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251. Abdominal obesity, sarcopenia, and osteoporosis are associated with frailty in men living with and without HIV

Author

Hawkins, Kellie L., primary, Zhang, Long, additional, Ng, Derek K., additional, Althoff, Keri N., additional, Palella, Frank J., additional, Kingsley, Lawrence A., additional, Jacobson, Lisa P., additional, Margolick, Joseph B., additional, Lake, Jordan E., additional, Brown, Todd T., additional, and Erlandson, Kristine M., additional

Published
2018
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252. Gut Microbial-Related Choline Metabolite Trimethylamine-N-Oxide Is Associated With Progression of Carotid Artery Atherosclerosis in HIV Infection

Author

Shan, Zhilei, primary, Clish, Clary B, additional, Hua, Simin, additional, Scott, Justin M, additional, Hanna, David B, additional, Burk, Robert D, additional, Haberlen, Sabina A, additional, Shah, Sanjiv J, additional, Margolick, Joseph B, additional, Sears, Cynthia L, additional, Post, Wendy S, additional, Landay, Alan L, additional, Lazar, Jason M, additional, Hodis, Howard N, additional, Anastos, Kathryn, additional, Kaplan, Robert C, additional, and Qi, Qibin, additional

Published
2018
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254. A prospective study of serum microbial translocation biomarkers and risk of AIDS-related non-Hodgkin lymphoma

Author

Epeldegui, Marta, primary, Magpantay, Larry, additional, Guo, Yu, additional, Halec, Gordana, additional, Cumberland, William G., additional, Yen, Priscilla K., additional, Macatangay, Bernard, additional, Margolick, Joseph B., additional, Rositch, Anne F., additional, Wolinsky, Steven, additional, Martinez-Maza, Otoniel, additional, and Hussain, Shehnaz K., additional

Published
2018
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255. Low thigh muscle mass is associated with coronary artery stenosis among HIV-infected and HIV-uninfected men: The Multicenter AIDS Cohort Study (MACS)

Author

Tibuakuu, Martin, primary, Zhao, Di, additional, Saxena, Ankita, additional, Brown, Todd T., additional, Jacobson, Lisa P., additional, Palella, Frank J., additional, Witt, Mallory D., additional, Koletar, Susan L., additional, Margolick, Joseph B., additional, Guallar, Eliseo, additional, Korada, Sai Krishna C., additional, Budoff, Matthew J., additional, Post, Wendy S., additional, and Michos, Erin D., additional

Published
2018
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257. The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus

Author

Sun, Jing, primary, Brown, Todd T, additional, Samuels, David C, additional, Hulgan, Todd, additional, D’Souza, Gypsyamber, additional, Jamieson, Beth D, additional, Erlandson, Kristine M, additional, Martinson, Jeremy, additional, Palella, Frank J, additional, Margolick, Joseph B, additional, Kirk, Gregory D, additional, and Schrack, Jennifer A, additional

Published
2018
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258. Frailty and subclinical coronary atherosclerosis: The Multicenter AIDS Cohort Study (MACS)

Author

Korada, Sai Krishna C., primary, Zhao, Di, additional, Tibuakuu, Martin, additional, Brown, Todd T., additional, Jacobson, Lisa P., additional, Guallar, Eliseo, additional, Bolan, Robert K., additional, Palella, Frank J., additional, Margolick, Joseph B., additional, Martinson, Jeremy J., additional, Budoff, Matthew J., additional, Post, Wendy S., additional, and Michos, Erin D., additional

Published
2017
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260. Validation of Preamplification to Improve Quantification of Cytomegalovirus DNA Using Droplet Digital Polymerase Chain Reaction

Author

Zhang, Weiying, Bream, Jay H., Leng, Sean X., and Margolick, Joseph B.

Abstract

Subclinical cytomegalovirus (CMV) replication is associated with strong cellular immune response and chronic inflammation, which could contribute to aging-related conditions such as cardiovascular disease and frailty. However, because of very low levels of CMV DNA present in people with chronic CMV infection, it has been difficult to explore the virologic and immunologic mechanisms of chronic low-level CMV infection and a sensitive method to monitor CMV replication is needed. Droplet digital PCR (ddPCR) has been shown to have higher precision and reproducibility than real-time quantitative PCR (qPCR) in quantifying low levels of CMV DNA, but it is not always sensitive enough for this purpose. Through rigorous validation experiments, we demonstrated that sensitivity and precision of quantification of very low levels of CMV DNA by ddPCR can be significantly increased by preamplification of samples with 10–20 cycles of conventional PCR, especially when testing CMV DNA in the presence of cellular DNA. With preamplification, we could reliably quantify down to two copies of CMV DNA, as opposed to five copies without preamplification. Further studies are needed to determine if ddPCR with preamplification can facilitate mechanistic studies of the characteristics and consequences of chronic CMV infection in aging adults.

Published
2021
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264. Frailty and subclinical coronary atherosclerosis: The Multicenter AIDS Cohort Study (MACS).

