Combining bictegravir and lenacapavir led to similar efficacy and safety profiles and increased treatment satisfaction compared to remaining on a more complicated treatment approach.
New research supports the use of bictegravir and lenacapavir to maintain virological suppression in HIV-1.
Single-tablet regimens have been the first-choice treatment for people with HIV-1 for nearly 20 years. Despite this, many people remain on regimens where they are required to take multiple pills and/or doses a day, resulting in a significant pill burden and difficulty in adhering to treatment. The ARTISTRY-1 trial tested the efficacy and safety of people with HIV on complex regimens switching to a STR of bictegravir–lenacapavir, which combines a widely-recommended integrase strand-transfer inhibitor with an equally-well recommended capsid inhibitor.
“We show that once-daily oral bictegravir–lenacapavir was non-inferior to complex regimens in maintaining virological suppression through 48 weeks, with similarly high suppression rates, similar adverse event rates in both groups, and increased treatment satisfaction through 48 weeks. Hence, the novel STR of bictegravir–lenacapavir offers an alternative treatment option for people on complex regimens,” the researchers wrote in The Lancet.
Researchers recruited 557 individuals with HIV who had been using a complex, multi-tablet regimen to maintain virological suppression (HIV-1 RNA concentrations < 50 copies/mL) for at least six months from 90 sites across 15 countries, including Australia. The recruited sample were mostly male at birth (n = 457, 82%), were a median 60 years of age and had been receiving HIV treatment for a median of 28 years. Over a third of the cohort (39%) were taking antiretroviral pills twice per day prior to the start of the study.
Participants were randomised on a 2:1 basis to either switch to the once-daily bictegravir-lenacapavir STR (n = 371) or to continue with their complex regimen (n = 186) for 48 weeks. The demographic and characteristics of participants in each group were mostly similar, although a larger proportion of patients in the STR group had been taking antiretroviral medication twice per day compared to the group that continued their complex regimen (41% versus 35%).
Only 1% of people in each group of a HIV-1 RNA viral load of at least 50 copies/mL after 48 weeks of treatment. In addition, CD4 cell counts remained stable in both groups (an increase of 18 cells per µL from baseline in the bictegravir-lenacapavir group and a decrease of 12 cells per per µL compared to baseline in the complex regimen group).
“With a median participant age of 60 years, this is the oldest study population ever enrolled in a registrational programme for HIV treatment,” the researchers wrote. “This is particularly relevant given that advances in antiretroviral therapy have allowed people with HIV to have near-normal life expectancies; consequently, most people with HIV in high-resource countries are aged 50 years or older.”
“The median treatment duration of 28 years, high level of historical antiretroviral resistance (67% with NRTI resistance), and high proportion of participants on a complex regimen because of antiretroviral resistance (81%) is consistent with their extensive HIV-1 treatment experience and underscores why optimisation to currently available STRs has not been possible thus far.”
Individuals in the bictegravir-lenacapavir group reported an improvement in treatment satisfaction as measured by the HIV Treatment Satisfaction Questionnaire status version after 48 weeks (an average increase of 7 points on a 67-point scale, with higher scores indicating greater treatment satisfaction), while there was no change in people who continued their complex treatment regimen.
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Adverse events occurred at a similar rate across both groups (82% in the bictegravir-lenacapavir group and 84% in the complex regimen group), but only 14% were grade 3 or worse adverse events. However, drug-related adverse events were more common in the bictegravir-lenacapavir group (14% versus 2%) – but only 1% of drug-related events were considered serious.
“Although the frequency of DRAEs was higher in the bictegravir–lenacapavir group than in the complex regimen group, this is consistent with an open-label trial design involving switching away from a long-standing familiar regimen,” the researchers noted. “Moreover, only one serious adverse event was considered related to bictegravir–lenacapavir, a newly diagnosed case of diabetes in a participant with hyperglycaemia at baseline.”
The researchers noticed one other positive change following the switch to bictegravir–lenacapavir.
“Switching to bictegravir–lenacapavir improved fasting lipid concentrations in a population in whom approximately 70% had a diagnosis of dyslipidaemia at baseline and over half of participants had two or more comorbidities associated with increased cardiovascular risk. These observations might indicate a potential beneficial effect of bictegravir–lenacapavir in people with HIV and metabolic or cardiovascular risk factors,” they said.
