Global Trends in HIV Acquisition and Transmission
At the 2026 Conference on Retroviruses and Opportunistic Infections (CROI), several studies reported on trends in new HIV infections in sub-Saharan Africa. Kosgei and colleagues (Abstract 893) assessed HIV incidence in a cohort of female sex workers and men who have sex with men (MSM) in Kenya. From December 2021 to September 2024, they followed 407 people without HIV with quarterly clinic-based HIV testing and monthly Oraquick self-testing for up to 72 weeks. Among 374 participants analyzed, the median age was 22 years, and 79% were female (88% were involved in transactional sex) and 22% were male (37% were involved in transactional sex). HIV incidence was 2.53 per 100 person-years overall and 3.27 per 100 person-years among female participants, in whom all 12 seroconversions occurred. Among incident cases, 80% had depressive symptoms and 50% had concurrent bacterial sexually transmitted infections (STIs), but only 17% were on preexposure prophylaxis (PrEP) at enrollment and subsequently discontinued.
Kuchukhidze and colleagues (Abstract 888) identified high HIV burden geographic areas to prioritize scale-up of lenacapavir (LEN) PrEP in South Africa. Using routine service delivery data, they identified reliable proxies of HIV incidence. They found that HIV positivity at first antenatal care visit and HIV positivity in the population that was HIV negative (proportion of people with HIV among 1000 people without HIV) were most correlated with district HIV incidence, with the highest incidence rates seen in KwaZulu-Natal, Eastern Cape, and Mpumalanga subdistricts. When LEN rollout is focused on subdistricts with 30% of the population, they estimated that geographic prioritization of LEN could avert one-third more new infections than uniform geographic allocation. John and colleagues (Abstract 895) assessed recent HIV infections among newly diagnosed people in Tanzania. Between September 2023 and October 2024, they offered people newly diagnosed with HIV a rapid test for recent infection (RTRI), and those with a recent test result and an HIV viral load of 1000 copies/mL or higher were defined as having a recent infection testing algorithm (RITA)-recent infection. Among 20,020 people with a new HIV diagnosis and a valid RTRI test (68% female; median age, 34 years), 3.9% had a RITA-recent infection. RITA-recent infections were higher among females than males (4.5% vs 2.9%, respectively; P <.001) and higher in those who engaged in commercial sex in the past year than in those who did not (5.5% vs 3.8%, respectively; P <.001). In an adjusted model, younger people aged 15 to 19 years (adjusted odds ratio [aOR], 2.0) and 20 to 24 years (aOR, 1.5) had higher odds of a RITA-recent infection than those aged 30 to 34 years, and those who reported sex with a partner who was HIV positive in the past year were more likely to have a RITA-recent infection (aOR, 1.35) than those who did not. These findings can be used to guide targeted, population-specific HIV prevention services to reduce incident infections.
Tasaneeyapan and colleagues (Abstract 894) assessed demographic and regional patterns of recent HIV infections among MSM in Thailand. Thailand has integrated RTRI with HIV case surveillance data within their routine testing services, using RITA to identify people who likely acquired HIV within the past 12 months (defined as having RTRI-recent test and baseline CD4+ count >200 cells/μL). Between September 2022 and March 2024, a total of 2475 individuals were newly diagnosed with HIV, of whom 1209 (49%) were MSM. Among the newly diagnosed MSM, 103 individuals (8.5%) were classified as RITA-case surveillance recent. In multivariable analyses, MSM aged 15 to 24 years were more than twice as likely to have a recent infection than those aged 35 to 44 years (aOR, 2.28), and living in the Northern, Northeastern, Southern, or Bangkok metropolitan areas was associated with higher adjusted odds of having a recent infection than living in the Central region (aOR, 3.84–6.89). They recommend tailoring resources to these priority populations and geographic regions to promote early diagnosis and interrupt ongoing transmission.
Patel and colleagues (Abstract 922) reported on trends in HIV prevalence and incidence among MSM and people who inject drugs (PWID) in India. They conducted 3 crosssectional surveys (2012–2013, 2016–2017, and 2022–2024) among 8245 MSM across 3 cities and 16,496 PWID across 6 cities recruited through respondent-driven sampling. HIV incidence remained persistently high between 2012 and 2013 and between 2022 and 2024 among MSM (1.3% vs 1.9%, respectively; P = .35) and PWID (4.9% vs 5.9%, respectively; P = .25), and HIV prevalence increased from 7% to 20% (adjusted prevalence ratio [aPR], 2.0) among MSM and from 19% to 40% (aPR, 2.0) among PWID during this period. These trends were similar across age groups and occurred in the setting of increasing HIV viral suppression rates from between the periods of 2012 to 2013 and 2022 to 2024 (aPR, 3.2 for MSM; aPR, 2.2 for PWID), although viral suppression rates were lowest among young key populations with HIV (ie, <30 years of age). These findings highlight the importance of scaling up combination prevention services, including PrEP, to achieve HIV epidemic control in India.
Solomon and colleagues (Abstract 901) presented on HIV and hepatitis C virus (HCV) infection incidences in a spatially targeted person-centered clinic in India. In New Delhi, prior data suggested that 70% of all new infections among PWID were attributed to a single venue. In October 2023, through a public-private collaboration, they established “The Blue Shed,” a person-centered facility providing medical services, harm reduction, and social services. Between October 2023 and August 2025, a total of 1276 people (median age, 27 years; 98% assigned male sex at birth) registered for services at this facility. Overall, 88% were unemployed/daily wage earners; 87% reported injecting drugs in the past month, and 60% had a history of sharing injection paraphernalia. The prevalence of HIV, HCV infection, and hepatitis B surface antigen positivity was 45.2%, 74.1%, and 7.5%, respectively. HIV and HCV infection incidences were very high (35.1/100 person-years and 44.3/100 person-years, respectively). Most people visited the facility for food, showers, and harm-reduction services, and per service used at each visit was associated with reduced HIV incidence (adjusted incident rate ratio [aIRR], 0.43; 95% CI, 0.28–0.67). The researchers suggest that additional tools (eg, long-acting [LA] prevention and treatment) will be needed to reduce HIV incidence in this population.
Figueroa and colleagues (Abstract 893) reported on HIV incidence and associated risk factors in a transgender and nonbinary (TNB) cohort in Argentina. They enrolled 499 TNB individuals into TransCITAR (Trans-Specific Cohort in Argentina), a prospective cohort in Buenos Aires, of which 219 were HIV negative, and tested participants every 6 months during a 60-month period. There were 19 seroconversions during a median 42.3 months of followup (most occurring in the first 18 months), resulting in an HIV incidence of 2.75 per 100 person-years. In a multivariable model, sex work (hazard ratio [HR], 6.26) and sexualized drug use (HR, 5.08) were associated with HIV seroconversion, and PrEP use was protective (HR, 0.04). The researchers call for early and tailored prevention strategies for TNB individuals in this region, including timely PrEP, gender-affirming care, harm reduction, and structural interventions to address social vulnerabilities.
Reisner and colleagues (Abstract 192) reported on HIV incidence in a nationwide cohort of transgender women in the US and Puerto Rico. Recent structural and policy shifts have reduced gender identity data collection, and transgender women have faced increased political and structural barriers to care. Between March 2023 and December 2024, they enrolled 2504 transgender women without HIV into the Enhanced Cohort Methods for HIV Research and Epidemiology (ENCORE), a hybrid digital hub-supported community cohort. The median age was 32 years, 28% were non-White, 30% experienced poverty, and 49% had public insurance or were uninsured; 16% had a PrEP indication and 18% reported PrEP use (mostly oral PrEP) in the last 6 months. Overall, there were 39 new HIV diagnoses (25 at baseline, 14 during follow-up). HIV incidence was 3.95 per 1000 person-years overall, 15.45 per 1000 person-years in Black participants, 7.46 per 1000 person-years in Latino participants, 5.65 per 1000 person-years in Asian participants, and 16.27 per 1000 person-years in PrEP-indicated participants.
Baseline structural vulnerabilities were associated with HIV seroconversion, including being unhoused (risk ratio [RR], 4.06), engaging in sex work (RR, 4.88), poverty (RR, 5.83), and having public insurance or being uninsured (RR, 13.60). Additionally, baseline stimulant use (RR, 6.43), having a PrEP indication (RR, 9.55), and PrEP use (RR, 4.73) were associated with HIV seroconversion. The researchers call for tailored interventions and safe, gender-affirming prevention services for transgender women, along with continued gender-inclusive research infrastructure.
Balkus and colleagues (Abstract 900) reported on trends in HIV diagnoses among cisgender women in 3 West Coast counties in the US. Using data from the National HIV Surveillance System for King County, Washington (including Seattle), Los Angeles County, and San Francisco County between 2015 and 2024, they showed that rates of new HIV diagnoses declined among cisgender women from 2015 to 2020 but began rising in 2021, with 40%, 15%, and 63% higher rates for King County, Los Angeles County, and San Francisco County, respectively, in 2024 than in 2019. In 2024, the proportion of cisgender women who reported being homeless or unhoused at diagnosis was higher than for the overall population of newly diagnosed individuals (28% vs 20% for King County, 27% vs 14% for Los Angeles County, and 39% vs 16% for San Francisco County), and 1% of cisgender women across all 3 counties were diagnosed with syphilis in the 12 months prior to HIV diagnoses. The researchers call for improved access to stigma-free HIV screening, prevention, and treatment for cisgender women.
Shintani and colleagues (Abstract 902) reported on HIV and STI trends with rising PrEP and doxycycline postexposure prophylaxis (doxy-PEP) use among MSM in Tokyo. They analyzed data from the Sexual Health Clinic cohort of 2355 MSM between 2017 and 2025. HIV incidence declined from 2.8 per 100 person-years in 2018 to 0.2 per 100 person-years in 2022 and has remained low through 2025. PrEP use increased substantially during this period, with 55% of participants using PrEP by June 2025. STI incidence remained stable during this period despite increasing uptake of PrEP and doxy-PEP; 30% of participants reported using doxy-PEP in 2025 (including 8% using doxy-PEP without PrEP). Although the reductions in HIV incidence demonstrate the prevention potential of PrEP scale-up even without a national prevention program, the emerging use of doxy-PEP without PrEP underscores the need for integrated and equitable guidance to maximize preventive impact.
Risk and Protective Factors for HIV and STIs
Martin and colleagues (Abstract 903) reported on HIV transmission risk among individuals with low-level viremia. The World Health Organization guidance states that individuals with low-level viremia (200–1000 copies/mL) have “almost zero or negligible” risk of transmitting HIV to their sexual partners. The researchers therefore sought to quantify this transmission risk in settings with infrequent monitoring. Among 415 monogamous, serodifferent couples in the Rakai Community Cohort (1995–2022), there were 93 seroconversions among 940 couple-years of follow-up. They estimated 2.9 (95% CI, 1.1–7.5) and 0.6 (95% CI, 0.2–2.1) transmissions per 100 person-years at a viral load of 1000 and 200 copies/mL, respectively. Among people reporting antiretroviral therapy (ART) use and low-level viremia, 28% experienced viral rebound to more than 1000 copies/mL within 16 to 28 months. After accounting for viral rebound, they estimated 1.3 (95% CI, 0.8–2.0) transmissions per 100 person-years from individuals with low-level viremia. This risk could be reduced by 94% with 90-day vs annual monitoring. These findings suggest that transmission risk from low-level viremia is reduced but may not be nonnegligible, especially in the setting of infrequent monitoring. The researchers emphasized that their study findings do not call into question “undetectable = untransmittable” (U=U), which still holds true for viral loads below 200 copies/mL. It is important to note that much of this research was performed prior to the availability of integrase strand transfer inhibitors and that phylogenetic testing was not performed on paired samples.
