Long-term complications in patients with poor immunological recovery despite virological successful HAART in Dutch ATHENA cohort

Lelyveld, S.F.L. van; Gras, Luuk; Kesselring, Anouk; Zhang, Shuangjie; Wolf, Frank de; Wensing, Annemarie M. J.; Hoepelman, Andy I. M.

doi:10.1097/qad.0b013e32834f32f8

Cited by 100 publications

(108 citation statements)

References 31 publications

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“…This stems from the clear evidence of an increased risk of mortality and increased clinical progression to AIDS and non-AIDS-related diseases among immunodiscordant patients [15,[88][89][90][91]. This increase in death risk is not a consequence of low nadir CD4 T-cell counts [6,92] or older age [93], and seems to be a consequence of low CD4 T-cell counts after HAART initiation. The association of CD4 T-cell count and AIDS defining events or death in HIV-1-treated patients [19] highlights the relevance of pursuing the pathophysiologic mechanisms involved in the lack of immune recovery in order to recognize early and classify immunodiscordant individuals and propose therapies adapted to each situation.…”

Section: Other Factors Associated With Immunodiscordant Responsesmentioning

confidence: 93%

Immunodiscordant responses to HAART – mechanisms and consequences

Massanella

Negredo

Clotet

et al. 2013

Expert Review of Clinical Immunology

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A relevant fraction of HIV-1-infected individuals (ranging from 15 to 30%) presenting virologically successful highly active antiretroviral therapy fail to recover CD4 T-cell counts. These individuals, called immunodiscordant or immunological nonresponders, are at increased risk of clinical progression and death. Although older age, lower nadir CD4 T-cell count and HCV co-infection are some of clinical predictive factors, immunological mechanisms rely on impaired thymic production and accumulation of apoptosis-prone CD4 T cells. Indeed, immunodiscordant individuals may show increased tissue fibrosis and damage of gut-associated lymphoid tissue that results in higher hyperactivation, inflammation and immunosenescence, altered Treg/Th17 ratio and increased T-cell death. A better knowledge of the final pathogenic mechanism and factors influencing CD4 T-cell recovery will help to select the optimal therapeutic strategies for them.

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Section: Other Factors Associated With Immunodiscordant Responsesmentioning

confidence: 93%

Immunodiscordant responses to HAART – mechanisms and consequences

Massanella

Negredo

Clotet

et al. 2013

Expert Review of Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…While some have found an increased risk [12•, 96-98] in individuals with lower nadir or recent CD4+ counts, a strong independent association was not clear in other studies [99]. However, patients with incomplete or declining immunological recovery despite virological successful cART have a higher risk of CVD [100,101].…”

Section: The Role Of Hiv Infection In Itself In the Pathogenesis Of Cmentioning

confidence: 94%

Risk of Cardiovascular Disease in an Aging HIV Population: Where Are We Now?

2015

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With more effective and widespread antiretroviral treatment, the overall incidence of AIDS- or HIV-related death has decreased dramatically. Consequently, as patients are aging, cardiovascular disease (CVD) has emerged as an important cause of morbidity and mortality in the HIV population. The incidence of CVD overall in HIV is relatively low, but it is approximately 1.5-2-fold higher than that seen in age-matched HIV-uninfected individuals. Multiple factors are believed to explain this excess in risk such as overrepresentation of traditional cardiovascular risk factors (particularly smoking), toxicities associated with cumulative exposure to some antiretroviral agents, together with persistent chronic inflammation, and immune activation associated with HIV infection. Tools are available to calculate an individual's predicted risk of CVD and should be incorporated in the regular follow-up of HIV-infected patients. Targeted interventions to reduce this risk must be recommended, including life-style changes and medical interventions that might include changes in antiretroviral therapy.

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“…1,2 However, successful cART and effective control of HIV-1 replication do not always correlate with CD4 + T-cell count recovery. [3][4][5][6][7] This inadequate immunological recovery increases AIDS and non-AIDS-related morbidity and mortality. [1][2][3]7,8 One of the reasons that could limit CD4 + T-cell recovery could be a dysfunctional immune system characterized by cells with shorter telomeres, an index of cellular aging.…”

Section: Introductionmentioning

confidence: 98%