For HIV-infected Adults with Positive PPD, TB Prophylaxis with Isoniazid for 36 Months Appears More Effective Than for 6 Months

DynaMed Weekly Update - Volume 6, Issue 18

Recommendations from the World Health Organization (WHO) call for at least 6 months of isoniazid therapy for tuberculosis (TB) prevention in adults who are HIV-positive and have either a positive or unknown tuberculin skin test (PPD) (WHO 2011 PDF). A recent randomized trial compared isoniazid prophylaxis for 36 months vs. 6 months in 1,995 HIV-positive patients in Botswana. Following 6 months of open-label isoniazid treatment, patients received either continued isoniazid or placebo in blinded fashion for an additional 30 months. Patients with CD4 cell count <200 cells/mcL were given antiretroviral therapy. The primary outcome was any incident TB (definite, probable, or possible) defined as clinical presentation consistent with TB and response to anti-TB therapy. The 6-month open-label phase was completed by 83% of patients, and 78% of patients attended at least 80% of their monthly refill visits.

Isoniazid prophylaxis for 36 months was associated with significantly reduced incidence rates of TB (0.72 vs. 1.26 per 100 person-years in ITT analysis, p = 0.047) (level 2 [mid-level] evidence). This difference was primarily due to the effect of continued prophylaxis in patients with positive PPD at baseline. In subgroup analyses, incidence rates were 0.57 vs. 2.22 per 100 person-years (p = 0.02) for patients with positive PPD, and 0.75 vs. 1.01 (not significant) for patients with negative PPD. There were no significant differences in overall severe adverse events or mortality (Lancet 2011 Apr 12 early online).

For more information, see the Tuberculosis in HIV-infected persons topic in DynaMed.