Adverse Events of Latent Tuberculosis Treatment With Isoniazid in People Living With HIV: A Case-Control Study in a Resource-Rich Setting

Abstract

Introduction Multiple risk factors, such as human immunodeficiency virus (HIV) infection and immunosuppressive therapies, increase the odds of latent tuberculosis infection (LTBI) reactivation and progression to active tuberculosis. A six-to-nine-month preventive treatment with isoniazid (INH) decreases the risk of LTBI reactivation, but its effectiveness can be limited by its long duration and adverse events (AEs), including liver toxicity. Due to comorbidities and polypharmacy, people living with HIV (PLHIV) may be at increased risk of INH-associated AEs. Our study aimed to assess the prevalence of AEs among patients receiving INH treatment for LTBI, to identify risk factors for their occurrence, and to evaluate whether PLHIV have higher odds of developing INH-associated AEs. Methods We conducted a single-center retrospective case-control study, including 130 outpatients with LTBI treated with INH between July 2019 and March 2022. Participants who developed AE (cases) were compared to controls, and a subgroup of PLHIV was compared to HIV-negative participants. Demographics, socioeconomic variables, comorbidities, and clinical variables were compared between study groups. Patient data were obtained from institutional electronic medical records, and outcomes were measured at regularly scheduled appointments. Results We included 130 participants, of which 54 were PLHIV. The PLHIV subgroup was significantly younger (p = 0.01) and demonstrated significantly higher prevalences of chronic liver disease, previous viral hepatitis, daily alcohol consumption, and intravenous drug use (IDU). One-third of the participants had an AE (45 cases, 34.6%), with liver toxicity being the most common (22.3%). Participants who developed AEs were significantly older (p = 0.030) and had a higher prevalence of economic hardship (p = 0.037), as well as higher scores of the Charlson comorbidity index (p = 0.002) than the controls. INH withdrawal occurred in 17 participants (13.1%) and was mainly associated with liver toxicity (p < 0.01) and gastrointestinal symptoms (p = 0.022). In the adjusted effect model, an age ≥ 65 years, economic hardship, and excessive alcohol consumption were significantly associated with higher odds of AEs, while HIV infection decreased the odds by 68.4% (p = 0.033). Conclusions In our study, INH-associated AEs were common, with liver toxicity being the most frequent. Older age, economic hardship, and excessive alcohol consumption increased the odds of INH-associated AEs, while PLHIV had lower odds of developing INH-associated AEs, even when adjusting for other variables in the multivariate analysis. Further studies should be conducted to assess if these results are replicable in a larger population and in different settings.

Screening for Latent Tuberculosis Infection in People Living with HIV: TUBHIVIT Project, a Multicentre Italian Study

“…Isoniazid did not interact with commonly used ART regimens, while rifampin interacted with many HIV drugs, such as TAF, dolutegravir, and boosted/PI. In contrast to our data, a previous study highlighted a higher number of adverse events (33.3%), mainly hepatotoxicity, in PLHIV taking isoniazid for LTBI [18]. Further prospective studies are warranted to elucidate this matter.…”