Pub Date : 2024-09-01Epub Date: 2024-05-30DOI: 10.1097/QAD.0000000000003944
Jingjing Zhao, Xiaojun Zhou, Yefeng Qiu, Rui Jia
Objective: Natural hosts of simian immunodeficiency virus (SIV), such as the African green monkey (AGM), possess the ability to avoid acquired immune deficiency syndrome (AIDS) despite lifelong infection. The underlying mechanisms are not completely understood. This study aimed to characterize the gut microbiome and metabolite profiles of different nonhuman primates (NHPs) to provide potential insight into AIDS resistance.
Design and methods: Fresh feces from Cynomolgus macaques (CMs), and Rhesus macaques (RMs), SIV- AGMs (AGM_N), and SIV+ AGMs (AGM_P) were collected and used for metagenomic sequencing and metabonomic analysis.
Results: Compared with CMs and RMs, significant decreases in the abundances of Streptococcus , Alistipes , Treponema , Bacteroides , and Methanobrevibacter ( P < 0.01), and significant increases in the abundances of Clostridium , Eubacterium , Blautia , Roseburia , Faecalibacterium , and Dialister ( P < 0.01) were detected in AGM_N. Compared with AGM_N, a trend toward increased abundances of Streptococcus and Roseburia were found in AGM_P. The levels of metabolites involved in lipid metabolism and butanoate metabolism significantly differed among AGM_P, AGM_N and CM ( P < 0.05).
Conclusions: Our data, for the first time, demonstrated distinguishing features in the abundances of butyrate-producing bacteria and lipid metabolism capacities between different NHP hosts of SIV infection. These findings may correlate with the different characteristics observed among these hosts in the maintenance of intestinal epithelial barrier integrity, regulation of inflammation, and provide insights into AIDS resistance in AGMs.
{"title":"Characterization of the gut butyrate-producing bacteria and lipid metabolism in African green monkey as a natural host of simian immunodeficiency virus infection.","authors":"Jingjing Zhao, Xiaojun Zhou, Yefeng Qiu, Rui Jia","doi":"10.1097/QAD.0000000000003944","DOIUrl":"10.1097/QAD.0000000000003944","url":null,"abstract":"<p><strong>Objective: </strong>Natural hosts of simian immunodeficiency virus (SIV), such as the African green monkey (AGM), possess the ability to avoid acquired immune deficiency syndrome (AIDS) despite lifelong infection. The underlying mechanisms are not completely understood. This study aimed to characterize the gut microbiome and metabolite profiles of different nonhuman primates (NHPs) to provide potential insight into AIDS resistance.</p><p><strong>Design and methods: </strong>Fresh feces from Cynomolgus macaques (CMs), and Rhesus macaques (RMs), SIV- AGMs (AGM_N), and SIV+ AGMs (AGM_P) were collected and used for metagenomic sequencing and metabonomic analysis.</p><p><strong>Results: </strong>Compared with CMs and RMs, significant decreases in the abundances of Streptococcus , Alistipes , Treponema , Bacteroides , and Methanobrevibacter ( P < 0.01), and significant increases in the abundances of Clostridium , Eubacterium , Blautia , Roseburia , Faecalibacterium , and Dialister ( P < 0.01) were detected in AGM_N. Compared with AGM_N, a trend toward increased abundances of Streptococcus and Roseburia were found in AGM_P. The levels of metabolites involved in lipid metabolism and butanoate metabolism significantly differed among AGM_P, AGM_N and CM ( P < 0.05).</p><p><strong>Conclusions: </strong>Our data, for the first time, demonstrated distinguishing features in the abundances of butyrate-producing bacteria and lipid metabolism capacities between different NHP hosts of SIV infection. These findings may correlate with the different characteristics observed among these hosts in the maintenance of intestinal epithelial barrier integrity, regulation of inflammation, and provide insights into AIDS resistance in AGMs.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-27DOI: 10.1097/QAD.0000000000003972
Emma J P N Gram, Ellen Moseholm, Anne B Nørløv, Charlotte Wilken-Jensen, Kristina Thorsteinsson, Birgitte T Pedersen, Sussie M Jørgensen, Jesper Bonde, Lars H Omland, Anne-Mette Lebech, Nina Weis
Objective: To evaluate if integrated cervical cancer screening (CCS) for women with HIV (WWH) in routine HIV care resulted in increased adherence to screening, and to describe the prevalence of human papillomavirus (HPV)-specific genotypes and the incidence of cellular abnormalities.
Design: Cohort study.
Methods: WWH who accepted the offer of combined CCS and HIV care (group 1), WWH who declined the offer (group 2), and WWH not offered CCS within HIV care (group 3) between 2013 and 2019 were included. Data was collected from The Danish HIV Cohort Study and The Danish Pathology Data Bank. Adherence to the CCS program was defined as fulfilled if WWH were screened annually.
Results: A total of 804 WWH were included. WWH who accepted CCS within HIV care (group 1; n = 218) had significantly higher adherence to screening in all study years 22-99% compared with the WWH who declined CCS (group 2; n = 232) 10-16% and WWH who were not invited for CCS (group 3; n = 354) 11-25%. There was no significant difference in the prevalence of HPV-specific genotypes and incidence of cellular abnormalities among the three groups.
Conclusion: Integrating CCS for WWH in routine HIV care resulted in higher adherence to the CCS guidelines. Combined services thereby represent an opportunity to engage WWH in HIV care into preventive services.
