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Background. We explored the association between antituberculosis drug pharmacokinetics and treatment outcomes among patients with pulmonary tuberculosis in Botswana. Methods. Consenting outpatients with tuberculosis had blood samples collected 1, 2, and 6 h after simultaneous isoniazid, rifampin, ethambutol, and pyrazinamide ingestion. Maximum serum concentrations (Cmax) and areas under the serum concentration time curve were determined. Clinical status was monitored throughout treatment. Results. Of the 225 participants, 36 (16%) experienced poor treatment outcome (treatment failure or death); 155 (69%) were infected with human immunodeficiency virus (HIV). Compared with published standards, low isoniazid Cmax occurred in 84 patients (37%), low rifampin Cmax in 188 (84%), low ethambutol Cmax in 87 (39%), and low pyrazinamide Cmax in 11 (5%). Median rifampin and pyrazinamide levels differed significantly by HIV status and CD4 cell count category. Only pyrazinamide pharmacokinetics were significantly associated with treatment outcome; low pyrazinamide Cmax was associated with a higher risk of documented poor treatment outcome, compared with normal Cmax (50% vs. 16%; P ! .01). HIV-infected patients with a CD4 cell count <200 cells/μL had a higher risk of poor treatment outcome (27%) than did HIV-uninfected patients (11%) or HIV-infected patients with a CD4 cell count ⩾200 cells/μL (12%; P = .01). After adjustment for HIV infection and CD4 cell count, patients with low pyrazinamide Cmax were 3 times more likely than patients with normal pyrazinamide Cmax to have poor outcomes (adjusted risk ratio, 3.38; 95% confidence interval, 1.84-6.22). Conclusions. Lower than expected antituberculosis drug Cmax occurred frequently, and low pyrazinamide Cmax was associated with poor treatment outcome. Exploring the global prevalence and significance of these findings may suggest modifications in treatment regimens that could improve tuberculosis cure rates. [ABSTRACT FROM AUTHOR]

A sensitive and accurate tuberculosis (TB) serodiagnostic test would aid in the control of TB, but results of current tests are relatively unreliable for persons infected with human immunodeficiency virus (HIV). We evaluated a new prototype immunochromatographic strip test and 5 commercially available serodiagnostic TB tests in a prospective study comprised of 465 consecutively enrolled patients with suspected TB from 2 hospitals in Botswana. Consenting adults underwent HIV testing, &ges;2 sputum smears and cultures, and mycobacterial blood culture. Patients were defined as having TB on the basis of any positive smear or culture. Between January and September 2002, 465 of 498 consecutive patients consented to enrollment. A total of 384 patients (83%) were infected with HIV, and 175 (38%) had TB; the mycobacterial blood culture was the sole source of diagnosis for 26 patients (15%) with TB. Among the tests evaluated, the sensitivity was 0%- 63%, the specificity was 39%-99%, the positive predictive value was 0%-39%, and the negative predictive value was 63%-65%. We conclude that the serodiagnostic tests evaluated in this study lacked sufficient sensitivity as sole tests for TB in this population. [ABSTRACT FROM AUTHOR]

The article presents a study on the effectiveness of extended isoniazid therapy as treatment for tuberculosis in adults with HIV infection in Botswana. The study uses a randomized and placebo-controlled trial in which Cox regression analysis is used to estimate the effect of antiretroviral therapy and compare incident tuberculosis in groups. It is inferred that 36 months' isoniazid prophylaxis is effective for the prevention of tuberculosis than in 6-month prophylaxis in individuals with HIV.

The article presents a study on isoniazid tuberculosis preventive therapy (IPT) in Botswana where HIV-infected adults have access to antiretroviral therapy (ART). It uses of National IPT Program guidelines in the first screening of persons living with HIV (PLWH) while the second screening of the subjects was trial specific. It reveals that PLWH are relatively safe and well-tolerated considering six months of IPT and that adherence to IPT is more effective than receiving ART with IPT.