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Article

Geographic Transmission and Epidemic History of HIV-1 CRF01_AE, CRF07_BC, and HCV Subtype-6w among Taiwanese Persons Who Inject Drugs

by
Yen-Ju Chen
1,2,
Jason C. Huang
2,
Hung-Chin Tsai
3,
Yu-Hui Lin
4,
Kuo-Feng Hsu
5,* and
Hsin-Fu Liu
6,7,*
1
Research Assistant Center, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan 701033, Taiwan
2
Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
3
Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan
4
Department of Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
5
Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114202, Taiwan
6
Department of Medical Research, Mackay Memorial Hospital, Taipei 25169, Taiwan
7
Institute of Biomedical Sciences, MacKay Medical College, New Taipei City 25245, Taiwan
*
Authors to whom correspondence should be addressed.
Viruses 2022, 14(10), 2142; https://doi.org/10.3390/v14102142
Submission received: 18 August 2022 / Revised: 19 September 2022 / Accepted: 25 September 2022 / Published: 28 September 2022
(This article belongs to the Special Issue Virology Research in Taiwan)
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Versions Notes

Abstract

:
Persons who inject drugs (PWID) and their risk-related behaviors (e.g., unprotected sex and sharing needles/syringes/other injection equipment) have caused severe public health problems, especially in the rapid spread of HIV-1 and HCV. Here, we reconstructed the epidemic history of HIV-1 circulating recombinant form (CRF) 01_AE, CRF07_BC, and HCV subtype-6w among Taiwanese PWID. The timescales were estimated using phylogenetic and Bayesian coalescent analyses. The results revealed that CRF01_AE started to circulate in the Taiwanese PWID population in central Taiwan at 1992.5 (95% credible region: 1988.8–1995.9) and spread to other regions of Taiwan, while CRF07_BC was first identified in southern Taiwan at 2000.0 (95% CR: 1997.8–2002.2) and then spread northward to central-northern Taiwan. All HCV-6 strains were from Asia (that is, China, Myanmar, Taiwan, and Vietnam) and originated in 1928.1 (95% CR: 1890.2–1966.0). Furthermore, subtype-6w isolates from different regions of Taiwan appeared to share a common source that existed in the mid-1990s (95% CR: 1985.0–2001.8) or thereabouts. The routes of drug trafficking and the resulting high prevalence of HIV-1/HCV co-infections among PWID might have contributed to the virus transmission and promoted its spread worldwide. Long-term monitoring and policy implementation in at-risk populations would be useful for disease control.

1. Introduction

In 2021, 38.4 million people globally were estimated to have lived with HIV and the worst region is still sub-Saharan Africa [1]. A systematic review revealed that of the 16 million people who inject drugs (PWID), one-fourth lived in East and Southeast Asia [2]. PWID and their risk-related behaviors (e.g., unprotected sex and sharing syringes/heroin solutions/other injection equipment) have caused server public health problems, especially regarding the rapid spread of HIV-1 and HCV. According to the distribution data for the HIV-1 subtypes and the circulating recombinant forms (CRFs) in Asia, the HIV-1 subtype B’ and CRF01_AE are the main subtypes among PWID in Thailand [3,4,5], Myanmar [6], and Vietnam [7], while CRF07_BC is the predominant strain among PWID in China and Taiwan [8,9,10,11,12]. The strain CRF07_BC is derived from the Thai subtype B’ and Indian subtype C lineages [13]. Since 1997, CRF07_BC has been isolated from PWID in several provinces of China [8,9]. This strain is presumed to originate in Yunnan province [14,15] and has spread northwest to Xinjiang province and east to Guangxi province [13,16]. In this context, Yunnan plays an important role as an entry point for heroin trafficking into China [17] and is considered an epicenter of HIV/AIDS in China [13].
In Taiwan, most HIV-1 infected cases in the PWID were CRF07_BC [10,11,12]. Phylogenetic analyzes revealed that Taiwanese CRF07_BC strains clustered with CRF07_BC isolates from Xinjiang (97CN54, 97CN001, and 98CN009) and Guangxi (CNGL179) provinces of China [10,11,12]. Furthermore, it has been suggested that CRF07_BC initially circulated in southern Taiwan (Tainan) and then to other regions of Taiwan later [10,11]. Although predominate in PWID, CRF07_BC has also been spread to men who have sex with men (MSM) and heterosexuality [11]. Besides CRF07_BC, an outbreak of CRF01_AE infection was identified among PWID in Central-North Taiwan [10,11]. Evidence suggests that CRF01_AE was introduced into Taiwanese PWID through unprotected sex [11].
Both HIV-1 and HCV are considered blood-borne diseases, which are transmitted mainly through blood contact with infections. The prevalence of chronic hepatitis C in the Taiwanese population is approximately 2.1%, which was among the countries with the higher prevalence in Asia [18]. Paintsil et al. pointed out that HCV dried on inanimate surfaces can remain infectious for up to six weeks at normal room temperature [19]. Currently, the new HCV infection has shifted to PWID and other high-risk groups, including HIV-infected people and MSM who did not take effective safety measures. Traditional HCV treatment was a combination therapy (interferon injection plus oral ribavirin medicine), which successfully cured 70–80% of genotype 1 and >90% of genotype 2 patients [20,21,22,23,24]. With direct-acting antivirals (DAAs) that were launched in 2014, the successful cure rate increased to 95%.
During the explosive 2004–2006 outbreak of HIV-1 CRF07_BC among Taiwanese PWID, almost all of them (~99.3%) were HIV-1/HCV co-infections [10,11,25]. Previous studies on the geographical distribution of HCV showed that different dominant types existed throughout the world [26,27] and profound prevalence changes were observed in different genotypes of HCV over time [28,29]. Four predominant subtypes, namely 6a, 1a, 1b, and 3a, were identified in blood specimens from Taiwanese PWID infected with HCV. In particular, subtype-6w (1.4%) was detected at the same time in this subpopulation (see Table A1). Several studies have attempted to reconstruct the epidemic history of HIV-1 outbreaks among PWID in Asia [17,30,31]. In our previous study, we included HIV diagnosis when submitting virus nucleotide sequences to GenBank. To avoid errors in the calculation, we used the specimen collection date for all isolates to estimate the epidemic period. Furthermore, we focused only on PWID infected with HIV-1 CRF01_AE, CRF07_BC, and HCV-6. Since HCV subtype-6w is uncommon and no literature has yet described its transmission routes and studies in Taiwanese IDUs focused only on subtype-6w, we conducted an investigation of HCV to track its transmission routes of subtype-6w and estimate the time of emergence of genotype-6 among Asian PWID.

2. Materials and Methods

2.1. Subjects

The research procedures for the current study are shown in Figure A1. A total of 1427 PWID were recruited from Taipei City Hospital, Sindian Drug Abuse Treatment Center, Taipei Detention Center and Prison, Taoyuan Woman’s Prison (Northern Taiwan), Taichung Detention Center and Prison, Yunlin Second Prison, Nantou Detention Center (Central Taiwan), Tainan Detention Center, and Kaohsiung Prison (Southern Taiwan). Among the blood samples collected, 611 cases collected between 2004 and 2005 were shown to be infected with HIV-1 while 9 cases collected between 2005 and 2008 were HCV-6w. To track the routes of Taiwanese HIV-1 CRF01_AE, CRF07_BC, and HCV-6w transmission, we integrated sequences of Asian isolates available from the NCBI database (https://www.ncbi.nlm.nih.gov/nucleotide/, accessed on 8 July 2021) in our evolutionary analysis. All Taiwanese PWID were obtained by direct sequencing in our laboratory and those retrieved from GenBank were listed in Table A2.
Sociodemographic data and information on the types of illegal drugs used, history of drug abuse, risk factors associated with HIV-1 transmission, and years of the first HIV/HCV positive diagnosis were collected using a self-administered questionnaire. Peripheral blood samples were collected to allow analysis of virus genotype. Informed consent was obtained from all participants. Our research protocol was approved by the prisons and detentions administration system, as well as the Institutional Review Board of the National Yang-Ming University, Taiwan.

