Adapting mHealth Interventions (PrEPmate and DOT Diary) to Support PrEP Retention in Care and Adherence Among English and Spanish-Speaking Men Who Have Sex With Men and Transgender Women in the United States: Formative Work and Pilot Randomized Trial.

BACKGROUND: A growing number of mobile health (mHealth) technologies are being developed to support HIV preexposure prophylaxis (PrEP) adherence and persistence; however, most tools have focused on men who have sex with men (MSM), and few are available in Spanish. To maximize the potential impact of these tools in reducing gender and racial/ethnic disparities and promoting health equity, mHealth tools tailored to Spanish-speaking people and transgender women are critically needed. OBJECTIVE: The aim of this study is to adapt and tailor 2 mHealth technologies, PrEPmate and DOT Diary, to support daily PrEP adherence and persistence among Spanish-speaking MSM and English- and Spanish-speaking transgender women and to evaluate the feasibility and acceptability of these tools. METHODS: PrEPmate, an interactive, bidirectional, text messaging intervention that promotes personalized communication between PrEP users and providers, and DOT Diary, a mobile app that promotes self-management of PrEP use and sexual health through an integrated electronic pill-taking and sexual activity diary, were previously developed for English-speaking MSM. We conducted 3 focus groups with 15 English- and Spanish-speaking transgender women and MSM in San Francisco and Miami to culturally tailor these tools for these priority populations. We then conducted a 1-month technical pilot among 21 participants to assess the usability and acceptability of the adapted interventions and optimize the functionality of these tools. RESULTS: Participants in focus groups liked the "human touch" of text messages in PrEPmate and thought it would be helpful for scheduling appointments and asking questions. They liked the daily reminder messages, especially the fun facts, gender affirmations, and transgender history topics. Participants recommended changes to tailor the language and messages for Spanish-speaking and transgender populations. For DOT Diary, participants liked the adherence tracking and protection level feedback and thought the calendar functions were easy to use. Based on participant recommendations, we tailored language within the app for Spanish-speaking MSM and transgender women, simplified the sexual diary, and added motivational badges. In the technical pilot of the refined tools, mean System Usability Scale scores were 81.2/100 for PrEPmate and 76.4/100 for DOT Diary (P=.48), falling in the "good" to "excellent" range, and mean Client Satisfaction Questionnaire scores were 28.6 and 28.3 for PrEPmate and DOT Diary, respectively (maximum possible score=32). Use of both tools was high over the 1-month pilot (average of 10.5 messages received from each participant for PrEPmate; average of 17.6 times accessing the DOT Diary app), indicating good feasibility for both tools. CONCLUSIONS: Using a user-centered design approach, we culturally tailored PrEPmate and DOT Diary to support daily PrEP use among Spanish-speaking MSM and English- and Spanish-speaking transgender women. Our positive findings in a technical pilot support further testing of these mHealth interventions in an upcoming comparative effectiveness trial.

Phase 1 randomized pharmacokinetic and safety study of a 90-day tenofovir vaginal ring in the United States.

