Twice weekly tuberculosis preventive therapy in HIV infection in Zambia

Figures show that in 1994 25-32% of childbearing women in Zambias urban areas were infected with HIV. Latent tuberculosis (TB) infection is also common in the region. TB is an HIV-associated infection which is both curable and preventable. Evidence also indicates that TB may precipitate the progression of HIV disease through immune activation. A randomized double-blind placebo-controlled trial was conducted to estimate the efficacy of preventive therapy for TB in HIV-infected adults in Lusaka. During a 2-year period 1053 HIV-positive individuals with no evidence of clinical TB were randomly assigned to receive 6 months of isoniazid twice weekly (H) or 3 months of rifampicin twice per week (R) plus pyrazinamide (Z) or a placebo. Therapy was taken twice per week and was self-administered. Study subjects were followed for 1631 person-years for a median of 1.8 years. The treatment of 29 subjects was stopped due to adverse drug reactions. 59 cases of TB and 37 of probable TB were diagnosed during the study period and 185 deaths were reported. 115 subjects (11%) failed to return to the study clinic at any time after enrollment. The incidence of TB was lower among subjects in the H and RZ groups than it was among those receiving placebo as was the incidence of TB/probable TB. The effect of preventive therapy was greater among subjects with a tuberculin skin test (TST) of 5 mm or greater among those with a lymphocyte count of 2x10(9)/l or higher and in those with hemoglobin of 10 g/dl or higher. There was no difference in mortality rates between the preventive therapy and placebo groups. The effect of preventive therapy declined after the first year of the study so that by 18 months the rates of TB in the treated groups were similar to those in the placebo group.