2.2. HIV-1 and HCV Subtyping

Viral RNA was extracted from plasma samples using the QIAamp Viral RNA mini kit (QIAGEN, Hilden, Germany). Random primer (Promega) was used in reverse transcription to generate cDNA for reverse transcriptase-polymerase chain reaction (RT-PCR). Anti-HCV antibodies from serum samples were detected using an enzyme immunoassay system (Murex 3nd, Abbott Laboratories, North Chicago, IL, USA). Specimens determined with anti-HCV antibodies or confirmed as HIV-1 positive were further analyzed. The genotypes/subtypes of HCV and HIV-1 infections were determined according to the methods described previously [10,25,32]. A set of primers, OF9-2 (forward) 5′-CGACATTACGCAGAAGTTGCCC-3′ and OR9 (reverse) 5′-AGTGTTGCTTAAGGCCTCCTGC-3′, were used to amplification of the HCV NS5B gene near full-length. Proviral nucleotide sequences were obtained by direct sequencing of PCR products using a DNA analyzer (ABI 3730, Applied Biosystems, Foster City, CA, USA).

2.3. Phylogenetic Analysis

Sequence alignment analysis with various reference strains from the Los Alamos HIV-1 database (https://www.hiv.lanl.gov/content/index, accessed on 28 May 2021) and the HCV database (https://hcv.lanl.gov/content/index, accessed on 8 July 2021) was performed using the BioEdit v7.2.6.1 program [33]. The MEGA X program [34] was used to find the best fit nucleotide substitution model and to construct phylogenetic trees using neighbor-joining (NJ) and maximum likelihood (ML) methods. For example, taking the HIV-1 env gene, the substitution model GTR + G was incorporated into the ML method, while TN93 + G (GTR and HKY models are not available here) was used to calculate the evolutionary distance for the NJ tree followed by bootstrap analysis with 1000 replicates [35]. Considering the best-fit models for the HCV NS5B gene, the substitution models for both the ML and NJ tree were K2 + G + I. At least four strains of all subtypes were used as reference sequences and isolates from Asian PWID were included for phylogenetic analysis (see Figure A2). Bootstrap values (≥70%) were used as an indicator of the significance of the clusters.

2.4. Nucleotide Sequence Accession Numbers

The HIV-1 env sequences (OM287868–OM287928) and the HCV NS5B sequences (OM287929–OM287937) were obtained from the current study and deposited in GenBank.

2.5. Bayesian Coalescent Inference

Evolutionary rates were obtained using the Bayesian Markov chain Monte Carlo (MCMC) approach implemented in BEAST v2.5.1 [36]. General time-reversible (GTR) [37,38,39] substitution models with gamma-distributed among-site rate variation involving six categories [40] were used to estimate evolutionary rates and construct tree topologies. Constantly sized, exponentially growing, and Bayesian skyline coalescent models were used for each case [41] and each MCMC chain was run for at least 10,000,000 states and sampled in every 1000 states. Posterior probability densities were calculated, and the convergence of the chains was verified using the Tracer v1.7.1 [42] with 10% of each chain discarded as burn-in.

2.6. Statistical Analysis

The Pearson χ2 test and Fisher’s exact test were performed in univariate analysis of demographic data. The difference between groups with a p-value < 0.05 was considered statistically significant. The p-values were two-tailed and unadjusted for multiple comparisons.

3. Results

3.1. Geographical Distribution of HIV-1 CRF01_AE, CRF07_BC, and HCV Subtype-6w among Taiwanese PWID

From 2004 to 2005, almost all Taiwanese HIV-1 positive PWID were infected with CRF07_BC. However, we found another small-scale outbreak strain that circulated in this population in central-north Taiwan. These were judged according to their time of crime and the place of sentences.
As shown in Figure A3, the distribution of Taiwanese PWID infected with HIV-1 CRF01_AE (n = 24), HIV-1 CRF07_BC (n = 982), and HCV subtype 6w (n = 9) during 2004–2008. The dates of HIV diagnosis and sample collection for most CRF01_AE infections were mainly in 2005 (Figure A2 and Table A2). The CRF07_BC sequences of Taiwanese PWID were grouped into several distinct phylogenetic clusters based on collection places [11] (details shown in Table A2). Based on the dates of HIV diagnosis, our data implied that CRF01_AE started to circulate in the Taiwanese PWID population in Central Taiwan and then spread to other regions of the island. In contrast, CRF07_BC first appeared in the south and moved northward to expand to central-north Taiwan (Figure A2 and Table 1).
The nine Taiwanese PWID infected with HCV-6w were identified when serving their prison sentences. Among them, five were HCV mono-infections and the other four cases were HIV/HCV coinfections. Six of the cases were from northern Taiwan (Taipei Detention Center, Sindian Drug Abuse Treatment Center and Taoyuan Woman’s Prison), two were from central Taiwan (Taichung Prison and Yunlin Second Prison), and one was from southern Taiwan (Kaohsiung Prison) (Figure A3).

3.2. An Estimated Timescale of the Spread of CRF01_AE and CRF07_BC among Taiwanese PWID

When estimating the time scale of the spread of HIV-1 CRF01_AE and CRF07_BC in Asia, we adopted the data set based on GTR + Γ6 constant model to pinpoint the time of the most recent common ancestor (tMRCA) of the HIV-1 strains circulating in this area. Compared to the results of the three models, similar conclusions could be reached (Table 1). After systematic analyses, we followed the likelihood of constant size, exponential growth, and the Bayesian skyline model (CRF01_AE: −15,559.7307, −15,548.8808, and −15,719.0827; CRF07_BC: −4939.2117, −4933.7994, and −4957.3370) and found that the exponential growth model was the best to present its transmission.
The estimated phylogeny using the env gene showed that all Taiwanese CRF01_AE and reference strains formed a single clade. However, there are two different risk groups in Taiwan [11], namely PWID and other sexual groups (e.g., homo, hetero, and bisexuals). The former population that contained sequences from Taipei Detention Center, Taipei Prison, Yunlin Second Prison, and Taichung Prison have a common point. Almost all samples were obtained in 2005 (Table S2). All CRF01_AE strains from Asia (i.e., China, Myanmar, Taiwan, and Vietnam) were dated 1979.0 (95% credible region, CR: 1973.1–1984.0). Concerned about drug addicts, CRF01_AE was introduced to China in 1986.5 (95% CR: 1980.0–1990.8) and then spread to Vietnam in 1988.4 (95% CR: 1984.7–1991.8), Taiwan in 1992, and Myanmar in 1994.6 (95% CR: 1990.2–1999.8). Additionally, CRF01_ AE was first introduced to other Taiwanese sexual groups in 1988.0 (95% CR: 1984.5–1991.1) and then spread to Central Taiwan in 1992.5 (95% CR: 1988.8–1995.9) and Northern Taiwan in 1994.1 (95% CR: 1989.5–1998.4) (Table 1 and Figure 1a). A comparison with our previous findings [11] suggested that CRF01_AE was introduced into Taiwanese PWID through unprotected sex and then caused a local epidemic among PWID through the exchange of injection equipment.
As summarized in Table 1, all CRF07_BC strains from Asia (i.e., China, Myanmar, and Taiwan) were rooted in 1987.9 (95% CR: 1981.0–1993.9). CRF07_ BC was introduced to China at 1987.9 and spread to Myanmar at 1995.0 (95% CR: 1987.6–2002.0) and to Taiwan at 1999.9 (95% CR: 1997.8–2001.9). Subsequently, this strain spread to other regions of Taiwan in 2001.3 (95% CR: 1998.6–2004.0), 2002.9 (95% CR: 2001.2–2004.2), and 2000.0 (95% CR: 1997.8–2002.2) in Northern, Central, and Southern Taiwan, respectively. The CRF07_BC strains from different regions of Taiwan seem to share a common source that existed in 2000 or thereabouts (95% CR: 1997.8–2001.9) and was part of the Southern Taiwan PWID. This suggests that southern Taiwan was the entry site for CRF07_ BC (Table 1 and Figure 1b).

