Trial design and enrolment characteristics of LATA (Long-Acting Treatment in Adolescents): A randomised, open-label, non-inferiority, 96-week trial evaluating the virological efficacy, safety, acceptability and quality-of-life of the dual long-acting injectable regimen cabotegravir/ rilpivirine compared to daily oral therapy in virologically suppressed adolescents with HIV-1 infection, aged 12 to

BackgroundPeople with HIV (PWH) develop more chronic illnesses at younger ages. Frequent healthcare interactions can help with early detection and management of chronic disease. We aimed to describe the frequency and timing of testing related to chronic disease among PWH receiving long-acting (LA) antiretroviral therapy (ART) versus oral ART in the OPERA® cohort.MethodsWe identified treatment-experienced, suppressed (viral load < 50 copies/mL) adults initiating cabotegravir plus rilpivirine (CAB+RPV) LA injections or a new oral ART regimen between 21JAN2021 and 30JUN2022. Each PWH initiating CAB+RPV LA was matched to 1-3 PWH initiating oral ART based on age, sex, and location. We followed matched groups until regimen discontinuation, death, loss to follow-up, or 30JUN2023 and calculated the proportions of PWH receiving metabolic testing and risk score calculations (ASCVD, FIB-4, eGFR, and VACS Mortality Index) over follow-up.ResultsBaseline characteristics between 730 CAB+RPV LA and 2,178 oral ART users were similar (Table 1). Lipid (Figure 1) and serum glucose (Figure 2) testing occurred among a greater proportion of CAB+RPV LA than oral ART users over follow-up (lipids: 75% vs. 68%; glucose: 97% vs. 86%). Similarly, there were greater proportions of CAB+RPV LA PWH receiving those tests than oral ART PWH, among the subset of PWH who were due for those screenings. A smaller proportion of oral ART users received recommended lipid (14%) and glucose (34%) testing within 1-3 months after baseline compared to 22% and 52%, respectively, of CAB+RPV LA users. Risk scores were calculated among a greater proportion of CAB+RPV LA users (68-96%) than oral ART users (66-86%). Risk score components (usually lab values) were also updated sooner after baseline among CAB+RPV LA users, providing earlier opportunity for intervention as appropriate (Table 2).ConclusionCompared to oral ART users, a larger proportion of CAB+RPV LA users received recommended lipid and serum glucose testing; the same held true for risk score calculations related to mortality and cardiovascular, liver, and renal health, which also occurred sooner after baseline among CAB+RPV LA users. Regular clinic visits for CAB+RPV LA injections may provide an opportunity for earlier detection and management of chronic disease conditions.DisclosuresRachel P. Weber, PhD, EMD Serono: Research support to my employer|Gilead Sciences: Research support to my employer|Merck & Co.: Research support to my employer|TheraTechnologies: Research support to my employer|ViiV Healthcare: Research support to my employer Gerald Pierone, Jr., MD, GSK: Grant/Research Support|VIIV: Grant/Research Support Michael G. Sension, MD, Gilead: Grant/Research Support|Gilead: Honoraria|Viiv: Honoraria Anthony M. Mills, MD, Abbott: Grant/Research Support|Emit Bio: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Jennifer S. Fusco, BS, EMD Serono: Research support to my employer|Gilead Sciences: Research support to my employer|Merck & Co.: Research support to my employer|TheraTechnologies: Research support to my employer|ViiV Healthcare: Research support to my employer Brooke Levis, PhD, EMD Serono: Research support to my employer|Gilead Sciences: Research support to my employer|Merck & Co.: Research support to my employer|TheraTechnologies: Research support to my employer|ViiV Healthcare: Research support to my employer Gayathri Sridhar, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds (Public Company)|ViiV Healthcare: Full Time Employee Vani Vannappagari, MBBS, MPH, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Full time Employee|ViiV Healthcare: Stocks/Bonds (Public Company) Jean A. van Wyk, MBChB, MFPM, ViiV Healthcare: Employee|ViiV Healthcare: Stocks/Bonds (Public Company) Gregory P. Fusco, MD, MPH, EMD Serono: Research support to my employer|Gilead Sciences: Research support to my employer|Merck & Co.: Research support to my employer|TheraTechnologies: Research support to my employer|ViiV Healthcare: Research support to my employer

