BACKGROUND: Gay, bisexual, and other men who have sex with men (GBMSM) represent a high-risk group for HIV transmission in Romania, yet they possess few resources for prevention. Despite having no formal access to pre-exposure prophylaxis (PrEP) through the health system, GBMSM in Romania demonstrate a high need for and interest in this medication. In anticipation of a national rollout of PrEP, this study tests the efficacy of a novel strategy, Prepare Romania, that combines two evidence-based PrEP promotion interventions for GBMSM living in Romania.
METHODS: This study uses a randomized controlled trial design to examine whether GBMSM living in Romania receiving Prepare Romania, a culturally adapted counseling and mobile health intervention (expected n = 60), demonstrate greater PrEP adherence and persistence than those assigned to a PrEP education control arm (expected n = 60). Participants from two main cities in Romania are prescribed PrEP and followed-up at 3 and 6 months post-randomization. PrEP adherence data are obtained through weekly self-report surveys and dried blood spot testing at follow-up visits. Potential mediators (e.g., PrEP use motivation) of intervention efficacy are also assessed. Furthermore, Prepare Romania\'s implementation (e.g., proportion of enrolled participants attending medical visits, intervention experience) will be examined through interviews with participants, study implementers, and healthcare officials.
CONCLUSIONS: The knowledge gained from this study will be utilized for further refinement and scale-up of Prepare Romania for a future multi-city effectiveness trial. By studying the efficacy of tools to support PrEP adherence and persistence, this research has the potential to lay the groundwork for PrEP rollout in Romania and similar contexts. Trial registration This study was registered on ClinicalTrials.gov, identifier NCT05323123 , on March 25, 2022.

BACKGROUND: Clinical risk score tools require validation in diverse settings and populations before they are widely implemented. We aimed to externally validate an HIV risk assessment tool for predicting HIV acquisition among pregnant and postpartum women. In the context of prevention of mother-to-child transmission programs, risk score tools could be used to prioritize retesting efforts and delivery of pre-exposure prophylaxis (PrEP) to pregnant and postpartum women most at risk for HIV acquisition while minimizing unnecessary perinatal exposure.
METHODS: Data from women enrolled in a cross-sectional study of programmatic HIV retesting and/or receiving maternal and child health care services at five facilities in Western Kenya were used to validate the predictive ability of a simplified risk score previously developed for pregnant/postpartum women. Incident HIV infections were defined as new HIV diagnoses following confirmed negative or unknown status during pregnancy. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUC) and Brier score.
RESULTS: Among 1266 women with 35 incident HIV infections, we found an AUC for predicting HIV acquisition of 0.60 (95% CI, 0.51, 0.69), with a Brier score of 0.27. A risk score >6 was associated with a 2.9-fold increase in the odds of HIV acquisition (95% CI, 1.48, 5.70; p = 0.002) vs scores ≤6. Women with risk scores >6 were 27% (346/1266) of the population but accounted for 52% of HIV acquisitions. Syphilis, age at sexual debut, and unknown partner HIV status were significantly associated with increased risk of HIV in this cohort.
CONCLUSIONS: The simplified risk score performed moderately at predicting risk of HIV acquisition in this population of pregnant and postpartum women and may be useful to guide PrEP use or counseling.

