thioacetazone and AIDS-Related-Opportunistic-Infections

Topics: Adjuvants, Immunologic; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; Drug Therapy, Combination; Humans; Rifabutin; Thioacetazone; Tuberculosis

Prospective randomised clinical trial comparing the safety and efficacy of rifampicin- and thiacetazone-containing regimens in human immunodeficiency virus (HIV)-infected adults with pulmonary tuberculosis (TB) at the National Tuberculosis Treatment Centre, Kampala, Uganda.. To assess demographic, clinical and laboratory risk factors associated with toxicity during treatment with streptomycin, thiacetazone and isoniazid (STH) of HIV-1 infected adults with pulmonary TB.. Nested case-control study of all subjects randomized to the STH treatment arm. Baseline demographic, clinical, microbiological, hematological and radiographic characteristics were compared between subjects who developed and those who did not develop adverse drug reactions (ADR).. Of the 90 subjects randomized to STH, 13 developed ADR yielding an incidence rate of 19.6 events per 100 person years of observation (PYO). Eleven of the 13 ADR were cutaneous hypersensitivity reactions, including one fatal case of Stevens-Johnson syndrome. Eight of 13 patients who developed ADR were tuberculin anergic, compared to 12 of 77 patients who did not develop ADR (P < 0.001). An absolute lymphocyte count below 2000 cells/mm3 was also associated with ADR (P = 0.02).. Initial anergy to tuberculin and lymphocytopenia, markers of advanced HIV infection and immunosuppression, were associated with increased risk for adverse drug reactions during STH chemotherapy.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Case-Control Studies; Clonal Anergy; Confidence Intervals; Developing Countries; Drug Eruptions; Drug Therapy, Combination; Female; HIV-1; Humans; Incidence; Jaundice; Lymphopenia; Male; Middle Aged; Odds Ratio; Prospective Studies; Rifampin; Risk Factors; Stevens-Johnson Syndrome; Survival Rate; Thioacetazone; Tuberculosis, Pulmonary; Uganda

A study conducted by the Uganda-Case Western Reserve University Research Collaboration in Kampala, Uganda, a country with high incidence rates of tuberculosis (TB) and human immunodeficiency virus type 1 (HIV-1) infection.. To assess clinical, microbiologic and radiographic factors associated with risk for relapse in HIV-infected adults treated for initial episodes of pulmonary TB.. Nested case-control study within a randomized prospective clinical trial comparing the safety and efficacy of thiacetazone- and rifampicin-containing regimens for TB treatment in HIV-infected adults.. The analysis was based on 119 patients who completed therapy. Median follow-up for all subjects was 22.3 months. Ten patients relapsed a median of 12.7 months after the end of therapy; seven of these were initially treated with the thiacetazone (T)-containing regimen. Each relapse case was matched to four controls by length of follow-up after initial TB treatment. In a univariate analysis risk for relapse was associated with treatment with the T-containing regimen (OR = 4.2, P = 0.08), age > or = 30 yrs (OR = 2.9, P = 0.16), and irregular compliance (OR = 3.6, P = 0.1). Baseline anergy on Mantoux tuberculin skin testing, cavitary disease, radiographic extent of disease and sputum bacillary burden, two month culture negativity, and residual cavitary disease at the end of treatment did not differ between relapses and controls.. Older HIV-1 infected patients, those with poor treatment compliance, and those being treated with T-containing regimens, may be at increased risk for relapse after TB treatment and require closer post-treatment surveillance. Risk for relapse in HIV-infected adults with pulmonary TB after treatment with a nine month rifampicin-containing regimen was low (3.1 per 100 person-years observation) compared with those treated with a thiacetazone-containing regimen (10.1 per 100 person-years observation).

