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.

"Honesty, Communication and Trust Are What Bring Peace of Mind": Narratives of HIV Risk Among Hispanic/Latino Men Who Have Sex with Men in the Southern United States.

For Hispanic/Latino MSM (HLMSM) in the South, HIV burden remains high, and HIV elimination is a national priority. Between July and September 2016, using a strengths-based approach informed by resilience theory, we conducted qualitative interviews with HIV-negative HLMSM in five southern cities in the United States with elevated HIV prevalence. We analyzed data using a qualitative content analysis approach, assessing for interrater reliability. A brief behavioral survey was also conducted. We enrolled 51 HLMSM (mean age = 33 years, range = 15-63). HLMSM discussed the climate of fear about HIV and homosexuality impeding HIV prevention, including the impact of stigma and taboo. Three main strengths-based strategies emerged for preventing HIV: assessing partner risk, establishing boundaries for sexual interactions, and self-education. Future HIV prevention efforts may benefit from balancing risk-based approaches with those that emphasize resilience, address partner trustworthiness and safety, and focus on providing novel outlets for HIV prevention education.

How women living with HIV in the UK manage infant-feeding decisions and vertical transmission risk - a qualitative study.

BACKGROUND: The World Health Organization (WHO) recommends that women with HIV breastfeed for a minimum of one year. In contrast, across high-income countries, HIV and infant-feeding guidelines recommend exclusive formula feeding if parents want to avoid all risk of postpartum transmission. However, recently these guidelines (including in the United Kingdom (UK)) increasingly state that individuals with HIV should be supported to breast/chest feed if they meet certain criteria; such as an undetectable maternal HIV viral load and consent to additional clinical monitoring. Between 600 and 800 pregnancies are reported annually in women with HIV in the UK, with low rates of vertical transmission (0.22%). Informed infant-feeding decision-making requires clinical support. Currently, little research addresses how individuals with HIV in high-income countries navigate infant-feeding decisions with their clinical teams and familial and social networks, and the resources needed to reach an informed decision. METHODS: Semi-structured remote interviews were conducted between April 2021 - January 2022 with UK-based individuals with a confirmed HIV diagnosis who were pregnant or one-year postpartum. Using purposive sampling, pregnant and postpartum participants were recruited through NHS HIV clinics, community-based organisations and snowballing. Data were analysed thematically and organised using NVivo 12. RESULTS: Of the 36 cisgender women interviewed, 28 were postpartum. The majority were of Black African descent (n = 22) and born outside the UK. The majority of postpartum women had chosen to formula feed. Women's decision-making regarding infant-feeding was determined by (1) information and support; (2) practicalities of implementing medical guidance; (3) social implications of infant-feeding decisions. CONCLUSION: The evolution of UK HIV and infant-feeding guidelines are not reflected in the experiences of women living with HIV. Clinicians' emphasis on reducing the risk of vertical transmission, without adequately considering personal, social and financial concerns, prevents women from making fully informed infant-feeding decisions. For some, seeking advice beyond their immediate clinical team was key to feeling empowered in their decision. The significant informational and support need among women with HIV around their infant-feeding options must be addressed. Furthermore, training for and communication by healthcare professionals supporting women with HIV is essential if women are to make fully informed decisions.

Gay and Bisexual Men's Perceptions about a Potential HIV Vaccine within a Post-COVID-19 Era: A Qualitative Study.

To end the HIV epidemic, there is need for targeted strategies to reduce HIV incidence for those most vulnerable, including an HIV vaccine. This study seeks to understand the perceptions that non-PrEP using gay and bisexual men and other men who have sex with men (GBMSM) have about a potential HIV vaccine, while contextualizing their perspectives within the context of heightened vaccine hesitancy that has emerged since the COVID-19 pandemic. Between March and May of 2022, GBMSM (N = 20) participated in in-depth interviews, which assessed their perceptions about an HIV vaccine. Interviews were analysed using a codebook approach to thematic analysis. We oversampled for those unvaccinated against COVID-19 as a proxy for vaccine hesitation. Participants expressed a range of enthusiastic support, cautious optimism and skepticism when presented with the possibility of an HIV vaccine. Factors that drove willingness to receive an HIV vaccine included community-oriented altruism, individualized risk-benefit assessment, and/or the perception that a vaccine could provide a beneficial shift in sexual experiences. Participants also expressed hesitations about receiving an HIV vaccine, including concerns about potential side-effects and efficacy, as well as mistrust in the vaccine development process. Notably, participants often evaluated the vaccine in comparison to PrEP and condoms. Participants offered specific insights into information they would like to receive about an HIV and where/how they would like to receive it. Our findings can help inform future HIV vaccine implementation efforts by offering insights into the factors that motivate and deter GBMSM to receive an HIV vaccine.