UNASSIGNED: Understanding and identifying the immunological markers and clinical information linked with HIV acquisition is crucial for effectively implementing Pre-Exposure Prophylaxis (PrEP) to prevent HIV acquisition. Prior analysis on HIV incidence outcomes have predominantly employed proportional hazards (PH) models, adjusting solely for baseline covariates. Therefore, models that integrate cytokine biomarkers, particularly as time-varying covariates, are sorely needed.
UNASSIGNED: We built a simple model using the Cox PH to investigate the impact of specific cytokine profiles in predicting the overall HIV incidence. Further, Kaplan-Meier curves were used to compare HIV incidence rates between the treatment and placebo groups while assessing the overall treatment effectiveness. Utilizing stepwise regression, we developed a series of Cox PH models to analyze 48 longitudinally measured cytokine profiles. We considered three kinds of effects in the cytokine profile measurements: average, difference, and time-dependent covariate. These effects were combined with baseline covariates to explore their influence on predictors of HIV incidence.
UNASSIGNED: Comparing the predictive performance of the Cox PH models developed using the AIC metric, model 4 (Cox PH model with time-dependent cytokine) outperformed the others. The results indicated that the cytokines, interleukin (IL-2, IL-3, IL-5, IL-10, IL-16, IL-12P70, and IL-17 alpha), stem cell factor (SCF), beta nerve growth factor (B-NGF), tumor necrosis factor alpha (TNF-A), interferon (IFN) alpha-2, serum stem cell growth factor (SCG)-beta, platelet-derived growth factor (PDGF)-BB, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and cutaneous T-cell-attracting chemokine (CTACK) were significantly associated with HIV incidence. Baseline predictors significantly associated with HIV incidence when considering cytokine effects included: age of oldest sex partner, age at enrollment, salary, years with a stable partner, sex partner having any other sex partner, husband\'s income, other income source, age at debut, years lived in Durban, and sex in the last 30 days.
UNASSIGNED: Overall, the inclusion of cytokine effects enhanced the predictive performance of the models, and the PrEP group exhibited reduced HIV incidences compared to the placebo group.

Pre-exposure prophylaxis (PrEP) has the potential to prevent new HIV infections, but it is unclear how state policies governing sexual and reproductive health services (SRH) impact access for cisgender women. The objective of this review is to identify barriers to PrEP access for cisgender women in the United States. Using the CDC Atlas Program, 20 states with the highest HIV incidence among cisgender women were included in this analysis. Through a search conducted in May-July 2022 of CDC, PrEPWatch.org, and other State Department and Insurance websites, Medicaid expansion status, pharmacist PrEP prescribing laws, financial support programs, and Traditional Medicaid coverage of PrEP, HIV testing, and emergency contraception were reviewed. Of the included states, nearly half did not expand Medicaid at the state level. Emergency contraception and HIV testing was covered under Traditional Medicaid for almost all included states, but insurance stipulations and eligibility requirements remain. Although PrEP is covered under all Traditional Medicaid plans, six states require pre-authorization. Three states have HIV testing mandates, four allow pharmacists to prescribe PrEP and six have financial support programs to cover the cost of PrEP. Medicaid expansion, pre-authorization requirements for PrEP prescriptions and emergency contraception, and limitations on pharmacist prescribing abilities were identified as barriers to SRH access for cisgender women. Medicaid expansion should be prioritized as an approach to expanding access to HIV prevention services at the state level.

BACKGROUND: Optimizing uptake of pre-exposure prophylaxis (PrEP) for individuals at risk of HIV acquisition has been challenging despite clear scientific evidence and normative guidelines, particularly for key populations (KPs) such as men who have sex with men (MSM), female sex workers (FSWs), transgender (TG) people and persons who inject drugs (PWID). Applying an iterative Programme Science cycle, building on the effective programme coverage framework, we describe the approach used by the Centre for Infectious Disease Research in Zambia (CIDRZ) to scale up PrEP delivery and address inequities in PrEP access for KP in Lusaka, Zambia.
METHODS: In 2019, CIDRZ partnered with 10 local KP civil society organizations (CSOs) and the Ministry of Health (MOH) to offer HIV services within KP-designated community safe spaces. KP CSO partners led KP mobilization, managed safe spaces and delivered peer support; MOH organized clinicians and clinical commodities; and CIDRZ provided technical oversight. In December 2021, we introduced a community-based intervention focused on PrEP delivery in venues where KP socialize. We collected routine programme data from September 2019 to June 2023 using programme-specific tools and the national electronic health record. We estimated the before-after effects of our intervention on PrEP uptake, continuation and equity for KP using descriptive statistics and interrupted time series regression, and used mixed-effects regression to estimate marginal probabilities of PrEP continuity.
RESULTS: Most (25,658) of the 38,307 (67.0%) Key Population Investment Fund beneficiaries were reached with HIV prevention services at community-based venues. In total, 23,527 (61.4%) received HIV testing services, with 15,508 (65.9%) testing HIV negative and found PrEP eligible, and 15,241 (98.3%) initiating PrEP. Across all programme quarters and KP types, PrEP uptake was >90%. After introducing venue-based PrEP delivery, PrEP uptake (98.7% after vs. 96.5% before, p < 0.001) and the number of initiations (p = 0.014) increased significantly. The proportion of KP with ≥1 PrEP continuation visit within 6 months of initiation was unchanged post-intervention (46.7%, 95% confidence interval [CI]: 45.7%, 47.6%) versus pre-intervention (47.2%, 95% CI: 45.4%, 49.1%).
CONCLUSIONS: Applying Programme Science principles, we demonstrate how decentralizing HIV prevention services to KP venues and safe spaces in partnership with KP CSOs enabled successful community-based PrEP delivery beyond the reach of traditional facility-based services.

