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The determinants of persistent human papillomavirus (HPV) infection remain largely unknown, and existing studies have predominantly focused on the female population. Individual genetic background may influence the persistence of HPV infection, we the evidence overall and among human immunodeficiency virus (HIV)-positive males are very limited. We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with anal HPV persistence, based on a cohort designed to study the natural history of anal HPV infection among HIV-positive males in Taizhou, China from 2016 to 2022. A total of 322 HIV-positive males with anal HPV infection, with a mean age of 43.0 (standard deviation [SD]: 13.8) years, were included in this GWAS. The median follow-up time was 1.8 (interquartile range [IQR]: 1.5-2.0) years. The persistence of any type of HPV infection was 53.4%. After adjusting for age and sexual orientation, there were 2 SNPs with p < 1 × 10 -5 and 24 SNPs with p < 1 × 10 -4 . The most closely associated with HPV persistence in additive models were rs7359031 (LOC105370461, odds ratio [OR] T/C  = 0.36, 95% confidence interval [CI]: 0.24-0.56; p = 6.67 × 10 -6 ) located at 14q21.1, and rs11046048 (PYROXD1, OR C/A  = 0.41, 95% CI: 0.28-0.60; p = 7.80 × 10 -6 ) located at 12p12.1. Other SNPs were mainly located at 6q23.3 (HBS1L-MYB) and 6p21.33 (CCHCR1, PSORS1C3). LOC105370461, PYROXD1, HBS1L-MYB, CCHCR1, and PSORS1C3 may be susceptible genes for HPV persistence. We appeal further studies to validate these associations and examine the underlying mechanisms., (© 2024 Wiley Periodicals LLC.)

Objectives: This study aims to estimate the incidence and persistence/clearance of anal human papilloma virus (HPV) infection and related factors among men with HIV in Taizhou, China., Design: A prospective cohort study., Methods: Men with HIV were recruited and followed up from 2016 to 2021. Questionnaire surveys were used to collect social-demographic and behavioral characteristics, and anal swabs were collected for HPV Genotyping., Results: A total of 675 men with HIV were recruited and followed up. After an average follow-up time of 1.75 years, HPV39 (3.8/100 person-years), HPV52 (3.6/100 person-years), HPV51 (3.1/100 person-years), HPV58 (2.5/100 person-years) and HPV16 (2.4 cases/100 person-years) in the high-risk types showed the highest incidence rate. In marriage with woman [adjusted hazard ratio (aHR) = 0.44, 95% confidence interval (CI) 0.20-0.99] showed an inverse association with HPV incidence, while bisexuality or undetermined sexual orientation (aHR = 2.62, 95% CI 1.08-6.36) showed a positive association. For those infected at baseline, the top three high-risk HPV with the lowest clearance density were HPV52 (32.2/100 person-years), HPV58 (38.1/100 person-years), and HPV16 (43.5/100 person-years). Daily consumption of 1-28 g alcohol (aHR = 0.62, 95% CI 0.41-0.95) showed an inverse association with HPV clearance, while illicit drug use (aHR = 3.24, 95% CI 1.59-6.59) showed a positive association., Conclusion: Anal HPV infection and clearance were both active in men with HIV in China. Marriage status and sexuality were associated with the incidence of HPV infection, while substance use including alcohol and illicit drug were associated with HPV clearance. More studies are needed to explore the risk factors of HPV persistence., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Objective: We aimed to examine whether HIV infection was independently associated with frailty status and its individual components., Methods: This cross-sectional investigation included people living with HIV (PLWH) and HIV-negative individuals from the baseline survey of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, China. Frailty phenotype was based on five components: weight loss, low physical activity, exhaustion, weak grip strength and slow gait speed. Frailty was defined as the presence of at least three components, and prefrailty was defined as one or two components. Logistic regression models were used to analyse the factors associated with frailty and its components., Results: In all, 2475 people living with HIV (age 45.5 ± 14.9 years; 76.2% male) and 4948 HIV-negative individuals (age 45.5 ± 14.8 years; 76.3% male) were included. Among PLWH, median CD4 count was 395 cells/μL and 78% were currently on antiretroviral therapy (ART). Frailty and prefrailty were significantly more prevalent in PLWH (3.2% vs 1.9% and 32.9% vs 27.9%) overall and at ages 18-39 (1.4% vs 0.2% and 22.7% vs 19.0%), 40-59 (2.5% vs 0.9% and 30.9% vs 27.9%) and 60-90 years (8.4% vs 7.4% and 57.1% vs 45.8%). HIV infection was associated with frailty and prefrailty [adjusted odds ratio (aOR) = 1.48, 95% confidence interval (CI): 1.06-2.08; and aOR = 1.18, 95% CI: 1.05-1.33, respectively] after adjusting for confounding variables, but were strengthened with further adjustment for multimorbidity (aOR = 1.62, 95% CI: 1.14-2.28; and aOR = 1.22, 95% CI: 1.09-1.37), and were no longer significant with further adjustment for depressive symptoms and sleep disorders (aOR = 1.02, 95% CI: 0.71-1.46; and aOR = 1.06, 95% CI: 0.94-1.20). Among individual components, HIV infection was positively associated with weak grip strength and slow gait speed, but negatively associated with low physical activity and exhaustion in all the adjusted models described., Conclusions: Frailty and prefrailty occur more often and earlier in PLWH. However, grip strength and gait speed are affected to a greater extent, highlighting their potential as screening and intervention targets to prevent or slow frailty among PLWH., (© 2022 British HIV Association.)

