Long-acting oral combo for HIV maintains viral suppression at Week 24
Results from a phase 2 clinical study evaluating the investigational oral combination of islatravir (ISL; Merck) and lenacapavir (LEN; Sunlenca, Gilead) showed the combination maintained a high rate of viral suppression at 24 weeks, when given once weekly, according to Amy Colson, MD, PhD, who presented the data at CROI 2024.
“Weekly oral regimens have the potential to address the pill fatigue and adherence challenges associated with daily oral therapy,” said Dr. Colson, who is the research director at the Community Resource Initiative.
“In addition to novel mechanisms of action, both drugs have potent antiviral activity at low doses and long half-lives compatible with weekly oral dosing.”
In this open-label, active-controlled study, 104 adults who were virologically suppressed on a regimen of bictegravir-emtricitabine-tenofovir alafenamide (B/F/TAF; Biktarvy, Gilead) were randomly selected to receive either oral ISL 2 mg and LEN 300 mg once weekly (n=52) or to continue daily oral B/F/TAF (n=52). The median age of participants was 40 years. Eighteen percent of participants were assigned female at birth, 50% were non-white, and 29% were Hispanic or Latinx. No participants in the B/F/TAF group had a viral load of more than 50 copies/mL at week 24.
As measured by the proportion of people with HIV-1 RNA less than or equal to 50 copies/mL at week 24, participants who switched to treatment with once-weekly ISL + LEN or continued B/F/TAF maintained comparable high rates of HIV suppression at week 24 (94.2% vs. 94.2%), according to Dr. Colson.
Only one participant had a viral load of more than 50 copies/mL at week 24, but the individual was later suppressed on ISL/LEN at week 30, according to Dr. Colson.
“He came into the study with a baseline viral load of 251 copies/mL prior to receiving islatravir and lenacapavir. His viral load then declined on therapy with islatravir and lenacapavir to 64 at week 24 and less than 50 at week 30,” she said.
Islatravir is an investigational nucleoside reverse transcriptase translocation inhibitor; LEN is a first-in-class, long-acting HIV capsid inhibitor, which is approved to treat people with multidrug-resistant HIV in combination with other antiretrovirals.
Grade 1 and 2 treatment-related adverse events (TRAEs) reported in the ISL + LEN group included dry mouth and nausea. No grade 1 and 2 TRAEs were reported in the B/F/TAF group. No grade 3 or 4 TRAEs related to the study drug in either treatment group were reported. Two participants discontinued ISL + LEN due to AEs unrelated to the drug. In addition, no differences were seen between treatment groups for changes in CD4+ T-cell counts or absolute lymphocyte counts.
The phase 2 study will continue in an open-label fashion through week 48, the company said.
“The combination was well tolerated, and there were no between-group differences in change in CD4 count or absolute lymphocyte count. The combination of islatravir and lenacapavir has the potential to become the first weekly oral complete regimen for the treatment of HIV-1 infection,” Dr. Colson said.
Read the original article by Marie Rosenthal here.