Ritonavir-Boosted Darunavir Plus Two Nucleoside Reverse Transcriptase Inhibitors versus Other Regimens for Initial Antiretroviral Therapy for People with HIV Infection: A Systematic Review.

Background: Darunavir is a second-generation protease-inhibitor used with ritonavir (DRV/r) and two nucleoside reverse-transcriptase inhibitors as an option in first-line antiretroviral treatment (ART).

Methods: We systematically reviewed randomized controlled trials (RCTs) of DRV/r versus other regimens in patients initiating ART. We searched five bibliographic databases and other key resources. We had no language limitations. We assessed bias risk with the Cochrane tool and used GRADE to assess evidence quality. We report findings in terms of risk ratio (RR) with 95% confidence intervals (CI).

Findings: Three RCTs met inclusion criteria. In plasma viral load suppression, DRV/r outperformed ritonavir-boosted lopinavir at 48 weeks (RR 1.13, 95% CI 1.03-1.25), 96 weeks (RR 1.11, 95% CI 1.02-1.21), and 192 weeks (RR 1.20, 95% CI 1.07-1.35). DRV/r was similar to dolutegravir at 48 weeks (RR 0.96, 95% CI 0.87-1.06) but less effective at 96 weeks (RR 0.84, 95% CI 0.75-0.93). At 96 weeks, DRV/r underperformed raltegravir (RR 0.94, 95% CI 0.88-0.99) but was similar to ritonavir-boosted atazanavir (RR 1.02, 95% CI 0.96-1.09). Overall bias risk was moderate. Evidence quality was also moderate.

Interpretation: Initial ART regimens using DRV/r should be considered in future World Health Organization guidelines.