thioacetazone and HIV-Infections

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

TB Treatment Centre, Kampala, Uganda.. To evaluate the impact of human immunodeficiency virus (HIV) co-infection on the bacteriologic and radiographic presentation of pulmonary tuberculosis (TB) in Uganda, a nation with high rates of Mycobacterium tuberculosis and HIV infection.. To compare baseline characteristics among HIV-infected and non-HIV-infected adults with initial newly-diagnosed episodes of culture-confirmed pulmonary TB screened for participation in a randomized prospective TB treatment trial.. Negative and paucibacillary (very scanty or scanty) sputum acid fast bacilli (AFB) smears were more frequent in HIV-infected patients presenting with pulmonary TB (P = 0.007). More HIV-infected individuals also had sputum cultures that required 7-8 weeks incubation until positivity than non-HIV-infected patients (P < 0.01). Lower lung field and diffuse pulmonary infiltrates were more frequent among HIV-infected patients. Rates of atypical X-ray presentations and cavitary disease were comparable between HIV-seropositive and -seronegative patients; however, atypical disease was more frequent in HIV-infected patients with small tuberculin reactions or tuberculin anergy (PPD = 0 mm).. HIV co-infection was associated with a higher frequency of negative and paucibacillary sputum AFB smears. The differences in the diagnostic yields of microscopy and culture between HIV-infected and non-HIV-infected individuals were small and do not, in our opinion, significantly affect the utility of these important diagnostic tests in developing countries. Examining more than one sputum specimen and monitoring cultured specimens for a full 8 weeks may assist in optimizing the diagnostic yield. Upper lobe infiltrates and cavitary disease are still the most frequent radiographic presentations of pulmonary TB in HIV-infected and non-HIV-infected adults in countries with a high prevalence of TB.

Topics: Adult; Antibiotics, Antitubercular; Antitubercular Agents; HIV Infections; HIV-1; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Prospective Studies; Radiography; Randomized Controlled Trials as Topic; Sputum; Thioacetazone; Tuberculosis, Pulmonary; Uganda

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

We have studied the relationship between the plasma concentration-time profile of thiacetazone over the 24 h between doses [AUC(0.24h)] and the incidence of cutaneous reactions among HIV-infected patients with tuberculosis in Kenya. Cutaneous reactions due to thiacetazone occurred in 4/14 [28.6%] HIV+ve patients compared with 3/47 [6.4%] HIV-ve patients [RR = 4.48, 95% CI-1.1 to 17.7], and all resolved on alternative therapy. Among the HIV+ve patients, those with cutaneous reactions had higher AUC(0.24h) values, although the difference was not significant. These results do not exclude pharmacokinetic change as being at least partly responsible for cutaneous reactions to TCZ in HIV+ve patients, and do not refute an immunological basis for the reaction. With regard to the operational use of TCZ in Africa, there is no indication that a modification of the dose will reduce the frequency of drug reactions.

Topics: Adolescent; Adult; Antitubercular Agents; Female; HIV Infections; Humans; Male; Middle Aged; Skin; Thioacetazone; Tuberculosis

Evidence from many countries suggests an association of human immunodeficiency virus (HIV) infection and tuberculosis of major public health significance. In order to begin assessing the impact of HIV on tuberculosis in Kenya, we have determined the HIV-1 seroprevalence among tuberculosis patients and compared the clinical characteristics of tuberculosis in HIV-positive and HIV-negative patients in two cross-sectional studies at the Infectious Disease Hospital (IDH) and the Ngaira Avenue Chest Clinic (NACC), Nairobi, Kenya. The diagnosis in 92% of all patients with pulmonary tuberculosis was confirmed by culture. The remainder were diagnosed on histological, clinical or radiological grounds. HIV seroprevalence among tuberculosis patients at IDH was 26.5% (52/196) compared to 9.2% (18/195) at NACC (P less than 0.001). There was no association between numbers of streptomycin injections in the previous 5 years and HIV infection. Positive sputum smear rates in HIV-positive patients were slightly lower than in HIV-negative patients at both study sites (71% vs 83% at IDH and 73% vs 82% at NACC) but the difference was not significant. Only Mycobacterium tuberculosis was isolated. Miliary disease was not associated with HIV infection. Persistent diarrhoea, oral candidiasis, generalized itchy rash, herpes zoster and generalized lymphadenopathy were all associated with HIV infection, but 46% (95% CI:38-54%) of all HIV-positive patients had none of the clinical features listed in the WHO Clinical Criteria for the Diagnosis of AIDS, apart from fever, cough and weight loss. Stevens-Johnson Syndrome was reported in 7/52 (13%) patients with HIV infection, and in 4/144 (3%) patients without (RR 4.85, 95% CI: 1.45-15.88).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Cross-Sectional Studies; Drug Combinations; Drug Therapy, Combination; Female; HIV Infections; HIV Seroprevalence; Humans; Isoniazid; Kenya; Male; Middle Aged; Opportunistic Infections; Risk Factors; Streptomycin; Thioacetazone; Tuberculosis, Pulmonary