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Case-Control Studies; Developing Countries; Drug Therapy, Combination; Female; Follow-Up Studies; HIV-1; Humans; Logistic Models; Lung; Male; Middle Aged; Patient Compliance; Prospective Studies; Radiography; Recurrence; Rifampin; Risk Factors; Sputum; Survival Rate; Thioacetazone; Tuberculosis, Pulmonary; Uganda

Among HIV-positive patients who received treatment for active tuberculosis, thiacetazone has been associated with cutaneous hypersensitivity and recurrent tuberculosis. No controlled trials have investigated the safety and efficacy of thiacetazone-containing regimens compared with alternative regimens among patients with HIV. In a randomised clinical trial of 191 HIV-positive patients with active pulmonary tuberculosis, we examined the safety and short-term efficacy of isoniazid, rifampicin, and pyrazinamide for two months followed by isoniazid and rifampicin for seven months (RHZ) compared with streptomycin, thiacetazone, and isoniazid for two months followed by thiacetazone and isoniazid for ten months (STH). Between May, 1990, and September, 1991, 191 HIV-positive adult Ugandan patients with acid-fast bacilli sputum smear-positive pulmonary tuberculosis (93% confirmed by culture) received either STH or RHZ. Subjects had a standard evaluation that included Mantoux skin test, complete blood count with differential white blood cell count, and chest radiography. After starting therapy, subjects were followed-up over one year for three outcomes: complications of anti-tuberculosis therapy, early sterilisation of cultures, and survival. Of 191 eligible subjects, 90 received STH and 101 received RHZ. The overall one-year survival was similar for STH and RHZ (65% vs 72%), but when controlled for baseline differences in Mantoux reaction size and absolute lymphocyte count, the relative risk of death for STH compared with RHZ was 1.57 (95% CI 1.0-2.48). Overall, 12 adverse drug reactions occurred in the STH arm (18.2 reactions per 100 person years [PYO]) compared with one in the RHZ arm (1.6 reactions per 100 PYO) for a relative risk of 11.7 (95% CI 1.52-90.0). 10 cutaneous reactions occurred in the STH arm (15.2 events per 100 PYO) compared with one event in the RHZ arm (1.6 events per 100 PYO) for a relative risk of 9.7 (95% CI: 1.24, 75.8). A greater proportion of RHZ patients compared with STH patients had sterilised their sputum within two months (74% vs 37%, p < 0.001). In developing countries, rifampicin-containing regimens should be given, when possible, to HIV-positive patients to reduce drug toxicity and to prolong survival.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Drug Eruptions; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Isoniazid; Male; Middle Aged; Pyrazinamide; Rifampin; Streptomycin; Survival Rate; Thioacetazone; Tuberculosis, Pulmonary; Uganda

Topics: Acetamides; Adult; AIDS-Related Opportunistic Infections; Amoxicillin; Anti-Bacterial Agents; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Clavulanic Acid; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Isoniazid; Linezolid; Mycobacterium bovis; Oxazolidinones; Thioacetazone; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; Drug Eruptions; HIV Infections; HIV-1; Humans; Thioacetazone; Tuberculosis; Virus Replication

Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; Cost Savings; Developing Countries; Humans; Malawi; Stevens-Johnson Syndrome; Thioacetazone; Tuberculosis, Pulmonary

Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; Drug Eruptions; Humans; Thioacetazone; Tuberculosis

