Association of Functional Impairment with Inflammation and Immune Activation in HIV Type 1–Infected Adults Receiving Effective Antiretroviral Therapy

Erlandson, Kristine M.; Allshouse, Amanda A.; Jankowski, C.M.; Lee, Eric J.; Rufner, Kevin M.; Palmer, Brent E.; Wilson, Cara C.; MaWhinney, Samantha; Kohrt, Wendy M.; Campbell, Thomas

doi:10.1093/infdis/jit147

Cited by 138 publications

(113 citation statements)

References 37 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…[23][24][25] Briefly, individuals with HIV-1 infection on antiretroviral therapy for a minimum of 6 months and no plasma HIV-1 RNA >200 copies/ml within the prior 6 months underwent physical function testing by the Short Physical Performance Battery and Fried's frailty assessment. Cases with low physical function, defined by a combination of deficits on both functional assessments, 23 were matched by age, gender, and time since HIV diagnosis to controls with high physical function (no deficits on either functional assessment). Stored samples and existing data were used for the current study.…”

Section: Study Populationmentioning

confidence: 99%

“…22 We have previously demonstrated a strong association between markers of inflammation and immune activation with physical function impairment among middle-aged HIVinfected persons on effective ART. 23 The goals of the present study were to (1) determine the relationship between CMVspecific humoral and cell-mediated immune responses and functional impairment in well-controlled HIV infection and (2) explore the impact of clinical characteristics, inflammation, and immune activation on those relationships.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

Erlandson

Allshouse

Rapaport

et al. 2015

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

Cytomegalovirus (CMV) is associated with poor outcomes, including physical function impairment, in older HIV-uninfected adults. Whether CMV is associated with physical functional impairment in HIV-infected adults is unknown. The primary objective of this study was to determine the relationship between CMV-specific humoral and cell-mediated immune responses with functional impairment in well-controlled HIV infection. In a case-control study, low-function cases were matched by age, gender, and time from HIV diagnosis to highfunction controls. Quantitative CMV IgG and %CMV-specific CD8 + and CD4 + T cells (interferon-c expression following CMV pp65 stimulation) were used to estimate physical function. Among 30 low-function cases and 48 high-function matched controls, CMV IgG ranged from <10 to 8,830 EU/ml, including four controls with results <10 EU/ml. Each log 10 increase in CMV IgG was associated with 5-fold greater odds of low function ( p = 0.01); these findings were robust to adjustment for concomitant CD4 + count, tobacco use, and age; to exclusion of subjects with CMV IgG <10 EU/ml; and to adjustment for hepatitis C viremia. %CMV-specific CD4 + or CD8 + T cells were not associated with low function. In bivariable models, the relationship between CMV IgG and physical function was attenuated and was no longer significant when including IL-6, CD4/CD8 ratio, or the Veterans Aging Cohort Study Index score. High levels of CMV-specific IgG were associated with impaired physical function. Attenuation of the strength of this association in bivariable models suggests an indirect relationship mediated by systemic inflammation and immune suppression.

show abstract

Section: Study Populationmentioning

confidence: 99%

mentioning

confidence: 99%

Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

Erlandson

Allshouse

Rapaport

et al. 2015

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

show abstract

“…Suppression of viral replication with effective antiretroviral treatment (ART) reduces immune activation, but even effective ART regimens are unable to reduce the levels of immune activation in HIV-infected individuals to levels seen in healthy individuals (1). Since this inflammation is linked to poor health outcomes, including elevated risks of death, cardiovascular disease (CVD), neurocognitive impairment, osteoporosis, and frailty even in treated individuals (1,2,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), understanding the mechanisms behind immune activation may lead to new treatments to improve the quality and length of life for HIV-1-infected individuals.…”

mentioning

confidence: 99%

Association between Latent Proviral Characteristics and Immune Activation in Antiretrovirus-Treated Human Immunodeficiency Virus Type 1-Infected Adults

