Significant increase of HBV infection in HIV infected patients with disease progression in China based on two MSM HIV infected cohorts

The date about the condition of HBV co infection with the disease progress of HIV is limited. To investigate whether the incidence of HBV co-infection is significantly higher in HIV patients with disease progression in China, we compared rates of HBV co-infection in HIV patients based on an acute and a chronic HIV infected cohort. Significance was assessed with Chi-square. HBV infection is diagnosed by the presence of hepatitis B surface antigen. The HBsAg positive rate increased from 6.18% in acute HIV infection to 11.44% in chronic HIV infection. Thirty-four acute HIV patients had been tested for HBV in their chronic phase, four of them had HBV -specific antigens and/or specific antibodies changes. The number of Hepatitis B virus-specific antibodies decreased from acute phase to chronic phase in four patients and two patients’ HBsAg changed from negative to positive. There is an increased prevalence of HBV infection in HIV patients with the disease progression in China.


Introduction
The issue of viral co-infection among human immunodeficiency virus (HIV) /acquired immunodeficiency syndrome (AIDS) patients represents a growing public health concern worldwide. HIV and hepatitis B virus (HBV) have same routes of transmission (1), and HIV/HBV coinfection is associated with liver-related disease and morbidity and mortality rates (2). HIV-infected persons are less likely to clear acute HBV infection spontaneously when their immune system is significantly compromised (3).
China has the highest prevalence of chronic HBV with carrier rates of more than 7% (4)  Since 2016, China has implemented a strategy of treatment immediately after HIV infection is detected. In this study, two cohorts of HIV infection were established in Youan hospital before 2016 (5) , one was the acute phase of HIV infection, the other was the chronic phase of HIV infection. Without treatment, we observed the situation of HBV co infection with the progress of HIV disease. The purpose of this study was to investigate if HBV co-infection is significantly increased in HIV patients with disease progression in China.

Study population
The data were collected from clinic-based MSM (men who have sex with men) cohorts in Beijing Youan Hospital from June 2006 to August 2015. Both acute and chronic HIV infection cohorts were incorporated in this study. The characteristic of patients are shown in Table 1. This study was approved by the Ethical Committee at Beijing Youan Hospital (YAH200605010) and written informed consent was obtained from all participants.

Detection of HBV Infection
HBV-specific antigens and specific antibodies in patient plasma were detected in the clinical laboratory at Youan hospital using the Elecsys® HBsAg Immunoassay (Roche diagnostics GmbH, Mannheim, Germany), the immunoassay analyzer cobase 411 (Roche diagnostics GmbH, Mannheim, Germany), or specific ELISA test kits (PRECHEK Bio, Anaheim, USA), respectively, according to manufacturer's instructions.
HBV infection is diagnosed by the presence of hepatitis B surface antigen (HBsAg), which is indicative of acute or chronic infection (6).

Liver Function Tests
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined in patient plasma by UV-LDH method test kit (Fortress Diagnostics Limited, United Kingdom).

Markers of HIV disease progression
Absolute blood CD4+ T-cell counts were measured using a FACSCalibur flow cytometer. Viral load was measured by the Amplicor HIV monitor ultrasensitive method with a detection limit of 40 copies/mL of plasma.

Statistical analyses
All statistical analyses were performed using SPSS 23.0 (Chicago, IL, USA). Two-sided p<0.05 was accepted as statistically significant. The Chi-square test for categorical variables were used for comparison between two groups.

Results
The data were collected from outpatient clinic-based MSM (men who have sex with men) cohorts managed in Beijing Youan Hospital from June 2006 to August 2012.
In the acute cohort, 23 out of 372 cases were HBsAg positive; HBsAg positive rate was 6.18%. In chronic cohort, were a total of 306 chronic HIV infected patients, 35 out of 306 patients were HBsAg positive, HBsAg positive rate was 11.44%. The rate of HBV co infection in chronic HIV infection was significantly higher than that in acute stage (p=0.015, Figure 1). The CD4 count decreased from average 445 in acute infection to 358 in chronic infection (p<0.001) ( Table 1).
In total, 34 acute patients had detected HBV in the chronic phase, 4 of them had HBV -specific antigens and (or) specific antibodies changes ( Table 2). CD4 counts decreased and viral load increased in these four cases from acute phase to chronic phase. The number of Hepatitis B virus-specific antibodies decreased from acute phase to chronic phase in four patients and two patients' HBsAg changed from negative to positive.

Discussion
We found HBV co-infection significantly increased from acute HIV infection to chronic HIV infection in China. Two cases in acute cohort have been detected HBV-specific antigens in chronic phase compared with HBV specific antibodies in acute HIV infection. All evidence suggested that the rate of HBV infection increased with the progression of HIV infection.
Data presented in this report obtained from one of major clinic in Beijing.
Most HBV infection is acquired during the perinatal period or early in childhood in high prevalence areas. In this study, we observed obvious increase in the rate of HBV infection with the disease progression and immune system damage in adult HIV patients. cccDNA has been shown to persist even in the liver of patients with successful cellular and humoral control of the infection (7). It suggests the possibility that HBV virus comes from cccDNA in the liver tissue. Other studies have shown that reactivation of HBV after undergoing anticancer therapy or rituximab-containing treatment (8,9).
Given that HIV/HBV co-infection results in higher morbidity and mortality of liver disease

Ethics approval and consent to participate
This study was approved by the Ethical Committee at Beijing Youan Hospital (YAH200605010) and written informed consent was obtained from all participants.

Consent for publication
Not applicable.

Availability of data and materials
All relevant data are within the manuscript. The datasets collected and/or analyzed during the current study are available on request from the author.