INTRODUCTION: Tenofovir-based oral pre-exposure prophylaxis is currently approved for HIV prevention; however, adherence in women has been low. A vaginal gel containing tenofovir (TFV) demonstrated partial protection to HIV but protection was not confirmed in additional studies. Vaginal rings offer user-controlled long-acting HIV prevention that could overcome adherence and protection challenges. TFV may also help prevent herpes simplex virus type 2 acquisition when delivered intravaginally. We evaluated the pharmacokinetics, safety, adherence and acceptability of a 90-day TFV ring. METHODS: Between January and June 2019, Microbicide Trials Network (MTN)-038 enrolled 49 HIV-negative participants into a phase 1, randomized (2:1) trial comparing a 90-day ring containing 1.4 grams (g) TFV to a placebo ring. TFV concentrations were quantified in plasma, cervicovaginal fluid (CVF), rectal fluid and cervical tissue, and TFV-diphosphate (TFV-DP) in cervical tissue. Used rings were analysed for residual TFV. Safety was assessed by adverse events (AEs); acceptability and adherence by self-report. RESULTS: Mean age was 29.5; 46 identified as cisgender-female and three gender non-conforming. There were no differences in the proportion of participants with grade ≥2 genitourinary AEs in the TFV versus placebo arms (p = 0.41); no grade ≥3 AEs were reported. Geometric mean TFV concentrations increased through day 34 in CVF/rectal fluid and day 59 in plasma, but declined across compartments by day 91. Geometric mean TFV-DP tissue concentrations exceeded the 1000 fmol/mg target through day 56, but fell to 456 fmol/mg at day 91. Among 32 rings returned at the end of the study, 13 had no or low (<0.1 g) residual TFV. Residual TFV did not differ by socio-demographics, sexual activity, Nugent Score or vaginal microbiota. Most participants reported being fully adherent to ring use: 85% and 81% in the TFV and placebo arms, respectively (p = 1.00). A majority of participants reported liking the ring (median 8 on a 10-point Likert scale) and reported a high likelihood of using the ring in the future, if effective (median 9). CONCLUSIONS: The 90-day TFV ring was well-tolerated, acceptable and exceeded target cervical tissue concentrations through day 56, but declined thereafter. Additional studies are needed to characterize the higher release from TFV rings in some participants and the optimal duration of use.

CROI 2023: Epidemiologic Trends and Prevention for HIV and Other Sexually Transmitted Infections.

At the 2023 Conference on Retroviruses and Opportunistic Infections (CROI), several investigators used tests of recent HIV infection to track which populations are currently most heavily impacted by HIV and to estimate HIV infection rates in those populations. Assisted partner notification for HIV was successfully applied for spouses of persons with HIV and sexual and injection partners of people who inject drugs; however, delays in linkage to care were seen for non-spousal partners in one study. Lack of awareness of HIV positive status remains an issue in various populations; several presentations focused on novel strategies for improving HIV testing uptake in these populations. Doxycycline administered as 200 mg post sexual exposure significantly reduced the risk of syphilis, chlamydia, and gonorrhea infection in men who have sex with men but did not prevent bacterial sexually transmitted infections (STIs) in cis-gender women; reasons for this discrepancy are currently being explored. Although oral HIV preexposure prophylaxis (PrEP) is increasingly being used in populations in greatest need of prevention tools, PrEP uptake and persistence remain low in a number of key populations, including people who inject drugs. Several innovative delivery models show early promise in addressing gaps along the PrEP continuum. The successful use of injectable cabotegravir PrEP in several populations was presented at this conference, although uptake remains low globally. The pipeline of novel long-acting and rapid-onset PrEP agents appears to be robust, including implants, vaginal rings, and topical inserts, with several presentations focusing on preclinical and early clinical trials.

Implementation of an intravenous sotalol initiation protocol: Implications for feasibility, safety, and length of stay.

INTRODUCTION: Oral sotalol initiation requires a multiple-day, inpatient admission to monitor for QT prolongation during loading. A 1-day intravenous (IV) sotalol loading protocol was approved by the United States Food and Drug Administration in March 2020, but limited data on clinical use and administration currently exists. This study describes implementation of an IV sotalol protocol within an integrated health system, provides initial efficacy and safety outcomes, and examines length of stay (LOS) compared with oral sotalol initiation. METHODS: IV sotalol was administered according to a prespecified initiation protocol to adult patients with refractory atrial or ventricular arrhythmias. Baseline characteristics, safety and feasibility outcomes, and LOS were compared with patients receiving oral sotalol over a similar time period. RESULTS: From January 2021 to June 2022, a total of 29 patients (average age 66.0 ± 8.6 years, 27.6% women) underwent IV sotalol load and 20 patients (average age 60.4 ± 13.9 years, 65.0% women) underwent oral sotalol load. The load was successfully completed in 22/29 (75.9%) patients receiving IV sotalol and 20/20 (100%) of patients receiving oral sotalol, although 7/20 of the oral sotalol patients (35.0%) required dose reduction. Adverse events interrupting IV sotalol infusion included bradycardia (seven patients, 24.1%) and QT prolongation (three patients, 10.3%). No patients receiving IV or oral sotalol developed sustained ventricular arrhythmias before discharge. LOS for patients completing IV load was 2.6 days shorter (mean 1.0 vs. 3.6, p < .001) compared with LOS with oral load. CONCLUSION: IV sotalol loading has a safety profile that is similar to oral sotalol. It significantly shortens hospital LOS, potentially leading to large cost savings.