3.3. An Estimated Timescale of the Spread of HCV Subtype-6w among Taiwanese PWID

Similarly to the estimation of the timescale of HIV-1 spread, we adopted the data set based on GTR + Γ6 + I constant model to pinpoint the tMRCAs of HCV-6 and found that the exponential growth model (likelihood in CS: −9744.679, EG: −9717.44, and BS: −9868.01) is the best way to present its transmission.
Phylogeny analysis using the NS5B gene showed that all Asian PWID and reference strains formed a single clade. As summarized in Table 2, all genotype-6 strains from Asia (i.e., China, Myanmar, Taiwan, and Vietnam) were rooted in 1928.1 (95% CR: 1890.2–1966.0). Subtypes 6a, -6n, and -6w had existed in the Taiwanese PWID population (Table A1). Taking subtype-6a for example, it was introduced into Vietnam at 1993.5 (95% CR: 1977.5–2001.3) and later into China at 1994.5 (95% CR: 1988.9–2000.9). Subtype-6n was initially introduced to China (1987.8, 1952.0–2005.0) and then spread to Myanmar (1990.4, 1954.7–2007.7). It is noteworthy that this strain was found to originate in Yunnan (1987.8, 1953.1–2007.0) and spread eastward to Suzhou, Zhenjiang, and Jiangsu in the early and mid-2000s. Furthermore, subtype-6w isolates from different regions in Taiwan seem to share a common source that existed in mid-1990 (95% CR: 1985.0–2001.8) or thereabouts (Table 2 and Figure 1c).

4. Discussion

Takebe et al. reported that CRF07_BC strains from different regions in China (including Xinjiang, Liaoning, and probably Guangdong and Sichuan) were likely to share a common ancestor that existed in Yunnan province around 1993 (95% CR: 1991.2–1995.2; gag) [13,31]. This suggests that CRF07_BC spreads almost simultaneously to various regions of China [13,31]. Furthermore, CRF07_BC also spread to Taiwan from the South around 1999.7 (95% CR: 1998.2–2001.1; env) and spread to the central-north part of Taiwan in 2002.1 (95% CR: 2001.3–2002.9; env) [10,13,30], resulting in a major HIV epidemic among PWID in Taiwan [10,11,12,13,31]. The dissemination routes of CRF07_BC in China and Taiwan were those reported in previous studies [11,13,30,31]. To compare the main differences between the use of the date of sample collection versus the date of HIV-1 diagnosis to estimate the time of the emergence of the CRF01_AE and CRF07_BC strains, and to consolidate the integrity of our data, we added more sequences from West Taiwan (e.g., Sindian, Taoyuan, Taichung, Yunlin, and Kaohsiung) in the analysis. As we all know that CRF07_BC circulated in southern Taiwan first, even adding the sequences from the most south area (i.e., Kaohsiung), the tMRCAs of CF07_BC among Taiwanese PWID were behind the estimates as previously reported [13,30,31]. The data obtained using the date of sample collection are more accurate than those using the date of diagnosis. This finding showed why it is necessary to use the correct date to estimate the time of emergence of HIV-1 subtypes or CRFs. Furthermore, our results revealed that the estimated introduction time of CRF01_AE in Taiwan PWID (1992 later) was earlier than that of CRF07_BC (1999.9), and because of the less aggressiveness of CRF01_AE [43], it only caused a local epidemic initially.
The estimated prevalence of HCV-6 in some regions of Southeast Asia, especially among patients with PWID and major thalassemia, is as high as 50% [44]. Injecting drug abuse is possibly responsible for the high frequency of this genotype in certain parts of Asia. HCV-6 has considerable genetic diversity with 23 subtypes (a–w). HCV-6 infected with HCV-6 respond better to interferon-based therapy compared to genotype 1, although the clinical characteristics and side effect profiles in patients are similar between HCV-6 and other genotypes [44]. Our study showed that HCV-6 was as common as genotype 1 (34.7% vs. 43.5%, Table S1) in the Taiwanese PWID population. According to a large-scale survey on the seroprevalence of HCV in Taiwan [45], the prevalence of injecting drug abuse and incomplete disinfection of medical utensils would cause a small-scale outbreak of HCV in local areas. Furthermore, residents have a higher prevalence of HCV when they were born in an earlier cohort [45]. As shown in Table A1, a cross-sectional study with 624 PWID recruited in Taiwan was conducted in 2007–2008. The overall prevalence of HIV and HCV infection was 44.1% (275/624) and 80.4% (502/624), respectively. The prevalence of HCV mono-infection and HIV/HCV co-infection was 36.4% (227/624) and 44.1% (275/624), respectively. The issues of HCV prevention include the following: to prevent healthy people from being contaminated with infected blood and to avoid reinfection with HCV in cured cases. For those who have been cured and non-infected, regular screening tests are encouraged. Through a series of analyses, our findings appear to support the hypothesis that HCV-6 originated in Southeast Asia (Table 2). HCV-6 is highly divergent from other genotypes and has distinct genetic differences from other strains, suggesting that there may be unclassified subtypes in Asia. Therefore, the accumulation of such genetic heterogeneity suggests that this genotype has circulated, adapted, and evolved in this area for a long period.
There are several limitations to this study. First, all Asian isolates (e.g., China, Malaysia, Myanmar, and Vietnam) were restricted and obtained from the NCBI website. Second, some Asian isolates were excluded from the evolutionary analysis because the sequences were too short or contained missing sequences. Despite the limitations, this study sheds light on the routes of drug trafficking and the resulting high prevalence of HIV-1/HCV coinfections among PWID that could have contributed to regional and global transmissions. In conclusion, for the first time, we report ‘the time of emergence of common HCV and HIV-1 strains among Taiwanese PWID’ and provide a comprehensive profile suggesting the initial circulation of CRF07_BC in southern Taiwan before spreading to other regions of Taiwan. Furthermore, the importance of using the date of sample collection versus the date of HIV-1 diagnosis was also highlighted when estimating the time of the emergence of the CRF01_AE and CRF07_BC strains. Long-term monitoring and implementation in the population at risk would be useful for disease control.

Author Contributions

Conceptualization, methodology, validation, formal analysis, and writing—original draft preparation, Y.-J.C.; investigation, K.-F.H.; resources, H.-C.T. and Y.-H.L.; data curation and writing—review and editing, J.C.H., K.-F.H. and H.-F.L.; supervision and project administration, H.-F.L. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by a grant from VGH-NYMU research (VGHUST108-G3-2-2) and was a continuation of the previous two projects (DOH95-DC-1109 and DOH97-DC-1202).

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of National Yang-Ming University (940008R, 10 November 2005; 970021, 16 May 2008) and Taipei City Hospital Research Ethics Committee (TCHIRB-10808010, 12 December 2018) for studies involving humans.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study. Also written informed consent has been obtained from the patient(s) to publish this paper.

Data Availability Statement

The data presented in this study are available in [Section 2.4 and Table A2]. Part of this paper was presented at the 8th Second Member Conference and Academic Symposium held in Taiwan in 2020.

Acknowledgments

We thank the PWID who participated in this study, the peer educators and social workers from the AIDS Prevention and Research Center who helped collect the questionnaires, and the staff of the Genomic Research Center of the National Yang Ming Chiao Tung University, as well as the health clinics of the various prisons and detention centers for their administrative support and technical assistance. The Sequencing Core Facility is supported by the National Research Program for Genomic Medicine (NRPGM) of the National Science Council. Most importantly, we would like to thank Wing-Wai Wong, who provided clinical samples but unfortunately passed away in October 2018, for his contribution to this study.

