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).

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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.

All electronic documents accessed October 28, 2011.