Recombinant characteristics of three novel HIV-1 second-generation recombinant forms composed of CRF01_AE and CRF07_BC isolated in Hebei province, China.

Human immunodeficiency virus 1 (HIV-1) is a fast-evolving, genetically diverse virus. The HIV-1 evolution rate is also significantly influenced by the frequency of HIV-1 spread in a population. Transmission via homosexual contact has become the predominant transmission route, leading to an increase in the HIV-1 epidemic in Hebei province, China. In this study, we report three novel HIV-1 CRF01_AE/CRF07_BC recombinant forms isolated from three men who have sex with men (MSM) in the cities of Shijiazhuang (20747) and Langfang (20809 and 20820). Phylogenetic analysis based on HIV-1 near-full-length genome (NFLG) sequences indicated that the three novel recombinant forms formed a distinct monophyletic branch that was separate from all known HIV-1 subtypes and circulating recombinant forms (CRFs). Breakpoint analysis showed that the three NFLGs displayed different recombinant patterns. NFLGs 20747 and 20809 had a recombinant pattern with subtype CRF01_AE gene fragments inserted into a CRF07_BC backbone, spanning from the gag to env gene regions, whereas NFLG 20820 had a recombinant pattern with subtype CRF07_BC gene fragments inserted into a CRF01_AE backbone. Subregion phylogenetic analysis confirmed that these three NFLGs comprised CRF01_AE and CRF07_BC. Our findings confirm the emergence of novel recombinant forms and highlight the need for continuous monitoring of the diversity of HIV-1 among sexually active populations, especially MSM, to better control the HIV-1 epidemic.

Genome mosaic structure of two novel HIV-1 recombinant forms (CRF01_AE/B) in men who have sex with men in Hebei, China.

BACKGROUND: Homosexual contact is the main route of human immunodeficiency virus type one (HIV-1) transmission in Cangzhou Prefecture, Hebei, China. Moreover, the number of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in this key population is ever increasing. METHODS: In this study, we identified two novel URFs (hcz0017 and hcz0045) from two men who have sex with men (MSM) based in Cangzhou Prefecture. Phylogenetic and recombinant breakpoint analyses, based on the near full-length genomes (NFLGs) of the two novel URFs, showed that they originated from a recombination between HIV-1 CRF01_AE and subtype B. RESULTS: HXB2 numbering revealed that the NFLGs of hcz0017 and hcz0045 each contained the following seven subregions: hcz0017: IB (790-1,171 nt), IICRF01_AE (1,172-2,022 nt), IIIB (2,023-4,469 nt), IVCRF01_AE (4,470-5,866 nt), VB (5,867-7,462 nt), VICRF01_AE (7,463-8,379 nt), VIIB (8,380-9,411 nt); hcz0045: ICRF01_AE (790-5,147 nt), IIB (5,148-5,614 nt), IIICRF01_AE (5,615-6,035 nt), IVB (6,036-6,241 nt), VCRF01_AE (6,242-7,325nt), VIB (7,326-8,254 nt), VIICRF01_AE (8,255-9,411 nt). Moreover, the two MSM from whom the novel URFs originated from were diagnosed as recently HIV-1-infected, suggesting that the high prevalence of HIV-1 among MSM was related to high-risk sexual activity such as unprotected anal sex and multiple sexual partners. CONCLUSIONS: Our results highlight the need to continually monitor HIV-1 diversity in Hebei and its neighboring provinces to achieve a more effective control of HIV-1 spread within the MSM community.

Genetic characterization of a novel HIV­1 CRF01_AE/ CRF07_BC recombinant form found among men who have sex with men in Baoding City, Hebei Province, China.

Large numbers of unique recombinant forms (URF) of human immunodeficiency virus (HIV-1) have been found among sexual transmission populations in China. Here, we report a novel second-generation URF of HIV-1 named BD201AQ that was isolated from an HIV-1-positive man who was infected through homosexual transmission in Baoding City, Hebei Province, China. Phylogenetic analysis based on the near-full-length genome (NFLG) sequence indicated that BD201AQ formed a monophyletic branch that did not cluster with other HIV-1 subtypes. Recombination analysis showed that the NFLG of BD201AQ had 12 segments, six CRF07_BC and six CRF01_AE segments, with CRF07_BC as the main framework. These findings indicate that the constant emergence of novel recombinant forms should receive more attention and that more measures should be taken to monitor the molecular epidemiological characteristics of HIV-1 and to prevent the spread of HIV-1 infections.

HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China.

BACKGROUND: To understand HIV-1 drug resistance in 11 prefectures of Hebei Province, China, we implemented a cross-sectional HIV-1 molecular epidemiological survey. METHODS: Blood samples were collected from 122 newly diagnosed drug-naïve HIV-1-positive individuals and 229 antiretroviral therapy (ART)-failure individuals from 11 prefectures in Hebei Province, China. Patient demographic data were obtained via face-to-face interviews using a standardized questionnaire when blood samples were collected. Genotyping of HIV-1 drug resistance (DR) was implemented using an in-house assay. RESULTS: In this study, the overall prevalence of HIV-1 DR was 35.5%. The prevalence of HIV-1 DR in participants experiencing treatment failure and ART-naïve participants was 51.9 and 5.9%, respectively. Mutations in protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), and non-NRTI (NNRTIs), as well as dual and multiple mutations were extensively seen in participants experiencing treatment failure. The proportions of NNRTI mutations (χ2 = 9.689, p = 0.002) and dual mutations in NRTIs and NNRTIs (χ2 = 39.958, p < 0.001) in participants experiencing treatment failure were significantly higher than those in ART-naïve participants. The distributions of M184V/I and M41L mutations differed significantly among three main HIV-1 genotypes identified. Viral load, symptoms in the past 3 months, CD4 counts, transmission route, and the duration of ART were found to be associated with HIV-1 DR. CONCLUSIONS: Our results suggest that new prevention and control strategies should be formulated according to the epidemic characteristics of HIV-1-resistant strains in Hebei Province, where antiretroviral drugs are widely used.

HIV-1 genetic diversity and its distribution characteristics among newly diagnosed HIV-1 individuals in Hebei province, China.

BACKGROUND: Since the first HIV-1 case in 1989, Hebei province has presented a clearly rising trend of HIV-1 prevalence, and HIV-1 genetic diversity has become the vital barrier to HIV prevention and control in this area. To obtain detailed information of HIV-1 spread in different populations and in different areas of Hebei, a cross-sectional HIV-1 molecular epidemiological investigation was performed across the province. METHODS: Blood samples of 154 newly diagnosed HIV-1 individuals were collected from ten prefectures in Hebei using stratified sampling. Partial gag and env genes were amplified and sequenced. HIV-1 genotypes were identified by phylogenetic tree analyses. RESULTS: Among the 139 subjects genotyped, six HIV-1 subtypes were identified successfully, including subtype B (41.0 %), CRF01_AE (40.3 %), CRF07_BC (11.5 %), CRF08_BC (4.3 %), unique recombinant forms (URFs) (1.4 %) and subtype C (1.4 %). Subtype B was identified as the most frequent subtype. Two URF recombination patterns were the same as CRF01_AE/B. HIV-1 genotype distribution showed a significant statistical difference in different demographic characteristics, such as source (P < 0.05), occupation (P < 0.05) and ethnicity (P < 0.05). The distributions of subtype B (P < 0.05), CRF01_AE (P < 0.05), CRF07_BC (P < 0.05) and subtype C (P < 0.05) showed significant differences in all ten prefectures, and the distributions of all six subtypes were significantly different in Shijiazhuang (P < 0.05) and Xingtai (P < 0.05), but not in other prefectures (P > 0.05). The differences in HIV-1 genotype distribution were closely associated with transmission routes. Particularly, all six subtype strains were found in heterosexuals, showing that HIV-1 has spread from the high-risk populations to the general populations in Hebei, China. In addition, CRF01_AE instead of subtype B has become the major strain of HIV-1 infection among homosexuals. CONCLUSIONS: Our study revealed HIV-1 evolution and genotype distribution by investigating newly diagnosed HIV-1 individuals in Hebei, China. This study provides important information to enhance the strategic plan for HIV prevention and control in China.

