection coverage was 93% of the total number of person-years. Adverse event rates were similar across both groups, apart from injection site reactions, which were more frequent in the cabotegravir group than in the TDF-FTC group (577 [38·0%] of 1519 vs 162 [10·7%] of 1516]) but did not result in injection discontinuation. Confirmed pregnancy incidence was 1·3 per 100 person-years (0·9-1·7); no congenital birth anomalies were reported. INTERPRETATION: Although both products for HIV prevention were generally safe, well tolerated, and effective, cabotegravir was superior to TDF-FTC in preventing HIV infection in women. FUNDING: National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and the Bill & Melinda Gates Foundation. Additional support was provided through the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. ViiV Healthcare and Gilead Sciences provided pharmaceutical support.

The Effect of Disclosure of PrEP Use on Adherence Among African Young Women in an Open-Label PrEP Study: Findings from HPTN 082.

To develop effective PrEP adherence interventions, it is important to understand the interplay between disclosure of pre-exposure prophalxis (PrEP) use, social support, and PrEP adherence. We leveraged the HPTN 082 study conducted among 451 adolescent girls and young women (AGYW) (ages 16 to 25 years, 2016 to 2019) in South Africa and Zimbabwe. Among the 349 who had month three disclosure and PrEP adherence data, 60% (n = 206) felt supported by adults, and 89% (n = 309) disclosed PrEP use to at least one person. PrEP disclosure was not associated with increased adherence, measured by intracellular tenofovir-diphosphate concentrations in dried blood spots. Women who reported having supportive adults, and disclosed to their parents, had higher adherence at 6 months with an increase of 177 fmol/punch (95% CI 12 to 343, t = 2.11, p = 0.04). PrEP interventions that help AGYW identify supportive relationships and effectively communicate the benefits of PrEP may improve PrEP adherence.Clinicaltrials.gov ID number: NCT02732730.

Access to healthcare among sexual and gender minority youth at risk for HIV: barriers and experiences of discrimination.

This study examined experiences of healthcare inaccessibility and lesbian, gay, bisexual, transgender, queer, plus (LGBTQ+) discrimination among sexual and gender minority youth at elevated risk for HIV in the United States. Participants for this cross-sectional survey study (N = 3330) were cisgender men, transgender men and women, and nonbinary individuals ages 18-34 recruited for a larger study examining HIV risk behavior between December 2017 and December 2019. Results indicated that 41.1% of participants had at least one lifetime experience of LGBTQ + healthcare discrimination, and 44.1% reported past 6-month experiences of discrimination or problems accessing healthcare. Transgender men and women were more likely than cisgender men and nonbinary participants to report experiences of discrimination, and transgender men were more likely to report problems accessing healthcare. A majority of participants (72.8%) reported that their most recent healthcare provider was aware of their sexual or gender identity. These results indicate a high prevalence of structural barriers in healthcare access for sexual and gender minority youth at elevated risk for HIV, including finical and logistical barriers as well as anticipated and experienced discrimination. We discuss these findings and highlight the importance of easily accessible and culturally competent care for this community.

Trust in the provider and accurate self-reported PrEP adherence among adolescent girls and young women in South Africa and Zimbabwe: HPTN 082 study.

BACKGROUND: Trust is an important cornerstone of patient-provider communication. Accurate reporting of pre-exposure prophylaxis (PrEP) adherence is vital for providers to determine who needs adherence support, especially adolescent girls and young women (AGYW) disproportionately affected by newly diagnosed HIV. METHODS: This is a secondary analysis of the HPTN 082 open-label PrEP demonstration trial. From 2016-2018, 451 AGYW aged 16-25 years were enrolled in South Africa (Cape Town and Johannesburg) and Zimbabwe (Harare). PrEP was initiated by 427, and 354 (83%) had month three patient-reported adherence responses and intracellular tenofovir diphosphate (TFV-DP) measurements. The patient-reported adherence response to 'In the past month, how often did you take the tablet?' was dichotomized as 'high' if the response was every day or most days, and 'low' if some days or not many days or never. The biomarker marker evidence of adherence in dried blood spots was defined as 'high' if TFV-DP ≥ 700, and 'low' if < 350 fmol/punch. We used multinomial logistic regression to examine if trust in the PrEP provider was associated with concordance between patient-reported adherence and intracellular tenofovir-diphosphate (TFV-DP). RESULTS: AGYW who reported trust in their providers were almost four-fold (aOR 3.72, 95% CI 1.20-11.51) more likely to have concordant adherence (high self-reported adherence and high TFV-DP concentrations) compared to discordant non-adherence (high self-reported adherence and low TFV-DP concentrations). CONCLUSION: Education and training of providers to build trusting relationships with AGYW may lead to more accurate reporting of PrEP adherence. With accurate reporting, adequate support can be provided to bolster adherence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02732730.

