Effect of tuberculosis preventive therapy on HIV disease progression and survival in HIV-infected adults

Purpose: To determine whether tuberculosis (TB) preventive therapies alter the rate of disease progression to AIDS or death and to identify significant prognostic factors for HIV disease progression to AIDS. Method: In a randomized placebo-controlled trial in Kampala, Uganda, 2,736 purified protein derivative (PPD)-positive and anergic HIV-infected adults were randomly assigned to four and two regimens, respectively. PPD-positive patients were treated with isoniazid (INH) for 6 months (6H; n = 536), INH plus rifampicin for 3 months (3HR; n = 556), INH plus rifampicin plus pyrazinamide for 3 months (3HRZ; n = 462), or placebo for 6 months (n = 464). Anergic participants were treated with 6H (n = 395) or placebo (n = 323). Results: During follow-up, 404 cases progressed to AIDS and 577 deaths occurred. The cumulative incidence of the AIDS progression was greater in the anergic cohort compared to the PPD-positive cohort (p <.0001). Among PPD-positive patients, the relative risk of the AIDS progression with INH alone was 0.95 (95% Cl 0.68-1.32); with 3HR it was 0.83 (95% Cl 0.59-1.17); and with 3HRZ it was 0.76 (95% Cl 0.52-1.08), controlling for significant baseline predictors. Among anergic patients, the relative risk of the AIDS progression was 0.81 (95% Cl 0.56-1.15). Survival was greater in the PPD-positive cohort compared to the anergic cohort (p = .0001). Conclusion: The number of signs or symptoms at baseline and anergic status are associated with increasing morbidity and mortality. Even though the tuberculosis preventive therapies were effective in reducing the incidence of TB for HIV-infected adults, their benefit of delaying HIV disease progression to AIDS was not observed.