Coadministration of Lopinavir/Ritonavir and Rifampicin in HIV and Tuberculosis Co-Infected Adults in South Africa

• Type of Material: Article
• Authors: Richard A. Murphy, Médecins Sans Frontières/Doctors Without Borders; Vincent Marconi, Emory University; Rajesh T. Gandhi, Massachusetts General Hospital; Daniel R. Kuritzkes, Brigham and Women’s Hospital and Harvard Medical School; Henry Sunpath, Nelson Mandela School of Medicine
• Language: English
• Date: 2012-09-28
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Murphy et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0044793
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 9
• Start Page: e44793
• End Page: e44793
• Grant/Funding Information: he project was supported in part by the IDSA Medical Scholars Program, the Arnold P. Gold Foundation Medical Student Scholarship, Partners AIDS Research Center, McCord Hospital, and by National Institutes of Health grants K24-RR016482 and P30 AI060354.
• Keywords: PHARMACOKINETICS; MULTIDISCIPLINARY SCIENCES; Multidisciplinary Sciences; Science & Technology - Other Topics; CLINICAL-EXPERIENCE; Science & Technology; HEALTHY-VOLUNTEERS; RITONAVIR
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Background: In HIV-infected patients receiving rifampicin-based treatment for tuberculosis (TB), the dosage of lopinavir/ritonavir (LPV/r) is adjusted to prevent sub-therapeutic lopinavir concentrations. In this setting, South African clinicians were advised to administer super-boosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily. We sought to determine - in routine practice - the tolerability and HIV treatment outcomes associated with super-boosted LPV/r compared to unadjusted LPV/r in combination with rifampicin-based TB treatment. Methodology/Principle Findings: We conducted a retrospective review of HIV-infected patients who receiving second-line ART with a LPV/r-containing regimen who required concomitant TB treatment. We identified 29 patients; the median age was 36 years (IQR 29-40), 22 (76%) were female, the median CD4 cell count and viral load at first-line ART failure was 86 cells/mm 3 (IQR 21-159) and 39,457 copies/mL (IQR 6,025-157,500), respectively. According to physician preference, 15 (52%) of 29 patients received super-boosted LPV/r (400 mg/400 mg) every 12 hours during TB treatment and 14 (48%) of 29 patients received standard dose LPV/r (400 mg/100 mg) twice daily during TB treatment. Among patients who received super-boosted LPV/r there was a trend towards a higher rate of symptomatic transaminitis (27% vs. 7%; p = 0.3), gastrointestinal toxicity (20% vs. 0%; p = 0.2) and a significantly increased need for treatment discontinuation (47% vs. 7%; p = 0.035. The durability of coadministered treatment was significantly shorter in patients who received super-boosted lopinavir/ritonavir with TB treatment compared to patients who received standard lopinavir/ritonavir dosing (log rank, P = 0.036). The rate of virologic failure was not higher in patients with unadjusted LPV/r dosing. Conclusions/Significance: We observed a high rate of toxicity and need for treatment discontinuation among patients on standard rifampicin-based TB treatment who received super-boosted LPV/r.