Development of a home-based pre-exposure prophylaxis care delivery system for long-acting injectable cabotegravir: a formative exploration of patient preferences.

Cabotegravir (CAB-LA), the only Food and Drug Administration-approved injectable pre-exposure prophylaxis (PrEP), is effective and may address PrEP uptake disparities among Black and Latino sexual and gender minority (SGM) men. Uptake of CAB-LA may require developing innovative non-clinic-based care delivery strategies in home-based settings. We explored SGM men's opinions on a future home-based CAB-LA PrEP care service to guide the adaptation of PrEP@Home, an existing home-based PrEP system for oral PrEP. Through 14 in-depth interviews with current or former SGM male participants in the PrEP@Home study, we explored the acceptability of a home-based injectable PrEP system and examined visit and communication-related preferences. All participants considered home-based CAB-LA care to be acceptable and 8/14 would utilize the system if available. Convenience and comfort with using a home-based system impacted the overall acceptance of the approach. Factors influencing acceptability included clinical teams' affiliation with healthcare systems, a credentialed two-person team, and staff identity verification methods. Logistical preferences included communicating pre-visit patient instructions, allowing flexible scheduling hours, and the use of text, phone calls, or mobile app communication methods based on urgency. Conclusively, a home-based CAB-LA PrEP delivery system was acceptable among the interviewed SGM men, guiding its development and future implementation.Trial registration: ClinicalTrials.gov identifier: NCT03569813.

Impact of the Coronavirus Disease 2019 Pandemic on Substance Use Disorder Risk Among People Living With Human Immunodeficiency Virus (HIV) Enrolled in HIV Care in the United States: An Interrupted Time Series Analysis.

Background: Rising overdose deaths globally and increased social isolation during the coronavirus disease 2019 (COVID-19) pandemic may have disproportionately impacted people with human immunodeficiency virus (PWH) with substance use disorders (SUD). We examined trends in SUD risk among PWH before and after the COVID-19 shelter-in-place (SIP) mandate. Methods: Data were collected between 2018 and 2022 among PWH enrolled across 8 US sites in the Centers for AIDS Research Network of Integrated Clinical Systems cohort. We evaluated changes in moderate/high SUD risk after SIP using interrupted time series analyses. Results: There were 7126 participants, including 21 741 SUD assessments. The median age was 51 (interquartile range, 39-58) years; 12% identified as Hispanic or Latino/Latina, 46% Black/African American, and 46% White. Moderate/high SUD risk increased continuously after the pandemic's onset, with 43% (95% confidence interval [CI], 40%-46%) endorsing moderate/high SUD risk post-SIP, compared to 24% (95% CI, 22%-26%) pre-SIP (P < .001). There were increases in the use of heroin, methamphetamine, and fentanyl, and decreases in prescription opioids and sedatives post-SIP. Further, there was a decrease in reported substance use treatment post-SIP compared to pre-SIP (P = .025). Conclusions: The rising prevalence of SUD through late 2022 could be related to an increase in isolation and reduced access to substance use and HIV treatment caused by disruptions due to COVID-19. A renewed investment in integrated substance use treatment is vital to address the combined epidemics of substance use and HIV following the COVID-19 pandemic and to support resilience in the face of future disruptions.

Efficacy of Behavioral Intervention, Text Messaging, and Extended Intervention to Address Alcohol Misuse in Sexual Minority Men with HIV: A Factorial Randomized Clinical Trial.

This clinical trial examined the individual and combined effects of three different approaches to reducing alcohol misuse among a sample of sexual minority men (SMM) with HIV. Specifically, we used a 2 × 2 × 2 randomized factorial design to compare: (a) behavioral intervention based in motivational interviewing (MI) vs. brief intervention (BI), (b) interactive text messaging (ITM) for alcohol use vs. no ITM, and (c) extended intervention (EI) length of nine months vs. a one-month intervention duration. Participants (N = 188) were SMM with HIV and alcohol misuse recruited in Miami, FL, and Boston, MA. Participants were randomized to one of eight intervention combinations and assessed at 6- and 12-month follow-ups. Large reductions of over 50% in drinks per week and heavy drinking days were observed in all conditions at follow-up. Those who received ITM, compared to those who did not, reported significantly lower drinks consumed per week at 6 and 12 months (incidence rate ratios = 0.73 [95% CI = 0.57, 0.90] and 0.72 [95% CI = 0.56, 0.87], respectively), and increased odds of cessation of alcohol misuse at 12 months, odds ratio = 1.46, 95% CI = 1.03, 2.08. Results provided no evidence of better alcohol use outcomes for either MI or EI relative to their comparison conditions, and no specific combination of intervention components demonstrated a notable benefit. This study suggests a two-session BI can effectuate substantial reductions in alcohol use in SMM with HIV and that adding one month of ITM can yield further improvements. Clinical Trials Number: NCT02709759.

