Journal of the International AIDS Society

BackgroundThe era of universal treatment for HIV has seen high rates of disengagement from antiretroviral therapy (ART) programs and re-engagement after interruptions, with modeled estimates of non-naive initiators >50% in many places. Most re-engagers are reluctant to admit prior antiretroviral exposure, and non-self-reported data on proportions of re-initiators are scarce. We synthesized data from multiple sources to explore the proportion of people who present for initiation with evidence of prior ART use in South Africa. MethodsWe enrolled a sequential sample of adults presenting to initiate ART or to re-initiate ART after an interruption >3 months and collected 1) self-reported previous treatment experience; 2) electronic medical record (EMR) evidence of prior ART clinic visits; 3) baseline blood tests for metabolites of tenofovir diphosphate; and 4) laboratory records indicating prior ART-related tests. Interviews were conducted with a sub-sample of clients who self-reported no prior ART use but had evidence of metabolites. ResultsAmong 89 enrolled participants (median age 32.5, 62% female), 16 (18%) self-reported previously taking ART >3 months prior to enrolment. An additional 33 (45%) who did not self-report prior exposure had EMR or laboratory evidence of prior ART use, for a total of 49 (55%) clients with known prior treatment exposure at initiation. Sensitivity of self-report was 40%, EMR 43%, metabolite testing 45%, and laboratory records 73%. Interviewees (n=11) reported opting to present as naive because they perceived that disclosure of prior disengagement would cause delays accessing treatment, require additional documentation, and elicit negative responses from healthcare workers. Study limitations included short duration of metabolite detectability (90 days), inability to link individuals within the EMR to discern ART experience at other facilities, and lack of baseline viral load testing. ConclusionsAt least 55% of clients initiating ART in South Africa have prior treatment experience, but only a third of re-initiators voluntarily reveal this. Laboratory records, which reflect long-term experience, yielded the most accurate results for ascertaining prior treatment exposure. As numbers re-engaging in HIV care after a treatment interruption increase, understanding reluctance to self-report ART experience and exploring opportunities to overcome barriers are critical for preventing repeated interruptions.

BackgroundConsistent engagement in antiretroviral therapy (ART) care is crucial for health outcomes and HIV transmission reduction. This study examined the first two years of ART engagement patterns in two public ART clinics in Lilongwe, Malawi. Routine retention support is provided using ART "Buddies" or a two-way texting (2wT) system for those with phones and interest. MethodsART engagement patterns were analysed across six-month intervals (>0-6, >6-12, >12-18, >18-24). Patients retained on ART were categorised as continuously engaged (attended all appointments within 13 days), cyclical engagement (returned late (14-59 days) at least once), and re-engaged (missed an appointment by [≥]60 days but returned to care). Clients who disengaged (lost to follow-up (LTFU), transferred out, stopped, or died) at any interval were assigned that outcome. Engagement patterns were visualised using a Sankey chart. ResultsAmong 6,303 clients, 1,030 (16%) were in the Buddy support group with phone access, 4,850 (77%) without phone, and 423 (7%) in the 2wT support group. 5,300 (84%) clients were grouped into 33 common engagement patterns over 24 months; 1,003 (16%) of clients illustrated fewer common patterns. By 24 months, 3,368 (53%) were retained on ART: 296 (70%) of 2wT; 2,793 (58%) of Buddy with phone access; and 3,367 (27%) of Buddy without phone access. Among the 3,368 clients retained on ART at 24 months, 1,836 (55%) were continuously engaged, 1,031 (30%) had cyclical engagement, and 500 (15%) re-engaged after LTFU. Overall, 1836 (29% of the total cohort of 6,303) continuously engaged in care over 24 months. In the six-month interval analysis, clients aged 50+ had the highest proportion (n=184, 70%) of continuous engagement overall, compared to individuals aged 35-49 years (n=832, 58%) and 18-34 years (n=820, 49%). 2wT clients showed the highest continuously engagement up to 18 months (70% at 0-6 months, 72% at >6-12 months, and 81% at >12- 18 months), compared to Buddy groups (with phone access:57%, 58%, 76%; without phone access: 30%, 33%, 62%). ConclusionA small proportion of clients were continuously on ART over the first 24 months of ART. Older clients and 2wT participants had more favourable ART engagement patterns; those without phone access faired worst. While most ART clients followed similar ART engagement patterns, a few showed varying trajectories. Tailored retention support based on engagement patterns could improve long-term retention in ART care.

