Combination antiretroviral therapy (ART) has turned HIV-1 infection into a chronic condition with near-normal life expectancy. For more than two decades, triple-drug therapy with two nucleoside reverse transcriptase inhibitors and a third drug has been the standard. Long-term treatment faces challenges such as aging patients, comorbidities, and cumulative drug exposure. These problems lead to the search for simpler strategies, and dual-drug therapy is recognized as a viable alternative to triple therapy. Doravirine and islatravir represent advances in HIV management beyond integrase inhibitors. Studies have shown that the combination of doravirine/islatravir (100 mg/0.75 mg or 100 mg/0.25 mg) improved HIV-1 suppression in heavily pretreated patients, where 85.7% achieved a ≥1.0 log10 decrease in viral RNA from days 1 to 8. In other trials, it was non-inferior to Biktarva, with viral suppression <50 copies/mL in 91.5–95.6% of patients at 48 weeks and comparable adverse events (10.2%).[1][2][3][7]