When assessing the effectiveness of pre-exposure prophylaxis (PrEP) programmes, interventions, or modalities, it is important to understand patterns of PrEP use. Continued use of PrEP is frequently referred to as PrEP "persistence." But persistence is not defined consistently, and differences impact the interpretation of study outcomes and public health policy. We conducted a scoping review to describe and compare definitions of PrEP persistence. We searched PubMed, Embase, Scopus and Global Health records (01/01/2012-01/26/2026) for results that discussed longitudinal anti-HIV agents for HIV prevention. We included HIV, prevention and text variations of "persist-." We screened abstracts for relevance, reviewed relevant full-text articles, and then extracted key outcomes. Screening and extraction were performed independently by two investigators; conflicts were reviewed and resolved by a third. Our search returned 1549 de-duplicated results. We reviewed 362 full-text articles, yielding 147 studies for extraction. Approximately one-third (42/147, 29%) provided only qualitative persistence definitions. Among studies with operational definitions (105/147; 71%), three-quarters (80/105; 76%) considered a prescription refill and/or clinic visit date, and more than half (60/105; 57%) relied exclusively on these dates. Adherence (e.g. reported or measured drug taking) was commonly considered; 28% (29/105) of studies with an operational persistence definition included adherence assessment, and 11% (12/105) used only adherence to assess persistence. Thresholds used to classify persistent versus non-persistent PrEP use varied considerably. Definitions of PrEP persistence are heterogeneous. Most considered engagement in PrEP services (e.g. a clinic visit or medication refill), but nearly one-third included or relied exclusively on adherence measures. The differences in definitions have important implications for cross-study comparisons. The heterogeneity observed among persistence definitions complicates comparisons of PrEP interventions and related public health decision-making. A single consensus definition of persistence is unlikely to suit all study settings, objectives, and designs; however, interpretability and comparability of results could be improved by increasing transparency and consistency in reporting. Our findings emphasize the importance of capturing clinically relevant, prevention-effective use when possible and of rigorously considering the implications of a chosen persistence definition on estimates and associated conclusions.

In Brazil, men who have sex with men (MSM) and transgender women (TGW) remain heavily affected by HIV. Long-acting pre-exposure prophylaxis (LA PrEP) with injectable cabotegravir (CAB-LA) or lenacapavir (LEN-LA) is more effective at preventing HIV acquisition than oral PrEP. Our objective was to assess the potential clinical and economic impact of offering CAB-LA or LEN-LA to MSM and TGW with high vulnerability to HIV acquisition in Brazil and determine the maximum cost at which they would be cost-effective. We used the CEPAC microsimulation model of HIV prevention and treatment to evaluate two strategies for MSM and TGW aged 18-49: (1) SOC: standard-of-care oral PrEP at current coverage, and (2) SOC+LA: offering oral and LA PrEP (either CAB-LA or LEN-LA). Input parameters are derived from Brazil-based data from 2010 to 2024 and published studies: HIV incidence (%/year, MSM: 3.4 [age 18-29 years], 1.1 [30-49 years]; TGW: 5.0 [18-29 years], 1.7 [30-49 years]), relative risk reduction, LA versus oral PrEP (66% [CAB-LA]; 89% [LEN-LA]), PrEP coverage (20% [oral PrEP]; 20% [LA PrEP]) and oral PrEP cost (programmatic+drug = $207/year). Outcomes include lifetime HIV risk, life expectancy (LE) and incremental cost-effectiveness ratio (ICER) of SOC+LA versus SOC in 2024 USD/year of life saved (YLS). We identified the maximum LA PrEP cost with ICER below the established Brazilian willingness-to-pay threshold of $8740/YLS. Compared to SOC, SOC+CAB-LA would decrease MSM lifetime HIV risk from 21.4% to 16.8%, increase undiscounted LE from 39.0 to 39.4 years. For TGW, SOC+CAB-LA would decrease lifetime HIV risk from 29.5% to 23.4%, increase LE from 36.0 to 36.9 years. Results for SOC+LEN-LA would be similar to SOC+CAB-LA. SOC+LA would remain cost-effective for MSM at cost below $710/year for CAB-LA and $740/year for LEN-LA. Findings are most sensitive to LA PrEP cost, HIV incidence, and whether and by how much LA PrEP increases coverage. Offering LA PrEP with cabotegravir or lenacapavir in addition to oral PrEP for MSM and TGW in Brazil could markedly improve clinical outcomes and be cost-effective at ∼$700/year. Cost agreements are critical to ensure these prevention options are accessible in high-incidence settings.