Retention in antiretroviral therapy care remains a major challenge in high-burden settings such as Malawi, where substantial loss to follow up undermines treatment outcomes and long-term epidemic control. Although machine learning models can accurately identify patients at high risk of disengagement, there is limited evidence on how these predictions can be translated into improved retention outcomes in practice. This study addresses this gap by linking machine learning-based risk stratification to the targeted allocation of retention interventions, providing a framework for evaluating their expected impact on ART retention outcomes. We developed a patient-level Monte Carlo simulation model that integrates individual predicted probabilities of loss to follow up from a validated Extreme Gradient Boosting model with intervention effect sizes derived from a meta-analysis of ART retention interventions conducted in sub-Saharan Africa. The study population included 1,705 ART patients receiving care at Lighthouse Trust clinics in Lilongwe, Malawi. Patients were stratified by predicted risk, and the highest-risk group (n = 512) was targeted for intervention. Six interventions were evaluated, including Expert Client support, psychosocial support, two-way text messaging, adherence clubs, community ART groups, and teen clubs, followed by subgroup-specific and combined approaches allocated based on predicted risk. The primary outcome was twelve-month ART retention, estimated over 5,000 simulation iterations. Subgroup and post-simulation analyses were conducted to assess heterogeneity in intervention response. Among patients classified as high risk (n = 512), baseline retention was 44.1%. Individual interventions improved retention to 52.7% with two-way texting (RR = 1.19; p < 0.001) and 55.0% with Expert Client support (RR = 1.25; p < 0.001). A combined intervention package produced larger gains, increasing retention to 64.0% (RR = 1.45; p < 0.001), corresponding to an absolute improvement of 19.9 percentage points. Intervention effects varied across subgroups, with significant improvements observed among newly initiated patients (43.0% to 58.9%; RR = 1.37; p < 0.001) and clinically unstable patients (28.3% to 39.1%; RR = 1.38; p = 0.01), while effects among adolescents were more modest (34.3% to 45.6%; RR = 1.33; p = 0.03). Despite these improvements, 46% of high-risk patients remained hard to retain after receiving multiple interventions. In this subgroup, expected retention increased only marginally from approximately 0.15 at baseline to 0.20 after intervention, with poor outcomes observed among patients who were virally unsuppressed, had depressive symptoms, or were younger. Machine learning-guided targeting of ART retention interventions can substantially improve retention outcomes, particularly when interventions are combined. However, a substantial subgroup of patients remains hard to reach and vulnerable to disengagement, indicating that existing strategies may be insufficient for individuals with complex clinical and psychosocial needs. This study contributes to knowledge by introducing an integrated framework that combines machine learning risk prediction, meta-analytic intervention effects, and patient-level Monte Carlo microsimulation to quantify twelve-month ART retention outcomes under risk-based targeting with subgroup-specific intervention allocation before real-world implementation. These findings highlight the potential of using individual risk to guide the delivery of retention interventions within routine ART programs to enable more efficient, proactive, and patient-centered allocation of retention resources.

IntroductionDespite advances in antiretroviral therapy (ART), notable proportion of individuals still present with advanced HIV disease (AHD) at treatment initiation, defined by CD4 counts <200cells/{micro}L or WHO stage 3/4 conditions. This group faces higher mortality and more opportunistic infections. While clinical guidelines are available, they do not adequately address the unique needs of AHD patients, particularly early in treatment. Addressing these gaps could improve care and outcomes. MethodsFrom 9/2022-6/2023 we surveyed a sequential sample of clients presenting for ART initiation or [&le;]6 months post-initiation at 18 primary healthcare facilities across three provinces. We elicited socio-demographic data, HIV care history, and service delivery preferences and expectations and linked survey responses to routine medical record data. We used descriptive statistics to summarise client characteristics and calculated relative risks and risk differences to compare outcomes between AHD and non-AHD clients. The primary outcomes were 6-month retention and viral load suppression, categorized as suppressed (<50 copies/mL), low-level viremia (50-1,000 copies/mL), or unsuppressed ([&ge;]1,000 copies/mL) at the 6-month viral load test. ResultsOf 1,098 clients (72% female, median age=33), 938 had CD4 count or WHO staging recorded at ART initiation. Of these 29% (n=275) had advanced HIV disease (AHD), with a median CD4 count of 108 cells/{micro}L. AHD clients were more likely to be male (44% vs.21%), older (38 vs.31 years), and seek care due to illness (63% vs. 33%). They also had higher rates of TB (42% vs.12%) and TB testing (76% vs. 67%). Service preferences and healthcare resource utilization were similar across groups. Retention at six months was similar (80% vs. 75%), but AHD clients had higher mortality (1.0% vs. 0.2%). AHD clients were more likely to experience low-level viremia (24% vs. 11%; RR=2.27, 95%CI=1.67-3.09) and less likely to achieve viral suppression (43% vs. 47%). ConclusionsAHD remains a barrier to optimal ART outcomes in South Africa. Low-level viremia in the first six months highlights the need for targeted care models with early detection, rapid ART initiation, and tailored support to address specific needs of AHD clients. Updating ART guidelines to specifically provide for AHD will be important in improving outcomes for this group. Study registrationClinicaltrials.gov NCT05454839, Clinicaltrials.gov NCT05454852