目的评估在常规HIV关怀中对感染HIV的妇女(WLWH)进行综合宫颈癌筛查(CCS)是否会提高筛查的依从性,并描述人乳头状瘤病毒(HPV)特异性基因型的流行情况和细胞异常的发生率:设计:队列研究:纳入 2013-2019 年间接受联合 CCS 和 HIV 护理提议的 WLWH(第 1 组)、拒绝接受提议的 WLWH(第 2 组)以及未在 HIV 护理中提供 CCS 的 WLWH(第 3 组)。数据收集自丹麦艾滋病队列研究(The Danish HIV Cohort Study)和丹麦病理数据库(The Danish Pathology Data Bank)。如果WLWH每年都接受筛查,则定义为符合CCS计划:结果:共纳入了 804 名 WLWH。与拒绝接受CCS的WLWH(第2组;n = 232)的10-16%和未被邀请接受CCS的WLWH(第3组;n = 354)的11-25%相比,在所有研究年份中接受CCS的WLWH(第1组;n = 218)的筛查依从性明显更高,达到22-99%。三组之间在HPV特异性基因型的流行率和细胞异常的发生率方面没有明显差异:结论:将针对WLWH的CCS整合到常规HIV护理中可提高CCS指南的依从性。因此,联合服务是将 WLWH 纳入 HIV 护理并提供预防服务的一个机会。
{"title":"Cervical cancer screening integrated in routine clinical care of women with HIV.","authors":"Emma J P N Gram, Ellen Moseholm, Anne B Nørløv, Charlotte Wilken-Jensen, Kristina Thorsteinsson, Birgitte T Pedersen, Sussie M Jørgensen, Jesper Bonde, Lars H Omland, Anne-Mette Lebech, Nina Weis","doi":"10.1097/QAD.0000000000003972","DOIUrl":"10.1097/QAD.0000000000003972","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate if integrated cervical cancer screening (CCS) for women with HIV (WWH) in routine HIV care resulted in increased adherence to screening, and to describe the prevalence of human papillomavirus (HPV)-specific genotypes and the incidence of cellular abnormalities.</p><p><strong>Design: </strong>Cohort study.</p><p><strong>Methods: </strong>WWH who accepted the offer of combined CCS and HIV care (group 1), WWH who declined the offer (group 2), and WWH not offered CCS within HIV care (group 3) between 2013 and 2019 were included. Data was collected from The Danish HIV Cohort Study and The Danish Pathology Data Bank. Adherence to the CCS program was defined as fulfilled if WWH were screened annually.</p><p><strong>Results: </strong>A total of 804 WWH were included. WWH who accepted CCS within HIV care (group 1; n = 218) had significantly higher adherence to screening in all study years 22-99% compared with the WWH who declined CCS (group 2; n = 232) 10-16% and WWH who were not invited for CCS (group 3; n = 354) 11-25%. There was no significant difference in the prevalence of HPV-specific genotypes and incidence of cellular abnormalities among the three groups.</p><p><strong>Conclusion: </strong>Integrating CCS for WWH in routine HIV care resulted in higher adherence to the CCS guidelines. Combined services thereby represent an opportunity to engage WWH in HIV care into preventive services.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-11DOI: 10.1097/QAD.0000000000003955
Kelly Fung, Sonia Hernandez-Diaz, Rebecca Zash, Ellen G Chadwick, Russell B Van Dyke, Carly Broadwell, Jennifer Jao, Kathleen Powis, Lynn M Yee, Paige L Williams
Objective: To characterize associations of exposure to newer antiretroviral medications in the first trimester with congenital anomalies among infants born to persons with HIV in the United States.
Design: Longitudinal cohort of infants born 2012-2022 to pregnant persons with HIV enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study.
Methods: First-trimester exposures to newer antiretrovirals (ARVs) were abstracted from maternal medical records. Trained site staff conducted physical exams and abstracted congenital anomalies from infant medical records. Investigators classified anomalies using the Metropolitan Atlanta Congenital Defects Program classification system. The prevalence of major congenital anomalies identified by age one year was estimated for infants exposed and unexposed to each ARV. Generalized estimating equation models were used to estimate the odds ratio (OR) of major congenital anomalies for each ARV exposure, adjusting for potential confounders.
Results: Of 2034 infants, major congenital anomalies were identified in 135 [6.6%; 95% confidence interval (CI): 5.6-7.8%]. Cardiovascular ( n = 43) and musculoskeletal ( n = 37) anomalies were the most common. Adjusted ORs (95% CI) of congenital anomalies were 1.03 (0.62-1.72) for darunavir, 0.91 (0.46-1.81) for raltegravir, 1.04 (0.58-1.85) for rilpivirine, 1.31 (0.71-2.41) for elvitegravir, 0.76 (0.37-1.57) for dolutegravir, and 0.34 (0.05-2.51) for bictegravir, compared to those unexposed to each specific ARV. Findings were similar after adjustment for nucleoside/nucleotide backbones.
Conclusions: The odds of congenital anomalies among infants with first-trimester exposure to newer ARVs did not differ substantially from those unexposed to these specific ARVs, which is reassuring. Continued evaluation of these ARVs with larger studies will be needed to confirm these findings.