Ssempijja and colleagues (Abstract 193) reported on the association between awareness of sex partner HIV status and population-level HIV incidence in the Rakai Community Cohort Study in Uganda. Between February 2010 and November 2020, awareness of sex partner HIV status increased from 44% to 73%, whereas HIV incidence declined over time during this period (overall, 0.72/100 person-years). In an adjusted model, an awareness of the HIV status of all partners was associated with a 49% reduction in HIV incidence (50% reduction in female participants and 54% reduction in male participants). Although the number of sex partners and marital status of never or previously married were associated with higher HIV incidence, the observed HIV incidence reduction was independent of number of sex partners and marital status. These findings highlight that serostatus awareness is a key protective factor and a crucial component of HIV prevention strategies.
Carlson and colleagues (Abstract 913) examined the influence of rurality on rates of new HIV and hepatitis C diagnoses in Tennessee, a largely rural state. They estimated that for each 10% increase in rurality, there was a 17.7% decrease in HIV infection rates, a 0.9% increase in HCV infection rates, and a 7.9% reduction in HIV/HCV infection rates. After accounting for modifiable mediating factors (eg, primary care physician density, chlamydia rate, and social vulnerability index), the effect of rurality on HIV risk was attenuated, and the effect on hepatitis C risk was nullified. These results suggest that HIV and possibly hepatitis C prevention should be strengthened in areas with poor health care access or high socioeconomic vulnerability to reduce rural-urban disparities.
LeCates and colleagues (Abstract 941) assessed the impact of behavioral and sociostructural risk factors on HIV risk among women in the urban South. In this retrospective cohort study of 333,263 cisgender women seen in the Grady Health System in Atlanta, Georgia, between 2012 and 2022, there were 617 women (0.19%) newly diagnosed with HIV. People with HIV were mostly Black (89%), with a mean age of 41 years. In a multivariable model, living in a high-incidence zip code (aOR, 4.5) and having a diagnosis of schizophrenia (aOR, 4.1), substance use disorder (aOR, 3.8), bipolar disorder (aOR, 3.4), or syphilis (aOR, 8.7) were associated with HIV. Population-attributable fractions were calculated and were highest for the sociostructural factors that were most prevalent: living in a high-incidence zip code accounted for 63% of HIV risk and elevated social vulnerability index accounted for 21%, compared with 13% for substance use disorder and 5% for bacterial STI diagnoses, which were uncommon. These findings suggest that incorporating sociostructural context into individual PrEP decision-making could help identify women who could benefit from prevention, particularly in high-incidence settings.
Javanbakht and colleagues (Abstract 899) examined the prevalence and correlates of transactional sex among men in Los Angeles, California. Between August 2014 and January 2025, they enrolled and followed 685 men in a prospective cohort study. At baseline, median age was 31 years, 43% were Black and 38% were Hispanic/Latino, and 53% were people with HIV (PWH). Across all study visits, 62% reported never engaging in transactional sex, 30% reported transactional sex at some but not all visits, and 8% reported it at every visit. Compared with those who reported transactional sex intermittently or not at all, participants who reported transactional sex at all visits had higher levels of unstable housing (63% vs 49% vs 27%, respectively; P <.001), methamphetamine use (75% vs 61% vs 37%, respectively; P <.001), and giving money, drugs, or other goods in exchange for sex (58% vs 26% vs 2%, respectively; P <.001). These findings support ongoing screening and integrating HIV prevention and care services with housing support and stimulant-focused treatment.
In an interactive symposium, Baral (Abstract 31) presented on the topic of structural determinants of HIV and STIs among gender-diverse communities. He began by pointing out that federal funding for surveillance, epidemiologic research, and structural intervention research and programs in gender-diverse individuals has been cut dramatically, despite these communities being disproportionately impacted by HIV. He shared data from the TWIST (Transgender Women's Internet Survey and Testing) study, an online behavioral survey of transgender women and transfeminine individuals undertaken annually in the US since 2019. Among a subset of 3057 TWIST participants, only one-third reported STI testing annually, with screening more common in those who reported condomless anal sex, those who disclosed their gender identity to a health care clinician, and those who were on current gender-affirming hormone therapy. Testing was less likely in younger individuals and those with severe depression. Among those tested for STIs, 16% reported having 1 or more bacterial STIs, with transgender women with HIV being 4.5-times more likely to report an STI diagnosis. Black and Hispanic participants were 2.3-and 1.6-times more likely to report an STI than White individuals, whereas those on genderaffirming hormone therapy were half as likely to report an STI diagnosis.
Regarding intersectional stigma, 63% of transgender women reported lifetime exposure to violence and harassment and 37% experienced social systems exclusion, which was significantly higher for transgender participants of color (prevalence ratio [PR], 1.71) and PWH (PR, 2.29). Furthermore, transgender women of color who reported social exclusion were nearly 4-times more likely to have HIV (PR, 3.82) and nearly twice as likely to have a bacterial STI (PR, 1.91). They determined that in states with more harmful health care policies, individuals who experienced health care stigma were less likely to report PrEP use (aOR, 0.7). They also examined the relationship between housing status and PrEP use, and concluded that those experiencing sheltered homelessness (eg, living in an emergency shelter or transitional housing) were more likely to be on PrEP than those who were stably housed (aOR, 1.78), suggesting successful PrEP outreach efforts in shelter settings; however, this relationship was seen only in transgender women aged 25 years and older.
Baral also reported results from a 2025 study of 496 transgender women (median age, 27 years) in Liberia. They determined that the weighted HIV prevalence was 23% and STI prevalence was 11%, with only 52% of participants ever undergoing testing for HIV. There was a high burden of gender-identity stigma, including family exclusion (25%), family gossip (34%), and friend rejection (20%). Importantly, structural determinants were predictors of HIV diagnosis among transgender women, including being criminalized (aPR, 1.92), having police refuse protection (aPR, 2.37), being scared in public spaces (aPR, 1.63), and experiencing physical violence (aPR, 1.41); and individual risk behaviors (eg, condomless sex, numerous sexual partners) were not predictive of HIV diagnosis. These findings point to the powerful role of structural determinants in driving disparities in HIV and STI outcomes in transgender women.
Several studies described the use of molecular epidemiology to characterize local HIV transmission chains and identify HIV transmission clusters. Dennis and colleagues (Abstract 890) examined whether network bridges can predict emerging HIV transmission hot spots in North Carolina. She explained that molecular clusters often contain embedded recent subclusters, which are focal areas of rapid transmission within established networks. They defined “bridging individuals” as those who connect distinct subclusters within larger clusters. Using HIV surveillance data in North Carolina from 2010 to 2025, they determined that viremic bridge members occupy highly central network positions that were highly connected (median degree, 9 vs 2 for nonbridges). Baseline viremic bridging predicted subcluster growth, even after adjusting for structural position and cluster size. Additionally, among clusters with recent and rapid subclusters, 78% of viremic-bridging ties span counties, suggesting that bridging positions can link focal growth across jurisdictions and serve as high-impact intervention points to prioritize responses before subclusters accelerate.
Serwin and colleagues (Abstract 877) reported on HIV-1 sub-subtype A6 international transmission patterns across several European countries. HIV-1 sub-subtype A6 is important to recognize because it confers increased likelihood of treatment failure with resistance during the administration of cabotegravir/rilpivirine. They analyzed publicly available HIV-1 sequences along with migration-related metadata from Poland, Czechia, Israel, and Germany from 2011 to 2023 and identified 4093 sequences (26%) forming broad transmission clusters. Over time, migrant inclusion in transmission links increased significantly from 6.3% in 2021 to 14.6% in 2023, as did transmission links involving female individuals, which increased from 2.2% to 5.8% during the study period. Although within-country transmission was most common, they noted substantial cross-border links between Germany and Poland and between Czechia and Poland. These findings suggest that cross-border transmission is an expanding component of the European HIV-1 A6 epidemic, likely a result of migration and recent war-related displacement, highlighting the need for coordinated, cross-jurisdictional prevention strategies focused on mobile populations to limit further HIV transmission.
Adams and colleagues (Abstract 876) compared 2 HIV cluster-detection methods in rural Washington state. They analyzed HIV surveillance data in this region from 2020 to 2024 to identify HIV transmission clusters employing (1) time-space methods that use spatiotemporal proximity, and (2) molecular HIV surveillance methods that use genetic distance. Each method identified 7 clusters, with molecular surveillance capturing mainly urban clusters and time-space identifying urban and rural clusters. In rural areas, 20% of new HIV diagnoses were included in clusters (time-space, 95%; molecular surveillance, 5%), compared with 40% in urban areas (time-space, 87%; molecular surveillance, 13%). Only 2% of people identified in a time-space cluster were also identified in a molecular cluster and only 3% identified in a molecular cluster were also found in time-space clusters. The researchers suggest that jurisdictions should use both methods to detect HIV transmission clusters, particularly in areas with increasing rural HIV diagnoses.
Bridges and colleagues (Abstract 882) explored heterogeneity in community priorities for HIV molecular epidemiology among 747 MSM (134 with HIV) participating in the American Men's Internet Survey. In aggregate, “ensuring privacy” was given the highest priority (17%) and community engagement was considered the least important (2%). Using latent class analysis, they identified 2 groups with distinct priorities. The “Use the Data” group (63%) prioritized the use of HIV molecular epidemiology to identify and respond to HIV clusters, study HIV evolution, and evaluate HIV prevention, and the “Protect the Data” group (37%) wanted to ensure data privacy, obtain permission to use it, provide disclosure about its use, and prevent law enforcement access to the data. These priorities did not differ by HIV status.
Hall and colleagues (Abstract 1055) examined how national and state HIV prevention funding trends influenced HIV diagnosis rates in the US. Using retrospective time-series regression modeling and funding and HIV diagnosis rate data collected from 2008 to 2023, they estimated that for each $1-million increase in annual federal funding to state health departments, there was an associated 0.015 decrease in new HIV diagnoses per 100,000 people (P = .066). Decreases were greater for males than for females (P = .029) and in Black people (P<.001) and Hispanic (P = .006) populations, and those aged between 13 and 24 years experienced the greatest effect over time. Additionally, the effect of HIV prevention funding was significantly different in Medicaid expansion vs nonexpansion states (P <.001), suggesting that concurrent policy solutions are needed to bolster federal funding reach for HIV prevention.
Glaubius and colleagues (Abstract 1091) modeled the potential impact of reaching Ending the HIV Epidemic (EHE) Targets in Missouri. Using an established HIV epidemic model, they analyzed 3 scenarios: (1) business as usual, in which service coverages remained constant at 2023 levels through 2030; (2) EHE targets reached including 95% people aware of their status, 95% linked to care, 95% viral suppression, and 50% PrEP coverage by 2030; and (3) Medicaid disruptions resulting in loss of ART or PrEP coverage among Medicaid recipients. In the business as usual scenario, new infections in 2030 increased 9% over 2020 levels, with 3453 new infections projected to occur cumulatively from 2024 to 2030. In contrast, reaching EHE targets reduced new infections by 35% during the 2024 to 2030 period. In the Medicaid disruption scenario, coverage of ART fell by up to 9% and PrEP by 7%, which could increase new infections by up to 10% in this period. These results highlight the importance of reaching EHE targets and preserving access to ART and PrEP in Missouri.
McGreevy and colleagues (Abstract 993) modeled Scotland and Ireland's progress toward 2030 Joint United Nations Program on HIV/AIDS (UNAIDS) HIV transmission elimination goals. Using a Markov HIV transmission model, they demonstrated that Scotland and Ireland have already achieved the UNAIDS HIV elimination target for their total population, and for heterosexual men, women, and PWID. In contrast, MSM are not expected to meet the 2030 UNAIDS target under current intervention conditions. However, with moderate increases in HIV testing, treatment, and PrEP utilization rates among MSM, they estimate that Scotland could achieve HIV transmission elimination targets by 2030 and Ireland by 2035.
