Effectiveness of Favipiravir monotherapy in the treatment of COVID-19: real world data analysis from Thailand.

Background: Previous studies showed that Favipiravir, a selective viral ribonucleic acid dependent-ribonucleic acid polymerase inhibitor, exhibited a trend of clinical improvement within 14 days and promoted viral clearance by day 7, without reduction of mortality rate in COVID-19. Methods: During the COVID-19 pandemic, Department of Medical Services (Thailand) formulated National Clinical Treatment Guidelines for COVID-19 and approved Favipiravir to eight medical centres. After treatment with Favipiravir monotherapy, we compared real-world data analysis to supportive treatment without antiviral agents. Findings: We analysed 12,888 COVID-19 patients between June 1, 2021, and July 31, 2021. This group study excluded 66 asymptomatic and 4634 COVID-19 patients treated with other antiviral agents. The 4896 mild, 2357 moderate, and 935 severe COVID-19 patients were analysed. All patients neither had previous SARS-CoV-2 infection nor received an mRNA vaccine during study period. Favipiravir monotherapy reduced the 28-day mortality risk in severe COVID-19 by relative risk (RR) = 0.72 (95% CI 0.58-0.91 P = 0.006) after adjustment for aging and hypertension. However, in mild and moderate COVID-19, Favipiravir monotherapy did not significantly reduce 28-day mortality risk by RR = 0.59 (95% CI 0.06-5.43 P = 0.65) after adjustment for aging, and RR = 0.60 (95% CI 0.32-1.13 P = 0.11) after adjustment for aging and obesity, respectively. In the patient with recovery, Favipiravir monotherapy exhibited a shortening time to recovery when compared to supportive treatment without antiviral agents (mean ± SD by 9.6 ± 7.1 vs. 12.9 ± 7.6 days: P < 0.0001, 10.0 ± 5.9 vs. 12.4 ± 5.3 days: P < 0.0001, and 11.2 ± 7.8 vs. 13.1 ± 8.0 days: P < 0.0001 in mild, moderate, and severe COVID-19 respectively). Interpretation: Real-world data analysis showed that favipiravir monotherapy was superior to supportive treatment without antiviral agents in shortening the recovery time in surviving patients and significantly reducing 28-day mortality risk in severe COVID-19. Funding: Department of Medical Services, Ministry of Public Health, Thailand.

Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. FINDINGS: The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. INTERPRETATION: MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING: US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination.

Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.

BACKGROUND: Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined. METHODS: Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens. RESULTS: Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome. CONCLUSIONS: Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.

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

BACKGROUND: 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. METHODS AND FINDINGS: 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. 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). 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. CONCLUSIONS: 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.

Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries.

Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5-6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2-4) drugs; 26% retained susceptibility to <2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens.

Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis.

BACKGROUND: Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. METHODS: To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. RESULTS: In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance. CONCLUSIONS: Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.

Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study.

BACKGROUND: The prevalence of extensively drug-resistant (XDR) tuberculosis is increasing due to the expanded use of second-line drugs in people with multidrug-resistant (MDR) disease. We prospectively assessed resistance to second-line antituberculosis drugs in eight countries. METHODS: From Jan 1, 2005, to Dec 31, 2008, we enrolled consecutive adults with locally confirmed pulmonary MDR tuberculosis at the start of second-line treatment in Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea, and Thailand. Drug-susceptibility testing for study purposes was done centrally at the Centers for Disease Control and Prevention for 11 first-line and second-line drugs. We compared the results with clinical and epidemiological data to identify risk factors for resistance to second-line drugs and XDR tuberculosis. FINDINGS: Among 1278 patients, 43·7% showed resistance to at least one second-line drug, 20·0% to at least one second-line injectable drug, and 12·9% to at least one fluoroquinolone. 6·7% of patients had XDR tuberculosis (range across study sites 0·8-15·2%). Previous treatment with second-line drugs was consistently the strongest risk factor for resistance to these drugs, which increased the risk of XDR tuberculosis by more than four times. Fluoroquinolone resistance and XDR tuberculosis were more frequent in women than in men. Unemployment, alcohol abuse, and smoking were associated with resistance to second-line injectable drugs across countries. Other risk factors differed between drugs and countries. INTERPRETATION: Previous treatment with second-line drugs is a strong, consistent risk factor for resistance to these drugs, including XDR tuberculosis. Representative drug-susceptibility results could guide in-country policies for laboratory capacity and diagnostic strategies. FUNDING: US Agency for International Development, Centers for Disease Control and Prevention, National Institutes of Health/National Institute of Allergy and Infectious Diseases, and Korean Ministry of Health and Welfare.

