Primary Prophylaxis to Prevent Tuberculosis Infection in Prison Inmates:A Randomized, Double-Blind, Placebo-Controlled Trial

<title>Abstract</title> Background. In many low- and middle-income countries, tuberculosis incidence in prisons is high, exposing incarcerated populations to an elevated risk of tuberculosis infection. Methods. We conducted a randomized, double-blind, placebo-controlled trial among HIV-negative male inmates of a high tuberculosis burden prison to determine whether twice-weekly isoniazid (900 mg) for 12 months prevents tuberculosis infection. The primary outcome was QuantiFERON–TB Gold Plus (QFT) conversion to ≥0.35 IU/ml at 6 months; the secondary outcome was conversion at any time point. Alternative QFT positivity thresholds (≥0.7, ≥2.0, and ≥4.0 IU/ml) were investigated as exploratory endpoints. Results. In total, 467 participants were randomly assigned to isoniazid (N=258) or placebo (N=209). In an interim analysis of participants who had completed six months of follow-up (N=171), QFT conversion occurred in 20.7% (19/92) and 21.5% (17/79) of participants in isoniazid and placebo arms (efficacy: 4.0%; P=0.88). The trial was then stopped for futility, and the remaining participants underwent QFT testing. Among all participants with a second QFT test at 6-months, conversion occurred in 19.7% (26/132) and 30.3% (37/122) of participants in isoniazid and placebo arms (efficacy: 35.1%; P=0.04). Protection was also seen among all individuals with a follow-up QFT (5/132 [3.8%] vs 14/122 [11.5%]; efficacy: 67.0%, P=0.01). In exploratory analyses, the isoniazid arm had significantly lower rates of conversion at ≥2.0 IU/ml (67.0% efficacy, P=0.01), but not at other cutoff values. Discontinuations and losses to follow-up were high in both arms (isoniazid, 126/258 [48.8%]; placebo, 87/209 [41.6%]; P=0.14), due to elective withdrawal (24.0% vs 21.5%; P=0.60) and transfer or release from prison (19.0% vs 18.2%; P=0.92). Conclusions. Our results suggest that 900 milligrams of isoniazid given twice weekly may confer partial protection against QFT conversion in high exposure environments; however, discontinuation rates in both arms were high, which would limit the clinical benefits of this prevention method.