[Darunavir as first-line therapy. The TITAN study]

Area of Science:

• Antiretroviral therapy
• HIV treatment
• Pharmacological efficacy

Background:

• Lopinavir/ritonavir (LPV/r) has been a long-standing first-line rescue treatment for HIV.
• No boosted protease inhibitor (PI/r) had previously shown superiority over LPV/r.

Purpose of the Study:

• To compare the efficacy and safety of darunavir/ritonavir (DRV/r) against LPV/r in HIV patients requiring rescue therapy.
• To evaluate DRV/r as a potential new gold standard in HIV first-line rescue treatment.

Main Methods:

• The TITAN study randomized 595 patients to receive either DRV/r (600/100 mg twice daily) or LPV/r, both combined with optimized antiretroviral drugs.
• Efficacy was assessed at 48 weeks based on viral load (VL < 400 copies/mL) using intention-to-treat and per-protocol analyses.

Main Results:

• DRV/r showed significantly higher efficacy than LPV/r (77% vs. 67-68%) at 48 weeks.
• Incidence of diarrhea and elevated triglycerides was higher with LPV/r.
• DRV/r demonstrated efficacy benefits, especially in patients with baseline protease mutations, and protected against treatment-emergent resistance.

Conclusions:

• DRV/r is superior to LPV/r in first-line HIV rescue therapy, establishing it as a new gold standard, particularly for patients with protease mutations.
• DRV/r preserves future therapeutic options by reducing protease and reverse transcriptase mutations.
• Potential for once-daily DRV/r administration in select patient populations warrants further investigation.