Liang

Sceats

Bayless

et al. 2014

J Virol

View full text Add to dashboard Cite

Generalized immune activation during HIV infection is associated with an increased risk of cardiovascular disease, neurocognitive disease, osteoporosis, metabolic disorders, and physical frailty. The mechanisms driving this immune activation are poorly understood, particularly for individuals effectively treated with antiretroviral medications. We hypothesized that viral characteristics such as sequence diversity may play a role in driving HIV-associated immune activation. We therefore sequenced proviral DNA isolated from peripheral blood mononuclear cells from HIV-infected individuals on fully suppressive antiretroviral therapy. We performed phylogenetic analyses, calculated viral diversity and divergence in the env and pol genes, and determined coreceptor tropism and the frequency of drug resistance mutations. Comprehensive immune profiling included quantification of immune cell subsets, plasma cytokine levels, and intracellular signaling responses in T cells, B cells, and monocytes. These antiretroviral therapy-treated HIV-infected individuals exhibited a wide range of diversity and divergence in both env and pol genes. However, proviral diversity and divergence in env and pol, coreceptor tropism, and the level of drug resistance did not significantly correlate with markers of immune activation. A clinical history of virologic failure was also not significantly associated with levels of immune activation, indicating that a history of virologic failure does not inexorably lead to increased immune activation as long as suppressive antiretroviral medications are provided. Overall, this study demonstrates that latent viral diversity is unlikely to be a major driver of persistent HIV-associated immune activation. IMPORTANCEChronic immune activation, which is associated with cardiovascular disease, neurologic disease, and early aging, is likely to be a major driver of morbidity and mortality in HIV-infected individuals. Although treatment of HIV with antiretroviral medications decreases the level of immune activation, levels do not return to normal. The factors driving this persistent immune activation, particularly during effective treatment, are poorly understood. In this study, we investigated whether characteristics of the latent, integrated HIV provirus that persists during treatment are associated with immune activation. We found no relationship between latent viral characteristics and immune activation in treated individuals, indicating that qualities of the provirus are unlikely to be a major driver of persistent inflammation. We also found that individuals who had previously failed treatment but were currently effectively treated did not have significantly increased levels of immune activation, providing hope that past treatment failures do not have a lifelong "legacy" impact.

show abstract

“…[39][40][41] Whether further reductions in already low levels of inflammation in HIV-infected individuals with suppressed viral load translate into meaningful clinical benefit remains , and TNF-a. 43 They found no changes after vitamin D repletion.…”

Section: Vitamin D Insufficiency and Inflammation In Chronic Hiv Infementioning

confidence: 99%

Vitamin D Levels and Markers of Inflammation and Metabolism in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

Hoffman

Lake

Wilhalme

et al. 2016

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Data on vitamin D insufficiency as a cause of inflammation and metabolic dysfunction in HIV-infected individuals are conflicting. We examined the relationships between levels of 25-hydroxyvitamin D [25(OH)D] and biomarkers of inflammation and metabolism in stored blood samples from a prospective trial of vitamin D repletion. Blood samples from HIV-infected individuals on antiretroviral therapy (ART) with HIV-1 RNA <200 copies/ml enrolled in a prospective study were analyzed for 25(OH)D levels, a broad panel of cytokines, highly sensitive C-reactive protein, D-dimer, adiponectin, leptin, and insulin. Correlations between markers and 25(OH)D levels were determined. The Wilcoxon Rank Sum test was used to compare markers between individuals 25(OH)D insufficient and sufficient at baseline and before and after repletion among those who were insufficient and repleted to ‡30 ng/ml after 12 weeks. Of 106 subjects with stored plasma [66 with 25(OH)D <30 ng/ml and 40 ‡ 30 ng/ml], the median age was 50, the CD4 count was 515 cells/mm 3 , 94% were male, and the median baseline 25(OH)D was 27 ng/ml. Higher 25(OH)D levels were associated with lower tumor necrosis factor (TNF)-a (r = -0.20, p = 0.04) and higher adiponectin levels (r = 0.30, p = 0.002). Following successful repletion to 25(OH)D ‡30 ng/ml there were no significant changes in inflammatory or metabolic parameters. Our study found associations between low 25(OH)D levels and TNF-a and adiponectin. Repletion did not result in changes in markers of inflammation or metabolism. These data support continued study of the relationship between vitamin D, inflammation, and metabolism in treated HIV infection.

show abstract

Association of Functional Impairment with Inflammation and Immune Activation in HIV Type 1–Infected Adults Receiving Effective Antiretroviral Therapy

Abstract: Functional impairment during successful antiretroviral therapy was associated with higher CD8(+) T-cell activation and interleukin 6 levels. Interventions to decrease immune activation and inflammation should be evaluated for their effects on physical function and frailty.

Cited by 138 publications

References 37 publications

Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

Association between Latent Proviral Characteristics and Immune Activation in Antiretrovirus-Treated Human Immunodeficiency Virus Type 1-Infected Adults

Vitamin D Levels and Markers of Inflammation and Metabolism in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

Contact Info

Product

Resources

About