Author

Korada, Sai Krishna C, Korada, Sai Krishna C, Zhao, Di, Tibuakuu, Martin, Brown, Todd T, Jacobson, Lisa P, Guallar, Eliseo, Bolan, Robert K, Palella, Frank J, Margolick, Joseph B, Martinson, Jeremy J, Budoff, Matthew J, Post, Wendy S, Michos, Erin D, Korada, Sai Krishna C, Korada, Sai Krishna C, Zhao, Di, Tibuakuu, Martin, Brown, Todd T, Jacobson, Lisa P, Guallar, Eliseo, Bolan, Robert K, Palella, Frank J, Margolick, Joseph B, Martinson, Jeremy J, Budoff, Matthew J, Post, Wendy S, and Michos, Erin D

Abstract

Background and aimsFrailty and cardiovascular disease share many risk factors. We evaluated whether frailty is independently associated with subclinical coronary atherosclerosis and whether any relationships differ by HIV-serostatus.MethodsWe studied 976 [62% HIV-infected] male participants of the Multicenter AIDS Cohort Study who underwent assessment of frailty and non-contrast cardiac CT scanning; of these, 747 men also underwent coronary CT angiography (CCTA). Frailty was defined as having ≥3 of 5 of the following: weakness, slowness, weight loss, exhaustion, and low physical activity. Coronary artery calcium (CAC) was assessed by non-contrast CT, and total plaque score (TPS), mixed plaque score (MPS), and non-calcified plaque score (NCPS) by CCTA. Multivariable-adjusted regression was used to assess the cross-sectional associations between frailty and subclinical coronary atherosclerosis.ResultsMean (SD) age of participants was 54 (7) years; 31% were black. Frailty existed in 7.5% and 14.3% of HIV-uninfected and HIV-infected men, respectively. After adjustment for demographics, frailty was significantly associated with prevalence of any CAC (CAC>0), any plaque (TPS>0), and mixed plaque (MPS>0) in HIV-uninfected but not in HIV-infected men (p-interactionHIV<0.05 for all). Among HIV-uninfected men, after adjustment for cardiovascular risk factors, frailty was significantly associated only with CAC>0 [Prevalence Ratio 1.27 (95%CI 1.02, 1.59)] and TPS>0 [1.19 (1.06, 1.35)]. No association was found for NCPS.ConclusionsFrailty was independently associated with subclinical coronary atherosclerosis among HIV-uninfected men, but not among HIV-infected men. Further work is needed to ascertain mechanisms underlying these differences and whether interventions that improve frailty (i.e. strength training) can improve cardiovascular outcomes.

Published
2017

265. Intestinal Microbiota-Produced Trimethylamine-N-oxide and its Association with Coronary Stenosis and HIV Serostatus

Author

Miller, P. Elliott, Haberlen, Sabina A., Brown, Todd T., Margolick, Joseph B., DiDonato, Joseph A., Hazen, Stanley L., Witt, Mallory D., Kingsley, Lawrence A., Palella, Frank J., Budoff, Matthew, Jacobson, Lisa P., Post, Wendy S., and Sears, Cynthia L.

Subjects
Male, Methylamines, HIV Seroprevalence, Coronary Stenosis, Humans, HIV Infections, Prospective Studies, Middle Aged, Article, Gastrointestinal Microbiome
Abstract

Recent evidence has shown a complex relationship between the gut microbiota, dietary nutrients, and cardiovascular disease (CVD). Trimethylamine-N-oxide (TMAO) production, initiated by the microbiota, has been associated with CVD events. We sought to test if this association exists in HIV-infected persons. After adjusting for aspirin use and CVD risk factors, HIV-infected men were more likely to have coronary stenosis in the second and third TMAO quartiles compared with the first quartile, but did not differ significantly in the fourth quartile. We found an inverted U-shaped association between TMAO levels and the presence of coronary artery stenosis among HIV-infected men.

Published
2016

266. Longitudinal Changes Over 10 Years in Free Testosterone Among HIV-Infected and HIV-Uninfected Men

Author

Slama, Laurence, Jacobson, Lisa P, Li, Xiuhong, Palella, Frank J, Margolick, Joseph B, Kingsley, Lawrence A, Wiley, Dorothy J, Pialoux, Gilles, Dobs, Adrian S, Brown, Todd T, and Multicenter AIDS Cohort Study

Subjects
Male, Aging, HIV-status, Time Factors, Multicenter AIDS Cohort Study, Clinical Sciences, Antiretroviral Therapy, HIV Infections, diurnal variation, Free testosterone, Clinical Research, Virology, Humans, Eunuchism, Testosterone, Highly Active, Prospective Studies, Aged, Prevention, Middle Aged, Cross-Sectional Studies, Infectious Diseases, Good Health and Well Being, Public Health and Health Services, Regression Analysis, HIV/AIDS, Infection
Abstract

