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Long Acting ART CROI 2026
Long-Acting ART for All: Real-world Updates From CROI 2026

Released: April 03, 2026

Monica Gandhi
Monica Gandhi, MD, MPH
Activity Information

Activity

Key Takeaways
  • Long-term, real-world data support the use of LA CAB + RPV and LEN in people with detectable HIV-1 RNA and adherence challenges to oral ART.
  • LA CAB + RPV appears to be effective in people with HIV and high BMI.
  • HBV reactivation is very common in people with HIV and active HBV coinfection, indicating that we must be vigilant about screening for active HBV prior to LA CAB + RPV initiation.

Although long-acting (LA) cabotegravir (CAB) plus rilpivirine (RPV) was originally approved for treatment of people with HIV and virologic suppression in 2021, one of the highlights of CROI 2026 was all the data about how healthcare professionals (HCPs) are actually using these agents in the real world. Fundamentally, HCPs are using LA CAB + RPV in those with viremia and adherence challenges. I think this conference demonstrated that we have entered a new era of antiretroviral therapy (ART), with emphasis on LA agents for all.

To this end, I think 4 abstracts really stood out.

LA CAB + RPV at HRSA Clinics
The first abstract that I will discuss was a large study on clinical outcomes of LA CAB + RPV for underserved populations at 8 low-income clinics funded by the Health Resources and Services Administration (HRSA). This study was designed to encourage the implementation of LA CAB + RPV and to examine virologic outcomes in those with and without viremia at initiation.

Of interest, the data showed that individuals who had detectable HIV-1 RNA when they started LA CAB + RPV did almost equally well compared to those who started with virologic suppression: after a year of treatment, people who had HIV-1 RNA between 50 and 200 copies/mL at baseline had a 7.2% risk of treatment failure, those who started with HIV-1 RNA greater than 200 copies/mL at baseline had no treatment failure, and those who started with an HIV-1 RNA less than 50 copies/mL at baseline had a 2.5% rate of treatment failure. This study confirms that using LA CAB + RPV for treatment of people with HIV-1 viremia leads to attainment and maintenance of virologic suppression over prolonged periods. [Coder link to: https://deceraclinical.com/education/activities/infectious-disease/eboni/59228-146464/content]

The rate of LA CAB + RPV discontinuation in this study was approximately 14%, and the most common reason for discontinuation was side effects. So, the real-world data tell us that LA CAB + RPV is not for everybody, but most people who initiate it persist on it.

LEN at Ward 86
Next, investigators from Ward 86, where I am director of HIV Special Program, presented data on real-world use of lenacapavir (LEN). This abstract summarizes data for 50 people with HIV who are on LA LEN and examines their reasons for switching from their previous ART. The predominant reason, as one would expect, was drug resistance and inability to achieve virologic suppression with other regimens. Of the 50 participants, 46 were on LEN + CAB with or without rilpivirine, making this the largest case series on this combination to date. 

I think these real-world data are particularly impactful because achieving viral suppression in that population of treatment-experienced people with HIV and high baseline resistance is very, very difficult. This patient population started with a virologic suppression rate of 44%. By 15 weeks, 100% of people who started LEN were virologically suppressed. A follow-up analysis at 140 weeks post LEN initiation reported that 97.5% of the 50 individuals on LEN maintained virologic suppression. I think these data emphasize how LEN can help achieve and sustain virologic suppression despite treatment experience and resistance to other agents.

Body Mass Index and LA CAB + RPV
The next abstract I will cover explores the relationship between body mass index (BMI) and efficacy of LA CAB + RPV. Whether or not a higher BMI is associated with virologic failure on LA CAB + RPV has been a major concern in the field. 

To determine whether BMI may be related to virologic failure rates on LA CAB + RPV, investigators used data from the OPERA cohort, an electronic medical record–based database that represents approximately 14% of people living with HIV in the United States. Investigators assessed virologic outcomes among people who initiated LA CAB + RPV with HIV-1 RNA less than 50 copies/mL across 3 BMI strata: BMI less than 30 kg/m2, BMI 30-40 kg/m2, and BMI greater than 40 kg/m2. The results indicated that there were no differences in virologic suppression rates across the 3 strata. I think these data put to rest the idea that we should avoid this regimen in those with higher BMIs.

LA CAB + RPV With HBV Coinfection
Finally, a very important topic in HIV medicine is what happens when a person with hepatitis B coinfection initiates LA CAB + RPV, which has no hepatitis B virus (HBV) coverage?

Another analysis using the OPERA cohort, presented at CROI, sought to answer this question. This study included 5275 individuals who initiated LA CAB + RPV. Of this group, 35 had active HBV, 74 had prior HBV without immunity, and 638 had prior HBV with immunity. Note that OPERA is a US-based cohort, with relatively few cases of active HBV or HBV infection without immunity to hepatitis B.

Among participants with active HBV, the rate of reactivation when switching to LA CAB + RPV was 52%, which is very high. In those with prior hepatitis B and no immunity, the rate of hepatitis B reactivation was 3%, which is low, but still higher than among people who had prior hepatitis B with immunity, who experienced less than 1% reactivation. Taken together, this indicates that we need to be very vigilant about screening for active HBV prior to LA CAB + RPV initiation. If an individual is surface antigen–positive, the World Health Organization guidelines recommend avoiding LA ART unless they refuse any other HIV treatment. The guidelines recommend a tenofovir-containing regimen to cover both viruses in the presence of coinfection, plus vaccination for those who are surface antibody negative.

Help for Adherence and Viremia
I think it is an exciting time to be an HIV HCP. Since LA ART was rolled out in 2021, it has been particularly gratifying to have a simpler option for those who have adherence challenges. Assisting those people is why we adopted LA ART early on for people with HIV-1 RNA viremia at Ward 86. It is incredibly satisfying now to see the expansion of LA ART for people with HIV and persistent viremia into so many other clinics.

Your Thoughts
What has been your experience with real-world implementation of LA ART? If your clinic has not implemented it yet, what are some resources you would need to do so? Leave a comment to join the discussion!