The ATEAM study: Advances in technology to enhance PrEP adherence monitoring (ATEAM) among young men who have sex with men.

Young age has consistently correlated with lower adherence to pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Digital medicine, a dynamic healthcare platform of wearable physiological sensors and mobile communication technology that can respond to medication nonadherence rapidly, has the potential in promoting PrEP adherence. We evaluated the feasibility and acceptability of Proteus Discover, a digital monitoring adherence system, to measure PrEP adherence and provide real-time feedback among cisgender YMSM and transgender women. One hundred HIV-negative young men and transgender women ages 16-24 years were enrolled in a 24-week randomized controlled crossover study to tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) coencapsulated with Proteus Discover versus TDF/FTC standard-of-care. Participants in the 12-week Proteus Discover arm received weekly SMS text messages to promote pill taking based on Proteus Discover adherence data. Dried blood spots (DBS) were collected at 4-week intervals for tenofovir diphosphate (TFV-DP) in red blood cells as the referent and questionnaires were completed to assess acceptability, usability, and patterns of use. Linear mixed models analyzed the relationship between 30-day adherence measured by DBS and Proteus Discover. PrEP adherence was high overall. Adherence, as measured by DBS, was correlated with adherence as measured by Proteus Discover (p value = 0.03). Most participants reported that Proteus Discover helped them take their PrEP daily and that the system was easy to use. However, a majority (53.5%-60.5%) disagreed with the statement that wearing the patch was not an issue. There was an incremental increase in TFV-DP in DBS with adherence by Proteus Discover. More research is warranted to explore optimizing PrEP adherence for youth through real-time monitoring.

COVID-19 symptom relationship to antibody response and ACE2 neutralization in recovered health systems employees before and after mRNA BNT162b2 COVID-19 vaccine.

BACKGROUND: The humoral response to SARS-CoV-2 can provide immunity and prevent reinfection. However, less is known about how the diversity, magnitude, and length of the antibody response after a primary infection is associated with symptoms, post-infection immunity, and post-vaccinated immunity. METHODS: Cook County Health employees provided blood samples and completed an online survey 8-10 weeks after a PCR-confirmed positive SARS-CoV-2 test (pre-vaccinated, N = 41) and again, 1-4 weeks after completion of a 2-dose series mRNA BNT162b2 COVID-19 vaccine (post-vaccinated, N = 27). Associations were evaluated between SARS-CoV-2 antibody titers, participant demographics, and clinical characteristics. Antibody titers and angiotensin-converting enzyme 2 (ACE2) neutralization were compared before and after the mRNA BNT162b2 COVID-19 vaccine. RESULTS: Antibody titers to the spike protein (ST4), receptor binding domain (RBD), and RBD mutant D614G were significantly associated with anosmia and ageusia, cough, and fever. Spike protein antibody titers and ACE2 neutralization were significantly higher in participants that presented with these symptoms. Antibody titers to the spike protein N-terminal domain (NTD), RBD, and ST4, and ACE2 IC50 were significantly higher in all post-vaccinated participant samples compared to pre-vaccinated participant sample, and not dependent on previously reported symptoms. CONCLUSIONS: Spike protein antibody titers and ACE2 neutralization are associated with the presentation of anosmia and ageusia, cough, and fever after SARS-CoV-2 infection. Symptom response to previous SARS-CoV-2 infection did not influence the antibody response from subsequent vaccination. These results suggest a relationship between infection severity and the magnitude of the immune response and provide meaningful insights into COVID-19 immunity according to discrete symptom presentation.

Pharmacokinetics of Emtricitabine/Tenofovir Disoproxil Fumarate Among Transgender Adolescents and Young Adults Without HIV Receiving Gender Affirming Hormones.

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).

Gender-Affirming Hormone Pharmacokinetics Among Adolescent and Young Adult Transgender Persons Receiving Daily Emtricitabine/Tenofovir Disoproxil Fumarate.

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).

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.

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.

Short Communication: Bioequivalence of Tenofovir and Emtricitabine After Coencapsulation with the Proteus Ingestible Sensor.