BackgroundAging in males is associated with lower testosterone levels and a decrease in diurnal variation of testosterone secretion. Cross-sectional studies have shown lower than expected testosterone levels among HIV-infected men, but whether age-related changes in serum testosterone differ by HIV serostatus are not known.MethodsHIV-infected men from the Multicenter AIDS Cohort Study (MACS), age ≥ 45 years at highly active antiretroviral therapy initiation, who had ≥ 2 samples from the subsequent 10 years, were matched to HIV-uninfected men by age, race, MACS site, and calendar time of samples. Linear mixed-effects regression models were used to determine whether free testosterone (FT) and its rate of change differed by HIV serostatus.ResultsOne hundred eighty-two HIV-infected and 267 HIV-uninfected men were included, median age: 48.8 years (interquartile range: 45.8-53.4), median numbers of FT measurements per participant 4 (interquartile range: 3-5), 65% were drawn in the adjusted morning (AM). Mean-adjusted FT levels were lower among HIV-infected than HIV-uninfected men in AM samples {-6.1 ng/dL [95% confidence interval (CI): -9.8 to -2.4], P = 0.001}, but not in afternoon samples [-1.7 ng/dL (-6.0 to 2.6), P = 0.441]. The rate of FT decline with age did not differ by HIV serostatus: 9.2 ng/dL (95% CI: -13.4 to -5.0) per 10 years for HIV-infected vs. 7.9 ng/dL (95% CI: -10.2 to -5.5) for HIV-uninfected men, P = 0.578.ConclusionsFT decreased similarly with increasing age regardless of HIV serostatus. The lower AM, but not adjusted afternoon, FT levels among HIV-infected men compared with HIV-uninfected men suggest a loss of diurnal variation in FT levels among HIV-infected men.

Published
2016

267. Accelerated Longitudinal Gait Speed Decline in HIV-Infected Older Men

Author

Schrack, Jennifer A, Althoff, Keri N, Jacobson, Lisa P, Erlandson, Kristine M, Jamieson, Beth D, Koletar, Susan L, Phair, John, Ferrucci, Luigi, Brown, Todd T, Margolick, Joseph B, and Multicenter AIDS Cohort Study

Subjects
Adult, Male, Aging, Multicenter AIDS Cohort Study, Incidence, Clinical Sciences, virus diseases, HIV Infections, Middle Aged, Cohort Studies, Good Health and Well Being, disability, Clinical Research, Virology, functional decline, Neurologic, Public Health and Health Services, Humans, HIV/AIDS, Gait Disorders, HIV-infection, Infection, gait speed, Aged
Abstract

BackgroundGait speed predicts functional decline, disability, and death and is considered a biomarker of biological aging. Changes in gait speed in persons aging with HIV may provide an important method of gauging health and longevity in an under assessed population. The objective of this study was to evaluate and quantify the rate of gait speed decline in HIV-infected (HIV⁺) men compared with HIV-uninfected (HIV⁻) men.MethodsThe study was nested in the Multicenter AIDS Cohort Study. The primary outcome was usual gait speed in meters per second measured between 2007 and 2013. Differences in the rate of gait speed decline and the incidence of clinically slow gait (

Published
2015

268. HIV-antibody complexes enhance production of type I interferon by plasmacytoid dendritic cells

Author

Veenhuis, Rebecca T., primary, Freeman, Zachary T., additional, Korleski, Jack, additional, Cohen, Laura K., additional, Massaccesi, Guido, additional, Tomasi, Alessandra, additional, Boesch, Austin W., additional, Ackerman, Margaret E., additional, Margolick, Joseph B., additional, Blankson, Joel N., additional, Chattergoon, Michael A., additional, and Cox, Andrea L., additional

Published
2017
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270. Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection

Author

Shan, Liang, primary, Deng, Kai, additional, Gao, Hongbo, additional, Xing, Sifei, additional, Capoferri, Adam A., additional, Durand, Christine M., additional, Rabi, S. Alireza, additional, Laird, Gregory M., additional, Kim, Michelle, additional, Hosmane, Nina N., additional, Yang, Hung-Chih, additional, Zhang, Hao, additional, Margolick, Joseph B., additional, Li, Linghua, additional, Cai, Weiping, additional, Ke, Ruian, additional, Flavell, Richard A., additional, Siliciano, Janet D., additional, and Siliciano, Robert F., additional

Published
2017
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271. Geriatric syndromes

Author

Hawkins, Kellie L., primary, Brown, Todd T., additional, Margolick, Joseph B., additional, and Erlandson, Kristine M., additional

Published
2017
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276. Dual HIV-1 infection associated with rapid disease progression

Author

Gottlieb, Geoffrey S, Nickle, David C, Jensen, Mark A, Wong, Kim G, Grobler, Jandre, Li, Fusheng, Liu, Shan-Lu, Rademeyer, Cecilia, Learn, Gerald H, Karim, Salim S Abdool, Williamson, Carolyn, Corey, Lawrence, Margolick, Joseph B, and Mullins, James I

Subjects
HIV infection -- Development and progression, HIV infection -- Care and treatment, HIV infection -- Demographic aspects, AIDS (Disease) -- Complications, AIDS (Disease) -- Care and treatment, AIDS (Disease) -- Demographic aspects
Published
2004

278. Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV

Author

Chen, Yue, primary, Shen, Chengli, additional, Guha, Debjani, additional, Ding, Ming, additional, Kulich, Scott, additional, Ashimkhanova, Aiymkul, additional, Rinaldo, Charles, additional, Seaberg, Eric, additional, Margolick, Joseph B., additional, Stosor, Valentina, additional, Martínez-Maza, Otoniel, additional, and Gupta, Phalguni, additional

Published
2016
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282. The association of medication use with clearance or persistence of oral HPV infection

Author

Lam, Jennifer O., primary, Sugar, Elizabeth A., additional, Cranston, Ross D., additional, Weber, Kathleen M., additional, Burk, Robert D., additional, Wiley, Dorothy J., additional, Reddy, Susheel, additional, Margolick, Joseph B., additional, Strickler, Howard D., additional, Wentz, Alicia, additional, Jacobson, Lisa, additional, Coles, Christian L., additional, Bream, Jay H., additional, Rositch, Anne F., additional, Guo, Yingshi, additional, Xiao, Weihong, additional, Gillison, Maura L., additional, and D’Souza, Gypsyamber, additional