HIV Testing
Perez Elias and colleagues (Abstract 158) presented results from a cluster randomized clinical trial of HIV rapid testing and digital risk assessment in primary care centers in Spain. From July 2023 to February 2025, they conducted a stepped wedge trial in which 8 primary care centers were randomly assigned sequentially to control, rapid HIV testing, and rapid testing plus a digital risk-assessment questionnaire, in which an automatic email was sent to the participant and their practitioner to perform an HIV test and refer to the PrEP clinic if risk was identified. Overall, 14,644 HIV tests were performed, including 692 HIV rapid tests, and 63 participants had positive HIV tests, including 23 new HIV diagnoses (5 by rapid test). Compared with the observation period, HIV screening rates increased in the rapid testing phase (IRR, 1.67; 95% CI, 1.30–2.14) and the rapid testing plus questionnaire phase (IRR, 1.83; 95% CI, 1.60–2.10), with no significant change observed in the control phase (IRR, 1.26; 95% CI, 0.80–1.63). Total HIV diagnoses increased significantly in all rapid testing plus questionnaire (IRR, 2.50) and control groups (IRR, 3.59) compared with the observation period; however, there were no significant increases in new HIV diagnoses observed in any group, suggesting the need for improved risk stratification to reach undiagnosed individuals.
Long and colleagues (Abstract 159) reported on enhanced opt-out HIV screening and linkage to care across 13 community health centers in the US. From 2021 to 2024, they implemented universal opt-out HIV screening that was integrated into electronic health record workflows, coupled with supported linkage to care services. Across 13 federally qualified health centers in Florida, New Mexico, and Puerto Rico in which data were collected, they screened 216,157 individuals for HIV and identified 1948 positive cases (0.9%) including 281 new diagnoses and 1667 who were previously diagnosed but out of care. Overall, 100% of positively diagnosed cases were successfully linked to care, 91% of whom were linked within 30 days of diagnosis. Having a positive HIV screen was associated with being assigned male sex at birth (aOR, 2.32), being non-Hispanic Black (aOR, 2.90), being uninsured (aOR, 1.84), being a current tobacco smoker (aOR, 1.38), having a mental health disorder (aOR, 1.35), and being Creole-speaking (aOR, 2.32), the latter of which was also associated with timely linkage to care (aOR, 4.35). These findings highlight the role of opt-out HIV screening in federally qualified health centers to identify new and previous out-of-care people with HIV and offer a scalable blueprint for nationwide adoption.
Hudon and colleagues (Abstract 160) presented on electronic health record-driven HIV screening in emergency departments (EDs) in the Southeastern US. Beginning in January 2022, they launched a universal HIV screening protocol using remnant blood from standard of care visits across 4 EDs in South Carolina in individuals who had not been tested for HIV in the past year. They created daily electronic health record (EHR) reports of all positive HIV tests in the region (from remnant blood or traditional clinician workup). From January 2022 to December 2023, there were 127 new HIV diagnoses identified, 32 of which were through the remnant blood screening protocol, accounting for 35% of diagnoses within their medical system. New diagnoses via remnant blood screening were more likely to be among females (31.3% vs 14.7%) and those who reported exclusive heterosexual (50% vs 32.6%) or bisexual activity (28.3% vs 10.5%) than clinician diagnoses. Diagnoses via clinicians were more likely among those who reported exclusive MSM activity (42.2% vs 6.3%) than those via remnant blood diagnoses. Among the 117 individuals with nonacute HIV diagnoses, there were on average 3.8 missed opportunities for HIV screening at prior visits within the past year; among the 10 individuals with acute HIV diagnoses, there were 3.4 missed opportunities for PrEP discussions in the past year. Within their medical system, 97% of new diagnoses were notified of the results, 86% of those aware were linked to care, and 86% of those achieved viral suppression. Based on the success of this program, the researchers recommend expanding remnant blood screening beyond EDs.
Guardiola and colleagues (Abstract 964) reported on HIV detection in EDs using a targeted screening protocol. Between 2021 and 2025, a total of 25 EDs in Catalonia, Spain, implemented an opt-in strategy to test every patient with targeted conditions as recommended by their national Consensus Document (CD). During this period, 47,198 HIV tests were performed, of which 45% were conducted under the CD-defined indications. Overall, 427 new HIV diagnoses were made, for an overall prevalence of 0.90%, with 51% occurring in CD-identified risk conditions, ie, STI (0.8%), chemsex (4.6%), PEP (0.4%), mononucleosis-like syndrome (1.6%), pneumonia (1.2%), and herpes zoster infection (1.4%). At one participating hospital, 58% of patients were linked to HIV care within 1 month, and all patients retained in care achieved virologic suppression.
Sizemore and colleagues (Abstract 965) reported on HIV testing and positivity rates among patients tested for STIs in 2 urban EDs in the US South. From September 2024 to August 2025, a total of 3674 ED patients were tested for STIs. STI positivity rates were higher in the community than in an academic ED setting (23.6% vs 14.3%, respectively; P <.0001); however, HIV testing rates were lower in the community than in an academic ED setting (18.3% vs 30.7%, respectively; P <.0001). The HIV positivity rate among patients tested for STIs was 12.2% for the academic ED and 7.1% for the community ED. They estimated 10 missed HIV infections in the academic ED and 40 missed HIV infections in the community ED among STI-tested patients who were not tested for HIV. Given the inconsistencies in HIV testing across sites, they recommend universal ED-based routine HIV screening with expanded linkage to care and prevention services.
Bye and colleagues (Abstract 966) assessed the impact of 2 novel clinical decision support tools on rates of HIV screening in EDs among patients tested for STIs. In January 2024, 11 freestanding EDs in Colorado implemented a comprehensive STI order panel including HIV antigen/anti-body testing, syphilis screening, gonorrhea and chlamydia testing, and optional vaginal trichomoniasis testing, and in January 2025, they implemented the Comprehensive STI Agile MD Pathway, which included an STI screening algorithm, the STI Order Panel, guidelines for treatment, and linkage to the infectious diseases clinic for STI, PrEP, and HIV care. HIV cotesting increased from 3% prior to the interventions (2022–2023) to 11.7% after the introduction of the first tool (2024) and to 16.3% after the introduction of the second tool (2025). These improvements were larger in the Denver metropolitan region (increased from 3.4% to 23%) than in the outlying areas (increased from 2.0% to 8.6%). Rates of positive screens in the metro region EDs increased from a baseline of 0.07% to 0.23% in 2025, whereas the rates of positive screens in the outlying EDs were lower and did not increase consistently.
Kyalo (Abstract 161) presented on the use of machine learning to optimize HIV risk prediction and case identification in Eastern Kenya. They applied a machine-learning algorithm with inputs including demographics, STI history, prior HIV testing, and partner characteristics to classify the risk of individuals as low, moderate, high, and very high risk for HIV. In a retrospective analysis of EHR data from 58 health facilities from January 2024 to March 2025, a total of 39,995 individuals were tested for HIV, with an HIV positivity rate of 1.6% (n = 620). In an adjusted model, individuals in the moderate, high, and very high-risk groups had 2.62, 5.21, and 16.59 higher odds, respectively, of testing positive than in the low-risk group. Patients tested in prevention of mother-to-child transmission service delivery points (aOR, 0.48) and repeat testers (aOR, 0.77) had lower odds of testing positive.
Raji and colleagues (Abstract 1122) reported on the effectiveness of integrated community testing campaigns to increase testing coverage and case detection among pregnant women in Nigeria. In 2024, they implemented community-based HIV and syphilis testing in nonfacility settings (eg, traditional birth attendants, faith homes, and other community settings). In 2023 (baseline), 2,810,560 pregnant women were tested in facilities, with a 0.29% HIV positivity rate and 0.17% syphilis positivity rate. In 2024, community testing reached 407,302 pregnant women, with an HIV yield of 0.21% and syphilis yield of 0.49%, contributing an additional 11% of cases that were HIV positive, and in 2025, a total of 640,917 pregnant women were tested, with an HIV yield of 0.23% and syphilis yield of 0.28%, contributing an additional 18% of cases that were HIV positive. Detection of coinfections also increased from 43 to 158 for HIV/hepatitis B virus (HBV) coinfections and 29 to 99 for HIV/HCV coinfections. These findings suggest that scaling community-based HIV and syphilis testing could facilitate dual HIV/syphilis elimination in Nigeria.
In a themed discussion, several researchers investigated the use of HIV self-testing to increase testing, identify new diagnoses, and reach untested individuals. De Nooy and colleagues (Abstract 975) used routine data to identify where HIV self-screening would have the biggest impact in South Africa. HIV self-test distribution was associated with 2.3 additional positive results per 100 tests, compared with 3 additional positive results per 100 tests for facility-based tests. The largest impact was observed through community distribution of HIV self-tests, in lower-and middle-prevalence districts, and in those with high treatment gaps. Namulema and colleagues (Abstract 974) reported on the use of HIV self-testing distributed by motorcycle-taxi drivers in Kampala, Uganda. They trained 6 motorcycle-taxi drivers to distribute HIV self-tests and provided testing education and support to fellow drivers, passengers, night food vendors, sex workers, and other community contacts. Individuals who tested negative were provided information about PrEP and male circumcision, and individuals who tested positive were escorted to the facility for confirmatory testing, partner notification, and linkage to care. Over a 12-month period, 2409 kits were distributed by the drivers and 97% of kits were utilized. There were 177 individuals (8%) with positive results, and upon facility testing, 25 were false positives, 13 declined confirmation, and 139 (6%) were confirmed positives. Through assisted partner notification, 147 partners were tested, of whom 32 (22%) were identified as new positive partners. These findings highlight the power of leveraging community and social networks to increase the reach of testing.
Closs and colleagues (Abstract 976) presented on the use of vending machines as stigma-free access points for HIV and syphilis testing and condoms in Memphis, Tennessee, which ranks second in the US for new HIV diagnoses. From May to August 2025, they deployed 3 stigma-free safer sex vending machines in a public library; a lesbian, gay, bisexual, transgender, queer, and other gender identities and sexual orientations (LGBTQ+) bar; and a university setting. Participants completed an online questionnaire, received free access to HIV/syphilis tests and condoms, and had follow-up with a case manager 1 week later. In the first 100 days of deployment, they reached 326 unique individuals from 62 zip codes; 49% were Black females, 42% were between the ages of 25 and 34 years, and 29% had not tested in the past year. There were 2 new diagnoses that were linked to care and 17 PrEP appointments were scheduled. These findings suggest that vending machines are a scalable, community-centered strategy to promote HIV prevention and sexual health.
Knights and colleagues (Abstract 910) reported on new HIV diagnoses in a county jail in Dallas, Texas. In a retrospective review of EHR data, there were 200 individuals newly diagnosed with HIV at the jail from 2015 to 2023, and rates significantly increased after a systematic, opt-out HIV testing program was implemented in 2020. Among people newly diagnosed with HIV in the jail, 43% reported heterosexual sex as their HIV risk factor, 66% reported active substance use, 44% had a bacterial STI, and 26% had unstable housing. Rates of new HIV diagnosis in the jail were 3-times the county rate and 9-times the national rate. The median CD4+ count at diagnosis was 529 cells/μL, suggesting that most diagnoses were made early in the disease course. These findings highlight the urgent need for comprehensive HIV testing in correctional settings.
Balasubramanian and colleagues (Abstract 886) reported on the potential impact of ending funding by the US Centers for Disease Control and Prevention (CDC) for HIV tests. Using the Johns Hopkins Epidemiologic and Economic model, they projected incidence forward under 2 scenarios where all CDC-funded HIV testing ends in February 2026, and (1) never resumes, and (2) returns to previous levels from January to December 2029. Across 25 states, they projected 12,714 additional infections by 2030, 10% more infections than if testing had continued. If testing resumed in January 2029, they estimated 10,397 excess infections, or 8% more infections than if testing had continued. They predicted more excess infections in states that perform more CDC-funded tests and have more rural HIV epidemics. Additionally, the proportion of people who can find an alternative means of testing impacted protected excess incidence; they projected 5% more infections if more than two-thirds found alternative testing, and 16% more infections if fewer than one-third were able to find an alternate test. These findings highlight the value of CDC testing activities in reducing HIV transmission in the US.