BACKGROUND: Acquired syphilis continues to affect millions of people around the world. It is crucial to study it in the context of HIV Pre-Exposure Prophylaxis (PrEP) to achieve the goals set out in the 2030 Agenda since the literature suggests increased risk behaviors for sexually transmitted infections. This study aimed to investigate the incidence and factors associated with acquired syphilis among PrEP users.
METHODS: This retrospective cohort included data on PrEP users from all over Brazil from 2018 to 2020, retrieved from the national antiretroviral logistics system. We calculated the proportion of syphilis before PrEP, the incidence during the user\'s follow-up, reinfections, and their possible associated factors. We conducted descriptive, bivariate, and multivariate analysis, estimating the crude Relative Risk, adjusted Odds Ratio (aOR), and their respective confidence intervals (95%CI).
RESULTS: Most of the 34,000 individuals who started PrEP were male (89.0%), white (53.7%), self-identified as male (85.2%), homosexual, gay, or lesbian (72.2%), and had 12 schooling years or more (67.8%). Of these, 8.3% had syphilis in the six months before starting PrEP, and 4% had it in the first 30 days of using the prophylaxis. We identified a loss-to-follow-up rate of 41.7%, although the loss and the cohort shared similar characteristics. The proportion of missed syphilis tests was high: 33.4% in the 30 days and 38.8% in the follow-up period. In the 19,820 individuals effectively monitored, the incidence of acquired syphilis was 19.1 cases per 100 person-years, and 1.9% of users had reinfection. The rate of missed syphilis tests at the 30-day follow-up was 33.4%, and the total follow-up test period was 38.8%. The multivariate analysis identified female gender (aOR 0.3; 95%CI 0.2-0.5), being white or Black (aOR 0.9; 95%CI 0.7-0.9 and aOR 0.7; 95%CI 0.7-0.99, respectively) as protective factors for syphilis. Being homosexual, gay, lesbian (aOR 2.7; 95%CI 2.0-3.7), or having a history of syphilis in the six months before PrEP (aOR 2.2; 95%CI 1.9-2.5) were risk factors for syphilis during PrEP use. Behaviors related to the risk of syphilis included accepting something in exchange for sex (aOR 1.6; 95%CI 1.3-1.9), irregular condom use (use in less than half of sexual intercourse sessions; aOR 1.7; 95%CI 1.53-2.1) and recreational drug use (poppers; aOR 1.5; 95%CI 1.53-2.1).
CONCLUSIONS: Syphilis in the context of PrEP has high rates and is associated with sociodemographic and behavioral factors. We recommend additional studies targeting prevention in this population to curb these figures.