IntroductionFor clients on HIV treatment in sub-Saharan Africa, disengagement from HIV care in the early treatment period is a critical obstacle to achieving UNAIDSs second 95 target. While South Africas Differentiated Service Delivery Guideline on Fast Track Initiation and Counseling (FTIC) define normative procedures, the effect of guideline implementation and the underlying drivers of disengagement remain unclear. MethodsThe PREFER mixed-methods study enrolled a prospective cohort of adult clients initiating ART, returning to care after a period of disengagement or already on ART for [&le;]6 months at 18 public sector healthcare facilities in South Africa. A survey collected data on demographic and clinical characteristics and preferences of participants who were followed up through routinely-collected medical visit records for up to 7 months after treatment initiation to estimate continuity of HIV care (attended all scheduled visits within 28 days). Focus group discussions (FGDs) were conducted approximately 12 months after enrollment among a subset of participants who had expressed concerns about treatment retention. ResultsDuring the study period 7/9/2022-30/6/2023, PREFER-SA enrolled 1,049 participants (72% female, median age=33 years, 24% with CD4 count<200cells/mm3); 122 of whom also participated in focus group discussions. By 6 months on ART, 23% were not continuously in HIV care. Those newly initiating ART at study enrollment were more likely to have disengaged or interrupted treatment by 6 months as those who had remained in care for [&ge;]1 visit. Disengagement was also more likely among men and younger (18-24 years) participants, those reporting food scarcity, and those initiated on regimens other than Dolutegravir. Disengagement did not differ by gender, relationship status, or CD4 count. Qualitative FGD results suggest participants experience barriers to adherence within and between all levels of the socio-ecologic model. Challenges related to the facility experience were most prominent. ConclusionsAmong adults initiating or re-initiating ART in South Africa, the highest risk of disengagement is immediately after initiation. We identified several potentially modifiable individual and social characteristics associated with early disengagement. Improving the patient facility experience and strengthening implementation of SAs Service Delivery Guidelines may increase retention during the early treatment period.

BackgroundTracing HIV treatment clients who have interrupted or disengaged from care is a common, guideline-recommended practice globally. Most guidelines prioritize tracing based on clinical condition or HIV transmission risk, not likelihood of client traits that may affect return to care after tracing. Targeting tracing to those most likely to return could increase efficiency substantially. We conducted a systematic review to identify characteristics of clients most likely to return after tracing. MethodsWe searched PubMed, EMBASE, and Web of Science for studies published between 1/2004 and 7/2025 that reported outcomes of tracing interventions in sub-Saharan Africa. Eligible studies reported characteristics of clients who interrupted care, were eligible for a tracing intervention with the intent to return them to care (i.e. not solely research to determine client outcomes after interruption) and were subsequently traced or had tracing attempted. Our primary outcome was client characteristics associated with return to care after tracing, compared to those who did not return after tracing or attempted tracing. ResultsWe identified 13,208 articles; 9 met the inclusion criteria. Older age and female sex were the most consistent predictors of return after tracing. Earlier tracing (relative to last missed visit) was associated with return in 3 studies; 1 found the opposite. Frequent contact attempts, rural location, and psychosocial factors (stigma, disclosure) were also associated with return. Clinical characteristics (CD4 counts and WHO stage) showed mixed or null associations with tracing effectiveness. ConclusionCharacteristics of clients who return to care after tracing, compared to those who are traced or for whom tracing is attempted and do not return, are rarely reported, making it difficult to evaluate this intervention. Using a "high-benefit" approach to targeting tracing--i.e. prioritizing based on likely benefit generated by a successful response, rather than clinical need--may potentially improve the efficiency of HIV programming.

IntroductionIn countries with high HIV prevalence, differentiated service delivery programmes (DSD) for antiretroviral therapy (ART) play a vital role in improving access to ART for people living with HIV (PLHIV). While the benefits of DSD for clients enrolled in these programmes have been described, it is unknown whether DSD additionally benefits clients who are ineligible for these programmes, through allowing more clinic resources to be directed towards them. We aimed to assess whether increases in DSD referrals are associated with better care for clients initiating ART. MethodsDe-identified, routinely collected TIER.Net data from 112 clinics in KwaZulu-Natal, South Africa were used to assess service delivery for clients initiated during 2022-2023. Outcomes were the probability of newly-initiated clients having an initiation CD4 count result, a 6-month viral load result (among those visiting at 6 months) and being retained for 6 months after initiation (<90 days late for all visits). Using generalized linear mixed effects models, we measured the association of clinic DSD referral with outcomes and derived marginal probabilities for each outcome for varying DSD levels. Risk differences were calculated, with confidence intervals estimated using bootstrapping. ResultsBetween August 2022 and October 2023, 26,226 PLHIV with a median age of 32 years were initiated on ART. Monthly DSD referral proportions at the clinics varied but increased on average from 21% in August 2022 to 29% in October 2023. Overall, 77% of clients had a CD4 count test at initiation, 72% of those attending their 6-month visit had a viral load test, and 70% were retained to 6 months. We found a positive relationship between DSD referrals and test completion, although this association was only weakly significant for viral load test; when DSD referrals increased from 20-30%, the probability of having a CD4 count and viral load test increased by 0.97% (95% CI: -0.27,2.58%) and 1.35% (95% CI: 0.11,2.95%) respectively. We found no evidence of an association with DSD referrals and 6-month retention. ConclusionsIn the first study of this topic, increases in DSD resulted in small improvements in care. With full DSD scale-up, however, programmatically meaningful effects could be achieved.

