Changing Epidemiology of Hepatitis B Virus and Hepatitis C Virus Coinfection in a Human Immunodeficiency Virus-Positive Population in China: Results From the Third and Fourth Nationwide Molecular Epidemiologic Surveys.

BACKGROUND: The transmission of human immunodeficiency virus (HIV) and hepatitis B virus (HBV)/hepatitis C virus (HCV) is similar in modes/routes and related risk factors. Understanding the long-term changing epidemiology of HIV, HBV, and HCV coinfection is important for evaluation of existing disease control policy and healthcare planning. We describe HBV and HCV coinfection based on the latest 2 nationwide molecular epidemiologic surveys of HIV infection in mainland China in 2007 and 2015. METHODS: Seroprevalence of HBV and HCV infections was determined in antiretroviral treatment (ART)-naive people living with HIV-1 (PLWH) from 2 nationwide surveys conducted in 2007 and 2015 from 31 provinces, municipalities, and autonomous regions in mainland China. Demographic characteristics, route of HIV transmission, and CD4+ cell count were captured in the national database. Logistic regression was used to study the association between coinfection status and possible relevant risk factors. RESULTS: A total of 6611 (n = 1571 in 2007; n = 5040 in 2015) ART-naive PLWH met the eligibility criteria. The prevalence of HBV and HCV coinfection in PLWH decreased from 61.1% in 2007 to 18.0% in 2015. Significant coinfection proportion reduction was found for HCV (from 53.7% to 4.9%), and a moderate decrease for HBV (17.8% to 13.9%). There was an increase of HBV/HIV coinfections among 12 provinces, municipalities, and autonomous regions, associated with domestic migration (adjusted odds ratio, 6.34 [95% confidence interval, 1.82-22.09]). CONCLUSIONS: A significant decrease of HBV and HCV coinfection in PLWH was observed. Due to limited health resources and high transmission efficiency, concerted efforts should be made to further control viral hepatitis epidemics in HIV-positive populations.

The inference of HIV-1 transmission direction between a man who has sex with men and his heterosexual wife based on the sequences of HIV-1 quasi-species.

Currently, homosexual transmission has become one of the main routes of HIV-1 spread in China. Furthermore, about 80% Chinese men, who have sex with men (MSM), feel forced to enter eventually into heterosexual marriages due to the Chinese traditional marriage culture, which may cause HIV-1 infection in families. In this study, we identified HIV-1 transmission in a family and the direction of HIV-1 transmission from a MSM to his wife and infant, which indicated Chinese MSM may have become a potential bridge of HIV-1 transmission to their wives and children. Therefore, we need to develop more effective defence measures to prevent the spread of HIV-1 in MSM families in China.

Genome Sequence of a Novel HIV-1 Circulating Recombinant Form (CRF103_01B) Identified from Hebei Province, China.

We reported a novel HIV-1 circulating recombinant form (CRF) among three epidemiologically unlinked patients through men having sex with men in Hebei Province, China. It was named CRF103_01B (this is temporary as we have not received the CRF number from HIV databases). A near full-length genome phylogenetic tree showed that CRF103_01B was generated by three B (Western origin) segments and CRF01_AE that was described as cluster 5 lineage of CRF01_AE (CRF01-5). The emergence of CRF103_01B increased the complexity of the HIV-1 epidemic in China.

Identification of a Novel HIV-1 Second-Generation (CRF01_AE/B) Among Men Who Have Sex with Men in Tianjin, China.

In this study, we report a novel HIV-1 second-generation recombinant form composed of CRF01_AE and subtype B detected from a married HIV-positive male subject infected through homosexual behavior in Tianjin in northern China. The near full-length genome analyses showed that two regions of subtype B inserted into the CRF01_AE backbone with four recombinant breakpoints observed in the pol gene region. Subregion tree analyses demonstrated that the CRF01_AE regions of the recombinant were greatly clustered with the CRF01_AE subcluster 4 lineage, which was found primarily among men who have sex with men (MSM) in northern China. To the best of our knowledge, this is the first detection of a novel HIV-1 second-generation recombinant form (CRF01AE/B) in Tianjin, which indicates active transmission networks of HIV-1 infection among MSM in this region. The emergence of the novel second-generation recombinant form highlights the increasing complexity of HIV-1 epidemic among MSM population and the importance to monitor potential novel circulating recombinant forms.

Characterization of a Novel HIV-1 Recombinant Form (CRF01_AE/CRF07_BC/CRF08_BC) Identified from Guangxi, China.