{"title":"First-trimester exposure to newer antiretroviral agents and congenital anomalies in a US cohort.","authors":"Kelly Fung, Sonia Hernandez-Diaz, Rebecca Zash, Ellen G Chadwick, Russell B Van Dyke, Carly Broadwell, Jennifer Jao, Kathleen Powis, Lynn M Yee, Paige L Williams","doi":"10.1097/QAD.0000000000003955","DOIUrl":"10.1097/QAD.0000000000003955","url":null,"abstract":"<p><strong>Objective: </strong>To characterize associations of exposure to newer antiretroviral medications in the first trimester with congenital anomalies among infants born to persons with HIV in the United States.</p><p><strong>Design: </strong>Longitudinal cohort of infants born 2012-2022 to pregnant persons with HIV enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study.</p><p><strong>Methods: </strong>First-trimester exposures to newer antiretrovirals (ARVs) were abstracted from maternal medical records. Trained site staff conducted physical exams and abstracted congenital anomalies from infant medical records. Investigators classified anomalies using the Metropolitan Atlanta Congenital Defects Program classification system. The prevalence of major congenital anomalies identified by age one year was estimated for infants exposed and unexposed to each ARV. Generalized estimating equation models were used to estimate the odds ratio (OR) of major congenital anomalies for each ARV exposure, adjusting for potential confounders.</p><p><strong>Results: </strong>Of 2034 infants, major congenital anomalies were identified in 135 [6.6%; 95% confidence interval (CI): 5.6-7.8%]. Cardiovascular ( n = 43) and musculoskeletal ( n = 37) anomalies were the most common. Adjusted ORs (95% CI) of congenital anomalies were 1.03 (0.62-1.72) for darunavir, 0.91 (0.46-1.81) for raltegravir, 1.04 (0.58-1.85) for rilpivirine, 1.31 (0.71-2.41) for elvitegravir, 0.76 (0.37-1.57) for dolutegravir, and 0.34 (0.05-2.51) for bictegravir, compared to those unexposed to each specific ARV. Findings were similar after adjustment for nucleoside/nucleotide backbones.</p><p><strong>Conclusions: </strong>The odds of congenital anomalies among infants with first-trimester exposure to newer ARVs did not differ substantially from those unexposed to these specific ARVs, which is reassuring. Continued evaluation of these ARVs with larger studies will be needed to confirm these findings.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-20DOI: 10.1097/QAD.0000000000003964
Penelope C Rose, Claire Davies, Mark F Cotton, Kennedy Otwombe, Sara H Browne, Florin Vaida, Steve Innes, Etienne De la Rey Nel
Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging cause of liver disease in HIV. Transient elastography (TE) with controlled attenuation parameter (CAP) measures liver stiffness as a marker of liver fibrosis and CAP as a measure of hepatic steatosis. Our aim was to evaluate longitudinal CAP and liver stiffness in children with perinatally acquired HIV (PHIV) on antiretroviral therapy (ART) from early life compared to children without HIV (HU).
Design: Prospective cohort study.
Methods: PHIV and HU were followed annually for two years. During the study, 60% of PHIV switched from older ART regimens to tenofovir disoproxil, lamivudine and dolutegravir (TLD). Longitudinal evolution of CAP and liver stiffness were investigated in two PHIV groups - on older ART and on TLD - compared to HU children using linear mixed effects models.
Results: 263 children and adolescents (112 PHIV, 151 HU) aged 7-20 years were followed. PHIV on older ART had CAP 8.61% (95% CI 4.42-12.97, P < 0.001) greater than HU and no significant difference in CAP between PHIV on TLD and HU. No significant difference in liver stiffness was found between PHIV on older ART regimens and PHIV on TLD compared to HU.
Conclusion: PHIV on older ART had higher CAP than HU, whereas in PHIV switched to TLD there was no difference in CAP compared to HU. There was no difference in liver stiffness between either PHIV group and HU. This suggests starting ART early in life might protect PHIV from developing hepatic fibrosis.
