Long-acting Antiretroviral Therapy Research Articles

P-577. Improved Testing for Chronic Disease Among Long-Acting Injectable Versus Daily Oral Antiretroviral Therapy Users in the OPERA Cohort

Abstract Background People 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. Methods We 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. Results Baseline 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). Conclusion Compared 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. Disclosures Rachel 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

P-535. Implementation of Injectable Cabotegravir/Rilpivirine for Treatment of HIV in Patients with Substance Use Disorders at a Syringe Exchange Clinic

Abstract Background Injectable Cabotegravir + Rilpivirine (CAB+RPV-LA) is a long-acting anti-retroviral therapy (ART) that has the potential to be utilized for people living with HIV (PLWH) who face significant barriers to daily ART. A key population that can benefit is PLWH with concomitant opioid use disorder (OUD) and housing instability. In this case series, we describe the implementation of a program that provides low-barrier access to CAB+RPV-LA for PLWH and OUD. Methods The electronic medical record (EMR) was reviewed to identify individuals aged 18 years or older with a documented HIV diagnosis and a history of intravenous drug use (IVDU) who were initiated on CAB+RPV-LA between June 2022 - January 2024 at the Sana Clinic at Prevention Point Philadelphia (PPP). Fifteen patients were identified as having initiated CAB+RPV-LA during this time period. Descriptive statistics were used to summarize demographics, clinical characteristics, and outcomes of the study population. Results A review of the patients started on CAB+RPV-LA found that 100% of patients (n =12) with follow-up labs after initiation had HIV viral load suppression and CD4 counts > 200. Three patients did not yet have follow-up labs since initiation due to their recent start on CAB+RPV-LA. Viral load on initiation ranged from undetectable to 1440. There were no missed doses during the two-year period. All patients had OUD and 67% had housing instability. Conclusion Overall, CAB+RPV-LA was effective in maintaining and obtaining viral suppression in PLWH and OUD. To our knowledge, there is currently no literature on the implementation of long-acting ART for HIV maintenance in patients with OUD at a syringe exchange. Our findings support that long-acting ART is a key tool in ending the HIV epidemic especially at clinics serving patients with comorbid substance use and housing instability. Disclosures All Authors: No reported disclosures

P-979. Clinician Willingness to Consider Long-Acting Therapies and Culturally Supportive Strategies in Caring for Heavily Treatment-Experienced Black, Indigenous, or People of Color (BIPOC) with HIV

Abstract Background Black, Indigenous, or People of Color (BIPOC) are overrepresented among heavily treatment-experienced (HTE) people with HIV (PWH). They face complex treatment challenges, exacerbated by socioeconomic disadvantages, and cultural insensitivities in healthcare settings that lead to suboptimal care and outcomes. To improve clinician competence in integrating long-acting agents into practice and providing culturally supportive care, an educational web-based initiative was designed in collaboration with the Association of Nurses in AIDS Care (ANAC). Methods A 60-minute CME activity, led by a multidisciplinary expert panel, was broadcast live on ClinicalSeriesLive and IDCareLive in August 2023 (on-demand until August 2024). Two vignettes of the treatment journey of HTE patients from BIPOC communities (Hispanic & African-American) were utilized to elevate awareness of unique challenges with care. Changes on knowledge/competence pre-/post-test questions and clinician perspectives and challenges (5-point Likert scale) were assessed. Results As of April 30th, 2024, 1,728 clinicians participated in these activities (92% were physicians, advanced practitioners, and nurses). Prior to the activity, only 38% of learners had prescribed or administered a long-acting antiviral agent for HTE patients. Patients’ ability to access long-acting antiretroviral (ARV) therapy was the most frequently cited barrier by clinicians when considering this option (43%). Regarding culturally supportive care pre-activity, 12% of learners sought to understand stigma faced by patients within their communities and 11% spoke patients’ languages or referred them to translation services. Post-activity, learners demonstrated increased confidence in selecting a long-acting therapy (59%), discussing options with HTE patients (64%), and developing strategies to deliver more culturally supportive care (73%). Improvements in pre/post paired responses to CME questions are shown in Table 1. Conclusion Web-based education on strategies to incorporate long-acting ARV therapies and culturally supportive care can improve clinician knowledge, uncover barriers, and stimulate practice change that improves care of HTE PWH from BIPOC communities. Disclosures Mamta K. Jain, MD, MPH, Abbvie: Grant/Research Support|Gilead Sciences: Grant/Research Support|Laurent: Grant/Research Support Onyema Ogbuagu, MD, Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Honoraria|GSK/ViiV: Advisor/Consultant|GSK/ViiV: Honoraria|Janssen: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Honoraria