Published
2016
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283. Elevated levels of monocyte activation markers are associated with subclinical atherosclerosis in men with and those without HIV infection

Author

McKibben, Rebeccah A, Margolick, Joseph B, Grinspoon, Steven, Li, Xiuhong, Palella, Frank J, Kingsley, Lawrence A, Witt, Mallory D, George, Richard T, Jacobson, Lisa P, Budoff, Matthew, Tracy, Russell P, Brown, Todd T, and Post, Wendy S

Subjects
CD4-Positive T-Lymphocytes, Male, Lipopolysaccharide Receptors, HIV Infections, Coronary Angiography, Cardiovascular, Medical and Health Sciences, Microbiology, Monocytes, monocyte activation, Cohort Studies, plaque, Risk Factors, Clinical Research, Receptors, Prevalence, Humans, 2.1 Biological and endogenous factors, Antigens, Aetiology, Tomography, Chemokine CCL2, Heart Disease - Coronary Heart Disease, Atherosclerotic, human immunodeficiency virus, Prevention, Coronary Stenosis, Myelomonocytic, Middle Aged, Biological Sciences, Atherosclerosis, CD, X-Ray Computed, Infectious Diseases, Heart Disease, Good Health and Well Being, inflammation, Differentiation, Cell Surface, HIV/AIDS, Calcium, Infection, Biomarkers
Abstract

BackgroundHeightened immune activation among human immunodeficiency virus (HIV)-infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and soluble CD14 (sCD14), and monocyte chemoattractant protein 1 (CCL2) with subclinical atherosclerosis among men with and those without HIV infection in the Multicenter AIDS Cohort Study.MethodsWe performed noncontrast computed tomography on 906 men (566 HIV-infected men and 340 HIV-uninfected men), 709 of whom also underwent coronary computed tomographic angiography. Associations between each biomarker and the prevalence of coronary plaque, the prevalence of stenosis of ≥50%, and the extent of plaque were assessed by logistic and linear regression, adjusting for age, race, HIV serostatus, and cardiovascular risk factors.ResultsLevels of all biomarkers were higher among HIV-infected men, of whom 81% had undetectable HIV RNA, and were associated with lower CD4(+) T-cell counts. In the entire population and among HIV-infected men, higher biomarker levels were associated with a greater prevalence of coronary artery stenosis of ≥50%. Higher sCD163 levels were also associated with greater prevalences of coronary artery calcium, mixed plaque, and calcified plaque; higher CCL2 levels were associated with a greater extent of noncalcified plaque.ConclusionssCD163, sCD14, and CCL2 levels were elevated in treated HIV-infected men and associated with atherosclerosis. Monocyte activation may increase the risk for cardiovascular disease in individuals with HIV infection.

Published
2015

284. A longitudinal study of human papillomavirus 16 L1, e6, and e7 seropositivity and oral human papillomavirus 16 infection

Author

Beachler, Daniel C, Viscidi, Raphael, Sugar, Elizabeth A, Minkoff, Howard, Strickler, Howard D, Cranston, Ross D, Wiley, Dorothy J, Jacobson, Lisa P, Weber, Kathleen M, Margolick, Joseph B, Reddy, Susheel, Gillison, Maura L, and D'Souza, Gypsyamber

Subjects
Adult, Male, Papillomavirus E7 Proteins, Uterine Cervical Neoplasms, Enzyme-Linked Immunosorbent Assay, Cervical Cancer, Medical and Health Sciences, Clinical Research, Prevalence, Humans, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Viral, Longitudinal Studies, Dental/Oral and Craniofacial Disease, Aetiology, Cancer, Oncogene Proteins, Human papillomavirus 16, Papillomavirus Infections, Middle Aged, Biological Sciences, Anus Neoplasms, Repressor Proteins, Oropharyngeal Neoplasms, Infectious Diseases, Case-Control Studies, Sexually Transmitted Infections, HIV/AIDS, Female, Public Health, Infection
Abstract

BackgroundIndividuals with human papillomavirus (HPV) infections can develop IgG antibodies to HPV proteins including the L1 capsid and E6 and E7 oncoproteins. Evidence on whether L1 antibodies reduce the risk of cervical HPV infection is mixed, but this has not been explored for oral HPV infections. Antibodies to HPV16's E6 oncoprotein have been detected in some oropharyngeal cancer cases years before cancer diagnosis, but it is unknown if these antibodies are associated with oral HPV16 DNA.MethodsEnzyme-linked immunosorbent assays tested for serum antibodies to HPV16's L1 capsid in 463 HIV-infected and 293 HIV-uninfected adults, and for antibodies to recombinantly expressed E6 and E7 oncoproteins to HPV16 in 195 HIV-infected and 69 HIV-uninfected cancer-free participants at baseline. Oral rinse samples were collected semiannually for up to 3 years and tested for HPV DNA using PGMY 09/11 primers. Adjusted Poisson, logistic, and Wei-Lin-Weissfeld regression models were used.ResultsHuman papillomavirus 16 L1 seroreactivity did not reduce the subsequent risk of incident oral HPV16 infection in unadjusted (hazard ratio, 1.4; 95% confidence interval, 0.59-3.3) or adjusted (adjusted hazard ratio = 1.1; 95% confidence interval, 0.41-3.0) analysis. Antibodies to HPV16 E6 and E7 oncoproteins were detected in 7.6% and 3.4% of participants, respectively, but they were not associated with baseline oral HPV16 DNA prevalence or oral HPV16 persistence (each P > 0.40).ConclusionsNaturally acquired HPV16 L1 antibodies did not reduce the risk of subsequent oral HPV16 infection. Human papillomavirus 16 E6 and E7 seropositivity was not a marker for oral HPV16 infection in this population without HPV-related cancer.

