ABSTRACT
Background World Health Organization recommend the use of isoniazid (INH) only, or INH and rifapentine therapy, to treat the latent tuberculosis infection (LTBI). The recent rise of isoniazid and multi-drug resistant (MDR) tuberculosis has complicated the choice of LTBI treatment regimen. The current lack of evidence on optimal regimens prevents the formulation of definitive recommendations for latent drug-resistant tuberculosis. We examine the risk of disease progression of individuals exposed to sensitive, INH, or MDR tuberculosis who received INH as part of routine tuberculosis management.
Methods This study is a prospective cohort study conducted in Lima, Peru. Between September 2009 and August 2012, we identified and enrolled 4,500 tuberculosis patients and their 14,044 household contacts. We measured the incident tuberculosis of the household contacts (HHCs) over a one-year follow-up. We used a Cox frailty proportional hazards model to evaluate whether the effect of INH preventive therapy (IPT) on tuberculosis progression varied by the resistance profile of the index case.
Findings We restricted the analyses to 4,216 HHCs who were ≤ 19 years old. 2,106 HHCs (50%) had initiated isoniazid prevention therapy at enrollment. We found that the protective effect of INH against tuberculosis was stronger in HHCs exposed to drug-sensitive or MDR TB than in those exposed to mono-INH-resistant strains (IPT vs. No-IPT aHR[95% confidence interval]: 0.32 [0.20-0.50] in INH-sensitive subgroup; 0.26 [0.08-0.77] in MDR; 0.80 [0.23 to 2.79] in mono-INH-resistant). When we further restricted the analyses to those who received a ≥ 3 months of INH, the protective effect of IPT became even stronger across all three groups (0.2 [0.1 to 0.4] in INH-sensitive subgroup; 0.16 [0.02-1.27] in MDR; 0.72 [0.16-3.16] in mono-INH-resistant).
Interpretation We found that INH prevention therapy protected against TB among contacts of INH-resistant TB patients. This finding suggests that INH may have a role in the management of MDR-LTBI.
Funding National Institutes of Health and the National Institute of Allergy and Infectious Diseases CETR (U19AI109755) and TBRU (U19AI111224)