- Some guidelines limit long-acting HIV treatment to those who have achieved viral suppression
- A San Francisco study compared efficacy among people with and without a detectable viral load
- Researchers found there was no difference in viral suppression between the two groups
HIV treatment (antiretroviral therapy; ART) is highly effective when used as directed. A key goal of ART is to suppress HIV and keep it suppressed. This allows the immune system to largely repair itself. The power of ART is so transformative that researchers increasingly project that many ART users will live well into their senior years.
Combinations formulated into one pill that can be taken once daily and are recommended by U.S. treatment guidelines for initial treatment of people with HIV include the following:
- Biktarvy (bictegravir + TAF + FTC)
- Dovato (dolutegravir + 3TC)
- Delstrigo (Dovato + TDF + FTC)
These regimens are highly effective and generally safe.
Another regimen, consisting of two pills once daily, that is also highly effective and recommended is the following:
- dolutegravir + tenofovir + either 3TC or FTC
Several years ago, a long-acting injectable formulation consisting of two HIV drugs— cabotegavir + rilpivirine—was approved for use in people with HIV (sold under the brand name Cabenuva in North America and Australia). At that time, the world’s leading HIV treatment guidelines, developed under the aegis of the U.S. Department of Health and Human Services (DHHS), restricted this long-acting injectable regimen to certain people: those whose HIV was already suppressed on oral treatment (and who wanted to switch to injectable treatment) and whose HIV was not resistant to these drugs.
Cabenuva is ultimately meant to be injected once a month or once every two months (larger doses are used in this case). The medicines in Cabenuva are injected deep into the buttocks (one injection per buttock) by a healthcare provider.
Some people with HIV have difficulty taking treatment every day because of at least the following issues:
- difficulty swallowing pills
- difficulty taking pills every day (and worried about missing a dose)
- difficulty storing pills (particularly if homeless)
- daily pill-taking is an unwelcome reminder of HIV
- inadvertent disclosure if someone sees their medicines
In theory, a regimen of long-acting injectable treatment can help patients minimize these problems in the long-term and can provide a more convenient treatment option.
In San Francisco
A team of researchers at a leading HIV clinic in San Francisco (Ward 86) conducted a study comparing the long-term effectiveness of injectable long-acting ART in two populations:
- people with an undetectable viral load on oral ART who sought to switch
- people with a detectable viral load who had difficulty with adherence to oral ART in the past
An analysis of data collected over 12 months found that rates of viral suppression were high and were not different whether participants began long-acting ART with or without a detectable viral load.
Study details
Researchers enrolled 370 people with HIV—241 were on oral ART and did not have detectable HIV, while 129 others had a detectable viral load as they were not on ART (and had a history of challenges with adherence). A pharmacist reviewed each participant’s medical information, including their treatment history and results of HIV drug resistance testing.
Participants were counselled by a pharmacy technician about long-acting injectable HIV treatment.
Participants were sent texts or received a telephone call reminding them about upcoming appointments. They could also simply drop in to the clinic without an appointment if they arrived within a week of the target date for their next injection.
The average profile of participants upon study entry was as follows:
- age – 45 years
- cisgender men – 80%; transgender women – 10%; cisgender women – 4%, nonbinary – 2% (the remaining participants had gender classified as “other” or this data were missing from their file)
- major ethno-racial groups: White – 41%; Black – 23%; Asian – 8%
- CD4+ cell count – 52% of participants had a CD4+ count less than 200 cells/mm3
- viral load – 35% of participants had a viral load of 30 copies/mL or greater (the lower limit of detection of the assay used in this study), while the remainder had a viral load that was suppressed on oral ART. Among people with detectable HIV, the average was 46,000 copies/mL
- living in unstable housing – 44%
- current or past drug use – 46%
Researchers did not include people who had HIV that was partially or wholly resistant to cabotegravir or rilpivirine.
According to the researchers, participants had to make a commitment to monthly in-person clinic visits. After three consecutive months of on-time monthly injections, participants could then transition to injections every two months if their viral load was suppressed.
Results
Overall, researchers found no difference in rates of viral suppression in participants regardless of whether or not they had a detectable viral load at the start of the study.
On average, it took 32 days after initial injection for participants to have their HIV suppressed.
After 48 weeks, 98% of participants whose viral load was initially detectable had a suppressed viral load. The figure among people whose viral load was initially suppressed on oral ART was 99%. Figures would have been higher, but a few people dropped out of the program (for undisclosed reasons).
Five people who achieved viral suppression with long-acting ART later switched to oral ART because of issues of convenience or side effects.
Bear in mind
The data from the present study show that long-acting injectable ART can be highly effective, even in people with adherence challenges. The success that Ward 86 has had in helping people achieve an undetectable viral load has been pivotal in getting leading HIV guidelines to modify the eligibility criteria for the use of long-acting injectable ART.
However, such treatment is not for everyone. The injections can cause temporary discomfort and pain in some people. They also require administration by a healthcare professional, making regular clinic visits (ultimately every two months) necessary.
The drugs in Cabenuva (cabotegravir + rilpivirine) are not effective against hepatitis B virus (HBV). Therefore, people with chronic HBV also have to take a daily pill with treatment for this virus, usually TDF + FTC (sold as Truvada and available in generic formulations) or TAF + FTC (Descovy).
—Sean R. Hosein
Resource
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV – DHHS
REFERENCE:
Spinelli MA, Heise MJ, Gistand N, et al. HIV viral suppression with use of long-acting antiretroviral therapy in people with and without initial viremia. JAMA. 2025 Apr 22;333(16):1451-1453.