HIV-1 can be successfully treated with long-acting injectable antiretroviral therapy

A dual regimen combining the integrase strand transfer inhibitor cabotegravir with the nonnucleoside reverse transcriptase inhibitor rilpivirine1 is the first complete long-acting, injectable, antiretroviral regimen for adults living with HIV-1.2,3 Randomized trials have shown noninferiority of injectable cabotegravir–rilpivirine compared with conventional therapy for maintaining an HIV-1 viral load of less than 50 copies/mL, with durable responses up to 152 weeks.1–3

Candidates for cabotegravir–rilpivirine should be carefully selected

Cabotegravir–rilpivirine is currently approved for treatment of HIV-1 infection in patients who have an undetectable viral load (HIV-1 RNA < 50 copies/mL).1 Contraindications include hepatitis B co-infection, known resistance to cabotegravir or rilpivirine, pregnancy or planned pregnancy, and use of some concomitant medications (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.231498/tab-related-content).2,3

Rarely, virologic failure occurs despite on-time injections

In a pooled analysis of randomized trials, virologic failure occurred in 1.25% (13/1039) of patients despite receiving injections on schedule.4 Factors associated with virologic failure include body mass index of 30 or greater, HIV-1 subtype A6/A1, and proviral rilpivirine resistance–associated mutations.4 However, some cases of virologic failure remain unexplained, and other risk factors are under investigation.4

The most common adverse events of treatment are injection site reactions

Long-acting cabotegravir–rilpivirine is administered via 2 gluteal intramuscular injections every 1 or 2 months.2,3 Most patients experience injection site reactions such as pain, nodules, induration, swelling, erythema or bruising.1 Most reactions are mild to moderate, and severity decreases over time; discontinuation owing to injection site reactions in clinical trials was uncommon (2%–3% over ~3 yr).3

Patient experience with cabotegravir–rilpivirine has varied, and implementation challenges exist

Users have expressed satisfaction with not having to take pills,5 which can reduce stigma, reduce inadvertent disclosure of HIV status, overcome swallowing issues and facilitate short-term travel, among other benefits.5 However, some users are inconvenienced by the frequency of visits for injection.5 Further, the requirement for intramuscular injections requires health care providers to adapt clinic workflows to incorporate frequent visits, procure and store the drug, and ensure appropriate training of staff.5

Footnotes

↵* Darrell Tan and Nisha Andany are co–senior authors.

Competing interests: Darrell Tan’s institution has received support from AbbVie and Gilead for investigator-initiated research studies, and from GSK for participation in industry-sponsored clinical trials. Dr. Tan is supported by a Tier 2 Canada Research Chair in HIV Prevention and STI Research. Nisha Andany has participated as a site investigator for HIV clinical trials sponsored by Gilead, Janssen and GSK (research funds paid to institution). No other competing interests were declared.

This article has been peer reviewed.

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