Pulmonary tuberculosis in HIV-infected patients in Zaire. A controlled trial of treatment for either 6 or 12 months.

BACKGROUND: We studied the efficacy of a short-course regimen of chemotherapy for pulmonary tuberculosis in Kinshasa, Zaire. We also assessed whether, among patients with human immunodeficiency virus (HIV) infection, treatment should be extended from 6 to 12 months. METHODS: HIV-seropositive and HIV-seronegative outpatients with pulmonary tuberculosis were treated with rifampin, isoniazid, pyrazinamide, and ethambutol daily for two months, followed by rifampin plus isoniazid twice weekly for four months. The HIV-positive patients who had no evidence of tuberculosis were then randomly assigned to receive either rifampin plus isoniazid or placebo twice weekly for a further six months. We also followed a comparison group of HIV-seronegative patients who received no further treatment for tuberculosis after six months. RESULTS: After six months, 260 of 335 HIV-seropositive and 186 of 188 HIV-seronegative participants could be evaluated, and their rates of treatment failure were similar: 3.8 and 2.7 percent, respectively. At 24 months, the HIV-seropositive patients who received extended treatment had a relapse rate of 1.9 percent, as compared with 9 percent among the HIV-seropositive patients who received placebo for the second 6 months (P < 0.01). Extended treatment did not improve survival, however. Among the HIV-seronegative patients, 5.3 percent relapsed. CONCLUSIONS: Among HIV-seropositive patients with pulmonary tuberculosis, extending treatment from 6 to 12 months reduces the rate of relapse but does not improve survival. The six-month program of partly intermittent antituberculous treatment may be an acceptable alternative when resources are limited.

Spectrum of immunodeficiency in HIV-1-infected patients with pulmonary tuberculosis in Zaire.

Tuberculosis (TB) is the most common opportunistic infection in African patients who die from AIDS, yet the stage of immunodeficiency at which TB develops is uncertain. We studied the immune status of HIV-infected outpatients with pulmonary TB in relation to their clinical presentation in a cross-sectional study of 216 HIV-seropositive and 146 HIV-seronegative ambulatory incident cases of smear-positive and culture-positive pulmonary TB in Kinshasa, Zaire. HIV-seropositive and seronegative patients had median CD4 lymphocyte counts of 316.5/microL and 830.5/microL, respectively. Of the HIV-seropositive patients, 32.9% had less than 200 CD4 lymphocytes/microL, 37% between 200 and 499, and 30.1% 500 or more. Clinical AIDS, as defined by the WHO clinical case-definition or a modified version, was of similar limited use as a predictor of immunodeficiency. Among HIV-seropositive patients, oral candidosis, lymphopenia, a negative tuberculin purified protein derivative test, and cutaneous anergy were strongly associated with CD4 counts of less than 200/microL, and seemed to be better markers of immune dysfunction. We conclude that pulmonary TB develops across a broad spectrum of HIV-induced immunodeficiency and that a diagnosis of pulmonary TB is of limited use as a marker of stage of HIV disease in African HIV-infected outpatients.

PIP: Between March 1989 and September 1991, physicians compared CD4 lymphocyte counts of 216 HIV-seropositive patients whose sputum smears tested positive for pulmonary tuberculosis (TB) with those of 146 HIV- negative patients who also tested positive for TB at a TB screening center in Kinshasa, Zaire. The researchers wanted to investigate the immune status of HIV-infected outpatients with pulmonary TB in relation to clinical criteria. HIV seropositive patients had much lower CD4 lymphocyte counts than did HIV seronegative patients (total CD4 count, 316.5/mcl vs. 830.5/mcl; CD4 count, 13% vs. 36%; p .001). 90.4% of HIV-positive patients had CD4 counts 800 compared with 48% of HIV- negative patients. 32.9% of HIV-positive patients had CD4 counts 200 while just 1.4% of HIV-negative patients did. As CD4 counts fell, weight loss, diarrhea during the previous month, past or present herpes zoster, and oral candidosis occurred more frequently (p = .004 for oral candidosis and p = .02 for the rest). Negative purified protein derivative RT23 (PPD) tests and cutaneous anergy occurred more often as immunodeficiency rose (p .001). Increased immunosuppression was also characterized by no detectable cavitation on chest radiography, anemia, and low total lymphocyte counts (p = .02 for absence of cavitation and p .001 for the others). These results suggested that pulmonary TB occurred along the continuum of immunodeficiency as defined by CD4 counts. Thus, it is not likely to be a marker of the severity of HIV infection. Instead weight loss, diarrhea during the previous month, past or present herpes zoster, oral candidosis, negative PPD test and cutaneous anergy, absence of detectable cavitation on chest radiography, anemia, and low total lymphocyte appeared to be better markers of the severity of HIV-related immunodeficiency.

Increased mortality and tuberculosis treatment failure rate among human immunodeficiency virus (HIV) seropositive compared with HIV seronegative patients with pulmonary tuberculosis treated with "standard" chemotherapy in Kinshasa, Zaire.