"It's already in your body and it's preventing": a qualitative study of African female adolescent's acceptability and preferences for proxy HIV prevention methods in Cape Town, South Africa.

BACKGROUND: Advances in biomedical HIV prevention will soon offer young women a choice of HIV prevention methods, including various pre-exposure prophylaxis (PrEP) modalities such as daily oral pills, dapivirine vaginal ring, and long-acting injectable agents. By understanding preferences for contraceptive methods, we may draw analogies for the HIV prevention needs of young women. The UChoose Study was an open-label randomised cross-over study designed to evaluate the acceptability and preference for several contraceptive options as a proxy for HIV prevention methods that use similar types of administration. The study enrolled healthy HIV uninfected young women aged 15 to 19 years. At enrolment, participants were randomly assigned to a contraceptive method for a period of 16 weeks in the form of monthly Nuvaring® (vaginal ring), daily combined oral contraceptive (daily pills), or bi-monthly injectable contraceptive (injectable). After 16 weeks, participants crossed over to another contraceptive method, and those who had received the injectable and the daily pills received the vaginal ring for another 16 weeks, whereas those who had received the vaginal ring were able to choose between the injectable and daily pills, to ensure that all participants tried the vaginal ring-the least familiar option to the study population. RESULTS: Thirty-three participants were purposively recruited to participate in seven focus group discussions (FGD) and completed a pre-survey for their assigned group. Our sample comprised 14 participants randomised to use of the vaginal ring and daily pills and 19 participants randomised to use of the vaginal ring and injectable. For most participants, their preferences for a prevention method were based primarily on their desire to avoid negative aspects of one method rather than their positive user experience with another method. Most participants expressed initial hesitancy for trying new contraception method products; however, a lack of familiarity was moderated by a strong interest in diverse user-controlled prevention methods. Participants valued methods that had infrequent dosing and simplified use requirements. The injection and vaginal ring were preferred over daily pills as a potential HIV prevention method. CONCLUSION: Expanding the availability of diverse products could provide adolescents with multiple choices in HIV prevention for the uninitiated. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02404038 ). Registered March 31, 2015-Registered.

Changes in Sexual Behaviors Due to Mpox: a Cross-Sectional Study of Sexual and Gender Minority Individuals in Illinois.

The spread of the monkeypox virus (mpox) in 2022 primarily within the sexual networks of men who have sex with men (MSM) triggered a potentially stigmatizing public health response in the USA. Despite mpox being primarily spread through skin-to-skin contact, most messaging has promoted abstinence and/or reduction in sexual risk behaviors. More research is needed on decreases in sexual risk behaviors among sexual and gender minority (SGM) youth and young adults (YYA) related to the most recent mpox epidemic and whether there are factors associated with these decreases in sexual risk behavior. Participants within an ongoing cohort study of SGM YYA who reside in Illinois were offered the opportunity to participate in an mpox survey between September 10th and September 20th, 2022. Analyses looked at demographic factors associated with sexual activity since the start of the outbreak, as well as associations with two sexual risk reduction factors. Survey participation was 68.7% (322/469). Three-quarters of participants (82.6%) reported sexual activity since June 1st. Most sexually active participants (83.5%) adopted at least one sexual risk reduction behavior due to mpox. Black and Latinx individuals were less likely to be sexually active but more likely to report risk reduction behaviors (31.3% and 22.6%, respectively). Participants who received the mpox vaccine were more likely to report sexual activity. SGM YYA in Illinois reported that their sexual behaviors were impacted by the mpox outbreak. However, associations between vaccination and sexual behavior demonstrate that those who are vaccinated do adopt protective methods despite not decreasing sexual activity. Therefore, sex-positive communications and harm reduction messaging may be more appropriate as opposed to abstinence-only prevention, which can further stigmatize an already marginalized group.

Individual and structural-level Correlates of Pre-exposure Prophylaxis (PrEP) lifetime and current use in a nationwide sample of young sexual and gender minorities.