目的:代谢功能障碍相关性脂肪性肝病(MASLD)是新出现的艾滋病肝病病因。带有控制衰减参数(CAP)的瞬态弹性成像(TE)可测量肝脏硬度,作为肝纤维化的标志,而CAP则可测量肝脏脂肪变性。我们的目的是评估围产期感染艾滋病病毒(PHIV)的儿童与未感染艾滋病病毒的儿童(HU)相比,从生命早期就开始接受抗逆转录病毒疗法(ART)的儿童的纵向 CAP 和肝脏硬度:设计:前瞻性队列研究:方法:每年对 PHIV 和 HU 进行为期两年的跟踪调查。研究期间,60%的PHIV从旧的抗逆转录病毒疗法转为替诺福韦酯、拉米夫定和多罗替拉韦(TLD)疗法。研究采用线性混合效应模型,调查了两组 PHIV(接受老式抗逆转录病毒疗法的 PHIV 和接受 TLD 的 PHIV)与 HU 儿童相比,CAP 和肝硬变的纵向演变情况。接受老式抗逆转录病毒疗法的 PHIV 患有 CAP 的比例为 8.61%(95% CI 为 4.42% 至 12.97%,P 结论:接受老式抗逆转录病毒疗法的 PHIV 患有 CAP 的比例较高:接受老式抗逆转录病毒疗法的 PHIV 的 CAP 比 HU 高,而改用 TLD 的 PHIV 的 CAP 与 HU 相比没有差异。PHIV 组和 HU 组的肝脏硬度没有差异。这表明,早期开始抗逆转录病毒疗法可能会保护 PHIV 免于发展成肝纤维化。
{"title":"Longitudinal controlled attenuation parameter and liver stiffness in children with and without perinatal HIV infection in South Africa.","authors":"Penelope C Rose, Claire Davies, Mark F Cotton, Kennedy Otwombe, Sara H Browne, Florin Vaida, Steve Innes, Etienne De la Rey Nel","doi":"10.1097/QAD.0000000000003964","DOIUrl":"10.1097/QAD.0000000000003964","url":null,"abstract":"<p><strong>Objectives: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging cause of liver disease in HIV. Transient elastography (TE) with controlled attenuation parameter (CAP) measures liver stiffness as a marker of liver fibrosis and CAP as a measure of hepatic steatosis. Our aim was to evaluate longitudinal CAP and liver stiffness in children with perinatally acquired HIV (PHIV) on antiretroviral therapy (ART) from early life compared to children without HIV (HU).</p><p><strong>Design: </strong>Prospective cohort study.</p><p><strong>Methods: </strong>PHIV and HU were followed annually for two years. During the study, 60% of PHIV switched from older ART regimens to tenofovir disoproxil, lamivudine and dolutegravir (TLD). Longitudinal evolution of CAP and liver stiffness were investigated in two PHIV groups - on older ART and on TLD - compared to HU children using linear mixed effects models.</p><p><strong>Results: </strong>263 children and adolescents (112 PHIV, 151 HU) aged 7-20 years were followed. PHIV on older ART had CAP 8.61% (95% CI 4.42-12.97, P < 0.001) greater than HU and no significant difference in CAP between PHIV on TLD and HU. No significant difference in liver stiffness was found between PHIV on older ART regimens and PHIV on TLD compared to HU.</p><p><strong>Conclusion: </strong>PHIV on older ART had higher CAP than HU, whereas in PHIV switched to TLD there was no difference in CAP compared to HU. There was no difference in liver stiffness between either PHIV group and HU. This suggests starting ART early in life might protect PHIV from developing hepatic fibrosis.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-24DOI: 10.1097/QAD.0000000000003956
Olutomi Sodeke, Kyle Milligan, Ijeoma Ezeuko, Ademola Oladipo, Anuri Emeh, Adebobola Bashorun, Oluwaniyi Orisawayi, Sanda Danjuma, Dennis Onotu, Adetinuke Mary Boyd, Andrew Abutu, Helen Chun, Snigdha Vallabhaneni
Background: To inform optimal management of HIV viremia on tenofovir, lamivudine, and dolutegravir (TLD), we examined viral load (VL) outcomes of a large cohort of adult PWH on TLD in Nigeria.
Methods: We conducted a retrospective study of adult PWH who had ≥1 VL after initiating TLD during January 2017-February 2023. VLs were categorized as undetectable (≤50 copies/ml), low low-level viremia (LLV, 51-199 copies/ml), high LLV (200-999 copies/ml), virologic nonsuppression (VLNS, ≥1000 copies/ml), and virologic failure (VF, ≥2 consecutive VLNS results). Among patients with ≥2 VLs on TLD, we described how viremia changed over time and examined virologic outcomes after VF. We identified predictors of subsequent VLNS using mixed-effects logistic regression and conducted planned contrasts between levels of VL result and regimen types.
Results: Analysis of 82,984 VL pairs from 47,531 patients demonstrated viral resuppression to ≤50 copies/ml at follow-up VL in 66.7% of those with initial low LLV, 59.1% of those with initial high LLV, and 48.9% of those with initial VLNS. Of 662 patients with a follow-up VL after VF, 94.6% stayed on TLD; of which 57.8% (359/621) were undetectable at next VL without regimen change. Previous low LLV [adjusted odds ratio (aOR) 1.74, 1.56-1.93], high LLV (aOR 2.35, 2.08-2.65), and VLNS (aOR 6.45, 5.81-7.16) were associated with increasingly higher odds of subsequent VLNS, whereas a previously undetectable VL (aOR 1.08, 0.99-1.71) on TLD was not.
Conclusions: Despite increased odds of subsequent VLNS, most PWH with detectable viremia on TLD, including those with VF, will resuppress to an undetectable VL without a regimen change.
