Yijia Li1,2, Jing Xie1,3, Huanling Wang1, Yang Han1, Nidan Wang1, Chloe L Thio4, Taisheng Li1,3. 1. Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. 2. Present address: University of Pittsburgh Medical Center, Pittsburgh, PA, USA. 3. Clinical Immunology Center, Chinese Academy of Medical Sciences, Beijing, China. 4. Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Abstract
BACKGROUND: In HBV-infected patients, hepatitis B e antigen (HBeAg) seroconversion is associated with better outcomes. Interleukin-18 (IL-18) controls hepatitis B replication in a mouse model. However, its role in treatment response in HIV-HBV-coinfected patients is unknown. METHODS: We enrolled 35 treatment-naive, HBeAg-positive, HIV-HBV-coinfected patients. HBV DNA, HIV RNA, CD4+ T-cell count, HBV surface antigen (HBsAg) quantification (qHBsAg), HBeAg quantification (qHBeAg) and IL-18 levels were measured prior to, at 24 and 48 weeks of HBV-active combination antiretroviral therapy (cART). Multivariate Poisson regression models with robust standard errors were used to determine factors associated with HBeAg seroconversion. RESULTS: Twenty-one patients received tenofovir (TDF) + lamivudine (3TC) based cART while 14 patients received 3TC-based cART. After 48 weeks of treatment, 10 patients experienced HBeAg seroconversion. Compared with non-seroconverters, seroconverters had higher median HIV RNA (5.22 versus 4.58 log copies/ml; P=0.030), lower median qHBsAg (3.97 versus 4.76 log IU/ml; P=0.011), lower median qHBeAg (1.61 versus 3.01 log PEIU/ml; P=0.004) and marginally higher median IL-18 (2.70 versus 2.53 log pg/ml; P=0.068) prior to ART. In the multivariate regression, higher baseline IL-18 (adjusted relative risk [aRR] 2.99 per 1 log pg/ml increase; P=0.035), high HIV RNA (aRR 1.84 per 1 log copies/ml; P=0.029) and low qHBeAg (aRR 0.71 per 1 log PEIU/ml; P=0.029) were significantly associated with HBeAg seroconversion. CONCLUSIONS: In HIV-HBV-coinfected patients with HBeAg positivity, higher IL-18 levels, HIV RNA load, as well as low qHBeAg prior to cART were associated with HBeAg seroconversion.
BACKGROUND: In HBV-infectedpatients, hepatitis B e antigen (HBeAg) seroconversion is associated with better outcomes. Interleukin-18 (IL-18) controls hepatitis B replication in a mouse model. However, its role in treatment response in HIV-HBV-coinfectedpatients is unknown. METHODS: We enrolled 35 treatment-naive, HBeAg-positive, HIV-HBV-coinfectedpatients. HBV DNA, HIV RNA, CD4+ T-cell count, HBV surface antigen (HBsAg) quantification (qHBsAg), HBeAg quantification (qHBeAg) and IL-18 levels were measured prior to, at 24 and 48 weeks of HBV-active combination antiretroviral therapy (cART). Multivariate Poisson regression models with robust standard errors were used to determine factors associated with HBeAg seroconversion. RESULTS: Twenty-one patients received tenofovir (TDF) + lamivudine (3TC) based cART while 14 patients received 3TC-based cART. After 48 weeks of treatment, 10 patients experienced HBeAg seroconversion. Compared with non-seroconverters, seroconverters had higher median HIV RNA (5.22 versus 4.58 log copies/ml; P=0.030), lower median qHBsAg (3.97 versus 4.76 log IU/ml; P=0.011), lower median qHBeAg (1.61 versus 3.01 log PEIU/ml; P=0.004) and marginally higher median IL-18 (2.70 versus 2.53 log pg/ml; P=0.068) prior to ART. In the multivariate regression, higher baseline IL-18 (adjusted relative risk [aRR] 2.99 per 1 log pg/ml increase; P=0.035), high HIV RNA (aRR 1.84 per 1 log copies/ml; P=0.029) and low qHBeAg (aRR 0.71 per 1 log PEIU/ml; P=0.029) were significantly associated with HBeAg seroconversion. CONCLUSIONS: In HIV-HBV-coinfectedpatients with HBeAg positivity, higher IL-18 levels, HIV RNA load, as well as low qHBeAg prior to cART were associated with HBeAg seroconversion.
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