thioacetazone and Acquired-Immunodeficiency-Syndrome

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

Concurrent infection with HIV-1 and Mycobacterium tuberculosis is increasingly common in East Africa. In the past, a drug regimen consisting of 2 months of intramuscular streptomycin plus 12 months of isoniazid and thiacetazone has been used in tuberculosis control programs with acceptable efficacy and low incidence of adverse reactions. Anecdotal reports of increasing cases of Stevens-Johnson syndrome prompted a 2 month prospective search for cases of severe cutaneous hypersensitivity reactions at Muhimbili Medical Centre in Dar es Salaam, Tanzania. Five such patients were admitted to a single ward during this time, 4 of whom were HIV-seropositive and all of whom were being treated with isoniazid and thiacetazone. These findings have implications for the management of tuberculosis in East Africa and perhaps other countries with high prevalence of both HIV-1 and tuberculosis.. Concurrent infection with HIV-1 and Mycobacterium tuberculosis (TB) is increasingly common in East Africa. In HIV-infected individuals, pulmonary TB tends to occur before the onset of opportunistic infections. A common treatment regimen in developing countries is two months of intramuscular streptomycin combined with twelve months of isoniazid and thiacetazone. TB control programs have found this approach to be of acceptable efficacy with a low incidence of adverse reactions. Anecdotal reports of increasing cases of Stevens-Johnson syndrome, however, prompted a two-month prospective search for cases of severe cutaneous hypersensitivity reactions at Muhimbili Medical Center in Dar es Salaam, Tanzania. Five such patients were admitted to an hospital ward over the two-month period, four of whom were HIV-seropositive and all of whom were being treated with isoniazid and thiacetazone. Two were also receiving streptomycin. Four had extensive mucosal involvement of the eyelids, lips, and mouth, consistent with Stevens-Johnson syndrome. The remaining patient had bullous skin lesions, without mucosal involvement, consistent with an exfoliative dermatitis. On admission, medications were discontinued and patients underwent routine management, including the administration of steroids. Four patients were discharged from the hospital 3-7 weeks after admission with improved conditions. One patient died suddenly after five weeks of hospitalization due to unknown causes. These patients give extra support to observations that thiacetazone is associated with the increased incidence of severe cutaneous hypersensitivity syndrome in people infected with HIV-1. Further studies are needed to quantify the excess morbidity and mortality resulting from this treatment regimen.

Topics: Acquired Immunodeficiency Syndrome; Adult; Comorbidity; Drug Combinations; Drug Eruptions; Drug Therapy, Combination; Female; HIV-1; Hospitals, University; Humans; Incidence; Isoniazid; Male; Population Surveillance; Prospective Studies; Stevens-Johnson Syndrome; Streptomycin; Tanzania; Thioacetazone; Tuberculosis, Pulmonary