Smoking and Type 1 Versus Type 2 Myocardial Infarction Among People With HIV in the United States.

ABSTRACT: Smoking is a myocardial infarction (MI) risk factor among people with HIV (PWH). Questions persist regarding the role of smoking behaviors and measurements (e.g., intensity, duration) on MI risk. We used Cox proportional hazards regression to compare the association of smoking parameterization with incidents of type 1 and type 2 MI and whether smoking intensity or duration improves MI risk prediction among PWH. Among 11,637 PWH, 37% reported currently smoking, and there were 346 MIs. Current smoking was associated with type 1 (84% increased risk) but not type 2 MI in adjusted analyses. The type 1 MI model with pack years had the best goodness of fit compared with other smoking parameterizations. Ever or never parameterization and smoking diagnosis data had significantly poorer model fit. These results highlight the importance of differentiating MI types and performing patient-based smoking assessments to improve HIV care and research rather than relying on smoking status from diagnoses.

Site-based and Digital Cohort Participation Among Transgender Women in the Eastern and Southern USA: Findings from the LITE Study.

BACKGROUND: Transgender women (TW) are highly burdened by HIV. There is increasing interest in digital (i.e., through internet-based interfaces) HIV research; yet few studies have assessed potential biases of digital compared to site-based data collection. This study examined differences in characteristics between TW participating via site-based versus digital-only modes in an HIV incidence cohort. METHODS: Between March 2018-Aug 2020, a multisite cohort of 1,312 adult TW in the eastern and southern USA was enrolled in site-based and exclusively digital modes. We evaluated differences in baseline demographics, socio-structural vulnerabilities, healthcare access, gender affirmation, mental health, stigma, social support, and HIV acquisition risk comparing site-based vs digital modes using chi square tests and Poisson regression modeling with robust standard errors. RESULTS: The overall median age was 28 (interquartile range=23-35) years and over half identified as people of color (15% Black, 13% Multiracial, 12% Another Race, 18% Latina/e/x). A higher proportion of site-based (vs. digital mode) participants resided in the Northeast, were younger, identified as people of color, experienced socio-structural vulnerabilities, had a regular healthcare provider, received medical gender affirmation, endorsed mental health symptoms and stigma, reported HIV acquisition risk but also greater experience with biomedical HIV prevention (pre-exposure and post-exposure prophylaxis), and had larger social networks (all p<0.05). CONCLUSION: Site-based and digital approaches enrolled TW with different demographics, life experiences, and HIV acquisition risks. A hybrid cohort model may achieve a more diverse and potentially representative sample of TW than either site-based or online cohorts alone for HIV research.

Ethnic identity and social support as mediators between childhood sexual abuse and depression among black men who have sex with men.

BACKGROUND: Survivors of childhood sexual abuse (CSA) often experience long-term adverse mental health effects, a trend that has been observed in research focusing on men who have sex with men (MSM), especially Black MSM. OBJECTIVE: The aim of this study was to investigate the direct and indirect effects of childhood sexual abuse on depression symptoms among Black MSM through early sexual debut, histories of incarceration, ethnic identity, and social support. In addition, we examine the role of social support and ethnic identity as mediators of depression symptoms. PARTICIPANTS AND SETTING: The HPTN 073 study enrolled and followed 226 HIV-uninfected Black MSM in three US cities (Los Angeles; Washington, DC; and Chapel Hill, North Carolina) from February 2013 to September 2015. Study participants were offered once-daily oral emtricitabine/tenofovir preexposure prophylaxis combined with counseling and followed for 52 weeks. METHODS: A path analysis was used to examine direct and indirect effects of CSA experiences on depression symptoms through incarceration, early sexual debut ethnic identity, and social support, and to see whether social support and ethnic identity mediated the relationship between incarceration and depression symptoms. RESULTS: Our results indicate that childhood sexual abuse was direct and positively associated with early sexual debut (ß = 0.21, p < .001). Both ethnic identity (ß = -0.14, p < .001) and social support (ß = -0.82, p < .001) were direct and negatively associated with depressive symptoms. CONCLUSION: Our research underscores the significant impact of CSA factors on the life trajectories of some Black MSM, including experiences such as incarceration, sexual debut, and depression symptoms.

