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

Richard A Murphy,Vincent C Marconi,Rajesh T Gandhi,Daniel R Kuritzkes,Henry Sunpath,Cristian Apetrei

doi:10.1371/journal.pone.0044793

Abstract

BackgroundIn 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 FindingsWe 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/mm3 (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/SignificanceWe 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.

Highlights

A significant proportion of HIV-infected patients in South Africa require second-line ritonavir-boosted protease inhibitor (PI)-based antiretroviral therapy (ART) as a result of virologic failure or intolerance of initial ART [1]
We identified 29 patients who received concomitant rifampicin and lopinavir/ ritonavir (LPV/r)-containing ART, representing 15% of patients who initiated second-line ART
The most common reason for treatment discontinuation was transaminitis in the presence of clinical symptoms or signs of hepatitis

Summary

Introduction

A significant proportion of HIV-infected patients in South Africa require second-line ritonavir-boosted protease inhibitor (PI)-based antiretroviral therapy (ART) as a result of virologic failure or intolerance of initial ART [1]. Among patients receiving TB treatment, clinicians in South Africa were advised to administer superboosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily [7]. Poor regimen tolerability was seen when adult patients with HIV and TB were treated with super-boosted LPV/r and rifampicin in the Netherlands, with suboptimal antiviral efficacy observed in coinfected patients who received standard LPV/r dosing [9]. 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

Methods

Results

Conclusion