Novel Interventions
Two presentations reported on the feasibility and early outcomes of barbershop-based HIV interventions. Lukyamuzi and colleagues (Abstract 1064) implemented a barbershop-based HIV prevention intervention in fishing communities in Uganda in the HIV Prevention Trials Network (HPTN) 111 study. Barbershops were randomly assigned 2:1 to the intervention or standard of care (referral to routine HIV prevention at HIV care centers). Intervention barbers were trained to deliver status-neutral HIV education, distribute HIV self-test kits, and facilitate peer support discussions. From March to June 2024, barbers recruited 250 male clients (median age, 29 years; 75% reported transactional sex in the past 3 months), and barber delivery of the intervention components was high, with 100% of participants in the intervention arm receiving HIV education, 92% taking a self-test kit, and 99% attending a peer group discussion. Feasibility and acceptability of the barber intervention were high, and participants in the intervention arm were more likely to report self-initiated HIV testing (81% in the intervention vs 33% in the standard of care arms; P<.001).
Perkins and colleagues (Abstract 1065) presented on Cutting Out Stigma, a barbershop-based education and multimedia intervention in Tennessee. In a 6-month pilot trial, they trained 50 barbers as men's health ambassadors to provide sexual health education, refer clients to HIV services, and share social media posts to reduce HIV stigma. There was broad reach within barbershops (733 patrons/month) and on social media (25,670 people/ month), and a substantial number of resource referrals (533 referrals/month). HIV and PrEP knowledge of barbers increased after the intervention. In a mixed-methods analysis, barbers expressed high enthusiasm and reported personal and community benefits. These results suggest that barbershops can be scalable, community-based settings to reduce stigma and promote sexual health in Black communities in the South.
Mancuso and colleagues (Abstract 1072) assessed the impact of school-based HIV prevention for adolescent mothers across 8 countries in East and South Africa. In a pooled analysis of 2810 adolescent mothers aged 15 to 19 years in the Population-Based HIV Impact Assessment surveys from 2019 to 2022, 10% of adolescent mothers reported receiving school-based HIV prevention programs in the past year. Increasing exposure to these programs was estimated to reduce condomless sex overall, but had minimal impact on PrEP interest, possibly due to variation in PrEP availability and high baseline interest in PrEP.
Agbaje and colleagues (Abstract 973) reported on the impact of peer-led microplanning for HIV prevention among adolescent girls and young women (AGYW) in Nigeria. Through a Global Fund grant, they implemented structured microplanning strategies, which included risk-stratified outreach, safe-space sessions, and participatory accountability with voices from support group sessions. Services provided included PrEP eligibility screening, HIV testing, referrals for gender-based violence, and ART initiation. From December 2024 to August 2025, they reached more than 1.6 million AGYWs with the peer-led microplanning intervention. Community-based testing achieved high coverage with a 0.13% HIV positivity rate, whereas facility testing had a 5-fold higher yield with a 0.65% positivity rate. Young women aged 20 to 24 years accounted for 77% of the 434 AGYWs who tested positive, and all were successfully linked to care.
Beloumou and colleagues (Abstract 1067) assessed the impact of an HIV prevention “social vaccine” on HIV testing in Cameroon. They used the Risk Communication and Community Engagement framework to implement HIV education and testing focused on students, teachers, tutors, and community leaders in high-prevalence regions, and 24 multimedia centers were established in participating communities to support these efforts. Between 2019 and 2023, they enrolled 1203 participants (median age, 18 years) across 45 localities. Overall, the HIV test acceptance rate was 98% and the HIV positivity rate was 1.4%. Individuals with positive tests were older, with the highest rates in those aged 30 to 39 years. Participants in rural areas had the highest positivity rates.
Heise and colleagues (Abstract 1073) examined the impact of state legislation allowing pharmacist dispensation of PrEP in California. In October 2019, California State Bill 159 (SB159) was introduced and broadened the authority for pharmacists to prescribe PrEP without physician approval. Using a claims-based dataset of PrEP prescriptions in an interrupted time series analysis, they observed a significant increase in pharmacist-prescribed PrEP from a median of 4.5 to 12 pharmacists per quarter from before to after SB159 implementation. However, PrEP prescriptions plateaued following SB159 implementation, with the growth rate decreasing from 7% to 1% per quarter among males. The researchers posit that this limited impact may have been due to inadequate pharmacist training, restrictions preventing prescription continuation, barriers to laboratory testing, difficult reimbursement pathways, and COVID-19 health care disruptions. Although shelter-in-place orders were associated with an initial 33% reduction in HIV diagnoses, these rebounded to 13% above prepandemic levels by late 2021. In 2024, new legislation (SB339) was enacted to address barriers identified in SB159, including authorizing follow-up PrEP prescribing by pharmacists and ensuring insurer coverage of pharmacist-furnished PrEP.
Haberer and colleagues (Abstract 1079) described the use of natural language processing of WhatsApp messages to identify unrecognized HIV prevention needs among young women in Kenya. They used this artificial intelligence method, which can extract meaning and subjective information from text, to analyze deidentified WhatsApp messages from 413 young women (median age, 22 years) from 4 clinical sites in Kenya. They calculated the VOICE (Vaginal and Oral Interventions to Control the Epidemic) HIV risk score based on questionnaire responses and determined that the median VOICE risk score was 7 for women who most often messaged a sex partner vs 5 for those who most often messaged a friend. Topics discussed correlated with the VOICE risk score, which was highest for romance/ affection topics and lowest for faith/positivity and transactions/family topics. The researchers suggest that future app development with natural language processing could alert people to their risk and guide them to seek HIV prevention services.
Green and colleagues (Abstract 1099) reported on the impact of an EHR intervention to improve linkage to comprehensive HIV prevention services in Arkansas. Within a multisite, federally qualified health center serving rural populations, they implemented an optimized EHR workflow that included standardized eligibility identification criteria, reporting tools to identify eligible patients, and workflow integration involving pharmacists to support referrals to prescribing services. In the year prior to implementation, 10,894 individuals tested negative for HIV and were assessed for eligibility for linkage to comprehensive HIV prevention services, but only 561 (5.1%) were identified as eligible; of those, 29 (5.2%) were linked to prescribing services. After implementation, 10,735 tested negative and 8778 (81.8%) were identified as eligible; of those, 6934 (79%) were linked to prevention services. These findings suggest that EHR-driven workflows and pharmacist-integrated care models can help expand access to comprehensive HIV prevention services.
Preexposure Prophylaxis
Oral PrEP
Molina and colleagues (Abstract 127) reported on the final results of the ANRS PREVENIR (Prevention of HIV in “Île-de-France”) study of daily vs on-demand coformulated tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) PrEP for MSM and transgender women (TGW) in Paris, which took place from May 2017 to May 2025. The main goal of the study was to evaluate the impact on the number of new diagnoses among MSM and TGW in the Paris region; secondary outcomes were uptake of the 2 regimens and safety and tolerability. They enrolled 3209 individuals, of whom 99% were MSM and only 14 were TGW; 82% were French-born. Although they reported a median of 10 partners in the prior 3 months at baseline, they reported a median of only 2 condomless sex acts in the prior 4 weeks. Participants were allowed to choose daily vs on-demand PrEP and to switch between regimens. At baseline, approximately half chose on-demand PrEP, and that number remained relatively constant over time. By 3 years, more than half of either group had switched to the other regimen at least once. They measured 13 breakthrough infections: 7 taking predominantly on-demand dosing, 3 taking predominantly daily dosing, and 3 spending approximately half of the time on either regimen. Overall incidence was 0.1% per year, with no significant difference between groups. Gastrointestinal adverse effects in the on-demand group were almost twice as frequent as those in the daily group (4.5% vs 2.3%, respectively), but discontinuation due to drugrelated adverse effects was low (0.3%/year). During that time, there was a steady increase in the number of people taking PrEP in the Paris region, peaking at more than 25,000 by 2025. Although the number of new HIV infections in the Paris region decreased significantly among MSM born in France (−33%), there was a significant increase in the number of new infections among MSM born outside of France (+73%) and among TGW (+95%). This suggests a focused need for PrEP delivery to these populations.
Injectable PrEP
Ndlovu and colleagues (Abstract 128) presented data from the end of the randomized blinded phase of PURPOSE 1 (Preexposure Prophylaxis Study of Lenacapavir and Emtricitabine/Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection), a phase III randomized clinical trial of injectable LEN vs oral PrEP in cisgender women aged 16 to 25 years in sub-Saharan Africa. Among 2134 participants receiving LEN, there were 2 new HIV acquisitions compared with a total of 77 HIV acquisitions in the 2 oral PrEP arms (FTC/TAF and FTC/ tenofovir disoproxil fumarate [TDF]), a 96% reduction in HIV acquisition compared with FTC/TDF. Of the 2 participants acquiring HIV, 1 was positive for HIV at week 65, but the week 52 stored sample showed a very low level of HIV-1 RNA, despite on-time injections and LEN blood levels in the expected range and above the predicted protective threshold. The other participant had discontinued LEN injections and switched to open-label FTC/TDF; she had a high viral load (134,000 copies/mL) at week 95, 16 months after her last LEN injection, and a very low levels of LEN in her blood. There were no new safety concerns and no additional discontinuations due to injection-site reactions (ISRs) compared with the previously reported results. These data reinforce the very high levels of efficacy of LEN used as PrEP in this population.
Cantos and colleagues (Abstract 129) presented data from PURPOSE 2 (Study of Lenacapavir for HIV PreExposure Prophylaxis in People Who Are at Risk for HIV Infection), a phase III randomized clinical trial of injectable LEN vs oral FTC/TDF in MSM and transgender and nonbinary participants globally. There was 1 new HIV acquisition to add to the 2 previously reported, resulting in an overall efficacy of 88% compared with FTC/TDF. This 1 new acquisition occurred despite on-time injections and LEN levels on par with levels seen in other participants. The acquisition was diagnosed at week 52 with a positive antigen/antibody test and a viral load of greater than 2 million copies/mL. There was no delay in diagnosis. In this study, there were no new safety concerns and no additional study discontinuations due to ISRs. Similar to PURPOSE 1, this study reinforces the high efficacy of LEN in this population.
Cox and colleagues (Abstract 130) presented data on resistance among breakthrough infections from participants randomly assigned to LEN in PURPOSE 1 and 2. Of the 5 total infections between the 2 studies, 3 participants had the N74D mutation and 1 participant had Q67H and K70R mutations. The fifth participant was on FTC/TDF at the time of HIV acquisition and had no resistance mutations detected. The authors postulated that the capsid mutations seen were due to ongoing monotherapy with LEN rather than from transmitted drug resistance. To support this hypothesis, they presented data from more than 24,000 samples in the Los Alamos database, of which only 4 had N74D. There were no N74D mutations in another database of nearly 1500 samples across various clades. Among the 89 infections acquired in the 2 studies on FTC/ TAF or FTC/TDF, only 5 had resistance mutations to these agents, with the majority from suboptimal adherence. The authors reinforced that HIV acquisition was rare among those on LEN and posited that the resistance mutations seen were from monotherapy on LEN.
Tao and colleagues (Abstract 1062) presented data on real-world medication use and potential interactions with LEN for PrEP. Using a national US database of prescription drugs, they concluded that 83% of PrEP users were taking concomitant prescription medications in 2024. Among those, only 0.5% of PrEP users had concomitant use of a strong or moderate CYP3A inducer that would require a LEN dose modification. Fewer than 13% of users had concomitant use of a sensitive CYP3A and a P-glycoprotein substrate that would require monitoring for adverse effects or dose modification when taken with LEN. The most common drug was erectile dysfunction medication (11%). The authors found it reassuring that drug-drug interactions may affect only a minority of PrEP users.
Parikh and colleagues (Abstract 986) presented data on diagnostic outcomes after detectable HIV-1 RNA level in persons on long-acting cabotegravir (CAB-LA) from the SeroPrEP (Seroconversion on PrEP) study. Those on CABLA were referred to the study from US clinics if they had a reactive HIV-1 RNA test with a nonreactive antigen/antibody test. Of 9 male participants in this analysis, 8 participants had a single detectable HIV-1 RNA level on clinical testing. Subsequent HIV-1 RNA testing was negative, indicating that these individuals had not acquired HIV. One participant had 2 positive HIV-1 RNA tests and was subsequently determined to have acquired HIV. The authors suggest that more than 1 positive HIV-1 RNA test may indicate HIV acquisition, but that larger studies are needed.
