<p>Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential</p>

Abstract

Cabotegravir and rilpivirine long-acting injectable antiretroviral therapy for the treatment of HIV-1 infection brings promise of a new mode of delivery and potential solutions to some problems of oral therapy, but also new challenges and unanswered questions. Adding to the increasing body of evidence for newer two-drug combinations, phase II and phase III trial data to date demonstrate cabotegravir and rilpivirine combination injectable therapy to be non-inferior to selected oral triple-therapy alternatives. Most importantly, this therapy is reported to be acceptable to individuals taking the 4-weekly or 8-weekly injections, despite frequent injection-site reactions. Key outstanding questions include management of missed or delayed dosing, drug interactions and management of virological failure, as well as the efficacy of cabotegravir and rilpivirine in all HIV-1 subtypes. We describe clinical evidence to date and efficacy and challenges in selected populations, including women; those with prior virological failure; individuals with a history of difficulty adhering to oral therapy and individuals with co-infections. We await real-world data and longer-term evidence while moving forward to this new era of antiretroviral therapy.

Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials

“…Cabotegravir (CAB) (GSK1265744) is an investigational INSTI and structural analog of dolutegravir. 11 Rilpivirine (RPV) is a next-generation non-NRTI (NNRTI) currently approved as a once-daily oral tablet to be used in combination with other antiretrovirals for the treatment of HIV infection. 12 , 13 Both compounds are formulated as LA agents to be administered intramuscularly (IM), with oral formulations of RPV and a new formulation of CAB in development.…”

Development and validation of a multiplex UHPLC‐MS/MS assay with stable isotopic internal standards for the monitoring of the plasma concentrations of the antiretroviral drugs bictegravir, cabotegravir, doravirine, and rilpivirine in people living with HIV

“…Finally, the combination of LAI cabotegravir/rilpivirine, injected monthly, has been demonstrated as effective as the daily, oral, three‐drug regimen in maintaining HIV virus suppression throughout a 48‐week period . The LAI cabotegravir/rilpivirine formulation (Cabenuva) is therefore currently being reviewed by the Food and Drug Administration.…”

HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: a systematic review and meta-analysis protocol

“…5 South African Medical Research Council (MRC), Cochrane South Africa, Pretoria, South Africa. 6 Chair of Biotechnology-UNESCO, University of Rome "Tor Vergata", Rome, Italy.…”

“…INSTI stop antiretroviral activity by blocking the integration of HIV proviral DNA into the genetic material of host cells. There are currently five drugs in this class; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), cabotegravir (CAB), bictegravir (BIC) [1][2][3][4][5][6][7]. These INSTIs are highly effective in both treatment-naïve as well as in treatment-experienced individuals who may harbor multidrug resistance to other drug classes, with a superior efficacy of DTG, CAB, and BIC both in vitro and in vivo [2,4,7].…”

“…In the group of second-generation INSTI, BIC has been recently approved by the US Food and Drug Administration (FDA) and exist only as part of the fixed dose combination bictegravir/emtricitabine/tenofovir alafenamide (BIC/3TC/TAF) [12,13]. CAB on its part exists in several formulations and coformulations and is still in the process for FDA approval [6,7]. DTG revealed however a slight greater efficacy over other INSTI, due to its low minimal inhibitory concentration, limited risk of cross-resistance with RAL and EVG, better drug tolerance, fewer drug interactions, higher potency, and genetic barrier to resistance than first-generation INSTI [3,11].…”