Cerebrospinal Fluid and Plasma Lopinavir Concentrations and Viral Response in Virologically Suppressed Patients Switching to Lopinavir/Ritonavir Monotherapy Once Daily. Issue 4 (May 2016)

• Record Type: Journal Article
• Authors: Tiraboschi, Juan M; Knobel, Hernando; Imaz, Arkaitz; Villar, Judith; Ferrer, Elena; Saumoy, Maria; González, Alicia; Rozas, Nerea; Vila, Antonia; Niubó, Jordi; Curto, Jordi; Podzamczer, Daniel
• Is Part Of: Antiviral therapy. Volume 21:Issue 4(2016)
• Page Start: 359
• Page End: 363
• Publication Date: 2016-05
• 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/IMP3015
• Languages: English
• ISSNs: 1359-6535

Abstract

Background: Lopinavir/ritonavir (LPV/r) monotherapy is used in selected virologically suppressed HIV-infected patients. Some would prefer a once-daily (OD) dose instead of the usual twice-daily dose to favour adherence. However, trough concentrations of the drug in blood and particularly in cerebrospinal fluid (CSF) may not be adequate to maintain viral suppression. Methods: Prospective, open-label pilot study to evaluate the efficacy and safety of LPV/r monotherapy OD. HIV-1-infected patients, virologically suppressed for at least 6 months were enrolled. HIV viral load (VL) was determined at baseline and at weeks 4, 8, 12, 16, 24, 36 and 48. Lumbar puncture was performed in a subgroup of patients to evaluate CSF VL and CSF LPV concentrations. Results: A total of 21 patients were included. At week 48, 85.7% ( n =18) showed viral suppression (VL<40 copies/ml). Two patients had viral failure (9.5%) and a third was withdrawn from the study because of gastrointestinal symptoms. Nine patients were enrolled in the substudy. CSF VL was <40 copies/ml in all cases. Median (range) LPV concentration was 9.78 ng/ml (1.93–78.3) in CSF and 1, 970 (154–16, 700) ng/ml in plasma; the CSF/plasma ratio was 0.004 (0.001–0.186). Conclusions: In this small pilot study, LPV/r monotherapy OD maintained plasma HIV RNA suppression at 48 weeks in most patients, with no cases of CSF viral escape. However, CSF LPV concentrations were close to the 50% inhibitory concentration threshold in several patients; hence, this intervention should be avoided in patients with advanced immune suppression and/or those individuals presenting with significant comorbidities such as hepatitis C coinfection.