An investigational once-weekly pill kept HIV suppressed as effectively as daily treatment over 48 weeks in two phase 3 trials, results that could eventually give people living with HIV an alternative to taking medication every single day.
The single tablet combines 2 milligrams of islatravir, made by Merck, with 300 milligrams of lenacapavir, made by Gilead Sciences. Detailed results from the ISLEND-1 and ISLEND-2 trials were presented at the 26th International AIDS Conference in Rio de Janeiro on July 29, with ISLEND-1 published simultaneously in the New England Journal of Medicine.
The drug is not approved. Merck and Gilead have said these data will form the basis of regulatory submissions. Nobody currently taking antiretroviral therapy should change anything based on trial results.
The Endpoint That Actually Matters
Both trials measured maintenance of viral suppression, meaning HIV RNA below 50 copies per milliliter. That endpoint is not a technicality. Sustained suppression is what preserves immune function and prevents progression to AIDS, and it is also what makes the virus untransmittable through sex.
Both trials enrolled adults already virologically suppressed for at least six months with no history of treatment failure. This is a switch study design, testing whether people doing well on daily therapy can move to a weekly pill without losing control of the virus. It does not test the regimen in people starting treatment for the first time.
ISLEND-1 was a double-blind trial comparing the weekly tablet against continued daily bictegravir, emtricitabine, and tenofovir alafenamide, sold as Biktarvy. The median participant age was about 49; half were older than 50, and 17% were older than 65. At 48 weeks, 93.4% of those who switched and 92.4% of those who stayed on daily therapy maintained suppression. No one on the weekly pill and one person on the daily comparator had a viral load of 50 or higher.
ISLEND-2 was an open-label trial enrolling 626 people across 13 countries who were on a range of standard daily regimens. At 48 weeks, 95.2% of switchers and 95.5% of those who continued their existing treatment maintained suppression.
No emergent resistance to either drug was detected in either trial.
Tolerability and the Hepatitis B Caveat
Treatment-related adverse events occurred in 13% of participants in both arms of ISLEND-1, most commonly nausea and headache, each in about 3%. Only 2% in each group stopped treatment because of an adverse event. In ISLEND-2, 18% of those on the weekly pill reported treatment-related adverse events compared with under 1% of those who did not change treatment, most commonly headache, diarrhea, and nausea. None were severe.
The clinically important caveat concerns hepatitis B. Neither islatravir nor lenacapavir is active against hepatitis B virus, unlike the tenofovir alafenamide contained in Biktarvy. Participants in these trials did not have hepatitis B co-infection, and about 80% in ISLEND-1 had evidence of immunity. Investigators strongly encouraged vaccination for those without it. One unvaccinated participant in ISLEND-1 developed hepatitis B and discontinued treatment.
Islatravir's development was paused in 2021 after declines in CD4 and total lymphocyte counts appeared at higher doses, prompting an FDA clinical hold. Trials resumed at lower doses. At the 2 milligram weekly dose used here, investigators reported no white blood cell decreases, and CD4 counts and body weight remained stable in both groups.
What Patients Said About the Daily Pill Burden
ISLEND-2 collected patient-reported outcomes, which is where the practical appeal shows up. Among those who switched, nearly two-thirds described their previous daily regimen as more burdensome than the weekly pill, while 1% said the same about the weekly tablet and about 30% saw no difference. At 48 weeks, more than 75% reported being more or much more satisfied with weekly treatment, 14% were equally satisfied, and about 3% preferred their prior regimen.
Adherence was high in both groups in both trials. In ISLEND-1, adherence was 98.9% in the weekly group and 95.5% in the daily group, and more participants in the weekly group reached at least 90% adherence.
Professor Jürgen Rockstroh of University Hospital Bonn, who presented ISLEND-1, said daily single-tablet therapy remains the cornerstone of HIV treatment today but the landscape is evolving, and described the results as showing the potential for the first once-weekly oral single-tablet option. Coverage of both presentations was published by aidsmap, which reported the detailed trial results.
The Limits of 48 Weeks of Data
These are 48-week results from trials designed to run 96 weeks. Durability beyond one year is not yet established, and neither is the resistance picture over longer follow-up or with imperfect adherence in real-world use.
A weekly schedule has an obvious failure mode: a missed dose represents a larger fraction of total exposure than a missed daily pill. How forgiving the regimen is when someone forgets remains an open question that clinical trial adherence rates approaching 99% do not answer.
The trials also excluded people with hepatitis B co-infection, people who were not already suppressed, and people with prior virologic failure. Pregnancy and pediatric data are not part of these results.
Cost and access are unresolved. Pricing has not been announced. Rockstroh noted that if more than one weekly co-formulation eventually reaches approval, competition could lower cost, which is a prediction rather than a finding. Merck is developing a second weekly combination pairing islatravir with ulonivirine, which is further back in the pipeline.
Reasonable Steps for People Living with HIV
Continue your current regimen exactly as prescribed. Interrupting antiretroviral therapy allows the virus to rebound and can select for resistance that limits future options.
If a weekly option interests you, raise it at your next appointment and ask whether you would be a candidate should it be approved, particularly whether you have documented hepatitis B immunity. If you do not, ask about vaccination now. That is useful regardless of what happens with this drug. Federal guidelines for antiretroviral therapy in adults and adolescents also caution that stopping drugs active against hepatitis B in a co-infected person can trigger serious liver injury, which is why co-infection status matters for any switch.
If you have trouble taking a daily pill because of scheduling, privacy, side effects, or cost, tell your clinician. Options already exist, including long-acting injectable regimens, and switching decisions should be based on your resistance history and current labs. Gilead and Merck reported topline results from both trials in June, ahead of the conference presentations.
People who need help paying for HIV medication can ask a clinic case manager about the Ryan White HIV/AIDS Program, AIDS Drug Assistance Programs, and manufacturer assistance.
Frequently Asked Questions
Is the weekly pill available now? No. It is investigational. The manufacturers have said these results will support regulatory submissions.
What did the trials find? At 48 weeks, viral suppression was maintained in 93.4% of switchers in ISLEND-1 and 95.2% in ISLEND-2, results noninferior to daily comparators.
Who was studied? Adults already virologically suppressed for at least six months with no history of treatment failure. People with hepatitis B co-infection were excluded.
Why does hepatitis B matter here? Neither drug treats hepatitis B, unlike the tenofovir alafenamide in some daily regimens. Vaccination and co-infection status become clinically important.
Were there safety concerns? Treatment-related adverse events were mostly mild, including headache and nausea. No emergent resistance was detected. Earlier CD4 declines seen with higher islatravir doses did not appear at this dose.
What is still unknown? Durability beyond 48 weeks, real-world adherence with a weekly schedule, use in people starting treatment, pregnancy and pediatric data, and price.
Should I ask to switch? Not yet. Do not change or stop an antiretroviral regimen without your prescriber. You can ask whether you would be a candidate if the drug is approved.
