Inflammation and Change in Body Weight With Antiretroviral Therapy Initiation in a Multinational Cohort of HIV-Infected Adults

Mave, Vidya; Erlandson, Kristine M.; Gupte, Nikhil; Balagopal, Ashwin; Asmuth, David M.; Campbell, Thomas; Smeaton, Laura; Kumarasamy, Nagalingeswaran; Hakim, James; Santos, Breno; Riviere, Cynthia; Hosseinipour, Mina C.; Sugandhavesa, Patcharaphan; Infante, Rosa; Pillay, Sandy; Cardoso, Sandra Wagner; Tripathy, Srikanth; Mwelase, Noluthando; Berendes, Sima; Andrade, Bruno B.; Thomas, David L.; Bollinger, Robert C.; Gupta, Amita

doi:10.1093/infdis/jiw096

Cited by 61 publications

(44 citation statements)

References 44 publications

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“…Some weight gain following ART initiation may be attributable to a “return to health” phenomenon; however, excessive weight gain can occur, with persons with the highest pre-ART HIV-1 RNA or lowest CD4 + T lymphocyte counts at risk for greater weight gain[10, 11]. Further exemplifying the fact that weight gain can represent differential effects depending on the host, weight gain among underweight persons has been associated with a decline in circulating high-sensitivity C-reactive protein levels[12] and improved survival[13], whereas weight gain among overweight or obese individuals has been associated with significant increases in circulating levels of the monocyte activation marker soluble CD14[12], no mortality benefit[13] and a ≥67% prevalence of multi-morbidity[14]. …”

Section: Burden Of Obesity and Visceral Adipositymentioning

confidence: 99%

“…The development of comorbid disease in HIV-infected persons is believed to have both traditional and HIV-/ART-specific contributors: Obesity, and particularly VAT accumulation, are associated with systemic[12, 47] and adipose tissue inflammation[48], insulin resistance, dyslipidemia[49] and increased oxidative stress[50]. At the same time, adipose tissue is a potential HIV reservoir, leading to recruitment of T lymphocytes and macrophages into adipose tissue.…”

Section: Consequences Of Obesity and Visceral Adipositymentioning

confidence: 99%

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The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection

Lake

2017

Curr HIV/AIDS Rep

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Purpose of Review To summarize knowledge of the prevalence, relevant physiology and consequences of obesity and visceral adiposity in HIV-infected adults, including highlighting gaps in current knowledge and future research directions. Recent Findings Similar to the general population, obesity prevalence is increasing among HIV-infected persons, and obesity and visceral adiposity are associated with numerous metabolic and inflammatory sequelae. However, HIV- and antiretroviral therapy (ART)-specific factors may contribute to fat gain and fat quality in treated HIV infection, particularly to the development of visceral adiposity, and sex differences may exist. Summary Obesity and visceral adiposity commonly occur in HIV-infected persons and have significant implications for morbidity and mortality. Future research should aim to better elucidate the HIV- and ART-specific contributors to obesity and visceral adiposity in treated HIV infection, with the goal of developing targeted therapies for the prevention and treatment of obesity and visceral adiposity in the modern ART era.

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Section: Burden Of Obesity and Visceral Adipositymentioning

confidence: 99%

Section: Consequences Of Obesity and Visceral Adipositymentioning

confidence: 99%

The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection

Lake

2017

Curr HIV/AIDS Rep

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“…18-22 A hypothesized mechanism for the increased cardiovascular risk, common to both, is immune system alteration. 23-29 While obesity has well-established associations with traditional risk factors for CVD including hypertension, hyperlipidemia, and diabetes, both HIV and obesity are associated with immune system alterations that may independently impact risk. 23-28 While both HIV and obesity are associated with altered immunity, their combined effect on inflammation, altered coagulation, and monocyte activation is unclear.…”

Section: Introductionmentioning

confidence: 99%

HIV and Obesity Comorbidity Increase Interleukin 6 but Not Soluble CD14 or D-Dimer

