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Background: Longer-acting cabotegravir (CAB) is a novel, safe, and efficacious pre-exposure prophylaxis (PrEP) for HIV prevention. As we near a time for CAB scale-up, the experience of global leaders in PrEP research and implementation can be leveraged to identify optimal strategies for scaling and integrating CAB into existing PrEP infrastructure worldwide., Methods: We recruited leaders of HIV prevention clinical trials and large PrEP programs through a combination of purposive and snowball sampling for participation in individual interviews. We conducted interviews using a semi-structured guide that compared CAB to oral PrEP and sought perspectives on barriers and strategies for CAB scale-up. Interviews were conducted virtually, audio recorded, and transcribed. We used thematic analysis, grounded in an adapted version of the Intervention Scalability Assessment Tool (ISAT), to identify critical elements for optimizing delivery of CAB., Results: From October 2021 to April 2022, we interviewed 30 participants with extensive experience in PrEP research, care, and programming. Participants worked in all seven WHO regions and reported a median of 20 years working in HIV and 10 years in PrEP. Participants agreed that CAB was efficacious and discrete, therefore having the potential to address current concerns about oral PrEP adherence and stigma. Participants indicated direct and indirect costs for provider training, expansion of existing medical infrastructure, and the current medication cost of CAB as major concerns for roll out. The true cost to the end-user and health system were unknown. There were some conflicting strategies on how to best address product targeting, presentation of efficacy, and timing of product availability with scale-up. Some thought that targeting CAB for the general population could normalize PrEP and decrease stigma, while others thought that prioritizing key populations could optimize impact by targeting those with highest risk. Overall, participants emphasized that to ensure successful CAB scale-up, communities and stakeholders must be involved at every stage of planning and implementation., Conclusions: Our evaluation found that although there is a clear and urgent need for additional HIV PrEP options beyond daily oral PrEP, CAB scale-up must be thoughtful, flexible, and based in lessons learned from oral PrEP rollout., (© 2024. The Author(s).)

Background: Methamphetamine is associated with increased HIV risk and suboptimal adherence to pre-exposure prophylaxis (PrEP). Interventions to support PrEP adherence for people who use methamphetamine are needed., Methods: We evaluated peer navigation to support adherence among people initiating PrEP who use methamphetamine. The H IV Prevention in M ethamphetamine U sers (HMU!) study enrolled participants from May 2018-January 2022 in Seattle, WA, and followed them for 6 months. Surveys collected sociodemographic, drug use, and sexual behavior data at enrollment, month 3, and month 6. Dried blood spots (DBS) were collected at months 1, 3, and 6 to measure PrEP adherence., Results: We enrolled 21 participants of a target sample of 40, of whom 20 were prescribed PrEP. Nine participants (43%) received peer navigation and 12 (57%) received standard of care or text messaging. At baseline, most participants reported at least weekly methamphetamine use (17, 81%) and condomless receptive anal intercourse (CRAI) (16, 76%). One-third reported CRAI with a partner with HIV. Among those who provided a DBS, 78% and 50% had results commensurate with ≥4 pills/week at the month 3 and 6 visit, respectively. More than half of those prescribed PrEP completed a month 6 visit (11, 55%). Retention was not associated with peer support compared to standard of care or text messaging ( p = .20)., Conclusions: We enrolled half our target sample size despite extensive recruitment efforts. As expected, participants had challenges with PrEP adherence and persistence. While peer navigation interventions should be studied further, additional interventions are likely needed to support PrEP uptake, adherence, and persistence among people who use methamphetamine., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We examined the impact of past-year intimate partner violence (IPV) on HIV outcomes among women living with HIV (WLHIV) in Durban, South Africa. We assessed past-year IPV using the WHO Violence Against Women Questionnaire. We conducted logistic regression to assess associations between demographic variables and IPV at baseline, and between IPV at baseline and longitudinal HIV outcomes. Among 235 WLHIV, 17% reported past-year emotional, physical, or sexual IPV. At baseline, HIV-disclosure to partner was associated with 4.35-fold odds of past-year IPV (95% CI 1.17-16.10) after controlling for children, education, and harmful alcohol use. In the prospective analysis, IPV was associated with not achieving the co-primary outcome of retention in care and viral suppression in univariate (OR = 2.32, 95% CI 1.04-5.18), but not in the multivariate model. In the context of rapid treatment scale-up, the high burden of IPV among WLHIV needs to be prioritized, with an emphasis on disclosure support., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: We analyzed the STREAM (Simplifying HIV TREAtment and Monitoring) study to determine risk factors associated with HIV viraemia and poor retention 18 months after initiation of antiretroviral therapy (ART)., Methods: The STREAM study was an open-label randomized controlled trial in Durban, South Africa, that enrolled 390 people living with HIV presenting for their first HIV viral load measurement ~6 months after ART initiation. We used modified Poisson regression with robust standard errors to describe associations between baseline characteristics and three HIV outcomes 18 months after ART initiation: HIV viraemia (>50 copies/mL), poor retention in HIV care, and a composite outcome of poor retention in care and/or HIV viraemia., Results: Approximately 18 months after ART initiation, 45 (11.5%) participants were no longer retained in care and 43 (11.8%) had viraemia. People with CD4 counts <200 and those with viraemia 6 months after ART initiation were significantly more likely to have viraemia 18 months after ART initiation (adjusted relative risk [aRR] 4.0; 95% confidence interval [CI] 2.1-7.5 and aRR 5.5; 95% CI 3.3-9.0, respectively). People who did not disclose their HIV status and had viraemia after ART initiation were more likely to not be retained in care 12 months later (aRR 2.6; 95% CI 1.1-6.1 and aRR 2.2; 95% CI 1.0-4.8). People with a CD4 count <200 and those with viraemia were more likely to not achieve the composite outcome 18 months after ART initiation., Conclusions: Viraemia after ART initiation was the strongest predictor of subsequent viraemia and poor care retention. Understanding early indicators can help target our interventions to better engage people who may be more likely to experience persistent viraemia or disengage from HIV care., (© 2024 British HIV Association.)