IntroductionAttrition from HIV treatment is high during patients first 6 months after antiretroviral therapy (ART) initiation and patients with less than 6 months on ART are systematically excluded from most differentiated service delivery (DSD) models, which are intended to reduce attrition. Despite eligibility criteria requiring greater than 6 months on ART, some patients enroll earlier. Using routinely-collected medical record data in Zambia, we compared loss to follow-up (LTFU) among patients enrolling in DSD models early (<6 months on ART) to LTFU among those who enrolled according to guidelines ([&ge;]6 months on ART) in order to assess whether the ART experience eligibility criterion is necessary. MethodsWe extracted data from electronic medical records for adults ([&ge;]15 years) who initiated ART between 01/01/2019 and 31/12/2019 and evaluated LTFU, defined as >90 days late for last scheduled medication pickup, at 18 months for "early enrollers" (DSD enrolment after <6 months on ART) and "established enrollers" (DSD enrolment after [&ge;]6 months on ART). We used a log-binomial model to compare LTFU risk between groups, adjusting for age, sex, urban/rural status, ART refill interval and DSD model. ResultsFor 6,340 early enrollers and 25,857 established enrollers there were no important differences between the groups in sex (61% female), age (median 37 years), or setting (65% urban). ART refill intervals were longer for established vs early enrollers (72% vs 55% were given 4-6-month refills). LTFU at 18 months was 3% (192/6,340) for early enrollers and 5% (24,646/25,857) for established enrollers. Early enrollers were 41% less likely to be LTFU than established patients (adjusted risk ratio [95% confidence interval] 0.59 [0.50-0.68]). ConclusionsPatients enrolled in DSD models in Zambia with < 6 months on ART were more likely to be retained in care than patients referred after they were established on ART. A limitation of the analysis is that early enrollers may have been selected for DSD participation due to providers and patients expectations about future retention. Offering DSD model entry to at least some ART patients <6 months after ART initiation may help address high attrition during the early treatment period.

IntroductionDespite improvements in treatment for people living with HIV (PWH), adherence remains a challenge for many. In this study we aimed to identify preferences for daily pill or long-acting injectable (LAI) antiretroviral therapy (ART) and for possible treatment package features, among PWH enrolled in Ryan White HIV/AIDS Program Part A (RWPA) Medical Case Management (MCM) programs. MethodsParticipants were recruited from six MCM programs from across the New York RWPA eligible metropolitan area (the five boroughs of New York City and Rockland, Putman, and Westchester counties). We developed a discrete choice experiment (DCE) with four attributes: (1) Type of ART Medication (daily pills or LAI), (2) Service Location and Mode, (3) Support, and (4) Rewards. We used an alternative-specific design in which the levels for the last three attributes were dependent on levels within the first (Type of ART). Latent class multinomial logit analysis (LCA) was used for preference estimation and hypothesis-free investigation of preference heterogeneity. ResultsFrom June 2022 through January 2023, 200 New York RWPA MCM clients completed the DCE. We selected a two-group LCA solution. A majority of participants had a higher preference for LAI regimens compared to daily pills (n=114 [57%] versus n=86 [43%]). Those who preferred LAI ART were younger (median age 49 versus 58.5 years, p<0.001), less likely to identify as straight/heterosexual (69% versus 82%, p=0.03), and more likely to identify as Latino/a (54% versus 30%; p<0.001). Preferences for service locations/mode, supports, and rewards were similar across LCA groups. Participants who preferred LAI ART were more likely to have heard of LAI ART before the survey (59% versus 41%, p=0.012). Overall, only 4% of participants self-reported having tried LAI ART. ConclusionsAssessing preferences among groups under-represented in clinical trials is essential to effective and equitable real-world implementation of innovative treatment options. Our study found that there were distinct groups that differed in their preferred ART regimen type and that New York RWPA MCM clients had limited familiarity with LAI ART. To inform regimen selection, we began pilot-testing educational materials and a patient-provider decision-making tool in 2023.