Taylor

So‐Armah

Tate

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objectives Obesity prevalence among people living with HIV (HIV+) is rising. HIV and obesity are pro-inflammatory states, but their combined effect on inflammation (measured by interleukin 6, IL-6), altered coagulation (D-dimer), and monocyte activation (soluble CD14, sCD14) is unknown. We hypothesized inflammation increases when obesity and HIV infection co-occur. Methods The VACS survey cohort is a prospective, observational, longitudinal study of predominantly male, HIV+ veterans and veterans uninfected with HIV; a subset provided blood samples. Inclusion criteria for this analysis were: body mass index (BMI) ≥ 18.5 kg/m2 and with biomarker measurements. Dependent variables were IL-6, sCD14, and D-dimer quartiles. Obesity/HIV status was the primary predictor. Unadjusted and adjusted logistic regression models were constructed. Results Data were analyzed for 1477 HIV+ and 823 uninfected participants. Unadjusted median IL-6 levels were significantly higher and sCD14 levels were significantly lower in obese/HIV+ when compared with non-obese/uninfected people (p-value <0.01 for both). In adjusted analyses, the odds ratio (OR) for increased IL-6 in obese/HIV+ was 1.76 (95%CI: 1.18, 2.47) when compared with non-obese/uninfected, and obesity/HIV+ remained associated with lower odds of elevated sCD14. We did not detect a synergistic association of co-occurring HIV and obesity on IL-6 or sCD14 elevation. D-dimer levels did not differ significantly between BMI/HIV status groups. Conclusion HIV-obesity comorbidity is associated with elevated IL-6, decreases in sCD14 and no significant difference in D-dimer. These findings are clinically significant as previous studies show these biomarkers are associated with mortality. Future studies should assess whether other biomarkers show similar trends and potential mechanisms for the unanticipated sCD14 and D-dimer findings.

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“…5–7 In addition, increasing BMI is associated with greater innate and adaptive immune activation, even in the setting of treated HIV infection. 8,9 As observed in the general population 10 , serum levels of systemic markers of inflammation such as C-reactive protein (CRP) and tumor necrosis factor (TNF)-α 11–13 are higher among HIV-infected adults with greater adiposity. There is also evidence that adiposity influences adaptive immune responses, with several recent studies suggesting that obesity independently influences immunologic recovery in individuals initiating ART.…”

Section: Introductionmentioning

confidence: 99%

“…Given the numerous deleterious inflammatory and metabolic sequelae of obesity 9,11 we hypothesized that greater BMI would be associated with a pattern of poor CD8+ T cell differentiation in HIV-infected adults that has been previously associated with mortality in this setting.…”

Section: Introductionmentioning

confidence: 99%

Higher Body Mass Index Is Associated With Greater Proportions of Effector CD8+ T Cells Expressing CD57 in Women Living With HIV

Mja

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background A low proportion of CD28−CD8+ T cells that express CD57 is associated with increased mortality in HIV infection. The effect of increasing BMI changes in the proportion of CD57+CD28−CD8+ T cells among HIV-infected individuals on ART is unknown. Setting In a U.S. cohort of HIV-infected women, we evaluated associations of BMI and waist circumference with 3 distinct CD8+ T cell phenotypes: % CD28−CD57+CD8+ T cells, % CD57+ of CD28−CD8+ T cells and % CD28− of all CD8+ T cells. Methods Multivariable linear regression analysis was used to estimate beta-coefficients for each of three T cell phenotypes. Covariates included HIV parameters (current and nadir CD4, current viral load), demographics (age, race, income, study site), and lifestyle (tobacco, alcohol use) factors. Results Of 225 participants, the median age was 46 years and 50% were obese (BMI>30 m2/kg). Greater BMI and waist circumference were both associated with higher %CD28−CD57+CD8+ T cells and %CD57+ of all CD28−CD8+ T cells in multivariable analysis, including adjustment for HIV viral load (all p<0.05). The association between greater BMI and the overall proportion of CD28− CD8+ cells in fully adjusted models (0.078, 95% CI: (−0.053 – 0.209) were not significant. Conclusions In this analysis, greater BMI and waist circumference are associated with greater expression of CD57 on CD28−CD8+ T cells and a greater proportion of CD57+CD28− CD8+ T cells. These findings may indicate that increasing BMI is immunologically protective in HIV-infected women. Future research is needed to understand the prognostic importance of these associations on clinical outcomes.

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Inflammation and Change in Body Weight With Antiretroviral Therapy Initiation in a Multinational Cohort of HIV-Infected Adults

Abstract: Being either overweight or underweight at ART initiation was associated with heightened systemic inflammation. While weight gain among overweight/obese persons predicted increased inflammation, weight gain among underweight persons predicted reduced inflammation.

Cited by 61 publications

References 44 publications

The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection

The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection

HIV and Obesity Comorbidity Increase Interleukin 6 but Not Soluble CD14 or D-Dimer

Higher Body Mass Index Is Associated With Greater Proportions of Effector CD8+ T Cells Expressing CD57 in Women Living With HIV

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