Background: Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from trials involving cisgender women are lacking., Methods: We conducted a randomized, open-label trial comparing doxycycline PEP (doxycycline hyclate, 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis against human immunodeficiency virus (HIV). The primary end point was any incident infection with Chlamydia trachomatis , Neisseria gonorrhoeae , or Treponema pallidum . Hair samples were collected quarterly for objective assessment of doxycycline use., Results: A total of 449 participants underwent randomization; 224 were assigned to the doxycycline-PEP group and 225 to the standard-care group. Participants were followed quarterly over 12 months. A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P = 0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All N. gonorrhoeae -positive isolates were resistant to doxycycline., Conclusions: Among cisgender women, the incidence of STIs was not significantly lower with doxycycline PEP than with standard care. According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low. (Funded by the National Institutes of Health; dPEP ClinicalTrials.gov number, NCT04050540.)., (Copyright © 2023 Massachusetts Medical Society.)

Transgender and gender nonbinary (TGNB) individuals are at high risk for HIV acquisition. However, TGNB individuals are often excluded from research and public health surveillance, both as participants and as reported sexual partners. This research study aimed to be inclusive, correctly classify TGNB participants, and accurately describe sex partners and sexual activity of participants to assess HIV risk while minimizing participant burden. The adaptation of survey questions designed for cisgender men to include TGNB participants and partners was feasible and relatively straightforward. However, additional work is still needed in this area to increase inclusivity and research participation by TGNB individuals. Clinical Trial Registration Number - NCT03584282., Competing Interests: No competing financial interests exist., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

Introduction: The global incidence of sexually transmitted infections (STIs) has been rapidly increasing over the past decade, with more than one million curable STIs being acquired daily. Young women in sub-Saharan Africa have a high prevalence and incidence of both curable STIs and HIV. The use of doxycycline as a prophylaxis to prevent STIs is promising; however, clinical trials, to date, have only been conducted among men who have sex with men (MSM) in high-income settings. We describe the characteristics of participants enrolled in the first trial to determine the efficacy of doxycycline post-exposure prophylaxis (PEP) to reduce STI incidence among women taking daily, oral HIV pre-exposure prophylaxis (PrEP)., Methods: This is an open-label 1:1 randomized clinical trial on the efficacy of doxycycline PEP compared with standard of care (e.g., quarterly STI screening and treatment) to reduce incident bacterial STIs - Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum - among Kenyan women aged ≥18 and ≤30 years. All were also taking HIV pre-exposure prophylaxis (PrEP). We describe the baseline characteristics, STI prevalence, and STI risk perception of participants., Results: Between February 2020 and November 2021, 449 women were enrolled. The median age was 24 years (IQR 21-27), the majority were never married (66.1%), 370 women (82.4%) reported having a primary sex partner, and 33% had sex with new partners in the three months prior to enrolment. Two-thirds (67.5%, 268 women) did not use condoms, 36.7% reported transactional sex, and 43.2% suspected their male partners of having sex with other women. Slightly less than half (45.9%, 206 women) were recently concerned about being exposed to an STI. The prevalence of STIs was 17.9%, with C. trachomatis accounting for the majority of infections. Perceived risk of STIs was not associated with the detection of an STI., Conclusion: Young cisgender women using HIV PrEP in Kenya and enrolled in a trial of doxycycline postexposure prophylaxis had a high prevalence of curable STIs and represent a target population for an STI prevention intervention., (© 2023. The Author(s).)