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).)

Neurocognitive impairment (NCI) persists among people living with HIV (PLWH) despite the success of combination antiretroviral therapy (cART). Although muscular waning or decreased handgrip strength has been widely reported to be associated with cognitive erosion in general elders, such association has not been examined in PLWH who commonly experience decreased handgrip strength and NCI. Furthermore, whether HIV infection modifies such association remains to be addressed. A cross-sectional analysis was conducted with 2808 HIV-positive and 5402 HIV-negative adults participating in the baseline survey of the CHART (Comparative HIV and Aging Research in Taizhou) cohort, China, 2017 - 2019. HIV-positive individuals showed weaker handgrip strength than HIV-negative controls (34.0 kg vs 37.7 kg). Multivariate logistic regression analysis indicated that both HIV infection (aOR = 4.35, p < 0.001) and every 5-kg decrease in "Handgrip strength" (aOR = 1.27, p < 0.001) were significantly associated with NCI, and there was a significant interaction between reduced handgrip strength and HIV infection on NCI (aOR = 1.14, p = 0.015). In stratified analyses adjusting for potential confounders, the association between reduced handgrip strength and NCI was significant among PLWH at all age groups but only significant among HIV-negative controls at 30 - 44 and 60 - 89 ages. Handgrip strength decline is significantly associated with the risk of NCI among PLWH. HIV infection may exacerbate the adverse effect of poor handgrip strength on NCI, especially at younger ages. Early detection of handgrip strength decline could facilitate delivery of compensatory strategies or assistive services to PLWH with or at high risk of NCI., (© 2021. Journal of NeuroVirology, Inc.)

Background: In the era of combination antiretroviral therapy (ART), the incidence, manifestations and severity of kidney diseases have dramatically changed in people living with HIV (PLWH). Little is known about the incidence of impaired kidney function (IKF) measured by serum creatine-based estimated glomerular filtration rate (eGFR) in PLWH., Methods: In this systematic review and meta-analysis, we searched PubMed, Ovid, Medline, Embase and Web of Science for studies published before May 7th, 2021, with estimates of incidence of IKF among PLWH. We independently reviewed each study for quality by using the Newcastle-Ottawa scale. The incidence and 95% confidence intervals (CIs) were calculated using random-effects model., Results: Sixty out of 3797 identifiable studies were eligible for the meta-analysis. A total of 19 definitions of IKF were described and categorized into three types: the threshold of eGFR, an absolute or percent decrease in eGFR, and certain eGFR threshold combined with decrement in eGFR. The eGFR< 60 ml/min/1.73m 2 was the most widely used definition or criterion for IKF, by which the pooled incidence rate of IKF was 12.50 (95%CI: 9.00-17.36) per 1000 person years (PYs). The second most-studied outcome was a > 25% decrease in eGFR, followed by eGFR< 90 ml/min/1.73m 2 , eGFR< 30 ml/min/1.73m 2 and a combination of eGFR threshold plus decreased eGFR. The reported incidence rates of IKF differ widely by different definitions of IKF. The highest pooled incidence was observed for those with > 25% decrease in eGFR, while the lowest was observed in those with eGFR < 30 ml/min/1.73m 2 . Substantial heterogeneity was identified across most estimates., Conclusion: Our study provides a comprehensive summary of eGFR-based definitions and incidence rates of IKF in PLWH, not only promoting our understanding of IKF, but also underscoring needs for a concerted action to unify definitions and outcomes of IKF and their applications in AIDS care., (© 2022. The Author(s).)

