Background: Protease inhibitors are key antiretroviral drugs but their high price limit their availability. Reducing their dose while maintaining efficacy could yield significant cost savings and improve access. The optimum dose of darunavir (DRV) in patients without resistance-associated mutations (RAMs) has not been established.
Methods: HIV-1 infected adults with a plasma HIV RNA level < 50 cp/ml for at least 12 months, receiving a combination of 2 NRTIs + DRV 800 mg/ritonavir (r) 100 mg once daily for at least six months, with no prior virologic failure (VF) and a pre-treatment genotypic resistance test with no DRV or NRTI RAMs, were enrolled in this multicenter phase II single-arm open-label study and switched to once daily DRV 400/r with the same NRTIs. The primary study endpoint was the proportion of patients with a plasma HIV RNA level < 50 cp/ml at 48 weeks without any change in the study regimen, in a modified intent-to-treat analysis.
Results: From March to October 2015, 113 patients (pts) were screened, 100 were enrolled and started the reduced DRV dosing regimen. At baseline, most patients were male (78%), with a median age of 44.3 years, a median duration of antiretroviral therapy of 43.6 months and a median CD4 T-cell count of 633 cells/mm3. 76% received TDF/FTC and 24% ABC/3TC. Three pts with major violations of entry criteria were excluded from the analysis. During follow-up, 1 pt withdrew consent (not considered a failure), 3 pts discontinued the study regimen, and 6 experienced VF (confirmed HIV RNA level > 50 cp/ml). The overall rate of virologic success at week 48 was 90.6% (87/96; 95% CI: 82.9-95.6). No RAM was detected in 3 amplifiable genotypes. Sixty-four pts (66%) presented a total of 213 adverse events, with only 14 (6.5%) grade 3 and 4 AEs, and a single AE (grade 2 osteoporosis) deemed to be drug-related.
Conclusions: In HIV-infected patients virologically suppressed with DRV/r (800mg/100mg) and 2 NRTIs, a reduction of the DRV dose to 400 mg/d maintained virologic efficacy. This reduced dose now deserves to be assessed in a randomized trial.

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