Technology-Based Interventions, with a Stepped Care Approach, for Reducing Sexual Risk Behaviors and Increasing PrEP Initiation Among Transgender and Gender Expansive Youth and Young Adults.

TechStep was a technology-based trial, with a stepped care approach, to reduce sexual risks and increase PrEP uptake among transgender and gender expansive youth and young adults (15-24 years old). From October 2019 to September 2021, 254 participants were randomized into: 1) Text (n = 82), or 2) Webapp (n = 87), or 3) Control (n = 85). At the 3-month follow-up assessment, those randomized to Text and Webapp and did not demonstrate improvement on primary outcomes were re-randomized to receive virtual eCoaching (Text + or Webapp +), or to remain in their initial condition without eCoaching. Results showed no effect on condomless encounters at 6-month, the primary endpoint, when comparing the Webapp + (0.33 decrease; 95%CI: -0.01, 0.67, p-value = 0.057) or the Text + (0.27 decrease; 95%CI: -0.13, 0.68, p-value = 0.181) conditions to the Control condition. However, in secondary analyses, condomless encounters were significantly reduced for Text compared to Control. The rate of PrEP uptake was low for all study arms.Trial registration: Clinical Trials # NCT04000724 (registered June 26, 2019).

PrEP Stigma as a Minority Stressor among Black Sexual Minority Men: A Mixed-Methods Study.

Black sexual minority men (BSMM) remain disproportionately affected by HIV, yet Pre-exposure prophylaxis (PrEP) uptake in this population remains relatively low. Informed by minority stress theory, PrEP stigma may manifest in and exacerbate societal marginalization based on sexuality and race. We used an exploratory sequential mixed-methods approach to determine if PrEP-specific stigma was associated with reduced PrEP uptake among BSMM, and qualitatively explored how PrEP use is stigmatized among BSMM. We analyzed cross-sectional data from a pilot sample of BSMM (n = 151) collected in late 2020 in the United States, testing for associations between PrEP stigma and PrEP use using modified Poisson regression. Subsequently, we selected participants (n = 23) from this sample for qualitative interviews starting in 2022. Responses to questions related to PrEP stigma were analyzed using thematic analysis. PrEP stigma was associated less than half the PrEP use (aPR = 0.43, 95% CI = 0.24, 0.75) among BSMM after adjustment. Qualitatively, we identified three major themes in how PrEP use is stigmatized among BSMM: PrEP-specific sexual stigma, intersections between PrEP and HIV stigma, and PrEP misinformation and disinformation. Aligned with minority stress theory, each theme was based in part in stigma related to sexuality or race. We found strong relationships between PrEP stigma and PrEP use independent of several sociobehavioral factors. Each of our themes were based in part in minority stressors, and underscore the importance of culturally competent PrEP promotion efforts towards BSMM. Addressing stigma is a core component of health equity efforts towards ending the HIV epidemic.

Use of doxycycline and other antibiotics as bacterial sexually transmitted infection prophylaxis in a U.S. sample of primarily gay and bisexual men.