BackgroundRetention in HIV care during the early treatment period is one of the most serious challenges facing HIV programs, but the timing and patterns of early disengagement from care remain poorly understood. We describe patterns of engagement in HIV care during the first and second 6-month periods after initiation. MethodsWe analysed retrospective datasets of routinely collected EMR data from [&ge;]18-year-old clients who initiated ART at public sector clinics in South Africa after 01/01/2018 and had [&ge;]14 months potential follow up. Using scheduled visit dates, we classified observed visits into "as planned" or "late" and characterized engagement in care as continuous (all scheduled visits attended [&le;]28 days late), cyclical (at least one visit >28 days late with a return visit observed) or disengaged (visit not attended and no return visit to the same facility observed). Results33,821 client records were included (65% female, median age 33). By six months after ART initiation, 57% had remained continuously in care, 14% had engaged cyclically, 11% had transferred to another facility, 1% had died and 16% had disengaged from care at the initiating facility. Among disengagers in the first 6 months, 58% did not return after their initiation visit, 10% disengaged within the first three months, and the remaining 32% disengaged between 3-6 months. By 12 months after initiation, the overall proportion disengaged was 23%, and only 38% of the cohort had maintained continuous engagement for the full 12 -month period.. Patterns of engagement that were established during the first 6 months on ART demonstrated little change in months 7-12, with participants who were cyclically engaged in months 0-6 were nearly twice as likely to disengage in months 7-12 as continuous engagers in months 0-6 (relative risk 1.8, 95% CI: 1.70-1.99). ConclusionsAs recently as 2018, fewer than 60% and 45% of clients starting ART in South Africa were continuously engaged in care (no interruptions >28 days) at 6 and 12 months, respectively, at their initiating facilities. The needs of continuous and cyclical engagers and disengagers during the first 6 months after initiation may differ and require different interventions or models of care.

IntroductionTreatment as prevention (TasP) and pre-exposure prophylaxis (PrEP) could impact the HIV epidemic among Female Sex Workers (FSW) but their cost-effectiveness is uncertain in this group. This study aims to model the cost-effectiveness of TasP and PrEP among FSW in Cotonou, Benin. MethodsA demonstration study assessed TasP and PrEP use among FSW in Cotonou. A dynamic HIV transmission model was developed to estimate the impact of this intervention and published elsewhere. Incremental economic costs of the study were collected prospectively capturing both provider and FSW costs. The incremental cost-effectiveness ratio per HIV infection and disability-adjusted life years (DALY) averted were estimated over a 20 year time horizon with costs converted to USD 2020 and both costs and DALYs discounted at 4.5% per year. Different cost scenarios were modelled to investigate the cost-effectiveness of the intervention as delivered by the government reflecting current day implementation and resource costs. ResultsThe mean provider annual economic cost per FSW on TasP was $646, with an initiation cost of $347 and mean annual user costs were $16. The mean initiation costs for PrEP were $268, mean annual provider costs were $359-$499 and annual user cost $15-$21 depending on adherence level. TasP was found to be cost saving for all cost scenarios examined compared to routine HIV care for FSW. PrEP was not cost-effective for any cost scenario, population coverage or adherence level examined. ConclusionOur results support TasP but not PrEP for FSW in our setting. A streamlined, outreach delivery model with reduced costs should be investigated to assess its cost-effectiveness in this setting.

IntroductionReplacing conventional, facility-based HIV treatment with less intensive differentiated service delivery (DSD) models could benefit DSD clients and the health system, but its value depends on maintaining or improving clinical outcomes. We compared retention and viral suppression between antiretroviral therapy (ART) clients enrolled in DSD models to those eligible for but not enrolled in DSD models in South Africa. MethodsWe applied a target trial emulation (TTE) methodology to data from South Africas electronic medical record system (TIER.Net) for 18 clinics across 3 provinces and estimated retention in care (attended clinic visit within 12 months) and viral suppression (<400 copies/ml3) at 12, 24, and 36 months after follow-up start date, defined as DSD enrollment date for the intervention arm and the first trial enrollment period clinic visit for the comparison arm. Clients were eligible for DSD models if they were [&ge;]18 years old, on ART [&ge;]12 months, and had two suppressed viral load (VL) measurements, per prevailing national guidelines. For the TTE, we designated eight 6-month target trial enrolment periods between 1 July 2017 and 1 July 2021. For each period, we estimated the risk differences for retention in care and viral suppression by comparing those enrolled in DSD models to those not enrolled, using a Poisson distribution with an identity link function. We report adjusted and unadjusted risk differences for clients enrolled in DSD models and for DSD-eligible clients not enrolled in a DSD model. Results and discussion49,595 unique individuals were eligible for DSD enrolment over eight target trials, contributing to a total of 148,943 trial-clients, of whom 17% (25,775) were enrolled in DSD models. The pooled adjusted risk difference for retention in care between clients enrolled in DSD and those not enrolled in DSD was 3.2% (95% confidence interval (CI) 1.6%; 4.7%) at 12 months, 4.2% (2.4%; 6.0%) at 24 months, and 4.4% (2.0%; 6.8%) at 36 months. For viral suppression, the adjusted risk difference comparing DSD to non-DSD was estimated to be 1.4% (-0.5%; 3.2%) at 12 months, 1.7% (-0.5%; 4.0%) at 24 months, and 1.4% (- 0.6%; 4.4%) at 36 months. Results remained consistent across target trials. Clients who were younger, lived in urban settings, or had less ART experience at trial enrolment had lower retention. ConclusionsClients enrolled in DSD models in South Africa had slightly better retention in care and similar viral suppression to those who were eligible for but not enrolled in DSD. With better or equivalent outcomes, DSD models can be assessed on the basis of non-clinic costs and benefits, such as changes in quality of care and resource utilization. RegistrationClinicaltrials.gov NCT04149782.

