The US Food and Drug Administration has approved the once-daily oral combination doravirine/islatravir (IDVYNSO) to replace existing antiretroviral regimens in adults with virologically suppressed HIV-1 (HIV-1 RNA <50 copies/mL) with no history of treatment failure and no known substitutions associated with resistance to doravirine, supported by Phase 3, randomized, active-controlled, noninferiority clinical trial data demonstrating noninferior efficacy and a comparable safety profile in switch populations vs standard antiretroviral therapy.
Approval was supported by Week 48 findings from the Phase 3 MK-8591A-052 and MK-8591A-051 randomized, active-controlled, noninferiority trials in adults with virologically suppressed HIV-1 who switched from baseline antiretroviral therapy. In Trial 052, doravirine/islatravir (DOR/ISL) was compared with bictegravir/emtricitabine/tenofovir alafenamide. At 48 weeks, rates of viral suppression were similar between groups, with approximately 92% vs 94% of patients, respectively, achieving HIV-1 RNA levels below 50 copies/mL.
In an earlier press release, follow-up 96-week data from the Phase 3 MK-8591A-052 and MK-8591A-051 trials supported continued use of DOR/ISL in patients with virologically suppressed HIV-1 who transitioned from baseline oral antiretroviral therapy. In these studies, viral suppression was maintained through 96 weeks in most patients who switched to the two-drug regimen, with outcomes comparable to those who continued baseline therapy. Safety findings remained stable over time, with no new adverse signals identified and low discontinuation rates.
DOR/ISL is a two-drug regimen that does not include an integrase strand transfer inhibitor and is tenofovir-free, representing an alternative option for patients requiring simplified treatment approaches. Islatravir is a nucleoside analog that inhibits viral replication through multiple mechanisms, including interference with reverse transcriptase activity. The availability of this regimen may support individualized treatment strategies, particularly in patients with comorbidities, tolerability concerns, or a need to reduce medication burden.
The regimen is intended as a complete therapy and should not be co-administered with other antiretrovirals.
It is contraindicated with strong cytochrome P450 3A inducers and with lamivudine or emtricitabine due to reduced drug exposure and potential loss of efficacy.