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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]

Background: In Southeast Asia, HIV-infected patients frequently die during TB treatment. Many physicians are reluctant to treat HIV-infected TB patients with anti-retroviral therapy (ART) and have questions about the added value of opportunistic infection prophylaxis to ART, the optimum ART regimen, and the benefit of initiating ART early during TB treatment. Methods: We conducted a multi-center observational study of HIV-infected patients newly diagnosed with TB in Thailand. Clinical data was collected from the beginning to the end of TB treatment. We conducted multivariable proportional hazards analysis to identify factors associated with death. Results: Of 667 HIV-infected TB patients enrolled, 450 (68%) were smear and/or culture positive. Death during TB treatment occurred in 112 (17%). In proportional hazards analysis, factors strongly associated with reduced risk of death were ART use (Hazard Ratio [HR] 0.16; 95% confidence interval [CI] 0.07-0.36), fluconazole use (HR 0.34; CI 0.18-0.64), and co-trimoxazole use (HR 0.41; CI 0.20-0.83). Among 126 patients that initiated ART after TB diagnosis, the risk of death increased the longer that ART was delayed during TB treatment. Efavirenz- and nevirapine-containing ART regimens were associated with similar rates of adverse events and death. Conclusion: Among HIV-infected patients living in Thailand, the single most important determinant of survival during TB treatment was use of ART. Controlled clinical trials are needed to confirm our findings that early ART initiation improves survival and that the choice of non-nucleoside reverse transcriptase inhibitor does not. [ABSTRACT FROM AUTHOR]

Background. Multidrug-resistant (MDR) tuberculosis (TB) has emerged as a global epidemic, with ~425,000 new cases estimated to occur annually. The global human immunodeficiency virus (HIV) infection epidemic has caused explosive increases in TB incidence and may be contributing to increases in MDR-TB prevalence. Methods. We reviewed published studies and available surveillance data evaluating links between HIV infection and MDR-TB to quantify convergence of these 2 epidemics, evaluate the consequences, and determine essential steps to address these epidemics. Results. Institutional outbreaks of MDR-TB have primarily affected HIV-infected persons. Delayed diagnosis, inadequate initial treatment, and prolonged infectiousness led to extraordinary attack rates and case-fatality rates among HIV-infected persons. Whether this sequence occurs in communities is less clear. MDR-TB appears not to cause infection or disease more readily than drug-susceptible TB in HIV-infected persons. HIV infection may lead to malabsorption of anti-TB drugs and acquired rifamycin resistance. HIV-infected patients with MDR-TB have unacceptably high mortality; both antiretroviral and antimycobacterial treatment are necessary. Simultaneous treatment requires 6-10 different drugs. In HIV-prevalent countries, TB programs struggle with increased caseloads, which increase the risk of acquired MDR-TB. Surveillance data suggest that HIV infection and MDR-TB may converge in several countries. Conclusions. Institutional outbreaks, overwhelmed public health programs, and complex clinical management issues may contribute to the convergence of the MDR-TB and HIV infection epidemics. To forestall disastrous consequences, infection control, rapid case detection, effective treatment, and expanded program capacity are needed urgently. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) is lifesaving in patients with advanced HIV infection, but the magnitude of benefit in HIV-infected patients receiving tuberculosis (TB) treatment remains uncertain, and population-based data from developing countries are limited. We prospectively collected data about HIV-infected TB patients from February 2003 through January 2004 in Ubon-ratchathani, Thailand. During 12 months, HIV was diagnosed in 329 (14%) of 2,342 patients registered for TB treatment. Of patients with known outcomes, death during TB treatment occurred in 5 (7%) of 71 who received ART and 94 (43%) of 219 who did not. Using multivariate analysis, we found a large reduction in the odds of death for patients receiving ART before or during TB treatment (odds ratio, 0.2; 95% confidence interval, 0.1-0.5), adjusting for CD4 count, smear status, co-trimoxazole use, and treatment facility. ART is associated with a substantial reduction in deaths during TB treatment for HIV-infected TB patients in Thailand. [ABSTRACT FROM AUTHOR]

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.

The article evaluates commonly available pulmonary tuberculosis (TB) screening tests using sputum bacteriology as a gold standard in HIV-infected persons who attended an urban voluntary counseling and testing clinic in Addis Ababa, Ethiopia. It notes that all 438 HIV-infected persons underwent TB screening regardless of symptoms. It cites that the current Ethiopian national guidelines simulations showed 63% sensitivity and 83% specificity for diagnosing TB disease among study patients.

Objective WHO's new Global Plan to Stop TB 2006-2015 advises countries with a high burden of tuberculosis (TB) to expand case-finding in the private sector as well as services for patients with HIV and multidrug-resistant TB (MDR-TB). The objective of this study was to evaluate these strategies in Thailand using data from the Thailand TB Active Surveillance Network, a demonstration project begun in 2004. Methods In October 2004, we began contacting public and private health-care facilities monthly to record data about people diagnosed with TB, assist with patient care, provide HIV counselling and testing, and obtain sputum samples for culture and susceptibility testing. The catchment area included 3.6 million people in four provinces. We compared results from October 2004- September 2005 (referred to as 2005) to baseline data from October 2002-September 2003 (referred to as 2003). Findings In 2005, we ascertained 5841 TB cases (164/100 000), including 2320 new smear-positive cases (65/100 000). Compared with routine passive surveillance in 2003, active surveillance increased reporting of all TB cases by 19% and of new smear-positive cases by 13%. Private facilities diagnosed 634 (11%) of all TB cases. In 2005, 1392 (24%) cases were known to be HIV positive. The proportion of cases with an unknown HIV status decreased from 66% (3226/4904) in 2003 to 23% (1329/5841) in 2005 ( P< 0.01). Of 4656 pulmonary cases, mycobacterial culture was performed in 3024 (65%) and MDR-TB diagnosed in 60 (1%). Conclusion In Thailand, piloting the new WHO strategy increased case-finding and collaboration with the private sector, and improved HIV services for TB patients and the diagnosis of MDR-TB. Further analysis of treatment outcomes and costs is needed to assess this programme's impact and cost effectiveness. [ABSTRACT FROM AUTHOR]