HIVQUAL-T: monitoring and improving HIV clinical care in Thailand, 2002-08.

OBJECTIVE: We report experience of HIVQUAL-T implementation in Thailand. DESIGN: Program evaluation. SETTING: Twelve government hospital clinics. PARTICIPANTS: People living with HIV/AIDS (PLHAs) aged ≥15 years with two or more visits to the hospitals during 2002-08. INTERVENTION: HIVQUAL-T is a process for HIV care performance measurement (PM) and quality improvement (QI). The program includes PM using a sample of eligible cases and establishment of a locally led QI infrastructure and process. PM indicators are based on Thai national HIV care guidelines. QI projects address needs identified through PM; regional workshops facilitate peer learning. Annual benchmarking with repeat measurement is used to monitor progress. MAIN OUTCOME MEASURE: Percentages of eligible cases receiving various HIV services. RESULTS: Across 12 participating hospitals, HIV care caseloads were 4855 in 2002 and 13 887 in 2008. On average, 10-15% of cases were included in the PM sample. Percentages of eligible cases receiving CD4 testing in 2002 and 2008, respectively, were 24 and 99% (P< 0.001); for ARV treatment, 100 and 90% (P= 0.74); for Pneumocystis jiroveci pneumonia prophylaxis, 94 and 93% (P= 0.95); for Papanicolau smear, 0 and 67% (P< 0.001); for syphilis screening, 0 and 94% (P< 0.001); and for tuberculosis screening, 24 and 99% (P< 0.01). PM results contributed to local QI projects and national policy changes. CONCLUSIONS: Hospitals participating in HIVQUAL-T significantly increased their performance in several fundamental areas of HIV care linked to health outcomes for PLHA. This model of PM-QI has improved clinical care and implementation of HIV guidelines in hospital-based clinics in Thailand.

Clinical characteristics and treatment outcomes among patients with tuberculosis in Bangkok and Nonthaburi, Thailand.

Tuberculosis (TB) is a public health problem in many large cities. We retrospectively studied the clinical characteristics and treatment outcomes of patients with active TB at 6 hospitals in Bangkok and Nonthaburi, Thailand during 2008-2009. Eight hundred thirteen patients were included in the study. The mean age of subjects +/- SD was 41 +/- 14 years and mean body weight +/- SD was 53 +/- 11 kilograms. The three leading co-morbid conditions were HIV infection (40%), diabetes (6%) and chronic liver disease (2%). Two-thirds of subjects had isolated pulmonary TB. Isoniazid, rifampicin and multi-drug resistance were seen in 13, 7 and 5%, respectively. After 1 year, 52% were cured or completed treatment, 19% transferred out, 12% defaulted, 9% were still on-going TB treatment, 7% had died and 1% had failed treatment. Survival rates at 2, 6 and 12 months were 93, 85 and 81% among HIV seropositive subjects; 96, 94 and 92% among HIV seronegative subjects and 98, 97 and 97% among subjects with unknown HIV status (p < 0.001). On multivariate analysis, death was associated with: TB/HIV co-infection (HR 2.8; 95% CI 1.6-5.0), low body weight (HR 1.6; 95% CI 1.2-2.3), being elderly (HR 1.4; 95% CI 1.1-1.8) and having extrapulmonary/disseminated TB (HR 2.2; 95% CI 1.1-4.2). HIV infection and diabetes were the most common co-morbidities among TB subjects in our study. The percent of patients with unfavorable outcomes was relatively high, particularly among HIV co-infected and elderly subjects. Further effort needs to be made to improve these unfavorable TB outcomes in Nonthaburi and Bangkok, Thailand.

