The impact of human immunodeficiency virus on response to treatment and recurrence rate in patients treated for tuberculosis: two-year follow-up of a cohort in Lusaka, Zambia.

To examine the effect of HIV on response to treatment and recurrence rate in patients with tuberculosis (TB), we have followed 239 previously untreated, adult, TB patients in a prospective cohort study in Lusaka, Zambia. One hundred and seventy-four (73%) were HIV-1 antibody positive. Patients with sputum smear positive, miliary, or meningeal TB were prescribed 2 months daily streptomycin, thiacetazone, isoniazid, rifampicin, pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. Thirty-five per cent of HIV-positive (HIV+ve) and 9% of HIV-negative (HIV-ve) patients were known to have died before the scheduled end of treatment. Surviving HIV+ve patients showed weight gain and improvement in symptoms and laboratory and radiological findings similar to HIV-ve patients. The risk of cutaneous drug reaction was 17% (95% CI: 12-25%) in HIV+ve, and 4% (1-13%) in HIV-ve patients. Severe rashes were attributed to thiacetazone. Recurrence of active TB was examined among 64 HIV+ve and 37 HIV-ve patients who successfully completed treatment, with mean follow-up after the end of treatment of 13.5 and 16.8 months, respectively. The rate of recurrence was 22/100 person years (pyr) for HIV+ve patients and 6/100 pyr for HIV-ve patients, giving a recurrence rate ratio of 4.0 (95% CI 1.2-13.8, P = 0.03).

PIP: In 1989, researchers followed 239 newly diagnosed adult patients with tuberculosis (TB), never previously treated for TB, for two years to examine the response to TB treatment among patients with and without HIV infection and the TB recurrence rate. They were patients in the medical wards and the chest clinic outpatients' department of the University Teaching Hospital in Lusaka, Zambia. 174 (73%) tested positive for HIV. HIV-positive patients were more likely than HIV-negative patients to have extrapulmonary and both pulmonary and extrapulmonary TB (35% and 26% for both, respectively vs. 17% and 12%, respectively; p 0.001). They were less likely to have positive sputum tests than HIV-negative patients (36% vs. 57% for smear; p = 0.005 and 39% vs. 55% for culture; p = 0.03). HIV-positive patients were more likely to receive standard TB therapy (62% vs. 37%), while HIV-negative patients were more likely to receive short course therapy (62% vs. 37%; p = 0.001). HIV-positive patients were more likely than HIV-negative patients to die before completion of treatment (35% vs. 9%). Surviving HIV-positive patients gained weight and experienced improvement in symptoms at the same rate as did surviving HIV-negative patients. They also had similar laboratory and radiological findings. HIV-positive patients had a higher risk of cutaneous drug reaction than HIV-negative patients (17% vs. 4%; hazard ratio = 5.1; p = 0.03). One HIV-positive patient with a rash died. Thiacetazone was responsible for the rashes. Among the HIV-positive and HIV-negative patients who successfully completed treatment, the active TB recurrence rate was greatest for HIV-positive patients (22 vs. 6/100 person years; rate ratio = 4; p = 0.03). Yet, all but one of the HIV-positive cases with recurrent TB responded well to TB treatment. High recurrence rates pose renewed potential sources of infection and a high cost of renewed treatment.

The impact of human immunodeficiency virus on mortality of patients treated for tuberculosis in a cohort study in Zambia.

We have examined the impact of human immunodeficiency virus (HIV) on mortality of patients treated for tuberculosis in a prospective study in Lusaka, Zambia. Patients with sputum smear-positive, miliary, or meningeal tuberculosis were prescribed 2 months' daily streptomycin, thiacetazone, isoniazid, rifampicin, and pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. 239 patients (65 HIV-negative and 174 HIV-positive) were followed to 2 years from start of treatment. The crude mortality rate ratio for HIV-positive compared with HIV-negative patients over 2 years was 5.00 (95% confidence interval 2.30-10.86). Median survival for HIV-positive patients from the start of treatment was 22 months. At least 34% of HIV-positive patients for whom cause of death was known died from tuberculosis, three-quarters of these during the first month of treatment. Risk factors for death in HIV-positive patients included multi-site tuberculosis, history of prolonged diarrhoea or fever, oral thrush, splenomegaly, anergy to tuberculin, low weight, anaemia or lymphopenia, and poor compliance with regimens containing rifampicin and pyrazinamide. Tuberculosis, even treated, was a major cause of death in patients with HIV infection.