Factors Associated with Usage of Oral-PrEP among Female Sex Workers in Nairobi, Kenya, Assessed by Self-Report and a Point-of-Care Urine Tenofovir Immunoassay.

Pre-exposure prophylaxis (PrEP) is highly effective at reducing HIV acquisition. We aimed to estimate usage of oral-PrEP, and factors associated with adherence among female sex workers (FSWs) in Nairobi, Kenya, using a novel point-of-care urine tenofovir lateral flow assay (LFA). The Maisha Fiti study randomly selected FSWs from Sex Worker Outreach Program clinics in Nairobi. Data were collected from 1003 FSWs from June-October 2019, including surveys on self-reported oral-PrEP adherence. Adherence was also measured using the LFA for HIV-negative FSWs currently taking oral-PrEP. Informed by a social-ecological theoretical framework, we used hierarchical multivariable logistic regression models to estimate associations between individual, interpersonal/community, and structural/institutional-level factors and either self-reported or LFA-assessed adherence. Overall, 746 HIV-negative FSWs aged 18-40 participated in the study, of whom 180 (24.1%) self-reported currently taking oral-PrEP. Of these, 56 (31.1%) were adherent to oral-PrEP as measured by LFA. In the multivariable analyses, associations with currently taking oral-PrEP included having completed secondary education, high alcohol/substance use, feeling empowered to use PrEP, current intimate partner, no recent intimate partner violence, having support from sex worker organisations, experiencing sex work-related stigma, and seeking healthcare services despite stigma. Associations with oral-PrEP LFA-measured adherence measured included having only primary education, experience of childhood emotional violence, belonging to a higher wealth tertile, and being nulliparous. Oral-PrEP adherence, measured by self-report or objectively, is low among FSWs in Nairobi. Programs to improve oral-PrEP usage among FSWs should work to mitigate social and structural barriers and involve collaboration between FSWs, healthcare providers and policymakers.

Ameliorating Racial Disparities in HIV Prevention via a Nurse-Led, AI-Enhanced Program for Pre-Exposure Prophylaxis Utilization Among Black Cisgender Women: Protocol for a Mixed Methods Study.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is a critical biomedical strategy to prevent HIV transmission among cisgender women. Despite its proven effectiveness, Black cisgender women remain significantly underrepresented throughout the PrEP care continuum, facing barriers such as limited access to care, medical mistrust, and intersectional racial or HIV stigma. Addressing these disparities is vital to improving HIV prevention outcomes within this community. On the other hand, nurse practitioners (NPs) play a pivotal role in PrEP utilization but are underrepresented due to a lack of awareness, a lack of human resources, and insufficient support. Equipped with the rapid evolution of artificial intelligence (AI) and advanced large language models, chatbots effectively facilitate health care communication and linkage to care in various domains, including HIV prevention and PrEP care. OBJECTIVE: Our study harnesses NPs' holistic care capabilities and the power of AI through natural language processing algorithms, providing targeted, patient-centered facilitation for PrEP care. Our overarching goal is to create a nurse-led, stakeholder-inclusive, and AI-powered program to facilitate PrEP utilization among Black cisgender women, ultimately enhancing HIV prevention efforts in this vulnerable group in 3 phases. This project aims to mitigate health disparities and advance innovative, technology-based solutions. METHODS: The study uses a mixed methods design involving semistructured interviews with key stakeholders, including 50 PrEP-eligible Black women, 10 NPs, and a community advisory board representing various socioeconomic backgrounds. The AI-powered chatbot is developed using HumanX technology and SmartBot360's Health Insurance Portability and Accountability Act-compliant framework to ensure data privacy and security. The study spans 18 months and consists of 3 phases: exploration, development, and evaluation. RESULTS: As of May 2024, the institutional review board protocol for phase 1 has been approved. We plan to start recruitment for Black cisgender women and NPs in September 2024, with the aim to collect information to understand their preferences regarding chatbot development. While institutional review board approval for phases 2 and 3 is still in progress, we have made significant strides in networking for participant recruitment. We plan to conduct data collection soon, and further updates on the recruitment and data collection progress will be provided as the study advances. CONCLUSIONS: The AI-powered chatbot offers a novel approach to improving PrEP care utilization among Black cisgender women, with opportunities to reduce barriers to care and facilitate a stigma-free environment. However, challenges remain regarding health equity and the digital divide, emphasizing the need for culturally competent design and robust data privacy protocols. The implications of this study extend beyond PrEP care, presenting a scalable model that can address broader health disparities. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/59975.

