HIV-1 CRF07_BC transmission dynamics in China: two decades of national molecular surveillance.

ABSTRACTBy analyzing an unprecedentedly large, longitudinal HIV-1 CRF07_BC sequence dataset collected from China in the past two decades, we sought to build CRF07_BC lengthwise transmission networks, and understand its transmission dynamics. We divided CRF07_BC into two clusters based on phylogenetic analysis and an estimation of the pairwise genetic distance at 0.7%. Of 6213 sequences, 3607 (58.1%) linked to ≥1 other sequence. CRF07_BC was divided into two clusters: 07BC_O and 07BC_N. The 07BC_O is the original CRF07_BC, circulating in people who inject drugs (PWID) and heterosexuals, predominantly in southwestern and northwestern provinces of China. The 07BC_N is a new cluster, identified mostly in men having sex with men (MSM) in the northern provinces of China. Bayesian analysis indicates that CRF07_BC has experienced two phases of exponential growth, which was first driven by 07BC_O then 07BC_N. Compared to 07BC_O, the proportion of the parameter of population transmission risk (TR) of 07BC_N has risen constantly. The power-law function analyses reveal that 07BC_N has increased over years with higher degree. In 07BC_N, only 13.16% of MSM were linked to other risk groups, but these links represent 41.45%, 54.25%, and 55.07% of links among heterosexual females, heterosexual males, and male PWID respectively. This study indicates that CRF07_BC has evolved into two clusters in China, and their distributions are distinct across risk groups and geographical regions. 07BC_N shows a greater risk of transmission, and has gradually replaced 07BC_O. Furthermore, the results show that strengthening the MSM interventions could lower the rapidity of 07BC_N transmission in all risk groups.

CRF01_AE and CRF01_AE Cluster 4 Are Associated With Poor Immune Recovery in Chinese Patients Under Combination Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) clades and clusters have different epidemic patterns and phenotypic profiles. It is unclear if they also affect patients' immune recovery (IR) in combination antiretroviral therapy (cART). METHODS: We conducted a cohort study on 853 patients under cART for evaluating the impacts of viral factor on host IR. We used generalized estimating equations for factors affecting CD4 recovery, Kaplan-Meier curves for probability of achieving IR, and Cox hazards model for factors influencing IR capability. RESULTS: Besides low baseline CD4 and old age, CRF01_AE and its cluster 4 were independently associated with lower CD4 cell level (P ≤ .003), slower IR (P ≤ .022), fewer patients (P < .001), and longer time achieving IR (P < .001), compared with CRF07_BC and CRF01_AE cluster 5. Higher percentage of CXCR4 (X4) viruses in the CRF01_AE and cluster 4-infected patients, compared with their respective counterparts (P < .001), accounted for the poor IR in infected patients (P < .001). Finally, we revealed that greater X4 receptor binding propensity of amino acids was exhibited in CRF01_AE clade (P < .001) and its cluster 4 (P ≤ .004). CONCLUSIONS: Our study demonstrates that the CRF01_AE clade and cluster are associated with poor IR in patients under cART, which is ascribed to a high proportion of viruses with X4 tropism. HIV-1 genotyping and phenotyping should be used as a surveillance tool for patients initiating cART. CCR5 inhibitors should be used with caution in regions with high prevalence of X4 viruses.

Transmission of HIV and HCV within Former Soviet Union Countries.

Background: Following the collapse of the Union of Soviet Socialist Republic (USSR) in 1991, trans-border mobility increased within the former Soviet Union (FSU) countries. In addition, drug-trafficking and injection drug use began to rise, leading to the propagation and transmission of blood-borne infections within and across the FSU countries. To examine the transmission of blood-borne infections within this region, we analyzed the phylogenetic relationship of publically available sequences of two blood-borne viruses, hepatitis C virus (HCV) and human immunodeficiency virus (HIV), from FSU countries. Methods: We analysed 614 and 295 NS5B sequences from HCV genotypes 1b and 3a, respectively, from 9 FSU countries. From 13 FSU countries, we analysed 347 HIV gag and 1282 HIV env sequences. To examine transmission networks and the origins of infection, respectively, phylogenetic and Bayesian analyses were performed. Results: Our analysis shows intermixing of HCV and HIV sequences, suggesting transmission of these viruses both within and across FSU countries. We show involvement of three major populations in transmission: injection drug user, heterosexual, and trans-border migrants. Conclusion: This study highlights the need to focus harm reduction efforts toward controlling transmission of blood-borne infections among the abovementioned high-risk populations in the FSU countries.

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.

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.

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.

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 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.