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Background Cabotegravir plus rilpivirine (CAB + RPV) is a guideline-recommended long-acting (LA) injectable regimen for the maintenance of human immunodeficiency virus-1 (HIV-1) virologic suppression. This post hoc analysis summarizes CAB + RPV LA results by baseline body mass index (BMI) category among phase 3/3b trial participants. Methods Data from CAB + RPV-naive participants receiving every 4 or 8 week dosing in FLAIR, ATLAS, and ATLAS-2M were pooled through week 48. Data beyond week 48 were summarized by study (FLAIR through week 96 and ATLAS-2M through week 152). HIV-1 RNA <50 and ≥50 copies/mL, confirmed virologic failure (CVF; 2 consecutive HIV-1 RNA ≥200 copies/mL), safety and tolerability, and plasma CAB and RPV trough concentrations were evaluated by baseline BMI (<30 kg/m2, lower; ≥30 kg/m2, higher). Results Among 1245 CAB + RPV LA participants, 213 (17%) had a baseline BMI ≥30 kg/m2. At week 48, 92% versus 93% of participants with lower versus higher BMI had HIV-1 RNA <50 copies/mL, respectively. Including data beyond week 48, 18 participants had CVF; those in the higher BMI group (n = 8) all had at least 1 other baseline factor associated with CVF (archived RPV resistance-associated mutations or HIV-1 subtype A6/A1). Safety and pharmacokinetic profiles were comparable between BMI categories. Conclusions CAB + RPV LA was efficacious and well tolerated, regardless of baseline BMI category. Clinical Trials Registration NCT02938520, NCT02951052, and NCT03299049. [ABSTRACT FROM AUTHOR]

Objectives: Cabotegravir + rilpivirine (CAB + RPV) dosed monthly or every 2 months is the first complete long‐acting (LA) regimen recommended by treatment guidelines for the maintenance of HIV‐1 virological suppression. This post hoc analysis summarizes outcomes for Asian participants through week 96. Methods: Data from Asian participants naive to CAB + RPV randomized to receive dosing every 4 weeks (Q4W) or every 8 weeks (Q8W) in the FLAIR (NCT02938520) and ATLAS‐2M (NCT03299049) phase 3/3b studies were pooled. The proportion of participants with plasma HIV‐1 RNA ≥50 and <50 copies/mL (per FDA Snapshot algorithm), incidence of confirmed virological failure (CVF; two consecutive HIV‐1 RNA ≥200 copies/mL), pharmacokinetics, safety, and tolerability through week 96 were assessed. Results: Overall, 41 Asian participants received CAB + RPV (Q8W, n = 17; Q4W, n = 24). At week 96, 83% (n = 34/41) of participants maintained HIV‐1 RNA <50 copies/mL, none had HIV‐1 RNA ≥50 copies/mL, and 17% (n = 7/41) had no virological data. No Asian participant met the CVF criterion. Drug‐related adverse events occurred in 44% (n = 18/41) of participants; none were Grade ≥3. All injection site reactions were Grade 1 or 2; median duration was 2 days and most resolved within 7 days (90%, n = 390/435). CAB and RPV trough concentrations remained well above their respective protein‐adjusted 90% inhibitory concentrations (CAB, 0.166 μg/mL; RPV, 12 ng/mL) through week 96. Conclusions: CAB + RPV LA demonstrated high efficacy, with no participants having CVF, and an acceptable safety profile in Asian participants through week 96. These data support CAB + RPV LA as a complete regimen for the maintenance of HIV‐1 virological suppression in Asian individuals. [ABSTRACT FROM AUTHOR]