BackgroundThe first year after HIV treatment initiation or re-initiation is the period of highest risk of a treatment interruption or disengagement, yet little is known about the timing, patterns, and effects of interruptions in the early treatment period. MethodsUsing routinely collected electronic medical record data from 543 Zambian facilities from 01/01/2018 to 28/02/2023, we described patterns of engagement during the first year of HIV treatment. We categorized clinic visits and other interactions based on whether they were attended as planned ([&le;]scheduled date), late [&le;]28 days, or late >28 days). We used these visit categories to define engagement patterns for months 0-6 and months 7-12 after initiation or re-initiation as 1) continuous (attended all scheduled clinic and medication pickup visits as planned; 2) cyclical (attended [&ge;]1 visits late >28 days but returned to and remained in care); or 3) disengaged (missed a scheduled visit by >28 days and had no evidence of return). FindingsWe enrolled 159,429 adult participants (61% female, median age 33). Of the 513,322 interactions observed in the 12 months after initiation, 53% occurred as planned, 22% were late [&le;]28 days late, 9% were >28 days late, and 17% were scheduled but never attended. In 0-6 months after initiation, 51% clients were continuously engaged, 12% cyclically engaged, and 33% disengaged. Two thirds of disengagers (21% of cohort) did not return after the initiation visit. During months 7-12, most clients who had been continuously engaged in months 0-6 (54%) remained continuous, while 18% moved to cyclical engagement. Among cyclical engagers in months 0-6, nearly half (47%) moved to being continuously engaged by month 12. Only 34% of the study population remained engaged continuously by the end of the 12-month period. InterpretationFewer than 60% of clients initiating ART care between 2018 and 2022 at Zambian facilities remained continuously engaged at month 6 and 34% at month 12. Cyclical engagement and frequent interruptions should be accepted as the norm and models of service delivery designed to accommodate them. FundingFunding for this study was provided by the Gates Foundation under INV-031690 to Boston University (SR principal investigator and award recipient). www.gatesfoundation.org. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Support for collection of the data used in this study was provided by the U.S. National Institutes of Healths National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Fogarty International Center (FIC) under Award Number U01AI069924. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

BackgroundAs countries in sub-Saharan Africa have scaled up access to antiretroviral therapy (ART) for HIV, patient attrition rates of up to 30% per year have created a large pool of individuals who initiate treatment with prior ART experience (non-naive re-initiators). Little is known about the proportion of non-naive re-initiators within the population presenting for treatment initiation. MethodsWe conducted a comprehensive, rapid review of recent peer-reviewed reports that presented data on proportions of adult patients initiating ART who were treatment naive and non-naive in sub-Saharan Africa. Searching PubMed, EMBASE, Web of Science, and international conference abstracts, we sought studies published after 1 January 2018 with data collected after January 2016, when universal HIV treatment access became the norm. We included clinical trials and observational studies and accepted self-report, laboratory discernment of antiretroviral metabolites, or viral suppression at initiation or previously reported in the medical record as evidence of prior exposure. We report results of each eligible study and identify gaps in the literature. ResultsOf 1,782 articles returned in our initial search, we found nine, describing ten cohorts, that contained sufficient information for the review, of which half were from South Africa. The proportion of the study samples with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample among self-reported naive patients). The vast majority of studies that were screened did not report proportions of initiators who were non-naive, and among the few that did, the metrics used to determine and report non-naive proportions were inconsistent and difficult to interpret. ConclusionThe proportion of patients initiating HIV treatment who are truly ART-naive is not well documented in the literature. From the studies identified, it seems likely that 20% to 50%--and likely at least 30%--of ART patients who present for ART are re-initiators. Standard reporting metrics and diligence in reporting this characteristic of ART initiation cohorts are needed, as is research to understand the reluctance of patients to report prior ART exposure.

Antiretroviral therapy (ART) retention is critical for achieving viral load suppression (VLS) among people living with HIV (PLHIV). Retention remains challenging in high-prevalence settings like Malawi. Short messaging service (SMS) interventions, particularly hybrid two-way texting (2wT), show promise in improving ART retention. We conducted a randomized control trial (RCT) at Lighthouse Trust in Lilongwe, Malawi, to evaluate the effectiveness of a hybrid 2wT system to improve early retention, appointment attendance, and VLS among new ART initiates within six months of ART initiation. After receiving routine ART initiation counseling, 452 new ART clients with mobile phones were randomized to 2wT or standard of care (SoC). The 2wT group received weekly motivational messages, appointment reminders, and had access to an open-ended SMS communication channel with healthcare workers. The SoC group received peer support at clinic visits and visit reminder phone calls. All participants were traced if they missed a clinic appointment by 14 days. Study outcomes included: retention in care (alive on ART), appointment adherence (attending within 2 days), and VLS (< 200 copies) at six months. Data from electronic medical records were analyzed using Chi-square tests and multivariable logistic regression. At six months post ART initiation, the 2wT group demonstrated significantly higher appointment adherence (59.6% vs. 46.8%, p = 0.008) and VLS (97.5% vs. 93.2%, p=0.007) compared to SoC. Among both 2wT and SoC, 91% remained in care (p=0.68). Although retention among 2wT and SoC at 6 months did not differ, 2wT clients were more likely to attend clinic visits on time and reach VLS in the first six months. The low-tech 2wT approach offers a scalable, appropriate intervention to enhance visit compliance and VLS among PLHIV with mobile phones. Implementing 2wT study over a longer time frame and among more clients would likely provide evidence for scaling 2wT more broadly.