P-578. Just “Short of a Cure”: Unique Considerations in Uptake and Use of Long-Acting Injectable Cabotegravir/Rilpivirine Among Long-Term Survivors with HIV

Abstract Background Understanding perspectives of subgroups of people with HIV (PWH) who have accessed long-acting cabotegravir/rilpivirine (CAB/RPV-LA) is crucial for optimizing implementation; especially among long-term survivors (LTS) who have lived through the trauma of the early epidemic to the innovation of today. Methods We analyzed semi-structured interviews collected from 08/2022-05/2023 via a parent study at four Ryan White clinics in Atlanta, Chicago, and San Francisco among early adopters of CAB/RPV-LA (received ≥3 injections or discontinued). Our analysis explored factors impacting CAB/RPV-LA uptake and use in LTS (living with HIV since 2000 or earlier) using a socioecological model of HIV care engagement. Results Among 20 LTS, median age was 56 (Q1-Q3 54-60) years and median time living with HIV was 27 (Q1-Q3 25-34) years. Thirteen (65%) identified as racial/ethnic minorities and seven (35%) as cis or trans women. We identified three primary themes: 1) The majority of LTS eagerly awaited CAB/RPV-LA and seemed unconflicted in their choice to switch from oral antiretroviral therapy (ART). Their confidence stemmed from experience using new iterations of oral ART over decades, with some citing CAB/RPV-LA as being a step closer to a cure. 2) Choosing to start CAB/RPV-LA was sometimes facilitated by input from longstanding, trusted relationships with healthcare providers or other PWH. 3) Reflections on the emotional gravity of witnessing loved ones die from AIDS-related illnesses early in the epidemic, and the mental imprisonment of around-the-clock pill taking required for their own survival, influenced use of CAB/RPV-LA. In fact, many reported transforming HIV-related psychological trauma and tragedy into education, support, and advocacy efforts: using CAB/RPV-LA was a unique mechanism to further benefit their community—indeed, it was an obligation to both PWH who have passed as well as PWH to come, who could learn from their experience. Conclusion The perspectives of LTS who initiated CAB/RPV-LA during early implementation revealed uptake and use was shaped by the emotional, psychosocial, and physical impact of living with HIV for decades. These data serve as a framework to tailor service delivery of current and future long-acting ART options in this population. Disclosures Moira McNulty, MD, Gilead Sciences, Inc.: Advisor/Consultant Katerina Christopoulos, MD, MPH, Janssen: Honoraria

P-558. Long-acting Injectable Cabotegravir/Rilpivirine Plus Subcutaneous Lenacapavir Effective in People with HIV with Viremia and Cabotegravir or Rilpivirine Resistance-Associated Mutations

