Cabotegravir/Rilpivirine: the last FDA-approved drug to treat HIV

ABSTRACT

Introduction

The development of long-acting (LA) drugs has changed the management of common medical conditions for human replication immunodeficiency virus (HIV). Cabenuva (cabotegravir/Rilpivirine) is the first LA antiretroviral injectable drug composed of nano-formulation of cabotegravir (CAB) and rilpivirine (RPV).

Areas covered

In this review article, we aim to have a brief overview of results of major clinical trials that administrated Cabotegravir/Rilpivirine for patients considering the efficacy and safety profiles. Moreover, we discuss about CAB and RPV chemical structure, mechanism of action, ‎activity against drug-sensitive and -resistant HIV, and pharmacodynamics/pharmacokinetics properties.

Expert opinion

Based on the results of the ATLAS and FLAIR trials, Cabotegravir/Rilpivirine regimen once-monthly has shown equal effectivity to oral combination antiretroviral therapy (cART) in maintaining HIV-1 suppression in patients. Furthermore, ATLAS-2 M study revealed the non-inferiority of Cabotegravir/Rilpivirine regimen every 8 weeks compared to every 4 weeks. The injectable LA ART reduces the number of treatment intake as well as increases adherence, especially in patients with HIV-related stigma. Administration of extended-release agents probably minimize the risk of treatment-related toxicity and resistance related to sub-optimal adherence to oral ART, so Cabotegravir/Rilpivirine can be suggested as a suitable alternative for HIV infection control in current era.

KEYWORDS:

• HIV
• Cabotegravir/Rilpivirine
• cabotegravir
• rilpivirine
• clinical trials
• review

Article highlights

• Conventional ART is associated with the higher risk of viral resistance due to reduced adherence, HIV-related stigma, and oral pill fatigue in patients.

• The development of extended-release ART such as Cabotegravir/Rilpivirine has changed the management of conventional treatment in HIV patients.

• Cabotegravir/Rilpivirine is the last FDA-approved combinational injectable drug to treat HIV composed of LA formulation of CAB (second-generation integrase strand transfer inhibitor) and RPV (nonnucleoside reverse transcriptase inhibitor).

• Clinical trials show effective impact and high satisfaction and adherence of Cabotegravir/Rilpivirine on HIV patients.

• The results collected from LATTE and LATTE-2 studies suggested the dosing regimen of monthly LA CAB and RPV as an injectable complete ART regimen.

• FLAIR study reported the similar efficacy of LA CAB/ RPV compared to oral triple therapy in ART-naïve HIV-patients.

• The ATLAS study demonstrated the non-inferiority of LA CAB/ RPV versus triple oral regimen in virologically suppressed patients.

• The outcomes of ATLAS-2M study suggested the efficacy and safety profile of LA CAB/RPV regimen every 8 weeks compared to every 4 weeks were non-inferior.

• In recent clinical trials, a small number of patients who received Cabotegravir/Rilpivirine experienced virological failures and confirmed resistant-associated mutations.

• To minimize the resistance to Cabotegravir/Rilpivirine, careful selection of patients who have higher adherence to injectable treatment and remain the systemic concentration of drugs in a standard level should be noted.

• Cabotegravir/Rilpivirine can pave the way and prompt future research to develop other injectable LA ART to decrease the frequency of treatment intake.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.