Randomized Controlled Trial of Automated Directly Observed Therapy for Measurement and Support of PrEP Adherence Among Young Men Who have Sex with Men.

Measurement of adherence to oral pre-exposure prophylaxis (PrEP) in real-time has been challenging. We developed DOT Diary, a smartphone application that combines automated directly observed therapy with a PrEP adherence visualization toolkit, and tested its ability to measure PrEP adherence and to increase adherence among a diverse cohort of young men who have sex with men (MSM). We enrolled 100 MSM in San Francisco and Atlanta and randomly assigned them 2:1 to DOT Diary versus standard of care. Concordance between DOT Diary measurement and drug levels in dried blood spots was substantial, with 91.0% and 85.3% concordance between DOT Diary and emtricitabine-triphosphate and tenofovir-diphosphate, respectively. There was no significant difference in the proportion of participants with detectable PrEP drug levels at 24 weeks between study arms. These results suggest DOT Diary is substantially better than self-reported measures of adherence, but additional interventions are needed to improve PrEP adherence over time.

RESUMEN: La medición de la adherencia a la profilaxis oral previa a la exposición (PrEP) en tiempo real ha constituido un desafío. Hemos desarrollado DOT Diary, una aplicación para teléfonos inteligentes que combina la terapia automatizada observada de forma directa con un kit de herramientas para visualizar la adherencia a la PrEP, y testeamos su capacidad para medir la adherencia a la PrEP, así como para aumentar la adherencia entre una cohorte variada de hombres jóvenes que tienen sexo con hombres (HSH). Reclutamos a 100 HSH en San Francisco y Atlanta y los asignamos aleatoriamente 2:1 a DOT Diary con respecto a la asistencia estándar. La concordancia entre la medición del DOT Diary y los niveles de fármacos en gotas de sangre seca fue sustancial, con un 91,0% y un 85,3% de concordancia entre el uso del DOT Diary y el de emtricitabina-trifosfato y tenofovir-difosfato, respectivamente. No hubo diferencias significativas en la proporción de participantes con niveles detectables del fármaco de la PrEP a las 24 semanas entre los brazos del estudio. Estos resultados sugieren que DOT Diary es sustancialmente superior a las medidas de adherencia que se notifican de forma personal, aunque hacen falta intervenciones adicionales para mejorar la adherencia a la PrEP a largo plazo.

Investigation of the Effect of Turn Residues on Tetrapeptide Aldol Catalysts with ß-Turn Propensity.

Peptide catalysts for a wide diversity of reaction types contain a common motif-residues that bias the sequence toward ß-turn secondary structure. In this work, we explore what role that secondary structure plays in the catalysis of aldol reactions for primary amine tetrapeptide aldol catalysts. Using a lead tetrapeptide ß-turn catalytic sequence, we varied the i + 1 and i + 2 residues to amino acids that would affect the ß-turn propensity. We then studied the correlation between secondary structure, aldol rate enhancement, and stereoselectivity of the reaction between hydroxyacetone and 4-nitrobenzaldehyde. Using the i + 3 amide chemical shift as a measure of ß-turn character, we found a rough correlation between the peptide structure and reaction kinetics but minimal effect on stereoselectivity. These trends may help aid the design of future catalytic sequences.

