Comprehensive Evaluation of the Immune Risk Phenotype in Successfully Treated HIV-Infected Individuals

Ndumbi, Patricia; Gilbert, Louise; Tsoukas, Christos

doi:10.1371/journal.pone.0117039

Cited by 21 publications

(12 citation statements)

References 45 publications

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“…Similar to the immune alterations observed in IRP, HIV-infected patients also present with low CD4/CD8 ratio, elevated CD8 counts and an expansion of the memory CD8 T-cell subsets [ 13 ]. It was recently reported that despite effective ART, HIV-infected patients with elevated IRP displayed a higher degree of immune senescence than their non-IRP counterparts [ 14 ]. The significant overlap in clinical and immunological phenotypes observed during normal ageing and HIV infection has raised the concept of premature senescence in HIV infection.…”

Section: Resultsmentioning

confidence: 99%

Elevation and persistence of CD8 T‐cells in HIV infection: the Achilles heel in the ART era

Cao

Mehraj

Kaufmann

et al. 2016

Journal of the International AIDS Society

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IntroductionHIV infection leads to a disturbed T-cell homeostasis, featured by a depletion of CD4 T-cells and a persistent elevation of CD8 T-cells over disease progression. Most effort of managing HIV infection has been focused on CD4 T-cell recovery, while changes in the CD8 compartment were relatively underappreciated in the past.MethodsA comprehensive literature review of publications in English language was conducted using major electronic databases. Our search was focused on factors contributing to CD8 T-cell dynamics in HIV infection and following antiretroviral therapy (ART).DiscussionNormalization of CD8 counts is seldom observed even with optimal CD4 recovery following long-term treatment. Initiation of ART in primary HIV infection leads to enhanced normalization of CD8 count compared with long-term ART initiated in chronic infection. Importantly, such CD8 elevation in treated HIV infection is associated with an increased risk of inflammatory non-AIDS-related clinical events independent of CD4 T-cell recovery. The mechanisms underlying CD8 persistence remain largely unknown, which may include bystander activation, exhaustion and immunosenescence of CD8 T-cells. The information provided herein will lead to a better understanding of factors associated with CD8 persistence and contribute to the development of strategies aiming at CD8 normalization.ConclusionsPersistence of CD8 T-cell elevation in treated HIV-infected patients is associated with an increased risk of non-AIDS-related events. Now that advances in ART have led to decreased AIDS-related opportunistic diseases, more attention has been focused on reducing non-AIDS events and normalizing persistent CD8 T-cell elevation.

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Section: Resultsmentioning

confidence: 99%

Elevation and persistence of CD8 T‐cells in HIV infection: the Achilles heel in the ART era

Cao

Mehraj

Kaufmann

et al. 2016

Journal of the International AIDS Society

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“…The progressive expansion of the T-cell repertoire committed to CMV (referred to as CMV-specific CD8 + T-cell memory inflation [29]) can deplete naive T cells and is associated with the immune risk phenotype in the general population [45]. The immune risk phenotype includes expansion of late-differentiated CD8 + T cells and an inverted CD4 + /CD8 + T-cell ratio; is a strong predictor of mortality; and is rarely seen in centenarians [46].…”

Section: CMV Immunosenescence and Agingmentioning

confidence: 99%

Cytomegalovirus and HIV: A Dangerous Pas de Deux

2016

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Human immunodeficiency virus (HIV)-infected adults who take stable antiretroviral therapy (ART) are at risk for early onset of agerelated diseases. This is likely due to a complex interaction between traditional risk factors, HIV infection itself, and other factors, such as underlying immune dysfunction and persistent inflammation. HIV disrupts the balance between the host and coinfecting microbes, worsening control of these potential pathogens. For example, HIV-infected adults are more likely than the general population to have subclinical bursts of cytomegalovirus (CMV) replication at mucosal sites. Production of antigens can activate the immune system and stimulate HIV replication, and it could contribute to the pathogenesis of adverse outcomes of aging, like cardiovascular disease and neurocognitive impairment. Further investigation of the relationships between CMV, immune dysfunction, and unsuccessful aging during chronic HIV infection is warranted.

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“…The IRP has been associated with higher risk of mortality and morbidities, including vascular disease and osteoporosis [12, 16]. Consistently, a pilot study on HIV-infected patients found that IRP is accompanied by telomere shortening, weak proliferative responses and enhanced production of proinflammatory cytokines[17]. An association between chronic CMV infection, immune senescence and activation was previously reported in HIV-infected patients [18], and CMV coinfection was recently identified as a risk factor for severe non-AIDS-defining events/non-AIDS-related death, cerebrovascular and cardiovascular events [5].…”

Section: Discussionmentioning

confidence: 91%

CMV+ Serostatus Associates Negatively with CD4:CD8 Ratio Normalization in Controlled HIV-Infected Patients on cART

Poizot‐Martin

Allavena²,

Duvivier

et al. 2016

PLoS ONE

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Cytomegalovirus (CMV) infection is common among HIV-infected patients but its repercussion on the course of CD4+ and CD8+ T cells after cART initiation remains elusive. The French Dat'AIDS cohort enrolled 5,688 patients on first-line cART, from which we selected patients who achieved HIV suppression for at least 12 months without modification of cART, and for whom CMV serostatus was available. Five hundred and three patients fulfilled the selection criteria (74% male, median age 43 yrs, 15.5% CDC stage C), of whom 444 (88.3%) were seropositive for CMV (CMV+). Multivariate analyses using mixed-linear models adjusted for the time from HIV suppression, sex, age, transmission risk group, duration of HIV follow-up, the interaction between time from HIV suppression and CMV+ serology, and the nadir CD4 count revealed a negative correlation between CMV+ and CD4:CD8 ratio (coeff. = -0.16; p = 0.001). This correlation was also observed among patients displaying optimal CD4 recovery (≥500 cells/mm3 at M12; coeff. = -0.24; p = 0.002). Hence, CMV+ serostatus antagonizes normalization of the CD4:CD8 ratio, although further analyses of the impact of co-morbidities that associate with CMV serostatus, like HCV infection, are needed to elucidate this antagonism formally. However, this might reflect a premature T cell senescence, thus advocating for a close monitoring of T cells in CMV co-infected patients. In addition, our results raise the question of the benefit of treatment for asymptomatic CMV co-infection in HIV-infected patients.

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Comprehensive Evaluation of the Immune Risk Phenotype in Successfully Treated HIV-Infected Individuals

Cited by 21 publications

References 45 publications

Elevation and persistence of CD8 T‐cells in HIV infection: the Achilles heel in the ART era

Elevation and persistence of CD8 T‐cells in HIV infection: the Achilles heel in the ART era

Cytomegalovirus and HIV: A Dangerous Pas de Deux

CMV+ Serostatus Associates Negatively with CD4:CD8 Ratio Normalization in Controlled HIV-Infected Patients on cART

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