{"title":"Longitudinal viral load outcomes of adults with HIV after detectable viremia on tenofovir, lamivudine, and dolutegravir.","authors":"Olutomi Sodeke, Kyle Milligan, Ijeoma Ezeuko, Ademola Oladipo, Anuri Emeh, Adebobola Bashorun, Oluwaniyi Orisawayi, Sanda Danjuma, Dennis Onotu, Adetinuke Mary Boyd, Andrew Abutu, Helen Chun, Snigdha Vallabhaneni","doi":"10.1097/QAD.0000000000003956","DOIUrl":"10.1097/QAD.0000000000003956","url":null,"abstract":"<p><strong>Background: </strong>To inform optimal management of HIV viremia on tenofovir, lamivudine, and dolutegravir (TLD), we examined viral load (VL) outcomes of a large cohort of adult PWH on TLD in Nigeria.</p><p><strong>Methods: </strong>We conducted a retrospective study of adult PWH who had ≥1 VL after initiating TLD during January 2017-February 2023. VLs were categorized as undetectable (≤50 copies/ml), low low-level viremia (LLV, 51-199 copies/ml), high LLV (200-999 copies/ml), virologic nonsuppression (VLNS, ≥1000 copies/ml), and virologic failure (VF, ≥2 consecutive VLNS results). Among patients with ≥2 VLs on TLD, we described how viremia changed over time and examined virologic outcomes after VF. We identified predictors of subsequent VLNS using mixed-effects logistic regression and conducted planned contrasts between levels of VL result and regimen types.</p><p><strong>Results: </strong>Analysis of 82,984 VL pairs from 47,531 patients demonstrated viral resuppression to ≤50 copies/ml at follow-up VL in 66.7% of those with initial low LLV, 59.1% of those with initial high LLV, and 48.9% of those with initial VLNS. Of 662 patients with a follow-up VL after VF, 94.6% stayed on TLD; of which 57.8% (359/621) were undetectable at next VL without regimen change. Previous low LLV [adjusted odds ratio (aOR) 1.74, 1.56-1.93], high LLV (aOR 2.35, 2.08-2.65), and VLNS (aOR 6.45, 5.81-7.16) were associated with increasingly higher odds of subsequent VLNS, whereas a previously undetectable VL (aOR 1.08, 0.99-1.71) on TLD was not.</p><p><strong>Conclusions: </strong>Despite increased odds of subsequent VLNS, most PWH with detectable viremia on TLD, including those with VF, will resuppress to an undetectable VL without a regimen change.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-02DOI: 10.1097/QAD.0000000000003973
Elizabeth Marie King, Stacey Tkachuk, Alice Tseng
{"title":"Aging on antiretrovirals: reviewing the need for pharmacologic data in elderly people with HIV.","authors":"Elizabeth Marie King, Stacey Tkachuk, Alice Tseng","doi":"10.1097/QAD.0000000000003973","DOIUrl":"10.1097/QAD.0000000000003973","url":null,"abstract":"","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.1097/QAD.0000000000004001
Lucia Taramasso, Chiara Dentone, Isabella Cama, Daniela Fenoglio, Tiziana Altosole, Alessia Parodi, Cristina Campi, Michele Piana, Sara Mora, Mauro Giacomini, Laura Labate, Sara Garbarino, Bianca Bruzzone, Gilberto Filaci, Matteo Bassetti, Antonio Di Biagio
Objective: The aim of this study was to characterize T cell activation, exhaustion, maturation and Treg frequencies in individuals who acquire perinatal HIV (PHIV), in individuals who acquired HIV as adult (AHIV), and in healthy controls (HC).
Design: This cross-sectional study included people with HIV ≥ 14 and <40 years, HIV-RNA < 50 copies/mL on antiretroviral therapy for at least 6 months, and HC.
Methods: We assessed the expression of PD-1, TIM-3, EOMES, CD38+ DR+, maturation status by CD4+ and CD8+T cells and the frequency of CD4+ and CD8+ Treg cells. Principal component analysis (PCA) and k-means cluster analysis investigated which combination of immunological parameters better associated with each group.
Results: 26 PHIV and 18 AHIV with median ages of 26 (8.0) and 28 (6.8) years were consecutively enrolled. PHIV showed significant higher frequency of naïve and lower frequency of terminal effector memory CD4+ and CD8+ T cells than AHIV. AHIV exhibited higher expression of exhaustion and activation markers. The statistical analysis returned two clusters with 94% of specificity and 88% of sensitivity identifying PHIV vs. AHIV. The 9 HC had a lower expression of exhaustion markers on both CD4+ and CD8+T lymphocytes than PHIV and AHIV.
Conclusions: These data may exclude major alterations of lymphopoiesis in PHIV, with even lower state of immune-activation and exhaustion compared with AHIV. This suggests that recent lack of virological control, may affect immune activation and exhaustion of CD4+ and CD8+ T cells.
{"title":"Distinct features of immune activation and exhaustion markers in people with perinatally-acquired HIV.","authors":"Lucia Taramasso, Chiara Dentone, Isabella Cama, Daniela Fenoglio, Tiziana Altosole, Alessia Parodi, Cristina Campi, Michele Piana, Sara Mora, Mauro Giacomini, Laura Labate, Sara Garbarino, Bianca Bruzzone, Gilberto Filaci, Matteo Bassetti, Antonio Di Biagio","doi":"10.1097/QAD.0000000000004001","DOIUrl":"10.1097/QAD.0000000000004001","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to characterize T cell activation, exhaustion, maturation and Treg frequencies in individuals who acquire perinatal HIV (PHIV), in individuals who acquired HIV as adult (AHIV), and in healthy controls (HC).</p><p><strong>Design: </strong>This cross-sectional study included people with HIV ≥ 14 and <40 years, HIV-RNA < 50 copies/mL on antiretroviral therapy for at least 6 months, and HC.</p><p><strong>Methods: </strong>We assessed the expression of PD-1, TIM-3, EOMES, CD38+ DR+, maturation status by CD4+ and CD8+T cells and the frequency of CD4+ and CD8+ Treg cells. Principal component analysis (PCA) and k-means cluster analysis investigated which combination of immunological parameters better associated with each group.</p><p><strong>Results: </strong>26 PHIV and 18 AHIV with median ages of 26 (8.0) and 28 (6.8) years were consecutively enrolled. PHIV showed significant higher frequency of naïve and lower frequency of terminal effector memory CD4+ and CD8+ T cells than AHIV. AHIV exhibited higher expression of exhaustion and activation markers. The statistical analysis returned two clusters with 94% of specificity and 88% of sensitivity identifying PHIV vs. AHIV. The 9 HC had a lower expression of exhaustion markers on both CD4+ and CD8+T lymphocytes than PHIV and AHIV.</p><p><strong>Conclusions: </strong>These data may exclude major alterations of lymphopoiesis in PHIV, with even lower state of immune-activation and exhaustion compared with AHIV. This suggests that recent lack of virological control, may affect immune activation and exhaustion of CD4+ and CD8+ T cells.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1097/QAD.0000000000003999
Timothy N Crawford, Torsten B Neilands, Lydia N Drumright, Rob J Fredericksen, Mallory O Johnson, Kenneth H Mayer, Laura Bamford, Abigail W Batchelder, Heidi M Crane, Latesha Elopre, Richard D Moore, A Lina Rosengren, Katerina A Christopoulos
Objective: To examine the effects of internalized HIV stigma on viral non-suppression via depressive symptoms, alcohol use, illicit drug use, and medication adherence and investigate whether social support moderates these effects.