Abstract Background Long-acting antiretroviral regimens have the potential to achieve virologic suppression in people unable to maintain adherence to daily oral antiretroviral therapy (ART). Long-acting injectable cabotegravir/rilpivirine (LAI CAB/RPV) is currently the only complete long-acting regimen and is recommended by IAS-USA for select patients with viremia. However, resistance-associated mutations (RAMs) among treatment-experienced people with HIV are common, precluding use of LAI CAB/RPV. LAI CAB/RPV plus subcutaneous lenacapavir (LEN) may provide therapeutic options for people with poor long-term adherence and cabotegravir or rilpivirine RAMs.Table 1.NNRTI Mutations by Patient Methods Patients at UMMC’s Adult Special Care Clinic were selected for LAI CAB/RPV plus LEN by a multidisciplinary panel. Criteria for selection included recurrent viremia despite intensive case management strategies, presence of historical or current RAMs to CAB or RPV, and partially- or fully-active cabotegravir based on mutation scores. Patients began therapy with LEN and LAI CAB/RPV on the same day. The prescribed regimen consisted of CAB/RPV 600/900 mg intramuscular at months 0 and 1 followed by every 2 months and LEN 600 mg oral daily x 2 days and 927 mg subcutaneous every six months. No oral lead-in of CAB/RPV was administered, and oral LEN was administered via directly-observed therapy. Results Nine patients were treated with LAI CAB/RPV plus LEN at UMMC. Mean baseline viral load was 36 251 copies/mL. All patients had RPV RAMs. One patient had CAB RAMs (N155H, T977A) conferring low-level resistance to CAB. The follow-up period ranged from 24-36 weeks. All patients maintained viral loads < 200 copies/mL during follow-up. Patients with baseline CD4 < 200 cells/µL demonstrated 208% increase in absolute CD4 count. No treatment-emergent resistance has occurred to date. Conclusion LAI CAB/RPV plus LEN achieved virologic suppression for up to 36 weeks of follow-up in PWH with incomplete adherence to oral ART and mutations to CAB or RPV. Further follow-up and larger sample size will be needed to determine long-term durability of this combination. Additional combinations of long-acting ART are vitally needed to achieve virologic suppression for all. Disclosures All Authors: No reported disclosures

Stakeholder Perspectives on the Role of Peer Mentors in the Implementation of Long-Acting Antiretroviral Therapy for Use by Adolescents and Young People in Western Kenya: Findings from a Formative Study, KuwaFree! LiveFree!

Long-acting antiretroviral treatment (LA ART) is a forthcoming option for adolescents and young people living with HIV (AYPLHIV), but perspectives on using peer mentors to implement LA ART for AYPLHIV are unknown. We conducted seven focus group discussions (n = 58 participants) from November 2021 to April 2022 in Kenya with four stakeholder groups, including AYPLHIV, healthcare providers, advocates, and policymakers. We used inductive coding and thematic analysis. Our stakeholders articulated peer mentors are crucial in the implementation of LA ART for AYPLHIV in leading communication, facilitating referrals, and providing empathy from lived experiences. Additionally, they can serve as early adopters, help navigate service points, and provide messaging on the benefits and drawbacks of LA ART. They emphasized the necessity of training peer mentors for the LA ART scale-up. Peer mentors are essential for linkage and referring of AYPLHIV to LA ART, and peer mentors' involvement should be integrated into a national implementation plan.

Long-acting antiretroviral therapy in low-income and middle-income countries: considerations for roll-out.

Long-acting ART (LA-ART) in low-income and middle-income countries (LMICs) may address specific issues that affect people living with HIV (PWH) and people at substantial risk of HIV infection. We reviewed products in use and under consideration in LMICS, current and anticipated challenges for implementation, and offer strategies for effective rollout. Factors to consider for effective implementation of LA-ART in LMICs are: managing co-conditions (pregnancy) and comorbidities (TB and hepatitis B); medication access, both cost and supply-related; and health systems delivery mechanisms for products. LA-ART present promising new alternatives in LMICs. Although they may tackle certain adherence concerns and systemic issues, which impact delivery of services, significant obstacles remain before their widespread implementation in people that require them most, particularly in countries most affected by HIV. We offer best practices from prior experiences and implementation studies for effective coordination of multiple stakeholders, critical for effective rollout.

Long-acting antiretroviral therapy in the context of viral suppression.