BACKGROUND: Doxycycline used as post-exposure prophylaxis (doxyPEP) within 72 hours of sex reduces the risk of bacterial sexually transmitted infections (STIs) in people assigned male sex at birth. Little is known about current use of antibiotics as STI prophylaxis in U.S. populations likely to benefit from doxyPEP. METHODS: We conducted an online survey in September 2023 of U.S. adults recruited via sexual networking apps used mainly by gay and bisexual men (GBM). Respondents were asked about the use of antibiotics around the time of sex to prevent bacterial STIs. RESULTS: Of 903 respondents, most (96.2%) identified as GBM; 19.0% were living with HIV and 42.5% using HIV pre-exposure prophylaxis. Half (49.1%) had heard of using antibiotics to prevent STIs and 95.6% were interested in use. Overall, 21.0% had used antibiotic STI prophylaxis and 15.9% had done so in the past year. Among those reporting any use, most (78.1%) had used doxycycline; some used amoxicillin (16.7%), azithromycin (14.5%), or other antibiotics (14.1%). Among those reporting use in the past year, 46.9% used it for some, 28.1% for most, and 25.0% for all sex acts with casual partners during that period. Most (78.3%) of STI prophylaxis users reported their condom use did not change during periods of STI prophylaxis use, 17.2% indicated their condom use declined, and 4.5% indicated their condom use increased. For doxyPEP specifically, 35.7% had heard of it and 13.0% had used it in the past year, of whom 21.0% had used a dosage other than the 200 mg dose shown to be effective. CONCLUSIONS: In this sample of primarily GBM, interest in bacterial STI prophylaxis was nearly universal. However, some of the use was not informed by current clinical guidance or evidence from research studies. Efforts are needed to increase awareness of effective dosing and monitor real-world use.

Weighing the Options: Which PrEP (Pre-exposure Prophylaxis) Modality Attributes Influence Choice for Young Gay and Bisexual Men in the United States?

Pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission, but uptake and adherence among young men who have sex with men (YMSM) remains suboptimal. New PrEP formulations may enhance PrEP use, but little is known about their acceptability. We enrolled 39 cis- and transgender YMSM (age 18-34) from Boston, MA; Jackson, MS; Birmingham, AL; and New Orleans, LA, who participated in video-based focus groups (n = 30) or in-depth interviews (n = 9) to examine how new PrEP products (e.g., injections, monthly pills, implants) are perceived and might be improved for YMSM. Focus groups were transcribed, coded, and analyzed using grounded theory and content analysis. Nearly half (46%) of participants were Black; 11% identified as Hispanic. Seventy-nine percent were PrEP experienced. Product preference was driven by the desire for flexible, safe, effective, and affordable PrEP options. A majority of participants preferred subcutaneous injections every 6 months or monthly pills dispersed in 3 or 4 doses. Subcutaneous injections and batched monthly pills were favored by those with demanding schedules and those who desired fewer provider visits; monthly pills were more appealing for those who feared needles. Despite broad preferences for longer-acting products for convenience, participants raised concerns regarding side effects and waning protection after missed doses. Participants felt that more education about safety and efficacy profiles of new products could influence their attitudes. These findings suggest that it is important to prioritize YMSM's dynamic lifestyles during product development, and that product safety and efficacy information should be accessible in youth-friendly language.

Family-centred interventions for people with substance use disorders in low-income and middle-income country settings: a scoping review protocol.

INTRODUCTION: Substance use disorder (SUD) and problematic substance use are global public health concerns with significant multifaceted implications for physical health and psychosocial well-being. The impact of SUD extends beyond the individual to their family while imposing financial and social burdens on the community. Though family-centred interventions have shown promise in addressing SUD, their implementation and impact in low-income and middle-income countries (LMICs) remain underexplored. METHODS AND ANALYSIS: Per Joanna Briggs Institute's scoping review protocol, a systematic search strategy was employed across OVID Medline, Embase, PsycINFO, Web of Science-Core Collection, Global Health and CINAHL from 22 February 2024 to 26 February 2024, to identify relevant studies focused on family-centred interventions for SUD in LMIC, devoid of publication time and language constraints. Two independent reviewers will screen the titles, abstracts and full texts, with discrepancies resolved through discussion or third-party reviews. The extracted data charted in a structured form will be visualised by diagrams or tables, focusing on the feasibility and impact of family-centred interventions for SUD in LMIC. For qualitative studies, the findings will be synthesised and presented in thematic clusters, and for studies that report quantitative outcomes, specific health, including SUD and psychosocial, outcomes will be synthesised, aligning with the Population, Concept and Context framework. ETHICS AND DISSEMINATION: These data on substance use, psychosocial outcomes and perspectives of individuals with SUD and their families will be presented in narrative format, highlighting patterns and identifying research gaps. This review aims to synthesise the existing evidence on family-centred interventions for improving substance use and/or psychosocial outcomes in individuals with SUD in LMIC and seeks to inform future policy and practice. Ethics approval is not required for this scoping review, and modifications to the review protocol will be disclosed. Findings will be disseminated through conference proceedings and peer-reviewed publication.