Objectives: This study aims to investigate the association between CD4 + T cell count and combined antiretroviral therapy (cART) with the prevalence of anal human papillomavirus (HPV) infection among HIV-positive male cohort in China., Methods: A survey was conducted in men from a HIV cohort in Taizhou, China between 2016 and 2019. A face-to-face questionnaire interview was administered, and an anal-canal swab was collected for HPV genotyping., Results: A total of 766 HIV-positive men were recruited. The HPV prevalence was lower among those with increased CD4 + T cell count than those with decreased or unchanged (46.5 vs. 56.6%, p = 0.033) from baseline. In multivariable models, having the current CD4 + T cell count of 350-499 cells/µL (aOR 0.28, 95% CI 0.13-0.64), and of ≥ 500 cells/µL (aOR 0.26, 95% CI 0.11-0.60) were associated with lower prevalence of any type HPV infection compared with those with < 200 cells/µL. Having taken NVP + 3TC + AZT was inversely associated with any high-risk (HR)-HPV (aOR 0.47, 95% CI 0.25-0.90) and any low-risk (LR)-HPV infection (aOR 0.40, 95% CI 0.18-0.88), compared with those taking EFV + 3TC + TDF., Conclusions: Increased CD4 + T cell count at follow-up was significantly associated with lower prevalence of anal HPV infection. Inverse associations between NVP + 3TC + AZT and HR-HPV or LR-HPV infecton were observed., (© 2022. The Author(s).)

Objective: Females are more vulnerable to renal impairment (RI) in people living with HIV (PLWH), but few studies have examined sex disparity in the association of HIV serostatus with RI., Methods: In total, 2,101 PLWH on antiretroviral treatment (ART) and 4,202 HIV-negative people were selected and frequency matched in 1:2 ratio by sex and age categories. RI was defined as estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m 2 . The interaction effect of sex with HIV serostatus and correlates of RI were assessed by logistic regression models., Results: In total, 78.2% of participants were males with median age 43.7 (IQR: 32.5-54.4) years. The prevalence of RI was comparable for PLWH and HIV-negative people overall (30.4% vs 30.1%) but significantly higher for HIV-positive females (37.1%) than HIV-negative females (30.1%). Multiple logistic regression identified an interaction between sex and HIV serostatus on RI (adjusted odds ratio [aOR] of the interaction term: 1.66, 95% CI: 1.23-2.26). HIV infection was significantly associated with RI in females (aOR: 1.55, 95% CI: 1.17-2.06) but not in males. Central obesity and nadir CD4 count were significantly associated with RI in HIV-infected females but not in HIV-infected males., Conclusions: Sex seems to modify the association between HIV infection and RI, suggesting a sex-specific mechanistic pathogenesis of RI in PLWH, which warrants further investigation and intervention., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.)

Hypertension is highly prevalent among people living with HIV (PLWH). We sought to characterize the hypertension incidence among PLWH on antiretroviral therapy, focusing on the effect of change in general and abdominal obesity on hypertension during follow-up. This was a prospective analysis of 229 treated PLWH aged over 40 years without hypertension at baseline. Overall a median follow-up of 2.9 years, 26.2% PLWH developed hypertension. In multivariable models, compared to those without obesity measures at both baseline and follow-up visit, PLWH with general obesity at both occasions (adjusted odds ratio [aOR] = 3.83, P  = 0.006) or at baseline only (aOR = 5.45, P  = 0.003), abdominal obesity (measured as waist circumference) at both occasions (aOR = 3.87, P  = 0.001) or at follow-up only (aOR = 2.27; 9 P  = 0.060), abdominal obesity (measured as waist-to-hip ratio) at both occasions (aOR = 2.27, P  = 0.077) were at increased risk of incident hypertension. Our data show that both general and abdominal obesity especially in the persistent status increase the hypertension risk in treated PLWH.

