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AimTo characterize cabotegravir population pharmacokinetics using data from phase 1, 2 and 3 studies and evaluate the association of intrinsic and extrinsic factors with pharmacokinetic variability.MethodsAnalyses were implemented in NONMEM and R. Concentrations below the quantitation limit were modelled with likelihood-based approaches. Covariate relationships were evaluated using forward addition (P

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]

Background Cabotegravir (CAB) + rilpivirine (RPV) dosed monthly or every 2 months is a complete long-acting (LA) regimen for the maintenance of human immunodeficiency virus type 1 virologic suppression. Across the phase 3/3b trials, the most frequently reported adverse events were injection site reactions (ISRs). Methods We present pooled ISR characteristics and outcomes for participants receiving CAB + RPV LA through week 96 of the FLAIR and ATLAS-2M studies, and survey results from healthcare providers (HCPs) giving injections (eg, injectors) in the ATLAS, FLAIR, and ATLAS-2M studies to determine optimal injection techniques. Surveys were anonymous, self-administered online questionnaires that queried provider demographics, injection experience, and techniques to minimize pre-/postinjection discomfort. Data were summarized using descriptive statistics. Results Overall, 8453 ISRs were reported by 801 participants receiving ≥1 injection of CAB LA/RPV LA. Most ISRs were mild to moderate in severity (grade 1–2, 99%), with a median duration of 3 days (interquartile range, 2–4 days), and rarely led to withdrawal (2%). Surveys were completed by 181 HCPs across 113 sites. Pushing the intramuscular injection at slow speed (66%), bringing the medication to room temperature (58%), and relaxing the gluteus muscle before injecting (53%) were ranked as effective preinjection/injection procedure practices for minimizing pain. Most injectors (60%) indicated that a prone position provided optimal patient comfort, and 41% had no preference on injection medication order. Conclusions Taken together, the data demonstrate favorable tolerability with CAB + RPV LA injections over the long term and simple techniques routinely used by injectors to help optimize the administration of CAB + RPV LA injections. [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 Previously reported post hoc multivariable analyses exploring predictors of confirmed virologic failure (CVF) with cabotegravir + rilpivirine long-acting (CAB + RPV LA) were expanded to include data beyond week 48, additional covariates, and additional participants. Methods Pooled data from 1651 participants were used to explore dosing regimen (every 4 or every 8 weeks), demographic, viral, and pharmacokinetic covariates as potential predictors of CVF. Prior dosing regimen experience was accounted for using 2 populations. Two models were conducted in each population—baseline factor analyses exploring factors known at baseline and multivariable analyses exploring baseline factors plus postbaseline model-predicted CAB/RPV trough concentrations (4 and 44 weeks postinjection). Retained factors were evaluated to understand their contribution to CVF (alone or in combination). Results Overall, 1.4% (n = 23/1651) of participants had CVF through 152 weeks. The presence of RPV resistance-associated mutations, human immunodeficiency virus-1 subtype A6/A1, and body mass index ≥30 kg/m2 were associated with an increased risk of CVF (P <.05 adjusted incidence rate ratio), with participants with ≥2 of these baseline factors having a higher risk of CVF. Lower model-predicted CAB/RPV troughs were additional factors retained for multivariable analyses. Conclusions The presence of ≥2 baseline factors (RPV resistance-associated mutations, A6/A1 subtype, and/or body mass index ≥30 kg/m2) was associated with increased CVF risk, consistent with prior analyses. Inclusion of initial model-predicted CAB/RPV trough concentrations (≤first quartile) did not improve the prediction of CVF beyond the presence of a combination of ≥2 baseline factors, reinforcing the clinical utility of the baseline factors in the appropriate use of CAB + RPV LA. [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]

