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Incidence of sub-therapeutic tuberculosis drug concentrations and associated treatment outcomes among predominantly HIV-infected tuberculosis patients, Botswana
Presented by Sekai Chideya, United States.
Chideya S.1, Peloquin C.2, Winston C.1, Wells C.1, Tappero J.3
1Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, Atlanta, Georgia, United States, 2National Jewish Medical and Research Center, Infectious Disease Pharmacokinetics Laboratory, Denver, Colorado, United States, 3Centers for Disease Control and Prevention, Global AIDS Program, Kampala, Uganda
Objectives: Sub-therapeutic concentrations of tuberculosis (TB) drugs have been frequently reported among people living with HIV/AIDS, and may be associated with poor treatment response as well as the development of TB drug-resistance. To determine the incidence of and potential associations between sub-therapeutic TB drug concentrations and treatment outcomes we monitored these factors among HIV-infected and HIV-uninfected TB patients in Botswana, where an estimated 77% of all TB patients are HIV-infected.
Methods: From 1997 through 1999 all consenting adult TB suspects at Gaborone, Botswana’s largest public outpatient clinic had serum drawn at 1, 2, and 6 h after initial isoniazid, rifampin, ethambutol and pyrazinamide dosing. After initiation of treatment with quality-assured TB medications, patients’ clinical statuses were monitored for 18 months to document incidence of poor treatment outcome (defined as treatment failure or death during TB treatment). Collected serum specimens were stored frozen until 2006, when pharmacokinetic analysis using high performance liquid chromatography was possible. Observed maximum serum concentrations were compared with published normal ranges.
Results: Overall, 227 enrolled patients had pharmacokinetics data; 157 (69%) were HIV-infected and none were taking antiretrovirals. Low concentrations of rifampin occurred in 190 (84%); ethambutol in 88 (39%); isoniazid in 84 (37%); and pyrazinamide in 11 (5%) of the 227 patients. Among HIV-uninfected patients drug concentrations were not associated with poor treatment outcome. However among HIV-infected patients with CD4 count <200, having low pyrazinamide was significantly associated with poor outcome (RR: 4.1, 95% CI = 2.7-6.1, p<.02).
Conclusions: Low concentrations of TB drugs may occur frequently among Botswana’s populace, regardless of HIV infection status, and low pyrazinamide may be associated with poor outcome among people living with AIDS. Further efforts to explain these pharmacokinetic aberrations and their link to HIV infection status, TB treatment outcomes and TB drug-resistance should be pursued.
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