Parikh and colleagues (Abstract 987) also reported on characterization of HIV acquisition on CAB-LA from the ImPrepCab Brazil (Implementation of Preexposure Prophylaxis of Injectable Cabotegravir) study. They diagnosed 4 HIV acquisitions among 1220 participants on CAB-LA. Of the 4 newly acquired infections, 3 had HIV-1 RNA level below 1000 copies/mL at diagnosis and delayed antibody detection (2–9 months after the first detectable HIV-1 RNA level). Major integrase strand transfer inhibitor (InSTI) mutations were observed in only 1 participant despite ongoing use of CAB-LA prior to HIV confirmation. The authors reiterated the high effectiveness of CAB-LA in preventing HIV acquisition but underscored the need for sensitive point-of-care diagnostics and additional data on responses to InSTI-based treatment in these clinical scenarios.
Fox and colleagues (Abstract 988) reported on a randomized crossover design trial comparing the acceptability and objective measures of ISRs of 1 CAB-LA dose vs 1 LEN dose among 63 participants. They report that participants experienced fewer ISR events after CAB-LA than after LEN injections (nodules, 57% vs 100%, respectively; induration, 20% vs 87%, respectively; and swelling, 36% vs 60%, respectively). ISRs also resolved more quickly after CAB-LA than after LEN injections (6% vs 82%, respectively, had nodules >180 days). Participants were queried at day 190 about the acceptability of local reactions and pain and CAB-LA was more likely to be considered “very or totally acceptable” (70% vs 37% with LEN). Overall, 85% of participants indicated a preference for CAB-LA over LEN at day 190. However, there are several caveats to this study. This ViiV-funded study did not provide information on methods of LEN administration, such as whether or not ice was used to reduce the pain associated with injections. Also, the regimen was a single injection and did not therefore replicate ISRs and acceptability of the different regimens in real-world practice.
Caruso and colleagues (Abstract 1003) presented data on weight change after CAB-LA initiation among PrEP-naive users and those switching to CAB-LA from daily TDF/ FTC. They followed 171 participants receiving CAB-LA for PrEP (86% of whom were taking daily TDF/FTC at CAB-LA initiation) through 4 injections. Mean weight change was +0.3 kg (range, −9 to +12 kg) among switchers and −0.3 kg (range, −10 to +5 kg) among those new to CAB-LA, with a median weight change across both groups of 0.0 kg. It is reassuring that neither group appeared to have weight change as a result of CAB-LA initiation.
PrEP Awareness, Willingness, and Uptake
Jones and colleagues (Abstract 939) presented data from the American Men's Internet Survey (AMIS) from the 2021, 2022, and 2023 cycles. Of the nearly 16,000 men who participated across the 3 cycles, almost all were aware of daily oral PrEP, and although awareness of on-demand and CAB-LA PrEP increased, it remained below 50% for both. Oral options were most preferred. Among those who had used PrEP in the past 12 months, only 1.4% and 3.5% reported CAB-LA use in 2022 and 2023, respectively. Black MSM were more likely than White MSM to report CABLA PrEP use (OR, 2.3) and rural MSM were less likely than urban MSM to use CAB-LA (OR, 0.4). The authors stated that previous studies indicated a strong preference for CAB-LA among rural MSM, so the lower use may represent access, delivery, clinician, or information barriers that disproportionately affect rural communities.
Mi and colleagues (Abstract 942) presented data on the interaction of health care stigma with state-level health care policies related to sexual orientation and gender identity among more than 5500 TGW participating in the TWIST study. Half of the participants reported experiencing health care stigma, which they defined as the perception, anticipation, or experience of sexual behavior or gender identity stigma in the context of health care in the prior 12 months. Only 9% of the participants were on PrEP in the previous 12 months. In states with more protective policy environments, there was no association of health care stigma with PrEP use. However, among states with more harmful policy environments, health care stigma was associated with a decreased likelihood of PrEP use (aOR, 0.70). The authors suggested that interventions to reduce stigma are likely to be most effective when implemented at a state-specific policy level.
Traver and colleagues (Abstract 1115) reported on baseline data from an ongoing randomized clinical trial comparing integrated infectious diseases and substance use disorder outpatient care vs treatment as usual at 4 sites in the US South. They noted that of 142 PWID hospitalized with acute bacterial or fungal infection, 38% met criteria for initiating PrEP, but none were on PrEP. PrEP awareness was below 50% and PrEP interest was just above 50%. Of all 47 persons interested in PrEP, common reasons for not using PrEP included not feeling at risk (40%), lack of prior PrEP awareness (28%), and lack of health care clinicians offering it (13%). The authors suggested that health care clinicians offer PrEP during and after hospitalization for PWID.
Hull and colleagues (Abstract 1002) presented data on awareness and preferences for PrEP among PWID in Vancouver, Canada. They recruited 359 participants from 6 addiction and primary care clinics, of whom 293 reported drug use in the past 6 months. In this study, PrEP awareness was only 24% among PWID, despite the existence of a public PrEP program for 6 years in British Columbia that includes indicators for use in PWID. Despite low knowledge, willingness to use PrEP was 67% and approximately 63% expressed a preference for every-6-month and every-2-month injectable PrEP over oral PrEP. Preference for every-6-month PrEP was higher among those with unstable vs stable housing (aOR, 1.76), but surprisingly was lower among persons injecting numerous times per day than in those injecting daily or less often (aOR, 0.55). The investigators called for advertisements for injectable medications to be tailored for persons with unstable housing and advertising for oral PrEP to be tailored for those with more frequent drug use.
Lukyamuzi (Abstract 984) presented data on the interest in LA PrEP among men in the Kalangala Islands in Uganda, a setting with high heterosexual HIV transmission. Of 239 participants queried at the end of a 52-week study, 94% expressed interest in LA injectable (LAI) PrEP. LEN was more preferred than CAB-LA (47% vs 18%, respectively), although 28% stated they liked both options equally. When asked about interest in taking a monthly pill for prevention, 93% also stated they were interested. Preference for LAI PrEP was higher than for a monthly pill (43% vs 17%, respectively), although 38% stated that they liked both options equally. The authors suggest that implementation and future PrEP trials should prioritize this population and examine actual uptake and sustained use.
PrEP in Pregnancy
Marzinke and colleagues (Abstract 789) and Ford and colleagues (Abstract 790) presented a pharmacokinetic analysis that indicated that dose adjustments for CAB-LA are not required for pregnant women. Both groups evaluated data from 75 women in the HPTN 084 (A Phase 3 Double Blind Safety and Efficacy Study of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Preexposure Prophylaxis in HIV-Uninfected Women) trial who continued CAB-LA during pregnancy. They reported that from the prepregnant period through the third trimester, there was a median 26% reduction (IQR, 2–40) in total CAB Ctrough concentrations. However, 98% of unbound CAB concentrations remained above the unbound pharmacologic threshold for protection. Therefore, no dose adjustment is needed for pregnant persons at initiation or follow-up of CAB-LA injections.
Hannan and colleagues (Abstract 810) reported on HIV incidence and oral PrEP effectiveness in pregnant and postpartum South African women. Of the 1920 pregnant women enrolled, only 14% were on oral PrEP and only 23% ever used PrEP during follow-up, despite having oral PrEP routinely offered during antenatal care. They recorded 24 incident infections (incidence rate [IR], 1.61/100 person-years) and the incidence was highest in women aged younger than 24 years (IR, 2.36). Only 1 of these infections occurred in a woman on PrEP, indicating a 76% reduction in HIV incidence among women on PrEP. Incidence was highest in the prenatal period. This suggests that more intensive programs are needed to provide pregnant women with PrEP during the prenatal and postpartum periods.
Namale and colleagues (Abstract 811) reported on PrEP uptake among pregnant and breastfeeding women in 6 high-volume facilities in Kampala, Uganda. Among 3258 women, 87% accessed PrEP. Uptake was significantly lower among women reporting partner violence than in those without partner violence (17% vs 89%, respectively; P <.001). Uptake was also lower among women with partners with HIV than in those with partners without HIV or with unknown serostatus (48% vs 74% vs 88%, respectively; P <.001). In adjusted analyses, those who were married/cohabiting (aPR, 1.34), single/never married (aPR, 1.36), and separated/divorced (aPR, 1.36) were more likely to use PrEP than other categories. However, PrEP uptake was less likely among women who reported partner violence (aPR, 0.24) than in those who did not. The authors suggested that these data support the integration of violence screening and referral within antenatal and postnatal care.
Ngumbau and colleagues (Abstract 812) presented data on PrEP use trajectories among women initiating PrEP in pregnancy. Among 600 pregnant women vulnerable to HIV who were initiating daily oral PrEP as part of a randomized clinical trial in Western Kenya, 52% discontinued PrEP at least once before 9 months postpartum; median time to first discontinuation was 5.8 months. Women were more likely to discontinue PrEP if they experienced stillbirth or neonatal loss (RR, 2.56), started antenatal care in their second trimester (HR, 1.61), were primigravida (HR, 1.40), or experienced adverse effects (HR, 1.66). They were less likely to discontinue PrEP if they had high pill-taking selfefficacy (HR, 0.28) or if they had self-perceived HIV risk that was moderate (HR, 0.45) or great (HR, 0.08). The authors called for interventions that enhance self-efficacy and refine risk perception for pregnant women.
Oguttu and colleagues (Abstract 815) evaluated the uptake of CAB-LA PrEP when offered to postpartum women in Botswana immediately after delivery. Of 951 women who met epidemiologic HIV risk criteria (aged 18–30 years, or older than 30 years with fewer than 3 pregnancies) and had no contraindications to participating in the study, 500 (approximately half) chose to initiate CAB-LA and enroll in the study. Of these, only 14% had taken PrEP previously, 52% had any history of condom use, 62% had at least 1 partner 5 or more years older than them, 71% thought they had at least some risk of getting HIV in their lifetime, and 32% stated that their baby had at least some risk of getting HIV. The authors concluded that maternity wards are a practical and strategic entry point for initiating CAB-LA PrEP in young women, based on epidemiologic criteria and not individual risk factors.
From the same study, Shava and colleagues (Abstract 814) conducted a substudy in 20 CAB-LA acceptors and 20 decliners among 40 postpartum women. Acceptors and decliners had similar perceptions of HIV risk and reported sexual behavior. However, despite acknowledging that injectable PrEP can be more private than oral PrEP, there were differences in self-perceived family support (95% of acceptors vs 30% of decliners), friend support (90% of acceptors vs 70% of decliners), and concerns about partner problems due to PrEP disclosure (35% of acceptors vs 95% of decliners). They concluded that anticipated support from partners and family remains crucial for the uptake of PrEP, despite the increased privacy of an injection. They called for shifts in policy and culture, addressing stigma, and increasing PrEP knowledge.
PrEP Rollout
Hill and colleagues (Abstract 162) presented global data on the PrEP-to-need ratio (eg, the number of persons on PrEP for every new HIV infection in that country). He pointed out that with a background HIV incidence of 2.4 per 100 person-years, which describes many key populations globally and was seen in the PURPOSE I and II trials of LEN, 41 people given LEN were needed for each infection averted. However, with the cut in US aid, he pointed out substantial reductions in PrEP use from the beginning through the end of 2025, ranging from a 7% reduction in Kenya to a 98% reduction in Nigeria. UNAIDS modeling suggests that there will be an increase from the current 1.3 million new HIV infections per year to 1.45 million new infections by 2030, given these cuts. Hill then went on to calculate the PrEP-to-need ratio for countries around the world. Only 4 countries achieved a PrEP-to-need ratio of more than 40: Norway, Australia, Denmark, and the UK. An additional 10 countries achieved 10 to 40 people on PrEP per HIV acquisition, including the US, Canada, and several European countries. He stated that 42 countries had 1 to 10 people on PrEP for every HIV acquisition, including Mexico, Brazil, other countries in Europe, and South and East Africa. Finally, 126 countries distributed fewer than 1 PrEP prescription for each acquisition, and these countries were widespread throughout the world. There are only 2.3 million people estimated to be on PrEP, whereas the UNAIDS target is 21.2 million. Of the 2.3 million, he estimated that 96.3% were on oral PrEP, with only 2.9% on CAB-LA and 0.9% on LEN. Therefore, he stated that PrEP is having no-to-low impact on HIV incidence in low-and middle-income countries (LMICs). However, ART has been broadly distributed throughout the world, so the same should be able to be done for PrEP. He called for the following: $500 million for the first 10 million doses of LEN for LMICs; bringing the price down to less than $1000 per year for injectable PrEP for countries outside the voluntary licensing agreement; task shifting, HIV self-testing, and same-day PrEP initiations for implementation; and reopening clinics for key populations globally.
