Impact of human immunodeficiency virus type-1 infection on the initial bacteriologic and radiographic manifestations of pulmonary tuberculosis in Uganda. Makerere University-Case Western Reserve University Research Collaboration.

SETTING: TB Treatment Centre, Kampala, Uganda. OBJECTIVE: 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. DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

Risk factors for relapse in human immunodeficiency virus type 1 infected adults with pulmonary tuberculosis.

SETTING: 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. OBJECTIVE: To assess clinical, microbiologic and radiographic factors associated with risk for relapse in HIV-infected adults treated for initial episodes of pulmonary TB. DESIGN: 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. RESULTS: 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. CONCLUSION: 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).

Randomised trial of thiacetazone and rifampicin-containing regimens for pulmonary tuberculosis in HIV-infected Ugandans. The Makerere University-Case Western University Research Collaboration.

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.

Reduced sensitivity of tuberculosis serodiagnosis in patients with AIDS in Uganda.

SETTING: The diagnostic utility of serodiagnosis of tuberculosis in HIV-infected persons was studied in Kampala, Uganda. OBJECTIVE: This study was undertaken to evaluate the utility of a recently described serologic assay for the diagnosis of tuberculosis in HIV-infected patients. DESIGN: The study was undertaken as a cross-sectional survey of 349 subjects, including human immunodeficiency virus-infected and uninfected patients with tuberculosis and control subjects. Serum from each subject was assayed by enzyme-linked immunosorbent assay (ELISA) for IgG antibody to the 30,000 dalton antigen of Mycobacterium tuberculosis. RESULTS: Test sensitivity dropped from 0.62 in non HIV-infected tuberculous patients to 0.28 in HIV-infected patients. CONCLUSIONS: ELISA serodiagnosis of tuberculosis may have a markedly decreased utility in populations where HIV infection is prevalent.

Influence of tuberculosis on human immunodeficiency virus (HIV-1): enhanced cytokine expression and elevated beta 2-microglobulin in HIV-1-associated tuberculosis.

Tuberculosis results in activation of T cells and macrophages that may harbor latent human immunodeficiency virus (HIV-1). Although such activation is beneficial to the host in terms of mycobacterial disease, it may be deleterious in terms of HIV-1. In Ugandan HIV-1-seropositive patients with pulmonary tuberculosis, antigen-induced blastogenesis and production of tumor necrosis factor-alpha (a cytokine that induces expression of HIV-1 in latently infected cells) were 3-10 times greater than in controls. The mean serum beta 2-microglobulin level was 5.22 mg/L in recently diagnosed patients, significantly greater than levels in HIV-negative patients with tuberculosis or asymptomatic HIV-1-seropositive subjects. beta 2-microglobulin was significantly lower in subjects who had completed at least 2 months of antituberculous therapy. These observations suggest that HIV-1-associated tuberculosis is accompanied by immune activation that may result in increased HIV expression and accelerated progression to AIDS.