Gut microbiota dysbiosis has been associated with many neurological diseases. However, how microbiota composition and metabolism relate to neurocognitive impairment (NCI) in HIV-infected individuals is largely unknown. In this study, a total of 102 HIV infected participants were classified into two groups-those with NCI and those without-using the global deficit score (GDS). Fecal samples were collected from the participants for 16S rRNA gene sequencing and untargeted metabolomics. The plasma level of 25 hydroxy-vitamin D (25(OH)D) was also evaluated. Although α-diversity and β-diversity were comparable, the HIV patients with NCI were significantly different from those without NCI in terms of abundance of several gut microbiota. The decreased abundance of butyrate-producing bacteria (BPB) and increased abundance of Klebsiella were related with NCI and carotid intima-media thickness (CIMT). Significant differences in fecal metabolites were also found between individuals with versus without NCI, including increased bile acids and bioactive lipids, decreased vitamin D, terpenoids, and resolvin D1 in the NCI group. Furthermore, the perturbed metabolic profile was closely related to BPB and Klebsiella . In addition, a low level of vitamin D was associated with NCI and CIMT. Both fecal and plasma vitamin D were positively correlated with BPB. Our results show that BPB and Klebsiella and the associated metabolites are associated with NCI in people with HIV. In addition, vitamin D, both in feces and blood, was associated with NCI and BPB, suggesting a protective effect of vitamin D on NCI., 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 Dong, Lin, Chen, Shi, Yuan, Li, Zhu, Xu, Shen, Wang, Shu, Ding and He.)

Background: HIV infection and normal aging share immune and inflammatory changes that result in premature aging and non-communicable diseases (NCDs), but the exact pathophysiology is not yet uncovered. We identified the common metabolic pathways underlying various NCDs in treated HIV infection., Methods: We performed untargeted metabolomics including 87 HIV-negative (-) normal controls (NCs), 87 HIV-positive (+) NCs, and 148 HIV+ subjects with only one type of NCDs, namely, subclinical carotid atherosclerosis, neurocognitive impairment (NCI), liver fibrosis (LF) and renal impairment. All HIV+ subjects were virally suppressed., Results: HIV+ patients presented widespread alterations in cellular metabolism compared to HIV- NCs. Glycerophospholipid (GPL) metabolism was the only one disturbed pathway presented in comparisons including HIV- NCs across age groups, HIV+ NCs across age groups, HIV+ NCs vs HIV- NCs and each of HIV+ NCDs vs HIV+ NCs. D-glutamine and D-glutamate metabolism and alanine-aspartate-glutamate metabolism were presented in comparisons between HIV+ NCs vs HIV- NCs, HIV+ LF or HIV+ NCI vs HIV+ NCs. Consistently, subsequent analysis identified a metabolomic fingerprint specific for HIV+ NCDs, containing 42 metabolites whose relative abundance showed either an upward (mainly GPL-derived lipid mediators) or a downward trend (mainly plasmalogen phosphatidylcholines, plasmalogen phosphatidylethanolamines, and glutamine) from HIV- NCs to HIV+ NCs and then HIV+ NCDs, reflecting a trend of increased oxidative stress., Interpretation: GPL metabolism emerges as the common metabolic disturbance linking HIV to NCDs, followed by glutamine and glutamate metabolism. Together, our data point to the aforementioned metabolisms and related metabolites as potential key targets in studying pathophysiology of NCDs in HIV infection and developing therapeutic interventions., Funding: China National Science and Technology Major Projects on Infectious Diseases, National Natural Science Foundation of China, Yi-wu Institute of Fudan University, and Shanghai Municipal Health and Family Planning Commission., Competing Interests: Declaration of Competing Interest We declared no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Metabolic syndrome (MS) is common among obese people. Little is known about the magnitude and characteristics of MS in people living with HIV (PLWH) in Asian countries in general and China in particular. Using baseline data collected between February 2017 through January 2020 from the Comparative HIV and Aging Research in Taizhou (CHART) cohort in China, we examined MS among 2,227 PLWH and 5,264 matched people without HIV, respectively. MS was defined using the criteria set forth by the International Diabetes Federation (IDF). Approximately 76.7% of PLWH had body mass index (BMI) < 24.0 kg/m 2 , significantly higher than people without HIV (50.3%). Among participants with BMI < 24.0 kg/m 2 , PLWH had a significantly higher prevalence of MS than people without HIV (20.6% vs. 14.5%; aOR: 1.41, 95% CI: 1.19-1.68) overall, and at an age of 18-29 (10.4% vs. 3.4%, aOR: 3.49, 95% CI: 1.99-6.11) and 30-44 years (17.3% vs. 8.5%, aOR: 2.03, 95% CI: 1.47-2.81), respectively. Among participants with BMI ≥ 24.0 kg/m 2 , MS prevalence was not significantly different between PLWH and people without HIV overall, but significantly lower in PLWH than people without HIV for those aged over 60 years (65.9% vs. 77.8%, aOR: 0.53, 95% CI: 0.32-0.88). Among PLWH, MS was significantly associated with older age and higher CD4 cell count, and with stavudine (d4T) use only in the group of BMI < 24.0 kg/m 2 . Our finding is indicative of a relatively higher risk for early onset of MS among HIV-infected young adults with lower BMI. Research is needed to elucidate the pathogenic mechanism for MS among PLWH.

