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.

Polytopic fractional delivery of an HIV vaccine alters cellular responses and results in increased epitope breadth in a phase 1 randomized trial.

BACKGROUND: Elicitation of broad immune responses is understood to be required for an efficacious preventative HIV vaccine. This Phase 1 randomized controlled trial evaluated whether administration of vaccine antigens separated at multiple injection sites vs combined, fractional delivery at multiple sites affected T-cell breadth compared to standard, single site vaccination. METHODS: We randomized 90 participants to receive recombinant adenovirus 5 (rAd5) vector with HIV inserts gag, pol and env via three different strategies. The Standard group received vaccine at a single anatomic site (n = 30) compared to two polytopic (multisite) vaccination groups: Separated (n = 30), where antigens were separately administered to four anatomical sites, and Fractioned (n = 30), where fractions of each vaccine component were combined and administered at four sites. All groups received the same total dose of vaccine. FINDINGS: CD8 T-cell response rates and magnitudes were significantly higher in the Fractioned group than Standard for several antigen pools tested. CD4 T-cell response magnitudes to Pol were higher in the Separated than Standard group. T-cell epitope mapping demonstrated greatest breadth in the Fractioned group (median 8.0 vs 2.5 for Standard, Wilcoxon p = 0.03; not significant after multiplicity adjustment for co-primary endpoints). IgG binding antibody response rates to Env were higher in the Standard and Fractioned groups vs Separated group. INTERPRETATION: This study shows that the number of anatomic sites for which a vaccine is delivered and distribution of its antigenic components influences immune responses in humans. FUNDING: National Institute of Allergy and Infectious Diseases, NIH.

Efficacy and safety of long-acting cabotegravir compared with daily oral tenofovir disoproxil fumarate plus emtricitabine to prevent HIV infection in cisgender men and transgender women who have sex with men 1 year after study unblinding: a secondary analysis of the phase 2b and 3 HPTN 083 randomised controlled trial.

BACKGROUND: Injectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials. Both trials had the primary aim of establishing the HIV prevention efficacy of long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) compared with tenofovir disoproxil fumarate plus emtricitabine daily oral PrEP. Long-acting PrEP was associated with diagnostic delays and integrase strand-transfer inhibitor (INSTI) resistance. This report presents findings from the first unblinded year of the HIV Prevention Trials Network (HPTN) 083 study. METHODS: The HPTN 083 randomised controlled trial enrolled HIV-uninfected cisgender men and transgender women at elevated HIV risk who have sex with men, from 43 clinical research sites in Africa, Asia, Latin America, and the USA. Inclusion criteria included: a negative HIV serological test at the screening and study entry, undetectable HIV RNA levels within 14 days of study entry, age 18 years or older, overall good health as determined by clinical and laboratory evaluations, and a creatinine clearance of 60 mL/min or higher. Participants were randomly allocated to receive long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP. After study unblinding, participants remained on their original regimen awaiting an extension study. HIV infections were characterised retrospectively at a central laboratory. Here we report the secondary analysis of efficacy and safety for the first unblinded year. The primary outcome was incident HIV infection. Efficacy analyses were done on the modified intention-to-treat population using a Cox regression model. Adverse events were compared across treatment groups and time periods (blinded vs unblinded). This trial is registered with ClinicalTrials.gov, NCT02720094. FINDINGS: Of the 4488 participants who contributed person-time to the blinded analysis, 3290 contributed person-time to the first unblinded year analysis between May 15, 2020, and May 14, 2021. Updated HIV incidence in the blinded phase was 0·41 per 100 person-years for long-acting injectable cabotegravir PrEP and 1·29 per 100 person-years for daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP (hazard ratio [HR] 0·31 [95% CI 0·17-0·58], p=0·0003). HIV incidence in the first unblinded year was 0·82 per 100 person-years for long-acting PrEP and 2·27 per 100 person-years for daily oral PrEP (HR 0·35 [0·18-0·69], p=0·002). Adherence to both study products decreased after study unblinding. Additional infections in the long-acting PrEP group included two with on-time injections; three with one or more delayed injections; two detected with long-acting PrEP reinitiation; and 11 more than 6 months after their last injection. Infection within 6 months of cabotegravir exposure was associated with diagnostic delays and INSTI resistance. Adverse events were generally consistent with previous reports; incident hypertension in the long-acting PrEP group requires further investigation. INTERPRETATION: Long-acting injectable cabotegravir PrEP retained high efficacy for HIV prevention in men and transgender women who have sex with men during the first year of open-label follow-up, with a near-identical HR for HIV risk reduction between long-acting injectable cabotegravir and daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP during the first year after unblinding compared with the blinded period. Extended follow-up further defined the risk period for diagnostic delays and emergence of INSTI resistance. FUNDING: Division of AIDS at the National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and Gilead Sciences.