Design: Longitudinal observational clinical cohort of patients in HIV care in the US.Methods: Data from the CFAR Network for Integrated Clinical Systems (2016-2019) were used to conduct structural equation models (SEM) to test the indirect effects of internalized HIV stigma on viral non-suppression through depressive symptoms, illicit drug use, alcohol use, and medication adherence. Moderated mediation with an interaction between social support and internalized HIV stigma was examined.
Results: Among 9,574 individuals included in the study sample, 81.1% were male and 41.4% were Black, non-Hispanic. The model demonstrated good fit (root mean square error of approximation = 0.028; standardized root means square residual = 0.067). The overall indirect effect was significant (b = 0.058; se = 0.020; β = 0.048; 95%CI = .019-.098), indicating that internalized HIV stigma's impact on viral non-suppression was mediated by depressive symptoms, illicit drug use, and medication adherence. An interaction was observed between internalized HIV stigma and social support on alcohol use, however, there was no moderated mediation for any of the mediators.
Conclusions: Internalized HIV stigma indirectly impacts viral non-suppression through its effects on depressive symptoms, illicit drug use, and medication adherence. Social support may buffer the impact, but more research is needed. Understanding the pathways through which internalized stigma impacts viral suppression is key to improving health of people with HIV.
{"title":"Internalized HIV stigma and viral suppression: examining the mediating and moderating roles of substance use and social support.","authors":"Timothy N Crawford, Torsten B Neilands, Lydia N Drumright, Rob J Fredericksen, Mallory O Johnson, Kenneth H Mayer, Laura Bamford, Abigail W Batchelder, Heidi M Crane, Latesha Elopre, Richard D Moore, A Lina Rosengren, Katerina A Christopoulos","doi":"10.1097/QAD.0000000000003999","DOIUrl":"https://doi.org/10.1097/QAD.0000000000003999","url":null,"abstract":"<p><strong>Objective: </strong>To examine the effects of internalized HIV stigma on viral non-suppression via depressive symptoms, alcohol use, illicit drug use, and medication adherence and investigate whether social support moderates these effects.</p><p><strong>Design: </strong>Longitudinal observational clinical cohort of patients in HIV care in the US.Methods: Data from the CFAR Network for Integrated Clinical Systems (2016-2019) were used to conduct structural equation models (SEM) to test the indirect effects of internalized HIV stigma on viral non-suppression through depressive symptoms, illicit drug use, alcohol use, and medication adherence. Moderated mediation with an interaction between social support and internalized HIV stigma was examined.</p><p><strong>Results: </strong>Among 9,574 individuals included in the study sample, 81.1% were male and 41.4% were Black, non-Hispanic. The model demonstrated good fit (root mean square error of approximation = 0.028; standardized root means square residual = 0.067). The overall indirect effect was significant (b = 0.058; se = 0.020; β = 0.048; 95%CI = .019-.098), indicating that internalized HIV stigma's impact on viral non-suppression was mediated by depressive symptoms, illicit drug use, and medication adherence. An interaction was observed between internalized HIV stigma and social support on alcohol use, however, there was no moderated mediation for any of the mediators.</p><p><strong>Conclusions: </strong>Internalized HIV stigma indirectly impacts viral non-suppression through its effects on depressive symptoms, illicit drug use, and medication adherence. Social support may buffer the impact, but more research is needed. Understanding the pathways through which internalized stigma impacts viral suppression is key to improving health of people with HIV.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1097/QAD.0000000000004000
Jillian Neary, Daisy Chebet, Sarah Benki-Nugent, Hellen Moraa, Barbra A Richardson, Irene Njuguna, Agnes Langat, Evelyn Ngugi, Dara A Lehman, Jennifer Slyker, Dalton Wamalwa, Grace John-Stewart
Objectives: Children with HIV may experience adverse neurocognitive outcomes despite antiretroviral therapy (ART). Cytomegalovirus (CMV) is common in children with HIV. Among children on ART, we examined the influences of early HIV viral load (VL) and CMV DNA on neurocognition.
Design: We determined the association between pre-ART VL, cumulative VL, and CMV viremia and neurocognition using data from a cohort study.
Methods: Children who initiated ART before 12 months of age were enrolled from 2007-2010 in Nairobi, Kenya. Blood was collected at enrollment and every 6 months thereafter. Four neurocognitive assessments with 12 domains were conducted when children were a median age of 7 years. Primary outcomes included cognitive ability, executive function, attention, and motor. Generalized linear models were used to determine associations between HIV VL (pre-ART and cumulative; N = 38) and peak CMV DNA (by 24 months of age; N = 20) and neurocognitive outcomes.