ObjectiveEvaluate factors associated with discontinuation of long‐acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) and describe virologic outcomes in those that returned to oral antiretroviral therapy (ART).MethodsThis is a retrospective cohort study at a single‐centre primary care HIV clinic. Included were adults who received at least one injection of LAI CAB/RPV between April 2021 and March 2024. Characteristics were compared between those that continued LAI CAB/RPV and those that discontinued treatment during the study period. HIV viral load (VL) outcomes were evaluated in those that returned to oral ART and included the most recent VL in the range of 1–24 weeks, 24–48 weeks and the most recently documented VL through September 2024.ResultsA total of 92 and 346 patients were included in the discontinuation and continuation cohorts, respectively. Being male sex assigned at birth and having psychiatric disease was associated with continuing LAI CAB/RPV, whereas having active substance use and being on a multi‐class regimen prior to initiation of LAI CAB/RPV was associated with discontinuation. In those with VL data after resuming oral ART, the percentage of those with HIV VL <50 copies per mL up to 24 weeks (n = 58) was 91.4%, up to 48 weeks (n = 53) was 90.6%, and using the most recent documented VL (n = 74) was 91.9%.ConclusionsHigh viral suppression rates were observed in those that returned to oral therapy after discontinuing LAI CAB/RPV. Individuals with substance use demonstrated a higher rate of LAI discontinuation, despite the potential benefit from LAIs in this population.

We investigated whether the rate of viral rebound decreases with increasing duration of viral suppression and, if so, whether rebound rates in patients previously failing antiretroviral regimens ultimately decline to levels as low as those seen in patients who have never experienced virological failure. All patients from the UK CHIC Study (n = 21 256) who achieved a viral load (VL) of < or = 50 copies/ml while receiving HAART were followed until viral rebound (two consecutive VL > 400 copies/ml). Patients could re-enter the analysis if they experienced a subsequent VL < or = 50 copies/ml. Rebound rates were calculated according to the number of regimens previously failed and duration of viral suppression. Of 12 648 patients on HAART 10 237 (80.9%) achieved a VL < or = 50 copies/ml. During 26 494 person-years (PY) of follow-up, 1853 (18.1%) patients experienced at least one viral rebound 'event', with 2460 events in total [rebound rate, 9.3 (range, 8.9-9.7)/100 PY). Within the first year of viral suppression, the rate of viral rebound was 8.3 (7.5-9.1)/100 PY in patients who had not previously failed treatment, increasing to 32.7 (27.6-37.8)/100 PY in patients who had failed more than four regimens. Irrespective of previous treatment failure, rebound rates in those who remained suppressed for > 4 years were similar to those in patients who had at no time experienced treatment failure. After around 4 years of viral suppression rebound rates in individuals with multiple prior treatment failures approach those of individuals with no prior treatment failure.

A long-acting injectable (LAI) antiretroviral therapy (ART) regimen is now available as a treatment option for virologically suppressed adults with HIV-1. This study assessed preference for a LAI regimen using an online survey of virally suppressed people living with HIV (PLWH) and physicians treating HIV in the US and Canada. Preference was elicited in a discrete choice experiment (DCE) with three choice options (switch to a LAI regimen, switch to another daily oral ART regimen, or stay on their current daily oral ART regimen) and four treatment attributes. A total of 553 PLWH and 450 physicians completed the survey. From the DCE results, 59% of PLWH were predicted to prefer a LAI over an alternative oral ART or staying on their current oral treatment, and 55–66% of physicians were predicted to recommend LAI for PLWH, depending on the treatment challenge scenario presented. PLWH indicated LAI would remove daily reminders of HIV (75%) and reduce feelings of being stigmatized (68%). A majority of PLWH and physicians preferred a LAI over oral ART to overcome treatment challenges such as daily pill burden and adherence. These benefits of LAI ART along with preferences of PLWH and physicians can help to inform ART choice.

