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 HIVseropositive 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. (N Engl J Med 1995;332:779-84.) From Projet SIDA, Kinshasa, Zaire (J.H.P., M.E.S., Y.B.M., C.B., J.K.M., R.W.R.); the Institute of Tropical Medicine, Antwerp, Belgium (J.H.P., F. Portaels, P.P.); the Belgian Agency for Development and Cooperation, Brussels (J.H.P., J.-C.W.); the Division of HIV and AIDS, Centers for Disease Control and Prevention, Atlanta (M.E.S.); the National Institute of Allergy and Infectious Diseases, Bethesda, Md. (C.B.); the Université Catholique de Louvain, Mont Godinne, Belgium (J.P., F. Pouthier); the Bureau National de la Tuberculose, Kinshasa, Zaire (J.-C.W.); the Centre de Dépistage de la Tuberculose, Kinshasa, Zaire (M.K.); and the Marion Merrell Dow Research Institute, Winnersh, United Kingdom (G.R.). Address reprint requests to Dr. Perriëns at Clinical Research and Product Development, Division of Research and Intervention Development, Global Program on AIDS, World Health Organization, Ave. Appia, CH-1211 Geneva 27, Switzerland. Supported by Projet SIDA with contributions from the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the Armed Forces Institute of Pathology (Washington, D.C.), and the Agency for Development and Cooperation (Brussels), with additional contributions from the Marion Merrell Dow Research Institute and the Belgolaise Bank (Brussels). I N 1988, when this study was planned, the recommendation of the Centers for Disease Control and Prevention for the treatment of known or suspected tuberculosis in patients with human immunodeficiency virus (HIV) infection was that at least three drugs (isoniazid, rifampin, and pyrazinamide) should be used during the first two months, with the addition of ethambutol in cases of disseminated disease or suspected resistance to isoniazid. Treatment for nine months was recommended, or for at least six months after conversion to a positive culture, although it was recognized that the optimal duration of therapy was unknown. 1 There was no specific recommendation for the use of intermittent therapy (therapy administered two or three times weekly), which is known to be effective in patients without HIV infection. 2-5 This study was conducted to compare the efficacy of a six-month, partly intermittent regimen for tuberculosis (administered daily during the first two months and then twice weekly) among HIV-infected and HIV-uninfected patients with pulmonary tuberculosis and to determine whether an additional six months of antituberculous chemotherapy improves outcomes among HIV-infected patients.