Case Series of People With HIV on the Long-Acting Combination of Lenacapavir and Cabotegravir: Call for a Trial.

Background: Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents. Methods: We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/- RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. Results: All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28-75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL <75 copies/mL) after starting LEN at a median (range) of 8 (4-16) weeks, with 16/34 (47%) suppressed at baseline. Conclusions: In this case series of 34 patients on LEN/CAB, high rates of virologic suppression (94%) were observed. Reasons for using LEN/CAB included adherence challenges and underlying resistance, mostly to NNRTIs. These data support a clinical trial of LEN/CAB among persons with NNRTI resistance.

Identifying Implementation Determinants and Strategies for Long-Acting Injectable Cabotegravir-Rilpivirine in People With HIV Who Are Virally Unsuppressed.

BACKGROUND: Early evidence suggests long-acting injectable cabotegravir and rilpivirine (LA-CAB/RPV) may be beneficial for people with HIV (PWH) who are unable to attain viral suppression (VS) on oral therapy. Limited guidance exists on implementation strategies for this population. SETTING: Ward 86, a clinic serving publicly insured PWH in San Francisco. METHODS: We describe multilevel determinants of and strategies for LA-CAB/RPV implementation for PWH without VS, using the Consolidated Framework for Implementation Research. To assess patient and provider-level determinants, we drew on pre-implementation qualitative data. To assess inner and outer context determinants, we undertook a structured mapping process. RESULTS: Key patient-level determinants included perceived ability to adhere to injections despite oral adherence difficulties and care engagement challenges posed by unmet subsistence needs; strategies to address these determinants included a direct-to-inject approach, small financial incentives, and designated drop-in days. Provider-level determinants included lack of time to obtain LA-CAB/RPV, assess injection response, and follow-up late injections; strategies included centralizing eligibility review with the clinic pharmacist, a pharmacy technician to handle procurement and monitoring, regular multidisciplinary review of patients, and development of a clinic protocol. Ward 86 did not experience many outer context barriers because of rapid and unconstrained inclusion of LA-CAB/RPV on local formularies and ability of its affiliated hospital pharmacy to stock the medication. CONCLUSIONS: Multilevel strategies to support LA-CAB/RPV implementation for PWH without VS are required, which may necessitate additional resources in some settings to implement safely and effectively. Advocacy to eliminate outer-context barriers, including prior authorizations and specialty pharmacy restrictions, is needed.

Demonstration Project of Long-Acting Antiretroviral Therapy in a Diverse Population of People With HIV.

BACKGROUND: Intramuscular cabotegravir (CAB) and rilpivirine (RPV) is the only long-acting antiretroviral therapy (LA-ART) regimen approved for people with HIV (PWH). Long-acting ART holds promise for improving outcomes among populations with barriers to adherence but is only approved for PWH who have virologic suppression with use of oral ART before initiating injectables. OBJECTIVE: To examine LA-ART in a population of PWH that includes those with viremia. DESIGN: Observational cohort study. SETTING: Urban academic safety-net HIV clinic. PATIENTS: Publicly insured adults living with HIV with and without viral suppression, high rates of unstable housing, mental illness, and substance use. INTERVENTION: Demonstration project of long-acting injectable CAB-RPV. MEASUREMENTS: Descriptive statistics summarizing cohort outcomes to date, based on pharmacy team logs and electronic medical record data. RESULTS: Between June 2021 and November 2022, 133 PWH at the Ward 86 HIV Clinic were started on LA-ART, 76 of whom had virologic suppression while using oral ART and 57 of whom had viremia. The median age was 46 years (IQR, 25 to 68 years); 117 (88%) were cisgender men, 83 (62%) had non-White race, 56 (42%) were experiencing unstable housing or homelessness, and 45 (34%) had substance use. Among those with virologic suppression, 100% (95% CI, 94% to 100%) maintained suppression. Among PWH with viremia, at a median of 33 days, 54 of 57 had viral suppression, 1 showed the expected 2-log10 reduction in HIV RNA level, and 2 experienced early virologic failure. Overall, 97.5% (CI, 89.1% to 99.8%) were projected to achieve virologic suppression by a median of 33 weeks. The current virologic failure rate of 1.5% in the cohort is similar to that across registrational clinical trials at 48 weeks. LIMITATION: Single-site study. CONCLUSION: This project demonstrates the ability of LA-ART to achieve virologic suppression among PWH, including those with viremia and challenges to adherence. Further data on the ability of LA-ART to achieve viral suppression in people with barriers to adherence are needed. PRIMARY FUNDING SOURCE: National Institutes of Health, City and County of San Francisco, and Health Resources and Services Administration.

First Demonstration Project of Long-Acting Injectable Antiretroviral Therapy for Persons With and Without Detectable Human Immunodeficiency Virus (HIV) Viremia in an Urban HIV Clinic.

BACKGROUND: Long-acting injectable antiretroviral therapy (LAI-ART) is approved for treatment-naive or experienced people with human immunodeficiency virus (HIV; PWH) based on trials that only included participants with viral suppression. We performed the first LAI-ART demonstration project to include PWH unable to achieve or maintain viral suppression due to challenges adhering to oral ART. METHODS: Ward 86 is a large HIV clinic in San Francisco that serves publicly insured and underinsured patients. We started patients on LAI-ART via a structured process of provider referral, multidisciplinary review (MD, RN, pharmacist), and monitoring for on-time injections. Inclusion criteria were willingness to receive monthly injections and a reliable contact method. RESULTS: Between June 2021 and April 2022, 51 patients initiated LAI-ART, with 39 receiving at least 2 follow-up injections by database closure (median age, 46 years; 90% cisgender men, 61% non-White, 41% marginally housed, 54% currently using stimulants). Of 24 patients who initiated injections with viral suppression (median CD4 cell count, 706 cells/mm3), 100% (95% confidence interval [CI], 86%-100%) maintained viral suppression. Of 15 patients who initiated injections with detectable viremia (median CD4 cell count, 99 cells/mm3; mean log10 viral load, 4.67; standard deviation, 1.16), 12 (80%; 95% CI, 55%-93%) achieved viral suppression, and the other 3 had a 2-log viral load decline by a median of 22 days. CONCLUSIONS: This small demonstration project of LAI-ART in a diverse group of patients with high levels of substance use and marginal housing demonstrated promising early treatment outcomes, including in those with detectable viremia due to adherence challenges. More data on LAI-ART in hard-to-reach populations are needed.