Aim: Cabotegravir long‐acting (LA) intramuscular (IM) injection is being investigated for HIV preexposure prophylaxis due to its potent antiretroviral activity and infrequent dosing requirement. A subset of healthy adult volunteers participating in a Phase I study assessing cabotegravir tissue pharmacokinetics underwent serial magnetic resonance imaging (MRI) to assess drug depot localization and kinetics following a single cabotegravir LA IM targeted injection. Methods: Eight participants (four men, four women) were administered cabotegravir LA 600 mg under ultrasonographic‐guided injection targeting the gluteal muscles. MRI was performed to determine injection‐site location in gluteal muscle (IM), subcutaneous (SC) adipose tissue and combined IM/SC compartments, and to quantify drug depot characteristics, including volume and surface area, on Days 1 (≤2 hours postinjection), 3 and 8. Linear regression analysis examined correlations between MRI‐derived parameters and plasma cabotegravir exposure metrics, including maximum observed concentration (Cmax) and partial area under the concentration–time curve (AUC) through Weeks 4 and 8. Results: Cabotegravir LA depot locations varied by participant and were identified in the IM compartment (n = 2), combined IM/SC compartments (n = 4), SC compartment (n = 1) and retroperitoneal cavity (n = 1). Although several MRI parameter and exposure metric correlations were determined, total depot surface area on Day 1 strongly correlated with plasma cabotegravir concentration at Days 3 and 8, Cmax and partial AUC through Weeks 4 and 8. Conclusion: MRI clearly delineated cabotegravir LA injection‐site location and depot kinetics in healthy adults. Although injection‐site variability was observed, drug depot surface area correlated with both plasma Cmax and partial AUC independently of anatomical distribution. [ABSTRACT FROM AUTHOR]

This study investigates the impact of severe renal impairment on the pharmacokinetics of cabotegravir, an investigational HIV‐1 integrase inhibitor. This was a phase I, open‐label, parallel‐group, multicenter study conducted in 8 participants with severe renal impairment (creatinine clearance <30 mL/min; no renal replacement therapy) and 8 healthy participants (creatinine clearance >90 mL/min; 2 women/group; 6 men/group) matched for sex, age (±10 years), and body mass index (±25%). Participants received a single 30‐mg oral cabotegravir tablet to determine total and unbound plasma cabotegravir concentrations. Arithmetic and geometric least squares means were calculated, and cabotegravir noncompartmental pharmacokinetic parameters were compared using geometric least squares mean ratios with 90% confidence intervals. Safety was assessed throughout the study. Geometric least squares mean ratios (90% confidence intervals) were 0.97 (0.84–1.14) for area under the plasma concentration‐time curve extrapolated to infinity, 1.01 (0.87–1.17) for maximum observed plasma concentration, 1.31 (0.84–2.03) for unbound cabotegravir 2 hours after dosing, and 1.51 (1.19–1.92) for unbound cabotegravir 24 hours after dosing. All adverse events were grade 1, except grade 3 lipase elevation in a participant with renal impairment. Severe renal impairment did not impact plasma cabotegravir exposure, and cabotegravir may be administered without dose adjustment in renal impairment among patients not receiving renal replacement. [ABSTRACT FROM AUTHOR]

Cabotegravir is an investigational integrase inhibitor in development for the treatment and pre‐exposure prophylaxis of HIV‐1 infection. Liver disease is a major cause of morbidity and mortality in HIV‐infected individuals and can impact the pharmacokinetics (PK) of HIV medications. This phase 1 study evaluated the PK of cabotegravir in individuals with moderate hepatic impairment (n = 8) versus healthy controls (n = 8). Participants received a single oral cabotegravir 30‐mg tablet and underwent PK sampling to determine total and unbound plasma cabotegravir concentrations. Calculated geometric least‐squares mean ratios (90% confidence intervals) for individuals with hepatic impairment versus healthy controls were 0.73 (0.50‐1.06) for AUC0‐∞, 0.69 (0.51‐0.93) for Cmax, 1.40 (0.80‐2.46) for unbound concentration (CU) 2 hours postdose, 1.55 (0.82‐2.94) for CU at 24 hours, 2.14 (1.57‐2.90) for unbound fraction (FU) at 2 hours, and 1.90 (1.14‐3.18) for FU at 24 hours. Adverse events (AEs) occurred in 2 individuals with hepatic impairment and 3 healthy controls and were grade 1/2 in severity. No participant discontinued because of AEs. Increased FU resulted in a modest decrease in total plasma exposure not considered clinically relevant. We conclude that cabotegravir may be administered without dose adjustment in patients with mild to moderate hepatic impairment. [ABSTRACT FROM AUTHOR]