Multidrug-resistant TB and HIV in Thailand: overlapping, but not independently associated, risk factors.

The HIV and multi-drug resistant tuberculosis (MDR-TB) epidemics are closely linked. In Thailand as part of a sentinel surveillance system, we collected data prospectively about pulmonary TB cases treated in public clinics. A subset of HIV-infected TB patients identified through this system had additional data collected for a research study. We conducted multivariate analysis to identify factors associated with MDR-TB. Of 10,428 TB patients, 2,376 (23%) were HIV-infected; 145 (1%) had MDR-TB. Of the MDR-TB cases, 52 (37%) were HIV-infected. Independent risk factors for MDR-TB included age 18-29 years old, male sex, and previous TB treatment, but not HIV infection. Among new patients, having an injection drug use history was a risk factor for MDR-TB. Of 539 HIV-infected TB patients in the research study, MDR-TB was diagnosed in 19 (4%); the only significant risk factors were previous TB treatment and previous hepatitis. In Thailand, HIV is common among MDR-TB patients, but is not an independent risk factor for MDR-TB. Populations at high risk for HIV-young adults, men, injection drug users - should be prioritized for drug susceptibility testing.

Social stigma and knowledge of tuberculosis and HIV among patients with both diseases in Thailand.

INTRODUCTION: Disease-related stigma and knowledge are believed to be associated with patients' willingness to seek treatment and adherence to treatment. HIV-associated tuberculosis (TB) presents unique challenges, because TB and HIV are both medically complex and stigmatizing diseases. In Thailand, we assessed knowledge and beliefs about these diseases among HIV-infected TB patients. METHODS: We prospectively interviewed and examined HIV-infected TB patients from three provinces and one national referral hospital in Thailand from 2005-2006. At the beginning of TB treatment, we asked patients standardized questions about TB stigma, TB knowledge, and HIV knowledge. Responses were grouped into scores; scores equal to or greater than the median score of study population were considered high. Multiple logistic regression analysis was used to identify factors associated with scores. RESULTS: Of 769 patients enrolled, 500 (65%) reported high TB stigma, 177 (23%) low TB knowledge, and 379 (49%) low HIV knowledge. Patients reporting high TB stigma were more likely to have taken antibiotics before TB treatment, to have first visited a traditional healer or private provider, to not know that monogamy can reduce the risk of acquiring HIV infection, and to have been hospitalized at enrollment. Patients with low TB knowledge were more likely to have severe TB disease, to be hospitalized at enrollment, to be treated at the national infectious diseases referral hospital, and to have low HIV knowledge. Patients with low HIV knowledge were more likely to know a TB patient and to have low TB knowledge. DISCUSSION: We found that stigma and low disease-specific knowledge were common among HIV-infected TB patients and associated with similar factors. Further research is needed to determine whether reducing stigma and increasing TB and HIV knowledge among the general community and patients reduces diagnostic delay and improves patient outcomes.

HIV care and treatment factors associated with improved survival during TB treatment in Thailand: an observational study.

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.

Characteristics of HIV-infected tuberculosis patients in Thailand.

To improve understanding about the epidemiology and clinical features of HIV-associated tuberculosis (TB) infection we conducted a prospective, multi-center observational study of HIV-infected TB patients in Thailand. We enrolled HIV-infected patients diagnosed with TB at public health facilities from three provinces and the national infectious diseases referral hospital in Thailand. Patients underwent standardized interviews, evaluations, and laboratory testing at the beginning of TB treatment. We analyzed demographic and clinical characteristics of patients and stratified our findings by level of immune-suppression and whether antiretroviral therapy (ART) was used before TB diagnosis. Of 769 patients analyzed, pulmonary TB was diagnosed in 461 (60%). The median CD4+ T-lymphocyte (CD4) count was 63 cells/microl [interquartile range (IQR), 23-163.5] and the median HIV RNA viral load was 308,000 copies/ml (IQR, 51,900-759,000) at the time of TB diagnosis. Methamphetamine use was reported by 304 patients (40%), marijuana by 267 patients (35%), and injection drug use by 199 patients (26%). Three hundred three patients (40%) reported having been previously incarcerated. Among sexually active patients, 142 (42%) reported never using condoms at all. Patients with CD4 counts <200 cells/microl were significantly more likely than patients with CD4 counts > or =200 cells/microl to have extra-pulmonary TB, fever, fatigue, muscle weakness, no hemoptysis, tachycardia, low body mass index, jaundice, or no pleural effusion. Of the 94 patients that received ART before TB diagnosis, the median time from ART initiation to TB diagnosis was 105 days (IQR, 31-468). HIV-infected patients who developed TB after ART initiation were more likely than other HIV-infected TB patients to have extra-pulmonary TB, a normal chest radiograph, low HIV RNA viral load, or a history of previous TB treatment.