The objective of this analysis was to describe individual and structural-level factors associated with pre-exposure prophylaxis (PrEP) use among a sample of sexual and gender minorities (SGM) at risk for HIV recruited using limited interaction strategies. SGM (N = 3330), ages 15-34, without HIV enrolled in a nationwide limited interaction cohort study from 2017 to 2020. A baseline cross-sectional single-survey design examined individual and structural-level correlates of PrEP lifetime use and current use using logistic regression. PrEP lifetime use and current use were reported by 31.2% and 23.9%, respectively, of SGM with PrEP data (n = 3077). PrEP use outcomes (lifetime or current use) in cisgender MSM were associated with being over age 18, Black or other race, Hispanic/Latina/x/o ethnicity, being gay, being out to one's healthcare provider, having health insurance, being a college graduate, and having a greater number of PrEP peers. PrEP use outcomes (lifetime use or current use) in transgender/non-binary participants were associated with being over age 24, being Latinx, being transgender vs. non-binary, being assigned male at birth, being out to their healthcare provider, living in the western or northeastern United States, and having more peers on PrEP. More work is needed to address lower PrEP uptake in SGM under 18 and those whose sex risk may be more dynamic (e.g., non-binary, pansexual/queer, and bisexual SGM) and such strategies should consider utilizing peers to provide information and ameliorate structural barriers.

RESUMEN: Este análisis describe los determinantes sociales asociados con el uso de la PrEP entre una cohorte contemporánea de minorías sexuales y de género (MSG) en riesgo de contraer el VIH en los Estados Unidos. Los participantes incluyeron MSG (N = 3330), de 15 a 34 años, sin VIH reclutados por redes sociales entre 2017­2020. Usando los datos de inscripción, una regresión analizó la historia del uso de la PrEP. Los factores asociados con el uso de la PrEP entre este grupo indicaron que los mayores de edad, los abiertos sobre su sexualidad con sus médicos, y los que conocían compañeros que usaban la PrEP, todos eran más propensos a haber usado la PrEP. Más esfuerzo se requiere para abordar el uso de la PrEP entre aquellos cuyos su riesgo sexual puede ser más dinámico.

Factors influencing adolescent girls and young women's uptake of community-based PrEP services following home-based HIV testing in Eastern Cape, South Africa: a qualitative study.

Home-based service delivery has been used to improve access to HIV testing and antiretroviral initiation across sub-Saharan Africa, but it has yet to be leveraged to improve pre-exposure prophylaxis (PrEP) uptake. We interviewed 37 adolescent girls and young women (AGYW) in Eastern Cape, South Africa to explore why they chose to initiate PrEP or not following home-based HIV testing and referral for PrEP, and what influenced time to PrEP initiation. Participants reported that home visits provided a source of trusted information and a way to involve family members in their PrEP initiation decisions, motivating some to start PrEP. AGYW who initiated PrEP were more likely to qualitatively perceive themselves to be at high risk for HIV compared with those who never initiated PrEP. Integrating home-based HIV testing with PrEP education and referral may be a valuable way to reduce familial barriers and boost PrEP uptake among AGYW in South Africa. Trial registration: NCT03977181. Retrospectively registered on June 6, 2019.

Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa.

BACKGROUND: Intracellular tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is used to monitor cumulative pre-exposure prophylaxis (PrEP) adherence. We evaluated TFV-DP in DBSs following daily oral PrEP (emtricitabine 200 mg/tenofovir diphosphate 300 mg) among pregnant and postpartum adolescent girls and young women (AGYW). METHODS: Directly observed PrEP was administered for 12 weeks in a pregnancy (14-24 weeks' gestation, n = 20) and postpartum (6-12 weeks postpartum, n = 20) group of AGYW aged 16-24 years in sub-Saharan Africa. Weekly DBS TFV-DP was measured by validated liquid chromatography-tandem mass spectrometry assay. Week 12 TFV-DP distributions were compared between groups with Wilcoxon test. Population pharmacokinetic models were fit to estimate steady-state concentrations and create benchmarks for adherence categories. Baseline correlates of TFV-DP were evaluated. RESULTS: Median age was 20 (IQR, 19-22) years. Of 3360 doses, 3352 (>99%) were directly observed. TFV-DP median (IQR) half-life was 10 (7-12) days in pregnancy and 17 (14-21) days postpartum, with steady state achieved by 5 and 8 weeks, respectively. Observed median (IQR) steady-state TFV-DP was 965 fmol/punch (691-1166) in pregnancy versus 1406 fmol/punch (1053-1859) postpartum (P = .006). Modeled median steady-state TFV-DP was 881 fmol/punch (667-1105) in pregnancy versus 1438 fmol/punch (1178-1919) postpartum. In pooled analysis, baseline creatinine clearance was associated with observed TFV-DP concentrations. CONCLUSIONS: TFV-DP in African AGYW was approximately one-third lower in pregnancy than postpartum. These Population-specific benchmarks can be used to guide PrEP adherence support in pregnant/postpartum African women. CLINICAL TRIALS REGISTRATION: NCT03386578.

