Determination of Isoniazid Acetylator Phenotype and its Clinical Implication in Rwandan Tuberculosis Patients

Abstract

The purpose was to determine the normal profile of the isoniazid acetylator phenotype, the effect of  tuberculosis (TB) on the profile, and the impact of the profile on early clinical responses following a treatment with the first line drug regimen. The study sample comprised 20 healthy volunteers and 22 TB naive patients. The tests for TB and HIV were conducted in the laboratory of the University Teaching Hospital Butare (CHUB). The phenotype was achieved by measuring the percentage of acetylisoniazid in the urine after a unique oral dose of isoniazid 10 mg/kg. TB patients were treated for two months with standard regimen combining rifampicin, isoniazid, pyrazinamide and ethambutol. A trimodal distribution profile was observed in both the healthy and tuberculosis groups, giving 30% versus 13.6% as slow acetylators, 45% versus 54.5% as intermediate acetylators, and 25% versus 23.2% as fast acetylators respectively. After a 2-month treatment of the TB patients, the sputum smear cultures were negative in about 81% independent of the acetylator or HIV status. Early side effects experienced were dominated by peripheral neuropathies mostly in slow and intermediate acetylators.

Key words: Acetylator, isoniazid, phenotype, tuberculosis, HIV, Rwanda