PIP: The impact of HIV on mortality is described in a prospective study of tuberculosis patients in Lusaka, Zambia, where more than 70% of newly diagnosed tuberculosis patients have concurrent HIV infection. Patients attending the University Teaching Hospital in Lusaka, Zambia, were recruited to a prospective cohort study from April to December 1989. Of the 239 patients included in the follow-up study, 174 (73%) were HIV-1 positive by ELISA. A higher proportion of HIV-positive patients were 25-34 years old, and they more often had a negative tuberculin response, anemia, or lymphopenia at recruitment. The probability of survival for HIV-negative and HIV-positive patients was, respectively: at 2 months 95% and 89%; at 6 months 95% and 76%; at 12 months 91% and 66%; at 18 months 87% and 55%; and at 24 months 87% and 48%. The median survival of HIV-positive patients was 22 months. The crude, 2-year mortality rate ratio for HIV-positive compared with HIV-negative patients was 5 (p 0.001). Mortality was higher for patients with both pulmonary and extrapulmonary disease than for those with either pulmonary or extrapulmonary disease alone; for individual sites, only lymph node disease was associated with a significantly higher mortality than other sites (p = 0.01). At presentation prolonged fever, prolonged diarrhea, oral Candida or splenomegaly, negative tuberculin response, anemia or lymphopenia and low weight were associated with higher mortality. Among the 39 patients seen at 2 months who had been prescribed short-course chemotherapy, subsequent mortality was lower in the group who reported receiving all 60 doses of either rifampicin or pyrazinamide or both (20 patients) than among those who had not (19 patients¿ (rate ratio 0.24, p = 0.02). 47 of the 81 patients died within 24 months of the start of treatment, 5 HIV-negative and 42 HIV-positive. 3 of 5 HIV-negative patients for whom information was available died of active tuberculosis. Among HIV-positive patients, 14 of 42 died of active tuberculosis and 2 more of complications of tuberculosis.

The impact of HIV on infectiousness of pulmonary tuberculosis: a community study in Zambia.

OBJECTIVE: To examine the impact of HIV on infectiousness of pulmonary tuberculosis (TB). DESIGN: A cross-sectional tuberculin survey carried out among household contacts of HIV-1-positive and negative patients with bacteriologically confirmed pulmonary TB. Contacts were also examined for active TB. SETTING: Index cases were recruited from patients attending the University Teaching Hospital in Lusaka, Zambia and household contacts were examined during visits to their homes within Lusaka. PATIENTS, PARTICIPANTS: A total of 207 contacts of 43 HIV-positive patients, and 141 contacts of 28 HIV-negative patients with pulmonary TB were examined. MAIN OUTCOME MEASURES: Proportion of contacts of HIV-positive and negative index cases with a positive tuberculin response (diameter of induration > or = 5 mm to a dose of 2 tuberculin units). RESULTS: Fifty-two per cent of contacts of HIV-positive pulmonary TB patients had a positive tuberculin response compared with 71% of contacts of HIV-negative patients (odds ratio, 0.43; 95% CI, 0.26-0.72; P < 0.001). This difference persisted after allowing for between-household variations in the tuberculin response. Tuberculin response in the contact was related to age of contact, intimacy with the index case and crowding in the household. However, the effect of HIV status of the index case was not confounded by these variables. Tuberculin response in the contact was also related to the number of bacilli seen in the sputum smear of the index case which partially explained the effect of HIV status of the index case. Active TB was diagnosed in 4% of contacts of HIV-positive and 3% of contacts of HIV-negative cases, respectively (P = 0.8). CONCLUSIONS: HIV-positive patients with pulmonary TB may be less infectious than their HIV-negative counterparts and this may partly be explained by lower bacillary load in the sputum.

PIP: Between April and December 1989, the chest clinic of the University Teaching Hospital in Lusaka, Zambia, confirmed pulmonary tuberculosis (TB) in 141 adults, 95 (67%) of whom were HIV-1 seropositive. Health workers made home visits to 71 of the index cases (43 HIV-1 positive and 28 HIV-1 negative) to learn whether the 348 household members would also develop TB, thus allowing researchers to determine the effect of HIV on infectiousness of TB. Contacts of HIV-1 positive patients developed TB at a lower rate than did those of HIV-1 negative patients (52% vs. 71%; odds ratio [OR] = 0.43; p .001). This difference continued even after controlling for between-household variations, indicating that confounding variables did not account for the difference. Age of contact, intimacy with the index case, and crowding in the household were associated with the tuberculin response in the contact, but they did not confound the effect of HIV status. Tuberculin response in the contact was associated with the number of bacilli in the sputum smear (crude OR = 3.13; p = .013, and adjusted OR =1.84; p = .28), suggesting that the number of bacilli somewhat explained the difference in infectiousness between HIV-1 positive and HIV-1 negative patients. 12 contacts (8 of HIV-positive cases and 4 of HIV-negative cases) developed active TB after the TB diagnosis in the index case. These findings clearly demonstrated that infection with Mycobacterium tuberculosis was less likely in household members of HIV-1 positive cases than in those of HIV-1 negative cases. The lower bacillary load in the sputum in HIV- 1 cases may have accounted somewhat for the lower infectiousness of pulmonary TB.

