Most patients with HIV taking the investigational combination of islatravir (ISL; Merck) plus lenacapavir (LEN; Sunlenca, Gilead) maintained a high rate (94.2%) of viral suppression at 24 weeks, according to Amy Colson, MD, PhD, who presented the data at CROI 2024, held in Denver (abstract 208).
Only one participant in the phase 2 clinical study had a viral load of more than 50 copies/mL at week 24, but the participant later suppressed on ISL+LEN at week 30, according to Dr. Colson, the research director of Community Resource Initiative (formerly AccessHealth MA), in Boston.
LEN is a first-in-class, long-acting HIV capsid inhibitor indicated for adults with multidrug-resistant HIV who are heavily treatment-experienced. ISL is an investigational nucleoside reverse transcriptase translocation inhibitor.
“Prior islatravir trials have shown declines in CD4 count and absolute lymphocyte count,” she said. “However, PK [pharmacokinetics] modeling suggests that such declines would not be expected with the 2-mg weekly islatravir dose chosen.”
The investigators wanted to know whether ISL+LEN was safe and effective as a weekly oral treatment. “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,” she said.
“Weekly oral regimens have the potential to address the pill fatigue and adherence challenges associated with daily oral therapy,” Dr. Colson said.
In this open-label, active-controlled study, 104 adults who were virologically suppressed on a regimen of bictegravir-emtricitabine-tenofovir alafenamide (BIC/FTC/TAF; Biktarvy, Gilead) were randomly selected to receive either oral ISL+LEN once weekly (n=52) or to continue daily oral BIC/FTC/TAF (n=52). The median age of participants was 40 years. Eighteen percent of the participants were assigned female at birth, 50% were non-white, and 29% were Hispanic or Latinx. No participants in the BIC/FTC/TAF group had a viral load of more than 50 copies/mL at week 24.
Results of the secondary end point, as measured by the proportion of people with HIV-1 RNA less than 50 copies/mL at week 24, showed that participants in both groups maintained comparably high rates of HIV suppression at week 24.
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 BIC/FTC/TAF group. No grade 3 and 4 TRAEs related to the study drug in either treatment group were reported. Two participants discontinued ISL+LEN because of AEs that were found to be unrelated to the study drug. In addition, no differences were seen between treatment groups for changes in CD4 T-cell counts or absolute lymphocyte counts.
“The prospect of a once weekly option for treating HIV is exciting,” said Rajesh T. Gandhi, MD, the director of HIV Clinical Services and Education at Massachusetts General Hospital, in Boston. “I look forward to larger trials testing this combination. If the promising data presented here are borne out, patients will be able to be treated for HIV by taking a pill once a week, which I expect some patients will prefer over taking daily treatments.”
Dr. Colson reported relationships with Gilead and ViiV Healthcare. Dr. Gandhi reported no relevant financial disclosures.
This article is from the June 2024 print issue.