Darunavir Minimum Plasma Concentration and Ritonavir-Boosted Darunavir Monotherapy Outcome in HIV-Infected Patients. Issue 5 (July 2014)

• Record Type: Journal Article
• Authors: Gutierrez-Valencia, Alicia; Torres-Cornejo, Almudena; BenMarzouk-Hidalgo, Omar J; Ruiz-Valderas, Rosa; Lluch, Amparo; Viciana, Pompeyo; López-Cortés, Luis F
• Is Part Of: Antiviral therapy. Volume 19:Issue 5(2014)
• Page Start: 443
• Page End: 447
• Publication Date: 2014-07
• Subjects: Antiviral agents -- Periodicals; Antiviral Agents -- therapeutic use; Virus Diseases -- therapy; Viruses -- drug effects; Antiviral agents; Periodical; Electronic journals; Periodicals; 616.9106
• DOI: 10.3851/IMP2722
• Languages: English
• ISSNs: 1359-6535

Abstract

Background: This study aimed to evaluate whether low darunavir (DRV) minimum plasma concentration (Cmin ) values contribute to virological outcomes during DRV/ritonavir monotherapy (mtDRV/rtv). Methods: This was a prospective observational single-arm 96-week efficacy study in virologically suppressed subjects on triple therapy switched to mtDRV/rtv (800/100 mg every 24 h). Previous virological failures (VF) on protease-inhibitor-based regimens were allowed if the historical resistance tests showed no major resistance mutation to DRV/rtv. VF was defined as two consecutive HIV RNA measurements of >200 copies/ml. Efficacy was analysed by per-protocol and by intention-to-treat analyses. Plasma DRV Cmin values were measured by LC-MS/MS. Results: A total of 150 subjects were included. At week 96, the efficacy rate on treatment was 83.6% (95% CI 77.2%, 90.0%) by per-protocol analysis and 67.6% (95% CI 60.0%, 75.2%) by intention-to-treat. In the whole cohort the median (IQR) DRV Cmin was significantly higher during the periods of undetectable than of detectable viraemia (1.82 μg/ml [1.47–2.46] versus 1.56 μg/ml [0.93–2.32]; P =0.006) as well as in the subjects with blips and VF. However, a cutoff point sufficiently sensitive and specific could not be found. Conclusions: The DRV Cmin values are related to viral control during mtDRV/rtv, but therapeutic drug monitoring cannot be recommended routinely as a precise cutoff point is unknown. Adherence is a key success factor on this regimen.