In a related poster, Cross and colleagues (Abstract 943) conducted mathematic modeling to estimate how many people would need to be on LA PrEP to achieve a substantial impact on the worldwide epidemic. They estimated that 2025 CAB-LA uptake was preventing only approximately 1700 new infections per year, and 2025 LEN uptake averted approximately 85 infections. They estimated that we would need 10 million persons in LMICs to take LA PrEP to reduce HIV acquisitions by 250,000 per year, but that will not happen unless it becomes affordable, including a cost of less than $1000 per year in high-income countries.
In a different model, Gelderblom and colleagues (Abstract 991) projected that we would need 10 million more people with HIV on treatment (to achieve “undetectable = untransmissible,” or U = U) or 100 million people on PrEP or a combination of both to reduce new infections by 1 million annually. They stated that nearly half of new infections globally occur in people not typically targeted for PrEP programs, and thus we would need numerous LA PrEP options and ultimately a vaccine to stop the HIV pandemic.
Moore and colleagues (Abstract 1087) presented modeling data on the impact of scaling up LEN use in the US. They looked at 2 scenarios: (1) status quo without changes in PrEP use from 2025; and (2) an increase in LEN use by 37%. In comparing 2017 with 2030, they found that the status quo would lead to a reduction in new infections by 15%, but with increased LEN, there would be an estimated reduction in new infections by 25% or an additional 13,700 infections averted. However, neither scenario would achieve the EHE goal of reaching a 90% reduction by 2030. Moreover, progress toward the EHE goals was lowest among those who were heterosexual, uninsured, aged 13 to 24 years, or living in the Northeast or South. The best modeling scenario they presented was if PrEP use increased and all PrEP users were on LEN, which would lead to a 38% reduction by 2030. The authors called on prioritizing those at greatest need to achieve the greatest impact on new HIV infections in the US.
Preer and colleagues (Abstract 978) presented US data on PrEP uptake using EHR data from almost 820,000 persons using PrEP in the US from 2012 to 2025. TDF/FTC was most commonly used (77%), followed by TAF/FTC (21%), CAB-LA (1.4%), and LEN (0.1%). The average age at PrEP initiation was 36 years. Geographically, 93% of PrEP users resided in urban areas and less than 6% in rural areas, despite the fact that 13% to 20% of the US population resides in rural areas. By Social Vulnerability Index (SVI), 41% of PrEP users were in the highest quartile and only 12% were in the lowest quartile. This suggests that more interventions are needed to increase PrEP uptake among persons residing in rural and low SVI areas.
Koh and colleagues (Abstract 1059) evaluated different types of PrEP uptake in more recent years (January 2022-December 2024) using pharmacy and medical claims from a US national claims database. During this more recent period (after CAB-LA was licensed in the US), only 4% of all 361,000 PrEP users were CAB-LA users. Medicaid coverage was higher among CAB-LA users than oral PrEP users (26% vs 14%, respectively). They also found that CAB-LA retention in care was only 56% at 1 year of followup and 26% at 2 years of follow-up. The authors suggested that as new LAI-PrEP modalities are rolled out, barriers should be proactively identified and addressed.
Krakower and colleagues (Abstract 885) presented modeling data on the potential impact of over-the-counter (OTC) TDF/FTC PrEP for MSM in the Atlanta metropolitan area. They concluded that if OTC PrEP resulted in a 10% increase in PrEP coverage, it would avert 3.2% of HIV infections over 10 years; a 50% increase would avert 15.4% of new infections. This would be accompanied by an increase from 2.5% (if PrEP were available by prescription only) to 4.8% (50% coverage) in the proportion of PrEP users with glomerular filtration rates below 60 mL/min; an increase in HBV reactivations from zero to 2.27 per 100 person-years among people with HBV infection, and an increase in FTC resistance from 0.68 to 8.4 events per 100 incident infections. The authors concluded that OTC PrEP could produce meaningful population-level HIV prevention benefits if it expanded beyond clinic-based care but suggested that HIV testing at PrEP initiation and targeted renal monitoring should be promoted.
Cannon and colleagues (Abstract 190) evaluated the population-level effectiveness of PrEP among cisgender men and transgender and nonbinary persons who have sex with men with a prior STI in King County, Washington. They evaluated HIV infection rates among persons diagnosed with gonorrhea or syphilis from January 2014 through June 2024 who were HIV negative and followed them for HIV seroconversion over time. There was an overall reduction in new HIV diagnoses over that time of 7% per year. They also found that HIV infection rates were higher among those aged 15 to 19 years and some people of color (American Indian/Alaska Native, Black, Native Hawaiian/Pacific Islander, multiracial). However, after adjusting for age, race, STI diagnosis, and calendar year, those who reported having taken PrEP had a 50% lower rate of HIV infection than those who had not taken PrEP (0.46/100 person-years vs 1.14/100 person-years, respectively). However, Black persons on PrEP did not have a substantial decline in incidence compared with those not on PrEP (1.2/100 person-years vs 1.4/100 person-years, respectively), although there were only 26 Black persons in the study, so these results must be interpreted with caution. Nonetheless, the authors point out that PrEP access alone is insufficient, and that other support tools may be needed to increase PrEP effectiveness in populations.
Hsu and colleagues (Abstract 979) presented data on CAB-LA use in the OPERA (Observational Pharmacoepidemiology Research and Analysis) cohort, an extraction of EHRs from 101 clinics in 23 US states and territories. During the first 3 years of CAB-LA PrEP use in the US, 1748 people received at least 1 CAB-LA injection. CAB-LA recipients had a median age of 33 years, 11% were women, and 9% were transgender. Race/ethnicity was 27% Black, 29% Latino, and 51% White. Of those receiving CAB-LA injections, 88% completed initiation but one-third discontinued CAB-LA during the study period, of whom 28% reinitiated CAB-LA after a median gap of 7 months. Of those receiving maintenance injections, 59% adhered to the recommended dosing schedule, and most injection delays were short. The team reported only 2 cases of HIV acquisition on CABLA, each of whom had received on-time injections. One of these was diagnosed 3 months after initiating CAB-LA, without a baseline HIV test. The second was diagnosed 21 months after initiation. An additional 2 patients acquired HIV after CAB-LA discontinuation. The authors concluded that breakthrough infections are rare on CAB-LA in real-world settings, and that discontinuation and reinitiation patterns suggest continued interest in CAB-LA PrEP.
Another presentation by Barnett and colleagues (Abstract 980) from the OPERA cohort compared PrEP coverage and HIV acquisition between CAB-LA users (1664) and oral PrEP users (38,329). PrEP coverage, defined as continuous use of CAB-LA or oral PrEP, was substantially higher among CAB-LA users (median, 93%) than in oral PrEP users (median, 58%). In this analysis, they reported an incidence rate of 0.09 per 100 person-years in persons on CAB-LA vs 4.9 per 1000 person-years in persons on oral PrEP (IRR, 5.4). However, the authors emphasized the importance of choice, as there were switches between the 2 regimens.
Elion and colleagues (Abstract 981) presented real-world data on CAB-LA use from the Trio Health Cohort, also drawn from EHRs from many clinics. Of nearly 1700 adults who initiated CAB-LA from December 2021 through February 2025, 89% completed initiation and 36% discontinued, of whom 14% reinitiated within 6 months. They reported 3 infections among those in this cohort. One was diagnosed after 7 on-time injections. A second person missed their second injection but otherwise received on-time injections and was found to have acquired HIV at their tenth injection. The third individual was diagnosed at their second injection and did not have HIV testing at initiation; therefore, this person could have already been infected when initiating CAB-LA. The first 2 patients did not have any resistance mutations; the third person was not tested. This again reinforces the high effectiveness of CAB-LA as well as the idea that a number of reasons could account for the discontinuation rates.
Corma-Gomez and colleagues (Abstract 1060) evaluated oral PrEP persistence and discontinuation among a multicenter cohort of 3200 men and women in Spain. Although PrEP is publicly funded and provided free of charge in Spain through the national health system, the investigators determined that the probability of continuing oral PrEP at 1 year was 77% and at 3 years was 55%. Discontinuation was higher among those aged younger than 39 years (aHR, 1.64; P <.001), among women engaged in transactional sex (aHR, 3.19; P <.001), and among those with adherence of fewer than 4 pills per week (aHR, 4.53; P <.001). The authors pointed out that underserved subpopulations remain underrepresented among those taking PrEP, and that universal access does not ensure equitable use.
Black women make up half of all new diagnoses in women. Cook and colleagues (Abstract 1081) presented data from the EBONI (Engaging Black Women on Cabo-tegravir LA for PrEP by Optimizing Novel Implementation Strategies) study of CAB-LA delivery to Black women from 20 sites in the US. Of 163 women enrolled, 25% were transgender. Overall, 44% started CAB-LA without having first taken oral PrEP. Persistence on CAB-LA was 74% at month 6 and 57% at month 12; 69% to 89% received on-time injections through month 12. Only 2% discontinued due to adverse events. At 12 months, 71% reported that in-person visits for CAB-LA provided more opportunities to discuss CAB-LA concerns and 55% reported that it provided more opportunities to discuss sexual health care concerns. None of the women acquired HIV during follow-up.
Liu presented data (Abstract 1128) on CAB-LA uptake and retention in a low-barrier clinic for people who use drugs in San Francisco. This health access point is a nurse-led drop-in clinic for PWID and people experiencing homelessness, integrating sexual health and infectious diseases services with substance use treatment and harm-reduction services. Of 425 clients without HIV, 20% were prescribed CAB-LA. Of these, 92% completed their second loading dose on time and 86% persisted on CAB-LA at 6 months after initiation. In multivariable analyses, factors associated with PrEP persistence included being gay or bisexual (aOR, 15.8; P=.007) and having a substance use disorder (aOR, 11.1; P=.04). The investigators concluded that integration of sexual health, infectious diseases, and substance use services facilitated CAB-LA initiations and that persistence was substantially higher than what has been historically reported for oral PrEP.
Buchbinder and colleagues (Abstract 1125) reported on the rollout of CAB-LA and doxy-PEP at 3 clinics in San Francisco from October 2022 through September 2025. Although doxy-PEP rollout was high (>7000 patients newly prescribed doxy-PEP, which was 20% of MSM and TGW clients at those clinics), CAB-LA rollout was modest (only 462 prescriptions) and level over time. CAB-LA was more likely to be prescribed for TGW than for cisgender men (OR, 3.1) and more likely to be prescribed to Latino clients than White clients (OR, 2.2). Doxy-PEP rollout was lower among Black patients than White patients (OR, 0.7) and lower among TGW than cisgender men (OR, 0.55). Reasons for these disparities are being explored and will guide citywide efforts to increase awareness and access for populations most affected by HIV and STIs.
Rosen (Abstract 1127) presented data on limited PrEP availability in substance use treatment programs across the US. Using data from the National Substance Use and Mental Health Surveillance System, an annual survey of substance use treatment facilities in the US from 2021 to 2024, approximately 13,000 to 14,000 programs were surveyed per year. The percentage of programs offering PrEP increased from 6% in 2021 to 10.6% in 2024 (P <.0001). Although there was an increase in all setting types, offers remained lower in residential and outpatient settings than in inpatient settings. Factors that correlated with programs offering PrEP included those that had programs for LGBTQ+ clients (aOR, 1.75), programs for PWH (aOR, 2.32), those that were affiliated with a hospital (aOR, 2.34), and large-vs small-sized programs (aOR, 1.69). This calls for more substance use treatment programs to develop strategies to offer PrEP services to clients who qualify.