Published
2015

285. Epigenetic therapy inhibits metastases by disrupting premetastatic niches

Author

Lu, Zhihao, Zou, Jianling, Li, Shuang, Topper, Michael J., Tao, Yong, Zhang, Hao, Jiao, Xi, Xie, Wenbing, Kong, Xiangqian, Vaz, Michelle, Li, Huili, Cai, Yi, Xia, Limin, Huang, Peng, Rodgers, Kristen, Lee, Beverly, Riemer, Joanne B., Day, Chi-Ping, Yen, Ray-Whay Chiu, Cui, Ying, Wang, Yujiao, Wang, Yanni, Zhang, Weiqiang, Easwaran, Hariharan, Hulbert, Alicia, Kim, KiBem, Juergens, Rosalyn A., Yang, Stephen C., Battafarano, Richard J., Bush, Errol L., Broderick, Stephen R., Cattaneo, Stephen M., Brahmer, Julie R., Rudin, Charles M., Wrangle, John, Mei, Yuping, Kim, Young J., Zhang, Bin, Wang, Ken Kang-Hsin, Forde, Patrick M., Margolick, Joseph B., Nelkin, Barry D., Zahnow, Cynthia A., Pardoll, Drew M., Housseau, Franck, Baylin, Stephen B., Shen, Lin, and Brock, Malcolm V.

Abstract

Cancer recurrence after surgery remains an unresolved clinical problem1–3. Myeloid cells derived from bone marrow contribute to the formation of the premetastatic microenvironment, which is required for disseminating tumour cells to engraft distant sites4–6. There are currently no effective interventions that prevent the formation of the premetastatic microenvironment6,7. Here we show that, after surgical removal of primary lung, breast and oesophageal cancers, low-dose adjuvant epigenetic therapy disrupts the premetastatic microenvironment and inhibits both the formation and growth of lung metastases through its selective effect on myeloid-derived suppressor cells (MDSCs). In mouse models of pulmonary metastases, MDSCs are key factors in the formation of the premetastatic microenvironment after resection of primary tumours. Adjuvant epigenetic therapy that uses low-dose DNA methyltransferase and histone deacetylase inhibitors, 5-azacytidine and entinostat, disrupts the premetastatic niche by inhibiting the trafficking of MDSCs through the downregulation of CCR2 and CXCR2, and by promoting MDSC differentiation into a more-interstitial macrophage-like phenotype. A decreased accumulation of MDSCs in the premetastatic lung produces longer periods of disease-free survival and increased overall survival, compared with chemotherapy. Our data demonstrate that, even after removal of the primary tumour, MDSCs contribute to the development of premetastatic niches and settlement of residual tumour cells. A combination of low-dose adjuvant epigenetic modifiers that disrupts this premetastatic microenvironment and inhibits metastases may permit an adjuvant approach to cancer therapy.

Published
2020
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286. T-cell immunity against cytomegalovirus in HIV infection and aging: relationships with inflammation, immune activation, and frailty.

Author

Tavenier, Juliette, Margolick, Joseph B., and Leng, Sean X.

Subjects
*HIV infections, *CYTOMEGALOVIRUS diseases, *PSYCHONEUROIMMUNOLOGY, *HIV, *OLDER people, *BIOMARKERS
Abstract

Both aging and treated human immunodeficiency virus (HIV) infection are characterized by low-level chronic inflammation and immune activation which contribute to the development of age-related diseases, frailty, and early mortality. Chronic cytomegalovirus (CMV) infection is highly prevalent in older adults and HIV-infected populations. A number of studies have shown that CMV induces broad and strong T-cell responses in CMV-seropositive older adults and HIV-infected individuals. CMV infection rarely develops into clinical disease in immunocompetent individuals. However, a large body of literature has shown adverse effects of chronic CMV infection on the health and longevity of these populations. It has been hypothesized that chronic CMV infection may be a driver of chronic inflammation and immune activation, and may further contribute to the development of frailty. Thus, there is a need to better understand the extent of the impact of chronic CMV infection on T-cell immunity and health in aging and HIV infection. In this review, we will address important considerations and challenges in the assessment of chronic CMV infection and CMV-specific T-cell responses. We will then review recent data on relationships between T-cell responses to CMV and levels of inflammatory markers and immune activation, as well as the onset of frailty. [ABSTRACT FROM AUTHOR]

Published
2019
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288. Predictors of electrocardiographic QT interval prolongation in men with HIV.