Causes of death in HIV-infected persons who have tuberculosis, Thailand.

Up to 50% of persons with HIV and a diagnosis of tuberculosis (TB) in Thailand die during TB treatment. In a prospective observational study, a team of physicians ascribed the cause of death after reviewing verbal autopsies (interviews of family members about events preceding death), laboratory data, and medical records. Of 849 HIV-infected TB patients enrolled, 142 (17%) died. The cause of death was TB for 38 (27%), including 6 with multidrug-resistant TB and 20 with disseminated TB; an HIV-associated condition other than TB for 50 (35%); and a condition unrelated to TB or HIV for 22 (15%). Twenty-three patients (16%) were judged not to have had TB at all. Death from all causes except those unrelated to TB or HIV was less common in persons receiving antiretroviral therapy (ART). In addition to increasing the use of ART, death rates may be reduced through expanded use of modern TB diagnostic techniques.

HIV-associated extrapulmonary tuberculosis in Thailand: epidemiology and risk factors for death.

BACKGROUND: We conducted a prospective, multicenter observational cohort study in Thailand to characterize the epidemiology of extrapulmonary tuberculosis (TB) in HIV-infected persons and to identify risk factors for death. METHODS: From May 2005 to September 2006, we enrolled, interviewed, examined, and performed laboratory tests on HIV-infected adult TB patients and followed them from TB treatment initiation until the end of TB treatment. We conducted multivariate proportional hazards analysis to identify factors associated with death. RESULTS: Of the 769 patients, pulmonary TB only was diagnosed in 461 (60%), both pulmonary and extrapulmonary TB in 78 (10%), extrapulmonary TB at one site in 223 (29%), and extrapulmonary TB at more than one site in seven (1%) patients. Death during TB treatment occurred in 59 of 308 patients (19%) with any extrapulmonary involvement. In a proportional hazards model, patients with extrapulmonary TB had an increased risk of death if they had meningitis, and a CD4+ T-lymphocyte count <200 cells/microl. Patients who received co-trimoxazole, fluconazole, and antiretroviral therapy during TB treatment had a lower risk of death. CONCLUSIONS: Among HIV-infected patients with TB, extrapulmonary disease occurred in 40% of the patients, particularly in those with advanced immune suppression. Death during TB treatment was common, but the risk of death was reduced in patients who took co-trimoxazole, fluconazole, and antiretroviral therapy.

Multi-drug resistant TB and HIV in Thailand: overlapping, but not independently associated risk factors.

The HIV and multi-drug resistant tuberculosis (MDR-TB) epidemics are closely linked. In Thailand as part of a sentinel surveillance system, we collected data prospectively about pulmonary TB cases treated in public clinics. A subset of HIV-infected TB patients identified through this system had additional data collected for a research study. We conducted multivariate analysis to identify factors associated with MDR-TB. Of 10,428 TB patients, 2,376 (23%) were HIV-infected; 145 (1%) had MDR-TB. Of the MDR-TB cases, 52 (37%) were HIV-infected. Independent risk factors for MDR-TB included age 18-29 years old, male sex, and previous TB treatment, but not HIV infection. Among new patients, having an injection drug use history was a risk factor for MDR-TB. Of 539 HIV-infected TB patients in the research study, MDR-TB was diagnosed in 19 (4%); the only significant risk factors were previous TB treatment and previous hepatitis. In Thailand, HIV is common among MDR-TB patients, but is not an independent risk factor for MDR-TB. Populations at high risk for HIV-young adults, men, injection drug users - should be prioritized for drug susceptibility testing.

