New Generation of Long-Acting Antiretrovirals Shows Promise

Early results of two experimental, long-acting antivirals show promise in treating HIV, according to data presented at the Conference on Retroviruses and Opportunistic Infections, which was held in San Francisco from March 9 to 12.

The drugs being studied are VH4524184 and VH4011499, ViiV Healthcare’s third-generation integrase strand transfer inhibitor and an investigational capsid inhibitor, respectively. Integrase strand transfer inhibitors block the integrase enzyme, which the HIV virus needs to implant its DNA into cells. Capsid inhibitors interfere with the HIV capsid, which is the protein shell around the virus.

“It’s clear long-acting injectable medicines deliver on unmet patient need and will play a critical role in achieving our ambition of ending HIV and AIDS,” Kimberly Smith, M.D., MPH, head of research & development at ViiV Healthcare, said in a news release. “Data shows that the potency and tolerability of our third-generation INSTI and our capsid inhibitor will make them a major part in the development of our next generation of long-acting injectable therapies.”

In the VH4524184 trial, 22 adult patients were given three dosages: 10 mg, 50 mg and 300 mg, to determine the safest and most effective dose. Higher doses resulted in higher declines of viral load, with a maximum viral load decline of -2.69 log10 copies/mL on the 300 mg dose. Side effects reported were classified as mild to moderate, and there were no discontinuations. Additionally, no drug resistance mutations were observed at the end of the study.

During the VH4011499 study, 23 adults with HIV and not previously on any antiretrovirals were given VH4011499 in oral doses of 25 mg, 100 mg or 250 mg. Effectiveness was measured by assessing changes in plasma HIV-1 RNA levels from baseline through day 11. Higher doses also corresponded with greater decreases in viral load. VH499 was well tolerated with all adverse events being mild to moderate in severity. There were no adverse events leading to withdrawal. On day 11, one patient on the 25mg dose developed a single mutation associated with reduced susceptibility to capsid inhibitors.

VH4011499 is still under investigation in two ongoing studies: NCT06012136 and NCT06724640.

Long-acting injectable HIV treatments are of interest because of their convenience and effectiveness, according to the National Institutes of Health. Other HIV treatment options, such as daily, oral antiretroviral medication, require regular adherence to remain effective.

Drugs like Apretude (cabotegravir) and Edurant and Edurant (rilpivirine), approved by the FDA in 2021, mean eligible patients can go weeks between injections, which lower viral loads to undetectable levels.

Patients on injectables Apretude and Edurant had only a 7% chance of their viral loads increasing, when compared with patients on daily, oral ART, who had a 25% chance of their viral loads becoming detectable according to clinical trial data presented at CROI 2024. The likelihood of daily ART patients discontinuing treatment was 26%, when compared with patients taking injections, who are 10% likely to discontinue treatment.