Michael Gwarisa
A monthly injectable HIV treatment combining long-acting cabotegravir and rilpivirine has been shown to outperform standard daily oral antiretroviral therapy (ART) among people who struggle to stick to treatment, according to findings from a major randomized clinical trial.
The study, published in February 2026 in the New England Journal of Medicine, provides strong evidence that long-acting injectable ART could help address one of the most persistent challenges in HIV care, poor adherence to daily medication.
For many people living with HIV, taking pills every day can be difficult due to factors such as stigma, pill fatigue, unstable living conditions, and mental health challenges. These barriers often lead to missed doses, increasing the risk of treatment failure and ongoing transmission.
The phase 3 ACTG A5359 LATITUDE trial, led by Aadia I. Rana and colleagues, evaluated the effectiveness of monthly injections of cabotegravir and rilpivirine in adults with a history of adherence challenges. The study was conducted across 33 sites in the United States and enrolled participants aged 18 years and older who were living with HIV, had previously received treatment, and had no resistance to the study drugs.
A total of 820 people were screened, with 453 enrolled in the first phase of the trial. Participants were first placed on standard oral ART with adherence support for up to 24 weeks. Those who achieved viral suppression were then randomly assigned to either continue oral therapy or switch to monthly injections for one year.
Of the initial group, 306 participants proceeded to the randomised phase, with 152 assigned to the injectable regimen and 154 to standard care. The participants reflected populations disproportionately affected by HIV, with the majority identifying as Black and a significant proportion reporting past or current drug use, as well as social and economic challenges.
After a median follow-up period of 48 weeks, the injectable treatment showed clear benefits. Treatment failure occurred in 19 percent of participants receiving injections compared to 36 percent among those on oral ART. By week 48, the overall risk of treatment failure was significantly lower in the injectable group.
Virologic failure was also less common among participants receiving injections, with only a small number of cases compared to those on standard therapy. In contrast, adherence remained a major issue in the oral treatment group, where many participants reported missing doses in the weeks leading up to clinic visits.
The safety profile of the injectable regimen was broadly similar to that of oral ART. About one-third of participants in both groups experienced at least one adverse event. Injection-site reactions such as pain and swelling were common but generally mild, and only a few participants discontinued treatment because of them.
Serious adverse events were reported in both groups, and two deaths occurred among participants receiving the injectable treatment. Investigators determined that neither was related to the study drugs. Pregnancies reported during the trial resulted in healthy births, with no congenital abnormalities observed.
Most participants receiving injections were able to attend their scheduled visits, suggesting that monthly treatment is feasible even among individuals with previous adherence challenges. While a small number missed injections or required temporary oral therapy, the majority maintained consistent treatment.
Long-acting injectable ART was first approved in 2021, but earlier trials largely excluded individuals with poor adherence or unsuppressed viral loads. This study helps fill that gap by showing that the approach can work in real-world populations who are often left behind by traditional treatment strategies.
The findings have already influenced treatment guidelines in the United States, which now recommend considering injectable therapy for people who struggle with adherence, have advanced disease, or face limited treatment options.
Researchers say the shift from daily pills to monthly injections could significantly reduce the burden of lifelong HIV treatment while improving outcomes. If widely adopted, injectable cabotegravir and rilpivirine could help more people achieve and maintain viral suppression, marking an important step forward in the global HIV response.
