Long-acting ART maintains HIV virologic suppression regardless of obesity status

Long-acting injectable antiretroviral therapy (ART) with cabotegravir plus rilpirvirine (CAB-RPV) is efficacious for the maintenance of HIV virologic suppression regardless obesity status, according to study results published in The Journal of Infectious Diseases.

In this post hoc analysis, researchers examined data captured from patients involved in 3 previous phase 3/3b trials (ClinicalTrials.gov Identifier: NCT02938520; NCT02951052; and NCT03299049) who received long-acting injectable CAB-RPV for HIV virologic suppression. Owing to the rising global prevalence of obesity, the researchers pooled data from these trials to further examine the efficacy, safety, and pharmacokinetics of CAB-RPV among adult patients stratified by low vs high baseline BMI category (<30 vs ≥30 kg/m²) and dosing regimen (every 4 vs 8 weeks). The primary endpoints were the percentage of patients with HIV viral loads below or at or above 50 copies/mL at weeks 48, 96, and 152; the incidence of virologic failure through 152 weeks; adverse events (AEs) from baseline through 152 weeks; and CAB and RPV plasma trough concentrations (C_trough) from week 4 through week 96.

The final analysis included 1245 patients, of whom 327 received treatment every 8 weeks and 918 received treatment 4 weeks, and 1032 (83%) had a low and 213 (17%) had a high baseline BMI. Overall, the median BMI was 25.1 (range, 15.30-54.02) kg/m². Of note, there were more women and Black or African American patients in the low vs high BMI group.

In regard to efficacy, results captured at week 48 showed high overall rates of virologic suppression across the groups. Stratified by dosing regimen, virologic suppression was observed among 94% and 93% of patients in the low BMI group who received treatment every 4 vs 8 weeks, respectively. For the high BMI group, virologic suppression was observed among 92% of patients in both dosing groups. Overall, virologic suppression was maintained among most patients at weeks 96 and 152 (range, 85%-87%) regardless of baseline BMI.

Virologic failure was confirmed among 15 (1%) patients in the overall population at 48 weeks. Of these patients, 1 discontinued treatment due to a false-positive pregnancy test result, 6 were in the low BMI group, and 8 were in the high BMI group. All 8 patients in the high BMI group had at least 1 other baseline characteristic associated with increased risk for virologic failure. Data captured at 96 weeks showed virologic failure occurred among 3 patients, all of whom were in the low BMI group.

The researchers noted that C_troughs for both CAB and RPV remained above protein-adjusted 90% inhibitory concentrations (0.166 µg/mL and 12 ng/mL, respectively) throughout the analysis among patients in both BMI groups.

In the safety analysis, the rate of AEs (range, 69%-86%) was comparable between patients in the low vs high BMI group, with treatment-related AEs reported by 14% to 29% of the overall population. Of patients in the low BMI group, 3% and 2% withdrew from the study due to treatment-related AEs by week 48 and between weeks 48 and 152, respectively. At both of these time points, the rate of study withdrawals due to treatment-related AEs was lower among patients in the high BMI group (<1% and 2%, respectively).

Limitations of this study include the higher frequency of safety assessments among patients who received treatment every 8 weeks, the greater number of patients in the low BMI group, and the use of descriptive data.

According to the researchers, “The safety profiles were generally comparable between BMI categories through Week 48 and up to Week 152, with no new safety signals observed.”

Disclosures: Multiple study authors declared affiliations with biotech, pharmaceutical, and or/device companies. Please see the original reference for a full list of disclosures.

By Erin Sirois, PharmD, MBA

References:

Elliot E, Polli JW, Patel P, et al. Efficacy, safety, and pharmacokinetics by BMI category in Phase 3/3b cabotegravir + rilpivirine long-acting trials. J Infect Dis. Published online December 22, 2023. doi:10.1093/infdis/jiad580