Severe skin reactions due to thiacetazone (T) in Human Immunodeficiency Virus (HIV) positive tuberculosis patients have been reported in several publications, one of them from Kenya. However, the abandoning of T may not be feasible in Kenya as this may increase the cost of drugs by about three-fold per regimen.. To compare the cost-effectiveness and total cost of three strategies in which T is replaced with ethambutol (E).. Three strategies are compared with a baseline strategy in which T is not replaced. The indicator for cost-effectiveness is the cost-per-averted-death attributable to T.. Education of patients on the possibility of side-effects and replacement of T with E is the most cost-effective strategy at HIV prevalence rates of 1-90%. Abandonment of T and replacement with E is the most cost-effective at over 90% HIV prevalence.. In Kenya, education of patients on the possibility of skin reactions should be preferred at low range HIV prevalence rates. Routine HIV testing would be the most attractive strategy in the middle range, and total replacement of T with E is to be preferred in the higher range of HIV prevalence.. In Kenya, the National Leprosy Tuberculosis Programme (NLTP) used previously reported data from Nairobi to compare the cost-effectiveness and total costs of a hypothetical strategy with three intervention strategies for the prevention and management of severe skin reactions caused by thiacetazone in treating HIV-positive patients with tuberculosis (TB). The hypothetical strategy was continued use of thiacetazone despite adverse skin reactions. The intervention strategies included patient education about possible side effects of anti-TB drugs (discontinue use if skin rash develops, report situation to clinic, replace thiacetazone with ethambutol when other skin diseases have been excluded), abandonment of thiacetazone and replacement with ethambutol, and HIV testing and pre- and post-test counseling. NLTP currently used the education strategy. It assumed a mortality rate of 5%. When the HIV prevalence rate is 1-90%, the education strategy is the most cost-effective strategy. In terms of total costs, the education strategy was also the most inexpensive strategy regardless of the HIV prevalence. At an HIV prevalence rate greater than 65%, the abandonment of thiacetazone strategy was the cheapest strategy. When the assumed mortality rate was 3%, the cost per averted death for the education strategy was reduced from about US$120 to about US$80 and the education strategy became the most cost-effective strategy over the entire range of HIV prevalence. In addition, the cost of HIV testing significantly increased the cost per averted death. Thus, the findings of this study are truly sensitive to different program conditions. Based on these findings, the authors recommended that the education strategy be applied with a range of HIV prevalence of 1-45%, that HIV testing be applied with a range of 46-72%, and that total abandonment be applied with an HIV prevalence greater than 72%.

Topics: AIDS Serodiagnosis; AIDS-Related Opportunistic Infections; Antitubercular Agents; Cost-Benefit Analysis; Drug Eruptions; Health Care Costs; HIV Infections; Humans; Kenya; Patient Education as Topic; Prevalence; Thioacetazone; Tuberculosis

Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; Drug Eruptions; Humans; Thioacetazone; Tuberculosis

Topics: AIDS Serodiagnosis; AIDS-Related Opportunistic Infections; Antitubercular Agents; Drug Costs; Drug Therapy, Combination; HIV Seroprevalence; Humans; Thioacetazone; Tuberculosis; Zambia

Topics: Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Drug Therapy, Combination; Female; HIV Seropositivity; Humans; Male; Patient Compliance; Rifampin; Risk Factors; South Africa; Thioacetazone; Tuberculosis

Tuberculosis is one of the most common infections in Zambian adults and children infected with HIV. In Africa, cutaneous hypersensitivity reactions attributed to thiacetazone during treatment of tuberculosis in adults infected with HIV-I have been well documented. This study monitored adverse drug reactions during treatment for tuberculosis over an 18 month period (1 April 1990 to 31 October 1991) in 237 children with a clinical diagnosis of tuberculosis (125 boys and 112 girls; 88/237 (37%) infected with HIV-I) and 242 control children (149 boys and 93 girls; 26/242 (11%) infected with HIV-I). Twenty two (9%) of the 237 children with tuberculosis developed hypersensitivity skin reactions during the course of treatment. Adverse skin reactions were seen more often in children infected with HIV than in those who were not (odds ratio 11.65, 95% confidence interval 3.07 to 34.88). These represented 19 (21%) of 88 children infected with HIV and three (2%) of 149 children not infected with HIV. These skin reactions occurred after a period of treatment ranging between two and four weeks among 14 children receiving the HST (isoniazid, streptomycin, thiacetazone) regimen and eight children receiving the HSTR (isoniazid, streptomycin, thiacetazone, rifampicin) regimen. Twelve (55%) of the 22 children who reacted adversely to treatment developed the Stevens-Johnson syndrome. All 12 of these children with the Stevens-Johnson syndrome were infected with HIV. The mortality among these children who developed the Stevens-Johnson syndrome was 91% (11 of 12 died within three days of the onset of the reaction). No further reactions were observed in the 11 children who recovered from the cutaneous hypersensitivity reactions after thiacetazone was discontinued over a period of six months of further treatment of tuberculosis. The results of this study were in part responsible for the recommendations put forward by the World Health Organization to avoid the use of thiacetazone in the treatment of tuberculosis in children infected with HIV.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Child; Child, Preschool; Drug Eruptions; Female; HIV Seropositivity; HIV-1; Humans; Incidence; Infant; Male; Prospective Studies; Stevens-Johnson Syndrome; Thioacetazone; Time Factors; Tuberculosis; Zambia

