Relapse and mortality among HIV-infected and uninfected patients with tuberculosis successfully treated with twice weekly directly observed therapy in rural South Africa.

OBJECTIVE: To determine post-treatment relapse and mortality rates among HIV-infected and uninfected patients with tuberculosis treated with a twice-weekly drug regimen under direct observation (DOT). SETTING: Hlabisa, South Africa. PATIENTS: A group of 403 patients with tuberculosis (53% HIV infected) cured following treatment with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice weekly to 2 months and HR twice weekly to 6 months in the community under DOT. METHODS: Relapses were identified through hospital readmission and 6-monthly home visits. Relapse (culture for Mycobacterium tuberculosis) and mortality given as rates per 100 person-years observation (PYO) stratified by HIV status and history of previous tuberculosis treatment. RESULTS: Mean (SD) post-treatment follow-up was 1.2 (0.4) years (total PYO = 499); 78 patients (19%) left the area, 58 (14%) died, 248 (62%) remained well and 19 (5%) relapsed. Relapse rates in HIV-infected and uninfected patients were 3.9 [95% confidence interval (CI) 1.5-6.3] and 3.6 (95% CI 1.1-6.1) per 100 PYO (P = 0.7). Probability of relapse at 18 months was estimated as 5% in each group. Mortality was four-fold higher among HIV-infected patients (17.8 and 4.4 deaths per 100 PYO for HIV-infected and uninfected patients, respectively; P<0.0001). Probability of survival at 24 months was estimated as 59% and 81%, respectively. We observed no increase in relapse or mortality among previously treated patients compared with new patients. A positive smear at 2 months did not predict relapse or mortality. CONCLUSION: Relapse rates are acceptably low following successful DOT with a twice weekly rifampicin-containing regimen, irrespective of HIV status and previous treatment history. Mortality is substantially increased among HIV-infected patients even following successful DOT and this requires further attention.     

DOT and timely treatment completion among Asian-born immigrant tuberculosis patients.

SETTING: A large urban tuberculosis (TB) control program. OBJECTIVES: To identify factors associated with directly observed therapy (DOT) participation and to quantify how early use of DOT affected treatment duration. DESIGN: A retrospective study of 731 Asian-born patients with drug-susceptible Mycobacterium tuberculosis isolates who were verified in New York City between 1993 and 1997 and completed treatment. RESULTS: Overall, 297 (41%) of 731 patients in the study participated in DOT for some or all of their TB treatment. DOT participation was significantly associated with TB disease in a pulmonary site (adjusted odds ratio [aOR] 2.85, 95% CI 1.86-4.35), more recent year of diagnosis (aOR 1.70, 95% CI 1.50-1.94) and male sex (aOR 1.86, 95% CI 1.30-2.66). Patients who received > or = 70% of their TB treatment at a health department chest clinic were also significantly more likely to participate in DOT (aOR 3.83, 95% CI 2.55-5.74). Among 297 DOT patients, those who completed treatment by 9 months received a greater amount of treatment by DOT during the first 4 months of treatment than those who took longer to complete treatment. CONCLUSION: Earlier DOT participation can lead to overall shorter treatment duration. Health care providers should encourage TB patients to participate in DOT as early as possible in their TB treatment.     

Community DOT for tuberculosis in a Brazilian favela: comparison with a clinic model.

SETTING: Rio de Janeiro City, Brazil. OBJECTIVE: To compare community-based directly observed treatment (DOT) for tuberculosis (TB), using community health workers (CHWs), with clinic-based DOT. DESIGN: In a longitudinal study in a cohort of TB patients in a region of Rio de Janeiro city, we evaluated treatment modalities and outcomes in 1811 patients diagnosed with TB between 1 January 2003 and 30 December 2004. Patients were offered DOT when they presented to out-patient clinics for an initial diagnosis. DOT was provided in the clinic or in the community, using CHWs, for patients living in a large favela. Outcomes of treatment were assessed using treatment registry databases. RESULTS: Of the 1811 TB patients, 1215 (67%) were treated under DOT; among these, 726 (60%) received clinic-based treatment and 489 (40%) community-based treatment. Patients offered community-based treatment were more likely to accept DOT (99%) than those offered clinic-based treatment (60%, P<0.001). Treatment success rates for new smear-positive and retreatment TB cases were significantly higher among those treated with community-based DOT compared to clinic-based DOT. CONCLUSION: We conclude that using CHWs to deliver DOT in the community may improve TB treatment outcomes in selected areas such as urban slums.     