Health-seeking behavior among HIV-infected patients treated for TB in Thailand.

In Asia, patients increasingly seek tuberculosis (TB) treatment in the private sector; however, few private sector practices follow international TB management guidelines. We conducted a study to measure the frequency and predictors of seeking TB diagnosis in the private sector among 756 HIV-infected TB patients in four Thai provinces during 2005-2006. Of enrolled patients, 97 (13%) first sought care at a private provider and 83 (11%) at a pharmacy. In multivariable analysis, the only factor independently associated with seeking care at a private provider was having a high TB stigma score. Factors independently associated with seeking care at a pharmacy included not knowing that TB can be cured and that TB care can be provided close to home. Patients reported that the most influential factor in choosing a provider was confidentiality (468; 62%). Further research is needed to evaluate whether educating the community about the confidentiality, availability, and success of curing TB at government health facilities can promote prompt utilization of public TB treatment services by HIV-infected patients in Thailand.

Improvements in physical and mental health among HIV-infected patients treated for TB in Thailand.

We conducted a prospective, observational study of human immunodeficiency virus (HIV) infected patients diagnosed with tuberculosis (TB) at public health facilities in Thailand to evaluate the impact of TB and HIV treatment on overall physical and mental health. Standardized data were collected from patients at the time of TB diagnosis, two months into TB treatment, and at completion of TB treatment. We calculated composite physical and mental health scores for patients that completed treatment, compared scores during treatment, and analyzed factors associated with improvements in these scores. Of 493 patients analyzed, 488 (99%) reported at least one physical health complaint and 210 (43%) had at least one mental health complaint at baseline. Improvement in physical health occurred in 377 (76%) and improvement in mental health occurred in 182 (37%). In a multivariable analysis, factors strongly associated with improvement in physical health were receiving TB treatment in Bangkok, age greater than 50 years, and improved mental health. Improvement in mental health was strongly associated with alleviation of physical symptoms, including bloody urine, foot pain, headache, muscle weakness, difficulty sleeping, chest pain, and dizziness.

Viral hepatitis and HIV-associated tuberculosis: risk factors and TB treatment outcomes in Thailand.

BACKGROUND: The occurrence of tuberculosis (TB), human immunodeficiency virus (HIV), and viral hepatitis infections in the same patient poses unique clinical and public health challenges, because medications to treat TB and HIV are hepatotoxic. We conducted an observational study to evaluate risk factors for HBsAg and/or anti-HCV reactivity and to assess differences in adverse events and TB treatment outcomes among HIV-infected TB patients. METHODS: Patients were evaluated at the beginning, during, and at the end of TB treatment. Blood samples were tested for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (BR), complete blood count, and CD4+ T lymphocyte cell count. TB treatment outcomes were assessed at the end of TB treatment according to international guidelines. RESULTS: Of 769 enrolled patients, 752 (98%) had serologic testing performed for viral hepatitis: 70 (9%) were reactive for HBsAg, 237 (31%) for anti-HCV, and 472 (63%) non-reactive for both markers. At the beginning of TB treatment, 18 (26%) patients with HBsAg reactivity had elevated liver function tests compared with 69 (15%) patients non-reactive to any viral marker (p = 0.02). At the end of TB treatment, 493 (64%) were successfully treated. Factors independently associated with HBsAg reactivity included being a man who had sex with men (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1-4.3) and having low TB knowledge (AOR, 1.8; CI, 1.0-3.0). Factors most strongly associated with anti-HCV reactivity were having injection drug use history (AOR, 12.8; CI, 7.0-23.2) and living in Bangkok (AOR, 15.8; CI, 9.4-26.5). The rate of clinical hepatitis and death during TB treatment was similar in patients HBsAg reactive, anti-HCV reactive, both HBsAg and anti-HCV reactive, and non-reactive to any viral marker. CONCLUSION: Among HIV-infected TB patients living in Thailand, markers of viral hepatitis infection, particularly hepatitis C virus infection, were common and strongly associated with known behavioral risk factors. Viral hepatitis infection markers were not strongly associated with death or the development of clinical hepatitis during TB treatment.