Background: Limited data exist on pregnant women living with HIV exposed to cabotegravir + rilpivirine (CAB + RPV). Outcomes in pregnant participants exposed to CAB + RPV, and pharmacokinetic washout data in those exposed to CAB + RPV long‐acting (LA) with live births, are presented. Methods: Women exposed to one or more doses of CAB + RPV (oral/LA) from ViiV Healthcare‐sponsored phase 2b/3/3b clinical trials and the compassionate use programme who became pregnant were included. Upon pregnancy in the trial programme, CAB + RPV was discontinued, an alternative antiretroviral regimen was initiated, and quarterly pharmacokinetic sampling for 52 weeks post‐last injection was obtained. CAB + RPV continuation or alternative antiretroviral regimen initiation was decided by pregnant compassionate use programme participants and their treating physicians. Results: As of 31 March 2021, 25 pregnancies following CAB + RPV exposure at conception were reported (five oral, 20 LA), including four who conceived during pharmacokinetic washout following treatment discontinuation. There were eight elective abortions, six miscarriages (five in first trimester), one ectopic pregnancy, and 10 live births (one oral, nine LA), including one infant born with congenital ptosis. Among participants exposed to CAB + RPV LA at conception with live births, plasma CAB and RPV washout concentrations during pregnancy were within the range of those observed in non‐pregnant women. Conclusion: In this first analysis of pregnancy outcomes following CAB + RPV exposure at conception, 10 live births, including one with congenital anomaly, were reported. Plasma CAB and RPV washout concentrations during pregnancy were within the range of those in non‐pregnant women. Pregnancy surveillance within ViiV Healthcare‐sponsored clinical trials is ongoing, with dedicated pregnancy studies planned. [ABSTRACT FROM AUTHOR]

배경 Cabotegravir (CAB) + rilpivirine (RPV) is the first guideline-recommended, complete long-acting (LA) injectable regimen for maintenance of HIV-1 virologic suppression. In a post-hoc, multivariable analysis, the presence of ≥2 of 3 baseline (BL) factors (archived RPV resistance-associated mutations [RAMs], HIV-1 subtype A6/A1, or BMI ≥30 kg/m2 ) modestly increased confirmed virologic failure (CVF) risk. Efficacy, safety, and pharmacokinetics of CAB+RPV by BL BMI category among Phase 3/3b trial participants through Week 48 (W48) were evaluated. 방법 Data were pooled from CAB+RPV-naive participants receiving every-4- or 8-week dosing (Q4W or Q8W) in the ATLAS, FLAIR, and ATLAS-2M studies. Baseline characteristics, HIV-1 RNA <50 and ≥50 copies/mL, CVF (2 consecutive HIV-1 RNA ≥200 copies/mL), injection site reaction adverse events (ISR AEs), and plasma CAB and RPV troughs were evaluated through W48 by lower or higher BMI category (<30 or ≥30 kg/m² ). 결과 Among 1245 CAB+RPV LA participants, 213 (17%) had a BL BMI ≥30 kg/m². At W48, 92% vs. 93% of participants with higher vs. lower BMI, respectively, had HIV-1 RNA <50 copies/mL. There were 8 vs. 5 CVFs in the higher vs. lower BMI group. All CVFs in the higher BMI group had at least one other BL risk factor (archived RPV RAMs [n=3], A6/A1 subtype [n=4], both [n=1]). No participant with higher BMI alone developed CVF at W48. Overall safety, including ISR AEs, was comparable between groups. CAB and RPV troughs remained above their respective PA-IC90 values regardless of BMI or dosing arm. 결론 CAB+RPV LA Q4W and Q8W maintained high virologic suppression rates through W48 in Phase 3/3b trials, regardless of BL BMI category. Injections were well-tolerated, with few ISR-related discontinuations. CAB+RPV offers a safe and effective long-acting treatment option in participants across a wide BMI range without need for daily oral dosing. [ABSTRACT FROM AUTHOR]