Protein dose-sparing effect of AS01B adjuvant in a randomized preventive HIV vaccine trial of ALVAC-HIV (vCP2438) and adjuvanted bivalent subtype C gp120.

BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled HIV vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at two dose levels in healthy HIV-uninfected adults. Trial registration URL https://clinicaltrials.gov/ct2/show/NCT03122223 and registration number NCT03122223. METHODS: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200µg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40µg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses. RESULTS: We enrolled 160 participants, 55% females, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40µg gp120/AS01B group were higher than in either of the 200µg gp120 groups. CONCLUSIONS: The 40µg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses.

Prevalence of Undiagnosed Monkeypox Virus Infections during Global Mpox Outbreak, United States, June-September 2022.

Since May 2022, mpox has been identified in 108 countries without endemic disease; most cases have been in gay, bisexual, or other men who have sex with men. To determine number of missed cases, we conducted 2 studies during June-September 2022: a prospective serologic survey detecting orthopoxvirus antibodies among men who have sex with men in San Francisco, California, and a retrospective monkeypox virus PCR testing of swab specimens submitted for other infectious disease testing among all patients across the United States. The serosurvey of 225 participants (median age 34 years) detected 18 (8.0%) who were orthopoxvirus IgG positive and 3 (1.3%) who were also orthopoxvirus IgM positive. The retrospective PCR study of 1,196 patients (median age 30 years; 54.8% male) detected 67 (5.6%) specimens positive for monkeypox virus. There are likely few undiagnosed cases of mpox in regions where sexual healthcare is accessible and patient and clinician awareness about mpox is increased.

Modifiers of COVID-19 vaccine efficacy: Results from four COVID-19 prevention network efficacy trials.

Questions remain regarding the effect of baseline host and exposure factors on vaccine efficacy (VE) across pathogens and vaccine platforms. We report placebo-controlled data from four Phase 3 COVID-19 trials during the early period of the pandemic. This was a cross-protocol analysis of four randomized, placebo-controlled efficacy trials (Moderna/mRNA1273, AstraZeneca/AZD1222, Janssen/Ad26.COV2.S, and Novavax/NVX-CoV2373) using a harmonized design. Trials were conducted in the United States and international sites in adults ≥ 18 years of age. VE was assessed for symptomatic and severe COVID-19. We analyzed 114,480 participants from both placebo and vaccine arms, enrolled July 2020 to February 2021, with follow up through July 2021. VE against symptomatic COVID-19 showed little heterogeneity across baseline socio-demographic, clinical or exposure characteristics, in either univariate or multivariate analysis, regardless of vaccine platform. Similarly, VE against severe COVID-19 in the single trial (Janssen) with sufficient endpoints for analysis showed little evidence of heterogeneity. COVID-19 VE is not influenced by baseline host or exposure characteristics across efficacy trials of different vaccine platforms and countries when well matched to circulating virus strains. This supports use of these vaccines, regardless of platform type, as effective tools in the near term for reducing symptomatic and severe COVID-19, particularly for older individuals and those with common co-morbidities during major variant shifts. Clinical trial registration numbers: NCT04470427, NCT04516746, NCT04505722, and NCT04611802.

Prevention, treatment and cure of HIV infection.

The development of antiretroviral therapy for the prevention and treatment of HIV infection has been marked by a series of remarkable successes. However, the efforts to develop a vaccine have largely failed, and efforts to discover a cure are only now beginning to gain traction. In this Review, we describe recent progress on all fronts - pre-exposure prophylaxis, vaccines, treatment and cure - and we discuss the unmet needs, both current and in the coming years. We describe the emerging arsenal of drugs, biologics and strategies that will hopefully address these needs. Although HIV research has largely been siloed in the past, this is changing, as the emerging research agenda is marked by multiple cross-discipline synergies and collaborations. As the limitations of antiretroviral drugs as a means to truly end the epidemic are becoming more apparent, there is a great need for continued efforts to develop an effective preventative vaccine and a scalable cure, both of which remain formidable challenges.

Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections.