Eighteen-year follow-up report of the surveillance and prevention of an HIV/AIDS outbreak amongst plasma donors in Hebei Province, China.

BACKGROUND: There has been a clear increase in HIV-1 infection cases in recent years in Hebei Province, China, and transmission via blood is one of the risk factors in the early. This article aimed to investigate the HIV infection rate and control efficiency among the paid blood donor population over a period of 18 years. METHODS: From 1995-2013, HIV/AIDS cases among former blood donors in Hebei Province were registered and closely monitored to collect data of all-cause mortality, intervention measures to prevent family transmission, disease transmission between couples as well as between mothers and infants, and HAART therapy outcomes. RESULTS: A total of 326 cases were identified as directly infected with HIV/AIDS during plasma donation in Hebei Province. Of these, 146 cases (44.8%) were identified in the same year as infection; 180 cases (55.2%) were identified 1-18 years after infection because they did not participate in the 1995 screening. The final case was identified in February 2012. By 2013, the mortality rate and survival rate of plasma donor-related HIV/AIDS was 54.9% and 45.1%, respectively. The identified transmission rate between couples was 11.3% (8/71); this rate during the same year as infection was 3.3% (1/30), and the rate 4-17 years after HIV infection was 17.1% (7/41). Approximately 91.2% (145/159) of married women of childbearing age did not have children after being informed of HIV infection. Only 8.8% (14/159) of these women had children after being informed of HIV infection. The mother-to-infant transmission rate was 38.5% (5/13). The HAART coverage rate has increased from 10.1% (16/159) in 2003 to 83.6% (127/152) in 2013. Since 1999, the HIV mortality rate has trended up; by 2013, the cumulative mortality rate reached 54.9% (179/326). After HAART was initiated in China, the death rate decreased to some extent. Second generation transmission (via couple or mother-to-infant transmission) among blood donor-related HIV cases accounted for approximately 4.0% (13/326). All first- or second-generation cases were infected with HIV-1 subtype B. CONCLUSIONS: In this accident of HIV-infection among plasma donors in Hebei Province, a total of 339 direct and second-generation cases have been identified over 18 years of monitoring. Favorable clinical results have been achieved using intervention measurements and antiviral therapy.

Identification of a new HIV-1 circulating recombinant form (CRF159_01103) derived from CRF103_01B and CRF01_AE in Hebei Province, China.

Recombinant HIV-1 genomes identified in three or more epidemiological unrelated individuals are defined as circulating recombinant forms (CRFs). CRFs can further recombine with other pure subtypes or recombinants to produce secondary recombinants. In this study, a new HIV-1 intersubtype CRF, designated CRF159_01103, isolated from three men who have sex with men with no epidemiological linkage, was identified in Baoding city, Hebei Province, China. CRF159_01103 was derived from CRF103_01B and CRF01_AE. Bayesian molecular clock analysis was performed on the CRF01-AE and CRF103_01B regions of CRF159_01103. The time of origin of CRF159_01103 was predicted to be 2018-2019, indicating that it is a recent recombinant virus. The emergence of CRF159_01103 has increased the complexity of the HIV-1 epidemic in Hebei Province.

Identification of Two Novel HIV-1 Recombinant Forms Originated from CRF01_AE and Subtype B in the Sexual Contact Population in Hebei Province, China.

Two near full-length genome (NFLG) sequences of HIV-1 with undefined subtypes were analyzed to confirm the recombinant characteristics. To analyze the gene recombination patterns and breakpoints of these two NFLGs, the phylogenetic trees based on the NFLG sequences and their subregions were constructed, respectively. Sequences 233 and 953 are novel second-generation recombinant forms of HIV-1 CRF01_AE and subtype B. The NFLG phylogenetic tree analysis showed that these two NFLG sequences formed a unique monophyletic branch, respectively. The recombination breakpoints analysis showed that the recombination pattern of both sequences was that a subtype B fragment was inserted into a CRF01_AE backbone. Subregions I, II, and III were from CRF01_AE, subtype B, and CRF01_AE, respectively. The recombination breakpoints relative to HXB2 of sequences 233 and 953 were 2400 and 4870, and 3363 and 4828, respectively. The emergence of novel recombinant forms of CRF01_AE/B demonstrates that we should carry out the ongoing surveillance of HIV-1 recombinant forms in the sexually transmitted population.