Cost-effectiveness of Frequent HIV Screening Among High-risk Young Men Who Have Sex With Men in the United States.

BACKGROUND: Of new HIV infections in the US, 20% occur among young men who have sex with men (YMSM, ages 13-24), but >50% of YMSM with HIV are unaware of their status. Using Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) data, we projected the clinical benefit and cost-effectiveness of frequent HIV screening among high-risk YMSM from age 15. METHODS: Using a mathematical simulation, we examined 3 screening strategies: Yearly, 6-monthly, and 3-monthly, each in addition to the Status quo (SQ, 0.7-10.3% screened/year, stratified by age). We used published data (YMSM-specific when available) including: HIV incidences (0.91-6.41/100PY); screen acceptance (80%), linkage-to-care/antiretroviral therapy (ART) initiation (76%), HIV transmission (0.3-86.1/100PY, by HIV RNA), monthly ART costs ($2290-$3780), and HIV per-screen costs ($38). Projected outcomes included CD4 count at diagnosis, primary HIV transmissions from ages 15-30, quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year saved [QALY]; threshold ≤$100 000/QALY). RESULTS: Compared to SQ, all strategies increased projected CD4 at diagnosis (296 to 477-515 cells/µL) and quality-adjusted life expectancy from age 15 (44.4 to 48.3-48.7 years) among YMSM acquiring HIV. Compared to SQ, all strategies increased discounted lifetime cost for the entire population ($170 800 to $178 100-$185 000/person). Screening 3-monthly was cost-effective (ICER: $4500/QALY) compared to SQ and reduced primary transmissions through age 30 by 40%. Results were most sensitive to transmission rates; excluding the impact of transmissions, screening Yearly was ≤$100 000/QALY (ICER: $70 900/QALY). CONCLUSIONS: For high-risk YMSM in the US, HIV screening 3-monthly compared to less frequent screening will improve clinical outcomes and be cost-effective.

PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: Results from HPTN 082, a randomized controlled trial.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study. METHODS AND FINDINGS: HIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV-negative women ages 16-25 were offered PrEP and followed for 12 months; women who accepted PrEP were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of drug level feedback on adherence, and there was limited awareness of PrEP at the time the study was conducted. CONCLUSIONS: In this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02732730.

Changes in Bone Mass After Discontinuation of Preexposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine in Young Men Who Have Sex With Men: Extension Phase Results of Adolescent Trials Network Protocols 110 and 113.

Human immunodeficiency virus-seronegative men aged 15-22 years who lost bone mineral density (BMD) during tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) showed BMD recovery 48 weeks following PrEP discontinuation. Lumbar spine and whole body BMD z-scores remained below baseline 48 weeks off PrEP in participants aged 15-19 years. Clinical Trials Registration. NCT01772823 (ATN 110) and NCT01769456 (ATN 113).

Socio-structural Factors Associated with Mental Health, Substance Use, and HIV Risk Among Black Sexual and Gender Minorities in the House and Ball Community.

The House and Ball Community (HBC), a tight-knit social and cultural network comprised primarily of Black sexual and gender minorities (SGM), offers unique opportunities for HIV prevention that leverage naturally occurring social support networks. However, experiences of socioeconomic marginalization, stigma, violence, and trauma may impede HIV prevention efforts. This study analyzed data from 551 Black SGM recruited at HBC events in 2 cities over 24 months. Logistic regression with generalized estimating equations examined associations between socio-structural stressors, mental health, substance use, and sexual behavior among HBC participants. Findings indicated high prevalence of depressive symptoms, history of trauma, intimate partner violence, and substance use, and significant associations between socioeconomic marginalization and depressive symptoms, substance use, and condomless anal sex. Future research is needed to better elucidate the temporal relationships between socioeconomic marginalization, mental health and substance use, and HIV transmission dynamics. Results highlight a need for integration of mental health services, substance use treatment, and HIV prevention for this community.