Rifampicin plus pyrazinamide versus isoniazid for treating latent tuberculosis infection: a meta-analysis.

SETTING: Six trials from Haiti, Mexico, the U.S.A., Brazil, Spain, Zambia and Hong Kong. OBJECTIVE: To evaluate the efficacy and safety of rifampicin plus pyrazinamide (RZ) vs. isoniazid (INH) for the prevention of tuberculosis (TB) among persons with or without human immunodeficiency virus (HIV) infection. DESIGN: Meta-analysis of randomised controlled trials (RCTs) and quasi-RCTs that compared RZ for 2-3 months with INH for 6-12 months. Endpoints were development of active TB, severe adverse effects and death. Treatment effects were summarised as risk difference (RD) with 95% confidence intervals (CI). RESULTS: Three trials conducted in HIV-infected patients and three trials conducted in non-HIV-infected persons were identified. The rates of TB in the RZ group were similar to those in the INH group, whether the subjects were HIV-infected or not (HIV-infected patients: pooled RD = 0%, 95% CI -1-2, P = 0.89; non-HIV-infected persons: pooled RD = 0%, 95% CI -2-1, P = 0.55). There was no difference in mortality between the two treatment groups (HIV-infected patients: pooled RD = -1%, 95% CI -4-2, P = 0.53; non-HIV-infected persons: pooled RD = 0%, 95% CI -1-1, P = 1.00). However, both subgroup analyses showed that a higher incidence of all severe adverse events was associated with 2RZ than INH among non-HIV-infected persons (RD = 29%, 95% CI 13-46, P = 0.0005 vs. RD = 7%, 95% CI 4-10, P < 0.0001). CONCLUSION: RZ is equivalent to INH in terms of efficacy and mortality in the treatment of latent tuberculosis infection. However, this regimen increases the risk of severe adverse effects compared with INH in non-HIV-infected persons.     

Manifestations and outcome of extra-pulmonary tuberculosis: impact of human immunodeficiency virus co-infection.

SETTING: Metropolitan New Orleans. OBJECTIVE: To determine the impact of human immunodeficiency virus (HIV) co-infection on the manifestations and outcome of extra-pulmonary tuberculosis (EPTB). DESIGN: Retrospective analysis of 136 patients diagnosed with EPTB between 1 January 1993 to 31 December 2001. Characteristics of EPTB were compared by HIV serostatus. RESULTS: Of those tested for HIV (n = 87), 42.5% were seropositive. Except for a higher frequency of disseminated TB among co-infected persons, the manifestations, laboratory diagnostic yield and outcome of EPTB were similar between HIV-infected and non-infected persons. The overall fatality rate was 20%; HIV-infected patients had a three-fold higher mortality compared to non-infected persons. In multivariate logistic regression analysis, factors associated with death were: HIV-seropositive (adjusted odds ratio [aOR] 5.2, 95% CI 1.1-24.65) compared to HIV-seronegative, disseminated and meningeal compared to lymphatic disease (aOR 16.87, 95% CI 12.31-123.34), and lack of TB treatment compared to receipt of TB treatment (aOR 29.23, 95% CI 14.47-191.23). CONCLUSION: Manifestations of EPTB were non-specific and did not differ between HIV-infected and non-infected persons. Severe disease, lack of TB treatment and HIV co-infection were associated withdeath. Approaches are needed to reduce EPTB morbidity and mortality, especially among HIV-infected persons.     

Provider-initiated diagnostic HIV counselling and testing in tuberculosis clinics in Thailand

SETTINGS: Twelve large public hospitals geographically distributed in Thailand. OBJECTIVES: To assess the uptake of diagnostic human immunodeficiency virus (HIV) counselling and testing (DCT), HIV prevalence in tuberculosis (TB) patients and HIV services provided to newly diagnosed HIV-infected TB patients. METHOD: We provided DCT in TB clinics to newly registered TB patients. Post-test counselling was provided at TB clinics for non-HIV-infected patients and at HIV voluntary counselling and testing centres for HIV-infected patients. HIV-infected patients were referred for HIV-related care during TB treatment. RESULTS: From July to October 2006, 8% of 1086 new TB patients were known to be HIV-infected at the time of TB diagnosis. Of 1000 patients with unknown HIV status, 93% were tested: HIV infection was diagnosed in 11%. Including patients with previously diagnosed HIV infection, 17% of all TB patients were HIV-infected. Of 99 newly diagnosed HIV patients, 36% received cotrimoxazole prophylaxis. Of 41 with CD4 < 200 cells/microl, 42% began antiretroviral treatment during TB treatment. CONCLUSION: The acceptance of DCT was high, but the provision of HIV services was disappointingly low. Increased staff capacity building, stronger coordination with the acquired immune-deficiency syndrome programme and better field supervision are needed to achieve universal access to care for HIV-infected TB patients.     

