Isoniazid preventive therapy and tuberculosis transcriptional signatures in people with HIV

Abstract

Objectives: To examine the association between isoniazid preventive therapy (IPT) or nontuberculous mycobacteria (NTM) sputum culture positivity and tuberculosis (TB) transcriptional signatures in people with HIV.

Design: Cross-sectional study.

Methods: We enrolled adults living with HIV who were IPT-naive or had completed IPT more than 6 months prior at HIV care clinics in western Kenya. We calculated TB signatures using gene expression data from qRT-PCR. We used multivariable linear regression to analyze the association between prior receipt of IPT or NTM sputum culture positivity with a transcriptional TB risk score, RISK6 (range 0-1). In secondary analyses, we explored the association between IPT or NTM positivity and four other TB transcriptional signatures.

Results: Among 381 participants, 99.7% were receiving antiretroviral therapy and 86.6% had received IPT (completed median of 1.1 years prior). RISK6 scores were lower (mean difference 0.10; 95% confidence interval (CI): 0.06-0.15; P < 0.001) among participants who received IPT than those who did not. In a model that adjusted for age, sex, duration of ART, and plasma HIV RNA, the RISK6 score was 52.8% lower in those with a history of IPT ( P < 0.001). No significant association between year of IPT receipt and RISK6 scores was detected. There was no association between NTM sputum culture positivity and RISK6 scores.

Conclusion: In people with HIV, IPT was associated with significantly lower RISK6 scores compared with persons who did not receive IPT. These data support investigations of its performance as a TB preventive therapy response biomarker.

Figure 1:. RISK6 Scores by IPT status, year of IPT receipt, and sputum culture result

RISK6 scores were calculated and stratified by history of IPT use (A), year of IPT receipt (B), or NTM sputum culture positivity (C). IPT, isoniazid preventive therapy; Mtb, Mycobacterium tuberculosis; NTM, non-tuberculous mycobacteria

Figure 2:. RISK6 scores versus IPT status by HIV viral load

RISK6 scores stratified by history of IPT use and presence of a detectable HIV viral load. Left panel, HIV viral load detectable (>50 copies/mL); right panel, HIV viral load undetectable (<50 copies/mL)

Figure 3:. Correlation between TB transcriptional signatures

Pearson’s correlation coefficients (r) between each of the five TB transcriptional signatures are depicted numerically as well as with a colored heat map ranging from −1 (blue) to +1 (red).