Study: Novel Investigational Combination Regimen Could Maintain Viral Suppression of HIV

Presented at IDWeek 2024, in Los Angeles, California, researchers announced results from the phase 2 clinical study that evaluated islatravir (Merck), an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), in combination with lenacapavir (Gilead Sciences Inc), a first-in-class HIV-1 capsid inhibitor as the first weekly oral HIV treatment.¹

Image credit: jarun011 | stock.adobe.com

“The future of HIV treatment is person-centered, with long-acting options tailored to help meet the needs and preferences of people affected by HIV,” Jared Baeten, MD, PhD, senior vice president and virology therapeutic area head at Gilead Sciences, said in a news release.¹

According to data published by the World Health Organization, at the end of 2023, an estimated 39.9 million individuals were living with HIV. Among this population, 1.4 million were children aged 0 to 14 years and 38.6 million were adults 15 years and older. Additionally, study authors noted that 1.3 million cases were acquired in 2023, displaying a 39% reduction of occurrence since 2010. Similarly, fatalities associated with HIV has reduced by 51%, as 630,000 individuals have died in 2023, compared to 1.3 million in 2010.²

Researchers conducted an open-label, active-controlled study (NCT05052996), that included virologically suppressed individuals that were on bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets (B/F/TAF, Biktarvy; Gilead Sciences Inc). The individuals were randomly assigned to receive oral islatravir 2 mg and lenacapavir 300 mg (ISL + LEN) once a week or continued their treatment with B/F/TAF.¹

The study authors noted that results displayed that the number of individuals with HIV-1 RNA <50 c/mL at 48 weeks, that switched to treatment with once weekly ISL+LEN or continued B/F/TAF upheld comparable high rates of HIV suppression (94.2% v. 92.3%, respectively). Further results found that no individuals treated with either ISL + LEN or B/F/TAF had a viral load of ≥ 50 copies/mL at Week 48.¹

“Daily single-tablet regimens have helped to transform HIV care but can be challenging for some people to maintain. Novel HIV treatment options that allow for less frequent oral dosing have the potential to help support adherence, and address stigma faced by some individuals taking daily oral therapy,” Elizabeth Rhee, MD, vice president of global clinical development at Merck Research Laboratories, said in a news release. “We are pleased to see these encouraging 48-week data for this once-weekly oral combination regimen and advance to phase 3 clinical trials in collaboration with Gilead.”¹

The most common treatment-related adverse events were reported by 19.2% of individuals treated with ISL+LEN, which included dry mouth and nausea. However, 5.8% of individuals treated with B/F/TAF experienced treatment-related adverse events, according to study authors.¹

The study authors noted that ISL+LEN has not been approved anywhere globally and the safety profile has not yet been established. Additionally, the weekly oral combination of IDL 2 mg + LEN 300 mg is being assessed in 2 phase 3 studies, as a fixed-dose combination regimen (NCT06630286 and NCT06630299), among individuals that are virologically suppressed with HIV.¹

“There is no ‘one size fits all’ approach. The complexities of HIV care require putting people first in the development of biomedical innovations as we keep striving to offer options for all those living with HIV. These data presented at IDWeek demonstrate our commitment to continuous scientific discovery aimed at further transforming the HIV treatment landscape,” Baeten said in a news release.¹

REFERENCES

1. Gilead and Merck Announce Phase 2 Data Showing a Treatment Switch to an Investigational Oral Once-Weekly Combination Regimen of Islatravir and Lenacapavir Maintained Viral Suppression in Adults at Week 48. Merck. News release. October 19, 2024. Accessed October 28, 2024. https://www.merck.com/news/gilead-and-merck-announce-phase-2-data-showing-a-treatment-switch-to-an-investigational-oral-once-weekly-combination-regimen-of-islatravir-and-lenacapavir-maintained-viral-suppression-in-adults-at-wee

2. HIV data and statistics. World Health Organization. July 22, 2024. Accessed October 28, 2024. https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/strategic-information/hiv-data-and-statistics