Author

Wu, Katherine C., Long Zhang, Haberlen, Sabina A., Ashikaga, Hiroshi, Brown, Todd T., Budoff, Matthew J., D'Souza, Gypsyamber, Kingsley, Lawrence A., Palella, Frank J., Margolick, Joseph B., Martínez-Maza, Otoniel, Soliman, Elsayed Z., Post, Wendy S., and Zhang, Long

Subjects
TALL-1 (Protein), CARDIAC arrest, VENTRICULAR arrhythmia, HIV infections, CELL adhesion, CARDIAC arrest prevention, LONG QT syndrome diagnosis, HIV infection complications, HIV infection epidemiology, ANTIGENS, ELECTROCARDIOGRAPHY, INTERLEUKINS, RESEARCH funding, RISK assessment, SERODIAGNOSIS, TUMOR necrosis factors, ANTIRETROVIRAL agents, LONG QT syndrome
Abstract

Objective: HIV-infected (HIV+) individuals may be at increased risk for sudden arrhythmic cardiac death. Some studies have reported an association between HIV infection and prolongation of the electrocardiographic QT interval, a measure of ventricular repolarisation, which could potentiate ventricular arrhythmias. We aimed to assess whether HIV+ men have longer QT intervals than HIV-uninfected (HIV-) men and to determine factors associated with QT duration.Methods: We performed resting 12-lead ECGs in 774 HIV+ and 652 HIV- men in the Multicenter AIDS Cohort Study (MACS). We used multivariable linear and logistic regression analyses to assess associations between HIV serostatus and Framingham corrected QT interval (QTc), after accounting for potential confounders. We also determined associations among QTc interval and HIV-related factors in HIV+ men. In a subgroup of participants, levels of serum markers of inflammation were also assessed.Results: After adjusting for demographics and risk factors, QTc was 4.0 ms longer in HIV+ than HIV- men (p<0.001). Use of antiretroviral therapy (ART), specific ART drug class use and other HIV-specific risk factors were not associated with longer QTc. Among the subgroup with inflammatory biomarker measurements, higher interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and B-cell activating factor levels were independently associated with longer QTc and their inclusion partially attenuated the HIV effect.Conclusions: HIV+ men had longer QTc, which was associated with higher levels of systemic inflammatory factors. This longer QTc may contribute to the increased risk for sudden arrhythmic cardiac death in some HIV+ individuals. [ABSTRACT FROM AUTHOR]

Published
2019
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290. Sexual role and HIV-1 set point viral load among men who have sex with men.

Author

Stansfield, Sarah E., Mittler, John E., Gottlieb, Geoffrey S., Murphy, James T., Hamilton, Deven T., Detels, Roger, Wolinsky, Steven M., Jacobson, Lisa P., Margolick, Joseph B., Rinaldo, Charles R., Herbeck, Joshua T., and Goodreau, Steven M.

Abstract

Graphical abstract Highlights • Set-point viral load is higher in insertive than receptive men who have sex with men. • This difference is limited to men presumed to be infected in longer relationships. • This pattern is predicted by mathematical models and confirmed in empirical analysis. Abstract Background HIV-1 set point viral load (SPVL) is a highly variable trait that influences disease progression and transmission risk. Men who are exclusively insertive (EI) during anal intercourse require more sexual contacts to become infected than exclusively receptive (ER) men. Thus, we hypothesize that EIs are more likely to acquire their viruses from highly infectious partners (i.e., with high SPVLs) and to have higher SPVLs than infected ERs. Methods We used a one-generation Bernoulli model, a dynamic network model, and data from the Multicenter AIDS Cohort Study (MACS) to examine whether and under what circumstances MSM differ in SPVL by sexual role. Results Both models predicted higher SPVLs in EIs than role versatile (RV) or ER men, but only in scenarios where longer-term relationships predominated. ER and RV men displayed similar SPVLs. EI men remained far less likely than ER men to become infected, however. When the MACS data were limited by some estimates of lower sex partner counts (a proxy for longer relationships), EI men had higher SPVLs; these differences were clinically relevant (>0.3 log 10 copies/mL) and statistically significant (p < 0.05). Conclusions Mode of acquisition may be an important aspect of SPVL evolution in MSM, with clinical implications. [ABSTRACT FROM AUTHOR]

Published
2019
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291. A quantitative approach for measuring the reservoir of latent HIV-1 proviruses.

Author

Bruner, Katherine M., Wang, Zheng, Simonetti, Francesco R., Bender, Alexandra M., Kwon, Kyungyoon J., Sengupta, Srona, Fray, Emily J., Beg, Subul A., Antar, Annukka A. R., Jenike, Katharine M., Bertagnolli, Lynn N., Capoferri, Adam A., Kufera, Joshua T., Timmons, Andrew, Nobles, Christopher, Gregg, John, Wada, Nikolas, Ho, Ya-Chi, Zhang, Hao, and Margolick, Joseph B.

Abstract

A stable latent reservoir for HIV-1 in resting CD4+ T cells is the principal barrier to a cure1-3. Curative strategies that target the reservoir are being tested4,5 and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation1. However, these quantitative outgrowth assays and newer assays for cells that produce viral RNA after activation6 may underestimate the reservoir size because one round of activation does not induce all proviruses7. Many studies rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of these assays is unclear, as the vast majority of proviruses are defective7-9. Here we describe a more accurate method of measuring the HIV-1 reservoir that separately quantifies intact and defective proviruses. We show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. These findings have implications for targeting the intact proviruses that are a barrier to curing HIV infection. An assay to measure the latent HIV-1 reservoir that separately quantifies intact and defective proviruses will facilitate evaluation of HIV-1 cure strategies by measuring the provirues that pose a barrier to cure. [ABSTRACT FROM AUTHOR]

Published
2019
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293. The association of medication use with clearance or persistence of oral HPV infection.