The effect of an HIV preexposure prophylaxis panel management strategy to increase preexposure prophylaxis prescriptions.

OBJECTIVE: The HIV preexposure prophylaxis optimization intervention (PrEP-OI) study evaluated the efficacy of a panel management intervention using PrEP coordinators and a web-based panel management tool to support healthcare providers in optimizing PrEP prescription and ongoing PrEP care. DESIGN: The PrEP-OI study was a stepped-wedge randomized clinical trial conducted across 10 San Francisco Department of Public Health primary care sites between November 2018 and September 2019. Each month, clinics one-by-one initiated PrEP-OI in random order until all sites received the intervention by the study team. METHODS: The primary outcome was the number of PrEP prescriptions per month. Secondary outcomes compared pre- and postintervention periods on whether PrEP was discussed and whether PrEP-related counseling (e.g., HIV risk assessment, risk reduction counseling, PrEP initiation/continuation assessment) was conducted. Prescription and clinical data were abstracted from the electronic health records. We calculated incidence rate ratios (IRR) and risk ratios (RR) to estimate the intervention effect on primary and secondary outcomes. RESULTS: The number of PrEP prescriptions across clinics increased from 1.85/month (standard deviation [SD] = 2.55) preintervention to 2.44/month (SD = 3.44) postintervention (IRR = 1.34; 95% confidence interval [CI] = 1.05-1.73; P  = 0.021). PrEP-related discussions during clinic visits (RR = 1.13; 95% CI = 1.04-1.22; P  = 0.004), HIV risk assessment (RR = 1.40; 95% CI = 1.14-1.72; P  = 0.001), and risk reduction counseling (RR = 1.16; 95% CI = 1.03-1.30; P  = 0.011) increased from the pre- to the postintervention period. Assessment of PrEP initiation/continuation increased over time during the postintervention period (RR = 1.05; 95% CI = 0.99-1.11; P  = 0.100). CONCLUSIONS: A panel management intervention using PrEP coordinators and a web-based panel management tool increased PrEP prescribing and improved PrEP-related counseling in safety-net primary care clinics.

Intersecting epidemics: the impact of coronavirus disease 2019 on the HIV prevention and care continua in the United States.

OBJECTIVE: To summarize the broad impact of the coronavirus disease 2019 (COVID-19) pandemic on HIV prevention and care in the United States with a focus on the status-neutral HIV care continuum. DESIGN: We conducted an editorial review of peer-reviewed literature on the topics of HIV-risk behaviors, sexually transmitted illness (STI) and HIV prevalence, HIV prevention and treatment trends, and evolving practices during the COVID-19 pandemic. METHODS: For relevant literature, we reviewed, summarized, and categorized into themes that span the HIV prevention and care continua, including sexual risk behaviors, mental health, and substance use. RESULTS: We identified important changes within each component of the HIV care continuum across the United States during the COVID-19 pandemic. Shifts in prevention practices, engagement with care, care provision, medication adherence, testing, and prevalence rates were observed during the pandemic. CONCLUSION: Although heightened disparities for people at risk for, and living with, HIV were seen during the COVID-19 pandemic, many health systems and clinics have achieved and maintained engagement in HIV prevention and care. This review highlights barriers and innovative solutions that can support durable and accessible health systems through future public health crises.

Sexual behavior and medication adherence in men who have sex with men participating in a pre-exposure prophylaxis study of combinations of Maraviroc, Tenofovir Disoproxil Fumarate and/or Emtricitabine (HPTN 069/ACTG 5305).