Recently, more and more kinds of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) were identified in the population in China. A novel HIV-1 recombinant virus (2016GXNNIDU016) was identified in this study, which was isolated from an HIV-1 infected intravenous drug user in Nanning, the capital of Guangxi, China. Phylogenetic analysis of the near full-length genome (NFLG) indicated that the sequence (2016GXNNIDU016) was a monophyletic branch that did not cluster with any previously identified genotype. Recombinant analysis showed that the NFLG of 2016GXNNIDU016 is composed of CRF07_BC, CRF01_AE, and CRF08_BC, including nine mosaic segments. Differing from previously documented CRF01_AE and CRF07/08_BC recombinant forms, 2016GXNNIDU016 increases the genetic complexity of HIV-1 in Guangxi. The constant emergence of novel recombinant forms should draw our attention to make more efforts in supervising and preventing the spread of HIV infection.

Another Near Full-Length Sequence of an HIV-1 CRF01_AE/CRF07_BC Recombinant Virus from a Man Who Has Sex with Men in Tianjin, China.

Surprisingly, more new unique recombinant forms (URFs) of CRF01_AE/CRF07_BC recombinant viruses were found in Tianjin, China, recently. Here we identified another novel HIV-1 recombinant virus (TJ20170315) isolated from an HIV-1 positive man who has sex with men in Tianjin, China. Phylogenetic analysis of the near full-length genome of TJ20170315 showed that it formed a monophyletic branch within the cluster of CRF01_AE reference sequences. Recombinant analysis showed that the virus kept the CRF01_AE parental backbone, and one CRF07_BC segment was inserted into gag, pol genes of the CRF01_AE backbone. Nowadays, multiple kinds of circulating recombinant forms (CRFs) and URFs were identified among men who has sex with men in China. The emergency of URFs highlights the complexity of HIV-1 infection in Tianjin, China, and implies that the next new CRF and HIV-1 epidemic are coming on the road.

Genomic Characterization of a Novel HIV-1 CRF01_AE/07_BC Recombinant Virus from a Married Man Who Has Sex with Men in Tianjin, China.

We report in this study a novel HIV-1 second-generation recombinant form (TJIH0172) composed of CRF01_AE and CRF07_BC isolated from a married HIV-positive male subject infected through homosexual behavior in Tianjin, China. The phylogenetic analysis of the near full-length genome of TJIH0172 reveals that one region of CRF07_BC inserted into the CRF01_AE backbone with two recombinant breakpoints observed in the vpu and env gene regions, respectively. The CRF01_AE regions (the regions I and III) of the recombinant are greatly clustered with the CRF01_AE subcluster 4 lineage, which is mainly circulating among men who have sex with men (MSM) in northern China. The CRF07_BC region (II) is clustered with two sequences (JX960600 and KF250366), which were discovered in the MSM population in Liaoning Province and Beijing city in northern China, respectively. The emergence of the novel recombinant strain from a married man who has sex with men in Tianjin, China, highlights the increasing complexity of the HIV-1 epidemic between MSM and their female partners and further molecular epidemiological investigation should be taken to track married MSM and their female partners to prevent HIV transmit from HIV high-risk populations to general populations.

Characterization of a Novel HIV-1 CRF01_AE/CRF07_BC Recombinant Virus Among Men Who Have Sex with Men in Tianjin, China.

We report here a novel human immunodeficiency virus type 1 (HIV-1) second-generation recombinant form comprising CRF01_AE and CRF07_BC isolated from an HIV-positive male subject infected among men who have sex with men (MSM) in Tianjin in north China. The phylogenetic analysis of the near full-length genome of TJIH0345 reveals that three regions of CRF01_AE were inserted into the CRF07_BC backbone with five recombinant breakpoints observed in the pol, vif, vpu, and env gene regions whose genome structure is distinctly different from other circulating recombinant forms and unique recombinant forms previously reported. The continued emergence of the novel recombinant strain in Tianjin, China, highlights the increasing complexity of the HIV-1 epidemic among the MSM population, and further molecular epidemiological investigation should be done to track the genetic evolution of HIV-1 strains to prevent HIV transmission.

Genomic Characterization of a Novel HIV-1 Second-Generation Recombinant Form (CRF01_AE/07_BC) from a Married Man Who Has Sex with Men in Zhejiang, China.

We report here a novel HIV-1 recombinant form detected from a married HIV-positive man infected through homosexual behavior in Zhejiang, China. The breakpoint analysis of near full-length genome demonstrated a complex genome organization comprising two circulating recombinant forms (CRFs), CRF01_AE and CRF07_BC, both well-known CRFs in China. The parental CRF01_AE region (II) of recombinant clustered together with a previously reported cluster 4 lineage. The CRF07_BC regions (I and III) clustered within CRF07_BC references. The ongoing generation of intersubtype recombinant viruses increases the complexity of the HIV-1 epidemic and illustrates the necessity of persistent surveillance of the transmission of HIV-1.