Long-acting antiretroviral therapy (ART), such as with cabotegravir and rilpivirine, is a new and exciting paradigm shift that could change the face of HIV treatment if it were universally available to all who want it. In countries where there is access, uptake has been slow - partly because of capacity issues and partly because of hesitancy around remaining clinical questions. We summarized clinical trial data and emerging real-world evidence to shed light on these questions. Phase 2b/3/3b clinical trials have shown CAB+RPV injections to be both well tolerated and efficacious. Real-world cohort (RWC) studies with larger numbers of people demonstrate high levels of adherence and persistence, and low rates of virological failure in clinical practice. Although the risk of virological failure in the context of CAB+RPV is low, it remains a pertinent issue because of the high risk of developing two-class resistance. The use of multiple definitions of virological failure in RWC studies currently makes understanding the available evidence difficult and could have deleterious effects on clinical decision-making. Longer term real-world evidence in diverse populations is needed to better understand the durability of CAB+RPV and its suitability in different contexts.

State of the ART (antiretroviral therapy): Long-acting HIV-1 therapeutics

Human immunodeficiency virus (HIV) impacts millions of individuals worldwide, and well over 2/3 of those living with HIV are accessing antiviral therapies that are successfully repressing viral replication. Most often, HIV treatments and prevention are administered in the form of daily pills as combinations of multiple drugs. An emergent and effective strategy for suppressing viral replication is the application of long-acting antiretroviral therapy (LAART), or antivirals that require less-frequent, non-daily doses. Thus far, the repertoire of LAARTs includes the widely used antiviral classes of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (INSTIs) and has recently expanded to include a capsid-targeting antiviral. Possible future additions are nucleoside reverse transcriptase inhibitors (NRTIs) and nucleoside reverse transcriptase translocation inhibitors (NRTTIs). Here, we discuss the different strategies of using long-acting compounds to treat or prevent HIV-1 infection by targeting reverse transcriptase, integrase, and capsid.

Outcomes of LA-ART at a syringe exchange

Abstract Cabotegravir + Rilpivirine (CAB+RPV-LA) is a long-acting anti-retroviral therapy (ART) that can be utilized for people with HIV (PWH) who face barriers to daily ART. Here, we describe the implementation of a program that provides low-barrier access to CAB+RPV-LA for PWH and opioid use disorder (OUD) at a syringe exchange.

Long-acting antiretroviral therapy effectiveness and patient satisfaction using patient questionnaires: data from a real-world setting

BackgroundAntiretroviral therapy (ART) for HIV infection has evolved substantially. The development of long-acting drugs, such as cabotegravir (CAB) and rilpivirine (RPV) might improve treatment satisfaction among people living with HIV (PLWH). The real-world effectiveness of long-acting ART and its effect on patient satisfaction needs to be assessed. This study investigated antiviral effectiveness and treatment satisfaction in PLWH who switched from conventional to long-acting ART (CAB + RPV).MethodsThis prospective cohort study included PLWH aged 18 years and older who switched to CAB + RPV and received the injections every 8 weeks between June 2022 and May 2023, after a 4-week oral lead-in phase. The eligibility criteria included viral suppression, absence of hepatitis B virus (HBV) DNA, and no prior RPV resistance mutations. Clinical data, including renal, lipid, and glucose biomarker levels, were monitored from the baseline to 44 weeks after switching. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire. A linear mixed-effects model was used to estimate changes in clinical data from baseline.ResultsThirty-eight male participants were enrolled. Some participants had detectable levels of viral replication; however, all participants maintained viral suppression (HIV-RNA < 50 copies/mL) at 44 weeks and no cases of virological failure were detected. The creatinine level decreased by − 0.04 mg/dL (95% confidence interval [CI]: − 0.07 to − 0.01), lipid and glucose profiles remained stable, and treatment satisfaction increased by 6.6 points (95% CI: 2.4 to 10.8) after switching to CAB + RPV.ConclusionsLong-acting ART provides effective viral suppression and enhances treatment satisfaction in PLWH switching from conventional ART. Long-acting ART can improve patient well-being; however, patient selection and monitoring to prevent HBV-related complications are important.

