• Taraz Samandari, Tefera B Agizew, Samba Nyirenda, Zegabriel Tedla, Thabisa Sibanda, Barudi Mosimaneotsile, Oaitse I Motsamai, Nong Shang, Charles E Rose, and James Shepherd.
• aCenters for Disease Control and Prevention Botswana, Gaborone and Francistown, Botswana bDivision of TB Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA cMinistry of Health, Gaborone, Botswana dDivision of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
• AIDS. 2015 Jan 28;29(3):351-9.

ObjectiveThirty-six months of isoniazid preventive therapy (36IPT) was superior to 6 months of IPT (6IPT) in preventing tuberculosis (TB) among HIV-infected adults in Botswana. We assessed the posttrial durability of this benefit.DesignA 36-month double-blind placebo controlled trial (1 : 1 randomization) with recruitment between November 2004 and July 2006 and observation until June 2011.MethodsOne thousand, nine hundred and ninety-five participants were followed in eight public health clinics. Twenty-four percent had a tuberculin skin test ≥5 mm (TST-positive). A minimum CD4 lymphocyte count was not required for enrolment. Antiretroviral therapy (ART) was provided in accordance with Botswana guidelines; 72% of participants retained by June 2011 had initiated ART. Multivariable analysis using Cox regression analysis included treatment arm, TST status, ART as a time-dependent variable and CD4 cell count at baseline and updated at 36 months.ResultsIn the posttrial period, 2.13 and 2.14 per 100 person-years accumulated, whereas 0.93 and 1.13% TB incidence rates were observed in the 36IPT and 6IPT arms, respectively (P = 0.52). The crude hazard ratio of TB during the trial and posttrial was 0.57 [95% confidence intervals (CI) 0.33, 0.99] and 0.82 (95% CI 0.46, 1.49), and when restricted to TST-positive participants was 0.26 (95% CI 0.08, 0.80) and 0.40 (95% CI 0.15, 1.08), respectively. Multivariable analysis showed that ART use was associated with reduced death (adjusted hazard ratio 0.36, 95% CI 0.17-0.75) but not TB (0.92, 95% CI 0.55-1.53) in the posttrial period.ConclusionThe benefit of 36IPT for TB prevention declined posttrial in this cohort. Adjunctive measures are warranted to prevent TB among HIV-infected persons receiving long-term ART in TB-endemic settings.

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