Determinants of drug-resistant tuberculosis: analysis of 11 countries.

SETTING: Eleven countries/territories. OBJECTIVES: Global information on the determinants of drug-resistant tuberculosis (TB) based on representative data is not available. We therefore studied the relationship between demographic characteristics, prior TB treatment, and human immunodeficiency virus (HIV) infection with anti-tuberculosis drug resistance. METHODS: Population-based representative data on new and previously treated patients with TB collected within an international drug resistance surveillance network. RESULTS: Of 9,615 patients, 8,222 (85.5%) were new cases of TB and 1,393 (14.5%) were previously treated cases. Compared with new cases, previously treated cases were significantly more likely to have resistance to one (OR = 2.5,95% CI 2.1-3.0; P < 0.001), two (OR = 4.6, 95%CI 3.7-5.6; P < 0.001), three (OR = 11.5, 95%CI 8.6-15.3; P < 0.001), and four (OR = 18.5, 95% CI 12.0-28.5; P < 0.001) drugs. An approximately linear increase in the likelihood of having multidrug-resistant tuberculosis (MDR-TB) was observed as the total time (measured in months) of prior anti-tuberculosis treatment increased (P < 0.001, chi2 for trend). In multivariate analysis, prior TB treatment for 6-11 months (OR = 7.6, 95% CI 2.6, 22.4; P < 0.001) and > or = 12 months (OR 13.7, 95% CI 4.5-41.6; P < 0.001), but not HIV positivity, was associated with MDR-TB. CONCLUSION: This study shows that prior but ineffective treatment is a strong predictor of drug resistance, and that HIV is not an independent risk factor for MDR-TB. The association between length of treatment and drug resistance may reflect longer treatment as a result of treatment failure in patients with drug resistance; it may also reflect irregular prior treatment for TB, leading to drug resistance.     

The epidemiology of HIV-associated tuberculosis in rural Cambodia.

SETTING: Banteay Meanchey Province, Cambodia. OBJECTIVE: The World Health Organization recommends human immunodeficiency virus (HIV) testing for all tuberculosis (TB) patients and TB screening for all HIV-infected persons in countries with a TB-HIV syndemic. We sought to determine whether evidence supports implementing these recommendations in South-East Asia. DESIGN: We conducted a cross-sectional survey and retrospective cohort study of patients newly diagnosed with HIV or TB from October 2003 to February 2005 to identify risk factors for HIV infection and TB, and for death during TB treatment. RESULTS: HIV infection was diagnosed in 216/574 (38%) TB patients. TB disease was found in 124/450 (24%) HIV-infected persons. No sub-groups of patients had a low risk of HIV infection or TB. Of 180 TB patients with HIV infection and a recorded treatment outcome, 49 (27%) died compared to 17/357 (5%) without HIV infection (relative risk [RR] 5.2, 95% confidence interval [CI] 3.1-8.7). HIV-infected TB patients with smear-negative pulmonary disease died less frequently than those with smear-positive pulmonary disease (RR 0.39, 95%CI 0.16-0.93). CONCLUSIONS: No sub-groups of patients had low risk for HIV infection or TB, and mortality among HIV-infected TB patients was high. These data justify using the WHO global TB-HIV recommendations in South-East Asia. Urgent interventions are needed to reduce the high mortality rate in HIV-infected TB patients.     

Has directly observed treatment improved outcomes for patients with tuberculosis in southern Thailand?

OBJECTIVE: To validate the practice of directly observed treatment (DOT) and evaluate its effect on treatment outcomes. METHODS: This follow-up study conducted in 24 districts in southern Thailand included 411 new, smear-positive, pulmonary tuberculosis (TB) patients who started treatment between February and September 1999. Patients and/or their observers were interviewed about their actual DOT practice during the first 2 months of treatment. Treatment outcomes were evaluated at the end of the second month and at the end of treatment. RESULTS: Of 411 patients, 379 were assigned to DOT but only 68 practised strict DOT for every dose during the first 2 months. Adjusted odds ratios (ORs) for 'no sputum conversion' and 'unsuccessful treatment' were 1.1 (95% CI 0.6-2.1) and 1.3 (95% CI 0.6-2.8), respectively, for those who practised strict DOT vs. the rest. CONCLUSIONS: Actual practice of DOT was quite different from what was intended at the assignment. Practice of strict DOT during the first 2 months was not associated with sputum conversion or treatment success in this study area.     