Objective/background: This study assessed the prevalence and correlates of various sleep disturbances in HIV-infected patients compared to sex- and age-frequency-matched HIV-uninfected controls in China., Methods: This cross-sectional analysis included 1469 HIV-infected cases and 2938 HIV-uninfected controls. Insomnia symptoms, poor sleep quality (Pittsburgh Sleep Quality Index [PSQI] >5) as well as their specific domains, were assessed., Results: Prevalence of insomnia symptoms, poor sleep quality, and long sleep duration were higher in HIV-infected vs uninfected participants (23.7% vs 19.8%, 24.1% vs 19.9%, and16.1% vs 8.7%, respectively; all p < 0.05), and remained significant after adjusting for age, sex and education. An Age-stratified analysis showed that such differences were significant only at ages 18-29 and 30-44 years for insomnia symptoms and poor sleep quality long sleep duration was significant across all age groups. Among HIV-infected patients, multivariate analysis indicated that older age, depressive symptoms and frailty score were the most consistent variables associated with sleep disorders (ie, insomnia symptoms, poor sleep quality, short and long sleep durations), as well as all associations (if significant) were positive, excluding the negative associations of older age and depressive symptoms with short sleep duration. Regarding HIV-specific factors, only current CD4 cell count ≥500 cells/μL was negatively associated with insomnia symptoms., Conclusions: The impact of HIV infection on sleep disturbances may differ across age groups and are more pronounced among young adults. Additionally, the phenomenon of prolonged sleep duration among HIV-infected patients should be noted, and its link to poor physical health warrants further investigation., (Copyright © 2019. Published by Elsevier B.V.)

Background: Inconclusive results have been reported in studies evaluating the association between HIV infection and subclinical atherosclerosis. Unsolved issues include whether the increased atherosclerosis burden observed in some studies is attributed to greater prevalence of traditional risk factors or HIV infection. Therefore, we evaluated the association of HIV infection with subclinical atherosclerosis as assessed by carotid artery intima-media thickness, while controlling for the effects of traditional risk factors as operationalised by the Framingham risk score (FRS)., Methods: We did a cross-sectional evaluation of data derived from the baseline assessment of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, an ongoing longitudinal study being done in Zhejiang province, China. HIV-positive and HIV-negative individuals aged 18 years and older were recruited between Feb 1, and Dec 10, 2017, and were frequency-matched for age and sex in a 1:2 ratio. Subclinical atherosclerosis was defined as carotid artery intima-media thickness of 780 μm or higher. Logistic regression was used to assess the associations of HIV-positive serostatus and FRS with subclinical atherosclerosis., Findings: 480 of 1425 (36·1%, 95% CI 33·6-38·6) HIV-positive and 784 of 2850 (27·5%, 95% CI 25·9-29·2) HIV-negative individuals had subclinical atherosclerosis (p<0·0001), and these patterns remained significant (adjusted odds ratio [adjOR] 1·72, 95% CI 1·47-2·01) in the adjusted model. After stratifying by age, higher prevalence of subclinical atherosclerosis was observed in HIV-positive than in HIV-negative individuals across the age groups 18-29 years (41 [16·0%] of 256 vs 13 [2·5%] of 512, p<0·0001), 30-44 years (128 [24·0%] of 533 vs 153 [14·4%] of 1066, p<0·0001), and 45-59 years (182 [46·6%] of 391 vs 294 [37·6%] of 782, p=0·0032), but not 60-75 years (163 [66·5%] of 245 vs 324 [66·1%] of 490, p=0·912). Significant negative interaction between HIV-positive serostatus and age on subclinical atherosclerosis was observed (p<0·0001). ORs adjusted for age, sex, and FRS were 8·84 (95% CI 4·50-17·34) for the age group 18-29 years, 2·09 (1·59-2·74) for 30-44 years, 1·54 (1·19-1·98) for 45-59 years, and 1·04 (0·75-1·44) for 60-75 years. Among HIV-positive individuals, none of the HIV-specific variables were significantly associated with carotid artery intima-media thickness estimates except for being antiretroviral therapy naive., Interpretation: HIV infection is associated with subclinical atherosclerosis, independent of classic risk factors. The association is stronger at younger ages, suggesting early onset of subclinical atherosclerosis among young adults. These findings highlight the need to modify HIV/AIDS treatment guidelines to incorporate cardiovascular evaluation in China., Funding: China National Science and Technology Major Projects on Infectious Diseases, National Natural Science Foundation of China, and Shanghai Municipal Health and Family Planning Commission., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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.