To evaluate their treatment outcomes 170 human immunodeficiency virus (HIV) seropositive and 597 HIV seronegative patients with active pulmonary tuberculosis (TB) treated for 1 yr with "standard" chemotherapy, including streptomycin, isoniazid, and, in most cases, thiacetazone, were traced at completion of therapy. All 582 survivors were invited for reevaluation, and 385 patients, of whom 82 (21.3%) were HIV seropositive, were evaluated. Of those, 325 consenting patients, of whom 67 (20.6%) were HIV seropositive, were followed for 12 months. One year after TB had been diagnosed 47 (31.3%) of the 150 HIV seropositive and 22 (4.4%) of the 501 HIV seronegative patients traced had died (p = 10(-6]. During the subsequent year the mortality of 67 HIV seropositive patients (26.3/100 patient-years) was higher than that of the 303 HIV seronegative patients (2.2/100 patients-years, p = 10(-6]. HIV seropositive patients had a higher overall TB therapy failure rate 24 months after the diagnosis of TB than did HIV seronegative patients (21.1/100 patient-years versus 8.1/100 patient-years, p = 0.002), mainly because their relapse rate of pulmonary TB (18.1/100 patient-years) was higher than that of HIV seronegative patients (6.0/100 patient-years, p = 0.03). Given their higher relapse rate after 1 yr of "standard" chemotherapy, the public health impact of routine maintenance therapy in HIV seropositive patients with pulmonary TB who complete such therapy should be assessed in comparison to the introduction of rifampicin-based short-course antituberculosis chemotherapy in developing countries.

A retrospective cohort study of the risk of tuberculosis among women of childbearing age with HIV infection in Zaire.

To determine the risk of active tuberculosis associated with HIV infection, we retrospectively studied a cohort of HIV-seropositive and HIV-seronegative women participating in an HIV perinatal transmission study in Kinshasa, Zaire. After a median follow-up of 32 months, new cases of proven pulmonary or clinically diagnosed tuberculosis occurred in 19 of the 249 HIV-seropositive women (7.6%, 3.1 cases per 100 person-years) compared with 1 of the 310 HIV-seronegative women (0.3%, 0.12 cases per 100 person-years), for a relative risk of 26 (95% confidence interval, 5 to 125). Proven pulmonary tuberculosis was diagnosed in 7 HIV-seropositive women (2.8%, 1.2 cases per 100 person-years) and 1 HIV-seronegative woman (0.3%, 0.12 cases per 100 person-years), for a relative risk of 10 (95% confidence interval, 1.5 to 47). We estimated that 66 cases of proven pulmonary tuberculosis in 100,000 person-years of follow-up in women of childbearing age could be attributed to HIV; this is 35% of their estimated total incidence of proven pulmonary tuberculosis. Among those followed for 2 yr, 27 (11%) of 243 HIV-seropositive women died during 2 yr of follow-up compared with none of 296 HIV-seronegative women (p less than 0.001). In HIV-seropositive women with proven or clinically diagnosed tuberculosis mortality was even higher: 5 (26%) of the 19 HIV-seropositive women with proven pulmonary or clinically diagnosed tuberculosis died during follow-up compared with 22 (10%) of the 224 HIV-seropositive women not diagnosed as having tuberculosis (relative risk 2.7; 95% confidence interval, 1.1 to 6.3).(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparison of 2 culture media for the isolation of Mycobacterium tuberculosis]. / Comparaison de deux milieux de culture pour l'isolement de mycobactéries tuberculeuses.

In Kinshasa, Zaire, 392 positive cultures were used to compare the isolation of mycobacteria on two different culture media (Löwenstein-Jensen and Ogawa (1%) with egg yolk). Although the Ogawa medium is reknown for being well adapted to the growth of atypical mycobacteria, we did not isolate more atypical mycobacteria from the tuberculous population of Kinshasa on Ogawa than were isolated in the previous years on Löwenstein-Jensen. However, significantly more M. tuberculosis were isolated on Ogawa (95% versus 88.4% on Löwenstein-Jensen). Other factors permitting, the use of the Ogawa medium is recommended.

HIV infection in patients with tuberculosis in Kinshasa, Zaire.

To better define the interrelationship of infection with human immunodeficiency virus (HIV) and tuberculosis (TB), we conducted three HIV serosurveys of inpatients and outpatients with confirmed or suspected TB in Kinshasa, Zaire. HIV seroprevalence in hospitalized sanatorium patients did not change significantly in serosurveys conducted in 1985 and 1987 (92/231 [40%] versus 85/234 [36%]). These proportions were significantly higher than the 17% HIV seroprevalence observed in a 1987 serosurvey of 509 consecutive patients with an initial diagnosis of pulmonary TB seen at an outpatient TB diagnostic center in Kinshasa (p less than 0.001). HIV seroprevalence was higher in sanatorium patients with extrapulmonary TB (22/46 [48%]) and suspected pulmonary TB (60/132 [45%]) than in patients with bacteriologically confirmed pulmonary TB (94/287 [33%]) (p less than 0.02). Mycobacterium sputum isolation rates were similar in HIV-seropositive (28/34 [82%]) and HIV-seronegative patients (135/159 [85%]). All isolates were Mycobacterium tuberculosis. Eighteen (21%) of 84 HIV-seropositive sanatorium patients in 1987, who were followed for two months after admission, had died, compared with 11 (9%) of 128 HIV-seronegative patients (p less than 0.01). However, clearance rates of acid-fast bacilli from sputum after standard therapy were equally good in HIV-seropositive and HIV-seronegative survivors. With the growing AIDS problem, the serious TB burden in sub-Saharan Africa may become even more onerous and may critically overload the stressed African health care systems.