Conflicts of Interest

All authors of this article do not have commercial or other associations that might pose a conflict of interest. In addition, the funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Appendix A

Viruses 14 02142 g0a1 550
Figure A1. Study flowchart. A total of 1427 Taiwanese PWID blood samples were collected from hospitals, detention centers, and prisons during 2004–2008. Four hundred sequences were used in phylogenetic and evolutionary analyzes.
Figure A1. Study flowchart. A total of 1427 Taiwanese PWID blood samples were collected from hospitals, detention centers, and prisons during 2004–2008. Four hundred sequences were used in phylogenetic and evolutionary analyzes.
Viruses 14 02142 g0a1
Viruses 14 02142 g0a2 550
Figure A2. Phylogenetic analysis of HIV-1 CRF01_AE, CRF07_BC, and HCV sequences among Asian PWID. (a) CRF01_AE, the NJ tree was constructed using MEGA under the TN93 + G model with 1000 bootstrap replicates. (b) CRF07_BC, TN93 + G and (c) HCV, K2 + G. The red point indicates the Taiwanese PWID sequences.
Figure A2. Phylogenetic analysis of HIV-1 CRF01_AE, CRF07_BC, and HCV sequences among Asian PWID. (a) CRF01_AE, the NJ tree was constructed using MEGA under the TN93 + G model with 1000 bootstrap replicates. (b) CRF07_BC, TN93 + G and (c) HCV, K2 + G. The red point indicates the Taiwanese PWID sequences.
Viruses 14 02142 g0a2
Viruses 14 02142 g0a3 550
Figure A3. Distribution of Taiwanese PWID infected with HIV-1 CRF01_AE (n = 24), HIV-1 CRF07_BC (n = 982), and HCV subtype 6w (n = 9) during 2004–2008. Each strain was labeled with a different color to denote patient characteristics, including collection place and year of HIV-1 diagnosis. The proportion of viral strains circulated into Northern-Central-Southern Taiwan per year, divided by total cases infected with the same strain, is shown in pie charts. Because Taiwanese PWID infected with HCV-6w were rare, we directly labeled their locations on the map.
Figure A3. Distribution of Taiwanese PWID infected with HIV-1 CRF01_AE (n = 24), HIV-1 CRF07_BC (n = 982), and HCV subtype 6w (n = 9) during 2004–2008. Each strain was labeled with a different color to denote patient characteristics, including collection place and year of HIV-1 diagnosis. The proportion of viral strains circulated into Northern-Central-Southern Taiwan per year, divided by total cases infected with the same strain, is shown in pie charts. Because Taiwanese PWID infected with HCV-6w were rare, we directly labeled their locations on the map.
Viruses 14 02142 g0a3
Table
Table A1. Distribution of HCV genotypes/subtypes in the different groups among Taiwanese PWID.
Table A1. Distribution of HCV genotypes/subtypes in the different groups among Taiwanese PWID.
2004–2006 HIV-1/HCV
Co-Infection (n = 165) a		2007–2008 HIV-1/HCV Co-Infection (n = 275) b2007–2008 HCV Mono-Infection (n = 227) bp-Value
Single infection <0.001
1a21 (12.7)64 (23.3)53 (23.3)
1b48 (29.1)25 (9.1)30 (13.2)
2a6 (3.6)10 (3.6)6 (2.6)
2b6 (3.6)21 (7.6)5 (2.2)
3a11 (6.7)24 (8.7)25 (11.0)
3b1 (0.6)3 (1.1)3 (1.3)
6a43 (26.1)80 (29.1)53 (23.3)
6n4 (2.4)1 (0.4)3 (1.3)
6w1 (0.6)2 (0.7)5 (2.2)
Subtotal_1141 (85.5)230 (83.6)183 (80.6)
Double infection <0.001
1a/1b5 (3.0)5 (1.8)0 (0.0)
1a/2a0 (0.0)4 (1.5)1 (0.4)
1a/2b0 (0.0)18 (6.5)5 (2.2)
1a/3a0 (0.0)1 (0.4)2 (0.9)
1a/6a1 (0.6)0 (0.0)1 (0.4)
1b/2a1 (0.6)0 (0.0)0 (0.0)
1b/2b1 (0.6)0 (0.0)0 (0.0)
1b/3a3 (1.8)0 (0.0)0 (0.0)
1b/3b0 (0.0)1 (0.4)0 (0.0)
1b/6a6 (3.6)4 (1.5)6 (2.6)
1b/6w1 (0.6)0 (0.0)0 (0.0)
2a/2b0 (0.0)1 (0.4)1 (0.4)
2a/3a0 (0.0)0 (0.0)3 (1.3)
2a/6a0 (0.0)8 (2.9)20 (8.8)
2b/6a0 (0.0)2 (0.7)1 (0.4)
3a/6a3 (1.8)1 (0.4)2 (0.9)
6a/6n1 (0.6)0 (0.0)0 (0.0)
Subtotal_222 (13.3)45 (16.4)42 (18.5)
Triple infection 0.261
1a/1b/3a1 (0.6)0 (0.0)0 (0.0)
1a/1b/6a1 (0.6)0 (0.0)0 (0.0)
1a/2a/3a0 (0.0)0 (0.0)1 (0.4)
1b/3a/6a0 (0.0)0 (0.0)1 (0.4)
Subtotal_32 (1.2)0 (0.0)2 (0.9)
a 180 blood samples randomly selected by the following strains (50 HIV-1 CRF07_BC-infected cases each from northern, central, and southern regions of Taiwan; 20 HIV-1 subtype B-infected cases; 10 HIV-1 CRF01_AE-infected cases) in years 2004–2006, among which 91.7% (165/180) were completed genotype identified by RT-PCR and phylogenetic analysis. b A total of 624 blood specimens were collected in the years 2007–2008; among them, 80.4% (502/624) were completed genotype identified by RT-PCR and phylogenetic analysis.
Table
Table A2. Location and collection date of Asian isolates from PWID infected with HIV-1 CRF01_AE, CRF07_BC, and HCV-6 and other related reference strains from GenBank.
Table A2. Location and collection date of Asian isolates from PWID infected with HIV-1 CRF01_AE, CRF07_BC, and HCV-6 and other related reference strains from GenBank.
InfectionsAccession Numbers/Sample IDLocationCollection Date
HIV-1 CRF01_AE
(reference strains)		90CF11697/F197340Central African Republic1990
90CF4071/AF197341Central African Republic1990
90CR402/U51188Central African Republic1990
HIV-1 CRF01_AE a
(Asian PWID)		HM215409Yunnan2007
HM215410Yunnan2006
HM215418Yunnan2007
HM215419Yunnan2007
HM215422Yunnan2006
HM215427Yunnan2006
JN223054Myanmar2009
JX112823Guangdong8 Nov 2007
JX112824Guangdong23 Jul 2007
JX112825Guangdong23 Jul 2007
JX112826Guangdong4 Jul 2007
JX112828Guangdong11 Jul 2007
JX112831Guangxi22 May 2007
JX112837Guangxi22 Oct 2007
JX112839Guangxi8 Nov 2007
JX112840Guizhou19 Jul 2007
JX112842Guizhou6 Sep 2007
JX112857Sichuan3 Dec 2006
JX112861Yunnan4 Jun 2002
JX112863Yunnan4 Jun 2002
KP401977Viet Nam6 Jan 2012
KP401980Viet Nam9 Jan 2012
KP401983Viet Nam9 Jan 2012
KP401984Viet Nam9 Jan 2012
KP401987Viet Nam10 Jan 2012
KP401992Viet Nam11 Jan 2012
KP401995Viet Nam12 Jan 2012
KP401997Viet Nam11 Jan 2012
KP401998Viet Nam7 Feb 2012
KP402000Viet Nam8 Feb 2012
KP402001Viet Nam8 Feb 2012
KP402003Viet Nam8 Feb 2012
KP402004Viet Nam8 Feb 2012
KP402005Viet Nam9 Feb 2012
KP402009Viet Nam13 Feb 2012
KP402010Viet Nam13 Feb 2012
KP402014Viet Nam15 Feb 2012
KP402015Viet Nam16 Feb 2012