Internalized HIV stigma and viral suppression: examining the mediating and moderating roles of substance use and social support.

OBJECTIVE: To examine the effects of internalized HIV stigma on viral non-suppression via depressive symptoms, alcohol use, illicit drug use, and medication adherence and investigate whether social support moderates these effects. DESIGN: Longitudinal observational clinical cohort of patients in HIV care in the US.Methods: Data from the CFAR Network for Integrated Clinical Systems (2016-2019) were used to conduct structural equation models (SEM) to test the indirect effects of internalized HIV stigma on viral non-suppression through depressive symptoms, illicit drug use, alcohol use, and medication adherence. Moderated mediation with an interaction between social support and internalized HIV stigma was examined. RESULTS: Among 9,574 individuals included in the study sample, 81.1% were male and 41.4% were Black, non-Hispanic. The model demonstrated good fit (root mean square error of approximation = 0.028; standardized root means square residual = 0.067). The overall indirect effect was significant (b = 0.058; se  = 0.020; ß = 0.048; 95%CI = .019-.098), indicating that internalized HIV stigma's impact on viral non-suppression was mediated by depressive symptoms, illicit drug use, and medication adherence. An interaction was observed between internalized HIV stigma and social support on alcohol use, however, there was no moderated mediation for any of the mediators. CONCLUSIONS: Internalized HIV stigma indirectly impacts viral non-suppression through its effects on depressive symptoms, illicit drug use, and medication adherence. Social support may buffer the impact, but more research is needed. Understanding the pathways through which internalized stigma impacts viral suppression is key to improving health of people with HIV.

Missed Opportunities: A Narrative Review on Why Nonoccupational Postexposure Prophylaxis for HIV Is Underutilized.

Postexposure prophylaxis (PEP) is an important tool for preventing HIV infection but remains underutilized. In this narrative review, we aim to summarize the frequency of missed opportunities for prescribing PEP among studies from around the world, discuss the complexities of the challenges facing PEP provision, and describe possible solutions. We identified 20 studies published in the last 10 years among 43 832 individuals, of whom an estimated 41 477 were eligible for PEP. Of those eligible for PEP, PEP was prescribed among 27 705 (66.8%). There was a significant difference in PEP prescriptions in acute compared with non-acute care settings (63.5% vs 94.5%; P < .001). Emergent themes contributing to PEP underutilization included lack of provider and patient awareness, reduced PEP acceptability, HIV stigma and homophobia, lack of access (either to care or to medication), and stigmatizing policies. Each of those issues should be the focus of future PEP implementation efforts.

Prevalence and Correlates of SARS-CoV-2 Vaccine Uptake and Hesitancy Among People With HIV Across the United States.

BACKGROUND: People with HIV (PWH) have higher risk of COVID-19 mortality. SARS-CoV-2 vaccination is highly effective among PWH, although vaccine hesitancy could limit the population-level impact. SETTING: From February 2021 to April 2022, PWH from 8 sites in the Centers for AIDS Research Network of Integrated Clinical Systems completed a vaccine hesitancy instrument as part of routine care. METHODS: Participants were defined as vaccine hesitant if they had not received the SARS-CoV-2 vaccine and would probably/definitely not receive it. We assessed factors associated with SARS-CoV-2 vaccine hesitancy using logistic regression adjusted for demographics, unsuppressed viral load (VL > 200 copies/mL), month, and time on ART; using inverse probability weighting for survey nonresponse. RESULTS: Overall, 3288 PWH with a median age of 55 were included; 18% were female and 94% were virally suppressed. At the time of survey, 27% reported they had not received the SARS-CoV-2 vaccine, and 9% (n = 279) reported vaccine hesitancy. Factors associated with vaccine hesitancy included female sex (adjusted odds ratio [AOR] = 2.3; 95% confidence interval (CI): 1.6-3.2), Black vs. White race (AOR 1.7; 95% CI: 1.2 to 2.4), younger age (AOR 1.4; 95% CI: 1.2 to 1.5), and unsuppressed VL (AOR 1.9; 95% CI: 1.3 to 3.0). CONCLUSION: Overall, over one-quarter of PWH in this multisite cohort were unvaccinated for SARS-CoV-2 when interviewed February 21-April 22. Vaccine hesitancy was reported by approximately 9% of PWH and was higher among women, Black PWH, younger PWH, PWH with unsuppressed VL, and those in the South/Midwest. Renewed efforts are needed to address concerns of PWH about vaccinations against COVID-19 as the pandemic evolves, and vaccines in general, given the potential for future pandemics.