Background: To determine whether the Centralized Chronic Medication Dispensing and Distribution (CCMDD) program in South Africa's differentiated ART delivery model affects clinical outcomes, we assessed viral load (VL) suppression and retention in care between patients participating in the program and those receiving the clinic-based standard of care., Methods: Clinically stable people living with HIV (PLHIV) eligible for differentiated care were referred to the national CCMDD program and followed up for up to 6 months. In this secondary analysis of trial cohort data, we estimated the association between routine patient participation in the CCMDD program and their clinical outcomes of viral suppression (<200 copies/mL) and retention in care., Results: Among 390 PLHIV, 236 (61%) were assessed for CCMDD eligibility; 144 (37%) were eligible, and 116 (30%) participated in the CCMDD program. Participants obtained their ART in a timely manner at 93% (265/286) of CCMDD visits. VL suppression and retention in care was very similar among CCMDD-eligible patients who participated in the program compared with patients who did not participate in the program (aRR: 1.03; 95% CI: 0.94-1.12). VL suppression alone (aRR: 1.02; 95% CI: 0.97-1.08) and retention in care alone (aRR: 1.03; 95% CI: 0.95-1.12) were also similar between CCMDD-eligible PLHIV who participated in the program and those who did not., Conclusion: The CCMDD program successfully facilitated differentiated care among clinically stable participants. PLHIV participating in the CCMDD program maintained a high proportion of viral suppression and retention in care, indicating that community-based ART delivery model did not negatively affect their HIV care outcomes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Incomplete HIV seroconversion and seroreversion are increasingly documented by testing and pre-exposure prophylaxis programs more than previously recognized. This analysis reports on incomplete seroconversion and seroreversion by specimen and test type among Project DETECT participants., Methods: Project DETECT included a longitudinal study of point-of-care tests. Participants were categorized as having "incomplete seroconversion" if all timepoints had ≥1 nonreactive test at study censoring. Among participants with incomplete seroconversion, we defined "seroreversion" as sustained regression to nonreactive for any test following a reactive result. We define "serowaffling" as any reactive result followed by a nonreactive and then reactive result. We used Fisher's exact tests to explore relationships between Fiebig stage at ART initiation and incomplete seroconversion, seroreversion, and serowaffling., Results: Twenty of 1940 Project DETECT participants met criteria for this subset. Ten participants had complete seroconversion after a median of 23 (IQR 16-47) days following initial positive tests. Ten participants had incomplete seroconversion, eight of whom had seroreversion. Incomplete seroconversion with persistent nonreactive tests was seen only with oral fluid (OF). Of eight participants with seroreversion, all experienced seroreversion of OF tests if the test was ever reactive ( n = 6); seroreversion occurred in fingerstick and venipuncture tests in two participants. Serowaffling occurred in nine (45%) participants. No associations were seen between Fiebig stage at ART start and complete seroconversion, seroregression, or serowaffling in our sample., Conclusions: OF tests may be particularly susceptible to providing false-negative results. Seroreversion and incomplete seroconversion among individuals on antiretroviral treatment may represent a growing problem for HIV testing and treatment programs.

Background: Heroin pipe distribution may encourage people who use heroin (PWUH) to transition from injecting to smoking heroin, reducing harms associated with injection drug use. A syringe services program (SSP) in Seattle, Washington, led by people who use drugs developed a heroin pipe distribution program., Methods: We conducted a pretest-posttest quasi-experimental study to evaluate the impact of heroin pipe distribution on drug consumption behaviors among PWUH between March and December 2019. SSP clients were surveyed during three weeklong timepoints before and four weeklong timepoints after heroin pipe distribution. Primary outcomes were change in proportion of SSP clients who exclusively injected heroin, exclusively smoked heroin, and both injected and smoked heroin in the past seven days comparing the pre- and post-intervention periods., Results: Across the seven observation timepoints, 694 unique respondents completed 957 surveys. Multiple responses from a single respondent in a given period were collapsed, resulting in 360 pre-intervention and 430 post-intervention records. Heroin use was reported in over half of pre-intervention (56%, 201/360) and post-intervention records (58%, 251/430). Compared to pre-intervention behaviors, the proportion of respondents who exclusively injected heroin was lower after the start of heroin pipe distribution (32%, 80/251 vs 43%, 86/201, p = 0.02), while the proportion of respondents who both injected and smoked heroin was higher (45%, 113/251 vs 36%, 72/201, p = 0.048). Just under half (44%, 110/251) of respondents who used heroin during the post-intervention period used a heroin pipe obtained from the SSP, of which 34% (37/110) reported heroin pipe distribution had reduced their heroin injection frequency. Self-reported hospitalization for a pulmonary cause was not associated with using a heroin pipe., Conclusions: The proportion of SSP clients who exclusively injected heroin was lower after implementation of heroin pipe distribution. Randomized studies with longer follow-up are needed to investigate whether heroin pipe distribution reduces heroin injection and improves health outcomes associated with drug use. Limited intervention exposure, loss to follow-up, and pipe availability from other sources pose methodological challenges to evaluations of route transition interventions in community settings. This pilot highlights the potential for organizations led by people who use drugs to develop, implement, and evaluate novel public health programming., (© 2022. The Author(s).)

