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Bictegravir Plus Lenacapavir Keep Control of HIV in People on Complex Regimens
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AIDS 2024, July 22-26, 2024, Munich
Mark Mascolini
People with an undetectable HIV load while taking a complex multidrug regimen largely maintained that response after switching to bictegravir (BIC) plus lenacapavir (LEN) for 48 weeks in a randomized open-label trial [1]. A handful of people taking 75 mg of bictegravir with 25 or 50 mg of LEN did not meet the goal of keeping viral load below 50 copies at 48 weeks by FDA snapshot analysis, but the snapshot missed 2 people without virologic data because they discontinued treatment. Everyone who stayed with their original complex regimen kept their viral load under 50 copies through 48 weeks by FDA snapshot. And 48-week response rates did not differ significantly between the three study arms.
Once-daily single-tablet regimens are the simplest oral therapies for HIV infection, but many people have to take complex multipill combinations because of resistance, intolerance, toxicity, drug-drug interactions, or contraindications to current single-pill regimens. A single-tablet regimen combining BIC, an integrase inhibitor with a high barrier to resistance, and LEN, a first-of-its-kind HIV capsid inhibitor, might prove a simpler option for some people now taking a multidrug combination.
ARTISTRY-1 aimed to compare three regimens in people with an undetectable viral load while taking a complex regimen: maintaining that same regimen, 75 mg of BIC plus 25 mg of LEN, or 75 mg of BIC plus 50 mg of LEN. This phase 2/3 randomized, open-label trial enrolled people at least 18 years old and maintaining a viral load below 50 copies for at least 6 months while taking complex ART [2]. The researchers defined complex antiretroviral therapy (ART) as a regimen containing a boosted protease inhibitor or a nonnucleoside plus at least 1 other antiretroviral from a class other than nucleosides/nucleotides, or a combination of at least 2 or more pills daily or requiring more than once-daily dosing, or a regimen containing a parenteral (nonoral) antiretroviral plus oral antiretrovirals.
Participants numbered 51 in the BIC/LEN 75/25-mg arm, 52 in the BIC/LEN 75/50-mg arm, and 25 in the complex ART arm. The 25-mg LEN group and the 50-mg LEN group were marginally older than the complex ART group (medians 62, 62, 58 years), they included lower proportions of whites (56.9%, 65.4%, 80.0%), higher proportions of blacks (35.3%, 30.8%, 20.0%), and similar proportions of Hispanics (14.0%, 17.6%, 16.0%).
Duration of ART was similar in the 25-mg LEN group, the 50-mg LEN group, and the complex ART group (medians 27.8, 27.0, 26.9 years), though the 25-mg LEN group had taken fewer regimens than the other two groups (medians 4, 7, 8). No one in this trial has historical resistance to integrase inhibitors, while large proportions had historical resistance to nucleosides/nucleotides (60.8%, 67.3%, 64.0%), nonnucleosides (49.0%, 53.8%, 56.0%), and protease inhibitors (PI) (35.3%, 32.7%, 44.0%).
Almost three quarters of participants (72%) were taking a PI, and 66% of those taking a PI were also taking an integrase inhibitor. A substantial minority (41.4%) relied on a twice-daily combination, 10.9% took 4 pills daily, and 27.3% needed 5 or more pills daily.
FDA snapshot analysis at 48 weeks determined that 100% (25 of 25) randomized to continued complex ART maintained a viral load below 50 copies. In the BIC/LEN 75/25 group, 92.2% (47 of 51) had a week-48 viral load under 50 copies (difference from complex ART -7.8%, 95% confidence interval [CI] -19.2 to 7.0, P = 0.30), and 90.4% (47 of 52) in the BIC/LEN 75/50 arm kept their viral load under 50 copies (difference from complex ART -9.6%, 95% CI -21.0 to 5.3, P = 0.17).
aDifference in % (95% CI): BIC + LEN - complex ART regimen calculated based on an unconditional exact method using two inverted one-sided tests. bBased on Fisher exact test.
cTwo participants had no virologic data in the Week 48 window as they discontinued study drug before Week 48 visit; one participant due to AE and one participant due to participant decision. dFour participants had no virologic data in the Week 48 window as they discontinued study drug before Week 48 visit due to AE, death, participant decision, and investigator decision (n = 1 for each).
Data shown as n (%). N-values represent numbers of participants.
aTwo participants had no virologic data in the Week 48 window as they discontinued study drug before Week 48 visit; one participant due to AE and one participant due to participant decision. bFour participants had no virologic data in the Week 48 window as they discontinued study drug before Week 48 visit due to AE, death, participant decision, and investigator decision (n = 1 for each).
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Proportions of participants who had 1 or more treatment-emergent adverse events measured 82.4% in the 25-mg LEN arm, 78.8% in the 50-mg LEN arm, and 76.0% in the complex ART arm. Respective proportions with 1 or more grade 3 or higher treatment-emergent adverse events were 13.7%, 7.7%, and 4.0%, proportions with 1 or more such events leading to stopping a drug early 2.0%, 1.9%, and 0%, 1 or more serious treatment-emergent adverse events 7.8%, 5.8%, and 12.0%, and deaths 0%, 1.9%, and 0%. Researchers judged the death (due to coronary artery disease) unrelated to study drugs.
Data shown as n (%). N-values represent numbers of participants. Only AEs with onset date on or before the nominal Week 48 visit date were included in this summary. aGrade 1 nausea on Day 1. bGrade 3 worsening of vomiting in a participant with preexisting episodes of nausea and vomiting. cUnrelated to study treatment. dCause of death: coronary artery disease.
References
1. Mounzer K, Slim J, Ramgopal M, et al. Efficacy and safety of bictegravir plus lenacapavir: 48-week outcomes in virologically suppressed people with HIV-1 on complex antiretroviral regimens at baseline. AIDS 2024, July 22-26, 2024, Munich. Abstract OAB2602,
2. ClinicalTrials.gov. Study to compare bictegravir/lenacapavir versus current therapy in people with HIV-1 who are successfully treated with a complicated regimen (ARTISTRY-1). ClinicalTrials.gov ID: NCT05502341. https://clinicaltrials.gov/study/NCT05502341
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