BACKGROUND: Interventions to reduce sexually transmitted infections (STIs) among men who have sex with men (MSM) are needed. METHODS: We conducted an open-label, randomized study involving MSM and transgender women who were taking preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) infection (PrEP cohort) or living with HIV infection (persons living with HIV infection [PLWH] cohort) and who had had Neisseria gonorrhoeae (gonorrhea), Chlamydia trachomatis (chlamydia), or syphilis in the past year. Participants were randomly assigned in a 2:1 ratio to take 200 mg of doxycycline within 72 hours after condomless sex (doxycycline postexposure prophylaxis) or receive standard care without doxycycline. STI testing was performed quarterly. The primary end point was the incidence of at least one STI per follow-up quarter. RESULTS: Of 501 participants (327 in the PrEP cohort and 174 in the PLWH cohort), 67% were White, 7% Black, 11% Asian or Pacific Islander, and 30% Hispanic or Latino. In the PrEP cohort, an STI was diagnosed in 61 of 570 quarterly visits (10.7%) in the doxycycline group and 82 of 257 quarterly visits (31.9%) in the standard-care group, for an absolute difference of -21.2 percentage points and a relative risk of 0.34 (95% confidence interval [CI], 0.24 to 0.46; P<0.001). In the PLWH cohort, an STI was diagnosed in 36 of 305 quarterly visits (11.8%) in the doxycycline group and 39 of 128 quarterly visits (30.5%) in the standard-care group, for an absolute difference of -18.7 percentage points and a relative risk of 0.38 (95% CI, 0.24 to 0.60; P<0.001). The incidences of the three evaluated STIs were lower with doxycycline than with standard care; in the PrEP cohort, the relative risks were 0.45 (95% CI, 0.32 to 0.65) for gonorrhea, 0.12 (95% CI, 0.05 to 0.25) for chlamydia, and 0.13 (95% CI, 0.03 to 0.59) for syphilis, and in the PLWH cohort, the relative risks were 0.43 (95% CI, 0.26 to 0.71), 0.26 (95% CI, 0.12 to 0.57), and 0.23 (95% CI, 0.04 to 1.29), respectively. Five grade 3 adverse events and no serious adverse events were attributed to doxycycline. Of the participants with gonorrhea culture available, tetracycline-resistant gonorrhea occurred in 5 of 13 in the doxycycline groups and 2 of 16 in the standard-care groups. CONCLUSIONS: The combined incidence of gonorrhea, chlamydia, and syphilis was lower by two thirds with doxycycline postexposure prophylaxis than with standard care, a finding that supports its use among MSM with recent bacterial STIs. (Funded by the National Institutes of Health; DoxyPEP ClinicalTrials.gov number, NCT03980223.).

Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults.

BACKGROUNDMosaic and consensus HIV-1 immunogens provide two distinct approaches to elicit greater breadth of coverage against globally circulating HIV-1 and have shown improved immunologic breadth in nonhuman primate models.METHODSThis double-blind randomized trial enrolled 105 healthy HIV-uninfected adults who received 3 doses of either a trivalent global mosaic, a group M consensus (CON-S), or a natural clade B (Nat-B) gp160 env DNA vaccine followed by 2 doses of a heterologous modified vaccinia Ankara-vectored HIV-1 vaccine or placebo. We performed prespecified blinded immunogenicity analyses at day 70 and day 238 after the first immunization. T cell responses to vaccine antigens and 5 heterologous Env variants were fully mapped.RESULTSEnv-specific CD4+ T cell responses were induced in 71% of the mosaic vaccine recipients versus 48% of the CON-S recipients and 48% of the natural Env recipients. The mean number of T cell epitopes recognized was 2.5 (95% CI, 1.2-4.2) for mosaic recipients, 1.6 (95% CI, 0.82-2.6) for CON-S recipients, and 1.1 (95% CI, 0.62-1.71) for Nat-B recipients. Mean breadth was significantly greater in the mosaic group than in the Nat-B group using overall (P = 0.014), prime-matched (P = 0.002), heterologous (P = 0.046), and boost-matched (P = 0.009) measures. Overall T cell breadth was largely due to Env-specific CD4+ T cell responses.CONCLUSIONPriming with a mosaic antigen significantly increased the number of epitopes recognized by Env-specific T cells and enabled more, albeit still limited, cross-recognition of heterologous variants. Mosaic and consensus immunogens are promising approaches to address global diversity of HIV-1.TRIAL REGISTRATIONClinicalTrials.gov NCT02296541.FUNDINGUS NIH grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069412, UL1 RR025758, P30 AI064518, UM1 AI100645, and UM1 AI144371, and Bill & Melinda Gates Foundation grant OPP52282.

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.

Laboratory validation and clinical performance of a saliva-based test for monkeypox virus.