IntroductionEconomic evaluations of HIV pre-exposure prophylaxis (PrEP) and associated implementation strategies guide evidence-based policies, programmes, and resource allocation. Since 2015, there has been an evolution in PrEP modalities, implementation strategies, and prioritization of key populations with unmet HIV prevention needs, alongside the scale-up of other HIV prevention interventions. Our systematic review describes the evolving landscape of economic evaluations of PrEP to help identify evidence gaps relevant to the current HIV epidemic and response (PROSPERO: CRD42016038440). MethodsWe searched five databases, without language restrictions, for peer-reviewed economic evaluations from inception to December 21, 2024. We describe the evolution of study characteristics over time, including perspective of analysis, region, population, PrEP modality/implementation strategy, and comparators. ResultsOf 5,046 studies identified, 114 met inclusion criteria, of which 81 examined HIV epidemics in 2015 or later and 16 adopted a societal perspective. HIV epidemics studied primarily spanned countries in Sub-Saharan Africa (N=45) and in North America (N=32). Modeled populations for receipt of PrEP primarily comprised: gay, bisexual, and other men who have sex with men (N=66), female sex workers (N=23), serodifferent partnerships (N=16), and persons who inject drugs (N=12). Most evaluated oral, daily PrEP (N=70), followed by on-demand PrEP (N=12), long-acting injectable PrEP (N=12), and others (e.g., vaginal ring, topical gel; N=7). Ten studies compared different PrEP modalities with each other. Three studies evaluated different implementation strategies to increase PrEP uptake, adherence, and persistence. Of the 108 studies that compared PrEP to a combination of other HIV prevention interventions, only 25 scaled up at least part of the comparator over time. DiscussionTo support decision-making, future economic evaluations should consider costs and benefits beyond the health system and consider comparators that better reflect the current HIV response across regions and populations. The increasing availability of novel PrEP modalities allows future studies to evaluate a mix of PrEP modalities and person-centered implementation strategies. ConclusionsThe growing number of PrEP economic evaluations have not kept pace with emerging PrEP modalities or the current HIV epidemic/response, resulting in challenges in making evidence-based policies, programmes, and resource allocation.

COVID-19 disrupted global health service delivery, particularly among children and adolescents living with HIV (CALHIV), increasing the risk of poor treatment adherence. This study assessed the impact of the COVID-19 pandemic on WHO-recommended early warning indicators (EWIs) of HIV drug resistance (HIVDR) among CALHIV. We conducted a descriptive, longitudinal, retrospective study among children (0-9 years) and adolescents (10-19 years) receiving antiretroviral therapy (ART) in five health facilities in the Littoral region of Cameroon. Seven EWIs were monitored: ART attrition, viral load (VL) suppression, VL coverage, appropriate second VL, ARV medicine stock-outs, antiretroviral drug refills at the pharmacy, and appropriate switch to second-line ART. EWI were collected from January 2018 to December 2021 and classified as "poor," "fair," or "desirable" according to WHO criteria. Trend analyses were performed using Pearsons Chi-squared test with Yates correction in R (version 4.1.1). In 2021, 817 participants were included, comprising 214 children and 603 adolescents. Overall performance was poor for most EWIs in both age groups, except for ART attrition and VL coverage, which showed desirable performance across years. A slight improvement in most indicators was observed between 2018 and 2019, followed by a significant decline in 2020 (p<0.001), coinciding with strict COVID-19 restrictions, and a subsequent improvement in 2021 (p<0.01) as mitigation measures were eased. Despite this recovery, children consistently experienced worse outcomes, including higher ART attrition (9.4% vs 4.4%, p<0.05), lower VL suppression (75.3% vs 82.1%, p<0.05), and poorer access to confirmatory VL testing (15.1% vs 69.5%, p<0.001). Overall, the COVID-19 pandemic negatively affected HIV service delivery during its early phase, although the health system demonstrated adaptive capacity one year later. Targeted public health actions are therefore needed to prevent their long-term effects and improve treatment outcomes in this vulnerable population, especially among children.