Randomized Controlled Trial of a Mobile Health Intervention to Promote Retention and Adherence to Preexposure Prophylaxis Among Young People at Risk for Human Immunodeficiency Virus: The EPIC Study.

BACKGROUND: Young men who have sex with men are among the most vulnerable to human immunodeficiency virus (HIV) infection. Although preexposure prophylaxis (PrEP) has demonstrated effectiveness, adherence and retention have been low among youth. METHODS: We conducted a randomized controlled trial to evaluate the impact of a youth-tailored, bidirectional text-messaging intervention (PrEPmate) on study retention and PrEP adherence. Young individuals at risk for HIV initiating PrEP within Chicago's safety-net system were randomized 2:1 to receive PrEPmate or standard of care (SoC) for 36 weeks. The primary retention outcome was study-visit completion, and the primary adherence outcome was tenofovir diphosphate (TFV-DP) concentrations ≥700 fmol/punch (consistent with ≥4 doses/week) assessed at 4, 12, 24, and 36 weeks. The impact of PrEPmate on retention and adherence was evaluated using generalized estimating equation logistic models with robust standard errors. RESULTS: From April 2015 to March 2016, 121 participants enrolled (mean age 24; 27% black, 36% Latino). Participants who received PrEPmate were more likely to attend study visits (86% PrEPmate vs. 71% SoC, odds ratio [OR] = 2.62, 95% confidence interval [CI] 1.24-5.54) and have TFV-DP levels consistent with ≥4 doses/week (72% PrEPmate vs. 57% SoC, OR = 2.05, 95% CI 1.06-3.94). PrEPmate efficacy did not differ significantly by age, race/ethnicity, education, or insurance. Overall, 88% reported PrEPmate to be very/somewhat helpful, and 92% would recommend PrEPmate to others. CONCLUSIONS: An interactive text-messaging intervention had high acceptability and significantly increased study-visit retention and PrEP adherence among young individuals at risk for HIV acquisition. CLINICAL TRIALS REGISTRATION: NCT02371525.

Pharmacokinetics of tenofovir monoester and association with intracellular tenofovir diphosphate following single-dose tenofovir disoproxil fumarate.

BACKGROUND: Tenofovir monoester is a relatively lipophilic intermediate formed during the hydrolysis of tenofovir disoproxil to tenofovir. Its clinical pharmacokinetic profile and influence on the cellular pharmacology of tenofovir diphosphate have not been reported. METHODS: Plasma, PBMC and dried blood spots (DBS) were obtained from HIV-uninfected adults participating in a randomized, cross-over bioequivalence study of single-dose tenofovir disoproxil fumarate (TDF)/emtricitabine unencapsulated or encapsulated with a Proteus® ingestible sensor. Plasma pharmacokinetics of tenofovir monoester and tenofovir were characterized using non-compartmental methods. Relationships with tenofovir diphosphate in DBS and PBMC were examined using mixed-effects models. RESULTS: Samples were available from 24 participants (13 female; 19 white, 3 black, 2 Hispanic). Tenofovir monoester appeared rapidly with a median (range) Tmax of 0.5 h (0.25-2) followed by a rapid monophasic decline with a geometric mean (coefficient of variation) t½ of 26 min (31.0%). Tenofovir monoester Cmax was 131.6 ng/mL (69.8%) and AUC0-4 was 93.3 ng·h/mL (47.9%). The corresponding values for plasma tenofovir were 222.2 ng/mL (37.1%) and 448.1 ng·h/mL (30.0%). Tenofovir monoester AUC0-∞ (but not tenofovir AUC0-∞) was a significant predictor of tenofovir diphosphate in both PBMC (P = 0.015) and DBS (P = 0.005), increasing by 3.8% (95% CI 0.8%-6.8%) and 4.3% (95% CI 1.5%-7.2%), respectively, for every 10 ng·h/mL increase in tenofovir monoester. CONCLUSIONS: Tenofovir monoester Cmax and AUC0-4 were 59.2% and 20.6% of corresponding plasma tenofovir concentrations. Tenofovir monoester was significantly associated with intracellular tenofovir diphosphate concentrations in PBMC and DBS, whereas tenofovir concentrations were not. Tenofovir monoester likely facilitates cell loading, thereby increasing tenofovir diphosphate exposures in vivo.