Identification of two near-identical novel HIV-1 unique recombinant forms (CRF01_AE/B) among men who have sex with men in baoding, hebei, China.

Men who have sex with men (MSM) are the most frequent infection route of the human immunodeficiency virus (HIV) in Baoding, China, creating chances for the occurrence of unique recombinant forms (URFs) of the virus, i.e., recombination of different subtypes caused by co-circulation of multiple subtypes. In this report, two near-identical URFs (BDD002A and BDD069A) isolated from MSM in Baoding were identified. Phylogenetic tree analysis based on nearly full-length genomes (NFLGs) revealed that the two URFs formed a distinct monophyletic cluster with a bootstrap value of 100%. Recombinant breakpoints analysis identified that the NFLGs of BDD002A and BDD069A were both composed of CRF01_AE and subtype B, with six subtype B mosaic segments inserted into the CRF01_AE backbone. The CRF01_AE segments of the URFs clustered closely with the CRF01_AE reference sequences, and the B subregions clustered with the B reference sequences. The recombinant breakpoints of the two URFs were almost identical. These results suggest that effective interventions are urgently needed to prevent the formation of complex HIV-1 recombinant forms in Baoding, China.

Changes of Viral Load, Drug Resistance, and CD4 Cell Count in HIV-1-Infected Patients Receiving Antiretroviral Therapy in Hebei Province, China, 2003-2019.

In this study, a total of 462 samples of whole blood were collected from 36 patients enrolled. During the entire course of antiretroviral therapy (ART) from 2003 to 2019, both the CD4 cell count and viral load (VL) of study patients were examined annually, and an HIV-1 genotypic drug resistance (DR) assay was carried out using an in-house method when the HIV-1 VL was >1,000 copies/mL. The results indicated that 13 (36.1%) experienced treatment failure and 23 (63.9%) experienced treatment success among 36 patients. The proportion of patients with effective treatment after the adjustment of ART regimens was significantly higher than before adjustment (χ2 = 33.796, p < .001). Furthermore, the frequencies of HIV-1 DR mutations before adjustment were higher than those after adjustment (t = 3.345, p = .002). In particular, among 23 patients with effective treatment after adjustment, the means ± standard deviations of the VLs and CD4 cell counts before adjustment were 3.85 ± 0.65 log RNA copies/mL and 226.83 ± 106.06 cells/mm3, respectively, compared with 2.19 ± 0.58 log RNA copies/mL and 367.68 ± 174.62 cells/mm3, respectively, after adjustment. Obviously, there were statistically significant differences in the changes in VL (t = 8.728, p < .001) and CD4 cell count (t = -4.476, p < .001) before and after adjustment. Therefore, patients who received updated ART regimens containing LPV/r and TDF after adjustment achieved better therapeutic effects compared with patients who received initial ART regimens harboring D4T/AZT or NVP. This suggests that future research is needed to initiate the surveillance of DR, VLs, and CD4 cell counts immediately after HIV diagnosis, and dynamic changes in these indicators so as to optimize ART effects.

Near-Full-Length Genomic Characteristics of Three Novel Human Immunodeficiency Virus-1 CRF01_AE/C Recombinant Forms Among Men Who Have Sex with Men in Hebei Province, China.

Subtypes circulating recombinant form (CRF)01_AE and C are two human immunodeficiency virus (HIV)-1 strains that are prevalent in different key populations such as men who have sex with men (MSM) in China. Co-circulating of different HIV-1 subtypes is easy to result in the generation of second-generation recombinants. In this study, three new HIV-1 CRF01_AE/C recombinants from three MSMs were detected in Hebei province, China. Phylogenetic tree and recombination analysis showed that the near-full-length genomic of S114 had seven recombination breakpoints, including four C fragments inserted into the CRF01_AE backbone; M363 had six recombination breakpoints, including three C fragments inserted into the CRF01_AE backbone; M162 had eight recombination breakpoints, including four C fragments inserted into the CRF01_AE backbone. Furthermore, phylogenetic tree analysis based on subregion gene fragments also identified this kind of CRF01_AE/C recombinant structure. This study suggests a more complex HIV-1 epidemiological trend in Hebei province, China and the urgency of continuous HIV-1 recombinant strain registry in sexually transmitted populations.

