HEALTH
For nearly three decades, life with HIV has meant one non-negotiable daily ritual: the pill, every day, without fail, for the rest of your life. Miss too many doses and the virus can come roaring back, potentially resistant to the very drugs meant to control it. That daily grind — small, relentless, and for many patients psychologically exhausting — has just taken its biggest hit yet.
At the 26th International AIDS Conference in Rio de Janeiro last week, researchers unveiled full results from two Phase 3 trials, ISLEND-1 and ISLEND-2, showing that a single tablet combining two drugs — islatravir and lenacapavir — taken just once a week, kept HIV suppressed just as effectively as the daily standard of care. The findings, published simultaneously in the New England Journal of Medicine, represent the strongest evidence yet that the daily HIV pill's decades-long reign may be numbered.
"Once-daily, combination single-tablet antiretroviral therapy is the cornerstone of HIV treatment today. However, the treatment landscape is evolving," said Professor Jürgen Rockstroh of University Hospital Bonn, who presented the ISLEND-1 findings. The new results, he said, "show the potential of islatravir/lenacapavir as the first once-weekly oral single-tablet treatment option."
THE NUMBERS BEHIND THE HEADLINE
Both trials tested a combination pill containing 2 milligrams of islatravir — developed by Merck — and 300 milligrams of lenacapavir, Gilead Sciences' capsid inhibitor already sold in injectable form under the brand names Sunlenca and Yeztugo. Put together in a single oral tablet, the combination attacks HIV through two entirely different mechanisms, which is part of why it can hold the virus down for a full seven days instead of just one.
ISLEND-1 randomly assigned adults with an undetectable viral load — who had been virally suppressed for at least six months with no history of treatment failure — to either switch from the widely used daily pill Biktarvy or stay on it. At 48 weeks, 93.4% of people who switched to the new weekly pill maintained viral suppression, compared to 92.4% of those who stayed on Biktarvy — a statistically non-inferior result, meaning the weekly pill performed just as well. Only one person in the entire study, someone who remained on Biktarvy, saw their viral load climb to detectable levels. Nobody on the new weekly combination did. Critically, no resistance to either islatravir or lenacapavir emerged in anyone during the trial.
ISLEND-2, an open-label trial spanning 13 countries including two sites in South Africa, tested the same weekly pill against a broader range of standard daily regimens in 626 participants. The results echoed ISLEND-1almost exactly: 95.2% of those who switched to the weekly pill maintained suppression, versus 95.5% of those who stayed on their existing daily treatment — again, statistically equivalent.
Both studies found the new regimen safe and generally well tolerated. Side effects were mostly mild — headache, nausea, and in the ISLEND-2 trial, some diarrhea — and serious adverse events were rare. Only 2% of participants in ISLEND-1 stopped treatment due to side effects, a number essentially unchanged from those who stayed on the daily comparator. Body weight, CD4 counts, and total lymphocyte counts all remained stable across both arms of both trials — an important reassurance, since an earlier, now-abandoned version of islatravir dosing had been linked to concerning drops in white blood cell counts back in 2021, triggering an FDA clinical hold. Researchers say that problem was traced to doses roughly ten times higher than what's used in the current weekly formulation, and it has not reappeared since trials resumed at the lower dose.
WHY PATIENTS ARE THE ONES DRIVING THIS
What might be the most striking data out of the two trials isn't clinical — it's personal. In ISLEND-2, researchers asked participants directly how the switch felt. Nearly two-thirds of people who moved to the weekly pill said their previous daily regimen had been more burdensome. Only 1% said the same about the new weekly tablet. At the 48-week mark, more than 75% of participants reported being "more" or "much more" satisfied with the weekly treatment, while just 3% said they preferred their old daily routine.
That patient preference data matters enormously in HIV care, where treatment success hinges less on a drug's raw potency and more on whether a person can realistically stick with it for the rest of their life. A pill that needs to be taken 52 times a year instead of 365 times a year isn't just a convenience — for many patients, it is the difference between years of quiet stress around an alarm clock and daily reminder apps, and something closer to normal life.