Author

Lam, Jennifer O, Lam, Jennifer O, Sugar, Elizabeth A, Cranston, Ross D, Weber, Kathleen M, Burk, Robert D, Wiley, Dorothy J, Reddy, Susheel, Margolick, Joseph B, Strickler, Howard D, Wentz, Alicia, Jacobson, Lisa, Coles, Christian L, Bream, Jay H, Rositch, Anne F, Guo, Yingshi, Xiao, Weihong, Gillison, Maura L, D'Souza, Gypsyamber, Lam, Jennifer O, Lam, Jennifer O, Sugar, Elizabeth A, Cranston, Ross D, Weber, Kathleen M, Burk, Robert D, Wiley, Dorothy J, Reddy, Susheel, Margolick, Joseph B, Strickler, Howard D, Wentz, Alicia, Jacobson, Lisa, Coles, Christian L, Bream, Jay H, Rositch, Anne F, Guo, Yingshi, Xiao, Weihong, Gillison, Maura L, and D'Souza, Gypsyamber

Abstract

PurposePersistent oral human papillomavirus (HPV) infection increases risk for oropharyngeal carcinoma, and people living with HIV have higher rates of oral HPV infection and related cancers. Some prescription medications have immunomodulatory effects, but the impact of medication use on oral HPV natural history is unknown.MethodsScope® oral rinse-and-gargle samples were collected semi-annually from 1,666 participants and tested for 37 types of oral HPV DNA using PCR; 594 HPV-infected participants with 1,358 type-specific oral HPV infections were identified. Data were collected on recent (past 6 months) use of medications. The relationship between medication use and oral HPV clearance was evaluated using Wei-Lin-Weissfeld regression, adjusting for biologic sex, prevalent versus incident infection, age, HIV status and CD4+ T cell count.ResultsOut of 11 medications examined, oral HPV clearance was significantly reduced in participants reporting recent use of antipsychotics (HR 0.75, 95% CI 0.57-0.99), anxiolytics/sedatives (HR 0.78, 95% CI 0.63-0.96) and antidepressants (HR 0.82, 95% CI 0.67-0.999). Among antipsychotics users, effect modification by HIV status was observed, with reduced clearance in HIV-infected (HR 0.67, 95% CI 0.49-0.91), but not HIV-uninfected participants (p-interaction = 0.009). After adjusted analysis, antipsychotic use remained significantly associated with reduced oral HPV clearance overall (aHR 0.75, 95% CI 0.57-0.99), and when restricted to only HIV-infected participants (aHR 0.66, 95% CI 0.48-0.90). After adjustment, anxiolytic/sedative use and antidepressant use were no longer significantly associated with reduced oral HPV clearance.ConclusionsSome medications were associated with decreased oral HPV clearance, most notably antipsychotic medications. These medications are prescribed for conditions that may have immunomodulating effects, so characteristics of underlying illness may have partially contributed to reduced oral HPV clearance.

Published
2016

294. Brief Report: Intestinal Microbiota-Produced Trimethylamine-N-Oxide and Its Association With Coronary Stenosis and HIV Serostatus.

Author

Miller, P Elliott, Miller, P Elliott, Haberlen, Sabina A, Brown, Todd T, Margolick, Joseph B, DiDonato, Joseph A, Hazen, Stanley L, Witt, Mallory D, Kingsley, Lawrence A, Palella, Frank J, Budoff, Matthew, Jacobson, Lisa P, Post, Wendy S, Sears, Cynthia L, Miller, P Elliott, Miller, P Elliott, Haberlen, Sabina A, Brown, Todd T, Margolick, Joseph B, DiDonato, Joseph A, Hazen, Stanley L, Witt, Mallory D, Kingsley, Lawrence A, Palella, Frank J, Budoff, Matthew, Jacobson, Lisa P, Post, Wendy S, and Sears, Cynthia L

Abstract

Recent evidence has shown a complex relationship between the gut microbiota, dietary nutrients, and cardiovascular disease (CVD). Trimethylamine-N-oxide (TMAO) production, initiated by the microbiota, has been associated with CVD events. We sought to test if this association exists in HIV-infected persons. After adjusting for aspirin use and CVD risk factors, HIV-infected men were more likely to have coronary stenosis in the second and third TMAO quartiles compared with the first quartile, but did not differ significantly in the fourth quartile. We found an inverted U-shaped association between TMAO levels and the presence of coronary artery stenosis among HIV-infected men.

Published
2016

295. Spontaneous and antigen-induced production of HIV-inhibitory [Beta]-chemokines are associated with AIDS-free status

Author

Garzino-Demo, Alfredo, Moss, Ronald B., Margolick, Joseph B., Cleghorn, Farley, Sill, Anne, Blattner, William A., Cocchi, Fiorenza, Carlo, Dennis J., DeVico, Anthony L., and Gallo, Robert C.

