Associations between isoniazid preventive therapy, non-tuberculous mycobacterial infection, and incipient TB signatures in people with HIV

Objective(s): To examine the association between isoniazid preventive therapy and incipient tuberculosis (TB) transcriptome-based signatures in persons with HIV (PWH) and to describe the association between non-tuberculous mycobacteria (NTM) and incipient TB signatures in PWH.

Design: Cross-sectional study using clinical information and specimens obtained at one visit from previous cohort.

Methods: Participants ages 18 to 70 years were enrolled at two clinics in western Kenya caring for PWH. Clinical information, including whether participants had previously received isoniazid preventive therapy, and laboratory studies were obtained at the initial visit. Incipient TB signatures were calculated using gene expression data from qRT-PCR with the Fluidigm 96.96 dynamic array platform. The primary signature of interest was the RISK6 signature. Mean RISK6 scores by IPT status were compared using the Mann-Whitney U test. Multivariable linear regression was used to analyze the association between prior receipt of IPT and RISK6 scores and the association between NTM and RISK6 scores.

Results: 386 participants (86.8% with prior history of IPT) were included in the analysis. Almost all (99%) participants were taking antiretroviral therapy (ART) at the time of study enrollment. Persons who had received IPT had an average RISK6 score that was 0.099 lower (95% CI: 0.057, 0.139; p < 0.001) than persons without IPT history. This association remained significant when adjusting for age, sex, and HIV viral load. There was no significant association between NTM and RISK6 scores.

Conclusions: History of IPT was associated with significantly lower RISK6 scores in people with HIV compared to people who had not received IPT. We did not detect an association between NTM and RISK6 scores.