Using Baidu Search Engine to Monitor AIDS Epidemics Inform for Targeted intervention of HIV/AIDS in China.

China's reported cases of Human Immunodeficiency Virus (HIV) and AIDS increased from over 50000 in 2011 to more than 130000 in 2017, while AIDS related search indices on Baidu from 2.1 million to 3.7 million in the same time periods. In China, people seek AIDS related knowledge from Baidu which one of the world's largest search engine. We study the relationship of national HIV surveillance data with the Baidu index (BDI) and use it to monitor AIDS epidemic and inform targeted intervention. After screening keywords and making index composition, we used seasonal autoregressive integrated moving average (ARIMA) modeling. The most correlated search engine query data was obtained by using ARIMA with external variables (ARIMAX) model for epidemic prediction. A significant correlation between monthly HIV/AIDS report cases and Baidu Composite Index (r = 0.845, P < 0.001) was observed using time series plot. Compared with the ARIMA model based on AIDS surveillance data, the ARIMAX model with Baidu Composite Index had the minimal an Akaike information criterion (AIC, 839.42) and the most exact prediction (MAPE of 6.11%). We showed that there are close correlations of the same trends between BDI and HIV/AIDS reports cases for both increasing and decreasing AIDS epidemic. Therefore, the Baidu search query data may be a good useful indicator for reliably monitoring and predicting HIV/AIDS epidemic in China.

Characterization of a New HIV-1 CRF01_AE/B Recombinant Virus Form Among Men Who Have Sex with Men in Shanghai, China.

To date, there are 16 types of CRF01_AE/B circulating recombinant forms identified, and most of them are distributed in Asian countries such as China, Malaysia, and Singapore. Previous HIV molecular epidemiological surveys showed that CRF01_AE (27.6%) and B (9.6%) subtypes are predominant strains in mainland of China. At the same time, the HIV-1 virus spreads faster in the men who have sex with men (MSM) population than in other risk groups. In Shanghai district, ∼66.0% of newly reported cases were infected through homosexual transmission. In this study, we report a novel recombinant strain of CRF01_AE/B. The near full-length genome phylogenetic tree showed that the strain clustered with the CRF01_AE reference sequence and placed in the peripheral position within the branch of the CRF01_AE strain. Subregional evolutionary results indicated that the CRF01_AE subtype was derived from cluster 4 of CRF01_AE, which is mainly distributed in northern China. The subtype B was correlated with the U.S./Europe B, which are widely prevalent in the Chinese MSM population. In recent years, a large number of recombinant forms between CRF01_AE and B strains are continuously emerging in China. Therefore, understanding the current epidemic recombinant forms will have significant implications for prevention and treatment of HIV/AIDS.

Near Full-Length Genome Sequence of a Novel HIV-1 Second-Generation Recombinant Form (CRF01_AE/CRF07_BC) Detected Among Men Who Have Sex with Men in Tianjin, China.

In recent years, men who have sex with men (MSM) have been the most affected population with fastest growing human immunodeficiency virus (HIV) prevalence in China. In our study, a novel CRF01_AE/07_BC HIV-1 recombinant form (TJIH0069), with four unique breakpoints in the pol, vpr, and nef gene regions, was identified among MSM in Tianjin City in north China. The CRF01_AE regions (regions I, III, and V) of the recombinant are all clustered together with a previously described sequence (HQ215555), which was exclusively circulating among MSM in Shijiazhuang city of Hebei Province in north China. The CRF07_BC regions (II and IV) are clustered with BJ070032 and JX960600, which were discovered from MSM population in north China. The continuous emergence of a similar pattern of recombinant strain between the two MSM-adapted existing circulating recombinant forms (CRFs) highlights the importance to monitor potential new CRFs for early and precise control and prevention.

Near Full-Length Genomic Characterization of HIV-1 CRF01_AE/B Recombinant Strains Identified in Hebei, China.

This study reports a novel HIV-1 recombinant form of CRF01_AE/B that was isolated from a 22-year-old male individual (HE150308) residing in Hebei province, China. The near full-length genome (NFLG) phylogenetic tree showed that the strain was clustered with CRF01_AE reference sequences and placed at the peripheral position within the branch of CRF01_AE strains. The bootscaning and similarity plot analysis revealed that the NFLG of this novel recombinant was composed of eight interlaced segments, including four CRF01_AE and four subtype B segments separated by seven breakpoints observed in the gag, pol, and nef regions of HIV-1 genome. Phylogenetic analysis demonstrated that the CRF01_AE subregions were from the previously identified CRF01_AE cluster 5, and the B subregions were correlated with the B strains originated from Europe and America. They were all the lineages widely prevalent in men who have sex with men (MSM) population in China. In recent years, a large number of recombinants between CRF01_AE and B strains are constantly emerging in the MSM population in China. This continual and recurrent recombination between CRF01_AE and B in high-risk group people deserves more attention and further monitoring.