Factors predicting non-completion of tuberculosis treatment among HIV-infected patients in Barcelona (1987-1996).

OBJECTIVE: To determine the predictive factors of non-completion of tuberculosis (TB) treatment among patients infected with the human immunodeficiency virus (HIV). DESIGN: Between 1987 and 1996, 2201 HIV-infected TB patients were detected by the Barcelona Tuberculosis Prevention and Control Programme. Patients who completed treatment were compared to those who abandoned. Bivariate analysis was made by chi(2) test to compare qualitative variables. Associations were measured by means of odds ratios (OR) with 95% confidence intervals (CI). Variables showing a statistically significant association were analysed at multivariate level by means of a logistic regression model. RESULTS: Treatment was carried to completion by 1065 patients (48.4%), 289 (13.1%) abandoned, 648 (29.5%) died during treatment, and 142 (6.5%) moved out of the city. Final outcome could not be established in 57 (2.5%). Intravenous drug users (IDU) represented 76.2% of patients. The rate of non-completion between 1987 and 1992 was 26.3% and for 1993-1996 it was 15.1%, a decrease of 42.6%. Living in neighbourhoods of a low socio-economic level (OR 1.61; 95% CI 1.222.13), homelessness (OR 3.56; 95% CI 2.01-6.31), history of TB (OR 1.61; 95% CI 1.12-2.33), and having presented with a current TB episode in 1987-1992 (OR 1.42; 95% CI 1.01-2.00), were risk factors for abandoning TB treatment. CONCLUSIONS: Social and health factors together influence non-completion of TB treatment in HIV-infected patients, while health interventions can improve treatment completion.     

Treatment of lymph node tuberculosis--a randomized clinical trial of two 6-month regimens

OBJECTIVE: The currently recommended treatment for lymph node tuberculosis is 6 months of rifampicin and isoniazid plus pyrazinamide for the first 2 months, given either daily or thrice weekly. The objective of this study was to assess the efficacy of a 6-month twice-weekly regimen and a daily two-drug regimen. METHODS: Patients with biopsy confirmed superficial lymph node tuberculosis were randomly allocated to receive either a daily self-administered 6-month regimen of rifampicin and isoniazid, or a twice-weekly, directly observed, 6-month regimen of rifampicin and isoniazid plus pyrazinamide for the first 2 months, in Madurai, South India, Patients were followed up for 36 months after completing treatment. RESULTS: Of 277 enrolled patients, data was available for analysis in 268. At the end of treatment, 116 of 134 [87%; 95% confidence interval (CI) 81-93%] patients in each treatment group had a favourable clinical response; 14 (11%; 95% CI 6-16%) and 17 (13%; 95% CI 7-19%) patients had a doubtful response, and 4 (3%; 95% CI 0-6%) and 1 (1%; 95% CI 0-2%) patients had an unfavourable response among those treated with the daily and twice-weekly regimen, respectively. During 36 months after completion of treatment, five patients [2 (2%; 95% CI 1-3%) and 3 (2%; 95% CI 1-3%) patients treated with the daily and twice-weekly regimen, respectively] had relapse of lymph node tuberculosis, of 260 assessed. Adverse reactions probably attributable to the treatment regimens occurred in 1% of the patients treated daily and in 11% of those treated twice-weekly (P < 0.001). At the end of 36 months after treatment, 126 of 134 (94%; 95% CI 90-98%) and 129 of 134 (96%; 95% CI 94-98%) of the patients treated with the daily and twice-weekly regimen, respectively, had a successful outcome. CONCLUSION: Both the self-administered daily regimen and the fully observed twice-weekly regimen were highly efficacious for treating patients with lymph node tuberculosis and may be considered as alternative options to the recommended regimens.     

Predictors of relapse among pulmonary tuberculosis patients treated in a DOTS programme in South India.