South Africa has the largest antiretroviral therapy (ART) programme in the world, with universal access available through the public health system. Yet, gaps in coverage persist. In the Western Cape (WC), an estimated 200,000 people living with HIV are not currently on ART-many of whom are known to the health services. Exploring how people who are not on ART differ from those who are on ART may help guide more effective strategies for re-engagement and retention in care. We conducted a cross-sectional analysis of routine person-level data from the WC Provincial Health Data Centre, including adults (≥15 years) known to be living with HIV who accessed public services between October 2022 and September 2024. ART status was inferred from visit and dispensing records. Relative risks (RRs) of current disengagement were estimated using multivariable log-binomial regression on 25 imputed data sets, adjusting for sex, age, years since diagnosis, diagnosis setting and baseline CD4 count. Of 494,071 adults included, 131,368 (27%) were currently disengaged from ART. Those at elevated risk included men (aRR 1.20, 95% CI 1.19-1.21), younger people aged 15-24 years (aRR 1.54, 95% CI 1.51-1.57), those with CD4 >500 cells/mm3 at diagnosis (aRR 1.26, 95% CI 1.24-1.28) and individuals diagnosed in hospital (aRR 1.41, 95% CI 1.39-1.43) or during pregnancy (aRR 1.20, 95% CI 1.18-1.22). However, the majority of those disengaged were not from these groups, proportionally representing the underlying population living with HIV. Model discrimination was poor (AUC 0.614), indicating that these characteristics do not reliably identify those disengaged. Most disengaged individuals are from larger, lower-risk demographic groups and would be missed by interventions targeting higher-risk demographics. Whole-population strategies that address common barriers to retention through more inclusive, person-centred care offer the greatest potential to improve ART coverage.

Migrants living with HIV often face high mobility, vulnerability and limited baseline information on HIV-1 genotype or treatment history. We aimed to assess the effectiveness and persistence of long-acting injectable cabotegravir and rilpivirine (LAI CAB+RPV) among migrants in Spain. This multicentre cohort study across 58 Spanish hospitals included virologically suppressed adults switching to CAB+RPV LAI before January 2025. Data collection started in June 2023. Baseline characteristics and outcomes were compared by migrant status, and multivariate Cox proportional hazards regression models were fitted to assess factors associated with virological failure (VF) and discontinuation. Propensity score matching (PSM) by gender, age, known genotype and prior VF was employed to control for confounding. Of 3135 participants, 951 (30.3%) were migrants, predominantly from Latin America. Median follow-up was 13.8 months (interquartile range 8.91-19.1). VF occurred in 0.9% of migrants versus 0.5% of Spanish-born individuals (odds ratio 1.89, 95% confidence interval [CI] 0.69-5.03; p = 0.22). In adjusted models, migrant status showed a non-significant trend towards higher VF (adjusted hazard ratio [aHR] 2.16, 95% CI 0.89-5.22; p = 0.079). At 12 months, 95.8% of migrants (461/481) persisted on LAI CAB+RPV treatment versus 98.3% of Spanish-born individuals (1348/1372) (p = 0.005). Discontinuation due to any adverse event was more frequent in migrants (3.3%vs. 1.8%). Migrant status was significantly associated with discontinuation due to both local (aHR 2.63, 95% CI 1.33-5.26; p = 0.005) and systemic adverse events (aHR 3.33, 95% CI 1.45-7.69, p = 0.005). In the PSM cohort (n = 932 per group), migrant status was independently associated with increased risk of VF (aHR 3.51, 95% CI 0.95-12.98, p = 0.045) and discontinuation due to systemic adverse events (aHR 2.88, 95% CI 1.01-8.17, p = 0.047). Nearly one-third of participants switching to LAI CAB+RPV were migrants. While VF was rare overall, migrants had a significantly higher risk of treatment discontinuation, partly driven by adverse events. These findings highlight the need for closer monitoring and tailored strategies to optimize persistence with LAI regimens in migrant populations.

