Long-Acting Injectable Antiretroviral Agents for HIV Treatment and Prevention

Abstract

Current oral antiretroviral agents provide highly effective treatment for patients infected with human immunodeficiency virus (HIV), and can be used as pre-exposure prophylaxis (PrEP) to prevent new HIV infections. Several single-tablet regimens with excellent antiviral efficacy have dramatically improved the quality of life of patients who can adhere to daily oral therapy. However, there is increasing demand on long-acting injectable antiretroviral agents for patients who cannot take oral agents or feel fatigue related to daily pill burden. Monthly long-acting (LA) cabotegravir (CAB) combined with rilpivirine (RPV) has recently been listed as optimizing agent for maintenance of HIV suppression in treatment-experienced patients whose viral load is undetectable for 3 to 6 months. Novel agents with different mechanism of action and long half-life extending dosing interval are being tested in phase 2 and 3 clinical trials. This review summarizes the data of efficacies and safety profiles of LA CAB with RPV regimen, and also new long-acting injectable antiretroviral agents in pipeline.

Considerations for long-acting antiretroviral therapy in older persons with HIV

“…It is therefore difficult to determine differences in response between younger and older (including elderly) individuals – a factor which could potentially limit the generalizability of LAI-ART's efficacy and rate of failure to older populations [60]. The median age of participants in noninferiority randomized control trials (ATLAS, FLAIR, LATTE-2) has ranged from 34–42 years (Table 3) [42,43,1–63]. Two trials (ATLAS-2 M, LATTE-2) did not report the number of enrolled participants aged 50 years or older; of other trials that did, only 228 patients enrolled were 50 years old or older, and of these, 99 were randomized to receive LAI-ART [42–45,61–63].…”

“…New approaches to drug delivery, such as long-acting formulations, are being developed to strengthen adherence to ART. Long-acting agents in various stages of development include oral therapies (islatravir), implants (tenofovir), microarray patches (rilpivirine), and vaginal rings (dapivirine), as well as long-acting injectable (LAI) injectables like lenacapavir and cabotegravir-rilpivirine (CAB/RPV; Cabenuva), a recently FDA-approved ART given every one to two months for the treatment of HIV infection [13][14][15]. Though CAB/RPV's novel mode of delivery holds promise in circumventing some of the issues with oral therapy, new challenges and unanswered questions remain, particularly around its use in aging populations.…”

HIV Pre-exposure Prophylaxis and Its Impact on the Gut Microbiome in Men Having Sex With Men

“…While Truvada ® and Descovy ® are taken orally, Apretude ® represents the third formulation of PrEP, which consists of the long-acting, injectable combination of cabotegravir (an integrase inhibitor) and rilpivirine (a non-nucleoside RT inhibitor, NNRTI), administered every 2 months by a specialized healthcare worker ( Kim, 2021 ). It was recently approved by the FDA, in 2021.…”

Preferences for long‐acting pre‐exposure prophylaxis among gay, bisexual and other men who have sex with men in Taiwan: findings from the 2021 HEART Survey

“…The U.S. Food and Drug Administration approved bimonthly injectable cabotegravir in December 2021 as the first longacting PrEP (long-acting cabotegravir [CAB-LA]) [7]. Other formulations and delivery sites are being tested for clinical efficacy, including monthly intramuscular injections, 6month subcutaneous injections and 12-month subdermal implants [8][9][10].…”