BACKGROUND: In Belgium, oral HIV pre-exposure prophylaxis (PrEP) is primarily provided in specialized clinical settings. Optimal implementation of PrEP services can help to substantially reduce HIV transmission. However, insights into implementation processes, and their complex interactions with local context, are limited. This study examined factors that influence providers\' adaptive responses in the implementation of PrEP services in Belgian HIV clinics.
METHODS: We conducted a qualitative multiple case study on PrEP care implementation in eight HIV clinics. Thirty-six semi-structured interviews were conducted between January 2021 and May 2022 with a purposive sample of PrEP care providers (e.g. physicians, nurses, psychologists), supplemented by 50 hours of observations of healthcare settings and clinical interactions. Field notes from observations and verbatim interview transcripts were thematically analysed guided by a refined iteration of extended Normalisation Process Theory.
RESULTS: Implementing PrEP care in a centralized service delivery system required considerable adaptive capacity of providers to balance the increasing workload with an adequate response to PrEP users\' individual care needs. As a result, clinic structures were re-organized to allow for more efficient PrEP care processes, compatible with other clinic-level priorities. Providers adapted clinical and policy norms on PrEP care (e.g. related to PrEP prescribing practices and which providers can deliver PrEP services), to flexibly tailor care to individual clients\' situations. Interprofessional relationships were reconfigured in line with organizational and clinical adaptations; these included task-shifting from physicians to nurses, leading them to become increasingly trained and specialized in PrEP care. As nurse involvement grew, they adopted a crucial role in responding to PrEP users\' non-medical needs (e.g. providing psychosocial support). Moreover, clinicians\' growing collaboration with sexologists and psychologists, and interactions with PrEP users\' family physician, became crucial in addressing complex psychosocial needs of PrEP clients, while also alleviating the burden of care on busy HIV clinics.
CONCLUSIONS: Our study in Belgian HIV clinics reveals that the implementation of PrEP care presents a complex-multifaceted-undertaking that requires substantial adaptive work to ensure seamless integration within existing health services. To optimize integration in different settings, policies and guidelines governing PrEP care implementation should allow for sufficient flexibility and tailoring according to respective local health systems.

BACKGROUND: Improving the delivery of existing evidence-based interventions to prevent and diagnose HIV is key to Ending the HIV Epidemic in the United States. Structural barriers in the access and delivery of related health services require municipal or state-level policy changes; however, suboptimal implementation can be addressed directly through interventions designed to improve the reach, effectiveness, adoption or maintenance of available interventions. Our objective was to estimate the cost-effectiveness and potential epidemiological impact of six real-world implementation interventions designed to address these barriers and increase the scale of delivery of interventions for HIV testing and pre-exposure prophylaxis (PrEP) in three US metropolitan areas.
METHODS: We used a dynamic HIV transmission model calibrated to replicate HIV microepidemics in Atlanta, Los Angeles (LA) and Miami. We identified six implementation interventions designed to improve HIV testing uptake (\"Academic detailing for HIV testing,\" \"CyBER/testing,\" \"All About Me\") and PrEP uptake/persistence (\"Project SLIP,\" \"PrEPmate,\" \"PrEP patient navigation\"). Our comparator scenario reflected a scale-up of interventions with no additional efforts to mitigate implementation and structural barriers. We accounted for potential heterogeneity in population-level effectiveness across jurisdictions. We sustained implementation interventions over a 10-year period and evaluated HIV acquisitions averted, costs, quality-adjusted life years and incremental cost-effectiveness ratios over a 20-year time horizon (2023-2042).
RESULTS: Across jurisdictions, implementation interventions to improve the scale of HIV testing were most cost-effective in Atlanta and LA (CyBER/testing cost-saving and All About Me cost-effective), while interventions for PrEP were most cost-effective in Miami (two of three were cost-saving). We estimated that the most impactful HIV testing intervention, CyBER/testing, was projected to avert 111 (95% credible interval: 110-111), 230 (228-233) and 101 (101-103) acquisitions over 20 years in Atlanta, LA and Miami, respectively. The most impactful implementation intervention to improve PrEP engagement, PrEPmate, averted an estimated 936 (929-943), 860 (853-867) and 2152 (2127-2178) acquisitions over 20 years, in Atlanta, LA and Miami, respectively.
CONCLUSIONS: Our results highlight the potential impact of interventions to enhance the implementation of existing evidence-based interventions for the prevention and diagnosis of HIV.