OBJECTIVE: To identify risk factors associated with relapse among cured tuberculosis (TB) patients in a DOTS programme in South India. DESIGN: Sputum samples collected from a cohort of TB patients registered between April 2000 and December 2001 were examined by fluorescence microscopy for acid-fast bacilli and by culture for Mycobacterium tuberculosis at 6, 12 and 18 months after treatment completion. RESULTS: Of the 534 cured patients, 503 (94%) were followed up for 18 months after treatment completion. Of these, 62 (12%) relapsed during the 18-month period; 48 (77%) of the 62 relapses occurred during the first 6 months of follow-up. Patients who took treatment irregularly were twice more likely to have a relapse than adherent patients (20% vs. 9%; adjusted odds ratio [aOR] 2.5; 95% CI 1.4-4.6). Other independent predictors of relapse were initial drug resistance to isoniazid and/or rifampicin (aOR 4.8; 95% CI 2.0-11.6) and smoking (aOR 3.1; 95% CI 1.6-6.0). The relapse rate among non-smoking, treatment adherent patients with drug-sensitive organisms was 4.8%. CONCLUSIONS: The relapse rate under the DOTS programme may be reduced by ensuring that patients take their treatment regularly and are counselled effectively about quitting smoking.     

Efficacy of an unsupervised 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis in HIV-infected adults. Uganda-Case Western Reserve University Research Collaboration.

SETTING: National Tuberculosis Treatment Centre, Mulago Hospital, Kampala, Uganda. OBJECTIVE: To assess the efficacy of a daily, self-administered 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis (TB) in human immunodeficiency virus (HIV) infected adults. DESIGN: Treatment outcomes in patients with pulmonary TB treated with a single 8-month regimen and followed in a prospective epidemiological study. RESULTS: Two hundred and sixty-five HIV-infected and 26 non-HIV-infected adults with initial episodes of pulmonary tuberculosis were treated with 2 months of daily isoniazid (INH), rifampicin (RMP), ethambutol and pyrazinamide followed by 6 months of daily INH + RMP. Median follow-up was 17.8 months. Ninety-five per cent of the HIV-infected and all of the non-HIV-infected patients who had sputum examined were sputum culture negative after 2 months of treatment. Twenty-two HIV-infected and no non-HIV-infected patients died during treatment. Relapse rates were 8.4% (5.9 per 100 person-years of observation [PYO], 95%CI 3.2-8.6) among HIV-infected patients and 4.5% (2.1/100 PYO, 95%CI 0-7.8) for non-HIV-infected patients. Adverse drug reactions occurred in 37% of the HIV-infected patients; most were minor and self-limiting. CONCLUSION: An 8-month RMP-containing regimen was well tolerated and effective in the treatment of HIV-infected adults with initial episodes of pulmonary TB. Relapse rates were similar to those reported with 6-month short-course regimens in HIV-infected individuals. Decisions about the duration of anti-tuberculosis treatment for HIV-infected adults must balance programme resources and the likelihood of poor compliance with longer regimens with the potential for a modest decrease in relapses with longer treatment.     

Control of anti-tuberculosis drug resistance in Botswana.

SETTING: Botswana, where in 2000 the prevalence of human immunodeficiency virus (HIV) infection among adults was 38%, and the tuberculosis (TB) rate was 591/100,000. A 1995-1996 survey demonstrated low levels of anti-tuberculosis drug resistance. OBJECTIVE: Because TB drug resistance may increase rapidly in HIV-infected populations, a second survey was undertaken in 1999 to determine any increase in anti-tuberculosis drug resistance. DESIGN: Sputum specimens positive for acid-fast bacilli from patients without prior TB treatment (new patients), and all sputum specimens from patients reporting prior TB treatment (retreatment patients) were collected nationwide. Specimens were cultured for Mycobacterium tuberculosis and tested for resistance to isoniazid, rifampicin, ethambutol, and streptomycin. RESULTS: From January to May 1999, 783 patients were consecutively enrolled from all districts. Of these, 483 (61.7%) were male, the median age was 33 years, and 82% were new patients. Drug resistance occurred in 6.3% of new patients (95 % confidence interval [CI] 4.6-8.6) and 22.8% of retreatment patients (95% CI 16.5-30.1). Resistance to at least isoniazid and rifampicin was found in 0.5% of new (95% CI 0.1-1.3) and 9.0% of retreatment patients (95% CI 5.1-14.5). CONCLUSION: Anti-tuberculosis drug resistance remains relatively low in Botswana, probably as a result of a well-functioning TB program. Periodic surveys will be essential to adequately determine any significant trend.     

A trial of the effect of micronutrient supplementation on treatment outcome, T cell counts, morbidity, and mortality in adults with pulmonary tuberculosis

BACKGROUND: Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. RESULTS: Micronutrients decreased the risk ofTB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, -14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. CONCLUSIONS: Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania.     