Risk factors for treatment non-completion among patients with syphilis.

Background: With recent increases in syphilis, there is growing interest in expanding screening; however, treatment rates have historically been low. Objectives: This study examines demographic and clinical factors that may contribute to non-completion of syphilis treatment. Design: This is a retrospective comparative cohort study of all patients with syphilis from January through November 2018 at an urban, tertiary care hospital. Methods: Demographics and clinical information were extracted from the electronic medical record. Descriptive statistics and odds ratios (ORs) were calculated. Results: Of 171 patients with syphilis, 89 (52.0%) completed treatment. Patients ages 40-49 were least likely to complete treatment (OR 0.14; 95% CI 0.03-0.72, p = 0.02) compared to those ages 18-24. Non-heterosexual patients were significantly more likely to complete treatment (OR 3.60; 95% CI 1.13-11.49, p = 0.03) compared to heterosexual patients. Patients diagnosed in the emergency department completed treatment at the lowest rate. Conclusion: A major gap in syphilis treatment still exists, which must be addressed to achieve optimal impact from syphilis screening programs.

Demographic and clinical factors associated with risk for not completing treatment among patients with syphilis Rates of syphilis, a common sexually transmitted infection, have been steadily increasing in the United States, now at their highest in decades. Left untreated, syphilis can lead to major health complications, and in pregnant women can cause abnormalities in newborn babies or stillbirth. To address this epidemic, screening programs are being developed to diagnose syphilis in vulnerable populations. However, screening without treatment is not an effective strategy, and historically syphilis treatment rates have been low. This is most likely because the treatment can require a lengthy antibiotic course and often several office visits. In this study, we looked back at the patients diagnosed with syphilis at our hospital for 11 months in 2018 to understand factors that might be associated with a risk of not completing treatment. In this sample, only slightly more than half of patients with syphilis completed treatment. We found that younger patients, patients who didn't identify as heterosexual, and patients with private insurance were all more likely to complete syphilis treatment. We also found that patients diagnosed in the emergency department completed treatment at the lowest rates. These findings suggest some areas where new strategies can be developed to help support patients with syphilis to get treated. Only with sufficient treatment of patients with syphilis can we make progress on the growing syphilis epidemic.

Long-Acting Injectable Pre-Exposure Prophylaxis Perceptions and Preferences Among Transgender and Nonbinary Young Adults in the United States.

Long-acting injectable pre-exposure prophylaxis for HIV prevention (LAI-PrEP) was approved for use in the United States in 2021, yet little is known about perceptions of LAI-PrEP among transgender and nonbinary young adults, a group that faces substantial barriers to HIV prevention. We investigated US transgender and nonbinary young adults' perceptions of and attitudes toward LAI-PrEP and how perceived advantages and disadvantages of LAI-PrEP related to the PrEP continuum of care. We conducted semi-structured interviews with 31 transgender and nonbinary young adults who reported oral PrEP use or were PrEP-eligible. We analyzed responses using both a deductive RADaR approach, to identify LAI-PrEP perceptions relevant to the PrEP continuum of care, and an inductive thematic analysis to explore key themes. In this study, all PrEP-experienced and most PrEP-naïve participants indicated an interest in LAI-PrEP, citing advantages over daily oral medication (e.g., fewer adherence challenges). Three key themes emerged: (1) Some participants linked perceived advantages of LAI-PrEP to experiences with gender-affirming care (e.g., familiarity with needles via hormone use). (2) Participants weighed trade-offs and contextual factors that influenced their LAI-PrEP preferences (e.g., interest contingent on whether location for receiving injection was geographically accessible). (3) Participants envisaged alternative delivery methods that could enhance LAI-PrEP acceptability and uptake (e.g., home injection). HIV prevention programs should incorporate the insights of transgender and nonbinary young adults to ensure that emerging HIV prevention technologies are accessible and responsive to the needs and concerns of people of all gender modalities.