배경 Cabotegravir (CAB) + rilpivirine (RPV) is the first complete long-acting (LA) regimen approved and rec- ommended by treatment guidelines for the maintenance of virologic suppression in people living with HIV-1. To date, limited data are available for those who discontinued CAB+RPV LA and resumed daily oral antiretrovirals (ARVs). Here, we describe results for participants who discontinued CAB+RPV LA during the Phase III/IIIb program and entered 12-month (12M) long-term follow-up (LTFU). 방법 All participants exposed to CAB+RPV LA and discontinued from ATLAS, FLAIR, or ATLAS-2M were included. Demographics, reason(s) for discontinuing LA therapy, and efficacy/safety of subsequent ARV therapy are evaluated 결과 1723 unique participants were randomized across Phase III/IIIb studies, with 150 participants (n=138 from maintenance and extension and n=12 after switch in the extension phase) discontinuing CAB+RPV LA and entering LTFU. The median age in LTFU group was 38 years, 70% were white, and 30% female (Figure 1). Median duration of CAB+RPV LA treatment before discontinuing was 36.7 weeks (0.9-144 weeks). Reasons for entering LTFU included AEs, participant withdrawal, and lack of efficacy (Figure 2). Participants primarily switched to INSTI- (58%) or bPI- (21%) containing regimens; 82% of switches oc- curred within 4-8 weeks of CAB+RPV LA discontinuation. Of 150 entering LTFU, 92 completed M12, 4 withdrew, and 54 are ongoing. At M12, 97% (84/87) with viral load data maintained HIV-1 RNA <50 copies/ml. Thirteen (9%) participants reported drug-related AEs while on oral ARVs, with no AE-related discontinuations. 결론 Through up to 144 weeks, approximately 9% of study participants in Phase III/IIIb trials discontinued CAB+RPV LA and entered LTFU with the majority resuming an INSTI- or bPI-based oral regimen. High rates of suppression were maintained on subsequent ARV, with no efficacy or safety concerns in participants who switched to oral ARVs, regardless of reason for switch. [ABSTRACT FROM AUTHOR]

배경 Cabotegravir (CAB) and rilpivirine (RPV) is the first guideline-recommended complete long-acting (LA) regimen for the maintenance of HIV-1 virologic suppression. In Phase 3 studies, oral CAB+RPV given once daily was utilized as an oral lead-in (OLI) for ≥4 weeks prior to initiating LA dosing to assess in- dividual safety and tolerability. The FLAIR extension phase demonstrated that initiating CAB+RPV direct-to-injection (DTI) had comparable safety, tolerability, efficacy, and pharmacokinetics compared with initiating with an OLI, offering a practical treatment simplification strategy. This post hoc analysis com- pares the safety of CAB+RPV during the OLI to LA administration periods across the Phase 3 program. 방법 Week 48 data from participants naive to CAB+RPV in the FLAIR, ATLAS, and ATLAS-2M studies were pooled. Safety outcomes were summarized separately during OLI and LA periods for those randomized at baseline to CAB+RPV, and also for those switching from oral comparator to CAB+RPV (either via DTI or OLI) during the FLAIR extension phase (Week 100-Week 124). 결과 1245 participants were in cluded in the pooled population; 918 and 327 received CAB+RPV LA Q4W and Q8W following an OLI, respectively. Further, 232 FLAIR extension-switch participants received CAB+RPV LA Q4W, either DTI (n=111) or following an OLI (n=121). The OLI period was well tolerated, with few Grade 3/4 AEs (1%, n=15/1245), serious AEs (<1%, n=9/1245), or AEs leading to withdrawal (<1%, n=10/1245); after continuing to LA therapy, AE rates were comparable between participants electing to receive OLI or DTI (Figure). No drug hypersensitivity reactions or other serious AEs occurred during the 4-week OLI that prohibited transition to LA therapy. 결론 A 4-week OLI of CAB+RPV was well tolerated in >1200 participants across the Phase 3 program. The safety profile of CAB+RPV LA dosing was similar regardless of whether participants received OLI or proceeded DTI, supporting optional CAB+RPV DTI as a simplification strategy. Data included in this abstract have been previously presented in full at the 18th European AIDS Conference; October 27-30, 2021; Virtual & London, UK; Poster PE2/75. [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]

