2 drugs in 1 pill better than complex regimens for HIV

The combination of bictegravir and lenacapavir, taken orally once daily, performed better than current complex treatment regimens in the phase II ARTISTRY-1 trial of people with HIV who are virologically suppressed.

The findings were presented at CROI 2024.

Bictegravir is an integrase strand transfer inhibitor, whereas lenacapavir is a first-in-class capsid inhibitor.

Good virologic suppression

In the ARTISTRY-1 trial, 128 participants who had been on a stable baseline regimen for at least 6 months were randomly assigned in a 2:2:1 ratio to bictegravir 75 mg + lenacapavir 25 mg (low-dose group, n=51), bictegravir 75 mg + lenacapavir 50 mg (high-dose group, n=52), or to continue with their current complex HIV regimen (n=25).

All three groups had good virologic suppression at 6 months, with consistently low viral loads throughout the study. None in the low-dose or complex-regimen group had experienced a viral load rebound (≥50 copies/mL) at week 24.

In the high-dose group, one patient experienced a viral load increase above the threshold but was suppressed without changing the regimen.

Favourable safety profile

Additionally, the bictegravir-lenacapavir combination demonstrated a favourable safety profile, with diarrhoea (7 percent), COVID-19 (6 percent), and constipation (5 percent) as the most common side effects reported in the low-dose and high-dose groups.

Drug-related adverse events leading to discontinuation were reported in the low-dose and high-dose groups (2 percent each) whereas zero in the complex-regimen group. Most treatment-emergent adverse events were grade 1 or 2, with the incidence of grade 3 or higher events being low and comparable across the treatment groups.

Single tablet for optimised treatment

Although single-tablet regimens are available in the market, about 8 percent of people living with HIV are not taking them and instead resort to a complex HIV regimen of 2-3 pills daily.

Reasons cited for not starting single-tablet options included drug resistance, intolerance, toxicity, drug-drug interactions, and contraindications, said Dr Antonio Urbina from Icahn School of Medicine in New York City, New York, US.

“The combination of bictegravir and lenacapavir offers the potential for a single tablet in this population, optimizing their treatment and reducing pill burden,” he added.

However, Urbina said the findings must be interpreted with caution as the study had only a small number of patients, who may require more than 24 weeks of follow-up.

Associate Professor Elizabeth Sherman from the Nova Southeastern University in Fort Lauderdale, Florida, US, commented that one of the more interesting findings is that most patients were on a boosted protease inhibitor at baseline and were able to remove the booster from their regimen because of the switch to the combination.

“This instantly mitigates several drug interactions and removes the food requirement, streamlining the patients' therapy while reducing pill burden,” she added.

More studies are warranted to determine if this cohort of patients can maintain viral suppression in the long term. Other questions would be whether the combination therapy could benefit patients without virologic suppression or those with untreated HIV.