Innovations in HIV Prevention and Treatment: The Future of HIV Care

The Human Immunodeficiency Virus (HIV) continues to pose a significant global health challenge, despite substantial progress in treatment and prevention. This review explored recent innovations in HIV prevention and treatment, highlighting advancements such as long-acting pre-exposure prophylaxis (PrEP), long-acting injectable antiretroviral therapy (ART), and emerging research into potential cures. It also examined integrated care approaches, digital health innovations, and innovative financing models that are shaping the future of HIV care. The review synthesized recent research, evaluated the impact of these innovations, and discussed future directions to advance global health goals. The methodology for this review involved a comprehensive analysis of current literature, clinical trial data, and expert opinions to provide a holistic overview of how these advancements are transforming HIV care and addressing existing challenges. Keywords: HIV Innovations, Prevention Strategies, Long-Acting ART, Integrated Care Models, Digital Health Technologies.

Preventing perinatal HIV acquisition; current gaps and future perspectives.

Although current treatment could eradicate vertical transmission, in 2022, 130 000 infants acquired HIV globally. HIV suppression with antiretroviral therapy (ART) transforms survival for people living with HIV (PLWH), and prevents transmission, including vertical. International guidelines recommend lifelong ART for PLWH, consequently perinatal HIV acquisition reflects implementation gaps in the HIV care cascade. We summarize these gaps, exploring potential novel approaches and therapeutic innovations towards eliminating vertical HIV transmission. Multifactorial challenges continue to underpin gaps in the HIV care cascade, including accessibility, availability and sustainability of HIV testing, prevention and treatment, alongside stigma, gender-based violence and poverty. Long-acting ART may be important in preventing perinatal HIV acquisition, with early data demonstrating tolerability and efficacy of injectable ART throughout pregnancy, both as HIV treatment and prevention. Carefully selected long-acting broadly neutralizing antibodies (bNAbs) matching circulating, exposing viral envelope sequences have demonstrated safety, clinical trials are ongoing to demonstrate efficacy. Emerging clinical studies should prioritize pregnant/lactating people and infants to ensure such therapies are well tolerated and efficacious. Alongside therapeutic innovation, programmatic strategies must address social and economic challenges, ensuring sustainable HIV treatment/prevention programmes and facilitating global elimination of blood-borne viruses.

Early Implementation and Outcomes Among People with HIV Who Accessed Long-Acting Injectable Cabotegravir/Rilpivirine at Two Ryan White Clinics in the U.S. South.

The use of long-acting injectable cabotegravir/rilpivirine (LAI-CAB/RPV) as maintenance therapy for persons with HIV (PWH), which may improve treatment access and outcomes, though real-world data on uptake are limited, was studied at two Ryan White clinics in Atlanta, Georgia. Among PWH referred from 4/1/2021 to 9/15/2022 to switch to LAI-CAB/RPV, characteristics were ascertained at time of referral; and disposition (initiated; ineligible; uninterested; pending) was recorded as of 9/15/2022. Among patients initiated on CAB/RPV, we assessed the drug procurement process and clinical outcomes through 6/1/2023. Among 149 PWH referred, 74/149 (50%) initiated CAB/RPV as of 9/15/2022, of whom, characteristics were median age 47 (Q1-Q3 36-55) years, 16% cisgender female, 72% Black race, median HIV duration 15 (Q1-Q3 9-19) years, and 64% had commercial health insurance. Of the 75 PWH not initiated, 35 were ineligible owing to a clinical concern (n = 16) or insurance issue (n = 19); 15 patients changed their mind about switching; and 25 were pending eligibility review or therapy initiation. Median time from CAB/RPV prescription to initiation was 46 (Q1-Q3 29-78) days. Of 731 total injections administered (median 11 injections/patient), 95% were given within 7 days of the target treatment date. Nearly all patients were virally suppressed upon referral and remained suppressed through follow-up. At two clinics in the U.S. South, half of the patients referred for LAI-CAB/RPV successfully accessed therapy nearly 2 years after U.S. drug approval. We identified barriers to uptake at the patient and structural levels, highlighting key areas to invest resource and personnel support to sustain and scale long-acting antiretroviral therapy programming.

