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Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis
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Cutrell, Amy G.a; Schapiro, Jonathan M.b; Perno, Carlo F.c; Kuritzkes, Daniel R.d; Quercia, Rominae; Patel, Parula; Polli, Joseph W.a; Dorey, Davidf; Wang, Yongweig; Wu, Sterlingh; Van Eygen, Veerlei; Crauwels, Hertai; Ford, Susan L.j; Baker, Markk; Talarico, Christine L.a; Clair, Marty Sta; Jeffrey, Jerrya; White, C. Thomasa; Vanveggel, Simoni; Vandermeulen, Katii; Margolis, David A.a,∗; Aboud, Michaele; Spreen, William R.a; van Lunzen, Janl
july 21 2021
Abstract
Objective:
Efficacy and safety of long-acting cabotegravir (CAB) and rilpivirine (RPV) dosed intramuscularly every 4 or 8 weeks has been demonstrated in three Phase 3 trials. Here, factors associated with virologic failure at Week 48 were evaluated post hoc.
Design and methods:
Data from 1039 adults naive to long-acting CAB+RPV were pooled in a multivariable analysis to examine the influence of baseline viral and participant factors, dosing regimen and drug concentrations on confirmed virologic failure (CVF) occurrence using a logistic regression model. In a separate model, baseline factors statistically associated with CVF were further evaluated to understand CVF risk when present alone or in combination.
Results:
Overall, 1.25% (n = 13/1039) of participants experienced CVF. Proviral RPV resistance-associated mutations (RAMs), HIV-1 subtype A6/A1, higher BMI (associated with Week 8 CAB trough concentration) and lower Week 8 RPV trough concentrations were significantly associated (P < 0.05) with increased odds of CVF (all except RPV trough are knowable at baseline). Few participants (0.4%) with zero or one baseline factor had CVF. Only a combination of at least two baseline factors (observed in 3.4%; n = 35/1039) was associated with increased CVF risk (25.7%, n = 9/35).
Conclusion:
CVF is an infrequent multifactorial event, with a rate of approximately 1% in the long-acting CAB+RPV arms across Phase 3 studies (FLAIR, ATLAS and ATLAS-2M) through Week 48. Presence of at least two of proviral RPV RAMs, HIV-1 subtype A6/A1 and/or BMI at least 30 kg/m2 was associated with increased CVF risk. These findings support the use of long-acting CAB+RPV in routine clinical practice.
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