Subjects
HIV (Viruses) -- Care and treatment, AIDS (Disease) -- Care and treatment, Cytokines -- Research, HIV antigens -- Research, Science and technology
Abstract

The [Beta]-chemokines RANTES, macrophage inflammatory protein (MIP)-1[Alpha], and MIP-1[Beta] suppress infection by macrophage-tropic strains of HIV and simian immunodeficiency virus (SIV) by binding and down-regulating the viral coreceptor, CCR5. Accordingly, we have examined whether higher levels of CCR5 ligands are associated with a more favorable clinical status in AIDS. A cross-sectional study of 100 subjects enrolled in the Multicenter AIDS Cohort Study at the Baltimore site was conducted to measure chemokine production and lymphocyte proliferation by peripheral blood mononuclear cells (PBMC). Statistical analyses of the data revealed that the production of HIV-suppressive [Beta]-chemokines by HIV antigen-stimulated PBMC was significantly higher in HIV-positive subjects without AIDS compared with subjects with clinical AIDS. Increased chemokine production was also correlated with higher proliferative responses to HIV antigens. Both parameters were significantly lower in the AIDS versus non-AIDS group. Notably, significantly higher levels of MIP-1[Alpha] were also observed with unstimulated PBMC from seronegative subjects at risk for HIV infection released as compared with seropositive and non-Multicenter AIDS Cohort Study seronegative subjects. The association of chemokine production with antigen-induced proliferative responses, more favorable clinical status in HIV infection, as well as with an uninfected status in subjects at risk for infection suggests a positive role for these molecules in controlling the natural course of HIV infection. lymphocyte proliferation

Published
1999

296. Age, comorbidities, and AIDS predict a frailty phenotype in men who have sex with men

Author

Althoff, Keri N, Jacobson, Lisa P, Cranston, Ross D, Detels, Roger, Phair, John P, Li, Xiuhong, Margolick, Joseph B, and Multicenter AIDS Cohort Study (MACS)

Subjects
Male, Adult, Multimorbidities, Aging, Multicenter AIDS Cohort Study, Epidemiology, Health Status, Clinical Sciences, HIV Infections, Motor Activity, Cohort Studies, 7.1 Individual care needs, Risk Factors, Clinical Research, Weight Loss, Humans, Gait, Fatigue, Hand Strength, Frailty, Prevention, Age Factors, virus diseases, Homosexuality, Middle Aged, Infectious Diseases, Good Health and Well Being, Case-Control Studies, HIV/AIDS, Management of diseases and conditions, Infection, Gerontology
Abstract

BackgroundAdults aging with HIV infection are at risk for age-related comorbidities and syndromes, such as frailty. The objective of this study was to evaluate the expression and predictors of the frailty phenotype (FP) among HIV-infected (HIV+) and HIV-uninfected (HIV-) men who have sex with men.MethodsA prospective, observational cohort study was nested in the Multicenter AIDS Cohort Study from October 2007-September 2011. FP conversion was defined as the onset of FP over two consecutive study visits. Adjusted odds ratios and 95% confidence intervals ([,]) for FP conversion were estimated using logistic regression models with generalized estimating equations.ResultsOf 10,571 completed study visits from 1,946 men who have sex with men, 12% and 9% were FP+ among HIV+ and HIV- men, respectively (p = .002). The proportion of FP+ visits increased with age regardless of HIV status, but was significantly greater in HIV+ compared to HIV- men aged 50-64 years. Of the 10,276 consecutive visit pairs contributed by participants, 5% (537) were classified as FP conversion, and 45% of the men with FP conversion had only one FP+ study visit. FP conversion was significantly associated with a history of AIDS (adjusted odds ratios = 2.26 [1.50, 3.39], but not with HIV+ alone (adjusted odds ratios = 1.26 [0.98, 1.64]). Among men who had one or more FP+ visits, 34% of HIV+ and 38% of HIV- men had less than two comorbidities.ConclusionsThese findings suggest that expression of the FP can be measured in men who have sex with men with and without HIV infection and reflects multisystem dysfunction in this population; further investigations are needed to better understand clinical utility.

Published
2014

299. Development and Evaluation of a Modified Fourth-Generation Human Immunodeficiency Virus Enzyme Immunoassay for Cross-Sectional Incidence Estimation in Clade B Populations

Author

Kirkpatrick, Allison R., primary, Patel, Eshan U., additional, Celum, Connie L., additional, Moore, Richard D., additional, Blankson, Joel N., additional, Mehta, Shruti H., additional, Kirk, Gregory D., additional, Margolick, Joseph B., additional, Quinn, Thomas C., additional, Eshleman, Susan H., additional, and Laeyendecker, Oliver, additional

Published
2016
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300. Association of serum cytokines with oral HPV clearance

Author

Lam, Jennifer O., primary, Bream, Jay H., additional, Sugar, Elizabeth A., additional, Coles, Christian L., additional, Weber, Kathleen M., additional, Burk, Robert D., additional, Wiley, Dorothy J., additional, Cranston, Ross D., additional, Reddy, Susheel, additional, Margolick, Joseph B., additional, Strickler, Howard D., additional, Wentz, Alicia, additional, Jacobson, Lisa, additional, Guo, Yingshi, additional, Xiao, Weihong, additional, Gillison, Maura L., additional, and D’Souza, Gypsyamber, additional

Published
2016
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