Long-acting injectable (LAI) antiretroviral medications are as effective as daily oral antiretroviral therapy (ART) and offer discreet, less frequent dosing. LAIs may be ideal treatment options for people who experience challenges with adherence to daily oral ART, including mobile men living with HIV (MLHIV). We conducted a qualitative substudy within two parent trials in 24 health facilities in Malawi that enrolled MLHIV ≥15 years not on ART. We conducted in-depth interviews with a stratified random sample of participants who had taken oral ART and self-reported mobility (travel) during the 6-month study (≥1 trip of ≥3 nights). Interviews described cabotegravir/rilpivirine and asked about clients' stated preferences for LAI vs. oral ART and their reasoning. Interviews were translated, transcribed, coded in Atlas.ti, and analyzed using framework analysis. We interviewed 29 mobile MLHIV from July 1, 2022, to August 30, 2022, median age 36 years (interquartile range: 31-41), mean 28 nights away in the past 6 months (SD: 40). Nearly all participants (26/29) expressed a preference for LAI over daily oral ART because LAI would reduce the risks of forgetting to take pills and unwanted disclosure. Three men preferred oral ART primarily because of fear of side effects from a new medication. A few men reported they would change their preference if injection site reactions prevented them from working. Mobile MLHIV in Malawi with previous ART adherence challenges expressed strong stated preferences for LAI over daily oral ART. Further research is needed to understand implementation challenges and potential effectiveness of LAI among harder-to-reach populations.

BackgroundMany women with HIV (WWH) have suboptimal adherence to oral antiretroviral therapy (ART) due to multilevel barriers to HIV care access and retention. A long-acting injectable (LAI) version of ART was approved by the US Food and Drug Administration in January 2021 and has the potential to overcome many of these barriers by eliminating the need for daily pill taking. However, it may not be optimal for all WWH. It is critical to develop tools that facilitate patient-provider shared decision making about oral versus LAI ART modalities to promote women’s adherence and long-term HIV outcomes.ObjectiveThis study will develop and pilot test a web-based patient decision aid called i.ART+support (i.ARTs). This decision aid aims to support shared decision making between WWH and their providers, and help women choose between oral and LAI HIV treatment.MethodsThe study will occur in 3 phases. In phase 1, we will utilize a mixed methods approach to collect data from WWH and medical and social service providers to inform i.ARTs content. During phase 2, we will conduct focus groups with WWH and providers to refine i.ARTs content and develop the web-based decision aid. In phase 3, i.ARTs will be tested in a randomized controlled trial with 180 women in Miami, Florida, and assessed for feasibility, usability, and acceptability, as well as to evaluate the associations between receiving i.ARTs and viral suppression, ART pharmacy refills, and clinic attendance.ResultsThis study was funded in March 2021. Columbia University’s IRB approved the study protocols (approval number IRB-AAAT5314). Protocols for phase 1 interviews have been developed and interviews with service providers started in September 2021. We will apply for Clinicaltrials.gov registration prior to phase 3, which is when our first participant will be enrolled in the randomized controlled trial. This is anticipated to occur in April 2023.ConclusionsThis study is the first to develop a web-based patient decision aid to support WWH choices between oral and LAI ART. Its strengths include the incorporation of both patient and provider perspectives, a mixed methods design, and implementation in a real-world clinical setting.International Registered Report Identifier (IRRID)DERR1-10.2196/35646

IntroductionAdherence to daily oral antiretroviral therapy (ART) and regular clinic appointments can be challenging for individuals who experience adverse social determinants of health. Long-acting injectable ART administered outside of traditional clinic settings may be a promising solution to adherence barriers, but additional research is needed to assess patients’ perspectives. This study assessed perspectives of people living with HIV (PLWH) who had difficulty with adherence to traditional HIV care models and evaluated feasibility and acceptability of receiving a long-acting ART injection at a location outside of a traditional HIV clinic to address barriers to HIV care.MethodsQualitative interviews (n = 26) were conducted with PLWH who had experienced barriers to adherence. Participants were referred to the study by staff from Project Trust, a drop in harm reduction and sexually transmitted infection/HIV clinic. The interviews were conducted between May and November 2021. Interviews were recorded, professionally transcribed, coded, and analyzed qualitatively using the integrated-Promoting Action on Research Implementation in Health Services framework.ResultsWe identified 6 main themes regarding the acceptability of receiving a long-acting injection to treat HIV, and the acceptability and feasibility of receiving injections at an alternative care site. Participants specified that they: (1) have a general understanding about their HIV care and the importance of ART adherence, (2) prefer a long-acting injection over a daily pill regimen, (3) expressed concerns about injection safety and efficacy, (4) had specific logistical aspects around the delivery of long-acting injections, including location of injection administration, that they believed would improve their ability to adhere, (5) have confidence that they can become undetectable and then complete the oral lead-in required to begin receiving the injection, and (6) see potential barriers that remain a concern for successful adherence to long-acting injections.ConclusionTo better treat HIV among people who are living with challenging social determinants of health, interventions that include a long-acting injection in a non-traditional care setting may prove to be a promising treatment option.