The HIV Index Is Associated With Retention in Care Among Latinx Persons Living With HIV in the CFAR Network of Integrated Clinical Systems Cohort.

The HIV Index is a validated self-report scale of engagement in HIV care previously correlated with future retention and virologic suppression. However, its performance in a monoethnic Latinx population has not been studied. We evaluated the HIV Index among Latinx persons living with HIV in the Centers for AIDS Research Network of Integrated Clinical Systems cohort and performed multivariable logistic regression to estimate its association with primary outcomes of suboptimal retention (not keeping 100% of HIV clinic appointments) and virologic suppression (HIV viral load <200 copies/mL). The mean Index score was 4.5 (standard deviation 0.6) in both analytic samples, indicative of feeling well-engaged. Higher Index scores were associated with lower odds of suboptimal retention (OR = 0.12, 95% CI [0.03, 0.54], p = .005), however, there was no association between Index score and virologic suppression. The HIV Index is useful for assessing engagement and retention among Latinx PLWH in routine care.

HIV-1 infection kinetics, drug resistance, and long-term safety of pre-exposure prophylaxis with emtricitabine plus tenofovir alafenamide (DISCOVER): week 144 open-label extension of a randomised, controlled, phase 3 trial.

BACKGROUND: Data characterising the long-term use and safety of emtricitabine plus tenofovir disoproxil fumarate as daily oral pre-exposure prophylaxis (PrEP) are scarce and there are uncertainties regarding the value of routine HIV-1 RNA testing during oral PrEP follow-up. METHODS: The DISCOVER trial was a randomised, controlled, phase 3 trial in which cisgender men and transgender women aged 18 years and older with a high likelihood of acquiring HIV were recruited from 94 clinics in Europe and North America and randomly assigned to receive either emtricitabine plus tenofovir disoproxil fumarate (200/25 mg) tablets daily, with matched placebo tablets, or emtricitabine plus tenofovir alafenamide (200/300 mg) tablets daily, with matched placebo tablets, for at least 96 weeks. After completion of the trial, participants were offered enrolment in this 48-week open-label extension study of emtricitabine plus tenofovir alafenamide. In participants diagnosed with HIV during the randomised and open-label phases of the study, we characterised HIV-1 test results and measured HIV-1 RNA viral load retrospectively when available. Adherence based on tenofovir diphosphate concentrations in dried blood spots and genotypic resistance were assessed in participants diagnosed with HIV. Safety assessments included adverse events, laboratory parameters, and, in a subset of participants, bone mineral density. HIV-1 incidence in participants initially randomly assigned to receive emtricitabine plus tenofovir alafenamide was estimated using a Poisson distribution. Changes from baseline in safety endpoints were described in participants assigned to received emtricitabine plus tenofovir alafenamide and in those who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase. This trial is registered with ClinicalTrials.gov, NCT02842086, and is ongoing. FINDINGS: Between Sept 13, 2016, and June 30, 2017, 5399 participants were enrolled and randomly assigned in DISCOVER. 2699 were assigned to receive emtricitabine plus tenofovir disoproxil fumarate and 2700 were assigned to receive emtricitabine plus tenofovir alafenamide, of whom 2693 and 2694, respectively, received at least one dose of study drug. 2115 (79%) assigned to emtricitabine plus tenofovir disoproxil fumarate switched to emtricitabine plus tenofovir alafenamide in the open-label phase, and 2070 (77%) continued with emtricitabine plus tenofovir alafenamide in the open-label phase. As of data cutoff (Dec 10, 2020), after 15 817 person-years of follow-up, 27 new HIV-1 diagnoses were observed across the total study period, with three occurring during the open-label phase. In participants who were initially assigned to emtricitabine plus tenofovir alafenamide, the incidence was 0·13 per 100 person-years (95% CI 0·061-0·23; ten of 2670). Stored plasma samples were available for 23 of 27 participants, including 22 with incident infection. In four (17%) of 23 participants, retrospective testing detected HIV-1 RNA before serological HIV-1 test positivity; one was a suspected baseline infection. Of the three incident cases, all three were non-adherent to PrEP and none developed drug resistance. Among participants taking emtricitabine plus tenofovir alafenamide for up to 144 weeks, markers of glomerular filtration and proximal renal tubule dysfunction (ß2-microglobulin to creatinine ratio and retinol-binding protein to creatinine ratio) improved or remained stable at 144 weeks compared with baseline, bone mineral density in hip and lumbar spine increased or remained stable from baseline to week 144 (n=191), cholesterol and glucose concentrations remained stable, and median bodyweight increased by less than 1 kg per year. In participants who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase (2115 [79%] of 2693), markers of glomerular filtration and proximal renal tubule dysfunction improved or remained stable, bone mineral density increased, cholesterol concentrations increased, glucose concentrations were similar, and median bodyweight increased more compared with those who remained on emtricitabine and tenofovir alafenamide. INTERPRETATION: Routine HIV-1 RNA testing for follow-up of individuals on daily oral PrEP provides modest additional clinical benefit. Long-term use of emtricitabine and tenofovir alafenamide as daily oral PrEP is safe and well tolerated and can be an especially appropriate choice for people with bone or renal morbidities. FUNDING: Gilead Sciences.

