Michael Gwarisa
Two new once-daily HIV treatments taken as a single pill have shown strong results in late-stage clinical trials, raising hopes for simpler treatment options for people living with the virus.
The studies were presented at the Conference on Retroviruses and Opportunistic Infections 2026 in Denver, United States. Researchers tested whether the new drugs could work as well as existing treatments while reducing the number of pills patients must take.
One trial evaluated a new combination for people starting HIV treatment for the first time. Another examined whether older patients who have lived with HIV for decades could safely switch from complex treatment regimens to a single daily pill.
Experts say the findings could expand the range of treatment options available to clinicians and patients.
New treatment tested for first-time patients
The first study tested a new single-tablet therapy combining doravirine and islatravir.
Researchers compared it with an established treatment made up of bictegravir, emtricitabine and tenofovir alafenamide, which is widely used as a first-line HIV therapy.
The trial was led by Jürgen Rockstroh of University Hospital Bonn in Germany.
He said the study focused on people who had never taken HIV medication before, a group often used to evaluate how well a new therapy performs under demanding conditions.
“The new thing about this data is that it is in treatment-naive populations,” Rockstroh said, describing the group as a kind of “stress test” for a new regimen.
The double-blind trial involved more than 500 participants across 116 sites in 20 countries. Many participants began the study with high levels of the virus in their blood, including more than a third with viral loads above 100,000 copies.
Researchers also aimed to recruit a diverse group of participants, addressing long-standing criticism that HIV trials often focus heavily on white men in wealthier countries.
About 21 percent of participants came from Africa. Roughly one third identified as Black or African American, 40 percent as Latinx and about 10 percent as Asian. Around a quarter of participants were women.
Rockstroh said this diversity represented progress, even though the number of female participants remained relatively small.
Similar results after 48 weeks
Participants were randomly assigned to receive either the experimental doravirine and islatravir pill or the standard treatment.
After 48 weeks, both regimens showed nearly identical effectiveness.
About 92 percent of participants taking the new drug combination achieved viral suppression, defined as HIV-1 RNA levels below 50 copies per millilitre of blood. In the group taking the existing treatment, 91 percent achieved the same outcome.
Because the results were so similar, the new therapy was considered “non-inferior,” meaning it performed as well as the current standard treatment.
Only a small number of participants stopped the experimental therapy because it did not work effectively. Two individuals developed resistance to the drugs, both of whom had extremely high viral loads at the start of the trial.
Rockstroh noted that drug level testing in one case suggested the patient may not have been taking the medication consistently.
Researchers also examined side effects, including weight gain, which has become a concern with some HIV medications.
Both treatment groups experienced similar increases in body weight, with participants gaining an average of nearly four kilograms during the study period.
Rockstroh said this may be partly explained by the “return-to-health” effect often seen when people begin effective HIV treatment.
“When people start therapy and their immune system improves, weight gain is common,” he said.
He added that longer follow-up studies would be needed to determine whether meaningful differences emerge over time.
Despite similar results to existing therapies, Rockstroh said the new drug combination could still be valuable.
“I think a lot of clinicians ask whether we really need another single-tablet regimen,” he said.
“But having options matters. You cannot force someone to take a tablet they do not want.”
Simplifying treatment for long-term patients
The second study explored whether a different single-tablet therapy could simplify treatment for people who have lived with HIV for many years.
The trial tested a daily pill combining bictegravir and lenacapavir.
It was presented by Chloe Orkin from Queen Mary University of London.
Orkin said the participants represent a generation of people who experienced the early years of the HIV epidemic.
“These are people diagnosed in the early part of the epidemic,” she said.
“They lost loved ones and communities while HIV treatment gradually evolved.”
Participants had to be virally suppressed for at least six months before entering the study and were taking complex treatment regimens.
The group had a median age of 60, making it the oldest population ever included in a major HIV registration trial.
Many had lived with HIV for nearly three decades and had been taking antiretroviral therapy for an average of 28 years.
More than half also had additional health conditions, including high cholesterol, hypertension and diabetes, requiring them to take several other medications.
From multiple pills to one
Before joining the trial, many participants were taking complicated treatment schedules.
About 40 percent took two pills a day, while more than 20 percent took five or more daily. In extreme cases, patients were taking up to 11 pills a day.
Most of these regimens were needed because of past drug resistance or the need to combine multiple drug classes.
Participants were randomly assigned either to switch to the new bictegravir and lenacapavir pill or to continue their existing treatment.
Strong viral control maintained
After 48 weeks, the simplified regimen performed just as well as the complex regimens.
About 96 percent of people who switched to the new pill maintained an undetectable viral load.
Three participants briefly showed detectable virus levels, but the virus was later suppressed again without needing to change treatment.
Researchers also reported no cases of new drug resistance during the trial.
Patients’ immune health remained stable throughout the study, with CD4 counts staying consistent.
Switching to the new treatment also produced improvements in certain cholesterol levels, including total cholesterol, LDL cholesterol and triglycerides.
However, participants who switched to the simplified therapy gained slightly more weight than those who remained on their original regimens. The difference averaged about 0.6 kilograms.
Despite this small change, patient surveys showed higher satisfaction among those taking the single daily pill.
“We have participants at my site who were absolutely delighted to be on the regimen,” Orkin said.
Doctors see benefit for overlooked patients
During the conference discussion, clinicians said the study addressed an important need.
Many people who started HIV treatment decades ago remain on complicated drug combinations and sometimes feel overlooked as newer therapies are developed.
Rockstroh said the research highlighted the importance of continuing to develop options for this group.
“These are patients who feel they have been left behind by the development of new drugs,” he said.
While some simplified regimens already exist, he added that a single tablet could make treatment easier for many patients.
Hepatitis B considerations
Researchers also noted an important limitation.
Neither of the new drug combinations contains tenofovir, which protects against hepatitis B virus.
During the bictegravir and lenacapavir trial, one participant experienced a brief reactivation of hepatitis B before the virus became undetectable again.
In the doravirine and islatravir study, three participants developed hepatitis B infections during the trial.
During a conference discussion, Anton Pozniak questioned why hepatitis B vaccination was not required for participants.
Rockstroh said strict vaccination rules could exclude people in countries where vaccines are less accessible.
“If vaccination were mandatory, we might unintentionally exclude participants from regions with limited access,” he said.
Next steps toward approval
Drug companies are now seeking regulatory approval for the new therapies.
The pharmaceutical firm Merck said the US Food and Drug Administration is expected to make a decision on the doravirine and islatravir combination for certain patients later this year.
Meanwhile Gilead Sciences is pursuing approval for the bictegravir and lenacapavir regimen.
If approved, the new treatments could offer additional single-pill options for both newly diagnosed patients and people who have been living with HIV for many years.
Researchers say the findings highlight continuing progress in HIV care, with the goal of making lifelong treatment simpler and easier to maintain.