Improving Recruitment and Retention of Transgender Women in HIV Prevention Trials: Strategies to Make Trial Participation More Congruent with the Needs of Transgender Women.

Transgender women are disproportionately burdened by HIV. Though there is a substantial body of research exploring barriers and facilitators of HIV prevention among transgender women, many barriers remain unaddressed. This study identifies strategies to make HIV prevention trials more congruent with transgender women's preferences and needs to boost trial participation and ultimately enhance initiation and uptake of pre-exposure prophylaxis (PrEP). We conducted in-depth interviews with 15 sexually active, HIV-negative transgender women in New York City to understand: (1) preferences concerning long-acting injectable cabotegravir for PrEP and (2) ideas on how to make HIV prevention trial environments more comfortable. We identified five themes related to increasing transgender women's appeal to trials: (1) creating a more inclusive/welcoming environment, (2) providing compensation that is responsive to transgender women and community needs, (3) centering transgender women in recruitment and informational materials, (4) training study staff on gender-affirming practices, and (5) hiring transgender people as study staff. Participants wanted to see more gender diversity, representation, correct pronouns, gender-affirming practices, and compensation or reimbursements. Together, these practices may improve recruitment and retention of transgender women in HIV prevention trials.

Transactional sex and age-disparate sexual partnerships among adolescent girls and young women in Tanzania.

Introduction: Adolescent girls and young women (AGYW) continue to experience a high incidence of HIV in southern and eastern Africa, even in the context of large-scale HIV prevention interventions. In Tanzania, AGYW account for the largest proportion of new infections and have a higher risk of HIV acquisition than males of comparable age. Methods: We used routinely collected data from the PEPFAR/USAID-funded Sauti Project, a large combination HIV prevention program, to examine the relationship between transactional sex and sex with older partners among AGYW in Tanzania (2015-2020). Out-of-school AGYW 15-24 years completed a vulnerability index and were tested for HIV. We estimated weighted prevalence ratios (PR) and 95% confidence intervals (CI) for the associations of transactional sex (sex exchanged for money/services/gifts outside of sex work) and sex with older partners (≥5-years older, ≥10-years older) with prevalent HIV. Age cutoffs of 5 and 10 years were used to align partner age differences with age-disparate and intergenerational sex, respectively. We assessed potential synergism between exposures, and subgroup analyses explored associations among girls 15-19. Results: Sixty seven thousand three hundred fifty seven AGYW completed the vulnerability index and 14,873 had captured HIV testing records. Median age was 20 years (IQR 18-22). Transactional sex and age-disparate sex were common (35% and 28%, respectively); 13% of AGYW reported both behaviors. HIV prevalence was associated with both transactional sex (PR: 1.28; 95% CI 1.00-1.63) and age-disparate sex (PR:1.26, 95% CI 0.99-1.60). In common referent analysis, transactional sex remained strongly associated with HIV, even in the absence of age-disparate sex (PR 1.41; 95% CI 1.02-1.94). Discussion: Evidence of statistical synergism was not present, suggesting both transactional sex and age-disparate sex operate through similar pathways to increase HIV risk. Increased specificity within HIV prevention programs is needed to better meet the sexual and reproductive health needs of AGYW at high risk of HIV in Tanzania, including investment in tailored youth-friendly strategies for AGYW who have been marginalized from the current HIV response.

"We chose PrEP because I wanted to be sure that this child my wife was going to conceive was indeed mine." Factors influencing the choice of safer conception methods and experiences with its use: a qualitative study among HIV sero-discordant couples in Zimbabwe.