The impact of human immunodeficiency virus on presentation and diagnosis of tuberculosis in a cohort study in Zambia.

Two hundred and forty-nine patients with tuberculosis were recruited to a cohort study to investigate the interaction between tuberculosis and HIV in Lusaka, Zambia; findings at presentation are presented here. One hundred and eighty-two (73%; 95% confidence interval 67-79%) of the cases were HIV-1 antibody positive. The diagnosis of tuberculosis was confirmed by microscopy for acid-alcohol fast bacilli, culture of Mycobacterium tuberculosis, or histology in 74% of all cases. HIV negative and positive cases differed in site of disease: among HIV negative patients 72% had pulmonary disease alone, 16% extrapulmonary disease alone and 12% had both, whereas among HIV positive patients 40% had pulmonary disease alone, 34% extrapulmonary disease alone and 26% both (P < 0.001). HIV negative and positive cases were compared with regard to outcome of diagnostic procedures: 55% of HIV negative cases could be diagnosed at enrollment by sputum smear, but only 35% of HIV positive cases (P < 0.01). Among pulmonary cases confirmed by sputum culture, 76% of HIV negative patients had a positive sputum smear, compared with 57% of HIV positive patients (P = 0.09). Pleural and pericardial disease were difficult to confirm, but culture of pleural fluid was positive in 12/46 HIV positive patients, compared with 0/11 HIV negative patients. Lymph node disease was readily confirmed by biopsy. The tuberculin test was positive in only 30/110 (27%) of HIV positive cases, but in 21/38 (55%) of HIV negative cases (P < 0.01). Mycobacterium tuberculosis was cultured in 57% of HIV negative cases and 54% of HIV positive cases; no atypical mycobacteria were isolated. Initial resistance to isoniazid was present in isolates from 5% of cases with a positive culture.

Use of prednisolone in the treatment of HIV-positive tuberculosis patients.

Corticosteroids are beneficial in the treatment of some forms of tuberculosis, but their role in TB affecting HIV-positive patients is not clear. During a cohort study of tuberculosis patients in Lusaka, Zambia, prednisolone was prescribed for specific indications. Six of 47 (13 per cent) of patients who received prednisolone early in treatment developed herpes zoster, compared with 2 of 118 (2 per cent) of those who did not. Three patients who received prednisolone developed Kaposi's sarcoma, compared with none who did not. At 2 months patients who had received prednisolone showed a greater improvement in generalized lymphadenopathy and cough. Controlled studies of the risks and benefits of administration of corticosteroids to HIV-positive TB patients are urgently needed.

Impact of HIV on tuberculosis in Zambia: a cross sectional study.

OBJECTIVE: To examine the contribution of HIV infection to the apparently increasing incidence of tuberculosis in central Africa. DESIGN: Cross sectional study. SETTING: Outpatient clinic in teaching hospital, Lusaka, Zambia. PATIENTS: 346 Adult patients with tuberculosis. RESULTS: Overall, 206 patients (60%; 95% confidence interval 54% to 65%) were positive for HIV: in one or both assays used. The peaks for both tuberculosis and HIV infection were among men aged 25-34 years and women aged 14-24 years. Of patients with confirmed pulmonary tuberculosis, 73/149 (49%; 41% to 57%) were positive for HIV; 67/83 (81%; 70% to 89%) patients with pleural disease and 16/19 (84%; 60% to 97%) patients with pericardial disease were positive. HIV positive patients with positive sputum culture were less likely to have had a positive sputum smear, and their chest x ray films less often showed classic upper zone disease or cavitation. Of 72 patients who fulfilled clinical criteria for AIDS, 17 were negative for HIV. CONCLUSIONS: The high prevalence of HIV in patients with tuberculosis suggests that an epidemic of reactivating tuberculosis is arising in those who are infected with HIV. The redirection of public health priorities towards tuberculosis would focus on a major treatable and preventable complication of the AIDS epidemic.

PIP: To examine the contribution of HIV infection to the apparently increasing incidence of tuberculosis patients of an outpatient clinic in a teaching hospital in Lusaka, Zambia. Overall, 206 patients (60%) tested positive for HIV. The peaks for both tuberculosis and HIV infection were among men aged 25-34 years and women aged 14-24 years. Of patients with confirmed pulmonary tuberculosis, 49% were positive for HIV. 81% of patients with pleural disease and 84% of patients with pericardial disease were positive. HIV positive patients with a positive sputum culture were less likely to have had a positive sputum smear, and their chest x-ray films less often showed classic upper zone disease or cavitation. Of 72 patients who fulfilled clinical criteria for AIDS, 17 were negative for HIV. In conclusion, the high prevalence of HIV in patients with tuberculosis suggests that an epidemic of reactivating tuberculosis is arising in those who are infected with HIV. The redirection of public health priorities towards tuberculosis would focus on a major treatable and preventable complication of the AIDS epidemic.