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Incidence and risk factors for liver enzyme elevation in HIV-1 infected patients treated for tuberculosis: a secondary analysis of the multi-country ANRS 12300 REFLATE TB2 trial

Title
Incidence and risk factors for liver enzyme elevation in HIV-1 infected patients treated for tuberculosis: a secondary analysis of the multi-country ANRS 12300 REFLATE TB2 trial
Presenter
Celso Khosa
Authors
C. Khosa * (1), C. Chazallon (2), H. Perazzo (3), I. Massango (1), E. Messou (4), S. Eholié (5), D. Laureillard (6), G. Do Chau (7), X. Anglaret (2), J.-M. Molina (8,9), B. Grinsztejn (3), O. Marcy (2), N. De Castro (2,8), ANRS 12300 Reflate TB2 Study Group
Institutions
(1) Instituto Nacional de Saúde (INS), Centro de Investigação e Treino em Saúde da Polana Caniço (CISPOC), Maputo, Mozambique, (2) University of Bordeaux, Inserm, IRD, UMR 1219 Bordeaux Population Health Center, GHiGS team, Bordeaux, France, (3) Oswaldo Cruz Foundation, Evandro Chagas National Institute of Infectious Diseases, Rio de Janeiro, Brazil, (4) Programme PACCI/ANRS Research Center, Centre de Prise en Charge de Recherche et de Formation, Abidjan, Cote D''Ivoire, (5) Programme PACCI/ANRS Research Center, SMIT, Abidjan, Cote D''Ivoire, (6) University Hospital, Department of Infectious and Tropical Diseases, Nîmes, France, (7) Pham Ngoc Thach Hospital, Ho Chi Minh City, Viet Nam, (8) Hôpital Saint Louis - APHP, Paris, France, (9) Université de Paris, Paris, France

BACKGROUND: There are limited data describing the incidence and risk factors associated with Liver Enzyme Elevation (LEE) among patients co-infected with HIV and tuberculosis (TB) receiving antiretroviral therapy (ART). This study aimed to describe the incidence, severity and risk factors associated with LEE in patients enrolled in Reflate TB2 trial.
METHODS: ANRS 12300 Reflate TB2 was a multicenter, open-label, phase 3, non-inferiority randomized trial where ART-naïve adult HIV1-infected patients on standard TB treatment received either raltegravir 400 mg BID or efavirenz 600 mg QD both in association with tenofovir and lamivudine. Alanine aminotransferase (ALT) levels were assessed at weeks 0, 2, 4, 8, 12, 24, and 48. LEE was defined as any grade 2 or more ALT ['¥2.5 upper limit of normal (ULN)] during follow-up visits. The Overall incidence of LEE [per 100 persons-year (PY)] over the trial duration and baseline risk factors for LEE using univariate and multivariate cox proportional-hazards models [HR (95%CI)] were assessed.
RESULTS: A total of 453 patients [median age=35 years (IQR: 29-43), median baseline CD4 count=102 /µL (IQR: 38-239), median ALT level=24 IU/L (IQR: 15-38), 31% with disseminated Extrapulmonary TB were included in the analysis. Overall, 11% of patients (n=48) experienced LEE, corresponding to an incidence of 13.42 (95% CI: 9.89-17.79) events per 100 PY. Of 48 patients with LEE, 63% (n=30) were male, 58% (n=28) were from Vietnam, 65% (n=31) were younger than 35 years, 40% (n=19) had ALT elevation grade '¥3. Additionally, among those, 34 subjects (71%) had a baseline Karnofsky score above 80%, 32 (67%) declared current or past alcohol consumption, 35 (75%) had baseline CD4 counts '¤100/µL and their median baseline HIV RNA was 5.6 log10 copies/mL, 23 individuals (48%) had baseline ALT'¥ 40 IU/L. Inclusion in Vietnam [vs Ivory Coast, HR=3.16 (95%CI: 1.51-6.61), ALT'¥ 40 IU/L [vs <40 IU/L, HR=2.35 (95%CI: 1.27-4.37)] and Neutrophils < 1500/mm3 [Vs Neutrophils >1500.mm3, HR= 1.901 (95%CI: 1.002-3.605)] at baseline were independently associated with LEE.
CONCLUSIONS: The incidence of LEE was relatively high in HIV/TB co-infected patients receiving anti-TB treatment and ART, particularly among those from Vietnam and those with higher baseline ALT levels.

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