Adherence to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, Truvada®) is the primary determinant of HIV pre-exposure prophylaxis (PrEP) efficacy. Despite its importance, limitations exist in current methods of adherence quantification, restricting their implementation in the clinic. Proteus Discover (Proteus Digital Health®) can measure the time of each dose using an ingestible sensor that is coencapsulated with medication. In this study, the bioequivalence of coencapsulated TDF/FTC with the Proteus sensor was compared relative to unencapsulated drug. This was a 1:1 randomized cross-over study in which healthy participants received a single dose of unencapsulated and coencapsulated TDF/FTC. A 14-day washout separated each period. Blood was collected at predose and at 0.25, 0.5, 1, 2, 4, 6, 10, 24, 48, and 72 h postdose. Plasma concentrations were determined by LC-MS/MS methods, with a 10 ng/mL lower limit of quantitation (LLOQ) for both tenofovir (TFV) and FTC. Noncompartmental analysis was carried out with Phoenix® WinNonlin® for maximum concentrations (Cmax), area under the concentration-time curve from time 0 to the last measured time point (AUClast) and AUC extrapolated to infinity (AUCinf). Geometric mean ratios were calculated for each parameter and bioequivalence was defined as the 90% confidence interval (CI) of each ratio being within 80%-125%. Twenty-four participants (11 males; 19 white, 3 African American, and 2 Hispanic) completed both visits. Mean ± SD age was 28 ± 4 years and weight was 74 ± 14 kg. The 90% CIs for TFV Cmax, AUClast, and AUCinf were 89%-119%, 94%-111%, and 96%-111%, respectively. The 90% CIs for FTC Cmax, AUClast, and AUCinf were 96%-120%, 96%-108%, and 96%-108%, respectively. Bioequivalence was observed for the coencapsulation of TDF/FTC with the Proteus ingestible sensor, as assessed by a rigorously conducted pharmacokinetic study. Future studies will evaluate the utility and effectiveness of the sensor system as a tool to monitor PrEP adherence in clinical settings.

Preferences for Injectable PrEP Among Young U.S. Cisgender Men and Transgender Women and Men Who Have Sex with Men.

Young men who have sex with men account for approximately 20% of incident HIV infections in the U.S. Antiretroviral pre-exposure prophylaxis (PrEP) administered as a daily pill has been shown to decrease HIV acquisition in at-risk individuals. New modalities for PrEP are being developed and tested, including injectable PrEP; however, acceptability of these emerging modalities has not yet been examined in youth. We conducted six focus groups with 36 young men and transgender men and women who have sex with men in Boston, Chicago, and Los Angeles in 2016 to assess interest in and preference for different PrEP modalities. Youth were purposively recruited based on diversity of age, race/ethnicity, and prior PrEP experience. Data were coded using content coding based on key domains of the interview guide, in particular around the central themes of interest in and barriers and facilitators to injectable PrEP use. Participants were knowledgeable about oral PrEP but suggested barriers to broader uptake, including stigma, marginalization, and access to information. While participants were split on preference for injectable versus oral PrEP, they agreed quarterly injections may be more manageable and better for those who have adherence difficulties and for those who engage in sex more frequently. Concerns specific to injectable PrEP included: severity/duration of side effects, pain, level of protection prior to next injection, distrust of medical system and injections, and cost. Understanding barriers to and preferences for diverse prevention modalities will allow for more HIV prevention options, improved products, and better interventions, thus allowing individuals to make informed HIV prevention choices.

Safety and Feasibility of Antiretroviral Preexposure Prophylaxis for Adolescent Men Who Have Sex With Men Aged 15 to 17 Years in the United States.

Importance: Adolescents 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. Objective: To 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 Participants: Adolescent 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. Exposures: All participants completed an individualized evidence-based behavioral intervention and were provided with daily TDF/FTC as PrEP for 48 weeks. Main Outcomes and Measures: The 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. Results: Among 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 Relevance: Adolescent 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 Registration: clinicaltrials.gov Identifier: NCT01769456.

An HIV Preexposure Prophylaxis Demonstration Project and Safety Study for Young MSM.

BACKGROUND: Young 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. METHODS: Eligible 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). RESULTS: Between 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. CONCLUSIONS: Acceptability 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.

Young Women Living with HIV: Outcomes from a Targeted Secondary Prevention Empowerment Pilot Trial.

