- A once-weekly oral HIV treatment is as effective as a widely used once-daily regimen, according to a large clinical trial.
- More than 93% of participants maintained viral suppression, and none experienced virological failure during the study.
- A weekly treatment could give people with HIV another option while potentially reducing “pill fatigue” associated with taking daily medication.
- Participants in the trial already had well-controlled HIV and high medication adherence, which could limit the generalizability of the study results.
A once-weekly oral medication controlled HIV as effectively as a standard once-daily treatment in a large international clinical trial.
The findings suggest that the combination of the antiretroviral drugs islatravir and lenacapavir in a single weekly pill could offer a new treatment option for people with HIV who have the virus under control.
Researchers compared the two-drug weekly pill with Biktarvy (bictegravir-emtricitabine-tenofovir alafenamide), a widely used three-drug combination taken once daily.
After 48 weeks, no participants receiving the weekly pill had a viral load of 50 copies per milliliter or higher, the threshold for viral suppression. The results were published on July 29 in The New England Journal of Medicine.
Charles Flexner, MD, professor of Medicine, Physiology, Pharmacology & Therapeutics, and International Health at the Johns Hopkins University School of Medicine, said the trial “demonstrates very convincingly that [a pill] containing two anti-HIV drugs given once a week is just as effective at preventing the virus from replicating or reproducing as one of the standard, gold-standard, three-drug combination pills taken once a day.”
Flexner wasn’t involved in the research, but has served as a paid consultant for Gilead and Merck, the makers of the weekly pill.
The phase 3 trial, called ISLEND-1, included 607 adults treated across 106 sites in 12 countries.
The study was randomized, double-blind, and designed to determine whether the weekly regimen was “noninferior” to daily treatment, meaning it did not perform meaningfully worse than the established therapy.
The trial was funded by Gilead Sciences and Merck Sharp & Dohme, the companies developing lenacapavir and islatravir.
Study participants had a median age of 49, and 15% of participants were 65 or older. About 21% were female, 31% were Black, 26% were Hispanic, and 11% were Asian.
All participants maintained a viral load below 50 copies per milliliter for at least six months while taking Biktarvy. They had no history of virologic treatment failure, had never used islatravir or lenacapavir, and did not have active hepatitis B.
Researchers randomly assigned 304 participants to switch to once-weekly islatravir-lenacapavir and 303 to continue taking Biktarvy once daily.
At week 48, none of the participants assigned to the weekly treatment arm had a viral load of at least 50 copies per milliliter, whereas one participant on the daily regimen exceeded that threshold.
In both groups, more than 93% of participants maintained viral suppression, and none experienced virological failure during the course of the study.
CD4-positive T-cell counts, a measure of immune function, also remained relatively stable.
Medication adherence, measured by pill counts, averaged nearly 99% for the weekly regimen and approximately 96% for the daily regimen.
Adverse events were reported in 79.3% of the weekly-treatment group and 78.5% of the daily-treatment group. Most of these were mild to moderate and included:
Serious adverse events occurred in 5.3% of participants receiving the weekly treatment and 4.6% of those receiving daily therapy. Six people, or 2%, in the weekly group and five, or 1.7%, in the daily group, stopped treatment because of adverse events.
Michael Saag, MD, director of the Center for AIDS Research at the University of Alabama at Birmingham, said that longer follow-up of the therapy’s safety profile remains important. Saag wasn’t involved in the research.
“With any new regimen, longer-term safety issues may emerge,” he told Healthline. “However, both islatravir and lenacapavir, individually, have a good bit of long-term safety data from many other clinical trials and experience in clinical practice.”
Notably, the weekly pill does not suppress hepatitis B, whereas two of the drugs in the daily regimen are active against both HIV and hepatitis B. People with active hepatitis B were excluded from the trial. One unvaccinated participant taking the weekly pill developed hepatitis B during the study.
Another major limitation is that the study did not enroll those most likely to benefit from less-frequent dosing: people who have difficulty consistently taking daily HIV treatment.
Participants in the trial had achieved at least 6 months of viral suppression, suggesting they were adherent to their dosing schedule.
Modern antiretroviral therapy, or ART, allows people with HIV to suppress the virus to undetectable levels. Maintaining viral suppression also prevents the sexual transmission of HIV.
However, treatment must be taken consistently; missing doses can allow the virus to begin reproducing again.
Taking a daily medication, even a single pill, for years can create a psychological burden, known colloquially as “pill fatigue.”
The study authors describe pill fatigue as the “mental, emotional, or behavioral weariness associated with taking medication on a regular basis.”
For someone treating their HIV for decades, daily pills are also often a stigmatizing reminder of the condition.
A weekly pill would reduce the number of scheduled doses from 365 per year to 52.
Saag said the growing range of HIV treatment options represents an important shift in how the virus is treated.
“We have come a long way from the horrible days of the epidemic in the 1980s and early 1990s, when we had no effective long-acting retroviral treatment,” he noted. “All of these new developments and novel treatment choices should be celebrated.”
HIV treatment has evolved over several decades from complex “cocktails” involving numerous pills to highly effective single-tablet daily therapies.
However, injections aren’t right for everyone.
Some people dislike needles or find it difficult to attend regularly scheduled clinic appointments. A self-administered weekly pill could occupy a middle ground: reducing treatment frequency without requiring injections and clinic visits.
Stigma may also influence treatment decisions and adherence.
Chloe Orkin, MBE, professor of Infection and Inequities and Dean for Healthcare Transformation at Queen Mary University of London, and senior author of the study, said expanding treatment options could help address some of those barriers.
“Stigma still affects people living with HIV, so offering more choices could help people to take their treatment better and have better health outcomes, just as it has done in other conditions,” she told Healthline.
More results are forthcoming as well. The continuing trial will provide 96-week data that should offer a clearer picture of longer-term effectiveness and safety.
If that evidence remains favorable, experts say that expanding therapy options based on an individual’s needs will be another step forward for HIV treatment.
“I think this is a great advance for people with this chronic infection, that they will now have more choices about how they manage their HIV,” Flexner said. “Different people undoubtedly are going to choose different modalities, but at least we have entered an era where we can offer them that choice.”
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