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Yuan Nie,* Xizi Deng,* Yun Lan, Linghua Li, Feng Li, Fengyu Hu Research Institute, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengyu Hu; Feng LiResearch Institute, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, No. 627, Dongfeng Road, Yuexiu District, Guangzhou, Guangdong 510030, People’s Republic of ChinaEmail gz8hhfy@126.com; gz8h_lifeng@126.comBackground: Human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection can accelerate HBV-induced liver disease. A previous study showed that variation in the HBV pre-S region and quasispecies heterogeneity (Sn, mean genetic distance, dS, dN, and dS/dN) are both related to HBV-induced terminal liver disease in HBV mono-infection. Currently, data are lacking on quasispecies variation of the HBV pre-S region in HIV/HBV co-infection. Investigating the quasispecies variation of the HBV pre-S region and its related factors in HIV/HBV co-infection will help to better explore the pathogenic mechanism of HIV/HBV co-infection.Methods: According to the HIV antibody results obtained before treatment, chronic HBV-infected patients were divided into HIV/HBV co-infected and HBV mono-infected groups. The clinical characteristics of all patients were collected, and DNA was extracted from the serum. The HBV pre-S region was amplified by nested PCR and was further TA cloned. BioEdit software 7.0 was used for sequence alignment with reference to the standard sequence of the matched HBV genotype. We used 1:1 propensity score matching (PSM) to control for baseline confounding factors between the two groups.Results: After 1:1 PSM, we identified 100 patients with similar propensities: 50 HIV/HBV co-infected patients and 50 HBV mono-infected patients. HBV quasispecies indices were lower in the HIV/HBV co-infected group than those in the HBV mono-infected group. A significant correlation was observed between all quasispecies indices and soluble cluster of differentiation 163 (sCD163) and interleukin-18 (IL-18) in the HIV/HBV co-infected group; however, this phenomenon was not found in the HBV mono-infected group.Conclusion: Combined HIV infection reduces quasispecies heterogeneity in the HBV pre-S region, and the quasispecies heterogeneity is related to the sCD163 and IL-18 levels.Keywords: HIV, HBV, quasispecies, pre-S region, inflammation

Yuan Nie,1,2,* Xi-Zi Deng,1,* Yun Lan,1 Feng Li,1 Feng-Yu Hu1 1Research Institute, Guangzhou Eighth People’s Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng-Yu HuResearch Institute,Guangzhou Eighth People’s Hospital Affiliated to Guangzhou Medical University, No. 627, Dongfeng Road, Yuexiu District, Guangzhou 510030, Guangdong, People’s Republic of ChinaEmail gz8hhfy@126.comBackground: Combined HIV infection can accelerate HBV-induced liver disease. It is known that HBV Pre-S deletion is closely related to HBV-associated terminal liver disease in HBV mono-infection. Currently, data on HBV Pre-S quasispecies feature deletion in HIV/HBV co-infected patients are lacking.Methods: The characteristics and blood samples of patients with chronic HBV infection were collected and classified into an HIV/HBV co-infection group and an HBV mono-infection group according to HIV antibody results before treatment. HBV DNA in serum was extracted. The HBV Pre-S region was amplified by nested-PCR and was further T-A cloned. Using the standard sequence of the matched genotype HBV as a reference, BioEdit 7.0 software was employed for sequence alignment.Results: HBV Pre-S regions were successfully amplified from 147 patients, including 71 cases in the HIV/HBV co-infected group and 76 cases in the HBV mono-infected group. The proportion of the HIV/HBV co-infected group with Pre-S quasispecies deletion was lower than that of the HBV mono-infected group. By analyzing the frequency of Pre-S quasispecies in the two groups, the frequency of Pre-S quasispecies in HIV/HBV co-infected patients with Pre-S quasispecies was higher than HBV mono-infected patients. The frequency of Pre-S quasispecies deletion of the S protein promoter region in the HIV/HBV co-infected group was significantly higher than that in the HBV mono-infected group.Conclusion: High-frequency Pre-S quasispecies deletions are predominant in HIV/HBV co-infected patients; however, low-frequency Pre-S deletions are predominant in HBV mono-infected patients, providing a reference for the pathogenesis of the accelerated progression of liver disease in HIV/HBV co-infection.Keywords: human immunodeficiency virus, hepatitis B virus, quasispecies, Pre-S region, deletion