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Objectives: People with HIV (PWH) are more likely to develop ECG abnormalities. Substantial evidence exists for genetic contribution to ECG parameters among general population. However, whether and how would host genome associate with ECG parameters among PWH is unclear. Our research aims to analyze and compare genetic variants, mapped genes, and enriched pathways of ECG parameters among PWH and HIV-negative controls., Design: A cross-sectional study., Method: We performed a large original genome-wide association study (GWAS) of ECG parameters among PWH ( n  = 1730) and HIV-negative controls ( n =  3746). Genome-wide interaction analyses were also conducted., Results: A total of 18 novel variants were detected among PWH, six for PR interval including rs76345397 at ATL2 , 11 for QRS duration including rs10483994 at KCNK10 and rs2478830 at JCAD , and one for QTc interval (rs9815364). Among HIV-negative controls, we identified variants located at previously reported ECG-related genes ( SCN5A , CNOT1 ). Genetic variants had a significant interaction with HIV infection ( P  < 5 × 10 -8 ), implying that HIV infection and host genome might jointly influence ECG parameters. Mapped genes for PR interval and QRS duration among PWH were enriched in the biological process of viral genome replication and host response to virus, respectively, whereas enriched pathways for PR interval among HIV-negative controls were in the cellular component of voltage-gated sodium channel complex., Conclusion: The present GWAS indicated a distinctive impact of host genome on quantitative ECG parameters among PWH. Different from HIV-negative controls, host genome might influence the cardiac electrical activity by interfering with HIV viral infection, production, and latency among PWH., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Genome-wide association studies (GWAS) have identified some variants associated with subclinical atherosclerosis (SCA) in general population but lacking sufficient validation. Besides traditional risk factors, whether and how would genetic variants associate with SCA among people with HIV (PWH) remains to be elucidated., Method: A large original GWAS and gene-environment interaction analysis of SCA were conducted among Chinese PWH (n = 2850) and age/sex-matched HIV-negative controls (n = 5410). Subgroup analyses by age and functional annotations of variants were also performed., Results: Different from HIV-negative counterparts, host genome had a greater impact on young PWH rather than the elders: one genome-wide significant variant (rs77741796, P = 2.20 × 10 -9 ) and eight suggestively significant variants (P < 1 × 10 -6 ) were identified to be specifically associated with SCA among PWH younger than 45 years. Seven genomic loci and 15 genes were mapped to play a potential role on SCA among young PWH, which were enriched in the biological processes of atrial cardiac muscle cell membrane repolarization and molecular function of protein kinase A subunit binding. Furthermore, genome-wide interaction analyses revealed significant HIV-gene interactions overall as well as gene-environment interactions with alcohol consumption, tobacco use and obesity among PWH. The identified gene-environment interaction on SCA among PWH might be useful for discovering high-risk individuals for the prevention of SCA, particularly among those with tobacco use and alcohol consumption., Conclusion: The present study provides new clues for the genetic contribution of SCA among young PWH and is the starting point of precision intervention targeting HIV-related atherosclerosis., (© 2022. The Author(s).)

Background: Mitochondrial DNA (mtDNA) profiles and contributions of mtDNA variants to CD4+T-cell recovery in Euramerican people living with HIV (PLWH) may not be transferred to East-Asian PLWH, highlighting the need to consider more regional studies. We aimed to identify mtDNA characteristics and mutations that explain the variability of short-term CD4+T-cell recovery in East-Asian PLWH., Method: Eight hundred fifty-six newly reported antiretroviral therapy (ART)-naïve Chinese PLWH from the Comparative HIV and Aging Research in Taizhou (CHART) cohort (Zhejiang Province, Eastern China) were enrolled. MtDNA was extracted from peripheral whole blood of those PLWH at HIV diagnosis, amplified, and sequenced using polymerase chain reaction and gene array. Characterization metrics such as mutational diversity and momentum were developed to delineate baseline mtDNA mutational patterns in ART-naïve PLWH. The associations between mtDNA genome-wide single nucleotide variants and CD4+T-cell recovery after short-term (within ~48 weeks) ART in 724 PLWH were examined using bootstrapping median regressions., Results: Of 856 participants, 74.18% and 25.82% were male and female, respectively. The median age was 37 years; 94.51% were of the major Han ethnicity, and 69.04% and 28.62% were of the heterosexual and homosexual transmission, respectively. We identified 2,352 types of mtDNA mutations and mtDNA regions D-loop , ND5 , CYB , or RNR1 with highest mutational diversity or volume. Female PLWH rather than male PLWH at the baseline showed remarkable age-related uptrends of momentum and mutational diversity as well as correlations between CD4+T <200 (cells/μl) and age-related uptrends of mutational diversity in many mtDNA regions. After adjustments of important sociodemographic and clinical variables, m.1005T>C, m.1824T>C, m.3394T>C, m.4491G>A, m.7828A>G, m.9814T>C, m.10586G>A, m.12338T>C, m.13708G>A, and m.14308T>C (at the Bonferroni-corrected significance) were negatively associated with short-term CD4+T-cell recovery whereas m.93A>G, m.15218A>G, and m.16399A>G were positively associated with short-term CD4+T-cell recovery., Conclusion: Our baseline mtDNA characterization stresses the attention to East-Asian female PLWH at risk of CD4+T-cell loss-related aging and noncommunicable chronic diseases. Furthermore, mtDNA variants identified in regression analyses account for heterogeneity in short-term CD4+T-cell recovery of East-Asian PLWH. These results may help individualize the East-Asian immune recovery strategies under complicated HIV management caused by CD4+T-cell loss., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Wei, Lin, Ding, Sun, Zhao, He, Ma, Li, Zhou, Chen, Shen, Gao and He.)