Current status of treatment completion and fatality among tuberculosis patients in Spain.

OBJECTIVES: To determine treatment completion among patients with tuberculosis (TB), and to analyse factors associated with treatment default and fatality. METHODS: A prospective cohort study of patients who began treatment between 1 June 1999 and 31 May 2000 in areas where members of the SEPAR Tuberculosis and Respiratory Infections Group work. Factors associated with treatment default and fatality were studied using logistic regression, calculating odds ratios (OR) and their 95% confidence intervals (95%CI). RESULTS: The study involved 142 physicians from 76 different hospitals who provided information on 1515 cases. Eighty-two per cent of the patients completed treatment correctly, 14% defaulted, 5% died, 0.5% failed, and 8.7% interrupted treatment due to transfer or other reasons. The variables associated with default were intravenous drug use (IVDU) (OR 6.00, 95%CI 2.59-13.89) and immigration (OR 8.57, 95%CI 3.78-19.45); sex, age, homelessness, incarceration, directly observed treatment (DOT) or hospitalisation were not associated with default. Variables found to be predictive of fatality were alcoholism (OR 6.38, 95%CI 2.09-19.48), human immunodeficiency virus (HIV) infection (OR 7.08, 95%CI 2.08-29.15) and age >64 years (OR 10, 95%CI 2.9-34.07), whereas sex, IVDU, homelessness, DOT and hospitalisation were not. CONCLUSIONS: In industrialised countries, IVDU patients and immigrants should be targeted for DOT, while to reduce fatality rates stricter monitoring is required for patients who are alcoholic, HIV-infected, or aged >64 years.     

Influence of highly active anti-retroviral therapy (HAART) on the natural history of extra-pulmonary tuberculosis in HIV patients.

OBJECTIVE: To determine factors related to survival in acquired immune-deficiency syndrome (AIDS) patients with extra-pulmonary tuberculosis (EPTB), when this condition is the first AIDS-defining disease. DESIGN: A retrospective cohort-study of 549 AIDS patients with EPTB as the first AIDS-defining disease. Potential candidates to predict survival were sex, human immunodeficiency virus (HIV) exposure, the coexistence of pulmonary and EPTB at diagnosis, tuberculin skin test, directly observed therapy for tuberculosis (DOT), and highly active anti-retroviral therapy (HAART). The Kaplan-Meier method and Cox regression models were used to assess factors associated with survival. RESULTS: Estimated 3-year survival was 47.0% for those diagnosed before 1993, 72.6% for patients with first AIDS diagnosis during 1995-1996 and 84.6% for those diagnosed after 1996. A negative tuberculin test (hazard ratio [HR] = 1.6, 95% CI 1.1-2.3), not being on DOT (HR 2.2; 95% CI 1.3-3.7) and having pulmonary tuberculosis involvement also (HR 1.3; 95% CI 1.1-1.7) were independently associated with poorer survival. The survival of patients significantly improved after the introduction of HAART (HR 0.4; 95% CI 0.2-0.6). CONCLUSION: The survival of HIV patients with EPTB as their first AIDS-defining disease has substantially improved during the last decade. A negative tuberculin skin test and not receiving DOT are associated with poorer survival among HIV-infected patients whose first AIDS-defining disease is EPTB.     

Improvements in treatment success rates with directly observed therapy in Rio de Janeiro City.

SETTING: Rio de Janeiro City, Brazil. OBJECTIVE: To evaluate the effect of directly observed therapy (DOT) on treatment success, by comparing the treatment success rates between patients treated under DOT with those who received self-administered therapy (SAT). DESIGN: A longitudinal study in a cohort of tuberculosis (TB) patients. Of 9929 new pulmonary TB cases, 1190 (12%) were treated under DOT and 8739 (88%) under SAT. All patients received a three-drug regimen consisting of rifampicin (RMP), isoniazid (INH) and pyrazinamide for 2 months followed by 4 months of RMP and INH. RESULTS: Patients under DOT were more likely to convert to sputum-negative at the end of the second month than those treated under SAT (86.3% vs. 61.9%, P < 0.001). DOT alone was significantly associated with successful treatment (OR 1.6, 95%CI 1.37-1.86, P < 0.001), even when controlled by sex, age and positive smear or culture at enrollment (OR 1.56, 95%CI 1.33-1.82, P < 0.001). CONCLUSION: This pilot DOTS implementation phase showed that DOT is highly effective and feasible in a large urban centre of a developing country.