HIV infection and aging are each associated with neurocognitive impairment (NCI). This study examined the combined effects of HIV infection and aging on NCI. We performed a cross-sectional survey among 345 HIV-infected and 345 HIV-uninfected participants aged at least 40 years. The International HIV Dementia Scale (IHDS) and Chinese version of Mini-mental State Examination (MMSE) were administered to screen for NCI. HIV-infected individuals had higher prevalence of NCI than uninfected individuals (46.7% vs 15.1% for IHDS using cut-off of ≤ 10; 17.1% vs 2.6% for MMSE). Significant main effects of HIV and age were observed on IHDS and MMSE composite scores and all domains except for HIV on attention and calculation. Significant interaction effects between HIV and age were observed on motor speed, orientation, registration and recall, and mainly attributed to the inferior performance of HIV-infected patients aged over 60 years. Among HIV-infected individuals, in multivariable logistic models, older age, depressive symptoms and history of nevirapine treatment were associated with NCI using both IHDS and MMSE, whereas lower education current smoker and current CD4 ≥ 800 cells/μL were associated only with NCI using IHDS, and hypertension was associated only with NCI using MMSE. Findings suggest that HIV and older age may confer interactive effects on cognitive function in several domains with older HIV-infected adults experiencing greater NCI, which requires further longitudinal investigation. Furthermore, HIV early diagnosis and treatment may prevent or reverse NCI, but extra attention should be given to adverse effects including metabolic changes associated with long-term treatment.

Hypertension is a growing problem in the HIV population. The relationship between low nadir CD4 count and hypertension in the HIV-infected population has been reported. However, the effect of nadir CD4 on hypertension due to a different body mass index (BMI) is yet to be fully elucidated. In this cross-sectional study, 345 HIV-infected participants aged ≥40 years were recruited. They were frequency matched and compared with age, sex, and education with HIV-uninfected adults (n = 345). Hypertension prevalence was lower in HIV-infected than in HIV-uninfected participants (23.8% vs. 31.9%; p = .011), but this association was not significant after adjusting for potential confounders. Among HIV-infected individuals, older age, overweight, with a family history of cardiovascular diseases, and nadir CD4 count <50 cells/μl were independently associated with hypertension. Stratifying individuals with BMI category revealed that nadir CD4 count-regardless if it was operationalized as a dichotomous variable (<50 cells/μl) or continuous variable-was found to be associated with hypertension among individuals who were underweight and obese, but not among those who were normal weight and overweight. Among HIV-uninfected individuals, older age and having a waist circumference above cutoff were significantly associated with hypertension. This is one of the first studies to demonstrate that the association of nadir CD4 and hypertension is observed in underweight and obese HIV-infected patients. While these results suggest that the relationship between nadir CD4 count and hypertension might be mediated by body weight, future longitudinal studies will be needed to validate the findings, including its causal pathways.

We assessed the factors that influenced improvement or progression in human immunodeficiency virus (HIV)-infected patients who were receiving combination antiretroviral therapy (cART). This was a retrospective cohort study of HIV-infected patients receiving cART in Taizhou, Zhejiang, China, 2009-2015. Liver fibrosis was assessed by Fibrosis-4 (FIB-4) score. Improvement of liver fibrosis was defined as having > 30% decrease in FIB-4 from baseline, whereas progression of liver fibrosis was defined as having > 30% increase in FIB-4 score from baseline. A total of 955 HIV-infected patients were included. Of these, 808 (84.6%) were HIV-monoinfection, 125 (13.1%) were HIV/hepatitis B virus (HBV) coinfection and 29 (3.0%) were HIV/hepatitis C virus (HCV) coinfection. The median duration of treatment was 15 months. After treatment, 37.1% participants had > 30% decreases in FIB-4 index, 14.8% had > 30% increases in FIB-4 index, while the remaining 48.2% had stabilized FIB-4 index. In multivariate analysis, improvement of liver fibrosis was negatively associated with an older age, but was positively associated with baseline FIB-4 index and > 30% increases in CD4 cell count after ART. Progression of liver fibrosis was positively associated with an older age, but was negatively associated with gender and HIV transmission mode (male homosexual vs. male heterosexual, female heterosexual vs. male heterosexual), and baseline FIB-4 index. Our findings indicate that improvement of liver fibrosis could be achieved by early initiation of ART through better CD4 cell recovery. Liver fibrosis and hepatotoxicity associated with ART should be monitored as early as possible and throughout till the end of treatment, with special attention to the elderly and heterosexual men.