KP402017Viet Nam16 Feb 2012
KP402019Viet Nam20 Feb 2012
KP402020Viet Nam20 Feb 2012
KP402021Viet Nam20 Feb 2012
KP402022Viet Nam21 Feb 2012
KP402024Viet Nam21 Feb 2012
KP402026Viet Nam21 Feb 2012
KP402027Viet Nam22 Feb 2012
KP402030Viet Nam22 Feb 2012
HIV-1 CRF01_AE a
(Asian PWID)		KP402031Viet Nam22 Feb 2012
KP402037Viet Nam28 Feb 2012
KP402039Viet Nam9 Mar 2012
KP402040Viet Nam9 Mar 2012
KP402043Viet Nam14 Mar 2012
KP402044Viet Nam15 Mar 2012
KP402045Viet Nam28 Mar 2012
KP402046Viet Nam29 Mar 2012
KP402050Viet Nam16 Apr 2012
KP402051Viet Nam10 May 2012
KP402052Viet Nam15 May 2012
KP402056Viet Nam29 Feb 2012
KU820849Myanmar8 Nov 2014
Group 1
(Taiwanese PWID only)		D212Taipei Detention Center4 May 2005
D261Taipei Prison18 May 2005
D291Yunlin Second Prison9 Jun 2005
D299Yunlin Second Prison9 Jun 2005
D301Yunlin Second Prison9 Jun 2005
D308Yunlin Second Prison9 Jun 2005
D336Yunlin Second Prison31 Aug 2005
D370Yunlin Second Prison31 Aug 2005
D376Yunlin Second Prison31 Aug 2005
D412Taipei Detention Center6 Oct 2005
D423Taipei Detention Center6 Oct 2005
D455Taipei Detention Center6 Oct 2005
D568Yunlin Second Prison22 Dec 2005
D580Yunlin Second Prison22 Dec 2005
D737Taichung Prison26 Mar 2008
Group 2
(Taiwanese other sexual-groups, e.g., homo-, hetero-, and bisexuals)		4V370Taipei City Hospital7 Jan 2005
4V396Taipei City Hospital14 Feb 2005
4V428Taipei City Hospital17 Mar 2005
4V481Taipei City Hospital30 May 2005
4V503Taipei City Hospital14 Jul 2005
4V507Taipei City Hospital20 Jul 2005
4V545Taipei City Hospital13 Sep 2005
4V569Taipei City Hospital4 Oct 2005
4V590Taipei City Hospital28 Oct 2005
4V614Taipei City Hospital11 Nov 2005
4V680Taipei City Hospital3 Jan 2006
4V689Taipei City Hospital4 Jan 2006
4V691Taipei City Hospital12 Jan2006
4V714Taipei City Hospital24 Feb 2006
4V724Taipei City Hospital20 Feb 2006
4V740Taipei City Hospital7 Mar 2006
4V744Taipei City Hospital9 Mar 2006
4V795Taipei City Hospital9 May 2006
4V872Taipei City Hospital21 Aug 2006
HIV-1 CRF07_BC
(reference strains)		AF286226/97CN001China1997
/C54AChina1997
/C54DChina1997
/C54China1997
/CN54China1997
AF286230/98CN009China1998
AF503396/CNGL179China-
HIV-1 CRF07_BC a
(Asian PWID)		JN223069Myanmar2009
JX392363Gansu2002
JX392364Ningxia2002
JX392365Ningxia2002
JX392366Ningxia2002
JX392367Ningxia2005
JX392368Qinghai2006
JX392369Qinghai2005
JX392370Sichuan1999
JX392371Sichuan1998
JX392372Sichuan1999
JX392373Sichuan2003
JX392374Sichuan2002
JX392375Yunnan1996
JX392376Yunnan1997
JX392377Yunnan2001
JX392378Sichuan2006
JX392379Sichuan2006
JX392380Sichuan2006
JX392381Sichuan2006
JX392382Sichuan2006
JX392384Xinjiang2006
KF250368Guangdong2007
KF250369Guangdong2007
KF250370Guangdong2007
KF250371Guangdong2007
KF250375Ningxia2007
KF250376Sichuan2006
KF250377Xinjiang2007
KF250378Yunnan1996
KF250379Yunnan1996
KF250380Yunnan1996
KU820832Myanmar28 Nov 2013
Group 1
(Taiwanese PWID only)		D74Tainan Detention Center30 Dec 2004
D75Tainan Detention Center30 Dec 2004
D76Tainan Detention Center30 Dec 2004
D97Tainan Detention Center30 Dec 2004
D114Tainan Detention Center30 Dec 2004
D118Tainan Detention Center30 Dec 2004
D120Tainan Detention Center30 Dec 2004
Group 2
(Taiwanese PWID only)		4V780Taipei City Hospital27 Apr 2006
4V784Taipei City Hospital24 Apr 2006
4V793Taipei City Hospital8 May 2006
4V807Taipei City Hospital17 May 2006
4V844Taipei City Hospital11 Jul 2006
D126Tainan Detention Center30 Dec 2004
D338Yunlin Second Prison31 Aug 2005
D734Taichung Prison26 Mar 2008
D757Taichung Prison26 Mar 2008
D776Taichung Prison26 Mar 2008
Group 3
(Taiwanese PWID only)		4V457Taipei City Hospital27 Apr 2005
4V467Taipei City Hospital9 May 2005
D733Taichung Prison26 Mar 2008
D735Taichung Prison26 Mar 2008
D736Taichung Prison26 Mar 2008
D771Taichung Prison26 Mar 2008
D775Taichung Prison26 Mar 2008
D780Taichung Prison26 Mar 2008
D839Taichung Prison26 Mar 2008
D845Taichung Prison26 Mar 2008
D850Kaohsiung Prison9 Apr 2008
D863Kaohsiung Prison9 Apr 2008
D902Kaohsiung Prison9 Apr 2008
D907Kaohsiung Prison9 Apr 2008
D947Kaohsiung Prison9 Apr 2008
D966Taoyuan Woman’s Prison6 May 2008
D970Taoyuan Woman’s Prison6 May 2008
D1007Taoyuan Woman’s Prison6 May 2008
HCV-6
(reference strains)		DQ278892/GZ52557China2002
KC191671/10MYKJ032Malaysia2010
Subtype 6a
(reference strains)		HQ912954/PR58China2008
HQ912955/PR144China2008
KC844037/ZS221China2009
KC844038/ZS674China2011
AY859526/6a33Hong Kong2004
AY973865/cs6a-16Hong Kong2004
AY973866/cs6a-18Hong Kong2004
DQ480512/6a77Hong Kong2004
DQ480513/6a35Hong Kong2004
DQ480514/6a63Hong Kong2004
DQ480515/6a64Hong Kong2004
DQ480516/6a61Hong Kong2004
DQ480517/6a73Hong Kong2004
DQ480518/6a65Hong Kong2004
DQ480519/6a66Hong Kong2004
DQ480520/6a67Hong Kong2004
DQ480521/6a69Hong Kong2004
DQ480522/6a72Hong Kong2004
DQ480523/6a62Hong Kong2004
DQ480524/6a74Hong Kong2004
Y12083/EUHK2Hong Kong1997
EU246930/D9Viet Nam-
Subtype 6a
(Asian PWID)		JX102891Viet Nam22 Aug 2008
JX102895Viet Nam30 Aug 2008
JX102896Viet Nam30 Aug 2008
JX102897Viet Nam30 Aug 2008
JX102908Viet Nam31 Aug 2008
JX102957Viet Nam21 May 2008
JX102963Viet Nam21 Feb 2008
JX102965Viet Nam21 May 2008
JX102973Viet Nam21 May 2008
JX102975Viet Nam29 May 2008
JX103004Viet Nam5 Sep 2008
JX103010Viet Nam15 Oct 2008
JX103038Viet Nam28 Jun 2009
JX103047Viet Nam1 Jul 2009
JX103051Viet Nam3 Jul 2009
JX103104Viet Nam7 Sep 2009
JX103106Viet Nam7 Sep 2009
JX103117Viet Nam9 Sep 2009
JF721080Guangdong15 Nov 2010
JF721081Guangdong15 Nov 2010
JF721082Guangdong15 Nov 2010
JF721083Guangdong15 Nov 2010
JF721084Guangdong15 Nov 2010
JF721085Guangdong15 Nov 2010
JF721086Guangdong15 Nov 2010
Subtype 6a
(Asian PWID)		JF721087Guangdong15 Nov 2010
JF721088Guangdong15 Nov 2010
JF721089Guangdong15 Nov 2010
JF721090Guangdong15 Nov 2010
JF721091Guangdong15 Nov 2010
JF721092Guangdong15 Nov 2010
JF721093Guangdong15 Nov 2010
JF721094Guangdong15 Nov 2010
JF721095Guangdong15 Nov 2010
JF721096Guangdong15 Nov 2010
JF721097Guangdong15 Nov 2010
JF721098Guangdong15 Nov 2010
JF721099Guangdong15 Nov 2010
JF721100Guangdong15 Nov 2010