UNLABELLED: Women account for 1 in 5 new HIV infections in the US, make up 24% of people living with HIV, and represent a quarter of AIDS diagnoses. Despite the need for continued prevention among young women living with HIV, there is very little in the literature on how best to reduce sexual risk and increase the health and well-being of young women living with HIV. This article explores the primary and secondary outcomes of a randomized controlled pilot trial of an intervention entitled EVOLUTION: Young Women Taking Charge and Growing Stronger. This behavioral intervention aimed to decrease sexual risk and empower young women living with HIV by enhancing young women's knowledge and skills pertaining to HIV risk reduction as well as to the factors that increase women's vulnerability, such as sexual inequality, gender, and power imbalances. Findings from this trial demonstrate that group-based behavioral interventions for young women living with HIV have promise to reduce the total number of sexual partners and reduce unprotected vaginal and anal intercourse. However, more work is needed to understand how best to address the challenges young women face in their day to day lives that impact their sexual risk as well as their overall health and access to care and treatment.

Relationship Dynamics and Sexual Risk Reduction Strategies Among Heterosexual Young Adults: A Qualitative Study of Sexually Transmitted Infection Clinic Attendees at an Urban Chicago Health Center.

Few studies have examined risk-reduction alternatives to consistent condom use for HIV prevention among heterosexual young adults. We used qualitative methodology to explore risk reduction strategies and contextual factors influencing attempts to reduce risk in an urban, high morbidity sexually transmitted infection (STI) clinic. Focus groups were conducted October-December 2014 with heterosexually identified men (n = 13) and women (n = 20) aged 18-29 seeking STI screening at an urban clinic. Groups were audio recorded, transcribed verbatim, and analyzed for thematic content using Atlas.ti software. Quantitative information included sociodemographics, HIV/STI testing history, and 6-month sexual behaviors. Among 33 predominantly African-American participants with a median age of 22, risk-reduction strategies included monogamy agreements, selective condom use with casual and high-risk partners, and frequent HIV/STI testing, though testing was commonly used as a post-hoc reassurance after risk exposure. Many men and women used implicit risk assessment strategies due to mistrust or difficulty communicating. Concurrency was common but rarely discussed within partnerships. Despite attempts to reduce risk, monogamy agreements were often poorly adhered to and not openly discussed. Alcohol and substance use frequently interfered with safer sexual decisions. Participants were aware of HIV/STI risk and commonly practiced risk-reduction strategies, but acknowledged faulty assumptions and poor adherence. This work provides insights into risk-reduction approaches that are already used and may be strengthened as part of effective HIV/STI prevention interventions.

EVOLUTION--taking charge and growing stronger: the design, acceptability, and feasibility of a secondary prevention empowerment intervention for young women living with HIV.

UNLABELLED: In the United States, youth of 13-24 years account for nearly a quarter of all new HIV infections, with almost 1000 young men and women being infected per month. Young women account for 20% of those new infections.This article describes the design, feasibility, and acceptability of a secondary prevention empowerment intervention for young women living with HIV entitled EVOLUTION: Young Women Taking Charge and Growing Stronger. The nine session intervention aimed to reduce secondary transmission by enhancing social and behavioral skills and knowledge pertaining to young women's physical, social, emotional, and sexual well-being,while addressing the moderating factors such as sexual inequality and power imbalances. Process evaluation data suggest that EVOLUTION is a highly acceptable and feasible intervention for young women living with HIV. Participants reported enjoying both the structure and comprehensive nature of the intervention. Both participants and interventionists reported that the intervention was highly relevant to the lives of young women living with HIV since it not only provided opportunities for them to broaden their knowledge and risk reduction skills in HIV, but it also addressed important areas that impact their daily lives such as stressors, relationships,and their emotional and social well-being. Thus, this study demonstrates that providing a gender-specific,comprehensive group-based empowerment intervention for young women living with HIV appears to be both feasible and acceptable.

What HIV-positive young women want from behavioral interventions: a qualitative approach.

Young women living with HIV in the United States face many social and psychological challenges, including involvement in health care and secondary prevention efforts. The factors that put these young women at risk for HIV acquisition initially, such as poverty, gender roles, cultural norms, and limited perceived control over sexual relationships, continue to place them at risk for both adverse mental and physical health outcomes that impact their daily lives and secondary prevention efforts. This study utilized focus groups with young HIV-positive women in order to better understand their perceived problems and pressures and to inform a developmentally appropriate secondary prevention intervention for young HIV-positive women that could be implemented in clinical care settings. Focus groups with young HIV-positive women were convened in three U.S. cities: Baltimore, Chicago, and Tampa. A total of 17 young, HIV-positive women, age range 17­24 (mean age=21), participated in the focus groups. This article describes the psychological and social challenges these young women face as well as their suggestions regarding secondary HIV prevention intervention components.