HPTN 069/ACTG 5305 was designed to evaluate potential new PrEP regimens that included maraviroc, tenofovir disoproxil fumarate, and/or emtricitabine. The current analyses assessed antiretroviral (ARV) plasma concentrations in relation to sexual behavior in 224 cisgender men who have sex with men and 2 transgender women at risk for HIV. Poisson generalized estimating equations (GEE) regression were used to test for associations between self-reported sexual behavior, sociodemographic, behavioral variables, and study drug levels The median (IQR) age was 30 [25, 37] years old; 48.2% had completed college; 27.4% were Black and 21.7% Latino. At weeks 24 and 48, one third of participants reported condomless anal sex (CAS) in the prior month with more than one partner. CAS was associated with daily ARV drug use (χ2 = 12.64, p = 0.002). Older individuals and those with greater education were more likely to ingest ARV drugs daily (χ2 = 9.36, p = 0.009 and χ2 = 8.63, p = 0.013, respectively), while neither race nor ethnicity was associated with daily ARV drug use. Participants who reported recent condomless anal sex and/or advanced education had higher rates of daily ARV drug use. These data support the need for ongoing adherence counseling in clinical trials of new PrEP modalities.

Acceptability and Preference for 3-Month Versus 1-Month Vaginal Rings for HIV-1 Risk Reduction Among Participants in a Phase 1 Trial.

Background: The monthly dapivirine vaginal ring provides partial protection against HIV, and a longer duration ring may reduce user burden and improve adherence. We examined acceptability and preference for 3-month versus 1-month rings for HIV-1 risk reduction in a phase 1 clinical trial. Materials and Methods: In Microbicide Trials Network-036/International Partnership for Microbicides 047, 49 HIV-negative participants aged 18-45 were randomized to one of two 3-month rings or the 1-month ring. Acceptability ratings were collected at enrollment, week 4, and study exit (week 13). At exit, ring preference was assessed quantitatively among all participants and a randomly selected subset of 24 participants completed in-depth interviews. Quantitative and qualitative findings were integrated to explore factors influencing acceptability and preference. Results: Acceptability of each ring was initially moderate and increased during the trial. Ratings were lower in the 3-month ring arms than the 1-month arm at each time point, including baseline. Most participants (34/47; 72%) preferred a 3-month ring at exit; however, this proportion was significantly lower within some subgroups characterized by site, education, race/ethnicity, and experiences with ring use. Qualitative interviews revealed reservations about hygiene and safety of the 3-month ring, including discomfort with use during menses, but these were usually outweighed by its increased convenience. Conclusions: Both ring durations were highly acceptable at study exit. Although most participants preferred a 3-month ring, preference was more divided in certain subgroups, highlighting the benefit of offering different duration options. Providing additional support to address concerns about hygiene and safety may improve acceptability of a 3-month vaginal ring.

Users' Preferred Characteristics of Vaginal Rings for HIV Prevention: A Qualitative Analysis of Two Phase I Trials.

Vaginal rings address a critical need for an independently initiated, long-acting HIV prevention method, but their design must be acceptable to promote uptake and adherence. Human-centered design (HCD) may help address design preference questions. In two Phase I studies of vaginal rings for HIV prevention conducted in the United States, we used qualitative interviews to assess participants' perceptions and opinions of the physical characteristics of the ring they used and of a ring's physical characteristics after comparing four ring designs presented via a visual tool. Users were found to prefer ring designs that appear easy to use, are physically comfortable, that function well, and are aesthetically pleasing. The parameters for these features varied widely. Product developers and marketers should consider marketing messages in which the target users feel this product is made to meet their needs and desires. Product developers are encouraged to design using HCD early in ring development (Clinical Trial Registration number: NCT03234400 and NCT03670355).

Phase 1 pharmacokinetics and safety study of extended duration dapivirine vaginal rings in the United States.

