Progress toward longer-acting antiretroviral regimens for adult HIV treatment

Long-acting injectable antiretroviral therapy may improve adherence, virologic outcomes, quality of life and treatment satisfaction for people with HIV. Cabotegravir plus rilpivirine (CAB/RPV), the first complete long-acting injectable regimen for HIV treatment, has demonstrated efficacy, safety, tolerability, and real-world feasibility. Recent studies also support its use in individuals with viremia and adherence challenges. Lenacapavir and ibalizumab provide durable efficacy for individuals with multidrug-resistant HIV.

This review summarizes clinical trials and observational studies evaluating long-acting HIV therapies including their benefits, limitations and future implications. Literature published between 2017 and 2026 was identified through PubMed, Clinicaltrials.gov and abstracts or conference proceedings from Conference on Retroviruses and Opportunistic Infections (CROI), International Antiviral Society (IAS), IDWeek, European AIDS Clinical Society (EACS) and HIV Glasgow conferences.

Despite promising findings, limitations of long-acting ART include the risks of virologic failure, the prolonged pharmacologic tail, lack of hepatitis B treatment activity, limited pregnancy safety data, and implementation challenges. Ongoing research is evaluating novel combinations of long-acting agents, including emerging oral therapies, to expand treatment options. Long-acting antiretroviral treatments have the potential to address unmet needs and broaden individualized treatment options in HIV care.