JF721101Guangdong15 Nov 2010
JF721102Guangdong15 Nov 2010
JF721103Guangdong15 Nov 2010
JF721104Guangdong15 Nov 2010
JF721105Guangdong15 Nov 2010
JF721106Guangdong15 Nov 2010
JF721107Guangdong15 Nov 2010
JF721108Guangdong15 Nov 2010
JF721109Guangdong15 Nov 2010
JF721110Guangdong15 Nov 2010
JF721111Guangdong15 Nov 2010
JF721112Guangdong15 Nov 2010
JF721113Guangdong15 Nov 2010
JF721114Guangdong15 Nov 2010
JF721115Guangdong15 Nov 2010
JF721116Guangdong15 Nov 2010
JF721117Guangdong15 Nov 2010
JF721118Guangdong15 Nov 2010
JF721119Guangdong15 Nov 2010
JF721120Guangdong15 Nov 2010
JF721121Guangdong15 Nov 2010
JF721122Guangdong15 Nov 2010
JF721123Guangdong15 Nov 2010
JF721124Guangdong15 Nov 2010
JF721125Guangdong15 Nov 2010
JF721126Guangdong15 Nov 2010
JF721127Guangdong15 Nov 2010
JF721128Guangdong15 Nov 2010
JF721129Guangdong15 Nov 2010
JF721130Guangdong15 Nov 2010
JF721131Guangdong15 Nov 2010
JF721132Guangdong15 Nov 2010
JF721133Guangdong15 Nov 2010
JF721134Guangdong15 Nov 2010
JF721135Guangdong15 Nov 2010
JF721136Guangdong15 Nov 2010
Subtype 6a
(Asian PWID)		JF721137Guangdong15 Nov 2010
JF721138Guangdong15 Nov 2010
JF721139Guangdong15 Nov 2010
JF721140Guangdong15 Nov 2010
JF721141Guangdong15 Nov 2010
JF721142Guangdong15 Nov 2010
JF721143Guangdong15 Nov 2010
JF721144Guangdong15 Nov 2010
JF721145Guangdong15 Nov 2010
JF721146Guangdong15 Nov 2010
JF721147Guangdong15 Nov 2010
JF721148Guangdong15 Nov 2010
JF721149Guangdong15 Nov 2010
JF721150Guangdong15 Nov 2010
JF721151Guangdong15 Nov 2010
JF721152Guangdong15 Nov 2010
JF721153Guangdong15 Nov 2010
JF721154Guangdong15 Nov 2010
JF721155Guangdong15 Nov 2010
JF721156Guangdong15 Nov 2010
JF721157Guangdong15 Nov 2010
Subtype 6e
(reference strains)		DQ314805/GX004China-
LC435023/N12-2804-CamCambodia22 Aug 2012
LC435027/N16-2804-CamCambodia3 Sep 2016
EU246931/D42Viet Nam-
EU246932/D88Viet Nam-
EU408326/537798USA-
Subtype 6e
(Asian PWID)		AB523168Viet Nam2007
AB523178Viet Nam2007
AB523179Viet Nam2007
AB523190Viet Nam2007
AB523248Viet Nam2007
AB523321Viet Nam2007
AB523326Viet Nam2007
AB523330Viet Nam2007
AB523339Viet Nam2007
AB523345Viet Nam2007
AB523346Viet Nam2007
HM009307Hong KongJan 2006
HQ318922Zhenjiang2009
HQ318923Zhenjiang2009
HQ318924Zhenjiang2009
HQ318925Zhenjiang2009
HQ318926Zhenjiang2009
HQ318927Zhenjiang2009
JX102902Viet Nam30 Aug 2008
JX102969Viet Nam21 May 2008
JX102982Viet Nam29 May 2008
JX103102Viet Nam10 Jul 2009
JX103119Viet Nam10 Sep 2009
Subtype 6h
(reference strains)		D84265/VN004Viet Nam-
Subtype 6h
(Asian PWID)		AB523188Viet Nam2007
AB523257Viet Nam2007
AB523259Viet Nam2007
AB523289Viet Nam2007
AB523290Viet Nam2007
AB523312Viet Nam2007
AB523332Viet Nam2007
HM009308Hong Kong2006
JX102967Viet Nam21 May 2008
JX103044Viet Nam1 Jul 2009
Subtype 6n
(reference strains)		DQ278894/KM42China2002
DQ835768/D86/93Thailand-
EU246937/TH22Thailand-
EU246938/TH31Thailand-
Subtype 6n
(Asian PWID)		HQ318920Zhenjiang2009
HQ318921Zhenjiang2009
JQ303547Suzhou2011
JQ303548Suzhou2011
JQ303549Suzhou2011
JQ303550Suzhou2011
JQ303551Suzhou2010
JQ303552Suzhou2010
JQ303553Suzhou2011
JQ303554Suzhou2010
KC878938Jiangsu2011
KC878983Jiangsu2011
KM285079Yunnan2011
KM285080Yunnan2011
KM285081Yunnan2012
KM285082Yunnan2012
KM285083Yunnan2012
KM285084Yunnan2009
KM285085Yunnan2010
KM285086Yunnan2012
KM285087Yunnan2009
KM285088Yunnan2012
KM285089Yunnan2012
KM285090Yunnan2012
KM285091Yunnan2012
KM285092Yunnan2012
KM285093Yunnan2012
KM285094Yunnan2010
KM285095Yunnan2010
KM285096Yunnan2011
KM285097Yunnan2009
KM285098Yunnan2011
KR108496Malaysia2009
KR108497Malaysia2009
Subtype 6n
(Asian PWID)		KT735662Yunnan2014
KT735668Yunnan2014
KT735681Yunnan2014
KT735687Yunnan2014
KT735689Yunnan2014
KT735695Yunnan2014
KT735697Yunnan2014
KT735698Yunnan2014
KT735704Yunnan2014
KT735709Yunnan2014
KT735715Yunnan2014
KT735718Yunnan2014
KT735723Yunnan2014
KT735726Yunnan2014
KT735727Yunnan2014
KT735732Yunnan2014
KT735733Yunnan2014
KT735736Yunnan2014
KT735743Yunnan2014
KT735759Yunnan2014
KT735779Yunnan2014
KT735804Yunnan2014
KT735814Yunnan2014
KT735820Yunnan2014
KT735821Yunnan2014
KT735822Yunnan2014
KT735827Yunnan2014
KT735834Yunnan2014
KT735855Yunnan2014
KT735878Yunnan2014
MH458979Myanmar2014
MH458983Myanmar2014
MH458986Myanmar2014
MH458995Myanmar2014
Subtype 6r
(reference strains)		EU408328/QC245Canada-
LC435024/N12-2911-CamCambodia22 Aug 2012
LC435028/N16-2911-CamCambodia3 Sep 2016
Subtype 6v
(reference strains)		EU158186/NK46China2004
EU798760/KMN-02China-
EU798761/KM046China-
FJ435090/KM181China-
Subtype 6u
(reference strains)		EU246940/D83Viet Nam-
EU408330/DH012China2001
EU408331/DH014China2001
EU408332/DH028China2001
Subtype 6u
(Asian PWID)		JQ303555Suzhou2011
KM285099Yunnan2012
KM285100Yunnan2009
KM285101Yunnan2012
KM285102Yunnan2009
Subtype 6u
(Asian PWID)		KM285103Yunnan2011
KM285104Yunnan2009
KM285105Yunnan2011
KM285106Yunnan2011
KM285107Yunnan2011
KM285108Yunnan2011
KM285109Yunnan2009
KM285110Yunnan2012
KM285111Yunnan2011
KM285112Yunnan2011
KM285113Yunnan2010
KM285114Yunnan2009
KM285115Yunnan2012
KM285116Yunnan2012
KM285117Yunnan2011
KM285118Yunnan2009
KT735674Yunnan2014
KT735690Yunnan2014
KT735700Yunnan2014
KT735712Yunnan2014
KT735744Yunnan2014
KT735810Yunnan2014
MH458978Myanmar2014
MH458980Myanmar2014
MH458984Myanmar2014
MH458993Myanmar2014
Subtype 6w
(reference strains)		EU643834/HCV-6-D140Taiwan2005
EU643836/HCV-6-D370Taiwan2005
HCV subtype 6w
(Taiwanese PWID only)		D140Taipei Detention Center20 Jan 2005
D370Yunlin Second Prison31 Aug 2005
D778Taichung Prison26 Mar 2008
D866Kaohsiung Prison9 Apr 2008
ND141Taoyuan Woman’s Prison27 May 2008
ND153Taoyuan Woman’s Prison27 May 2008
ND187Taoyuan Woman’s Prison27 May 2008
ND414Sindian Drug Abuser Treatment Center18 Jun 2008
ND415Sindian Drug Abuser Treatment Center18 Jun 2008
Note: a The lengths of the env fragment in CRF01_AE and CRF07_BC were up to 537 and 552 bp, respectively. The length of the query shorter than the standard was labeled with a different color, such as ‘light gray, <500 bp’ and ‘dark gray, <300 bp’.