INTRODUCTION: Vaginal rings are a promising approach to provide a woman-centred, long-acting HIV prevention strategy. Prior trials of a 25 mg dapivirine (DPV) ring have shown a favourable safety profile and approximately 30% risk reduction of HIV-1 infection. Extended duration rings replaced every three months may encourage user adherence, improve health service efficiency and reduce cost overall. We evaluated safety, pharmacokinetics, adherence and acceptability of two three-month rings with different DPV dosages, compared with the monthly DPV ring. METHODS: From December 2017 to October 2018, MTN-036/IPM-047 enrolled 49 HIV-negative participant in Birmingham, Alabama and San Francisco, California into a phase 1, randomized trial comparing two extended duration (three-month) rings (100 or 200 mg DPV) to a monthly 25 mg DPV ring, each used over 13 weeks, with follow-up completed in January 2019. Safety was assessed by recording adverse events (AEs). DPV concentrations were quantified in plasma, cervicovaginal fluid (CVF) and cervical tissue, at nominal timepoints. Geometric mean ratios (GMRs) relative to the comparator ring were estimated from a regression model. RESULTS: There were no differences in the proportion of participants with grade ≥2 genitourinary AEs or grade ≥3 AEs in the extended duration versus monthly ring arms (p = 1.0). Plasma and CVF DPV concentrations were higher in the extended duration rings compared to the monthly ring. Plasma GMRs were 1.31 to 1.85 and 1.41 to 1.86 and CVF GMRs were 1.45 to 2.87 and 1.74 to 2.60 for the 100 and 200 mg ring respectively. Cervical tissue concentrations were consistently higher in the 200 mg ring (GMRs 2.36 to 3.97). The majority of participants (82%) were fully adherent (ring inserted at all times, with no product discontinuations/outages) with no differences between the monthly versus three-month rings. Most participants found the ring acceptable (median = 8 on 10-point Likert scale), with a greater proportion of participants reporting high acceptability (9 or 10) in the 25 mg arm (73%) compared with the 100 mg (25%) and 200 mg (44%) arms (p = 0.01 and p = 0.15 respectively). CONCLUSIONS: The extended duration DPV rings were well-tolerated and achieved higher DPV concentrations compared with the monthly DPV ring. These findings support further evaluation of three-month DPV rings for HIV prevention.

Adapting technology-based HIV prevention and care interventions for youth: lessons learned across five U.S. Adolescent Trials Network studies.

BACKGROUND: U.S. sexual and gender minority youth experience individual, interpersonal, and structural-level barriers to HIV prevention and care. Innovative, youth-driven approaches to mobile and electronic interventions that support use of new biomedical prevention, testing, and treatment options may address these barriers. Adapting evidence-based interventions for youth must balance core intervention components with responsiveness to the distinct needs of end-users. METHODS: The UNC/Emory Center for Innovative Technology (iTech) adapts and evaluates technology-based interventions for youth living with or at risk for HIV. We analyzed formative research (focus groups and individual usability sessions) across five iTech studies: two apps promoting HIV testing and pre-exposure prophylaxis (PrEP), one app promoting behavioral risk reduction and PrEP, one PrEP adherence app, and one mobile-optimized website for increasing viral suppression, with the aim of informing best practices for technology-based intervention development. Each study presented prototypes of adapted mHealth interventions to samples of their target end-user population for use and/or evaluation. RESULTS: One hundred and thirty-eight youth across seven geographically diverse sites provided feedback during the intervention adaptation process. We found high interest in and acceptability of all five intervention prototypes. Cross-study themes included: (I) Desire for multiple privacy protections (e.g., password, fingerprint) to keep HIV status, sexual identity, and sexual behavior confidential. (II) Strong but varied preferences for the look and feel of platforms. Imagery should be discrete but representative. Participants valued customizable platforms and positive themes, motivational language, and humor. Youth wanted information presented using multiple modalities (e.g., text, video, image) to increase engagement. (III) Youth preferred engagement features and functions consistent with familiar platforms (e.g., Snapchat, Instagram). Gamification features that resulted in tangible versus virtual rewards were predicted to increase engagement. Intervention messaging functions were perceived as useful; customization was desired as a way to control frequency, mode (e.g., SMS, in-app message, push notification), and content. (IV) Youth voiced varied preferences for platform content including: featuring young role models from the lesbian, gay, bisexual, transgender, queer and/or questioning (LGBTQ) community, incorporating mental health resources, and maintaining a holistic health-focus (not HIV-centric). CONCLUSIONS: We found high acceptability and consistent feedback in youths' evaluations of these mHealth interventions; divergence was most commonly found in preferred content versus features and functions. Identifying broadly accepted aspects of mHealth interventions for youth supports the feasibility of adaptation (versus de novo creation) and should guide the focus of future formative research phases. Continued research is needed to better understand how to balance usability preferences with finite resources for customization.