BACKGROUND: Safer conception services are needed to minimize HIV transmission among HIV sero-discordant couples desiring pregnancy. Few studies have evaluated the choices couples make when they are offered multiple safer conception methods or real-world method acceptability. This paper addresses an important knowledge gap regarding factors that influence the choice of safer conception methods, couples' actual experiences using safer conception methods, and why some couples switch safer conception methods. METHODS: Between February and June 2019, we conducted semi-structured in-depth interviews among 14 men and 17 women, representing 17 couples who exited the SAFER study-a pilot safer conception study for HIV sero-discordant couples in Zimbabwe that offered couples a choice of ART with monthly viral load monitoring (ART/VL), oral PrEP, vaginal insemination, and semen washing. All couples in SAFER had used at least two safer conception methods. RESULTS: We found that safer conception method choice often centered around a desire for intimacy, condomless sex, and certainty in the conception process, particularly for men. Method-related attributes such as familiarity, perceived ease of use, side effects, and perceived level of effectiveness in preventing HIV and achieving pregnancy influenced method choice, switching, and satisfaction. Concerns were expressed about each safer conception method and couples were willing to try different methods until they found method(s) that worked for them. The majority of participants reported having positive experiences using safer conception, especially those using ART/VL + PrEP, citing that they were able to attempt pregnancy for the first time with peace of mind and experienced joy and satisfaction from being able to achieve pregnancy safely. CONCLUSIONS: The differences in method preferences and experiences voiced by participants in this study and in other studies from the region point to the importance of having a variety of safer conception options in the service delivery package and addressing concerns about paternity, intimacy, and method-related attributes to enable HIV sero-discordant couples to safely achieve their reproductive goals.

Ending the HIV Epidemic in Metropolitan Atlanta: a mixed-methods study to support the local HIV/AIDS response.

INTRODUCTION: Four counties within the Atlanta, Georgia 20-county eligible metropolitan area (EMA) are currently prioritized by the US "Ending the HIV Epidemic" (EHE) initiative which aims for a 90% reduction in HIV incidence by 2030. Disparities driving Atlanta's HIV epidemic warrant an examination of local service availability, unmet needs and organizational capacity to reach EHE targets. We conducted a mixed-methods evaluation of the Atlanta EMA to examine geographic HIV epidemiology and distribution of services, service needs and organization infrastructure for each pillar of the EHE initiative. METHODS: We collected 2021 county-level data (during June 2022), from multiple sources including: AIDSVu (HIV prevalence and new diagnoses), the Centers for Disease Control and Prevention web-based tools (HIV testing and pre-exposure prophylaxis [PrEP] locations) and the Georgia Department of Public Health (HIV testing, PrEP screenings, viral suppression and partner service interviews). We additionally distributed an online survey to key local stakeholders working at major HIV care agencies across the EMA to assess the availability of services, unmet needs and organization infrastructure (June-December 2022). The Organizational Readiness for Implementing Change questionnaire assessed the organization climate for services in need of scale-up or implementation. RESULTS: We found racial/ethnic and geographic disparities in HIV disease burden and service availability across the EMA-particularly for HIV testing and PrEP in the EMA's southern counties. Five counties not currently prioritized by EHE (Clayton, Douglas, Henry, Newton and Rockdale) accounted for 16% of the EMA's new diagnoses, but <9% of its 177 testing sites and <7% of its 130 PrEP sites. Survey respondents (N = 48; 42% health agency managers/directors) reported high unmet need for HIV self-testing kits, mobile clinic testing, HIV case management, peer outreach and navigation, integrated care, housing support and transportation services. Respondents highlighted insufficient existing staffing and infrastructure to facilitate the necessary expansion of services, and the need to reduce inequities and address intersectional stigma. CONCLUSIONS: Service delivery across all EHE pillars must substantially expand to reach national goals and address HIV disparities in metro Atlanta. High-resolution geographic data on HIV epidemiology and service delivery with community input can provide targeted guidance to support local EHE efforts.

Low HIV drug resistance prevalence among recently diagnosed HIV-positive men who have sex with men in a setting of high PrEP use.