BackgroundLong-acting injectable antiretroviral therapy offers an alternative to daily oral HIV treatment, potentially improving adherence and reducing stigma. While its adoption has been successful in some settings, evidence on its acceptability in sub-Saharan Africa, outside clinical trials, remains limited. MethodsWe conducted a mixed-methods study among people living with HIV (PLHIV) in two tertiary hospitals in Nairobi, Kenya--a public facility (Kenyatta National Hospital) and a private facility (Aga Khan University Hospital). A cross-sectional survey of 356 participants assessed awareness, willingness to switch, and predictors of acceptability. In addition, 30 participants took part in three focus group discussions (FGDs) exploring perceptions, concerns, and system-level considerations. Quantitative data were analyzed using descriptive and inferential statistics, while qualitative data were analyzed thematically. ResultsOverall, 72.2% of survey participants indicated willingness to switch to LAI-ART. Prior awareness of LAI-ART was the strongest independent predictor of acceptability (aOR 4.03, 95% CI: (1.45-11.18). Drivers of interest included reducing pill burden (77.8%), improving adherence (55.6%), and maintaining privacy (45.5%). Despite high acceptability, FGDs revealed cautious optimism, with concerns about side effects, treatment rigidity, and logistical challenges such as travel and clinic access. ConclusionThese findings suggest that while LAI-ART is seen as promising, its uptake will depend on education, trust-building, and reliable delivery systems. Successful introduction in Kenya will require patient-centered communication, system readiness, and equitable access strategies.

We piloted a Motivational Interviewing (MI) training program for lay counsellors in South Africa (SA) to assess its impact on retention and viral suppression among newly diagnosed individuals living with HIV (PLHIV) at 12 months post-diagnosis. We randomized eight primary healthcare clinics (PHC) in Johannesburg to either the intervention clinics (n=4) where all lay counsellors were supported for 12 months before the PLHIV enrolment or the standard of care (n=4 clinics). Overall, 548 adults ([&ge;] 18 years) PLHIV were recruited after HIV diagnosis from March 2020 to August 2021 (n=291 intervention, n=257 control). We conducted Poisson regression modelling to assess the intervention effect on patient attendance status (out of care - being [&ge;]28 days late for the last appointment) and viral suppression (<50 copies/ml) at 12 months, reporting risk ratios (RR) with 95% confidence intervals (CIs). Of the 548 eligible participants enrolled, 56.3% were [&ge;]28 days late (52.9% intervention vs 60.9% controls, RR 0.9, 95% CI: 0.7-1.0). Retention at 12 months positively correlated with baseline counselor MI skill levels (Cultivating change talk, RR 1.6, 95%CI: 1.1-2.5; Softening sustain talk, RR 1.5, 95%CI: 0.8-2.9; Empathy, RR 1.4, 95%CI: 1.0-1.8; Partnership RR 1.5, 95%CI: 1.2-1.9). Among those retained at 12 months, 65.3% of intervention participants were virally suppressed compared to 49.3% controls (RR 1.3, 95%CI: 1.0-1.7). Compared to control participants, the intervention group reported more positive counseling experiences, fewer concerns about HIV disclosure (RR 0.8 for high vs low-medium concerns, 95% CI: 0.7-1.0) and ART (RR 0.8, 95% CI: 0.7-1.0), and were more likely to express high confidence to take treatment in public (47.4% vs 28.8%, RR 1.4, 95% CI: 1.0-1.8) after counselling.

IntroductionUnderstanding provider preferences for the design of HIV treatment packages could enhance the implementation of programs to support the adoption of long-acting injectable antiretroviral therapy (LAI ART) by people living with HIV who are interested in initiating this treatment modality. MethodsWe recruited providers from New York City (NYC), Rockland, Putman, and Westchester County Ryan White Part A Medical Case Management (MCM) programs to complete a discrete choice experiment (DCE) containing twelve tasks with two alternatives and an opt-out option, with additional survey questions about implementation readiness and choice motivations. The alternatives included four attributes--Type of ART Medication (monthly or bimonthly LAI ART), Service Location and Mode, Support for Clients, and Rewards for Clients-- with 2-4 levels each. We ran latent class multinomial logit analyses (LCA) with 1-5 classes to estimate preferences and explore hypothesis-free preference heterogeneity. We estimated attribute influence using relative importances and preferences using zero-centered part-worth utilities for each level. ResultsOne hundred seventy-seven providers completed the survey (July 2022-January 2023). About half (52%) were 40-59 years old, 72% identified as women, and the plurality (41%) identified as Latino/a. We chose the two-group LCA solution. Bimonthly LAI ART was preferred over monthly LAI ART overall and in both groups. Group 1 (n=45) preferred more traditional adherence supports (e.g., injections at the clinic by appointment, injection appointment reminders) whereas Group 2 (n=132) preferred more client-centered supports (e.g., injections at home by appointment, free transportation to injection appointments if at a clinic). Both groups preferred higher monetary value gift cards for clients for every on-time injection. The top-ranking motivations indicated that participants prioritized patient convenience over job satisfaction and administrative or financial feasibility for the agency. The scores for all implementation measures indicate readiness to implement LAI ART in both groups. ConclusionsOur implementation science-focused study suggests that providers of MCM services in NYC and surrounding counties are motivated to offer services to support clients access and adherence to LAI ART. More work is needed to understand how programs have, in fact, integrated supports for LAI ART into their services.