PurposePeople living with HIV (PLHIV) have reported challenges associated with daily oral antiretroviral therapy (ART), including missed doses, negative psychological impact, and difficulty remaining discreet while at home or traveling. Recently approved long-acting injectable (LAI) ART may help eliminate these concerns. The purpose of this study was to examine patient preferences and estimate health state utilities associated with oral and LAI treatment for ART.MethodsFour health state vignettes were developed based on published literature, clinician interviews, and a pilot study. All vignettes included the same description of HIV, but differed in treatment regimens: (A) single daily oral tablet, (B) two daily oral tablets, (C) injections once monthly, and (D) injections every two months. PLHIV in the UK reported their preferences and valued the health states in time trade-off utility interviews.ResultsThe sample included 201 PLHIV (83.1% male; mean age = 44.9y). The health states frequently selected as most preferable were D (n = 119; 59.2%) and A (n = 75; 37.3%). Utility differences among health states were relatively small, which is typical for treatment process utilities (mean utilities: A, 0.908; B, 0.905; C, 0.900; D, 0.910). Statistically significant differences in utility were found for one vs. two tablets and injections every month vs. every two months (p < 0.001). Participants’ quotations highlight the wide range of reasons for treatment process preferences.ConclusionsCurrent results indicate that many PLHIV would prefer LAI ART. The reported utilities may be useful in economic modeling comparing oral vs. LAI ART.

930. COVID-19 symptom and viral load rebound among individuals reporting nirmatrelvir/ritonavir use compared to propensity score matched individuals not taking COVID-19 treatment

The effectiveness of long-acting injectable (LAI) antipsychotics in preventing relapses of first-episode psychosis is currently debated. The study aimed to investigate the number of psychiatric hospitalizations comparing the LAI cohort versus the oral cohort during different phases of the illness, pre-LAI treatment, during LAI treatment, and after LAI treatment. A naturalistic study was conducted on two independent cohorts of early psychosis patients receiving treatment from a specific early intervention service. The first cohort comprised 228 patients who received LAIs, while the second cohort comprised 667 patients who had never received LAIs. This study was designed as a longitudinal observational study conducted within a naturalistic clinical setting in two cohorts of early psychosis patients. Repeated series ANCOVA (ANCOVA-r) was used to study the number of hospitalizations in the different study periods (T1 = from the date of the first psychiatric record to the beginning of the mirror period; T2 = the mirror period; T3 = from the LAI implementation to the LAI discontinuation; and T4 = from the LAI discontinuation to the end). In all cases, discontinuation of LAI involved the return to oral treatment. In all, 35 patients had not T4 as they were still on LAI treatment at the time of database closing (September 2020), and their data were not included in the analysis of the effect of the LAI discontinuation. The patients in the LAI cohort were younger, more frequently males, presented more schizophrenia diagnoses, and had a higher number of hospitalizations (2.50 ± 2.61 versus 1.19 ± 1.69; p < 0.001) than the oral cohort. The number of hospitalizations at the end of the follow-up was higher in the LAI cohort [0.20 (standard deviation (SD)) = 0.79] versus 0.45 [SD = 0.45 (SD = 1.13); F(23.90), p < 0.001]. However, after the introduction of LAIs, the differences in hospitalization rates between the two cohorts became less pronounced. Once LAI treatment was ceased, the hospitalization rate increased again. In our study, early psychosis patients receiving LAIs experienced a greater decrease in hospitalizations after introducing the LAI treatment than those treated solely with oral medication. These findings support using LAIs as a viable strategy for preventing rehospitalization and improving the overall course of treatment for individuals with early psychosis.