Perspectives Among Health Care Providers and People with HIV on the Implementation of Long-Acting Injectable Cabotegravir/Rilpivirine for Antiretroviral Therapy in Florida.

Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) for antiretroviral therapy (ART) could benefit many people with HIV (PWH). However, its impact will largely be determined by providers' willingness to prescribe it and PWH's willingness to take it. This study explores the perceived barriers and facilitators of LAI CAB/RPV implementation among PWH and HIV care providers in Florida, a high prevalence setting. Semi-structured qualitative interviews were conducted in English with 16 PWH (50% non-Hispanic White, 50% cis men, and 94% on oral ART) and 11 providers (27% non-Hispanic Black, 27% Hispanic, 73% cis women, and 64% prescribed LAI CAB/RPV) throughout the state. Recruitment occurred between October 2022 and October 2023 from HIV clinics. Interviews were recorded, professionally transcribed, and then double coded using thematic analysis. The Consolidated Framework for Implementation Research guided the interview guide and coding. While PWH viewed LAI CAB/RPV as effective, predominant barriers included administration via injection, challenges of attending more clinic visits, and a feeling that this made HIV the center of one's life. Providers additionally expressed concerns about the development of integrase resistance. Barriers noted by PWH and providers outside of the clinic included transportation, stigma, access inequities, and payor issues. Within clinics, providers identified the need for extra staffing and the increased burden on existing staff as barriers. These barriers decreased the perceived need for LAI CAB/RPV among PWH and providers, especially with the high effectiveness of oral ART. Many of the identified barriers occur outside of the clinic and will likely apply to other novel long-acting ART options.

Key informant views on potential acceptability and feasibility of long-acting antiretroviral treatment for HIV in Kenya

BackgroundIn 2020, 14% of diagnosed persons living with HIV (PLWH) in Kenya were not taking antiretroviral therapy (ART), and 19% of those on ART had unsuppressed viral loads. Long-acting antiretroviral therapy (LA-ART) may increase viral suppression by promoting ART uptake and adherence. We conducted key informant (KI) interviews with HIV experts in Kenya to identify product and delivery attributes related to the acceptability and feasibility of providing LA-ART to PLWH in Kenya.MethodsInterviews were conducted via Zoom on potential LA-ART options including intra-muscular (IM) injections, subcutaneous (SC) injections, implants, and LA oral pills. KI were asked to discuss the products they were most and least excited about, as well as barriers and facilitators to LA-ART roll-out. In addition, they were asked about potential delivery locations for LA-ART products such as homes, pharmacies, and clinics. Interviews were recorded and transcribed, and data were analyzed using a combination of inductive and deductive coding.ResultsTwelve KI (5 women, 7 men) participated between December 2021 and February 2022. Overall, participants reported that LA-ART would be acceptable and preferable to PLWH because of fatigue with daily oral pills. They viewed IM injections and LA oral pills as the most exciting options to ease pill burden and improve adherence. KI felt that populations who could benefit most were adolescents in boarding schools and stigmatized populations such as sex workers. SC injections and implants were less favored, as they would require new training initiatives for patients or healthcare workers on administration. In addition, SC injections would require refrigeration and needle disposal after use. Some KI thought patients, especially men, might worry that IM injections and implants would impact fertility, given their role in family planning. Pharmacies were perceived by most KI as suboptimal delivery locations; however, given ongoing work in Kenya to include pharmacies in antiretroviral delivery, they recommended asking patients their views.ConclusionThere is interest and support for LA-ART in Kenya, especially IM injections and LA oral pills. Identifying patient preferences for modes and delivery locations and addressing misconceptions about specific products as they become available will be important before wide-scale implementation.