HIV Prevention Interventions for Adolescents.

PURPOSE OF REVIEW: The goal of this paper is to review recent data on biomedical, behavioral, and structural HIV prevention interventions for adolescents and young adults. RECENT FINDINGS: While it is accepted that HIV prevention interventions must take an integrated approach to achieve maximum effectiveness, to date, there have been limited, rigorously evaluated combination prevention interventions for adolescents. There are currently a range of effective biomedical, behavioral, and structural approaches that can be integrated into prevention packages to address the prevention needs of adolescents, including oral PrEP, male circumcision, rapid HIV testing, numerous behavioral interventions, and structural interventions such as cash transfers and community mobilization to address gender-based violence. There is still a need for rigorously evaluated, innovative combination prevention packages for adolescents. Prevention approaches must take into account the context of young people's lives and address the multiple levels of influence on their lives including parents, partners, and communities.

Integrated Next Step Counseling (iNSC) for Sexual Health and PrEP Use Among Young Men Who Have Sex with Men: Implementation and Observations from ATN110/113.

Pre-exposure prophylaxis (PrEP) for the prevention of HIV infection among young men who have sex with men is a critical part of the HIV prevention landscape in the US. Given the unique challenges and resources of young MSM negotiating safer sex practices, including PrEP, counseling and supportive discussions to optimize both PrEP use and sexual health protection more generally may facilitate reaching HIV prevention goals. Within the context of a large, open-label PrEP study (ATN110/113), support for sexual health promotion and PrEP use was provided through use of integrated Next Step Counseling (iNSC) as part of study visits. We detail iNSC and, using session documentation collected throughout this study, we characterize iNSC implementation and the content generated from these discussions. We detail features of iNSC, training of counselors and the implementation of iNSC in a multi-site PrEP study with young MSM in the US. Case report forms completed by iNSC counselors at study visits at weeks 4, 8, 12, 24, 36, and 48 were evaluated. Implementation of each intervention step for each discussion is summarized at and across timepoints, as well as features of specific steps (e.g., kinds of facilitators and barriers). Implementation differences by group (e.g., race/ethnicity, age) were examined. iNSC case report forms from 1000 sessions involving 178 unique participants ages 15-22 from sessions conducted between 2013 and 2015 were reviewed. High fidelity to iNSC steps in terms of inclusion in sessions was reported; 98-100% of sessions included critical steps for sexual health protection discussions and 96-98% for PrEP use discussions. The vast majority of sessions appeared to flow in line with iNSC's emphasis on exploration and open discussion prior to considering specific needs and related strategies. Nearly three-quarters of sessions noted 'commitment to staying negative' as a motivator towards sexual health protection (more commonly reported by those identifying as White), while 'assuming partner is negative' was the most common challenge (less common for the older cohort), and 'having access' to a sexual health protection tool or strategy (besides PrEP) was the most common "need" (more common for those identifying as White or Latino). Carrying dose(s) to have them on-hand when needed was the most common PrEP adherence facilitator, drug and alcohol use was the most common challenge noted, and access to a dose when needed was the most common "need" (more common for participants self-identified as White). iNSC was implemented consistently throughout ATN110/113, and patient-centered discussions about sexual health protection and PrEP-use appeared feasible to incorporate into clinical care visits.

Debrief Reports to Expedite the Impact of Qualitative Research: Do They Accurately Capture Data from In-depth Interviews?

"Debrief reports" (DRs) use structured forms to capture key concepts from in-depth interviews and focus group discussions. They are completed by interviewers and rapidly disseminated to key team members to facilitate identification of potential problems with study procedures, recruitment, or participant engagement and to inform critical adjustments, which can be especially pertinent in intervention studies. Their reliability and validity have yet to be formally evaluated. To assess the accuracy of DRs in capturing key content, raters analyzed a random sub-sample of 20 pairs of de-identified transcripts and their linked DRs from the VOICE-D trial. Analyses generally supported the accuracy of DRs; however, pertinent information from transcripts was occasionally missed or recorded with discrepancies or lack of detail. Longer transcripts and DR sections describing complex topic areas were more likely to involve discrepancies. Recommendations are offered for further research and optimizing the use of DRs.