Background: Women in Africa face disproportionate risk of human immunodeficiency virus (HIV) acquisition, accounting for more than half of new infections in Africa and similarly face a disproportionate burden of sexually transmitted infections (STIs). Very high STI prevalence is being observed globally, especially among people taking pre-exposure prophylaxis (PrEP) for HIV prevention. Doxycycline post-exposure prophylaxis (dPEP) has been proposed as an STI prevention strategy to reduce chlamydia, syphilis, and possibly gonorrhea, and trials are ongoing among cisgender men who have sex with men (MSM) and transgender women who are taking PrEP in high-income settings. We designed and describe here the first open-label trial to determine the effectiveness of dPEP to reduce STI incidence among cisgender women., Methods: We are conducting an open-label 1:1 randomized trial of dPEP versus standard of care (STI screening and treatment and risk-reduction counseling without dPEP) among 446 Kenyan women aged ≥ 18 and ≤ 30 years old women taking PrEP. Women are followed for 12 months, with quarterly STI testing, treatment, and adherence counseling. The primary trial outcome will be the combined incidence of Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, compared between the randomized groups. We will also assess dPEP acceptability, tolerability, safety, impact on sexual behavior, adherence, and occurrence of antimicrobial resistance (AMR) in N. gonorrhoeae and C. trachomatis isolates. Finally, we will estimate cost per incident STI case and complications averted accounting for nonadherence and benefits relative AMR or side effects., Discussion: The results of this trial may have immediate implications for the global epidemic of STIs and sexual health. If effective, dPEP could put STI prevention into women's hands. While dPEP may be able to prevent STIs, it carries important risks that could counter its benefits; global debate about the balance of these potential risks and benefits requires data to inform policy and implementation and our study aims to fill this gap., Trial Registration: ClinicalTrials.gov NCT04050540 ., (© 2022. The Author(s).)

Background: Point-of-care (POC) nucleic acid tests (NATs) have potential to diagnose acute HIV infection and monitor persons taking pre-exposure prophylaxis or antiretroviral therapy (ART). POC NATs have not yet been evaluated in the US., Methods: From June 2018-March 2019, we conducted a cross-sectional evaluation of the Simple Amplification-Based Assay version II (SAMBA II) POC NAT. People with HIV (PWH) and persons testing for HIV were tested with the SAMBA II qualitative (Qual) whole blood (WB) test. From April-September 2019, the Qual test was used on persons who were ART-naive, and SAMBA II Semi-quantitative (Semi-Q) WB was used with ART-experienced PWH. Both were performed on unprocessed venipuncture (VP) and, when indicated by protocol, fingerstick (FS) WB and plasma. SAMBA results were compared with Abbott RealTime HIV-1 polymerase chain reaction results on plasma. We calculated sensitivity, specificity, and concordance between tests., Results: SAMBA was used in 330 visits among 280 participants: 202 (61.2%) visits from PWH, and 128 (38.8%) from HIV-negative persons. Qual test sensitivity with ART-naive participants was 91.4% [32/35, 95% confidence interval (CI): 77.6% to 97.0%] using VP WB and 100% (27/27, 95% CI: 87.5% to 100%) using FS WB. Specificity was 100% using both specimen types. Concordance between the gold standard and Semi-Q at 1000 copies/mL among PWH on ART was 97.7% (86/88, 95% CI: 92.1% to 99.4%) and 100% (30/30, 95% CI: 88.7% to 100%) using VP and FS WB, respectively., Conclusions: The SAMBA II POC NATs showed high sensitivity, specificity, and concordance with the gold standard assay, indicating its potential use in diagnostics and monitoring. Future work will evaluate POC NAT implementation in the US., Competing Interests: S.M.A., A.R., N.G. and H.L. are employed by Diagnostics for the Real World (DRW), the creators of the SAMBA II test. DRW provided 2 SAMBA II machines for investigational use. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)