Aims This study aimed to investigate whether cabotegravir (CAB), an integrase inhibitor in development for treatment and prevention of human immunodeficiency virus-1, influences the pharmacokinetics (PK) of a levonorgestrel (LNG) and ethinyl oestradiol (EO)-containing oral contraceptive (OC) in healthy women. Methods In this open-label, fixed-sequence crossover study, healthy female subjects received LNG 0.15 mg/EO 0.03 mg tablet once daily Days 1-10 alone and with oral CAB 30 mg once daily Days 11-21. At the end of each treatment period, subjects underwent predose sampling for concentrations of follicle-stimulating hormone, luteinizing hormone, and progesterone and serial PK sampling for plasma LNG, EO, and CAB concentrations. Results Twenty women were enrolled, and 19 completed the study. One subject was withdrawn due to an adverse event unrelated to study medications. Geometric least squares mean ratios (90% confidence interval) of LNG + CAB vs. LNG alone for LNG area under the plasma concentration-time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.12 (1.07-1.18) and 1.05 (0.96-1.15), respectively. Geometric least squares mean ratio (90% confidence interval) of EO + CAB vs. EO alone for EO area under the plasma concentration-time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.02 (0.97-1.08) and 0.92 (0.83-1.03), respectively. Steady-state CAB PK parameters were comparable to historical values. There was no apparent difference in mean luteinizing hormone, follicle-stimulating hormone, and progesterone concentrations between periods. No clinically significant trends in laboratory values, vital signs, or electrocardiography values were observed. Conclusions Repeat doses of oral CAB had no significant effect on LNG/EO PK or pharmacodynamics, which supports CAB coadministration with LNG/EO OCs in clinical practice. [ABSTRACT FROM AUTHOR]

A randomized, partial-blind, repeat-dose, 3-period crossover study (NCT02027454) assessed the effect of cabotegravir on QT interval in healthy subjects. To achieve a supratherapeutic dose, each subject received cabotegravir 150 mg (30 mg × 5 tablets) every 12 hours for a total of 3 doses over 2 days, matching placebo (every 12 hours) over 2 days, or a single open-label 400-mg dose of the positive control moxifloxacin, with a 21-day washout between treatments. Blood samples for pharmacokinetic analyses were collected up to 24 hours after the third dose on day 2. QT interval data were obtained by continuous Holter monitoring for approximately 24 hours at baseline (day -1) and from 2 hours before to 24 hours after the third dose on day 2. Plasma cabotegravir exposure was approximately 3-fold above clinically relevant doses. After 3 doses of 150 mg of cabotegravir administered every 12 hours, all upper limits of 2-sided 90% confidence intervals for ΔΔQTcF (difference in time-matched change from baseline for QTcF between cabotegravir and placebo) were <10 milliseconds. There was no relationship between cabotegravir plasma concentrations and ΔΔQTcF. No subject receiving cabotegravir had a QTcF value > 450 milliseconds. There were no serious or grade 3 or 4 adverse events or clinically significant changes in laboratory values, vital signs, or electrocardiogram results. These data demonstrate that cabotegravir at a supratherapeutic dose had no effect on cardiac repolarization. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. Methods: Adult participants with virologic suppression (plasma HIV-1 RNA ,50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the longacting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV oncedaily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA $50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA $200 copies/mL) were secondary endpoints. Results: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged $50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA $50 copies/mL) and key secondary (HIV-1 RNA ,50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. Conclusion: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression. [ABSTRACT FROM AUTHOR]