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Viruses 14 02142 g001a 550Viruses 14 02142 g001b 550
Figure 1. The estimated timescale of the spread of (a) HIV-1 CRF01_AE, (b) CRF07_BC, and (c) HCV genotype-6 in Asian PWID population (CN: China, MM: Myanmar, MA: Malaysia, TW: Taiwan, and VN: Vietnam). In this particular figure, we adopted the data set based on GTR + Γ6/GTR + Γ6 + I constant model to show the tMRCAs of HIV-1 and HCV strains circulating in this area.
Figure 1. The estimated timescale of the spread of (a) HIV-1 CRF01_AE, (b) CRF07_BC, and (c) HCV genotype-6 in Asian PWID population (CN: China, MM: Myanmar, MA: Malaysia, TW: Taiwan, and VN: Vietnam). In this particular figure, we adopted the data set based on GTR + Γ6/GTR + Γ6 + I constant model to show the tMRCAs of HIV-1 and HCV strains circulating in this area.
Viruses 14 02142 g001aViruses 14 02142 g001b
Table
Table 1. Evolutionary characteristics of CRF01_AE and CRF07_BC.
Table 1. Evolutionary characteristics of CRF01_AE and CRF07_BC.
HIV-1 CRFsGenetic RegionGTR + Γ6 Constant SizeGTR + Γ6 Exponential GrowthGTR + Γ6 Bayesian Skyline
Rate of Evolution atMRCA bRate of EvolutiontMRCARate of EvolutiontMRCA
CRF01_AEenv2.6 (1.8–3.5) 1.3 (0.9–1.6) 7.8 (5.4–10.4)
Reference strains 1979.9
(1971.9–1986.1)		 1979.5
(1973.9–1984.6)		 1988.8
(1987.9–1989.7)
China (all PWID) 1989.6
(1985.9–1992.7)		 1986.5
(1980.0–1990.8)		 1996.1
(1994.2–1997.8)
Guangdong 1996.8
(1992.6–2003.3)		 1993.7
(1989.1–1997.9)		 2002.9
(2000.8–2005.3)
Guangxi 2000.3
(1993.8–2004.2)		 1996.1
(1991.3–2000.0)		 2003.8
(2001.0–2005.4)
Guizhou 2000.8
(1994.4–2004.4)		 1996.2
(1991.7–2000.3)		 2004.1
(2001.0–2005.5)
Sichuan 2004.5
(2003.2–2005.6)		 2001.0
(1998.3–2003.6)		 2005.5
(2005.0–2005.9)
Yunnan 1989.7
(1986.0–1993.0)		 1986.5
(1980.0–1990.9)		 1996.7
(1994.6–2001.2)
Myanmar (all PWID) 1999.2
(1995.5–2002.5)		 1994.6
(1990.2–1999.8)		 2002.2
(2000.4–2004.5)
Taiwan (all) 1989.9
(1987.0–1992.3)		 1988.0
(1984.5–1991.1)		 1996.0
(1991.8–1997.8)
PWID, Central Taiwan 1996.3
(1993.0–1999.7)		 1992.5
(1988.8–1995.9)		 2001.2
(2000.3–2001.6)
PWID, Northern Taiwan 1999.0
(1995.5–2002.4)		 1994.1
(1989.5–1998.4)		 2001.5
(2000.6–2003.5)
Other sexual-groups 1989.9
(1987.0–1992.3)		 1988.0
(1984.5–1991.1)		 1996.0
(1991.8–1997.8)
Vietnam (all PWID) 1990.5
(1987.4–1993.3)		 1988.4
(1984.7–1991.8)		 1994.1
(1991.9–1996.0)
CRF07_BCenv1.4 (0.6–2.3) 1.3 (0.7–1.9) 5.3 (2.8–8.3)
Reference strains 1992.0
(1986.5–1995.7)		 1994.1
(1990.8–1996.0)		 1995.7
(1994.6–1996.0)
China (all PWID) 1970.6
(1943.5–1989.8)		 1987.9
(1981.0–1993.9)		 1994.3
(1992.2–1995.6)
Gansu 1998.9
(1994.5–2001.9)		 1999.7
(1996.4–2001.9)		 2000.3
(1997.2–2001.9)
Guangdong 1976.1
(1954.6–1992.2)		 1989.3
(1981.5–1997.1)		 1997.1
(1996.4–1997.8)
Ningxia 1976.4
(1955.9–1991.8)		 1989.3
(1981.9–1997.0)		 1997.0
(1996.2–1997.7)
Qinghai 1993.9
(1986.6–2002.1)		 1995.7
(1991.9–2000.5)		 1999.0
(1996.6–2004.4)
Sichuan 1986.2
(1974.3–1994.2)		 1991.5
(1985.5–1996.4)		 1997.0
(1996.2–1997.7)
Xinjiang 1997.9
(1992.0–2004.9)		 1999.0
(1994.4–2003.8)		 2001.3
(1996.9–2005.6)
Yunnan 1970.7
(1943.6–1989.9)		 1987.9
(1981.0–1993.9)		 1994.3
(1992.2–1995.6)
Myanmar (all PWID) 1980.9
(1949.6–2004.3)		 1995.0
(1987.6–2002.0)		 1997.1
(1996.2–1997.9)
Taiwan (all PWID) 1999.7
(1997.0–2002.4)		 1999.9
(1997.8–2001.9)		 2001.7
(1999.8–2003.5)
Central Taiwan 2003.3
(2001.9–2004.6)		 2002.9
(2001.2–2004.2)		 2004.2
(2003.5–2005.0)
Northern Taiwan 2001.9
(1998.3–2004.0)		 2001.3
(1998.6–2004.0)		 2003.7
(2002.6–2004.9)
Southern Taiwan 1999.8
(1997.0–2002.3)		 2000.0
(1997.8–2002.2)		 2001.7
(1999.8–2003.5)
a Rates are expressed as 10−3 nucleotide substitutions per site per year. 95% highest posterior density (HPD) confidence intervals are shown in parenthesis. b tMRCA, Time of the most recent common ancestor. 95% HPDs are shown in parenthesis.
Table
Table 2. Evolutionary characteristics of HCV subtype 6w.
Table 2. Evolutionary characteristics of HCV subtype 6w.
Genetic RegionGTR + Γ6 + I Constant SizeGTR + Γ6 + I Exponential GrowthGTR + Γ6 + I Bayesian Skyline
Rate of Evolution atMRCA bRate of EvolutiontMRCARate of EvolutiontMRCA
Genotype-6 (all)NS5B1.3 (1.0–1.7)1916.6
(1866.9–1956.9)		1.0 (0.6–1.4)1928.1
(1890.2–1966.0)		3.6 (2.0–6.0)1973.2
(1951.0–1989.3)
Reference strains 1920.4
(1870.5–1959.3)		 1928.4
(1890.3–1966.0)		 1974.1
(1949.0–1989.9)
Subtype 6a (all) 1966.0
