A once-daily, single-tablet regimen combining bictegravir and lenacapavir maintained viral suppression at rates comparable to complex multi-tablet regimens in treatment-experienced adults with HIV-1, according to data from the Phase III data ARTISTRY-1 trial. Study results, published in The Lancet, showed that in the trial’s patient population that had a median age of 60 years, decades of prior antiretroviral therapy, high levels of historical resistance, and multiple comorbidities, nearly 96% of participants who switched to the fixed-dose combination sustained HIV-1 RNA levels below 50 copies per mL at 48 weeks, a benchmark of viral suppression.
“Simplifying HIV treatment from handfuls of pills at the start of the epidemic to one pill a day has improved clinical outcomes for most people living with HIV,” said principal investigator Chloe Orkin, MBBS, a professor at Queen Mary University of London. “However, until now, some people with resistant virus or clinical contraindications cannot take these simpler regimens and must instead take complex regimens which may place them at risk of drug interactions. The ARTISTRY-1 trial results demonstrate that a single tablet containing the drugs bictegravir and lenacapavir works just as well as their complex multi-tablet regimen and improved participants’ lipid profile.”
Single-tablet regimens for people have been used to treat people infected with HIV for nearly 20 years. But some patients, often those who are long-term survivors who were diagnosed early in the epidemic, remain on regimens consisting of multiple pills and doses per day because of drug resistance, contraindications, or drug–drug interactions. This gap in care is what has led to the develop of a novel single-tablet regimen for this population.
The ARTISTRY-1 was a randomized, open-label, active-controlled, non-inferiority Phase III clinical trial conducted in 15 countries. The 557 participants were randomly assigned in a 2:1 ratio to switch to once-daily oral bictegravir–lenacapavir 75 mg/50 mg or to continue their existing multi-tablet treatment regimen. The primary endpoint was the proportion of participants with HIV-1 RNA of 50 copies per mL or higher at week 48, using the U.S. Food and Drug Administration Snapshot algorithm.
The median age of enrollees was 60 years, with participant ages ranging from 22 to 84 years. Participants had been on HIV treatment for a median of 28 years and were taking a median of three antiretroviral pills per day, with some taking as many as 11. 81% were on complex regimens because of antiretroviral resistance and more than half had at least two comorbidities.
At week 48, one percent of participants in the bictegravir–lenacapavir group and one percent in the complex-regimen group had HIV-1 RNA of 50 copies per mL or higher, meeting the prespecified non-inferiority margin. Six participants (two percent) discontinued bictegravir–lenacapavir and one (one percent) discontinued their complex regimen because of adverse events. Five deaths occurred in the bictegravir–lenacapavir group, none of which were deemed related to study drug.
The positive effects of the single-pill treatment were seen in more than just maintaining healthy HIV-1 RNA levels. “Participants who switched to bictegravir–lenacapavir from a complex regimen reported greater treatment satisfaction than those continuing a complex regimen. This confirms that participants found multi-tablet treatment regimens more challenging,” the researchers wrote, further noting that such challenges “could over time jeopardize adherence and retention in care, which are both necessary to maintain virological suppression and avoid emergent resistance.”
Clinically, final approval of this treatment, would likely improve treatment optimization in an aging population with longstanding HIV infection. Additional data from the trial showed that lipids parameters improved after the switch, an important factor in a patient cohort in which roughly 70% had dyslipidemia at baseline and more than half had multiple cardiometabolic comorbidities.
The study’s authors noted that its open-label design was a limitation, although investigators noted that blinding would have been impractical given the diversity of background regimens and the role of patient-reported satisfaction in optimization strategies. A separate blinded Phase III trial comparing outcomes after switching to bictegravir–lenacapavir is ongoing and longer-term follow-up will look to assess treatment durability and safety.