Three Novel CRF01_AE/CRF07_BC Recombinant Forms of HIV-1 Identified in Shijiazhuang City, China.

BACKGROUND: Hebei, a province with a low Human Immunodeficiency Virus (HIV) prevalence, is also a region with the most abundant HIV-1 genetic diversity. HIV-1 recombinant forms have been the key factor influencing the effectiveness of HIV-1 control and therapy. OBJECTIVES: We aimed to study inter-subtype recombinant structures of new HIV-1-second generation recombinant forms. METHODS: Monitoring the HIV-1 subtype by phylogenetic and recombinant breakpoint analyses are the two most frequent methods among men who have sex with men (MSM). Here, three near full-length genomes (NFLGs) were obtained from HIV-1 seropositive MSM in Shijiazhuang City, China, who have never received antiretroviral therapy in 2021. RESULTS: Phylogenetic analysis indicated that three NFLGs were novel inter-subtype recombinant forms between CRF07_BC and CRF01_AE. For the NFLG 21S009, four CRF07_BC gene fragments were inserted into the pol, vif-vpr, vpu-env, and nef-3` LTR gene regions within a CRF01_ AE backbone, respectively. For the NFLG 21S095, four breakpoints were identified in HIV-1 pol and vpu regions. The NFLG 21S370 contained four gene recombinant breakpoints within HIV-1 pol and vpu-env gene regions. Of these three NFLGs, the NFLG 21S009 contained the most breakpoints, distributed in the pol, vif, vpr, vpu, env, and nef regions, respectively. In the gag-pol regions, three NFLGs had only one CRF07_BC gene fragment inserted into gene points between 4250 and 4792. CONCLUSION: Our findings provide strong evidence that the surveillance of novel recombinant forms is necessary for the increase in better control of HIV.

Near-Full-Length Genome Analysis of a HIV-1 CRF01_AE/B Recombinant Strain Among Men Who Have Sex with Men in Chengde City, China.

The unique recombinant form (URF) of HIV is formed by multiple subtypes which are cocirculating in some area, and the number of HIV recombinants is on the increase worldwide. In this study, we identified a URF named 2019638, composed of CRF01_AE and subtype B, in a man who has sex with men in Qinhuangdao, Hebei province, China. The near-full-length genome (NFLG) sequence was confirmed to be a novel URF. Within this NFLG, two CRF01_AE fragments were inserted into the pol and vif regions, respectively, using subtype B as the backbone. Moreover, the presence of the V106M and V179D point mutations in the reverse transcriptase (RT) region rendered the high-level resistance to efavirenz and nevirapine and intermediate resistance to doravirine. Our findings suggest that the HIV epidemic is evolving toward a high degree of recombination, and we need to continuously monitor HIV genetic diversity to control the further development of the AIDS epidemic.

Distribution pattern, molecular transmission networks, and phylodynamic of hepatitis C virus in China.

In China, few molecular epidemiological data on hepatitis C virus (HCV) are available and all previous studies were limited by small sample sizes or specific population characteristics. Here, we report characterization of the epidemic history and transmission dynamics of HCV strains in China. We included HCV sequences of individuals belonging to three HCV surveillance programs: 1) patients diagnosed with HIV infection at the Beijing HIV laboratory network, most of whom were people who inject drugs and former paid blood donors, 2) men who have sex with men, and 3) the general population. We also used publicly available HCV sequences sampled in China in our study. In total, we obtained 1,603 Ns5b and 865 C/E2 sequences from 1,811 individuals. The most common HCV strains were subtypes 1b (29.1%), 3b (25.5%) and 3a (15.1%). In transmission network analysis, factors independently associated with clustering included the region (OR: 0.37, 95% CI: 0.19-0.71), infection subtype (OR: 0.23, 95% CI: 0.1-0.52), and sampling period (OR: 0.43, 95% CI: 0.27-0.68). The history of the major HCV subtypes was complex, which coincided with some important sociomedical events in China. Of note, five of eight HCV subtype (1a, 1b, 2a, 3a, and 3b), which constituted 81.8% HCV strains genotyped in our study, showed a tendency towards decline in the effective population size during the past decade until present, which is a good omen for the goal of eliminating HCV by 2030 in China.

