EFFECT OF ISONIAZID PROPHYLAXIS ON INCIDENCE OF ACTIVE TUBERCULOSIS AND PROGRESSION OF HIV-INFECTION

Tuberculosis occurring with human immunodeficiency virus (HIV) infecti on is a serious and growing public health problem. We have carried out a randomised clinical trial of a 12-month course of isoniazid plus vi tamin B6 versus vitamin B6 alone in Port-au-Prince, Haiti, to assess t he efficacy of isoniazid in preventing active tuberculosis in symptom- free HIV-infected individuals. The effect of prophylaxis on the develo pment of HIV disease, AIDS, and death was also investigated. 118 subje cts were assigned treatment with isoniazid plus B6 (n=58) or B6 alone (n=60) between 1986 and 1989. The treatment groups were similar at stu dy entry in demographic, clinical, and immunological characteristics. Interim analysis in 1990 revealed no significant difference in tubercu losis outcome measures. Follow-up was continued until 1992, at which t ime significant protection by isoniazid against the development of tub erculosis was apparent, both for the whole study population and for su bjects positive for purified protein derivative of tuberculin (PPD). T he incidence of tuberculosis was lower in isoniazid recipients than in patients who received B6 alone (2.2 vs 7.5 per 100 person-years). The relative risk of tuberculosis was 3.4 (95% CI 1.1-10.6) for B6 alone versus isoniazid plus B6 (p<0.05). Isoniazid also delayed progression to HIV disease and AIDS and death. Thus isoniazid effectively decrease s the incidence of tuberculosis and delays the onset of HIV-related di sease in symptom-free HIV-seropositive individuals. Isoniazid prophyla xis should be considered for HIV-seropositive, PPD-positive subjects, and may also be appropriate for PPD-negative patients in areas where t uberculosis is highly endemic.