PrEP Delivery Models
Chamie and colleagues (Abstract 163) reported on the results of a randomized clinical trial of community precision health vs standard of care among 16 villages in Kenya and Uganda. The intervention consisted of training community health workers to conduct HIV testing and linkage to prevention and treatment services. Clinicians in the intervention communities were also trained to provide dynamic choice prevention and Life Event Assessment and Planning (LEAP) interventions for PWH. Community health workers were trained to use a smartphone application that allowed them to communicate bidirectionally with clinics, allowing for linkage from referrals and attempts to bring people back for retention if they missed appointments. After 2 years, more than 84,000 people split evenly across intervention and control communities underwent a RITA to measure HIV seroincidence. Seroincidence was 0.06 per 100 person-years in the intervention group and 0.19 per 100 person-years in the control group, a reduction of 70% (P <.001). Findings were consistent across country, age group, and sex. Biomedical prevention was undertaken by 1.67% of the population in the intervention group and 0.4% in the control group, which is a 4-fold greater uptake in the intervention arm (P<.001). Although the care cascade trended to being better in the intervention arm, there were no significant differences between arms. Thus, the authors posited that biomedical HIV prevention likely contributed to the reduction in HIV seroincidence in intervention communities, and proposed that this scalable, sustainable intervention be rolled out.
Davey and colleagues (Abstract 131) presented data on a dynamic choice model of oral PrEP delivery and testing methods among postpartum women who had discontinued or poor adherence to oral PrEP after birth. They enrolled 266 women with a median age of 25 years, of whom 38% were married or cohabitating, 62% reported their partner was HIV negative, and 60% reported no sexual activity in the past month. Women were allowed to choose their method of PrEP delivery: 49% chose rapid clinic pickup, 46% chose home delivery, and 5% chose community delivery. Over time, 45% switched delivery method, although community delivery remained exceedingly low. Women were also allowed to choose the method of HIV testing; 57% chose clinic-based rapid testing and 43% chose selftesting. At the end of an approximately 6-month period (funding was cut and the study was terminated early), adherence was better in the dynamic choice arm than in the arm with counseling based on urine tenofovir feedback as measured by self-report and picking up PrEP pills (47% vs 34%, respectively; aOR, 1.7; P=.03). Prevention effective adherence (coverage when reporting sexual practices) was also better in the dynamic choice arm (72% vs 58%; aOR, 1.7; P = .1), but the difference did not achieve statistical significance. The study was also underpowered to assess objective adherence using urine levels, as only approximately half in each arm had urine tenofovir levels available. This suggests that offering dynamic choice of location of pickup and type of HIV testing may help postpartum women to adhere to PrEP.
Buchbinder and colleagues (Abstract 990) presented data on an online pharmacist-delivery model of oral PrEP for persons assigned male sex at birth under a collaborative practice agreement in California. Participants were randomly assigned 2:1 to receive online pharmacy-delivered PrEP with same-day courier delivery (PrEP-3D) or enhanced standard of care with active PrEP navigation. Of 107 enrolled participants, 70 received the PrEP-3D intervention and 37 received enhanced standard of care. PrEP uptake and persistence through 12 months of follow-up were significantly better among the PrEP-3D arm than the enhanced standard of care arm (79.2% vs 52.5%, respectively; OR, 3.5). Participants rated the PrEP-3D intervention as excellent. The authors concluded that pharmacist-prescribed and delivered PrEP holds promise for improving PrEP uptake and adherence among persons assigned male sex at birth.
Koch (Abstract 1068) presented data on pharmacy-initiated PrEP in 2 nonurban Southern California EHE jurisdictions using 12 pharmacies. Pharmacies had iPad self-intake, HIV testing, and PrEP counseling with same-day initiation and follow-up support. Using community health worker and geotargeted social media outreach, they were able to reach 102 persons, 90% of whom were Latino and 15% of whom were Black; 40% reported low income and 55% were uninsured or publicly insured. They achieved same-day PrEP initiations in all participants; visits averaged less than 60 minutes and the 3-month retention rate was 78%. Two of the persons had reactive HIV rapid tests and were linked to confirmatory testing and treatment. The study demonstrated that community pharmacies can rapidly initiate persons on PrEP and support short-term retention, including in lower-income men, who are often underserved in traditional health care settings.
Rutstein and colleagues (Abstract 1063) presented data on the use of peer navigators to increase PrEP uptake and persistence among heterosexual men recruited from STI clinics in Malawi (HPTN 112; Improving HIV Prevention Among Heterosexual Men Seeking STI Services in Malawi [NJIRA]). In this study, men aged 15 years or older who were initiating PrEP services were randomly assigned 2:1 to receive peer navigation (counseling, community tracing for missed PrEP visits, point-of-care STI testing, and PrEP “restart kits”) vs standard of care. They enrolled 200 men from March to November 2024, of whom 155 chose daily oral PrEP, 13 chose event-driven oral PrEP, and 16% chose CAB-LA. Three participants had acute HIV at enrollment, indicating that this was a high-risk group. Unfortunately, at week 26, PrEP persistence was extremely low and not statistically different between the arms (7% in the peer navigation arm vs 12% in the standard of care arm). Attendance at the PrEP visit was better in the peer navigation arm (81% vs 53% in the standard of care arm). However, a large drop-off in PrEP care occurred immediately after initiation. The authors called for additional strategies to promote PrEP persistence in this population.
Springer and colleagues (Abstract 1071) presented data on a randomized clinical trial of mobile health unit use vs patient navigation to increase PrEP in criminal legal-system-involved people who use drugs in Texas and Connecticut. They enrolled 568 participants, randomly assigned 1:1 to the 2 arms. Although PrEP uptake was faster in the mobile health unit than in the peer navigator arm, only 22 persons (7.6%) recruited from the mobile health unit initiated PrEP compared with 7 persons (2.5%) in the peer navigator arm (HR, 3.1; P=.009). Despite this overall low uptake, the authors suggest that bringing services to where people are might lead to an increase in PrEP initiation and reduction in HIV incidence.
Novel PrEP Agents
Dobard and colleagues (Abstract 125) presented data on the efficacy of an islatravir implant on protection against M184V simian HIV (SHIV) rectal challenge in rhesus macaques. Islatravir, a nucleoside reverse transcriptase translocation inhibitor (NRTTI), is closely related to MK-8527, another NRTTI currently being tested in 2 phase III clinical trials. They asked whether the M184V mutation would lower the efficacy of islatravir when delivered via implant. They determined that an M184V SHIV mutation reduced sensitivity to islatravir 12-fold and to MK-8527 24-fold in vitro. They altered the M184V SHIV mutation to make it stable and used a 4-fold higher dose for rectal challenge, because the M184V SHIV is less transmissible than wild type. Of 6 macaques treated with an islatravir implant, none became infected with numerous rectal challenges with wild-type SHIV. However, 4 of 5 rhesus macaques became infected when rectally challenged with M184V SHIV. Thus, they raised concerns that a single-drug PrEP regimen with an NRTTI may not confer protection against M184V, which is the most common resistance-associated mutation, but is estimated to be present in fewer than 1% of human transmissions. In the discussion session after the presentation, questions were raised about whether stabilization of the M184V mutation and the 4-fold higher challenge dose might not reflect physiologic parameters in this challenge model. Data on actual infections are awaited from the phase III clinical trials of MK-8527, a sister compound to islatravir.
Kapoor and colleagues (Abstract 126) presented population pharmacokinetic modeling data from phase II studies of MK-8527. Based on these data, they selected the 11-mg oral dose per month as an appropriate dose for 2 phase III studies, one in cisgender women and the other in cisgender men and transgender and nonbinary persons having sex with men. The onset of action appears to occur within 1 hour of oral dosing, with a forgiveness window of ±7 days between doses. Although pregnancy is expected to lower drug levels by 10% to 30%, this is still expected to maintain efficacious dosing, so no dose adjustment is needed in pregnancy, and women who become pregnant in the phase III trial will be allowed to continue with dosing after undergoing informed consent. For every 10 kg lower weight, they expect a 10% increase in blood levels; however, they anticipate that there would not need to be dose adjustment for adolescents weighing at least 35 kg; adolescents as young as age 16 years will be recruited for the phase III trials.
Le (Abstract 997) reported preclinical data on a subcutaneous ultra-LAI and removable in situ forming implant (ISFI) with dolutegravir alone and in combination with levonorgestrel as a once-yearly injectable for PrEP and as a multipurpose prevention technology for HIV PrEP and contraception. They studied their products in mouse and macaque models. They stated that the dolutegravir ISFI was well tolerated, with minimal systemic inflammation response and mild-to-moderate local inflammatory responses. It stayed above the protective target level for more than 2 years after a single injection in mice, and they stated from modeling work in the macaque model that it would be projected to last for 116 to 350 days. The multipurpose technology ISFI elicited plasma concentrations at target levels for 180 days after a single injection in mice.
Postexposure Prophylaxis
Sapin and colleagues (Abstract 999) presented data from a real-world evaluation of HIV PEP in pocket (PIP), proactively providing a 28-day supply of PEP and instructing users to initiate PEP as soon as possible and within 72 hours of a potential HIV exposure. The team prospectively recruited PIP users who were matched 1:2 with daily PrEP users from the Ontario PrEP Cohort Study based on age, HIV risk score, and city of residence. They then compared health care costs in US dollars associated with PIP vs PrEP along with quality-of-life outcomes. There were no HIV seroconversions in the groups during follow-up. PIP was associated with direct annual health care cost savings of up to $1488 per person. The PIP and PrEP groups had comparable self-reported HIV-related anxiety and sexual satisfaction. The study demonstrates that a practical, on-demand HIV prevention approach can be cost-saving for individuals at lower HIV risk.
Fusco and colleagues (Abstract 998) presented data on the single-tablet regimen bictegravir/FTC/TAF for PEP in an ED in Naples, Italy. Of 405 individuals referred to the ED in the study period, bictegravir/TAF/FTC was started in 381 persons and confirmed in 273 persons (72%) referred to the infectious diseases service. Participants who continued with PEP were more likely to have reported high-risk sexual exposures than occupational or low-risk contacts. Among those who continued, the 28-day course was completed in 96%. Among those who completed, 9% reported self-limited adverse effects. No HIV seroconversions were documented. Early syphilis was diagnosed in 15 persons. PrEP was recommended to 161 persons, 63% of whom initiated. The authors concluded that PEP with bictegravir/FTC/TAF is a valuable and effective option for PEP, combining high efficacy with excellent tolerability.
Sexually Transmitted Infections
Marrazzo (Abstract 25) gave a plenary about global STIs. She noted that in 2024, there were 2.2 million STIs diagnosed in the US. That represents a decrease from 2014 in chlamydia of 1% but an increase in gonorrhea of 37%, an increase in syphilis of 155%, and an increase in congenital syphilis of nearly 700%. The rise of syphilis in women is mirrored in the rise in congenital syphilis. She reminded the audience of a recent publication of a randomized clinical trial that demonstrated that 1 dose of benzathine penicillin G was noninferior to 3 doses in serologic response at 6 months in the treatment of early syphilis. She also discussed the global rise in gonorrhea antimicrobial resistance, including to ciprofloxacin and to azithromycin. Although cases of reported ceftriaxone resistance remain low globally, this is a concern. Two new oral treatments for gonorrhea, zoliflodicin and gepotidacin, have recently received US Food and Drug Administration (FDA) approval. Marrazzo ended by calling for innovation in the development and delivery of STI diagnostic tests, new antimicrobial agents, new STI vaccines, and better approaches to the prevention of congenital syphilis.
