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Clinical Trial
. 2024 Jul 25;230(1):e34-e42.
doi: 10.1093/infdis/jiad580.

Efficacy, Safety, and Pharmacokinetics by Body Mass Index Category in Phase 3/3b Long-Acting Cabotegravir Plus Rilpivirine Trials

Emilie R Elliot  1 , Joseph W Polli  1 , Parul Patel  1 , Louise Garside  2 , Richard Grove  3 , Vincent Barnett  4 , Jeremy Roberts  5 , Sri Byrapuneni  6 , Herta Crauwels  7 , Susan L Ford  4 , Rodica Van Solingen-Ristea  7 , Eileen Birmingham  8 , Ronald D'Amico  1 , Bryan Baugh  8 , Jean van Wyk  9
Affiliations
Clinical Trial

Efficacy, Safety, and Pharmacokinetics by Body Mass Index Category in Phase 3/3b Long-Acting Cabotegravir Plus Rilpivirine Trials

Emilie R Elliot et al. J Infect Dis. .

Abstract

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.

Keywords: BMI; HIV-1; cabotegravir; long-acting; rilpivirine.

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Conflict of interest statement

Potential conflicts of interest. E. R. E., J. W. P., P. P., R. D., and J. v. W. are employees of ViiV Healthcare and may be stockholders of GSK. L. G., R. G., V. B., J. R., and S. L. F. are employees and may be stockholders of GSK. S. B. currently performs services for GSK LLC, on behalf of ViiV Healthcare, in connection with the author’s statistical analysis support on the ATLAS-2M study. H. C., R. V. S.-R., E. B., and B. B. are employees of Janssen Research and Development, Pharmaceutical Companies of Johnson & Johnson and may be stockholders of Johnson & Johnson. R. V. S.-R. holds a patent for “Method of treating HIV with cabotegravir and rilpivirine.” All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Summary of ISRs through week 48. AE grade is the maximum grade reported by the participant at each visit. Few ISRs were classified as grade 3 (approximately 1% of ISR events), consistent across both BMI categories and dosing regimens. There were no grade 4 or 5 ISR events. Abbreviations: AE, adverse event; BMI, body mass index; CAB, cabotegravir; ISR, injection site reaction; LA, long-acting; Q4W, every 4 weeks; Q8W, every 8 weeks; RPV, rilpivirine; W, week.
Figure 2.
Figure 2.
Median (5th and 95th percentile) plasma CAB and RPV troughs through week 48. Data beyond week 48 are not shown, as ATLAS-2M did not assess PK after week 48 except for the single values at week 96 and FLAIR PK were not consistently assessed after week 48. Participant numbers for CAB administration are shown. RPV participant numbers were identical, with the following exceptions: Q8W, <30 kg/m2: week 16, n = 259; Q8W, ≥30 kg/m2: week 4, n = 58; week 8, n = 58; Q4W, <30 kg/m2: week 8, n = 743; week 16, n = 730; week 24, n = 718; week 32, n = 715; week 44, n = 450; week 48, n = 691; Q4W, ≥30 kg/m2: week 4, n = 152; week 12, n = 101; week 24, n = 147; week 40, n = 143; week 48, n = 144. Abbreviations: BMI, body mass index; CAB, cabotegravir; PA-IC90, protein-adjusted 90% inhibitory concentration; PK, pharmacokinetics; Q4W, every 4 weeks; Q8W, every 8 weeks; RPV, rilpivirine.
Figure 3.
Figure 3.
Median (5th and 95th percentile) plasma CAB Ctrough through week 48 in participants with BMI ≥30 kg/m2 by needle length. The majority (78%, n = 3889 of 4970) of injections in participants with BMI ≥30 kg/m2 were administered with needles <1.6 inches (<4.06 cm) in length versus the recommended longer 2-inch (5.08 cm) needle due to issues with procurement. Abbreviations: BMI, body mass index; CAB, cabotegravir; Ctrough, trough concentration; PA-IC90, protein-adjusted 90% inhibitory concentration; Q4W, every 4 weeks; Q8W, every 8 weeks.
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References

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