Identification of Novel UGT1A1 Variants Including UGT1A1 454C>A through the Genotyping of Healthy Participants of the HPTN 077 Study.

Cabotegravir (CAB) is an integrase strand-transfer inhibitor of HIV that has proven effective for HIV treatment and prevention in a long-acting injectable formulation, typically preceded by an oral formulation lead-in phase. Previous in vitro studies have demonstrated that CAB is primarily metabolized via glucuronidation by uridine diphosphate glucuronosyltransferase (UGT) 1A1 and 1A9. In this study, we performed next-generation sequencing of genomic DNA isolated from the HPTN 077 participants to explore the variants within UGT1A1 and UGT1A9. Additionally, to enable correlation of UGT1A1 and UGT1A9 genotypes with plasma CAB-glucuronide levels, we quantified glucuronidated CAB following both oral administration of CAB and intramuscular injection of long-acting CAB. From these studies, 48 previously unreported variants of UGT1A1 and UGT1A9 were detected. Notably, 5/68 individuals carried a UGT1A1 454C>A variant that resulted in amino acid substitution P152T, and the use of in silico tools predicted a deleterious effect of the P152T substitution. Thus, the impact of this mutant on a range of UGT1A1 substrates was tested using a COS-7 cell-based assay. The glucuronide conjugates of CAB, dolutegravir, and raltegravir, were not formed in the COS-7 cells expressing the UGT1A1 P152T mutant. Further, formation of glucuronides of raloxifene and 7-ethyl-10-hydroxycamptothecin were reduced in the cells expressing the UGT1A1 P152T mutant. Using the same approach, we tested the activities of two UGT1A9 mutants, UGT1A9 H217Y and UGT1A9 R464G, and found that these mutations were tolerated and decreased function, respectively. These data provide insight into previously unreported genetic variants of UGT1A1 and UGT1A9.

Correction to "Identification of Novel UGT1A1 Variants Including UGT1A1 454C>A through the Genotyping of Healthy Participants of the HPTN 077 Study".

[This corrects the article DOI: 10.1021/acsptsci.0c00181.].

DOT Diary: Developing a Novel Mobile App Using Artificial Intelligence and an Electronic Sexual Diary to Measure and Support PrEP Adherence Among Young Men Who Have Sex with Men.

Young men who have sex with men (YMSM) are highly vulnerable to HIV. While pre-exposure prophylaxis (PrEP) has demonstrated effectiveness, adherence has been low among YMSM and difficult to measure accurately. In collaboration with a healthcare company, we configured an automated directly-observed therapy (aDOT) platform for monitoring and supporting PrEP use. Based on interest expressed in focus groups among 54 YMSM, we combined aDOT with an electronic sexual diary to provide feedback on level of protection during sex and to motivate app use. In an 8-week optimization pilot with 20 YMSM in San Francisco and Atlanta, the app was found to be highly acceptable, with median System Usability Scale scores in the "excellent" range (80/100). App use was high, with median PrEP adherence of 91% based on aDOT-confirmed dosing. Most (84%) participants reported the app helped with taking PrEP. These promising findings support further evaluation of DOT Diary in future effectiveness studies.

Virtual CROI 2020: Highlights of Epidemiology, Public Health, and Prevention Research.

