Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov 17;77(10):1423-1431.
doi: 10.1093/cid/ciad370.

Expanded Multivariable Models to Assist Patient Selection for Long-Acting Cabotegravir + Rilpivirine Treatment: Clinical Utility of a Combination of Patient, Drug Concentration, and Viral Factors Associated With Virologic Failure

Chloe Orkin  1 , Jonathan M Schapiro  2 , Carlo F Perno  3 , Daniel R Kuritzkes  4 , Parul Patel  5 , Rebecca DeMoor  6 , David Dorey  7 , Yongwei Wang  5 , Kelong Han  6 , Veerle Van Eygen  8 , Herta Crauwels  8 , Susan L Ford  9 , Christine L Latham  5 , Marty St Clair  5 , Joseph W Polli  5 , Simon Vanveggel  8 , Kati Vandermeulen  8 , Ronald D'Amico  5 , Harmony P Garges  5 , Andrew Zolopa  5 , William R Spreen  5 , Jean van Wyk  10 , Amy G Cutrell  5
Affiliations

Expanded Multivariable Models to Assist Patient Selection for Long-Acting Cabotegravir + Rilpivirine Treatment: Clinical Utility of a Combination of Patient, Drug Concentration, and Viral Factors Associated With Virologic Failure

Chloe Orkin et al. Clin Infect Dis. .

Abstract

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.

Keywords: cabotegravir; long-acting antiretroviral therapy; multivariable analysis; rilpivirine; virologic response.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest . C. O. reports personal fees and grants from ViiV Healthcare, GSK, Gilead Sciences, MSD, and Janssen; grants from AstraZeneca; travel support from Gilead Sciences and ViiV Healthcare; and is the president of the Medical Women's Federation (UK) and a governing council member of the International AIDS Society. J. M. S. reports personal consulting fees, honoraria, travel support, participation on a Data Safety Monitoring or Advisory Board, and nonfinancial support from Gilead Sciences, Merck, ViiV Healthcare, Pfizer, Moderna, GSK, Teva, and AbbVie. C. F. P. reports consulting fees and payment or honoraria from Gilead Sciences, ViiV Healthcare, GSK, AstraZeneca, Janssen, and Merck; and participation on a Data Safety Monitoring or Advisory Board for ViiV Healthcare, Gilead Sciences, Merck, and Janssen. D. R. K. has received grants from ViiV Healthcare, Gilead Sciences, Merck, and the National Institutes of Health; reports payment for expert testimony from Gilead Sciences; consulting fees from Gilead Sciences, GSK, Janssen, AbbVie, Merck, and ViiV Healthcare; payment or honoraria from Gilead Sciences and Janssen; and participation on a Data Safety Monitoring or Advisory Board for GSK and ViiV Healthcare. P. P., Y. W., C. L. L., M. S. C., J. W. P., R. D’A., H. P. G., A. Z., W. R. S., J. v. W., and A. G. C. are employees of ViiV Healthcare and stockholders of GSK. R. D., D. D., K. H., and S. L. F. are employees and stockholders of GSK. H. C., S. V., and K. V. are employees and may be stockholders of Janssen, Pharmaceutical Companies of Johnson & Johnson. V. V. E. is an employee and may be a stockholder of Janssen, Pharmaceutical Companies of Johnson & Johnson, and has a pending patent for HIV infection treatment in children.

Figures

Figure 1.
Figure 1.
Data collation. BFA, baseline factor analysis; BMI, body mass index; CAB, cabotegravir; MVA, multivariable analysis; PK, pharmacokinetics; Q4W, every 4 weeks; Q8W, every 8 weeks; RAM, resistance-associated mutation; RPV, rilpivirine.
Figure 2.
Figure 2.
Time to CVF by regimen. Confidence intervals around point estimates are shown for each of the 3 groups. CVF, confirmed virologic failure; Q4W, every 4 weeks; Q8W, every 8 weeks.
See this image and copyright information in PMC

References

    1. U.S. Department of Health and Human Services . Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Available at:https://clinicalinfo.hiv.gov/en/guidelines. Accessed 29 June 2023.
    1. Saag MS, Gandhi RT, Hoy JF, et al. . Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2020 recommendations of the International Antiviral Society-USA panel. JAMA 2020; 324:1651–69. - PMC - PubMed
    1. Orkin C, Bernal Morell E, Tan DHS, et al. . Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study. Lancet HIV 2021; 8:e668–e78. - PubMed
    1. Swindells S, Lutz T, Van Zyl L, et al. . Week 96 extension results of a phase 3 study evaluating long-acting cabotegravir with rilpivirine for HIV-1 treatment. AIDS 2022; 36:185–94. - PMC - PubMed
    1. Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. . Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med 2020; 382:1112–23. - PubMed

Publication types

MeSH terms