BackgroundCabotegravir/rilpivirine (CAB/RPV) is the first long-acting injectable (LAI) antiretroviral therapy (ART) approved for virologically suppressed adults with HIV-1. While clinical trials have provided safety and efficacy data for this new...

Incidences and factors associated with viral suppression or rebound among HIV patients on combination antiretroviral therapy from three counties in Kenya

Background Suboptimal adherence to daily/weekly oral tuberculosis preventive treatment (TPT) regimens among tuberculosis (TB) contacts poses a challenge to TB infection management. Long-acting injectable (LAI) formulations of TPT are in development and may help overcome some of the barriers to oral TPT. We assessed the acceptability of LAI TPT among healthcare workers (HCWs) in a high burden setting. Methods We surveyed physicians and nurses at TB clinics in the country of Georgia from June–July 2024 using a Unitaid 40-question survey. Questions explored overall preference for LAI versus oral TPT, preferences for frequency of injection administration, and attitudes toward LAI TPT. We compared HCWs’ overall preference for LAI TPT by HCW characteristics and opinions of TPT formulation using prevalence ratios (PR) and 95% confidence intervals (CI). Results Among 127 HCWs, median age was 57 years (interquartile range: 47–63), 86% were female, and 59% were physicians. Overall, 52% favored using LAI versus oral TPT and 36% remained unsure. Further, 66% were in favor of a 1-injection LAI regimen over oral therapy; 65% were in favor of a 2-injection LAI regimen (1x/month for 2 months); 63% were in favor of a 3-injection regimen (1x/month for 3 months). Preference for LAI versus oral TPT did not differ by age group or occupation. Male HCWs were non-significantly more likely to prefer LAI compared to female HCWs (PR 1.3, 95% CI 0.9, 2.0). HCWs who believed that oral TPT is effective (versus did not believe) were non-significantly more likely to prefer LAI (PR 1.4, 95% CI 0.7–2.6). The belief that TPT should be a priority of the National TB Program (versus should not be a priority) was non-significantly associated with being in favor of LAI TPT (PR 1.3, 95% CI 0.7–2.6). HCWs’ primary concerns regarding LAI were the potential for long-lasting and unexpected side effects, need for multiple injections, and lower efficacy. HCWs reported that if patients had severe liver disease, chronic comorbidities, or struggled to adhere to oral regimens, they would be more likely to recommend LAI over oral TPT. Conclusion There was high acceptability for LAI TPT among doctors and nurses in a high burden setting. There may be potential to increase acceptability if LAI are as efficacious and safe as oral TPT regimens. Disclosures All Authors: No reported disclosures

This study investigates (1) the proportion of people with psychosis who are on long-acting injectable antipsychotics; (2) the difference in the demographic, clinical, substance use and adverse drug reaction profiles of people taking long-acting injectables compared to oral antipsychotics; and (3) the differences in the same profiles of those on first-generation antipsychotic versus second-generation antipsychotic long-acting injectables. Data were collected as part of the Survey of High Impact Psychosis. For this study, participants with diagnoses of schizophrenia or schizoaffective disorder who were on any antipsychotic medication were included (N = 1049). Nearly a third (31.5%) of people with psychosis were on long-acting injectables, of whom 49.7% were on first-generation antipsychotic long-acting injectables and 47.9% were on second-generation antipsychotic long-acting injectables. This contrasts with oral antipsychotics where there was a higher utilisation of second-generation antipsychotics (86.3%). Of note, compared to those on the oral formulation, people on long-acting injectables were almost four times more likely to be under a community treatment order. Furthermore, people on long-acting injectables were more likely to have a longer duration of illness, reduced degree of insight, increased cognitive impairment as well as poor personal and social functioning. They also reported more adverse drug reactions. Compared to those on first-generation antipsychotic long-acting injectables, people on SGA long-acting injectables were younger and had had a shorter duration of illness. They were also more likely to experience dizziness and increased weight, but less likely to experience muscle stiffness or tenseness. Long-acting injectable use in Australia is associated with higher rates of community treatment order use, as well as poorer insight, personal and social performance, and greater cognitive impairment. While long-acting injectables may have the potential to improve the prognosis of people with psychosis, a better understanding of the choices behind the utilisation of long-acting injectable treatment in Australia is urgently needed.

The arrival of untreatable multidrug-resistant HIV-1 in sub-Saharan Africa.