Improved diagnostic tests and accessibility are essential for controlling the outbreak of monkeypox. We describe a saliva-based polymerase chain reaction (PCR) assay for monkeypox virus, in vitro test performance, and clinical implementation of that assay in Los Angeles, San Francisco, and Palm Springs, CA. Finally, using prespecified search terms, we conducted a systematic rapid review of PubMed and Web of Science online databases of studies reporting the performance of oral pharyngeal or saliva-based tests for the monkeypox virus. The assay showed in silico inclusivity of 100% for 97 strains of monkeypox virus, with an analytic sensitivity of 250 copies/ml, and 100% agreement compared to known positive and negative specimens. Clinical testing identified 22 cases of monkeypox among 132 individuals (16.7%), of which 16 (72.7%) reported symptoms, 4 (18.2%) without a rash at the time of testing. Of an additional 18 patients with positive lesion tests, 16 (88.9%) had positive saliva tests. Our systematic review identified six studies; 100% of tests on oropharyngeal specimens from 23 patients agreed with the PCR test result of a lesion. Saliva-based PCR tests are potential tools for case identification, and further evaluation of the performance of such tests is warranted.

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.

Lessons Learned from an HIV Pre-Exposure Prophylaxis Coordination Program in San Francisco Primary Care Clinics.

HIV pre-exposure prophylaxis (PrEP) has shown high efficacy and effectiveness for HIV prevention; however, many individuals with PrEP indications are not receiving PrEP. PrEP Coordinators work closely with patients and health care providers to increase PrEP access, and they provide unique insights into the inner workings of PrEP care and service delivery. In this study, we discuss key challenges and recommendations for improved PrEP service delivery (including training PrEP Coordinators to manage PrEP panels, making PrEP a part of routine care and optimizing electronic health records, designating a PrEP "champion" who can strengthen communication and leadership, using a proactive approach to increase PrEP retention, and training providers and PrEP Coordinators to meet youth-specific needs) from our discussions with the PrEP Coordinators who led PrEP panel management in San Francisco Department of Public Health primary care clinics.

Feasibility and Acceptability of Home-Collected Samples for Human Immunodeficiency Virus Preexposure Prophylaxis and Severe Acute Respiratory Syndrome Coronavirus 2 Laboratory Tests in San Francisco Primary Care Clinics.

BACKGROUND: Due to the difficulty of conducting laboratory testing during the pandemic shelter-in-place orders, the objective of this study was to examine the feasibility and acceptability of conducting home-collected samples for preexposure prophylaxis (PrEP) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) laboratory tests. METHODS: We conducted a pilot study among patients on PrEP in San Francisco primary care clinics. Individuals on PrEP provided home-collected laboratory samples using dried blood spot for fourth-generation human immunodeficiency virus antigen/antibody test, serum creatinine, syphilis antibody, and hepatitis C antibody, as needed; 3-site (oropharyngeal, rectal, and urine) swabbing for sexually transmitted infections; and nasopharyngeal swabbing for SARS-CoV-2 polymerase chain reaction. We examined feasibility and acceptability of collecting these laboratory samples using predefined benchmarks to determine feasibility or acceptability. RESULTS: Of 92 individuals who consented to participate, 73 (79.3%) mailed back their home-collected kit. Nearly 87.7% noted being extremely to moderately satisfied with the ability to complete the laboratory tests without having to come into a clinic. Approximately 49.3% of participants chose this home-collection method as their first choice for providing laboratory samples. Mean time from collection of samples by the participant to receipt of test results was reduced from the first quarter of the study (17 days) to the last quarter of the study (5 days). CONCLUSIONS: We report high levels of feasibility and acceptability with the use of home-collected laboratory samples for patients on PrEP. Our results indicate that home-collected laboratory samples for patients on PrEP is a viable option that should be offered as an alternative to clinic-collected laboratory samples.

Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women.

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).

Population Impact and Efficiency of Improvements to HIV PrEP Under Conditions of High ART Coverage Among San Francisco Men Who Have Sex With Men.

BACKGROUND: Key components of Ending the HIV Epidemic (EHE) plan include increasing HIV antiretroviral therapy (ART) and HIV pre-exposure prophylaxis (PrEP) coverage. One complication to addressing this service delivery challenge is the wide heterogeneity of HIV burden and health care access across the United States. It is unclear how the effectiveness and efficiency of expanded PrEP will depend on different baseline ART coverage. METHODS: We used a network-based model of HIV transmission for men who have sex with men (MSM) in San Francisco. Model scenarios increased varying levels of PrEP coverage relative under current empirical levels of baseline ART coverage and 2 counterfactual levels. We assessed the effectiveness of PrEP with the cumulative percentage of infections averted (PIA) over the next decade and efficiency with the number of additional person-years needed to treat (NNT) by PrEP required to avert one HIV infection. RESULTS: In our projections, only the highest levels of combined PrEP and ART coverage achieved the EHE goals. Increasing PrEP coverage up to 75% showed that PrEP effectiveness was higher at higher baseline ART coverage. Indeed, the PIA was 61% in the lowest baseline ART coverage population and 75% in the highest. The efficiency declined with increasing ART (NNT range from 41 to 113). CONCLUSIONS: Improving both PrEP and ART coverage would have a synergistic impact on HIV prevention even in a high baseline coverage city such as San Francisco. Efforts should focus on narrowing the implementation gaps to achieve higher levels of PrEP retention and ART sustained viral suppression.

