DOR/ISL Shows Noninferiority to BIC/FTC/TAF as Initial HIV Treatment

Denver – Emerging data presented at the Conference on Retroviruses and Opportunistic Infections (CROI) this week offer further support for a novel two-drug regimen of doravirine and islatravir as an initial treatment option for people living with HIV. The findings, from the ongoing phase 3 MK-8591A-053 trial, demonstrate that the combination was noninferior to the commonly prescribed bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in maintaining viral suppression at 48 weeks.

This research builds on previous studies indicating the potential of DOR/ISL as a viable alternative to standard HIV therapies, particularly for individuals seeking regimens with fewer medications or experiencing challenges with tolerability or drug-drug interactions. As Jürgen K. Rockstroh, MD, professor of medicine at the University of Bonn, explained to Healio, “Over time, people may need to adjust their HIV treatment regimens because of comorbidities, concerns about toxicities, tolerability challenges or a desire for regimens with fewer medications.”

Study Details and Findings

The MK-8591A-053 trial involved 536 participants randomly assigned to receive either daily DOR/ISL or BIC/FTC/TAF, alongside matching placebo groups. The primary endpoint was the percentage of participants achieving HIV-1 RNA levels below 50 copies/mL, indicating viral suppression, at week 48. Results showed a high rate of viral suppression in both groups: 91.8% for those on DOR/ISL and 90.6% for those on BIC/FTC/TAF. Healio provides further coverage of the conference presentations.

Whereas the vast majority of participants maintained viral suppression, a minor number experienced virological failure. Among those receiving DOR/ISL, six individuals had HIV-1 RNA of at least 50 copies/mL. Resistance testing was performed on five of these, revealing treatment-emergent mutations in two cases. In the BIC/FTC/TAF group, nine participants had detectable viral loads, and resistance testing – conducted on six – did not identify any treatment-emergent resistance.

The study too reported similar rates of drug-related adverse events and treatment discontinuation due to adverse events between the two groups (14% and 1.1% for DOR/ISL versus 18% and 2.2% for BIC/FTC/TAF). This suggests a comparable safety profile for the investigational regimen.

Understanding the Components

Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI), a class of drugs that block the reverse transcriptase enzyme, which HIV uses to replicate. Phase 3 data from 2017 initially demonstrated its safety and effectiveness in treating HIV-1. Islatravir (ISL) is an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), representing a newer class of HIV drugs. NRTTIs work by interfering with the movement of the reverse transcriptase enzyme, disrupting viral replication.

Implications for HIV Treatment

The findings from the MK-8591A-053 trial, combined with previous data – including 96-week results in individuals with suppressed HIV – strengthen the case for DOR/ISL as a potential new treatment option for people living with HIV. Rockstroh emphasized the potential benefit of an “INSTI-free” option, referring to integrase strand transfer inhibitors, a commonly used class of HIV drugs. “People living with HIV need additional treatment options – some people may develop an intolerance to INSTIs or have concerns about drug-drug interactions,” he noted.

The development of two-drug regimens is a significant area of research in HIV treatment. Simplifying treatment to fewer drugs can potentially reduce side effects, improve adherence, and lower costs. However, it’s crucial to understand that two-drug regimens are not suitable for all patients, and careful consideration of individual factors is necessary.

What Does This Mean for Patients?

These results do not immediately change treatment guidelines. Currently, the standard of care for initial HIV treatment typically involves a three-drug regimen, often including an integrase inhibitor. However, the availability of DOR/ISL could expand options for individuals who are unable to tolerate or have developed resistance to existing therapies. It’s important to remember that any changes to HIV treatment should be made in consultation with a qualified healthcare provider.

Ongoing Research and Future Directions

Researchers are continuing to evaluate the long-term efficacy and safety of DOR/ISL. Further studies are also exploring the potential of islatravir as a foundational component for other two-drug regimens, including both daily and once-weekly dosing schedules. Rockstroh highlighted his belief in the potential of islatravir to serve as an “anchor” for a series of innovative treatment options. The ongoing investigation of these novel regimens underscores the commitment to improving the lives of people living with HIV through continued research and development. Microsoft’s recent warning about IRS phishing attacks highlights the importance of cybersecurity for all individuals, including those managing their health information online.

For more information, Jürgen K. Rockstroh, MD, can be reached at [email protected].