Once-weekly treatment with islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor, and lenacapavir, a first-in-class HIV-1 capsid inhibitor, led to sustained high rates of viral suppression at week 48 among people with HIV, according to the secondary endpoint results of a phase II study presented at IDWeek 2024.

This open-label, active-controlled, multicentre study included 104 adults (median age 40 years, 18.3 percent female) who were virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide(B/F/TAF). These participants were randomized in a 1:1 ratio to either oral islatravir 2 mg + lenacapavir 300 mg once weekly or to continue on oral B/F/TAF once daily. [IDWeek 2024, abstract 577]

By week 48, individuals who switched from B/F/TAF to islatravir + lenacapavir regimenor continued to receive B/F/TAF had similar rates of HIV suppression (HIV-1 RNA <50 copies/mL; 94.2 percent and 92.3, respectively).

Moreover, none of the participants in either treatment group had HIV-1 RNA ≥50 copies/mL at week 48.

Of note, six participants (three of each group) discontinued the study prior to week 48 due to medical or personal reasons unrelated to the study drug, but all of these individuals had a viral load of HIV-1 RNA <50 copies/mL at the time of discontinuation, said Dr Amy Colson, Research Director at the Community Resource Initiative in Boston, Massachusetts, US.

“[Taken together,] switching from daily oral B/F/TAF to weekly oral islatravir + lenacapavir maintained virologic suppression in a large portion of individuals at week 48,” she noted.

Safety parameters

Treatment-related adverse events (TRAEs, such as dry mouth and nausea) occurred in 19.2 percent of those in the islatravir + lenacapavir arm, while only 5.8 percent were reported in the B/F/TAF arm. Colson noted that in an open-label switch study, “there is often a higher rate of reported TRAEs in the experimental arm.”

No grade 3/4 and serious TRAEs and AEs leading to study drug discontinuation were observed in either treatment group.

There were also no significant grade 3/4 laboratory abnormalities reported, except for ALT elevation, which was reported in a participant with acute hepatitis B infection in the islatravir + lenacapavir arm, noted Colson.

In terms of mean changes in CD4+ T-cell count and absolute lymphocyte count from baseline to week 48, there were no significant differences observed between the two groups.

Both CD4+ T-cell and absolute lymphocyte counts remained stable through week 48 in both treatment groups, said Colson.

Overall, the combination of islatravir and lenacapavir “was very well tolerated as demonstrated by the absence of any TRAEs,” she noted.

First weekly oral drug

“Islatravir + lenacapavir has the potential to become the first weekly oral complete regimen for the treatment of HIV-1 infection,” said Colson.

“Furthermore, these phase II results support the progression of this weekly oral islatravir + lenacapavir regimen to phase III, as two phase III studies have already been planned,” she added.