We investigated the prevalence and correlates of prefrailty/frailty, determined on the basis of the Fried criteria, in Chinese patients with and those without human immunodeficiency virus (HIV) infection. HIV-infected patients were more likely to be frail or prefrail than controls, and this association remained significant after adjustment for potential confounders (odds ratio, 3.79). After additional adjustment for neurocognitive impairment and depressive and insomnia symptoms, this association remained significant but attenuated (odds ratio, 2.16). In the HIV-infected group, these 3 variables were independently associated with prefrailty/frailty. These findings suggest that neurocognitive impairment and depressive and/or insomnia symptoms may account for a higher prevalence of prefrailty/frailty in HIV-infected patients but require further longitudinal investigation., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Objective: To examine the prevalence and correlates of hepatitis C virus (HCV) co-infection as well as plasma HCV viral load among newly diagnosed HIV-infected adults during 2009-2012 in Taizhou prefecture of Zhejiang province, China., Methods: Five hundred and seventy-two adults who were newly diagnosed as HIV-infection were screened for anti-HCV immunoglobulin G (IgG). Plasma HCV RNA was quantified if positive for HCV IgG., Results: Forty-two (7.3%) out of the 572 HIV-infected adults were tested positive for HCV IgG. HCV infection was more likely to occur among participants who were infected with HIV through blood transmission (OR = 49.46, 95% CI: 13.71-178.48). Otherwise, HCV infection was less likely to occur among participants who were under 46-86 years of age (OR = 0.12, 95% CI: 0.02-0.58), those with mode of homosexual transmission of HIV (OR = 0.11, 95% CI: 0.01-0.86), with education of high school or above (OR = 0.13, 95% CI: 0.02-0.78). Thirty-three (78.6%) of the total 42 HIV-HCV patients with coinfection had detectable plasma HCV RNA, whereas 9 (21.4%) had undetectable plasma HCV RNA (i.e., lower than 5.0 × 10² IU/ml) or known as relative HCV viral suppression. No significant associations were noticed on factors as: HCV viral suppression and demographics, HIV transmission route and CD4⁺T-cell counts according to univariate regression analyses., Conclusion: Prevalence of HCV co-infection was relatively high among newly diagnosed HIV-infected adults in this study area. Majority of the HIV-HCV coinfected patients had detectable plasma HCV RNA, of which the long term impact on disease progression deserves called for further research.

Objective: To examine homosexual and heterosexual behaviors, behavioral networks and HIV infection among men who have sex with men (MSM) in Eastern China., Methods: A cross-sectional survey was conducted among MSM in 2013 in a rural prefecture of Zhejiang province. Participants were interviewed for their sexual behaviors and sexual networks and were tested for HIV infection., Results: A total of 620 MSM from gay bath houses and bars participated in the survey. Of them, 58.2% aged 18 to 39 years and 49.5% were currently married with a female. The age of first homosexual contact was 26.7 years on average, ranging from 12 to 66 years. 91.0% had multiple male sex partners and 86.1% also had female sex partners in lifetime. 70 (11.3%) of the participants were tested HIV-positive. A total of 620 independent egocentric sexual networks involving 620 study participants and 1,971 reported sexual partners in the past 12 months were constructed, including 70 networks for the 70 HIV-positive participants with their 221 sexual partners and 550 networks for the 550 HIV-negative participants with their 1,750 sexual partners. The median network degree was 3 (IQR 2-4) overall and was not different between HIV-positive participants (Median: 3; IQR: 2-4) and HIV-negative participants (Median: 3; IQR: 2-4) (Mann-Whitney test, Z=-0.015, P=0.998). The proportion of networks with a multiple male sexual partnership was 63.7% overall, 62.8% for HIV-positive participants and 63.8% for HIV-negative participants (χ2=0.025, P=0.875). The proportion of networks with both male and female sexual partners was 44.8% overall, 47.1% for HIV-positive participants and 44.5% for HIV-negative participants (χ2=0.169, P=0.681). Consistent condom use and knowledge of HIV infection status were rare within the network partners., Conclusions: The currently high HIV prevalence and complicated bisexual networks among MSM in the study area provides enhanced evidence for developing tailored prevention strategies for HIV transmission among and beyond the MSM population.

