A novel single-tablet regimen (STR) combining the drugs bictegravir and lenacapavir provided similar viral suppression as multi-pill antiretroviral therapy among older adults with HIV, according to a phase 3 clinical trial published today in The Lancet. The STR also increased treatment satisfaction among participants for 48 weeks of follow-up, or about 11 months. 

The trial enrolled 557 adults with HIV-1 infection who had sustained viral suppression and long treatment histories and remained on complex regimens because of prior drug resistance, intolerance, or contraindications that precluded use of existing single-tablet options. Participants did not have infections that showed resistance to bictegravir or any previous exposure to lenacapavir.

Viral suppression high in both groups

For the study, researchers from Queen Mary University of London randomly assigned participants in a 2:1 ratio to switch to once-daily oral bictegravir–lenacapavir or continue their current regimen. Participants’ median age was 60 years, and they had been taking HIV treatment for a median of 28 years. At baseline, participants were taking a median of three antiretroviral pills per day, with some taking as many as 11. Nearly 40% took antiretroviral pills twice daily.

At 48 weeks, 1% of participants in both groups had an HIV-1 RNA level of 50 copies per milliliter or higher, meeting the prespecified noninferiority margin of 4%. Rates of viral suppression below 50 copies per milliliter were high in both groups—96% in the single-tablet group and 94% in the complex-regimen group. 

Overall adverse event rates were similar between groups. Eighty-two percent of participants receiving bictegravir–lenacapavir and 84% of those continuing complex therapy reported at least one adverse event, most of which were mild or moderate. Serious adverse events occurred in 14% and 12% of participants,respectively. Five deaths occurred in the single-tablet group, none considered related to the study drug.

Simpler regimen tied to improvements in lipid profile

Switching to the STR was associated with improvements in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels, while remaining stable or increasing slightly in the complex-regimen group. Body weight remained stable in both groups.

Participants who switched to the STR also reported significantly greater treatment satisfaction at 48 weeks than those who continued complex therapy.

This STR [single-tablet regimen] could present the first opportunity to optimise treatment while maintaining virological suppression in people taking complex regimens who have not benefitted from available STRs.

The authors conclude that bictegravir–lenacapavir offers a new treatment optimization option for patients who are not candidates for currently available single-tablet regimens.

“Bictegravir–lenacapavir was generally well tolerated, led to improvement in the lipid profile, and provided greater treatment satisfaction among participants who switched from a complex regimen,” they write. “This STR could present the first opportunity to optimise treatment while maintaining virological suppression in people taking complex regimens who have not benefitted from available STRs due to antiretroviral resistance or other reasons.”