Results: In adjusted models, higher peak CMV viremia by 24 months of age was associated with lower cognitive ability and motor z-scores. Higher pre-ART HIV VL was associated with lower executive function z-scores. Among secondary outcomes, higher pre-ART VL was associated with lower mean nonverbal and metacognition z-scores.
Conclusion: Higher pre-ART VL and CMV DNA in infancy were associated with lower executive function, nonverbal and metacognition scores and cognitive ability scores in childhood, respectively. These findings suggest long-term benefits of early HIV viral suppression and CMV control on neurocognition.
目的:尽管接受了抗逆转录病毒疗法(ART),但感染艾滋病毒的儿童可能会出现不良的神经认知结果。巨细胞病毒(CMV)在 HIV 感染儿童中很常见。在接受抗逆转录病毒疗法的儿童中,我们研究了早期 HIV 病毒载量(VL)和 CMV DNA 对神经认知的影响:设计:我们利用一项队列研究的数据确定了抗逆转录病毒疗法前 VL、累积 VL 和 CMV 病毒血症与神经认知之间的关系:2007-2010 年间,肯尼亚内罗毕对 12 个月前开始接受抗逆转录病毒疗法的儿童进行了登记。入组时采集血液,之后每 6 个月采集一次。在儿童的中位年龄为 7 岁时,对他们进行了四次神经认知评估,共涉及 12 个领域。主要结果包括认知能力、执行功能、注意力和运动能力。采用广义线性模型来确定 HIV VL(ART 前和累积;N = 38)和 CMV DNA 峰值(24 个月之前;N = 20)与神经认知结果之间的关系:在调整模型中,24 个月时较高的 CMV 病毒血症峰值与较低的认知能力和运动 Z 评分相关。抗逆转录病毒治疗前较高的 VL 值与较低的执行功能 z 评分有关。在次要结果中,较高的ART前VL与较低的平均非语言和元认知Z分数相关:结论:婴儿期较高的ART前VL和CMV DNA分别与较低的执行功能、非语言和元认知得分以及儿童期认知能力得分有关。这些研究结果表明,早期艾滋病病毒抑制和CMV控制对神经认知有长期益处。
{"title":"Association between HIV and cytomegalovirus and neurocognitive outcomes among children with HIV.","authors":"Jillian Neary, Daisy Chebet, Sarah Benki-Nugent, Hellen Moraa, Barbra A Richardson, Irene Njuguna, Agnes Langat, Evelyn Ngugi, Dara A Lehman, Jennifer Slyker, Dalton Wamalwa, Grace John-Stewart","doi":"10.1097/QAD.0000000000004000","DOIUrl":"https://doi.org/10.1097/QAD.0000000000004000","url":null,"abstract":"<p><strong>Objectives: </strong>Children with HIV may experience adverse neurocognitive outcomes despite antiretroviral therapy (ART). Cytomegalovirus (CMV) is common in children with HIV. Among children on ART, we examined the influences of early HIV viral load (VL) and CMV DNA on neurocognition.</p><p><strong>Design: </strong>We determined the association between pre-ART VL, cumulative VL, and CMV viremia and neurocognition using data from a cohort study.</p><p><strong>Methods: </strong>Children who initiated ART before 12 months of age were enrolled from 2007-2010 in Nairobi, Kenya. Blood was collected at enrollment and every 6 months thereafter. Four neurocognitive assessments with 12 domains were conducted when children were a median age of 7 years. Primary outcomes included cognitive ability, executive function, attention, and motor. Generalized linear models were used to determine associations between HIV VL (pre-ART and cumulative; N = 38) and peak CMV DNA (by 24 months of age; N = 20) and neurocognitive outcomes.</p><p><strong>Results: </strong>In adjusted models, higher peak CMV viremia by 24 months of age was associated with lower cognitive ability and motor z-scores. Higher pre-ART HIV VL was associated with lower executive function z-scores. Among secondary outcomes, higher pre-ART VL was associated with lower mean nonverbal and metacognition z-scores.</p><p><strong>Conclusion: </strong>Higher pre-ART VL and CMV DNA in infancy were associated with lower executive function, nonverbal and metacognition scores and cognitive ability scores in childhood, respectively. These findings suggest long-term benefits of early HIV viral suppression and CMV control on neurocognition.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.1097/QAD.0000000000003996
Trine Engelbrecht Hybel, Emma Frasez Sørensen, Marie Hairing Enemark, Jonas Klejs Hemmingsen, Anita Tranberg Simonsen, Kristina Lystlund Lauridsen, Michael Boe Møller, Court Pedersen, Gitte Pedersen, Niels Obel, Carsten Schade Larsen, Francesco d'Amore, Stephen Hamilton-Dutoit, Magnus Stougaard, Maja Ølholm Vase, Maja Ludvigsen
Objective: Individuals with human immunodeficiency virus (HIV) experience an increased risk of lymphoma, making this an important cause of death among people with HIV. Nevertheless, little is known regarding the underlying genetic aberrations, which we therefore set out to characterize.
Design: We conducted next-generation panel sequencing to explore the mutational status of diagnostic lymphoma biopsies from 18 patients diagnosed with lymphoma secondary to HIV infection.