Engaging youth in mHealth: what works and how can we be sure?

BACKGROUND: Youth participating in mobile health (mHealth) intervention trials often engage with the technologies [e.g., applications (app) or mobile-optimized websites] only partially, often prematurely discontinuing use altogether. Limited engagement can impact the interventions effect on behavior change and compromise researchers' ability to test and estimate the true efficacy of their interventions. While mHealth interventions have been shown to be feasible and acceptable to youth, across diverse health conditions, strategies to increase engagement have been less well studied. Specifically, within HIV prevention and care mHealth interventions, there is not consensus as to which components represent the "key ingredients" to support maximal engagement of youth. Further, successful intervention evaluation requires the ability to systematically track users' engagement with intervention components (i.e., paradata) to evaluate its effects on behavior change. METHODS: As part of the Adolescent Medicine Trials Network UNC/Emory Center for Innovative Technology (iTech) portfolio of HIV/AIDS Interventions, we present diverse strategies used across five mHealth protocols seeking to promote youth engagement, track and measure engagement through paradata, and incorporate these components into mHealth intervention evaluations. RESULTS: We describe the importance of defining and measuring engagement using case studies from iTech to illustrate how different research teams select mHealth features to promote youth engagement over time, taking into account features embedded in the technology design, key mechanisms of change and trial outcomes (e.g., HIV testing, pre-exposure prophylaxis uptake and adherence, HIV treatment adherence). Finally, we discuss how the research teams plan to evaluate engagement's role on their intervention's outcomes. CONCLUSIONS: Based on this synthesis, we discuss strategies to enhance mHealth engagement during intervention development and design, ensure its monitoring and reporting throughout the trial, and evaluate its impact on trial outcomes.

HIV self-testing and STI self-collection via mobile apps: experiences from two pilot randomized controlled trials of young men who have sex with men.

BACKGROUND: Young men who have sex with men (YMSM) are disproportionately impacted by HIV and other sexually transmitted infections (STIs) in the United States (US) and have low rates of HIV/STI testing. Provision of HIV self-testing and STI self-collection can increase testing rates, and access to these kits through mobile applications (apps) could help facilitate YMSM using HIV self-testing and STI self-collection. METHODS: Data for this study comes from two pilot randomized controlled trials (RCTs) of mobile apps within the Adolescent Trials Network-LYNX and MyChoices-aimed to increase HIV/STI testing among YMSM (age 15-24) who had not recently tested for HIV and were at high risk for HIV acquisition across five US cities. Both apps include the ability to order a HIV self-test with rapid results and a kit for STI self-collection and mailing of samples for syphilis, gonorrhea and chlamydia to a lab for testing. Using assessments of app users (n=80) at pre-randomization and at 3- and 6-months post-randomization and online interview data from a purposive sample of app users (n=37), we report on experiences and lessons learned with HIV self-testing and STI self-collection kits ordered via the apps. RESULTS: Participants were on average 20.7 years of age (SD =2.4), and 49% were non-White or multiple race/ethnicity. Sixty-three percent had a prior HIV test. Over half (58%) had a prior STI test, but only 3% had tested within the past 3 months. Nearly two-thirds ordered an HIV self-testing kit; of whom, 75% reported using at least one self-test kit over the study period. STI self-collection kit ordering rates were also high (54%); however, STI self-collection kit return rates were lower (13%), but with a high positivity rate (5.3%). Both HIV self-testing and STI self-collection kits were highly acceptable, and 87% reported that it was extremely/very helpful to be able to order these kits through the apps. The most common reason for not ordering the HIV/STI kits was preferring to test at a clinic. In interviews, participants expressed feeling empowered by being able to test at home; however, they also raised concerns around STI sample collection. CONCLUSIONS: HIV self-testing and STI self-collection kit ordering via mobile apps is feasible, acceptable and may show promise in increasing testing rates among YMSM. The LYNX and MyChoices apps are currently being tested in a full-scale efficacy trial, and if successful, these innovative mobile apps could be scaled up to efficiently increase HIV/STI testing among youth across the US.