Double-dose lopinavir-ritonavir in combination with rifampicin-based anti-tuberculosis treatment in South Africa (original) (raw)
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PLoS ONE, 2012
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.
Rifampicin reduces plasma concentration of most HIV protease inhibitors. Lopinavir boosted with ritonavir (LPV/r) could be an option to treat TB-HIV patients. Our aim was to evaluate lopinavir interaction with rifampicin during TB-HIV therapy. TB-HIV patients who could not use efavirenz and with no genotypic resistance to lopinavir were included. Rifampicin 600 mg, isoniazid 400 mg and pyrazinamide 2000 mg were started at day one for 6 months and LPV/r plus two nucleoside/nucleotide reverse transcriptase inhibitors were introduced at day 30. LPV/r dose was started at 400/100 mg BID and escalated over 7 days to 800/200 mg BID. Pharmacokinetic sampling was performed at day 15 (rifampicin), 45, 90, 180 (rifampicin, lopinavir, ritonavir) and 210 (lopinavir, ritonavir). Viral load (VL) and CD4 counts were performed at baseline and days 30, 60, 120, and 180. Genotypic testing was done in baseline and in the last visit. Fifteen patients were enrolled. Five were excluded during exclusively TB therapy. After LPV/r introduction five patients were excluded, three due to adverse events, and two due to low adherence. Five patients finished the study, two of them with VL<50 copies/mL. LPV/r genotypic resistance was detected in one patient. Lopinavir concentrations were below 1 µg/mL in 4/10 patients (in one study point), and one in two study points. Lopinavir concentrations were above 4 µg/mL in 6/10 patients, at least in one pharmacokinetic sample. Although target drug concentrations of lopinavir were achieved for most patients, adverse events were frequent and low adherence was observed for both TB and HIV therapies, showing how difficult it is to treat both diseases simultaneously. Hepatic and pancreatic enzymes should be routinely monitored. J o ur nal o f A ID S & Cli n ic a l R es earc h
Annals of Clinical Microbiology and Antimicrobials, 2020
BackgroundTo evaluate the pharmacokinetic of plasma lopinavir (LPV) and ritonavir (RTV) when co-administered with three times weekly (TPW) rifabutin (RBT) at a dose of either 150 or 300 mg in African tuberculosis (TB) and HIV co-infected adult patients.MethodsThis is a pharmacokinetic study conducted in Ouagadougou among patients treated with a standard dosage of LPV/RTV 400/100 mg twice daily and RBT 150 mg TPW (arm A = 9 patients) or rifabutin 300 mg TPW (arm B = 7 patients) based regimens. Patients were recruited from the Bogodogo and Kossodo district hospitals in Ouagadougou from May 2013 to December 2015. Study inclusion criteria were that the patients were between 18 and 60 years of age, HIV-1 infected with pulmonary tuberculosis confirmed or suspected. Subsequent blood samples for pharmacokinetic monitoring were collected at 1, 2, 3, 4, 6, 8 and 12 h after combined drug ingestion for plasma drug monitoring using HPLC/MS assays.ResultsThe medians LPV Cmaxand Tmaxwere respectiv...
PLOS ONE, 2013
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.
Antiviral Therapy, 2011
Background: Coadministration of rifampicin dramatically reduces the concentrations of protease inhibitors. A pharmacokinetic study in healthy adults showed that doubling the dose of coformulated lopinavir/ritonavir was able to overcome the inducing effect of rifampicin. We evaluated this strategy in children treated with rifampicinbased antituberculosis therapy attending antiretroviral clinics in South Africa. Methods: Plasma concentrations of lopinavir were measured in children (aged 0.64-2.43 years) established on antituberculosis treatment who commenced antiretroviral therapy comprising double the usual recommended dose of lopinavir/ritonavir oral solution (460/115 mg/ m 2 twice daily) plus two nucleoside reverse transcriptase inhibitors. Control children (0.57-4.23 years old) without tuberculosis received standard doses of lopinavir/ritonavir (230/57.5 mg/m 2 twice daily). Results: Pre-dose lopinavir concentrations were reduced by >80% in children with tuberculosis (median 0.7 mg/l, IQR 0.1-2.0) compared with controls (4.2 mg/l, IQR 3.4-8.1; P<0.001) and were below the minimum recommended concentration of 1 mg/l in 12 of 20 (60%) children with tuberculosis versus 2 of 24 (8%) controls (P<0.001). Conclusions: Double doses of coformulated lopinavir/ ritonavir results in inadequate lopinavir concentrations in young children treated concurrently with rifampicin. Suitable regimens are urgently needed for treating young children with HIV-associated tuberculosis.
PLoS ONE, 2014
Background: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured.
Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 1995
This pilot study was conducted at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda, where tuberculosis (TB) is an epidemic health problem aggravated by the HIV-1 pandemic. To evaluate the feasibility of a larger phase III trial utilizing rifabutin as a substitute for rifampicin in short-course therapy for pulmonary TB. Single-blind randomized trial in 50 patients with new onset smear- and culture-positive pulmonary tuberculosis and HIV-1 infection. Comparison of daily, intermittently supervised 6-month treatment regimens of rifabutin versus rifampicin, together with isoniazid, ethambutol and pyrazinamide. Rifabutin- and rifampicin-containing regimens had comparable efficiency. However, rifabutin-treated patients had significantly more rapid clearance of acid-fast bacilli from sputum at 2 months (P < 0.05, Fisher exact test) and over the entire study period (P < 0.05, logrank test) than rifampicin-treated patients. The presence of cavitary disease was associated wit...
The Lancet Infectious Diseases, 2021
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