Long-acting Treatment and Prevention of HIV Are Here

Monica Gandhi, MD, MPH


July 08, 2022

Although oral antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) have been revolutionary in terms of reducing the morbidity, mortality, and incidence of HIV infection, some populations still have a hard time taking a pill every day for HIV treatment or prevention. In the United States, a recent review showed that among over 200,000 people living with HIV (PLWH), 40% reported their adherence to daily oral ART to be less than 80%. The barriers to daily pill-taking are numerous and include substance use, housing insecurity, food insecurity, mental illness, forgetfulness, stigma, "pill fatigue," and other structural barriers.

I am the medical director of a large HIV clinic in San Francisco for publicly-insured patients ("Ward 86" HIV Clinic) and can attest that although oral ART has been a miraculous advance, I have many patients who find it difficult to take even a single combination ART pill daily. In terms of PrEP, adherence is really the Achilles' heel of oral PrEP effectiveness.

Now enter long-acting ART, an incredibly exciting advance in HIV medicine, where two medications can be given intramuscularly every 4 or 8 weeks for HIV treatment. These intramuscular (IM) long-acting medications are cabotegravir (CAB), an integrase strand transferase inhibitor (INSTI), and rilpivirine (RPV), a nonnucleoside reverse transcriptase inhibitor.

Long-acting IM CAB and RPV were studied in treatment-naive patients in the FLAIR study, where participants were first put on 20 weeks of oral ART (with dolutegravir-abacavir-lamivudine), documented as being virologically suppressed (with undetectable HIV viral loads), and then switched over to the long-acting CAB-RPV combination. At 96 weeks, the long-acting CAB-RPV combination continued to be noninferior to the standard of care arm, with virologic suppression maintained in 87% of participant on the IM combination.

The ATLAS study examined long-acting CAB-RPV every 4 weeks in participants with treatment experience. Participants had to be maintained on their prior oral ART regimen with virologic suppression for at least 6 months before being switched over to the long-acting ART regimen in ATLAS. At 96 weeks, participants on the long-acting ART regimen were doing incredibly well, with 98% of participants maintaining virologic suppression.

And finally, long-acting CAB-RPV has also been studied as a regimen given every 8 weeks at a higher dose (900-mg RPV + 600-mg CAB instead of the "maintenance" every-4-weeks dose of 600-mg RPV + 400-mg CAB) in the ATLAS-2M study. By 96 weeks, participants did well with the every 8 week injectable regimen, with 91% of participants maintaining virologic suppression. Of note, it is important to remember that virologic failures on long-acting CAB-RPV can have resistance mutations that develop to the INSTI class.

Given the positive findings of all these studies, the FDA approved long-acting CAB-RPV in January 2021 for the every-4-weeks dose, approved the combination every 8 weeks in February 2022, and dropped the requirement of an oral lead-in period of oral CAB-RPV in failure of the easier (and studied) direct-to-inject option in March 2022.

The pivotal trials to examine IM CAB vs oral tenofovir disoproxil fumarate (TDF)–emtricitabine (FTC) among men and transgender women who have sex with men and in cis women were the HIV Prevention Trials Network (HPTN) 083 and 084 studies, respectively. The HPTN 083 trial showed that IM CAB every 8 weeks was superior to oral PrEP, with a 66% reduction in HIV incidence in the CAB arm compared with the TDF-FTC arm. HPTN 084 also demonstrated that long-acting CAB administered every 8 weeks was superior to daily oral TDF-FTC, with an 89% reduction in HIV incidence. These results represent major advances in our ability to reduce HIV incidence and roll-out will be both domestic and global.

At Ward 86, we are extremely excited about the advent of long-acting ART and PrEP for our clinic population. Because we have high rates of adherence challenges to daily oral ART among our patients, we have started using long-acting CAB-RPV even in patients without virologic suppression on oral therapy first. We developed a protocol to use long-acting ART in these particular patients (with adherence challenges and without sustained virologic suppression on oral ART) and have made this protocol publicly accessible.

We have over 70 PLWH who have started on long-acting ART so far, and all of them are doing well. As a medical provider to several of these patients, I can attest that long-acting ART has been truly life-changing given the challenges to taking daily oral ART. We are all thrilled in the HIV community about this revolution in treatment and prevention with long-acting agents and look forward to more agents coming in the near future.

Join Medscape's new blog initiative! We're looking for physicians, nurses, PAs, specialists, and other healthcare professionals who are willing to share their expertise in one to two paid blog posts per month. Please email for more information.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

About Dr Monica Gandhi
Monica Gandhi, MD, MPH, is an infectious diseases doctor, professor of medicine, and associate chief in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California, San Francisco (UCSF). She is also director of the UCSF Center for AIDS Research (CFAR) and medical director of the HIV Clinic ("Ward 86") at San Francisco General Hospital. Her research focuses on HIV and women; adherence measurement in HIV treatment and prevention; and, most recently, on how to mitigate the COVID-19 pandemic.

Connect with her on Twitter: @MonicaGandhi9


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.