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3159 Bone Turnover Biomarkers May Discriminate Low Bone Mineral Density in HIV-Infected Adults
- Lauren Frances Collins, Anandi Sheth, Caitlin Moran, Laura Ward, Kehmia Titanji, Kirk Easley, Jeffrey Lennox, M. Neale Weitzmann, Igho Ofotokun
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, p. 36
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- Article
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OBJECTIVES/SPECIFIC AIMS: Persons living with HIV (PLWH) are at increased risk for fragility bone disease. Current osteoporosis screening guidelines do not account for HIV status, and clinical risk assessment tools are not sensitive in PLWH. We examined the value of traditional osteoporosis risk factors, HIV-specific indices, and bone turnover biomarkers in predicting low bone mineral density (BMD) in PLWH. METHODS/STUDY POPULATION: Demographic and clinical characteristics, dual energy x-ray absorptiometry (DXA)-derived BMD, HIV indices (viral load, CD4 count, antiretroviral therapy [ART]), and biomarkers of bone turnover (C-terminal telopeptide of collagen [CTx], osteocalcin [OCN]) were evaluated in a cross-sectional analysis of PLWH (n=248) and HIV- controls (n=183). The primary outcome was low BMD, defined as osteopenia or osteoporosis by WHO criteria. Multivariable logistic and modified Poisson regression models were used to assess associations between low BMD and covariates of interest. RESULTS/ANTICIPATED RESULTS: Overall, median age was 44 years, 48% were male, 88% were black, median body mass index (BMI) was 28 kg/m2, 72% smoked cigarettes, and 53% used alcohol; characteristics did not differ by HIV status. PLWH had a mean CD4 of 408 cells/mm3, 55% were ART-naïve, and 45% had viral suppression on ART. Overall, 25% (109/431) had low BMD, including 31% of PLWH compared to 16% of HIV- controls. In multivariable models, HIV was significantly associated with low BMD (aOR 2.46, 95%CI 1.39-4.34; aRR 1.90, 95%CI 1.18-3.07). Adjusting for HIV, three traditional risks– age, race, and BMI– were independently associated with low BMD in the full cohort. However, bone turnover markers, CTx and OCN, were better able to discriminate low vs. normal BMD in PLWH compared to HIV- controls. In PLWH, mean serum CTx was 23% higher in low vs. normal BMD (mean CTx difference=0.06 ug/mL); in HIV- controls, no association with BMD was observed (mean CTx difference=0 ug/mL). In PLWH, mean serum OCN was 38% higher in those with low vs. normal BMD (mean OCN difference=2.48 ug/mL); in HIV- controls, mean serum OCN was only 16% higher in those with low vs. normal BMD (mean OCN difference=1.08 ug/mL). DISCUSSION/SIGNIFICANCE OF IMPACT: In PLWH as opposed to HIV- controls, serum biomarkers reflecting a high bone turnover state, may discriminate individuals with low versus normal BMD. Because changes in biomarkers precede changes in BMD, these markers should be explored further either alone or in combination with traditional risk assessment tools to improve early screening for osteoporosis in PLWH.
Chapter 25 - HIV infection
- from Section 7 - Infectious disease
- Edited by Michael F. Lubin, Emory University, Atlanta, Thomas F. Dodson, Emory University, Atlanta, Neil H. Winawer, Emory University, Atlanta
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- Book:
- Medical Management of the Surgical Patient
- Published online:
- 05 September 2013
- Print publication:
- 15 August 2013, pp 282-291
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Summary
The epidemic of human immunodeficiency virus (HIV) infection that began in the late twentieth century has become one of the dominant health issues worldwide for the early twenty-first century. Advances in the prevention of HIV infection have reduced the global incidence of infection and advances in treatment have dramatically extended the lifespan of infected patients. In the developed world a 20-year-old who begins antiretroviral therapy is estimated to have a life expectancy of an additional 43.1 years while a treated patient in the developing world has an additional life expectancy of 26.7 years [1,2]. In 2009 of the estimated 33.3 million people worldwide living with HIV approximately 5 million were on antiretroviral therapy [3]. Since an additional 1.8 million people become infected with HIV each year, the effect of increased longevity will produce increasing opportunities for internists and surgeons to collaborate in the management of HIV-infected patients.
The clinical course of HIV infection has been well described and should be familiar to most physicians. HIV infection is associated with abnormalities in the number and function of CD4-positive T-lymphocytes. Because the CD4-positive T-lymphocytes are essential to the regulation of the human immune system, progressive immune dysfunction is a natural consequence of HIV infection in most patients. This progressive immune dysregulation is associated with decreased cell-mediated immune function, alterations in the humoral immune response, chronic inflammation and depressed mucosal immunity. The late stages of HIV infection are associated with pathologic processes in many organ systems and eventual death due to opportunistic infections or tumors. This natural history of the disease has been dramatically altered by the widespread use in the developed world of highly active antiretroviral therapy (HAART). HAART is an acronym that refers to combinations of antiretroviral agents that have been shown in clinical trials to result in undetectable plasma HIV RNA levels in the majority of patients. These combinations may include two nucleoside analogs plus either a protease inhibitor, an integrase inhibitor or a non-nucleoside reverse transcriptase inhibitor. Guidelines for the use of these agents in HIV-infected adults and children have been developed, are frequently updated, and are available through the Internet [4].
22 - Medical care of the HIV-infected surgical patient
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- By Jeffrey L. Lennox, Emory University, School of Medicine, Atlanta, GA
- Edited by Michael F. Lubin, Emory University, Atlanta, Robert B. Smith, Emory University, Atlanta, Thomas F. Dodson, Emory University, Atlanta, Nathan O. Spell, Emory University, Atlanta, H. Kenneth Walker, Emory University, Atlanta
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- Book:
- Medical Management of the Surgical Patient
- Published online:
- 12 January 2010
- Print publication:
- 10 August 2006, pp 307-316
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Summary
The epidemic of HIV infection that began in the late twentieth century has become one of the dominant health issues worldwide for the early twenty-first century. In the developed world, advances in the treatment of HIV infection have dramatically extended the lifespan of infected patients. As a result of these therapeutic advances, deaths from HIV infection in the USA fell by over 50% between 1995 and 2000. In developing areas of the world, HIV continues to spread among sexually active adults and their offspring. In some areas of Africa as much as 20% of the adult population is infected. HIV infection rates are also accelerating in the developed nations of Asia, and in areas of the former Soviet Union. The combined effects of increased longevity and accelerated worldwide dissemination are likely to result in increasing opportunities for internists and surgeons to collaborate in the management of HIV-infected patients.
The clinical course of HIV infection has been well described and should be familiar to most general internists. HIV infection is associated with abnormalities in the number and function of CD4 positive T-lymphocytes. Because the CD4 positive lymphocytes are essential to the regulation of the human immune system, progressive immune dysfunction is a natural consequence of HIV infection in most patients. This progressive immune dysregulation is associated with decreased cell-mediated immune function, alterations in the humoral immune response, chronic inflammation and depressed mucosal immunity.