Level 2: Mid-level evidence
WHO recommendations call for at least six months of isoniazid therapy for TB prevention in adults who are HIV-positive and have either a positive or unknown tuberculin skin test (purified protein derivative [PPD]).
A randomized trial compared isoniazid prophylaxis for 36 months vs. six months in 1,995 HIV-positive patients in Botswana (Samandari T et al. Lancet. 2011;377:1588-1598).
Following six 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 six-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 intention-to-treat analysis, P=0.047). This difference was primarily attributable 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.
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