(1929.6–1987.2)		 1971.0
(1947.4–1988.4)		 1990.4
(1984.5–1994.8)
Reference strains 1966.1
(1926.3–1987.1)		 1971.0
(1947.4–1988.4)		 1990.4
(1984.5–1994.8)
China (PWID) 1995.8
(1991.3–2000.5)		 1994.5
(1988.9–2000.9)		 2000.0
(1995.4–2003.6)
Vietnam (PWID) 1994.9
(1989.7–2001.7)		 1993.5
(1977.5–2001.3)		 1999.3
(1995.2–2004.9)
Subtype 6e (all) 1991.3
(1983.3–1998.6)		 1989.3
(1978.8–1997.6)		 1998.0
(1993.6–2001.4)
Reference strains 1991.3
(1983.3–1998.6)		 1989.3
(1978.8–1997.6)		 1998.2
(1994.0–2003.0)
China (PWID) 2003.7
(2000.5–2005.8)		 2003.5
(1999.4–2005.7)		 2003.3
(2002.4–2005.9)
Hong Kong 2004.8
(2002.3–2005.9)		 2004.7
(2002.0–2005.9)		 2004.9
(2003.0–2006.0)
Zhenjiang 2005.4
(2003.6–2007.2)		 2005.1
(2002.6–2006.8)		 2006.2
(2002.9–2007.6)
Vietnam (PWID) 1991.3
(1982.9–1998.3)		 1989.3
(1979.5–1998.4)		 1999.3
(1993.6–2003.0)
Subtype 6h (all) 1965.3
(1940.6–1984.7)		 1964.6
(1928.2–1987.9)		 1982.6
(1962.3–1993.6)
Reference strains 1993.9
(1990.0–1996.0)		 1993.8
(1990.2–1996.0)		 1994.8
(1992.5–1996.0)
China (PWID) 2006.0
(n/a)		 2005.3
(n/a)		 2006.0
(n/a)
Vietnam (PWID) 1994.0
(1981.7–1996.0)		 1993.4
(1987.2–1996.0)		 1998.4
(1993.5–2006.0)
Subtype 6n (all) 1965.9
(1941.6–1984.7)		 1964.7
(1929.5–1988.3)		 1983.7
(1963.1–1993.6)
Reference strains 1979.1
(1946.8–2001.1)		 1975.7
(1934.5–2001.3)		 1983.7
(1963.1–1993.6)
China (PWID) 1984.7
(1950.8–2004.8)		 1987.8
(1952.0–2005.0)		 2003.2
(2000.6–2005.0)
Jiangsu 2008.2
(2006.7–2009.8)		 2007.8
(2006.1–2009.6)		 2009.2
(2008.2–2010.0)
Suzhou 2003.7
(2000.9–2007.4)		 2002.7
(1998.8–2007.3)		 2004.7
(2002.8–2008.2)
Yunnan 1984.7
(1950.8–2004.8)		 1987.8
(1953.1–2007.0)		 2003.2
(2000.4–2005.0)
Zhenjiang 2006.8
(2004.3–2008.5)		 2006.3
(2003.3–2008.3)		 2007.9
(2006.8–2008.8)
Myanmar (PWID) 1985.1
(1951.2–2006.5)		 1990.4
(1954.7–2007.7)		 2004.1
(2000.7–2008.1)
Malaysia (PWID) 2010.9
(2009.0–2012.9)		 2009.5
(2005.7–2013.1)		 2011.8
(2009.3–2013.7)
Subtype 6r
Reference strains 1974.6
(1945.1–1994.2)		 1976.1
(1955.8–1993.0)		 1997.9
(1993.8–2001.6)
Subtype 6v
Reference strains 1954.6
(1910.7–1984.7)		 1961.5
(1925.2–1987.7)		 1988.2
(1972.4–1998.9)
Subtype 6u (all) 1918.3
(1867.2–1957.7)		 1929.3
(1892.6–1967.3)		 1976.3
(1957.3–1990.2)
Reference strains 1918.3
(1967.2–1957.7)		 1929.3
(1892.6–1967.3)		 1976.4
(1957.9–1993.7)
China (PWID) 1999.4
(1997.5–2000.9)		 1992.4
(1958.7–2001.0)		 1999.2
(1990.5–2001.0)
Suzhou 2009.7
(2008.3–2010.8)		 2009.4
(2007.9–2010.7)		 2010.4
(2009.3–2011.0)
Yunnan 1999.5
(1997.5–2000.9)		 1992.4
(1958.7–2001.0)		 1999.2
(1990.5–2001.0)
Myanmar (PWID) 2007.2
(1999.4–2010.3)		 2006.4
(1998.9–2009.9)		 2009.2
(2007.7–2011.2)
Subtype 6w
Reference strains 2000.4
(1995.2–2004.0)		 1999.8
(1993.6–2009.8)		 2002.5
(2000.2–2004.5)
Taiwan (PWID) c 1996.7
(1990.0–2002.2)		 1994.2
(1985.0–2001.8)		 2000.0
(1987.6–2004.2)
a Rates are expressed as 10−3 nucleotide substitutions per site per year. 95% highest posterior density (HPD) confidence intervals are shown in parenthesis. b tMRCA, Time of the most recent common ancestor. 95% HPDs are shown in parenthesis. If there were extreme values for estimating shown “unavailable, n/a”. c Nine participants recruited in different parts of Taiwan. Sample collection from Taipei Detention Center, Sindian Drug Abuser Treatment Center, Taoyuan Women’s Prison, Taichung Prison, and Kaohsiung Prison were 1, 2, 3, 2, and 1, respectively.
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Chen, Y.-J.; Huang, J.C.; Tsai, H.-C.; Lin, Y.-H.; Hsu, K.-F.; Liu, H.-F. Geographic Transmission and Epidemic History of HIV-1 CRF01_AE, CRF07_BC, and HCV Subtype-6w among Taiwanese Persons Who Inject Drugs. Viruses 2022, 14, 2142. https://doi.org/10.3390/v14102142

AMA Style

Chen Y-J, Huang JC, Tsai H-C, Lin Y-H, Hsu K-F, Liu H-F. Geographic Transmission and Epidemic History of HIV-1 CRF01_AE, CRF07_BC, and HCV Subtype-6w among Taiwanese Persons Who Inject Drugs. Viruses. 2022; 14(10):2142. https://doi.org/10.3390/v14102142

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Chen, Yen-Ju, Jason C. Huang, Hung-Chin Tsai, Yu-Hui Lin, Kuo-Feng Hsu, and Hsin-Fu Liu. 2022. "Geographic Transmission and Epidemic History of HIV-1 CRF01_AE, CRF07_BC, and HCV Subtype-6w among Taiwanese Persons Who Inject Drugs" Viruses 14, no. 10: 2142. https://doi.org/10.3390/v14102142

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