Safety and pharmacokinetics of oral and long-acting injectable cabotegravir or long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study

Combined intramuscular long-acting cabotegravir and long-acting rilpivirine constitute the first long-acting combination antiretroviral therapy (ART) regimen approved for adults with HIV. The goal of the IMPAACT 2017 study (MOCHA [More Options for Children and Adolescents]) was to assess the safety and pharmacokinetics of these drugs in adolescents. In this phase 1/2, multicentre, open-label, non-comparative, dose-finding study, virologically suppressed adolescents (aged 12-17 years; weight ≥35 kg; BMI ≤31·5 kg/m2) with HIV-1 on daily oral ART were enrolled at 15 centres in four countries (Botswana, South Africa, Thailand, and the USA). After 4-6 weeks of oral cabotegravir (cohort 1C) or rilpivirine (cohort 1R), participants received intramuscular long-acting cabotegravir or long-acting rilpivirine every 4 weeks or 8 weeks per the adult dosing regimens, while continuing pre-study ART. The primary outcomes were assessments of safety measures, including all adverse events, until week 4 for oral cabotegravir and until week 16 for long-acting cabotegravir and long-acting rilpivirine, and pharmacokinetic measures, including the area under the plasma concentration versus time curve during the dosing interval (AUC0-tau) and drug concentrations, at week 2 for oral dosing of cabotegravir and at week 16 for intramuscular dosing of cabotegravir and rilpivirine. Enrolment into cohort 1C or cohort 1R was based on the participant's pre-study ART, meaning that masking was not done. For pharmacokinetic analyses, blood samples were drawn at weeks 2-4 after oral dosing and weeks 4-16 after intramuscular dosing. Safety outcome measures were summarised using frequencies, percentages, and exact 95% CIs; pharmacokinetic parameters were summarised using descriptive statistics. This trial is registered at ClinicalTrials.gov, NCT03497676, and is closed to enrolment. Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled: 30 in cohort 1C and 25 in cohort 1R. At week 16, 28 (97%, 95% CI 82-100) of the 29 dose-evaluable participants in cohort 1C and 21 (91%; 72-99) of the 23 dose-evaluable participants in cohort 1R had reported at least one adverse event, with the most common being injection-site pain (nine [31%] in cohort 1C; nine [39%] in cohort 1R; none were severe). One (4%, 95% CI 0-22) participant in cohort 1R had an adverse event of grade 3 or higher, leading to treatment discontinuation, which was defined as acute rilpivirine-related allergic reaction (self-limiting generalised urticaria) after the first oral dose. No deaths or life-threatening events occurred. In cohort 1C, the week 2 median cabotegravir AUC0-tau was 148·5 (range 37·2-433·1) μg·h/mL. The week 16 median concentrations for the every-4-weeks and every-8-weeks dosing was 3·11 μg/mL (range 1·22-6·19) and 1·15 μg/mL (<0·025-5·29) for cabotegravir and 52·9 ng/mL (31·9-148·0) and 39·1 ng/mL (27·2-81·3) for rilpivirine, respectively. These concentrations were similar to those in adults. Study data support using long-acting cabotegravir or long-acting rilpivirine, given every 4 weeks or 8 weeks, per the adult dosing regimens, in virologically suppressed adolescents aged 12 years and older and weighing at least 35 kg. The National Institutes of Health and ViiV Healthcare.

The New Era of Long-Acting Antiretroviral Therapy: When and Why to Make the Switch.

Despite the availability of safe and effective oral combination antiretroviral therapy, barriers to maintaining viral suppression remain a challenge to ending the HIV epidemic. Long-acting injectable antiretroviral therapy was developed as an alternative to daily oral therapy. This review summarizes the current literature on the efficacy of long-acting cabotegravir plus rilpivirine for the treatment of HIV-1, reasons to switch to injectable therapy, and barriers to switching. Long-acting cabotegravir plus rilpivirine is safe and effective in maintaining HIV-1 virologic suppression. Ideal candidates for switching to long-acting cabotegravir plus rilpivirine are virologically suppressed on oral regimens with good adherence and no history of virologic failure or baseline resistance. Indications to switch to injectable therapy include patient preference, the potential for improved adherence, and avoidance of adverse effects. Implementation research is needed to assess and overcome system barriers. Long-acting cabotegravir plus rilpivirine is a novel alternative to oral antiretrovirals, with the potential to improve adherence and quality of life in people with HIV.

