Patient characteristics stratified by TB stigma, TB knowledge, and HIV knowledge.

<p>TB, tuberculosis; HIV, human immunodeficiency virus; CD4, CD4+ T-lymphocyte.</p>a<p>Those with available results only.</p>b<p>Patients who had extra-pulmonary TB other than peripheral lymphatic TB or had all of the following characteristics: self-reported weight loss >10% of body weight, coughing up blood, difficulty breathing in past 4 weeks before TB diagnosis, and cavitary TB or >1/3 involvement of either lung at the initial evaluation.</p>c<p>Patients who reported having a cough lasting greater than one month before TB diagnosis or had other symptoms that lasted longer than 14 days and self-assessed these symptoms as being severe.</p>d<p>High TB stigma defined as TB stigma score ≥1; low TB knowledge defined as TB knowledge score<5; and low HIV knowledge defined as HIV knowledge score<5.</p

Baseline TB stigma, TB knowledge, and HIV knowledge among HIV-infected TB patients in Thailand.

<p>TB, tuberculosis; HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome.</p>a<p>Those with available answers.</p>b<p>Five hundred patients had high TB stigma; 75 did not respond to one or more TB stigma questions.</p>c<p>One hundred and seventy-seven had low TB knowledge; 171 did not respond to one or more TB knowledge questions.</p>d<p>Three hundred and seventy-nine patients had low HIV knowledge; 69 did not respond to one or more HIV knowledge questions.</p

Bivariable and multiple logistic regression analyses of predictors for having low TB knowledge^a among HIV-infected TB patients.

<p>TB, tuberculosis; HIV, human immunodeficiency virus; OR, odds ratio; AOR, adjusted odds ratio; CI, confidence interval; CD4, CD4+ T-lymphocyte; variables for which p≤0.20 in bivariable analyses and potential confounders were included in multiple logistic regression analysis.</p>a<p>TB knowledge score<5; TB knowledge score is a summary score of the number of TB knowledge questions (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006360#pone-0006360-t002" target="_blank">table 2</a> - each question is worth 1 point) that a patient correctly answered.</p>b<p>Compared with being treated in Bangkok.</p>c<p>Patients who had extra-pulmonary TB other than peripheral lymphatic TB or had all of the following characteristics: self-reported weight loss >10% of body weight, coughing up blood, difficulty breathing in past 4 weeks before TB diagnosis, and cavitary TB or >1/3 involvement of either lung at the initial evaluation.</p

Bivariable and multiple logistic regression analyses of predictors for having low HIV knowledge^a among HIV-infected TB patients.

<p>TB, tuberculosis; HIV, human immunodeficiency virus; OR, odds ratio; AOR, adjusted odds ratio; CI, confidence interval; variables for which p≤0.20 in bivariable analyses and potential confounders were included in multiple logistic regression analysis.</p>a<p>HIV knowledge score<5; HIV knowledge score is a summary score of the number of HIV knowledge questions (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006360#pone-0006360-t002" target="_blank">table 2</a> - each question is worth 1 point) that a patient correctly answered.</p>b<p>Compared with being treated in Bangkok.</p>c<p>Patients who had extra-pulmonary TB other than peripheral lymphatic TB or had all of the following characteristics: self-reported weight loss >10% of body weight, coughing up blood, difficulty breathing in past 4 weeks before TB diagnosis, and cavitary TB or >1/3 involvement of either lung at the initial evaluation.</p

Bivariable and multiple logistic regression analyses of predictors for having high TB stigma^a among HIV-infected TB patients.

<p>TB, tuberculosis; HIV, human immunodeficiency virus; OR, odds ratio; AOR, adjusted odds ratio; CI, confidence interval; variables for which p≤0.20 in bivariable analyses and potential confounders were included in multiple logistic regression analysis.</p>a<p>TB stigma score ≥1; TB stigma score is a summary score of the number of TB stigma questions (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006360#pone-0006360-t001" target="_blank">Table 1</a>; each question was worth 1 point) that a patient answered consistent with stigma.</p>b<p>Compared with being treated in Bangkok.</p>c<p>Patients who had extra-pulmonary TB other than peripheral lymphatic TB or had all of the following characteristics: self-reported weight loss >10% of body weight, coughing up blood, difficulty breathing in past 4 weeks before TB diagnosis, and cavitary TB or >1/3 involvement of either lung at the initial evaluation.</p

Association between Regimen Composition and Treatment Response in Patients with Multidrug-Resistant Tuberculosis: A Prospective Cohort Study

<div><p>Background</p><p>For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen.</p><p>Methods and Findings</p><p>We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005–2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16–23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients’ baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph.</p><p>In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09–1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65–2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48–1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18–1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09–1.76, per drug when three effective drugs present in regimen).</p><p>The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse.</p><p>Conclusions</p><p>MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens.</p></div

Time to initial sputum culture conversion by average number of potentially effective drugs received per day.

<p>Initial sputum culture conversion was defined as at least two consecutive negative cultures of sputum samples collected at least 30 d apart.</p

Inclusion of patients in the analysis.

<p>MDR-TB is tuberculosis resistant to at least isoniazid and rifampin; XDR-TB is tuberculosis resistant to at least isoniazid, rifampin, one fluoroquinolone, and one second-line injectable drug.</p