INTRODUCTION: New South Wales (NSW) has one of the world's highest uptake rates of HIV pre-exposure prophylaxis (PrEP). This uptake has been credited with sharp declines in HIV transmission, particularly among Australian-born gay and bisexual men. Concerns have been raised around the potential for the emergence of tenofovir (TFV) and XTC (lamivudine/emtricitabine) resistance in settings of high PrEP use. Such an emergence could also increase treatment failure and associated clinical outcomes among people living with HIV (PLHIV). Despite low levels of nucleoside reverse-transcriptase inhibitor (NRTI) resistance relating to PrEP use in clinical settings, there are few published studies describing the prevalence of NRTI resistance among people newly diagnosed with HIV in a setting of high PrEP use. METHODS: Using HIV antiretroviral drug resistance data linked to NSW HIV notifications records of people diagnosed from 1 January 2015 to 31 December 2021 and with HIV attributed to male-to-male sex, we described trends in TFV and XTC resistance. Resistance was identified using the Stanford HIV Drug Resistance genotypic resistance interpretation system. To focus on transmitted drug resistance, resistance prevalence estimates were generated using sequences taken less than 3 months post-HIV diagnosis. These estimates were stratified by timing of sequencing relative to the date of diagnosis, year of sequencing, birthplace, likely place of HIV acquisition, and stage of HIV at diagnosis. RESULTS: Among 1119 diagnoses linked to HIV genomes sequenced less than 3 months following diagnosis, overall XTC resistance prevalence was 1.3%. Between 2015 and 2021, XTC resistance fluctuated between 0.5% to 2.9% and was 1.0% in 2021. No TFV resistance was found over the study period in any of the sequences analysed. Higher XTC resistance prevalence was observed among people with newly acquired HIV (evidence of HIV acquisition in the 12 months prior to diagnosis; 2.9%, p = 0.008). CONCLUSIONS: In this Australian setting, TFV and XTC resistance prevalence in new HIV diagnoses remained low. Our findings offer further evidence for the safe scale-up of PrEP in high-income settings, without jeopardizing the treatment of those living with HIV.

Interest in and Willingness to Use PrEP: A Cross-Sectional Study of Individuals with Problematic Substance Use Residing in a High HIV Prevalence Jurisdiction.

Although it is an effective HIV prevention method, pre-exposure prophylaxis (PrEP) is underutilized in the Southern US. Many people who use drugs (PWUD) have increased susceptibility to HIV which could be lessened by using PrEP. Potential barriers to PrEP use include lack of awareness of PrEP, low knowledge about HIV prevention, low self-efficacy for HIV prevention, inaccurate risk perceptions, and anticipated stigma. The current study examined predisposing, enabling, and reinforcing factors that may predict interest in PrEP. The purpose of the current study was to explore factors associated with interest in and willingness to use daily oral and long acting injectable PrEP among sexually active adult PWUD. The data were collected from adult participants (n = 270) residing in Harris County, TX, who self-reported problematic substance use and who reported oral, anal, or vaginal sex in the six months prior to completing the survey. The survey was distributed and completed online via Qualtrics Panels in March of 2022 and included measures of PrEP and HIV knowledge, PrEP stigma, sexual health self-efficacy, experiences of discrimination, health literacy, and medical mistrust. The majority of participants reported circumstances or behaviors that increased their susceptibility to HIV. Findings indicated that PrEP user stereotypes and PrEP anticipated disapproval by others were associated with interest in using daily oral PrEP and willingness to use long acting injectable PrEP. These results provide insight into reasons for low PrEP uptake among PWUD who live in a high HIV prevalence jurisdiction. Implications for HIV prevention intervention are discussed.

Using a Programme Science approach to substantially reduce the risk of HIV transmission and acquisition in sex transactions among female sex workers in Zimbabwe.

INTRODUCTION: We used a Programme Science platform, to generate evidence to support the implementation of programmes for sex workers in Africa. Female sex workers are estimated to make up 1.6% (1.3%-1.8%) of the population of women aged 15-49 years in Zimbabwe. We highlight how programme science can be used to help distinguish between when, where and with whom programmes need to be implemented and discuss two case studies that exemplify implementing better (Case study 1 (1 June 2019-30 June 2021) Optimizing implementation of a risk differentiated microplanning intervention) and implementing differently (Case study 2 (1 October 2016-30 September 2022) Reorientating implementation of DREAMS for young women selling sex). METHODS: Zimbabwe's nationally scaled programme for sex workers was established in 2009 in partnership with sex workers to provide comprehensive services for sex workers and generate evidence for programme design, implementation and scale up. Since inception, comprehensive data have been collected from all sex workers seeking services. As the scope of service provision has expanded so has the scope of data collection and analysis. At enrolment, sex workers are assigned an alphanumeric unique identifier which links consultations within and across programme sites. We conduct descriptive analyses of the Key Population (KP) programme data to guide programme implementation and redesign, embedding programmatic qualitative enquiry as required. RESULTS: Two case studies describing different approaches to programme optimization are presented. In the first, an optimization exercise was used to strengthen programme implementation ensuring that the KP programme got back on track after SARS-COV-2. In the second, an in-depth review of research and programme data led to a re-orientation of the DREAMS programme to ensure that young women at the highest risk of HIV acquisition were enrolled and had access to DREAMS social support interventions in turn strengthening their uptake of HIV prevention. CONCLUSIONS: Optimizing and sustaining HIV care and treatment programmes requires effective delivery with sufficient scale and intensity for population impact. Our programme science approach guided the scale up of the KP programme in Zimbabwe, providing evidence to support strategy, implementation and ongoing management, and importantly helping us distinguish between when we needed to just implement, implement better or implement differently.