Projected Benefits of Long-Acting Antiretroviral Therapy in Nonsuppressed People With Human Immunodeficiency Virus Experiencing Adherence Barriers.

In a demonstration project, long-acting, injectable cabotegravir-rilpivirine (CAB-RPV) achieved viral suppression in a high proportion of people with HIV (PWH) who were virologically nonsuppressed with adherence barriers. We projected the long-term impact of CAB-RPV for nonsuppressed PWH experiencing adherence barriers. Using the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) model, we compared 3 strategies: (1) standard of care oral integrase inhibitor-based ART (INSTI); (2) INSTI-based ART with supportive social services ("wraparound services" [WS]) (INSTI/WS); and (3) CAB-RPV with WS (CAB-RPV/WS). Model outcomes included viral suppression (%) and engagement in care (%) at 3 years, and life expectancy (life-years [LYs]). Base case cohort characteristics included mean age of 47y (standard deviation [SD], 10y), 90% male at birth, and baseline mean CD4 count 150/µL (SD, 75/µL). Viral suppression at 3 months was 13% (INSTI), 28% (INSTI/WS), and 60% (CAB-RPV/WS). Mean loss to follow-up was 28/100 person-years (PY) (SD, 2/100 PY) without WS and 16/100 PY (SD, 1/100 PY) with WS. Projected viral suppression at 3 years would vary widely: 16% (INSTI), 38% (INSTI/WS), and 44% (CAB-RPV/WS). Life expectancy would be 7.4 LY (INSTI), 9.0 LY (INSTI/WS), and 9.4 LY (CAB-RPV/WS). Projected benefits over oral ART would be greater for PWH initiating CAB-RPV/WS at lower CD4 counts. Across plausible key parameter ranges, CAB-RPV/WS would improve viral suppression and life expectancy compared with oral INSTI strategies. These model-based results support that long-acting injectable CAB-RPV with extensive support services for nonsuppressed PWH experiencing adherence barriers is likely to increase viral suppression and improve survival. A prospective study to provide further evidence is needed.

Cabotegravir and Rilpivirine Long-Acting Antiretroviral Therapy Administered Every 2Months is Cost-Effective for the Treatment of HIV-1 in Spain.

Current antiretroviral therapies (ARTs) have improved outcomes for people living with HIV. However, the requirement to adhere to lifelong daily oral dosing may be challenging for some people living with HIV, leading to suboptimal adherence and therefore reduced treatment effectiveness. Treatment with long-acting (LA) ART may improve adherence and health-related quality of life. The objective of this study was to evaluate the cost-effectiveness of cabotegravir + rilpivirine (CAB+RPV) LA administered every 2months (Q2M) compared with current ART administered as daily oral single-tablet regimens (STRs) from a Spanish National Healthcare System perspective. A hybrid decision-tree and Markov state-transition model was used with pooled data from three phaseIII/IIIb trials (FLAIR, ATLAS, and ATLAS-2M) over a lifetime horizon, with health states defined by viral load and CD4+ cell count. Direct costs (in €) were taken from Spanish public sources from 2021 and several deterministic and probabilistic analyses were carried out. An annual 3% discount rate was applied to both costs and utilities. Over the lifetime horizon, CAB+RPV LA Q2M was associated with an additional 0.27 quality-adjusted life years (QALYs) and slightly greater lifetime costs (€4003) versus daily oral ART, leading to an incremental cost-effectiveness ratio of €15,003/QALY, below the commonly accepted €30,000/QALY willingness-to-pay threshold in Spain. All scenario analyses showed consistent results, and the probabilistic sensitivity analysis showed cost-effectiveness compared with daily oral STRs in 62.4% of simulations, being dominant in 0.3%. From the Spanish National Health System perspective, CAB+RPV LA Q2M is a cost-effective alternative compared with the current options of daily oral STR regimens for HIV treatment. ATLAS, NCT02951052; ATLAS-2M, NCT03299049; FLAIR, NCT02938520.