"Treatment needs to fit into people's lives, not the other way around," said Dr. Kenneth Ngure of Jomo Kenyatta University of Agriculture and Technology, the incoming president of the International AIDS Society, in a statement tied to the conference. "People living with HIV need new treatment options that offer flexibility, and a weekly pill could broaden the choices available for adults with virological suppression."
HOW THIS FITS INTO THE BIGGER HIV TREATMENT PICTURE
The weekly pill isn't emerging in a vacuum — it's the latest entrant in a rapidly diversifying HIV treatment landscape that has moved well beyond the daily pill in recent years. Long-acting injectable options already exist, including twice-yearly lenacapavir injections (Sunlenca) for people with multidrug-resistant HIV and injectable lenacapavir for HIV prevention (Yeztugo), alongside injectable regimens like cabotegravir-rilpivirine that patients receive every one to two months at a clinic. Merck also markets a once-daily combination of islatravir and doravirine, sold as Idvynso, which was approved in the U.S. in April.
But injectables aren't for everyone. Some patients don't want the inconvenience of scheduling regular clinic visits for a shot; others simply dislike needles. A weekly pill threads the needle — pun intended — between the demanding grind of a daily regimen and the clinical commitment of an injectable, all while staying in a format patients already know how to manage: a pill bottle at home.
Merck is also developing a second once-weekly oral candidate, pairing islatravir with a different partner drug called ulonivirine, according to data also presented at the Rio conference. Asked why the pharmaceutical world needs two competing weekly pill options, Dr. Annie Luetkemeyer of the University of California San Francisco, who presented data on the islatravir-ulonivirine combination, said simply that more options are better for patients. Rockstroh added that competition between the two, if both eventually win approval, could help lower costs and expand access — a critical consideration in a field where drug pricing has long been a barrier, particularly in lower-income countries.
WHAT'S NEXT
Neither ISLEND-1 nor ISLEND-2 has yet led to an FDA submission — both trials are continuing to the 96-week mark before Gilead and Merck are expected to pursue regulatory filings for the combination as a formal treatment option. That means the once-weekly islatravir/lenacapavir pill is not yet available to patients and prescribers, and a realistic timeline for approval likely extends into 2027 at the earliest, pending further data and the regulatory review process.
It's also worth noting what this drug is not: it is a treatment for people already virally suppressed on existing therapy, not a cure, and not (yet) an option being studied for people newly diagnosed or with detectable viral loads. The trials specifically enrolled people who were already stable and undetectable, testing whether they could switch to something more convenient without losing ground. Whether a weekly regimen can also work as an initial treatment for newly diagnosed patients is a separate question still being studied.
EXPERT PERSPECTIVE
Beyond the topline numbers, HIV specialists say the significance of this data goes to something more fundamental about how chronic disease treatment is evolving generally: away from maximum-potency, high-frequency dosing and toward regimens engineered around what real patients can actually sustain for decades. Rockstroh's framing — that "the treatment landscape is evolving" — echoes a broader trend across chronic disease management, from long-acting diabetes and obesity drugs to extended-interval cancer therapies, where drugmakers increasingly treat adherence itself as a clinical variable worth engineering for, not just a patient behavior problem to manage after the fact.
WHAT THIS MEANS FOR YOU
If you are living with HIV and currently on a stable daily regimen, this pill is not available to you yet — the earliest realistic approval timeline is more than a year away, and it depends on additional trial data and FDA review. But it signals where HIV care is heading: toward more choices, less daily burden, and treatment options built around real life rather than rigid schedules. If you're not living with HIV, the story matters too, because it reflects a broader shift in how modern medicine is starting to treat convenience and quality of life as legitimate clinical endpoints — not afterthoughts — something that could eventually reshape how chronic conditions well beyond HIV are managed.
CONCLUSION
Three decades into the HIV epidemic, the disease has been transformed from a death sentence into a manageable chronic condition — but "manageable" has always come with an asterisk: a pill, every single day, forever. The ISLEND-1 and ISLEND-2 results don't cure anything, and they won't reach pharmacy shelves this year. But they offer the clearest glimpse yet of a near future where staying undetectable doesn't require a daily ritual at all — just one tablet, once a week, and the rest of your life to actually live.