Seib and colleagues (Abstract 197) reported on the GoGoVax (Efficacy Study of 4CMenB [Bexsero] to Prevent Gonorrhea Infection in Gay and Bisexual Men) trial, a randomized clinical trial of the 4CMenB vaccine to prevent gonorrhea acquisition in persons assigned male sex at birth. There have been several observational studies suggesting that this vaccine might offer 33% to 47% protection against acquisition of gonorrhea. GoGoVax was conducted in Australia in 7 clinics in 3 Australian states. To be eligible, participants had to meet the following criteria: assigned male sex at birth; had sex with a man in the last 6 months; aged 18 to 50 years; diagnosis of gonorrhea or infectious syphilis in the past 18 months; HIV negative and on PrEP, or HIV positive and virally suppressed with a CD4+ count higher than 350 cells/μL. Participants were randomly assigned 1:1 to receive 2 doses of 4CMenB vaccine 3 months apart or placebo. All participants were followed quarterly for 2 years. The mean age of the participants was 34 years, 90% were HIV negative, and 60% reported 10 or more partners in the previous 6 months. Unfortunately, the 4CMenB vaccine did not confer protection (IRR, 1.01; P = .97). This was despite high rates of gonorrhea in both study arms (48/100 person-years for the first episode, 60/100 person-years for all episodes), so this lack of effect was not an issue of statistical power. There were also no differences in various subgroup analyses, including by HIV status, sexual identity, age, history of gonorrhea, history of syphilis, number of sex partners, condom use, group sex, or length of follow-up. This reinforces the results from the DOXYVAC (Doxycycline Prophylaxis and Meningococcal Group B Vaccine to Prevent Bacterial Sexually Transmitted Infections in France) study,1 but there are 3 ongoing randomized clinical trials in the field that include women, a population that has not yet been studied.
Chen and colleagues (Abstract 194) presented data on a retrospective analysis of the addition of doxycycline with or without ceftriaxone in addition to benzathine penicillin to treat early syphilis in PWH. Their analysis was conducted using EHRs from their hospital in Taiwan, where some clinicians are adding a 7-day course of doxycycline to benzathine penicillin with or without a single dose of ceftriaxone in the treatment of early syphilis. Their data spanned January 2018 through December 2024. Of 1077 early syphilis episodes among 762 PWH, 42% were treated with benzathine penicillin alone, 53% with the addition of doxycycline, and 5% with all 3 antibiotics. In Cox proportional hazard analysis, a 4-fold reduction in syphilis titers at 12 months was associated with age (per 10 years, aHR, 0.9; P=.005), baseline rapid plasma reagin titer (aHR, 1.17; P <.001), initial vs repeat episode of early syphilis (aHR, 1.42; P <.001), and doxycycline-containing regimens (aHR, 1.45; P <.001). Despite study limitations, ie, that it is retrospective in design and did not take into account concomitant doxy-PEP use, the authors concluded that the addition of a 7-day course of doxycycline leads to faster resolution of syphilis titers in PWH.
Rivera-Villegas (Abstract 1015) presented data on 529 cases of syphilis among PWH in their cohort. Approximately 25 (5%) met criteria for ocular syphilis, with the most frequent presentation being optic neuritis (44%), followed by posterior uveitis (32%). Of the 72% of these patients who underwent cerebrospinal fluid venereal disease research laboratory (VDRL) testing, 12% were reactive consistent with neurosyphilis and 8% had otosyphilis. Patients with ocular syphilis had higher VDRL titers (median, 1:128) than those without ocular syphilis (median, 1:16; P <.001).
Mogaka and colleagues (Abstract 1017) reported on missed syphilis screening opportunities for pregnant women in Kenya. They conducted chart abstraction from January 2025 to February 2026 for women enrolled in the PrIMI (Improving Perinatal Outcomes Among Kenyan Pregnant Women with an Integrated STI Testing Model) study. Of 2684 women attending antenatal clinic visits with a median gestation of 23 weeks, 87% had been screened for syphilis at the time of data abstraction. Women with HIV were more likely to have missing syphilis testing than women without HIV (33% vs 10%, respectively; P <.001). Other factors associated with missing a syphilis test were age older than 24 years (13.8% vs 10.7% in those 24 years or younger; P = .02) and multiparous women (14.3% vs 9.1% in primigravidas women; P = .001). Syphilis positivity was nonsignificantly higher in women with HIV than in those without HIV (1.5% vs 0.7%, respectively). These gaps occurred despite the availability of point-of-care testing options. The authors called for identifying barriers and optimizing implementation strategies for pregnant women.
Molina (Abstract 196) presented data from a randomized open-label trial of pritelivir vs investigator choice of treatment for refractory mucosal herpes simplex virus (HSV)-1 or HSV-2 among immunocompromised persons. He noted that 6% to 7% of the US population is immunocompromised from factors such as HIV, posttransplant status, malignancy, or immunosuppressive drugs. Acyclovir resistance is present in up to 27% of immunocompromised patients, including 5% of PWH. Pritelivir is a small molecule with a novel mechanism of action that is active against HIV-1 and HIV-2. They randomly assigned 23 participants to the pritelivir arm and 15 to the investigator choice arm (intravenous foscarnet, intravenous or topical cidofovir, and topical imiquimod). At the end of a 28-day course of treatment, 63% of lesions in the pritelivir arm and 34% in the investigator choice arm were completely healed (P <.005). He noted that pritelivir has now received breakthrough designation by the US FDA and may be approved by the FDA in the future.
Doxy-PEP
Forster and colleagues (Abstract 1020) presented data on the modeled impact of doxy-PEP on syphilis incidence among MSM in 4 US cities. They projected that without doxy-PEP, syphilis infections among MSM are projected to rise by 1.71-fold across the 4 locations by 2030. However, if doxy-PEP coverage was 10%, it could avert 37% of infections at the lowest amount (Atlanta, Georgia), and 46% of infections at the highest amount (Miami, Florida). If coverage increased to 25%, doxy-PEP would avert 57% of syphilis cases in Atlanta to 68% in Miami. These data suggest that doxy-PEP could have a substantial impact on the growing rate of syphilis among MSM.
Barry and colleagues (Abstract 1038) reported on the impact of doxy-PEP on bacterial STIs among clients seen at the Magnet Sexual Health Clinic in San Francisco, California. They divided clients into those who reported always using doxy-PEP within 72 hours of sex since their last visit (high adherence) with those who reported often, sometimes, rarely, or never using doxy-PEP since their last visit (inconsistent adherence). Persons with high adherence had significant decreases in chlamydia and gonorrhea; there were too few cases of syphilis to see an impact on this STI, although they did see a significant decline in syphilis among persons reporting any doxy-PEP use.
Menza and colleagues (Abstract 1037) reported on the etiology of nongonococcal urethritis (NGU) at a sexual health clinic in Seattle and King County, Washington. From 2019 to 2025, the proportion of NGU cases caused by chlamydia decreased from 18% to 3% among MSM. Most NGU cases in MSM (77%) and men who have sex with women (70%) is idiopathic. It is unclear whether persons with idiopathic NGU benefit from antibiotic therapy.
Golden and colleagues (Abstract 1111) modeled the potential impact of decreased STI screening and partner treatment and doxy-PEP on antibiotic use in MSM in King County, Washington. They noted that some public health authorities are advocating for the discontinuation of gonorrhea/chlamydia screening and empiric treatment of sex partners of persons with these 2 STIs to decrease antimicrobial use, a practice they called antimicrobial stewardship. They modeled 4 scenarios in MSM: (1) current practice without doxy-PEP but continued gonorrhea/chlamydia screening; (2) antimicrobial stewardship without doxy-PEP; (3) current practice with 30% doxy-PEP use; and (4) antimicrobial stewardship with 30% doxy-PEP use. They found that antimicrobial stewardship changes could decrease the use of ceftriaxone and doxycycline for STIs by 56% relative to current practices in the absence of doxy-PEP. However, doxy-PEP is estimated to lead to a 27-fold increase in doxycycline use for STI prevention and treatment. Their model suggests that MSM of King County receive approximately 290,000 days of antimicrobials annually and that doxy-PEP increases the total number of days of antimicrobials in this population by approximately 190%. They acknowledge that doxy-PEP is a highly effective intervention for preventing syphilis.
Mittelstaedt and colleagues (Abstract 1047) also evaluated the impact of doxy-PEP prescribing on antibiotic use among MSM and TGW at a Boston sexual health clinic. They evaluated more than 1300 patients, of whom 855 started doxy-PEP from September 2022 through April 2025. Although non-doxy-PEP doxycycline prescriptions decreased by 60%, likely due to fewer chlamydia and syphilis diagnoses, doxy-PEP users received nearly 4-times as many weekly antibiotic prescriptions after starting doxy-PEP. Ceftriaxone prescriptions were unchanged, likely due to the limited efficacy of doxy-PEP in preventing gonorrhea. They did find that total prescriptions decreased by 20% among non-doxy-PEP users, which could have been from decreased transmission of STIs in sexual networks or other factors.
Gomez-Ayerbe (Abstract 1018) presented a case series of 9 syphilis cases among 313 participants on doxy-PEP.
The mean time from start of doxy-PEP to syphilis diagnosis was 37 weeks, and the overall rate (1.92 episodes/100 person-years) was substantially lower than expected. Most of the cases had minimal increases in rapid plasma reagin (although all were at least 1:4 except the 1 case with primary syphilis, which was 1:2). All responded to benzathine penicillin G. The authors note that diagnosis and interpretation of posttreatment rapid plasma regain titers may be altered by doxy-PEP.
Raccagni and colleagues (Abstract 1036) reported on antimicrobial susceptibility among MSM in Milan, Italy. Of 318 individuals positive for gonorrhea with 376 culturepositive gonorrhea episodes, 96% had tetracycline resistance, regardless of doxy-PEP use. However, doxy-PEP users were significantly more likely to have high-level resistance to doxycycline (OR, 1.87). There were no ceftriaxone-resistant isolates. The authors called for enhanced resistance surveillance.
Bien-Gund and colleagues (Abstract 1035) reported on doxy-PEP uptake among male US veterans diagnosed with bacterial STIs. Using national Veterans Administration EHRs of the more than 29,000 male veterans diagnosed with at least 1 bacterial STI from January 2022 through September 2025, they found that only 8.4% were prescribed doxy-PEP. Factors associated with being more likely to get a doxy-PEP prescription included being on HIV PrEP (aOR, 23.8; P <.001); having HIV (aOR, 7.2; P <.001); having recurrent STIs (aOR, 2.5; P <.001); having gonorrhea (aOR, 2.5; P <.001) or syphilis (aOR, 1.9; P <.001) or several STIs (aOR, 1.8; P <.001) compared with chlamydia; or living in the West (aOR, 2.3; P <.001) or the Northeast (aOR, 1.5; P <.001) compared with the South. Men older than 50 years were significantly less likely to get a prescription than men aged 18 to 30 years (aOR, 0.54; P < .001) and White men were less likely to get a prescription than Black men (aOR, 0.87; P = .02). This would suggest that a larger proportion of male veterans could benefit from doxy-PEP.
Notes
All abstracts cited in the text appear in the CROI 2026 Abstract eBook, available online at www.CROIconference.org
The IAS-USA has identified and resolved ahead of time any possible conflicts of interest that may influence CME activities with regard to exposition or conclusion. All financial relationships with ineligible companies for the authors and planners/reviewers are below.
Financial affiliations in the past 24 months: Dr Buchbinder reported grant support awarded to her institution from Gilead Sciences, Inc, Merck & Co, Inc, and ViiV Healthcare; receiving noncash provision of medicines, equipment, or administrative cash support from Gilead Sciences, Inc, and ViiV Healthcare; and serving as an advisor to Merck & Co, Inc. (Updated March 18, 2026) Dr Liu reported grant support awarded to his institution from Gilead Sciences, Inc., Merck, and ViiV Healthcare; noncash provision of medicines, equipment, or administrative support from Gilead Sciences, Inc., and ViiV Healthcare; and serving as a consultant for Gilead Sciences, Inc. (Updated March 23, 2026)
Additional Reference Cited in Text
JM Molina, B Bercot, L Assoumou, . Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): a multicentre, open-label, randomised trial with a 2 × 2 factorial design. Lancet Infect Dis. 2024;24(10):1093–1104. doi: 10.1016/S1473-3099(24)00236-6