Methods: Ion Torrent next-generation sequencing was performed with an AmpliSeq panel on diagnostic lymphoma biopsies from HIV-associated B-cell lymphomas (n = 18), comprising diffuse large B-cell lymphoma (n = 9), classic Hodgkin lymphoma (n = 6), Burkitt lymphoma (n = 2), follicular lymphoma (n = 1), and marginal zone lymphoma (n = 1). The panel comprised 69 lymphoid- and/or myeloid-relevant genes, in which either the entire coding sequence or a hotspot region was sequenced.
Results: Among the 18 lymphomas, we detected 213 variants. The number of detected mutations ranged from 4 to 41 per tumor distributed among 42 genes, including both exonic and intronic regions. The most frequently mutated genes included KMT2D (67%), TNFAIP3 (50%), and TP53 (61%). Notably, no gene was found to harbor variants across all the HIV-associated lymphomas, nor did we find subtype-specific variants. While some variants were shared among patients, most were unique to the individual patient and were often not reported as malignant genetic variants in databases.
Conclusion: Our findings demonstrate genetic heterogeneity across histological subtypes of HIV-associated lymphomas and thus help elucidate the genetics and pathophysiological mechanisms underlying the disease.
目的:人类免疫缺陷病毒(HIV)感染者罹患淋巴瘤的风险会增加,因此淋巴瘤是导致 HIV 感染者死亡的重要原因之一。然而,人们对其潜在的基因畸变知之甚少,因此我们着手研究其特征:设计:我们对 18 名被诊断为继发于 HIV 感染的淋巴瘤患者的诊断性淋巴瘤活检组织进行了下一代面板测序,以探索其突变状态:对HIV相关B细胞淋巴瘤(18例)的诊断性淋巴瘤活检组织(包括弥漫大B细胞淋巴瘤(9例)、典型霍奇金淋巴瘤(6例)、伯基特淋巴瘤(2例)、滤泡淋巴瘤(1例)和边缘区淋巴瘤(1例))使用AmpliSeq面板进行了Ion Torrent下一代测序。该研究小组包括 69 个淋巴和/或骨髓相关基因,对这些基因的整个编码序列或热点区域进行了测序:结果:在 18 个淋巴瘤中,我们检测到 213 个变异。每个肿瘤检测到的变异数量从4个到41个不等,分布在42个基因中,包括外显子区和内含子区。最常发生突变的基因包括KMT2D(67%)、TNFAIP3(50%)和TP53(61%)。值得注意的是,在所有艾滋病相关淋巴瘤中,没有发现任何基因存在变异,也没有发现亚型特异性变异。虽然有些变异在患者中是共有的,但大多数变异是个别患者所特有的,数据库中往往没有恶性基因变异的报告:我们的研究结果表明了HIV相关淋巴瘤组织学亚型的遗传异质性,从而有助于阐明该疾病的遗传学和病理生理学机制。
{"title":"Characterization of the genomic landscape of HIV-associated lymphoma reveals heterogeneity across histological subtypes.","authors":"Trine Engelbrecht Hybel, Emma Frasez Sørensen, Marie Hairing Enemark, Jonas Klejs Hemmingsen, Anita Tranberg Simonsen, Kristina Lystlund Lauridsen, Michael Boe Møller, Court Pedersen, Gitte Pedersen, Niels Obel, Carsten Schade Larsen, Francesco d'Amore, Stephen Hamilton-Dutoit, Magnus Stougaard, Maja Ølholm Vase, Maja Ludvigsen","doi":"10.1097/QAD.0000000000003996","DOIUrl":"https://doi.org/10.1097/QAD.0000000000003996","url":null,"abstract":"<p><strong>Objective: </strong>Individuals with human immunodeficiency virus (HIV) experience an increased risk of lymphoma, making this an important cause of death among people with HIV. Nevertheless, little is known regarding the underlying genetic aberrations, which we therefore set out to characterize.</p><p><strong>Design: </strong>We conducted next-generation panel sequencing to explore the mutational status of diagnostic lymphoma biopsies from 18 patients diagnosed with lymphoma secondary to HIV infection.</p><p><strong>Methods: </strong>Ion Torrent next-generation sequencing was performed with an AmpliSeq panel on diagnostic lymphoma biopsies from HIV-associated B-cell lymphomas (n = 18), comprising diffuse large B-cell lymphoma (n = 9), classic Hodgkin lymphoma (n = 6), Burkitt lymphoma (n = 2), follicular lymphoma (n = 1), and marginal zone lymphoma (n = 1). The panel comprised 69 lymphoid- and/or myeloid-relevant genes, in which either the entire coding sequence or a hotspot region was sequenced.</p><p><strong>Results: </strong>Among the 18 lymphomas, we detected 213 variants. The number of detected mutations ranged from 4 to 41 per tumor distributed among 42 genes, including both exonic and intronic regions. The most frequently mutated genes included KMT2D (67%), TNFAIP3 (50%), and TP53 (61%). Notably, no gene was found to harbor variants across all the HIV-associated lymphomas, nor did we find subtype-specific variants. While some variants were shared among patients, most were unique to the individual patient and were often not reported as malignant genetic variants in databases.</p><p><strong>Conclusion: </strong>Our findings demonstrate genetic heterogeneity across histological subtypes of HIV-associated lymphomas and thus help elucidate the genetics and pathophysiological mechanisms underlying the disease.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142043813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}