Background: Long-acting cabotegravir + rilpivirine (CAB+RPV LA) administered monthly or every 2 months is the first complete LA regimen recommended by treatment guidelines for maintaining HIV-1 virologic suppression. Across Phase 3/3b trials, the most frequently reported adverse events were injection site reactions (ISRs). Here, we present pooled ISR outcomes by regimen, sex, and body mass index (BMI) from the ATLAS-2M and FLAIR studies through Week (W) 96. Methods: Data from participants receiving CAB+RPV LA in ATLAS-2M and FLAIR were pooled and stratified by dosing regimen, sex, and baseline BMI category. Data from ATLAS-2M participants who transitioned from CAB+RPV in ATLAS were excluded. ISR characteristics were evaluated through W96. Results: 920 (Q8W, n=321; Q4W, n=599) participants received ≥1 injection of CAB LA/RPV LA across ATLAS-2M and FLAIR, representing 34,939 injections through W96 (Q8W, n=7954; Q4W, n=26,985) (Table). Overall, 8453 ISRs (Q8W, n=2345; Q4W, n=6108) were reported by 801 participants (Q8W, 89% [n=285]; Q4W, 86% [n=516]). Most were mild to moderate in severity(Grade 1, 83%; Grade 2, 16%; Grade 3, 1%), with a median (interquartile range) duration of 3 days (2–4), and 86% had a duration ≤7 days. The most commonly reported ISRs (% of injections) were pain (20%), nodule (1%), and discomfort (1%). ISRs incidence decreased over time, reported by 71%, 24%, and 15% of participants at W4, W48, and W96, respectively. ISR-related withdrawals were infrequent and comparable between dosing regimens, occurring in 2% (n=20) of participants (majority were injection intolerability [n=10]). ISR profiles over 96 weeks were generally comparable across regimen, sex, and baseline BMI category. Conclusion: The majority of ISRs were mild to moderate in severity, short-lived, and rarely led to treatment discontinuation. Outcomes were comparable by regimen, sex, and BMI category. These data further support the use of CAB+RPV LA as a complete maintenance regimen for HIV-1. [ABSTRACT FROM AUTHOR]

Background: Cabotegravir (CAB) and rilpivirine (RPV) is the first complete long-acting (LA) regimen recommended by treatment guidelines to maintain HIV-1 virologic suppression. Dosing every 4 weeks (Q4W) or every 8 weeks (Q8W) showed noninferior efficacy in Phase 3/3b trials. This post hoc analysis summarizes Asian participant (pt) outcomes through Week (W) 96. Methods: We pooled data from Asian pts naive to CAB+RPV (n=41) randomized to receive Q4W (n=24) or Q8W (n=17) dosing in Phase 3/3b FLAIR (NCT02938520) and ATLAS-2M (NCT03299049). The proportion of pts with HIV-1 RNA ≥50 and <50copies/mL (FDA Snapshot), incidence of confirmed virologic failure (CVF), adherence, and safety through W96 were assessed. Results: Median pt age was 39 years, 4 were female at birth, 1 had a body mass index ≥30 kg/m2; 0 were hepatitis B-reactive (non-reactive, n=12; negative, n=29). Pts enrolled at centers in Asia (59%, n=24), North America (27%, n=11), Europe (10%, n=4), Africa, and Australia (each 2%, n=1). At W96, 83% (n=34/41) of pts maintained HIV-1 RNA <50copies/mL, 0 had HIV-1 RNA ≥50copies/mL, and 17% (n=7/41) had no virologic data due to discontinuation. No pt met CVF criterion. 93% (n=38) of pts had non-injection site reaction [ISR] AEs; 95% (n=36/38) were Grade≤2, and 47% (n=18/38) were deemed drug-related. No pt had a Grade ≥3 drug-related AE. Serious AEs occurred in 12% (n=5/41) of pts. Most injection visits (97%, n=620/642) occurred within the ±7-day dosing window; one injection visit was missed and covered by oral CAB+RPV. The most common ISR was injection site pain (28% of injections, n=378/1360); all Grade≤2 with median 2-day duration. Pts withdrew due to drug-related non-ISR AEs (5%, n=2/41) and injection-related reasons (10%, n=4/41). Conclusion: CAB+RPV LA demonstrated high efficacy, with no pts having CVF, and acceptable safety in Asian pts through W96. These data support CAB+RPV LA as a complete regimen to maintain virologic suppression in Asian pts with HIV-1. [ABSTRACT FROM AUTHOR]