Abstract
Weekly rifapentine and isoniazid therapy (3HP) is the most frequent treatment for latent tuberculosis infection (LTBI). However, the association between major adverse drug reactions (ADRs) and drug metabolic enzyme single-nucleotide polymorphisms (SNPs) remains unclear. In this study, 377 participants who received the 3HP regimen were recruited and examined for genotyping of CYP5A6, CYP2B6, CYP2C19, CYP2E1, and NAT2 SNPs. In our study, 184 participants (48.4%) developed ADRs. Moreover, CYP2C19 rs4986893 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 2.231 [1.015–4.906]), CYP2E1 rs2070676 (CC vs. CG+GG, OR [95% CI]: 1.563 [1.022–2.389]), and CYP2E1 rs2515641 (CC vs. CT+TT, OR [95% CI]: 1.903 [1.250–2.898]) were associated with ADR development. In conclusion, CYP2C19 and CYP2E1 SNPs may provide useful information regarding ADRs in LTBI patients receiving the 3HP regimen.
Highlights
A total of 377 TB patients were recruited and administered the 3HP regimen. Of these 377 participants, 337 (89.3%) completed the treatment, 29 (7.7%) discontinued treatment owing to adverse drug reactions (ADRs), 8 (2.1%) switched to the 9 months (9H) regimen due to ADRs, and 3 (0.8%) transferred to another facility or refused further treatment (Table 1)
ADRs occurred in 184 participants (48.4%), and 596 adverse drug events were reported
Our study showed that cytochrome P450 enzymes, such as CYP2B6 and CYP2E1, were associated with the incidence of ADR (p < 0.05)
Summary
Up to one-third of the world’s population is estimated to be infected with Mycobacterium tuberculosis [1]. Infected individuals have no signs or symptoms of TB disease and are not infectious, they still have a risk of active TB infection and becoming infectious. In Taiwan, TB ranks the highest for the number of new cases and is the main cause of death annually from communicable diseases in Taiwan. A comprehensive effort to control TB by implementing directly observed therapy (DOT), a short-course program, for all patients with TB has been implemented since 2006 in Taiwan to reduce the incidence to half, from 67.4 per 100,000 population to 33.7 per 100,000 population, by 2016. The incidence rate has declined, it gradually slowed down to 43.9 per 100,000 population by
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