Abstract

Abstract Background Cabotegravir/rilpivirine (CAB/RPV) long-acting (LA) injectable was recently approved as a switch therapy for people living with HIV (PLWHIV) who are virologically suppressed on oral combination antiretroviral therapy (cART). Data demonstrates RPV resistance associated mutations (RAMs) correlated with CAB/RPV treatment failure. This is the first real-world retrospective, observational study evaluating epidemiology of RPV and CAB RAMs in a heavily treatment experienced population of PLWHIV. Methods A cohort of PLWHIV were screened for transition eligibility to CAB/RPV therapy in a large clinic in the Southeastern U.S. between April 1, 2021 and January 31, 2022. The following baseline characteristics were collected: gender, age, race, Charlson Comorbidity Index, current cART, and prior cART exposure. The Stanford University HIV Drug Resistance Database was utilized to evaluate the inferred resistance level for reverse transcriptase (RT), integrase strand transfer inhibitor (INSTI), and protease inhibitor (PI) sequences. Results Among 115 patients included, 64.3% were males who were predominately African American (83.4%), with a median age of 37 years old and Charlson Comorbidity Index of 1.65. Ten (8.69%) individuals had at least one RPV or CAB RAM. Among these, 7 (6%) and 3 (2.6%) displayed RPV and CAB resistance, respectively. The most prevalent types of RAMs for RPV specifically were Y181I/C (n = 4) and E138A (n = 2). Five of 7 individuals with RPV RAMs had history of cART use without documented exposure to RPV-containing regimens. Moreover, 2 of 3 individuals with CAB RAMs had history of cART with exposure to an integrase-containing regimen. Conclusion This is the first study that characterizes susceptibility patterns that may affect CAB/RPV in clinical practice. Within this rural Southeastern population, prevalence of RPV RAMs is higher than CAB RAMs, and RPV RAMs were commonly observed as transmitted resistance whereas CAB RAMs were typically associated with prior history of exposure to INSTI-containing regimen. It is pertinent to assess the genotypic resistance profile of RTs and history of cART exposure prior to transitioning to CAB/RPV to decrease the risk of virologic failure due to RAMs. Disclosures P. Brandon Bookstaver, PharmD, Spero Therapeutics: Advisor/Consultant.

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