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. 2020 Jun 10;70(12):2675-2682.
doi: 10.1093/cid/ciz732.

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 TB Trial

Kogieleum Naidoo  1   2 , Razia Hassan-Moosa  1 , Philile Mlotshwa  1 , Nonhlanhla Yende-Zuma  1   2 , Dhineshree Govender  1 , Nesri Padayatchi  1   2 , Salim S S Abdool-Karim  1   2   3
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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 TB Trial

Kogieleum Naidoo et al. Clin Infect Dis. .

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.

Keywords: HIV–TB integration; South Africa; antiretroviral treatment; liver injury; tuberculosis treatment.

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Figures

Figure 1.
Figure 1.
Study flow diagram. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase.
Figure 2.
Figure 2.
Kaplan-Meier estimates of cumulative probability of developing liver toxicity by study.
See this image and copyright information in PMC

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