CD4+ T cell counts and soluble programmed death-1 at baseline correlated with hepatitis B surface antigen decline in HIV/HBV coinfection during combined antiretroviral therapy

Xiaodi Li; Ling Xu; Lianfeng Lu; Xiaosheng Liu; Yang Yang; Yuanni Wu; Yang Han; Xiaoxia Li; Yanling Li; Xiaojing Song; Wei Cao; Taisheng Li

doi:10.3389/fcimb.2023.1178788

CD4⁺ T cell counts and soluble programmed death-1 at baseline correlated with hepatitis B surface antigen decline in HIV/HBV coinfection during combined antiretroviral therapy

Front Cell Infect Microbiol. 2023 May 3:13:1178788. doi: 10.3389/fcimb.2023.1178788. eCollection 2023.

Authors

Xiaodi Li¹, Ling Xu², Lianfeng Lu¹, Xiaosheng Liu^{1

3}, Yang Yang¹, Yuanni Wu¹, Yang Han¹, Xiaoxia Li¹, Yanling Li¹, Xiaojing Song¹, Wei Cao¹, Taisheng Li^{1

3

4}

Affiliations

¹ Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
² Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China.
³ Tsinghua-Peking Center for Life Sciences, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
⁴ State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Abstract

Background: Several studies have described the rapid decline and clearance of hepatitis B surface antigen (HBsAg) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection after initiating combined antiretroviral therapy (cART). Early decline of HBsAg levels is associated with HBsAg seroclearance in the treatment of chronic HBV infection. This study aims to evaluate the HBsAg kinetics and the determinants of early HBsAg decline in patients with HIV/HBV coinfection during cART.

Methods: A total of 51 patients with HIV/HBV coinfection were enrolled from a previously established HIV/AIDS cohort and followed for a median of 59.5 months after cART initiation. Biochemical tests, virology and immunology assessments were measured longitudinally. The kinetics of HBsAg during cART were analyzed. Soluble programmed death-1 (sPD-1) levels and immune activation markers (CD38 and HLA-DR) were measured at baseline, 1-year and 3-year during treatment. HBsAg response was defined as a decline of more than 0.5 log₁₀ IU/ml at 6 months from the baseline after initiation of cART.

Results: HBsAg declined faster (0.47 log₁₀ IU/mL) in the first six months and attained a decrease of 1.39 log₁₀ IU/mL after 5-year therapy. Seventeen (33.3%) participants achieved a decline of more than 0.5 log₁₀ IU/ml at the first 6 months of cART(HBsAg response) of which five patients achieved HBsAg clearance at a median of 11 months (range: 6-51 months). Multivariate logistic analysis showed the lower baseline CD4⁺ T cell levels (OR=6.633, P=0.012) and sPD-1 level (OR=5.389, P=0.038) were independently associated with HBsAg response after cART initiation. The alanine aminotransferase abnormality rate and HLA-DR expression were significantly higher in patients who achieved HBsAg response than in those who did not achieve HBsAg response after cART initiation.

Conclusion: Lower CD4 ⁺ T cells, sPD-1, and immune activation were related to a rapid HBsAg decline in patients with HIV/HBV-coinfection after the initiation of cART. These findings imply that immune disorders induced by HIV infection may disrupt immune tolerance to HBV, leading to a faster decline in HBsAg levels during coinfection.

Keywords: HBV; HBsAg decline; HIV; coinfection; immune activation; soluble PD-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD4-Positive T-Lymphocytes
Coinfection*
DNA, Viral
HIV Infections* / complications
HIV Infections* / drug therapy
Hepatitis B Surface Antigens
Hepatitis B virus / genetics
Hepatitis B* / complications
Hepatitis B* / drug therapy
Humans
Lymphocyte Count

Substances

Hepatitis B Surface Antigens
DNA, Viral

Grants and funding

The research was supported by the National Key Technologies R&D Program for the 13th Five‐year Plan (2017ZX10202101‐001), the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2021-I2M-1-037), the Key Clinical Specialties Program of Beijing and China and National High-Level Hospital Clinical Research Funding (2022-PUMCH-D-008).