Long-acting ART in people with adherence challenges

A major goal of HIV treatment (antiretroviral therapy, ART) today is to achieve and maintain a suppressed viral load in the blood. Some people with HIV are not able to reach this goal because they face barriers to daily pill taking, the most common mode of HIV treatment.

Researchers with the government-funded AIDS Clinical Trials Group (ACTG) conducted a study comparing the effect of injectable long-acting formulations of cabotegravir + rilpivirine (collectively called Cabenuva in North America) to that of standard oral ART. Overall, they found significantly fewer cases of virological failure in people on injectable ART.

Study details

Participants were adults who had a history of challenges to adherence on oral ART and who did not have chronic hepatitis B virus (HBV).  The drugs in Cabenuva do not have anti-HBV activity. Also, participants did not have HIV that was resistant to integrase inhibitors (the class of drugs to which cabotegravir belongs) or non-nucleoside analogues (the class of drugs to which rilpivirine belongs).

Potential participants were not excluded if they were experiencing homelessness or using substances.

The design of the trial was relatively complex but involved several steps after which participants were randomly divided into the following two groups where they received different treatments for 48 weeks:

• Group A – long-acting cabotegravir + rilpivirine injected every four weeks
• Group B – standard-of-care oral ART

After one year all participants were offered injectable ART.

Researchers enrolled 434 participants with the following average profile when they entered the study:

• age – 40 years
• 70% male, 30% female; 5% were transgender persons
• main ethno-racial groups: Black – 64%; White – 27%;
• CD4+ count – 270 cells/mm³
• viral load – 32% had a viral load less than 200 copies/mL; 25% had a viral load between 201 and 10,000 copies/mL; 28% had a viral load between 10,001 to 100,000 copies/mL; 14% had a viral load greater than 100,000 copies/mL
• time since HIV diagnosis – 13 years
• proportion of people who were currently using or had a history of injecting drugs – 14%

Results – safety

Researchers were able to analyze data from 135 people on the safety of injectable ART. They found that 57% had mostly mild-to-moderate adverse events related to the injection site, including pain, tenderness and the formation of a nodule. These were all temporary.

Overall, 93% of participants received their injections on time, 3% missed injection appointments, and 3% delayed receiving injections (figures do not total 100 due to rounding).

Focus on virological failure

The distribution of people with virological failure after 48 weeks was as follows:

• injectable ART – 7%
• oral ART – 25%

This difference was statistically significant.

The proportion of people with treatment failure (defined in this study as discontinuation of treatment due to an adverse event or virological failure) was distributed as follows:

• injectable ART – 10%
• oral ART – 26%

The proportion of people who permanently discontinued treatment was as follows:

• injectable ART – 21%
• oral ART – 25%

Taking all of these results into account, the committee overseeing the study recommended that the trial be halted and all participants were offered injectable ART.

Focus on confirmed virological failure

The cases of confirmed virological failure were as follows:

• injectable ART – 6 people
• oral ART – 28 people

Only two people in each group had new resistance mutations to integrase inhibitors.

The researchers conducting the study stated that injectable ART demonstrated overall “superiority” to standard oral ART in people who have adherence challenges and a prior history of not responding to treatment.

—Sean R. Hosein

REFERENCE:

Rana AI, Bao Y, Zheng L, et al. Long-Acting Injectable CAB/RPV Is Superior to Oral ART in PWH With Adherence Challenges: ACTG A5359. Conference on Retroviruses and Opportunistic Infections, March 3-6, 2024. Abstract 212.