Objective: To investigate the risky sexual behaviors, associated factors and characteristics of sexual network among clients receiving methadone maintenance treatment (MMT) at the clinics in Taizhou prefecture of Zhejiang province., Methods: A cross-sectional survey was conducted. Data was collected through questionnaire and from the national unified MMT system. Urine was collected to test heroin, methamphetamine, 3, 4-methylenedioxymethamphetamine (MDMA) and ketamine. Blood was collected to test infections on HIV, hepatitis C virus (HCV) and syphilis., Results: Totally, 362 clients were recruited. Most of the clients were male (88.7%), 31-40 year-olds (54.5%), married (61.6%) and having received junior high school education (56.6%). 85.1% of them received urine test with 82(26.6%)positive for heroin, 21 (6.8%) positive for methamphetamine, 19(6.2%) positive for MDMA and none for ketamine. 77.1% of them received blood test, and prevalence rates for HIV, HCV and syphilis were 1.1% , 36.7% and 3.6% . 19.5% of the clients who had sex in the past 6 months. Factors as having multiple sexual partners and positive for club drugs were under higher risk. Sexual networking seemed to be loose, linear and acyclic among this population but overlapping with the drug-using network., Conclusion: Effective and targeted interventions should be taken among the MMT clients since continuing drug use and HIV/STD related sexual behavior were found common in them, suggesting there was a risk of HIV/STD transmission in this population.

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.

Objective: To describe changes in sexual behaviors among HIV-infected individuals after their HIV diagnosis., Methods: All HIV-infected individuals diagnosed by the end of 2009 in Taizhou Prefecture were invited to participate in this 12-month prospective study. Assessments including the total number and types of sexual contacts, and condom use details for up to their most familiar eight sexual contacts were collected both at enrollment and 12-month follow-up., Results: 262 HIV-infected individuals were eligible for analysis. The total number of sexual contacts reported by participants was 4,017, 1,496 and 356 during the 12- month period prior to HIV diagnosis (T1), the 12-month period prior to the baseline survey (T2), and the 12-month follow-up period (T3), respectively. The difference in the number of sexual contacts between T2 and T1 was -5 in median (IQR -1, -14), and the difference between T3 and T2 was 0 in median (IQR: 0, -6). A larger proportion of spousal or long-term heterosexual contact was reported from T1(27.7%) to T2(42.5%) to T3(76.1%), whereas a smaller proportion of commercial heterosexual contacts was reported from T1 (48.6%) to T2 (33.2%) to T3 (7.0%) as well as a smaller proportion of non-commercial casual homosexual contacts was reported from T2 (8.4%) to T3 (3.8%).The proportion of consistent condom use increased significantly from T1 (9.3%) to T2 (35.3%) to T3 (91.5%)., Conclusion: Sexual behaviors did not change in a uniform manner for the participants in our study. Sexual behaviors and sexual networks vis-à-vis HIV diagnosis and follow-up were associated with the participant's characteristics and HIV infection and treatment status. The overall lesson is that individuals who are unaware of their HIV infection are the main drivers of secondary transmission. Early identification of HIV infection and access to antiretroviral therapy (ART) are both key strategies to the control and prevention.

Background: Contact tracing is especially useful for identifying an infection with few cases in the population, such as HIV in China. Little such research is available in China., Methods: Every newly diagnosed HIV case from 2008-2010 in Taizhou Prefecture, Zhejiang Province in China, was invited to participate as an "index case" in a contact tracing survey by providing contact information for up to eight sexual contacts who themselves were approached for voluntary HIV counseling and testing (VCT). 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., Results: A total of 463 HIV-infected individuals were newly identified during the study period, including 338 cases who were identified from routine surveillance programs and 125 cases who were identified from the present contact tracing survey. Among these 463 cases, 398 (86.0%) served as 'index cases' in the survey, including 290 (85.8%) out of the 338 cases identified from routine surveillance programs and 108 (86.4%) out of the 125 cases identified from the present survey. These 398 'index cases' reported a total of 1,403 contactable sexual contacts, of whom 320 (22.8%) received HIV testing and 125 (39.1%) tested positive for HIV. Willingness to receive HIV testing was high among spouses and long term heterosexual or homosexual partners but extremely low among casual and commercial sex partners of 'index cases'. Consistent condom use was rare for all participants. A total of 290 independent sexual network components were constructed, with high complexity., Conclusion: Contact tracing is useful for identifying new HIV infections from spouses or long term sexual partners of HIV-infected individuals. The complicated sexual networks existing between and beyond HIV-infected persons provide opportunities for rapid spread of HIV in such areas.