Disparate impact on CD4 T cell count by two distinct HIV-1 phylogenetic clusters from the same clade.

HIV-1 evolved into various genetic subtypes and circulating recombinant forms (CRFs) in the global epidemic. The same subtype or CRF is usually considered to have similar phenotype. Being one of the world's major CRFs, CRF01_AE infection was reported to associate with higher prevalence of CXCR4 (X4) viruses and faster CD4 decline. However, the underlying mechanisms remain unclear. We identified eight phylogenetic clusters of CRF01_AE in China and hypothesized that they may have different phenotypes. In the National HIV Molecular Epidemiology Survey, we discovered that people infected by CRF01_AE cluster 4 had significantly lower CD4 counts (391 vs. 470, P < 0.0001) and higher prevalence of X4-using viruses (17.1% vs. 4.4%, P < 0.0001) compared with those infected by cluster 5. In an MSM cohort, X4-using viruses were only isolated from seroconvertors in cluster 4, which was associated with low a CD4 count within the first year of infection (141 vs. 440, P = 0.003). Using a coreceptor binding model, we identified unique V3 signatures in cluster 4 that favor CXCR4 use. We demonstrate that the HIV-1 phenotype and pathogenicity can be determined at the phylogenetic cluster level in the same subtype. Since its initial spread to humans from chimpanzees, estimated to be the first half of the 20th century, HIV-1 continues to undergo rapid evolution in larger and more diverse populations. The divergent phenotype evolution of two major CRF01_AE clusters highlights the importance of monitoring the genetic evolution and phenotypic shift of HIV-1 to provide early warning of the appearance of more pathogenic strains.

Near Full-Length Genomic Characterization of a Novel HIV Type 1 Recombinant Form (CRF01_AE/B) Identified from Anhui, China.

HIV-1 recombinant forms contribute substantially to its genetic evolution. This study reports a novel HIV-1 second-generation recombinant form (AH150299) composed of CRF01_AE and subtype B, isolated from an HIV-positive female subject infected through heterosexual contact in Anhui province of eastern China. The analyses of the near full-length genome sequence showed that one subtype B segment was inserted into the CRF01_AE backbone, with two recombinant breakpoints observed in the vif/vpr and env/nef gene regions. Phylogenetic analysis demonstrated that the CRF01_AE region of the recombinant belongs to CRF01_AE cluster 4, and the B subregions were correlated with the B strains circulating among men who have sex with men in China. In recent years, the emergence of novel recombinant strains reflected the complexity of the HIV-1 epidemic in Anhui, suggesting the significance of continuous monitoring of the dynamic transmissions of HIV-1 in eastern China.

Near Full-Length Genome Sequence of a Novel HIV-1 Recombinant Form (CRF01_AE/07_BC) Detected Among Men Who Have Sex with Men in Zhejiang, China.

The prevalence of HIV type 1 among men who have sex with men (MSM) is increasing in China. We report here a novel HIV-1 recombinant form (CRF01_AE/CRF07_BC) detected from a male patient infected with HIV-1 by homosexual behavior in Zhejiang Province of eastern China. The near full-length genome analyses showed that the unique HIV-1 recombinant isolate (16ZJ305) has two recombinant breakpoints observed in the env and tat/rev gene regions. To date, several novel CRF01_AE/CRF07_BC recombinant forms have been identified, which may imply an active transmission network of HIV-1 infection among MSM. Further studies of the molecular epidemiology of the HIV-1 epidemic among MSM are necessary to gain a better understanding of the transmission network and track the genetic evolution.

Characterization of a New HIV-1 CRF01_AE/CRF07_BC Recombinant Virus in Tianjin, China.

HIV is notorious for its rapid evolution since its transmissions from monkey to human. Currently, HIV contains multiple subtypes, circulating recombinant forms (CRFs) and unique recombinant forms (URFs). Here, from an HIV-positive mother and her child in Tianjin, China, we identified a novel HIV-1 second-generation recombinant virus (TJ20170316 and TJ20170317) between CRF01_AE and CRF07_BC. Near full-length genomes (NFLGs) were obtained from both samples, and they shared very close sequences, except some point mutations. Phylogenetic analyses of the NFLGs showed that they consist of CRF01_AE backbone and part CRF07_BC sequences. Recombinant Identification Program and Simplot software identified four breakpoints in gag, pol, vif, and tat genes in TJ20170316, totally different from other reported CRFs and URFs. The emergence of such URFs in Tianjin, China, highlights the complexity of HIV-1 epidemic and more measures should be taken to prevent HIV transmissions.