Brief Report: Impact of COVID-19 on Cabotegravir Plus Rilpivirine Long-Acting Dosing Across 6 Ongoing Global Phase IIb and III Clinical Trials.

BACKGROUND: Cabotegravir + rilpivirine long-acting (LA) is a novel antiretroviral therapy (ART) administered intramuscularly monthly or every 2 months by a health care provider. The COVID-19 pandemic presents a potential challenge to patients' ability to attend scheduled clinic visits for dosing administration. SETTING: This analysis evaluated implementation fidelity across 6 phase IIb/III/IIIb cabotegravir + rilpivirine LA clinical trials in 16 countries during the COVID-19 pandemic. METHODS: COVID-19-impacted visits were defined as modified dosing visits for which oral therapy was provided to participants unable to attend the clinic or injection visits that were rescheduled. Data from December 1, 2019, to March 1, 2021, were aggregated and analyzed using descriptive statistics. RESULTS: Of 2127 participants in cabotegravir + rilpivirine LA trials, 1997 (94%) had LA dosing visits proceed as planned during the COVID-19 pandemic. Of 130 (6%) participants with injection visits affected by COVID-19, most were from North America (57%) and Europe (26%). Most participants with COVID-19-impacted visits used oral therapy with cabotegravir + rilpivirine (75%) or alternative oral standard-of-care ART (21%) to maintain continuous ART. The most common reasons for missed visits were clinic closure/staffing constraints (48%) and COVID-19-related travel restrictions (23%). Most (98%) participants who used oral ART maintained virologic suppression; 2 participants had viral load between 50 and 100 copies/mL. CONCLUSION: During the COVID-19 pandemic, most trial participants maintained their LA dosing schedules. Flexibility of the LA dosing regimen, with the ability to switch to oral therapy, facilitated continuous ART provision and implementation fidelity.

Perspectives of people living with HIV-1 on implementation of long-acting cabotegravir plus rilpivirine in US healthcare settings: results from the CUSTOMIZE hybrid III implementation-effectiveness study.

INTRODUCTION: The CUSTOMIZE hybrid III implementation-effectiveness study evaluated implementation of once-monthly long-acting (LA) cabotegravir + rilpivirine in diverse US healthcare settings. Here, we report patient participant perspectives after 12 months in CUSTOMIZE. METHODS: CUSTOMIZE was a phase IIIb, 12-month study conducted from July 2019 to October 2020 at eight diverse US HIV clinics that enrolled virologically suppressed people living with HIV-1 (PLHIV) on a stable oral regimen to receive monthly cabotegravir + rilpivirine LA injections after a 1-month oral lead-in. Participants were administered quantitative surveys before injections at months 1 (baseline), 4 and 12. A randomly selected subset of participants was interviewed at baseline and month 12. Data collection at month 12 was completed by October 2020 (during the COVID-19 pandemic). RESULTS: At baseline, 109 and 34 participants completed surveys and interviews, respectively; 87% were male; 35% were Black or African American. All participants who remained in the study at month 12 (n = 102) maintained HIV-1 RNA <50 copies/ml; two participants withdrew due to injection-related reasons. Mean total scores measuring acceptability and appropriateness of cabotegravir + rilpivirine LA were high at baseline (4.5-4.6 out of 5) and month 12 (4.7-4.9). At month 12, 74% of participants reported nothing interfered with receiving LA injections; injection pain or soreness was the most common concern (15%). Time spent in the clinic and coming to the clinic for monthly injections was very or extremely acceptable after 12 months for most participants (93% and 87%, respectively), with 64% reporting having spent ≤30 minutes in the clinic for injection visits. At month 12, 92% of participants preferred LA injections to daily oral tablets (3%); 97% plan to continue LA treatment going forward. In month 12 interviews, 24 (77%) of 31 participants reported the COVID-19 pandemic did not impact their ability to receive treatment. CONCLUSIONS: Once-monthly cabotegravir + rilpivirine LA was highly acceptable among PLHIV who were virologically suppressed on a stable antiretroviral regimen and interested in trying LA therapy, with few participants reporting challenges receiving LA injections. Implementation data from CUSTOMIZE suggest that monthly LA injections provide a convenient and appealing treatment option for PLHIV.

Perspectives of healthcare providers on implementation of long-acting cabotegravir plus rilpivirine in US healthcare settings from a Hybrid III Implementation-effectiveness study (CUSTOMIZE).

INTRODUCTION: CUSTOMIZE evaluated the implementation of long-acting (LA) cabotegravir + rilpivirine, a novel healthcare provider-administered injectable antiretroviral therapy regimen, in diverse US healthcare settings. Findings from staff-study participants (SSPs) through 12 months of implementation are reported. METHODS: CUSTOMIZE was a phase IIIb, 12-month, single-arm, hybrid III implementation-effectiveness study conducted from July 2019 to October 2020 at eight US clinics of five clinic types: private practice (n = 2), federally qualified health centre (n = 2), university (n = 2), AIDS Healthcare Foundation (n = 2) and health maintenance organization (n = 1). Eligible patient participants received monthly cabotegravir + rilpivirine LA injections after a 1-month oral lead-in. At baseline, month 4 and month 12, SSPs (n = 3 each per clinic), including physicians, nurses or injectors, and administrators, completed quantitative surveys and semi-structured interviews to assess implementation outcomes (acceptability, appropriateness and feasibility of intervention measures), programme sustainability and SSP perceptions of, attitudes towards, and expectations for cabotegravir + rilpivirine LA. Month 12 data collection occurred during the COVID-19 pandemic. RESULTS: In surveys, SSPs reported high mean total scores for acceptability, appropriateness and feasibility of cabotegravir + rilpivirine LA implementation at baseline (4.43, 4.52 and 4.38 of 5, respectively) and month 12 (4.45, 4.61 and 4.46 of 5, respectively), regardless of clinic type. At month 12, SSPs were positive about the implementation sustainability (mean Program Sustainability Assessment Tool score, 5.83 out of 7). At baseline, SSPs' top concern was patients' ability to maintain monthly appointments (81%); at month 12, 39% had this concern. The proportion of SSPs reporting patient injection pain or soreness as a barrier was consistent at month 12 versus baseline (48% vs. 46%). Most (78%) SSPs reported optimal implementation of cabotegravir + rilpivirine LA in their clinics was achieved in 1-3 months. In interviews, SSP-reported strategies for successful implementation included teamwork, using a web-based treatment planner and having a designated person to track appointment scheduling. In month 12 interviews, SSP-reported structural changes needed for implementation included changing clinic hours and purchasing refrigerators. CONCLUSIONS: In CUSTOMIZE, cabotegravir + rilpivirine LA was successfully implemented across a range of US healthcare settings. Barriers were mitigated with minor process adjustments.