High Rates of Drug-induced Liver Injury in People Living With HIV Coinfected With Tuberculosis (TB) Irrespective of Antiretroviral Therapy Timing During Antituberculosis Treatment: Results From the Starting Antiretroviral Therapy at Three Points In...

Overview

Journal Clin Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2019 Oct 18

PMID 31622456

Citations 10

Authors

Kogieleum Naidoo

Razia Hassan-Moosa

Philile Mlotshwa

Nonhlanhla Yende-Zuma

Dhineshree Govender

Nesri Padayatchi

Salim S S Abdool-Karim

Affiliations

Soon will be listed here.

Abstract

Background: New onset or worsening drug-induced liver injury challenges coinfected patients on antiretroviral therapy (ART) initiation during antituberculosis (TB) treatment.

Methods: Post hoc analysis within a randomized trial, the Starting Antiretroviral Therapy at Three Points in Tuberculosis trial, was conducted. Patients were randomized to initiate ART either early or late during TB treatment or after TB treatment completion. Liver enzymes were measured at baseline, 6-month intervals, and when clinically indicated.

Results: Among 642 patients enrolled, the median age was 34 years (standard deviation, 28-40), and 17.6% had baseline CD4+ cell counts <50 cells/mm3. Overall, 146/472 patients (52, 47, and 47: early, late, and sequential arms) developed new-onset liver injury following TB treatment initiation. The incidence of liver injury post-ART initiation in patients with CD4+ cell counts <200 cells/mm3 and ≥200 cells/ mm3 was 27.4 (95% confidence interval [CI], 18.0-39.8), 19.0 (95% CI, 10.9-30.9), and 18.4 (95% CI, 8.8-33.8) per 100 person-years, and 32.1 (95% CI, 20.1-48.5), 11.8 (95% CI, 4.3-25.7), and 28.2 (95% CI, 13.5-51.9) per 100 person-years in the early, late integrated, and sequential treatment arms, respectively. Severe and life-threatening liver injury occurred in 2, 7, and 3 early, late, and sequential treatment arm patients, respectively. Older age and hepatitis B positivity predicted liver injury.

Conclusions: High incidence rates of liver injury among cotreated human immunodeficiency virus (HIV)-TB coinfected patients were observed. Clinical guidelines and policies must provide guidance on frequency of liver function monitoring for HIV-TB coinfected patients.

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