There is evidence that in human immunodeficiency virus 1 (HIV-1) infected patients with tuberculosis the rate of recurrence of tuberculosis is increased in those patients treated with a standard thiacetazone-containing regimen. To assess the impact of HIV-1 on tuberculosis in Kenya, patients with tuberculosis were studied prospectively. After treatment with either a standard thiacetazone plus isoniazid regimen or a short-course thiacetazone-containing regimen, overall recurrence rate of tuberculosis was 34 times greater in 58 HIV-1-positive patients than in 138 HIV-1-negative patients (adjusted rate ratio 33.8, 95% CI 4.3-264). Recurrence in the HIV-1-positive group was strongly associated with a cutaneous hypersensitivity reaction due to thiacetazone during initial treatment (rate ratio 13.2, 95% CI 3.1-56.2). In all patients with a cutaneous hypersensitivity reaction ethambutol was substituted for thiacetazone. No significant association was found between recurrence among HIV-1-positive patients and initial resistance, initial treatment regimen, a diagnosis of AIDS (WHO definition), or poor compliance. DNA fingerprinting suggested that both relapse and new infection may have produced recurrence of tuberculosis. In patients who had a cutaneous hypersensitivity reaction, increased recurrence rate may have been related to interruption of treatment, subsequent poor compliance, or more advanced immunosuppression. Alternatively, a change to the combination of ethambutol and isoniazid in the continuation phase for 11 months only may not be adequate.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Cohort Studies; Drug Eruptions; Drug Therapy, Combination; Ethambutol; Female; HIV Seropositivity; HIV-1; Humans; Isoniazid; Kenya; Male; Recurrence; Risk Factors; Thioacetazone; Tuberculosis

Descriptions in the medical literature of human immunodeficiency virus type 1 (HIV-1) in children with tuberculosis (TB) are scanty. This study determined the seroprevalence of HIV-1 in 237 hospitalized children between the ages of 1 month and 14 years with a clinical diagnosis of TB (125 males and 112 females) and in 242 control children (149 males and 93 females). The overall HIV-1 seroprevalence rate in patients with TB was 37% (88 of 237) compared with 10.7% (26 of 242) among the control group (P < 0.00001: odds ratio 5.37, 95% confidence interval = 3.21 < 5.37 < 9.47). HIV-1 seropositivity in children with TB ranged from 53% (31 of 58) in the 12- to 18-month age group to 14% (9 of 61) in the 10- to 14-year-olds. The risk of TB attributable to HIV infection was 29%. The predominant clinical presentation in both seronegative (84.6%) and seropositive (89.7%) groups was that of pulmonary TB and there were no significant differences in clinical presentation between the two groups of patients. Only 54.8% of the patients attended follow-up clinics regularly whereas 32% were lost to follow-up within 3 months. Bacillus Calmette-Guérin vaccination coverage was 87.3% among TB patients and 90.5% in the controls. No significant differences in B. Calmette-Guérin vaccination rates between the seronegative and seropositive children were seen. Coinfection with HIV and TB in children is now one of the major public health problems in Zambian children.

Topics: Adolescent; AIDS-Related Opportunistic Infections; BCG Vaccine; Child; Child, Preschool; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Seropositivity; HIV-1; Humans; Infant; Isoniazid; Male; Prevalence; Prospective Studies; Streptomycin; Thioacetazone; Treatment Outcome; Tuberculosis; Zambia