Background: HIV and HCV coinfection leads to accelerated liver fibrosis, in which microbial translocation and systemic inflammation might play important roles., Objective: This study aimed to provide an extensive profile of the plasma microbial translocation and inflammation biomarkers associated with advanced liver fibrosis among HIV-HCV-coinfected patients., Methods: This cross-sectional study recruited 343 HIV-HCV-coinfected patients on combination antiretroviral therapy (cART) from a rural prefecture of Yunnan province in Southwest China. The plasma concentrations of sCD14 and 27 cytokines and chemokines were assayed and compared against advanced or mild levels of liver fibrosis., Results: Of the 343 HIV-HCV-coinfected patients, 188 (54.8%) had severe or advanced liver fibrosis (FIB-4 > 3.25). The patients with advanced liver fibrosis (FIB-4 > 3.25 vs. FIB-4 ≤ 3.25) had higher plasma levels of interleukin (IL)-1β, IL-6, IL-7, IL-9, IL-12, IL-15, IL-17, granulocyte macrophage colony stimulating factor (GM-CSF), Interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), IL-4, IL-10, IL-13, fibroblast growth factor 2 (FGF-basic), and Monocyte chemoattractant protein-1 (MCP-1). Multivariable logistic regression models showed that advanced liver fibrosis was associated with an increased plasma level of IL-1β, IL-6, IL-7, IL-12, IL-17, GM-CSF, IFN-γ, IL-4, IL-10, MCP-1, Eotaxin, and FGF-basic, with FGF-basic continuing to be positively and significantly associated with advanced liver fibrosis, after Bonferroni correction for multiple comparisons (adjusted odds ratio (aOR) = 1.92; 95%CI: 1.32-2.81; p = 0.001). Plasma sCD14 was also significantly associated with advanced liver fibrosis (aOR = 1.13; 95%CI: 1.01-1.30; p = 0.049)., Conclusions: HIV-HCV-coinfected patients are living with a high prevalence of advanced liver fibrosis which coexists with a mixture of elevated plasma inflammation and microbial translocation biomarkers. The significant associations of advanced liver fibrosis with FGF-basic and sCD14 may reveal pathogenic mechanisms and potential clinical intervention targets for liver fibrosis in HCV-HIV coinfection.

Increasing evidence shows that mitochondrial DNA (mtDNA) variations have an important effect on metabolic disorders, but such studies have not been conducted in HIV-infected patients in Asia. We investigated the distribution of mtDNA haplogroups and their correlation with metabolic disorders in HIV-infected patients. A cross-sectional survey was performed among 296 HIV patients older than the age of 40 years in a rural prefecture, Eastern China. The entire mtDNA sequence was amplified by polymerase chain reaction using four overlapping pairs of primers that have been standardly used. In this sample, mtDNA haplogroups B, D, M7, and F were the most dominant haplogroups. The overall prevalence of metabolic syndrome (MetS) was 36.1%, and was highest (77.8%) among those with haplogroup G and lowest (21.4%) among those with haplogroup M8. In multivariable analysis, haplogroups G and N9 were significantly associated with the presence of MetS [adjusted odds ratio (aOR) = 13.5, 95% confidence interval (CI): 1.9-94.7; aOR = 8.1, 95% CI: 1.8-36.1; respectively]. Moreover, patients with haplogroup G had increased odds of elevated glycated hemoglobin (HbA1c) (aOR = 10.1, 95% CI: 1.4-71.1), patients with haplogroup N9 had increased odds of elevated triglycerides (aOR = 13.5, 95% CI: 2.4-76.8). No significant association between mtDNA haplogroups and other MetS components was observed. Our data demonstrate the association between mtDNA haplogroups and MetS in HIV-infected patients. The Asian-specific mtDNA haplogroups G and N9 may confer higher risk for the development of MetS in HIV-infected patients, which requires further longitudinal investigation.