Programme science methodologies and practices that address "FURRIE" challenges: examples from the field.

INTRODUCTION: "Programme science" deploys scientific methods to address questions that are a priority to support the impact of public health programmes. As such, programme science responds to the challenges of making such studies: (1) feasible to undertake, (2) useful, (3) rigorous, (4) real-world-relevant, (5) informative, and undertaken by (6) equitable partnerships. The acronym "FURRIE" is proposed to describe this set of six challenges. This paper discusses selected HIV/STI (sexually transmitted infection) programme science case studies to illustrate how programme science rises to the FURRIE challenges. DISCUSSION: One way in which programme science is made more feasible is through the analysis and interpretation of data collected through service delivery. For some questions, these data can be augmented through methods that reach potential clients of services who have not accessed services or been lost to follow-up. Process evaluation can enhance the usefulness of programme science by studying implementation processes, programme-client interactions and contextual factors. Ensuring rigour by limiting bias and confounding in the real-world context of programme science studies requires methodological innovation. Striving for scientific rigour can also have the unintended consequence of creating a gap between what happens in a study, and what happens in the "real-world." Community-led monitoring is one approach to grounding data collection in the real-world experience of clients. Evaluating complex, context-specific strategies to strengthen health outcomes in a way that is informative for other settings requires clear specification of the intervention packages that are planned and delivered in practice. Programme science provides a model for equitable partnership through co-leadership between programmes, researchers and the communities they serve. CONCLUSIONS: Programme science addresses the FURRIE challenges, thereby improving programme impact and ultimately health outcomes and health equity. The adoption and adaptation of the types of novel programme science approaches showcased here should be promoted within and beyond the HIV/STI field.

A sub-national HIV epidemic appraisal in Kenya: a new approach for identifying priority geographies, populations and programmes for optimizing coverage for HIV prevention.

INTRODUCTION: The HIV Prevention 2025 Roadmap, developed by UNAIDS, recommends the adoption of a precision prevention approach focused on priority populations and geographies. With reduction in new HIV acquisitions in many countries, designing a differentiated HIV prevention response, using a Programme Science approach, based on the understanding of the epidemic and transmission dynamics at a sub-national level, is critical. METHODS: To support strategic planning, an epidemic appraisal at the sub-national level across 47 counties, with the 2019 population ranging from 0.14 million in Lamu to 4.40 million in Nairobi City, was conducted in Kenya using several existing data sources. Using 2021 Spectrum/EPP/Naomi model estimates of national and sub-national HIV incidence and prevalence, counties with high HIV incidence and prevalence were identified for geographic prioritization. The size of local key population (KP) networks and HIV prevalence in key and general populations were used to define epidemic typology and prioritize populations for HIV prevention programmes. Analysis of routine programme monitoring data for 2021 was used to assess coverage gaps in HIV prevention programmes, including prevention of vertical transmission, anti-retroviral therapy, KP programmes, adolescent girls and young women programme, and voluntary male medical circumcision programme. RESULTS: Ten counties with more than 1000 incident acquisitions in 2021 accounted for 57% of new acquisitions. Twenty-four counties were grouped into the concentrated epidemic type-due to their low prevalence in the general population, high prevalence in KPs and relatively higher density of female sex workers and men who have sex with men populations. Four counties reflected a generalized epidemic, where HIV prevalence was more than 10% and 30%, respectively, among the general and key populations. The remaining 19 counties were classified as having mixed epidemics. Gaps in programmes were identified and counties where these gaps need to be addressed were also prioritized. CONCLUSIONS: The HIV burden in Kenya is unevenly distributed and hence the mix of prevention strategies may vary according to the epidemic typology of the county. Prioritization of programmes based not only on disease burden and epidemic typology, but also on the prevailing gaps in coverage for reducing inequities is a key aspect of this appraisal.

Programme science in action: lessons from an observational study of HIV prevention programming for key populations in Lusaka, Zambia.

INTRODUCTION: 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.

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.

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.