At the 2020 Conference on Retroviruses and Opportunistic Infections, held virtually as a result of the emerging COVID-19 pandemic, trends in the HIV epidemic were highlighted, with decreasing HIV incidence reported across several countries, although key regions remain heavily impacted, including the US South. Adolescent girls and young women, men who have sex with men (MSM), transgender persons, and people who inject drugs continue to experience a high burden of new infections. Sexually transmitted infections during pregnancy can lead to a number of adverse outcomes in infants; novel strategies to detect and treat these infections are needed. Innovative HIV testing strategies, including self-testing and assisted partner services, are expanding the reach of testing; however, linkage to care can be improved. Novel preexposure prophylaxis (PrEP) delivery strategies are increasing uptake of PrEP in different groups, although adherence and persistence remain a challenge. Use of on-demand PrEP is increasing among MSM in the US. Strategies are needed to address barriers to PrEP uptake and persistence among cis- and transgender women. Several novel regimens for postexposure prophylaxis show promise.

Tail-phase safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in HIV-uninfected adults: a secondary analysis of the HPTN 077 trial.

BACKGROUND: Long-acting injectable cabotegravir is a novel integrase inhibitor currently in advanced clinical development for HIV prevention and treatment. We aimed to assess the terminal phase pharmacokinetics and safety of long-acting injectable cabotegravir in participants included in the HPTN 077 trial. METHODS: HPTN 077 was a multicentre, double-blind, randomised, placebo-controlled phase 2a trial done at eight sites in Brazil, Malawi, South Africa, and the USA. Participants (aged 18-65 years), who were HIV-uninfected and at low-risk for HIV, were randomly assigned (3:1) to long-acting injectable cabotegravir (800 mg given three times at 12 week intervals or 600 mg given five times, administered at one 4 week interval, and every 8 weeks thereafter) or placebo. Participants were followed up to 76 weeks after final injection. In a prespecified analysis of secondary and exploratory outcomes, we assessed the safety, measured by the proportion of participants with grade 2 or worse adverse events, and pharmacokinetics, measured by apparent terminal phase half-life (t1/2app) and estimated time to lower limit of quantification (LLOQ) of long-acting injectable cabotegravir during the injection phase (defined as the time between first injection and 12 weeks or 8 weeks after the last injection in cohort 1 or cohort 2 respectively) and tail phase (defined as the time between final injection and 52-76 weeks post-final injection). Safety was analysed in all participants who received at least one injection. Pharmacokinetic analyses included all participants who had received at least one injection and had at least three cabotegravir measurements higher than the LLOQ after the final injection. Pharmacokinetic outcomes were estimated using non-compartmental methods. The trial is completed, and was registered with ClinicalTrials.gov, NCT02178800. FINDINGS: Between Feb 9, 2015, and May 27, 2016, 177 participants (134 participants in the cabotegravir group [74 participants in cohort 1; 60 participants in cohort 2] and 43 participants in the placebo group [25 participants in cohort 1; 18 participants in cohort 2) were enrolled and received at least one injection and thus were included in the safety analysis. The incidence of grade 2 or worse adverse events was significantly lower during the tail phase than the injection phase (p<0·0001). At 52-60 weeks after final injection, nine (23%) of 40 male participants had detectable cabotegravir concentrations and at week 76, four (13%) of 30 male participants had detectable cabotegravir concentrations compared with 52 (63%) of 82 female participants and 27 (42%) of 64 female participants at the same timepoints. The median time from the last injection to the time when cabotegravir concentration decreased below the LLOQ was 43·7 weeks (IQR 31·1-66·6; range 20·4-152·5) for male participants and 67·3 weeks (29·1-89·6; 17·7-225·5) for female participants (p=0·0003). t1/2app was longer for female participants than male participants (geometric mean fold-change 1·33, 95% CI 1·06-1·68; p=0·014), and longer for participants with a high body-mass index (BMI) than those with a low BMI (1·31, 1·06-1·63; p=0·015). INTERPRETATION: The clinical significance of the long pharmacokinetic tail of cabotegravir observed in female participants compared with male participants, and those with higher BMI compared with a lower BMI, need to be addressed in future trials. FUNDING: National Institute of Allergy and Infectious Diseases.