Decreased bioavailability of rifampicin and other anti-tb drugs in patients with advanced HIV disease

Abstract

Background Malabsorption of drugs from the gastro‐intestinal tract due to HIV enteropathy and concurrent infections could lower the bioavailability of anti‐tuberculosis (TB) drugs in HIV infected individuals. Our aim was to study the pharmacokinetics of rifampicin (RMP), isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB) in HIV infected Indian subjects. The D‐xylose absorption test was also performed in all the patients. Method We studied 13 patients with smear positive pulmonary TB, 13 with HIV & diarrhoea and 14 with HIV & TB. Rifampicin (450mg), INH (600mg), PZA (1500mg) and EMB (1200mg) were administered orally. The plasma levels of RMP and INH at different time points and urinary levels of all drugs/metabolites were estimated. Results A significant decrease in peak concentrations of RMP in HIV & diarrhoea and HIV & TB patients was observed when compared to patients with TB, the values being 3.23, 3.27 & 8.27μg/ml respectively (P<0.001). Significant decrease in AUC of RMP was also observed in HIV patients. The bioavailability of INH was reduced in rapid acetylators in HIV patients with and without TB. The urinary excretion of all four drugs/metabolites and D‐xylose was reduced in both HIV groups of patients. Conclusion Patients with HIV & TB and/or diarrhoea have decreased bioavailability of first line anti‐TB drugs. This could have implications for TB treatment of HIV infected patients. Clinical Pharmacology & Therapeutics (2004) 75, P29–P29; doi:

Steady-State Pharmacokinetics of Nevirapine in HIV-1 Infected Adults in India

“…Earlier, we had shown that malabsorption of antituberculosis drugs occurs in patients with advanced HIV disease with and without diarrhea. 19 Adequate plasma concentrations of nevirapine that are not influenced by the stage of immune suppression, sex, and BMI observed in this study are encouraging. Hence, if patients take regular treatment, chances of failure due to inadequate drug levels are low.…”

Pharmacokinetics of rifabutin during atazanavir/ritonavir co-administration in HIV-infected TB patients in India

“…HIV infection has been reported to adversely impact anti-tuberculosis drug levels. 24 In view of the signifi cant correlations observed between C max , C 48h and AUC 0-24 of RBT and CD4 cell counts, one might consider increasing the RBT dose. A significant positive correlation between RBT and RTV C max , though unclear, further highlights the need to consider increasing RBT doses.…”

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“…While HIV could influence outcome in different ways, inability to achieve and sustain therapeutic levels of anti-TB drugs (possibly due to malabsorption) could be a major factor in causing poor treatment outcomes and emergence of drug resistance. We have found evidence of malabsorption and decreased bioavailability of anti-TB drugs in patients with advanced HIV disease and TB [51].…”

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