Leveraging A Digital Pill System to Understand Prevention-Effective Adherence to Oral Hiv Pre-Exposure Prophylaxis Among Men Who Have Sex with Men with Substance Use.

Daily oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, though efficacy depends on adherence. Digital pill systems (DPS) can enable direct, real-time adherence measurement. HIV-negative men who have sex with men (MSM) with substance use (excluding alcohol) utilized a DPS over 90 days and completed weekly surveys reporting sexual activity, condom use, and substance use. Responses indicating (1) any sexual activity and substance use or (2) condomless anal intercourse (CAI) in the prior week were categorized as high risk for HIV acquisition. PrEP adherence data for the 7-day period preceding each response was dichotomized as ≤ 3 and ≥ 4 doses/week, indicating prevention-effective adherence, and compared by HIV risk level. Thirteen MSM were analyzed (median age: 32). Of 113 surveys, 48.7% indicated high HIV risk, with 12.4% reporting CAI alone, 16.8% any sexual activity and substance use, and 19.5% both CAI and substance use. Weekly mean PrEP adherence was 90.3% (6.3 of 7 doses/week), with ≥ 4 doses/week recorded during 92.0% of weeks. The proportion of participants with ≥ 4 recorded doses/week was 88.9% during weeks with CAI alone, 89.5% during weeks with any sexual activity and substance use, 92.0% during weeks with both CAI and substance use, and 92.8% during lower risk weeks. Participants ingested ≥ 4 doses/week during 89.1% of all high-risk weeks and 94.8% of low-risk weeks. Overall, participants maintained high levels of PrEP adherence while engaging in HIV risk behaviors. DPS can be deployed concurrently with data collection tools to assess ingestion patterns during periods of elevated risk.

Pharmacologic Drug Detection and Self-Reported Adherence in the HPTN069/ACTG5305 Phase II PrEP Trial.

Adherence drives efficacy in PrEP clinical trials. We compared drug concentrations and self-reported adherence in HPTN069/ACTG5305, a double-blinded, randomized trial of the safety and tolerability of candidate PrEP regimens that included maraviroc (MVC), tenofovir (TDF), and emtricitabine (FTC). Plasma drug concentrations and self-reported adherence by computer-assisted self-interview (CASI) were assessed at study weeks 24 and 48. Descriptive statistics and a generalized linear model were used to assess the association between selected demographic factors, self-report of daily medication adherence and plasma drug concentrations consistent with daily adherence. Among 718 paired observations from 370 participants, 43% (306/718) reported daily adherence by CASI, 65% (467/718) had drug concentrations consistent with daily adherence and 11% (81/718) had CASI responses that reported daily adherence despite having drug concentrations consistent with less-than-daily adherence. In adjusted analyses, participants who were assigned male at birth (aOR 1.42 [95% CI 1.02, 1.97]), older (5-year increments aOR 1.10 [95% CI 1.09, 1.11]), White (aOR 2.2 [95% CI 1.88, 2.56]), had advanced education (aOR 3.89 [95% CI 2.97, 5.09]), were employed (aOR 1.89 [95% CI 1.50, 2.40]), or partnered/married (aOR 2 [95% CI 1.72, 2.32]) were more likely to have drug concentrations consistent with daily adherence. Participants who were not employed (aOR 2.7 [95% CI 1.31, 5.55]) or who were single/not partnered (aOR 2.33 [CI 95% 1.25, 4.34]) were more likely to have drug concentrations that did not reflect daily adherence despite self-reported PrEP adherence. These findings support the need for ongoing adherence counseling in clinical trials of new PrEP regimens.