[Retrospective cohort study on period of incubation and survival among former commercial plasma donors infected with HIV in Hebei province].

OBJECTIVE: To examine the state of incubation period and survival time of former commercial plasma donors (FCPDs) infected with HIV. METHODS: All objects infected with HIV were from Hebei province and found from general investigation for FCPDs in 1995. The infector cohort by 142 cases was used to estimate incubation period. In the infector cohort, the time which infectors entered the cohort was their infection time, which was the middle value of the origin date, which was January 1, 1995. The onset of AIDS was defined as an outcome event. End point of observation was Dec 31, 2010. There were 192 months in all from beginning to end. The AIDS cohort by 57 cases was used to estimate the survival of the patients. In the patient cohort, the time of AIDS onset was defined as the time entering the cohort, and death of AIDS was defined as an outcome event. The cumulative incidence ratio, cumulative mortality, illness intensity and mortality intensity were analyzed through Kaplan-Meier. RESULTS: During the observation period, 123 cases of 142 infectors developed into AIDS, the cumulative incidence was 86.42% (123/142) and the intensity was 8.53/100 person-years and the median time of incubation period was 112.0 months (95%CI: 108.8 - 115.2). The death dates of 57 patients were from 1 to 24 months after onset. The cumulative mortality was 100%, and the intensity was 250.66/100 person-years and the median survival time was 3.0 months (95%CI: 1.8 - 4.2). It was estimated that the median time was 115.0 months (9.6 years) from infection to death. CONCLUSION: The median times of incubation and median survival time were 112.0 and 3.0 months, respectively.

Efficacy, Safety, and Prognosis of Sequential Therapy with Tamoxifen and Letrozole versus Letrozole Monotherapy for Breast Carcinoma.

Objective: To explore the efficacy, safety, and patient prognosis of letrozole (LTZ) alone or in sequence with tamoxifen (TAM) for the treatment of breast carcinoma (BC). Methods: In this retrospective study, 150 patients with BC who received treatment in the First People's Hospital of Ningyang County between January 2012 and January 2017 were selected. According to different treatment methods, 99 cases receiving sequential therapy with TAM and LTZ were included in the research group, and the remaining 51 patients receiving LTZ monotherapy were selected as the control group. The efficacy, safety, survival rate, recurrence rate, and blood lipid indices (total cholesterol, TC; triglyceride, TG; high-density lipoprotein cholesterol, HDL-C; and low-density lipoprotein cholesterol, LDL-C) of the two groups were observed and compared. Results: The overall response rate of the research group was statistically higher than that of the control group, and the incidence of adverse reactions was significantly lower. No evident difference was observed in 1-, 3-, or 5-year survival rates between the two groups, while the 3-5-year recurrence rate was obviously lower, and the improvement of blood lipid indices was significantly better in the research group compared with the control group. Conclusion: LTZ alone or in sequence with TAM is effective and safe for the treatment of BC, which can significantly improve the prognosis and blood lipid indices of BC patients.

Identification of Three Novel HIV-1 Second-Generation Recombinant Forms (CRF01_AE/CRF07_BC) Among Men Who Have Sex with Men in Baoding, Hebei, China.

The number of the second-generation recombinants originated from these two subtypes is significantly increasing due to co-circulating of CRF01_AE and CRF07_BC in China, especially among men who have sex with men (MSM). In this study, we reported three new unique recombinant forms (URFs) among MSM in Baoding, China. Phylogenetic and recombinant analyses based on the near full-length genome revealed these three URFs were the second-generation recombinant strains originated from CRF01_AE and CRF07_BC. Nowadays, the MSM has become a main route that causes the viral recombination. Therefore, the further epidemiological surveillance should be conducted in the MSM population to strengthen our knowledge of HIV-1 evolution and genetic diversity.