Chronic inflammation is a unique contributor to cardiovascular disease (CVD) risk among people living with HIV, yet there is a lack of consensus on the predictive utility of inflammatory biomarkers in this population. We conducted a systematic review assessing the predictive value of inflammatory biomarkers for major adverse cardiovascular events in people living with HIV to inform their potential integration into CVD risk assessment. MEDLINE, Embase and Google Scholar were searched for articles published up to 01 May 2024. We included prospective cohort and nested case-control studies of adults living with HIV with inflammatory biomarker measurements in blood and at least one year of follow-up to major adverse cardiovascular events. Risk of bias was assessed using the Quality in Prognostic Studies (QUIPS) tool. Where at least two studies reported the same type of effect measure for a biomarker, results were pooled using an inverse variance heterogeneity model. Among 5156 screened citations, 21 studies reporting 31 inflammatory biomarkers met inclusion criteria. Meta-analysis showed high-sensitivity C-reactive protein (hsCRP) positively associated with future cardiovascular events (hazard ratio = 1.86 per log10 unit; 95% CI1.39-2.50, n = 5,254). Three biomarkers, interleukin 6 (IL-6), D-dimer, and N-terminal pro-brain natriuretic peptide (NT-proBNP), demonstrated positive, statistically significant associations with adverse cardiovascular outcomes in at least two non-overlapping studies, though heterogeneous effect measures precluded meta-analysis. Most research (14/21 studies) was conducted exclusively in high-income settings, and female representation was low (median proportion = 15.5%; IQR 8.4-20.9%). All but three studies had a moderate or high risk of bias in at least one domain. We identified several inflammatory biomarkers with potential prognostic value, but most associations were derived from single or heterogeneous studies. The certainty of evidence is reduced by methodological heterogeneity, few high-quality studies and the underrepresentation of low- and middle-income countries (LMICs). Consistent positive associations between inflammatory biomarkers and future CVD in people living with HIV support a central role of inflammation in HIV-related CVD. Representative, large-scale studies that include women and LMICs are needed to guide the integration of candidate biomarkers into CVD risk prediction models. CRD42024542944.

Indonesia has an escalated HIV epidemic among key populations, especially men who have sex with men (MSM). Diagnosis and immediate treatment of acute HIV infection (AHI), the earliest phase with the highest transmission risk, is beneficial for individual health and can reduce onward transmission. To inform whom to test for possible AHI using targeted, risk-stratified HIV-PCR testing, this study evaluated the performance of the validated, seven-item Amsterdam AHI risk score among Indonesian MSM, and developed a locally optimized score. We used the INTERACT prospective cohort of MSM (≥16 years) attending sexual health clinics in Jakarta and Bali (May 2023-February 2025) who were tested with add-on Xpert HIV-PCR (Cepheid) if their HIV antibody rapid testing was negative or inconclusive. We used generalized estimating equation models to generate risk scores, combining symptoms, risk factors and socio-demographics. The optimized risk score was internally validated using bootstrap resampling. We calculated area under the curve (AUC), sensitivity and specificity (ISRCTN41396071). Among 1887 individuals, 20 were diagnosed with AHI, and 1867 tested AHI negative across 3446 test visits. The Amsterdam score yielded an AUC of 0.82 (95% CI 0.75-0.90) with a sensitivity of 85.0% (64.0%-94.8%) and a specificity of 59.2% (57.5-60.8). The optimized risk score included one symptom (fever <2 weeks), one risk factor (condomless receptive anal intercourse <6 months) and two socio-demographic characteristics (age 16-30 years, not having received higher education), and achieved an AUC of 0.91 (0.87-0.96) with a sensitivity of 100% (83.9-100) and a specificity of 65.3% (63.6%-66.8%). Internal validation yielded an AUC of 0.86 (0.67-0.97). Applying this risk score would classify 35.1% of MSM as eligible for add-on HIV-PCR testing, identifying 83.9%-100% of individuals who have AHI. This four-item risk score of easily collected variables can facilitate efficient AHI detection in high-yield clinic settings, enhancing opportunities for HIV prevention. In the Indonesian context, younger MSM with lower educational attainment were particularly vulnerable to AHI.

While HIV self-testing (HIVST) presents a promising solution for early HIV detection, access to such testing remains limited in Canada. Achieving the United Nations 95% target for HIV status awareness requires scalable and cost-effective implementation approaches. The I'm Ready programme is a national, mail-based HIVST initiative targeting key high-risk populations supplemented by peer navigation supports to enhance engagement. This study aimed to explore the cost-effectiveness of the I'm Ready programme from the perspective of Canada's publicly funded healthcare system. We developed a Markov model to predict the lifetime costs and quality-adjusted life-years (QALYs) for high-risk individuals receiving HIVST through the I'm Ready programme compared to point-of-care testing in a physician's office (standard care). Probability and health utility values were obtained from published literature, while costs were obtained from the pilot I'm Ready programme or secondary Canadian data sources. Costs and outcomes were discounted 1.5% annually, with costs reported in 2024 Canadian dollars. At a 53% uptake, 100% HIVST sensitivity and 99.5% specificity, the I'm Ready programme was associated with an incremental cost of C$270 and a QALY gain of 0.01 per person, with an incremental cost-effectiveness ratio of $23,331/QALY compared to standard care. Key drivers of cost-effectiveness included cost and utility associated with antiretroviral therapy initiation, utility of the AIDS health state and testing uptake under standard care. At the current test uptake and diagnostic accuracy levels, the I'm Ready programme is cost-effective at the willingness-to-pay threshold of $50,000 per QALY. While findings reflect the Canadian health system context, this study offers broader insight into the value of HIVST as a public health tool to accelerate progress towards global HIV awareness targets.