Preventive Service Usage and New Chronic Disease Diagnoses: Using PCORnet Data to Identify Emerging Trends, United States, 2018-2022.

Background: Data modernization efforts to strengthen surveillance capacity could help assess trends in use of preventive services and diagnoses of new chronic disease during the COVID-19 pandemic, which broadly disrupted health care access. Methods: This cross-sectional study examined electronic health record data from US adults aged 21 to 79 years in a large national research network (PCORnet), to describe use of 8 preventive health services (N = 30,783,825 patients) and new diagnoses of 9 chronic diseases (N = 31,588,222 patients) during 2018 through 2022. Joinpoint regression assessed significant trends, and health debt was calculated comparing 2020 through 2022 volume to prepandemic (2018 and 2019) levels. Results: From 2018 to 2022, use of some preventive services increased (hemoglobin A1c and lung computed tomography, both P < .05), others remained consistent (lipid testing, wellness visits, mammograms, Papanicolaou tests or human papillomavirus tests, stool-based screening), and colonoscopies or sigmoidoscopies declined (P < .01). Annual new chronic disease diagnoses were mostly stable (6% hypertension; 4% to 5% cholesterol; 4% diabetes; 1% colonic adenoma; 0.1% colorectal cancer; among women, 0.5% breast cancer), although some declined (lung cancer, cervical intraepithelial neoplasia or carcinoma in situ, cervical cancer, all P < .05). The pandemic resulted in health debt, because use of most preventive services and new diagnoses of chronic disease were less than expected during 2020; these partially rebounded in subsequent years. Colorectal screening and colonic adenoma detection by age group aligned with screening recommendation age changes during this period. Conclusion: Among over 30 million patients receiving care during 2018 through 2022, use of preventive services and new diagnoses of chronic disease declined in 2020 and then rebounded, with some remaining health debt. These data highlight opportunities to augment traditional surveillance with EHR-based data.

Incentivizing adherence to pre-exposure prophylaxis for HIV prevention: a randomized pilot trial among male sex workers in Mexico.

Low adherence to preventative medications against life-long health conditions is a major contributor to global morbidity and mortality. We implemented a pilot randomized controlled trial in Mexico to measure the extent to which conditional economic incentives help male sex workers increase their adherence to pre-exposure prophylaxis (PrEP) for HIV prevention. We followed n = 110 male sex workers over 6 months. At each quarterly visit (at months 0, 3, and 6), all workers received a $10 transport reimbursement, a free 3-month PrEP supply, and completed socio-behavioral surveys. The primary outcome was an objective biomarker of medication adherence based on tenofovir (TFV) drug concentration levels in hair collected at each visit. Individuals randomized to the intervention received incentives based on a grading system as a function of PrEP adherence: those with high (> 0.043 ng/mg TFV concentration), medium (0.011 to 0.042 ng/mg), or low (< 0.011 ng/mg) adherence received $20, $10, or $0, respectively. Six-month pooled effects of incentives on PrEP adherence were analyzed using population-averaged gamma generalized estimating equation models. We estimated heterogeneous treatment effects by sex worker characteristics. The incentive intervention led to a 28.7% increase in hair antiretroviral concentration levels over 6 months consistent with increased PrEP adherence (p = 0.05). The effect of incentives on PrEP adherence was greater for male sex workers who were street-based (vs. internet) workers (p < 0.10). These pilot findings suggest that modest conditional economic incentives could be effective, at scale, for improving PrEP adherence among male sex workers, and should be tested in larger implementation trials. ClinicalTrials.gov Identifier: NCT03674983.