Identification of a New HIV-1 CRF68_01B/CRF01_AE Recombinant Form Among Men Who Have Sex with Men in Hebei Province, China.

In recent years, homosexual contact has been the most frequent route of human immunodeficiency virus type one (HIV-1) transmission in Hebei, China. The number of circulating recombinant forms (CRFs) and unique recombinant forms found in this key population were more and more. In this study, we identified a novel HIV-1 second-generation recombinant form originated from CRF68_01B and CRF01_AE among men who have sex with men (MSM) through the phylogenetic and recombinant breakpoints analyses based on the near full-length genome. Both CRF68_01B and CRF01_AE were circulating in the Hebei province of China, and this MSM was diagnosed as the recent HIV-1 infection in fact. The result reminds that we should constantly monitor HIV-1 diversity in Hebei and take further effective to control the recombination of not only HIV-1 major strains but also minor strains.

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

We analyzed the near full-length genome (NFLG) of an HIV-1-positive sample(027A) with an undetermined subtype to determine the recombinant characteristics and possible source of the parental virus. 027A is a novel HIV-1 second-generation recombinant form composed of CRF01_AE and subtype B, detected from a married HIV-1-positive male subject who was infected through homosexual transmission in Baoding, Hebei province, China. The NFLG phylogenetic tree analysis suggested that the strain was close to circulation recombinant forms' (CRFs') reference sequences involved with CRF01_AE, but formed a distinct monophyletic cluster separately from them. This indicated that the strain might be a unique CRF01_AE-related recombinant from. Furthermore, the results of RIP and jpHMM further demonstrated that the NFLG sequence of the strain was composed of CRF01_AE and subtype B. The strain was two CRF01_AE fragments inserted into B backbone. Phylogenetic analysis illustrated that the CRF01_AE subregions were from the previously identified CRF01_AE cluster 4, 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 recombinant originated from CRF01_AE and B strains are constantly emerging in 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.

Prevalence of resistance mutations associated with integrase inhibitors in therapy-naive HIV-positive patients in Baoding, Hebei province, China.

Antiretroviral therapy (ART) regimens containing integrase strand transfer inhibitors (INSTIs) are the recommended treatment for human immunodeficiency virus type 1 (HIV-1)-infected patients in the most recent guidelines in China. In this study, we investigated INSTI resistance mutations in newly diagnosed therapy-naive HIV-positive patients in Baoding City, Hebei Province (China) to provide guidance for implementing routine INSTI-associated HIV-1 genotypic resistance testing. Plasma samples were collected from HIV-1-infected patients without treatment at Baoding People's Hospital from January 2020 to December 2021. The part of HIV-1 pol gene encoding integrase was amplified, sequenced, and analyzed for INSTI resistance. Clinical data including demographic data, CD4+ T cell counts, HIV-RNA loads, and resistance mutations were collected. Treatment-naïve HIV-1 patients (n = 131) were enrolled. We identified ten genotypes, and the predominant genotype was CRF01_AE in 67 patients (51.15%), CRF07_ BC in 39 patients (29.77%), subtype B in 11 patients (8.40%), and other subtypes (CRF68_01B, 3.82%; CRF55_01B, 1.53%, CRF80_0107, 1.53%; URFs 1.53%; and CRF103_01B, CRF59_01B, and CRF65_cpx, 1.4% each). Four major (E138A, R263k, G140S, and S147G) and three accessory (H51Y, Q146QL, and S153F) INSTI-resistance mutations were observed (genotype CRF01_AE, three patients; genotype B, one patient; and genotype CRF07_BC, one patient), resulting in different degrees of resistance to the following five INSTIs: raltegravir, elvitegravir, dolutegravir, bictegravir, and cabotegravir. The overall resistance rate was 3.82% (5/131). All INSTI-resistant strains were cross-resistant. The primary INSTI drug resistance rate among newly diagnosed HIV-infected patients in Baoding was low, but monitoring and research on HIV INSTI resistance should be strengthened in Baoding because INSTI-based regimen prescriptions are anticipated to increase in the near future.