BACKGROUND: Pharmacy-delivered HIV prevention services might create more options for pregnant women to use HIV prevention tools earlier and more consistently during pregnancy. We quantified preferences for attributes of potential HIV prevention services among women of childbearing age in Western Kenya.
METHODS: From June to November 2023, we administered a face-to-face discrete choice experiment survey to women aged 15-44 in Kenya\'s Homa Bay, Kisumu and Siaya counties. The survey evaluated preferences for HIV prevention services, described by seven attributes: service location, travel time, type of HIV test, sexually transmitted infection (STI) testing, partner HIV testing, pre-exposure prophylaxis (PrEP) and service fee. Participants answered a series of 12-choice questions. Each question asked them to select one of two service options or no services-an opt-out option. We used hierarchical Bayesian modelling levels to estimate each attribute level\'s coefficient and understand how attributes influenced service choice.
RESULTS: Overall, 599 participants completed the survey, among whom the median age was 23 years (IQR: 18-27); 33% were married, 20% had a job and worked regularly, and 52% had been pregnant before. Participants, on average, strongly preferred having any HIV prevention service option over none (opt-out preference weight: -5.84 [95% CI: -5.97, -5.72]). The most important attributes were the availability of PrEP (relative importance 27.04% [95% CI: 25.98%, 28.11%]), followed by STI testing (relative importance 20.26% [95% CI: 19.52%, 21.01%]) and partner HIV testing (relative importance: 16.35% [95% CI: 15.79%, 16.90%]). While, on average, participants preferred obtaining services at the clinic more than pharmacies, women prioritized the availability of PrEP, STI testing and partner HIV testing more than the location or cost.
CONCLUSIONS: These findings suggest the importance of providing comprehensive HIV prevention services and ensuring PrEP, STI testing and partner HIV testing are available. If pharmacies can offer these services, women are likely to access those services at pharmacies even if they prefer clinics.

BACKGROUND: Adolescent girls and young women (AGYW) who may benefit from HIV pre-exposure prophylaxis (PrEP) face high levels of common mental disorders (e.g. depression, anxiety). Common mental disorders can reduce PrEP adherence and increase HIV risk, yet mental health interventions have not been well-integrated into PrEP delivery.
METHODS: We conducted a four-phase human-centred design process, from December 2020 to April 2022, to understand mental health challenges among AGYW in Johannesburg, South Africa and barriers to integrated mental health and PrEP services. In the \"Discover\" phase, we conducted in-depth interviews with AGYW and key informants (KIs) in Johannesburg. We conducted a rapid qualitative analysis, informed by the Consolidated Framework for Implementation Research (CFIR), to identify facilitators and barriers of integrated mental health and PrEP services and mapped barriers to potential implementation strategies. In the \"Design\" and \"Build\" phases, we conducted stakeholder workshops to iteratively adapt an evidence-based mental health intervention, the Friendship Bench, and refine implementation strategies for South African PrEP delivery settings. In the \"Test\" phase, we piloted our adapted Friendship Bench package.
RESULTS: Interviews with 70 Discover phase participants (48 AGYW, 22 KIs) revealed the importance of integrated mental health and PrEP services for South African AGYW. Interviewees described barriers and implementation strategies for mental health and PrEP services around the CFIR domains: intervention characteristics (e.g. challenges with AGYW \"opening up\"); outer Johannesburg setting (e.g. community stigma); inner clinic setting (e.g. judgemental healthcare providers); characteristics of counsellors (e.g. training gaps); and the implementation process (e.g. need for demand creation). The Design and Build workshops included 13 AGYW and 15 KIs. Implementation barriers related to the quality and accessibility of public-sector clinic services, lay counsellor training, and community education and demand creation activities were prioritized. This led to 12 key Friendship Bench adaptations and the specification of 10 implementation strategies that were acceptable and feasible in initial pilot testing with three AGYW.
CONCLUSIONS: Using a human-centred approach, we identified determinants and potential solutions for integrating mental health interventions within PrEP services for South African AGYW. This design process centred stakeholders\' perspectives, enabling rapid development of an adapted Friendship Bench intervention implementation package.