This retrospective cohort study was conducted from January 2009 to July 2016 to explore the occurrence and risk factors of self-reported fatigue within the first 6 months after receiving antiretroviral treatment (ART) among patients living with HIV in Taizhou City of Zhejiang province, Eastern China. In total, 1163 HIV-infected patients with a median follow-up duration of 27.8 months were included in the analysis. Among them, 261 (22.4%) reported fatigue within the first 6 months after ART. In the multivariable logistic regression analysis, self-reported fatigue within the first 6 months after ART was negatively associated with junior middle-school education or above, baseline CD4 cell count of 200-349 and >350 cells/μL (vs < 200 cells/μL), overweight at baseline (vs normal weight) but positively associated with ≥50 years old at initiation of ART (vs <30 years old), underweight at baseline, use of efavirenz (EFV) in the first-line regimen. Our data suggest that earlier initiation of ART and higher body mass index are preferred to restore the energy of HIV-infected patients with the EFV use in the era of ART in China.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), which primarily affects human immunodeficiency virus (HIV)-infected adults with advanced immunodeficiency. Xinjiang province in China is an endemic area for Kaposi's sarcoma (KS), however, currently, only limited data for KSHV infection among HIV-infected individuals living in this endemic area is available. A cross-sectional study of 86 HIV positive participants was conducted in Xinjiang, China from 2014 through 2015. Plasma samples were collected and screened for KSHV and HIV infection. HIV pol gene and KSHV ORF-K1 gene were amplified and sequenced, genotypes were determined by phylogenetic analysis. Over all, prevalence was 48.9% (42/86; 95%CI 38.4-59.3%) for KSHV. Only CRF07&#95;BC subtype has been identified among all these HIV positive individuals, while the subtype A and C of KSHV were detected in the participants. Meanwhile, we found that those with high CD4 counts (>500) showed a lower anti-KSHV titer, compared with other groups. Our study indicated a high prevalence of KSHV among HIV positive individuals in Xinjiang, China. Thus, management of HIV/AIDS patients should include KSHV screen and should consider the risk of KSHV-associated malignancies., (© 2017 Wiley Periodicals, Inc.)

Objective: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection has been proved to be a growing public health concern. The prevalence and genotypic pattern vary with geographic locations. Limited information is available to date with regard to HCV genotype and its clinical implications among those former commercial blood donor communities. The aims of this study were to genetically define the HCV genotype and associated clinical characteristics of HIV/HCV co-infected patients from a region with commercial blood donation history in central China., Methods: A cross sectional study, including 164 HIV infected subjects, was conducted in Shanxi province central China. Serum samples were collected and HCV antibody testing, AST and ALT testing were performed. Seropositive samples were further subjected to RT-PCR followed by direct sequence coupled with phylogenetic analysis of Core-E1 and NS5B regions performed in comparison with known reference genotypes., Findings: A total of 139 subjects were HCV antibody positive. Genotype could be determined for 88 isolates. Phylogenetic analysis revealed that the predominant circulating subtype was HCV 1b (65.9%), followed by HCV 2a (34.1%). The HCV viral load in the subjects infected with HIV1b was significantly higher than those infected with HCV 2a (P = 0.006). No significant difference for HCV RNA level was detected between ART status, CD4+ cell count level and HIV RNA level. Serum AST and ALT level were likely to increase with HCV RNA level, although no significance was observed. Those who had conducted commercial donation later than 1991 (OR 3.43, 95% CI: 1.12-10.48) and had a short duration of donation (OR 0.35, 95% CI: 0.13-0.96) were more likely to be infected with HCV 1b., Conclusion: These results suggest that HCV subtype 1b predominates in this population, and the impact of HIV status and ART on HCV disease progression is not significantly correlated.

Contact tracing, coupled with molecular epidemiologic investigation, is especially useful for identifying an infection with few cases in the population, such as human immunodeficiency virus (HIV) infection in China. No such research is available on Chinese men who have sex with men (MSM). From 2008 to 2010 in Taizhou Prefecture in China, every newly diagnosed HIV-infected MSM was invited to participate as an "index case" in a contact tracing survey by providing contact information for up to 8 sexual contacts, who themselves were approached to receive voluntary HIV counseling and testing. Those who tested HIV-positive were then subjected to another contact tracing survey. This process was repeated until no more sexual contacts were reported or tested positive. A total of 100 HIV-infected MSM served as "index cases," including the initial 49 cases identified through routine surveillance programs and 51 cases from the present survey. Traced MSM exhibited little willingness to receive voluntary counseling and testing. CRF01&#95;AE (HIV type 1) was the dominant subtype. Seven of 49 independent sexual networks were deemed HIV transmission clusters. Fear of stigma or discrimination may deter Chinese MSM from receiving voluntary counseling and testing. Nonetheless, the integration of behavioral network analysis and HIV phylogenetic analysis provides enhanced evidence for developing tailored prevention strategies for HIV-infected MSM.