Immune dysfunction and immune restoration disease in HIV patients given highly active antiretroviral therapy

Price, Patricia; Mathiot, Nadine D.; Krueger, R.; Stone, Shelley F.; Keane, N.M.; French, Martyn A.

doi:10.1016/s1386-6532(01)00200-1

Cited by 103 publications

(65 citation statements)

References 45 publications

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“…However, an acquired defect associated with tolerance induction may predispose some individuals to higher rates of autoimmune disease (12,16,(28)(29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of thyroid function and autoimmunity in HIV-infected women

Carvalho

Teixeira

Panico

et al. 2013

Arq Bras Endocrinol Metab

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Autoimmune thyroid diseases (AITD) are the main causes of thyroid dysfunction and the most common autoimmune diseases in the world. An association between AITD and infections with the human immunodeficiency virus (HIV), in combination with the effects of highly active antiretroviral therapy (HAART), has been suggested by several research groups. The aim of the present study was to evaluate the frequency of thyroid dysfunction and AITD in women > 35 years of age infected with HIV, and to identify factors associated with the emergence of these thyroid abnormalities. HIV-infected women (n = 153) selected from the infectious disease outpatient clinic at a University Hospital in Rio de Janeiro were characterized based on their circulating CD4 + lymphocytes levels, viral loads, serum TSH levels, and the presence of FT4 and anti-thyroperoxidase antibodies (TPO-Ab). A total of 129 participants were on HAART and 24 were not. The frequency of thyroid disorders was 7.8% (12/153 patients) and all were on HAART at the time of diagnosis, yielding a prevalence of 9.3% in patients receiving HAART compared with 0% in patients not on HAART. AITD, hyper, and hypothyroidism were detected in 4.6%, 3.1%, and 4.1% of HAART patients. It was not detected any thyroid dysfunction or autoimmunity in HIVinfected women not on HAART. This study demonstrated an association between HAART and the development of AITD. In addition AITD only developed in HAART patients also presenting with undetectable viral loads and slightly elevated CD4 + T cell counts. Arq Bras Endocrinol Metab. 2013;57(6):450-6Keywords Autoimmune thyroid disease; thyroid dysfunction; hypothyroidism; hyperthyroidism; HIV; anti-retroviral therapy; immunity RESUMO Doenças tiroidianas autoimunes (DTAI) são a maior causa de disfunção tiroidiana e são as doenças autoimunes mais comuns no mundo. A associação entre DTAI e infecções com o vírus da imunodeficiência humana (HIV), em combinação com a terapia antirretroviral altamente ativa (HAART), foi sugerida por vários grupos de pesquisadores. O objetivo do presente estudo foi avaliar a frequência de disfunção tiroidiana e DTAI em mulheres com mais 35 anos de idade infectadas com o HIV e identificar fatores associados com a emergência dessas anormalidades tiroidianas. As mulheres infectadas com HIV (n = 153), selecionadas do ambulatório de doenças infecciosas de um hospital universitário do Rio de Janeiro, foram caracterizadas com base no nível de linfócitos CD4 + circulantes, carga viral, níveis de TSH sérico e presença de anticorpos FT4 e antitiroperoxidase (TPO-Ab). Um total de 129 participantes se tratava com HAART e 24 não. A frequência de desordens da tiroide foi 7,8% (12/153 pacientes) e todas estavam em tratamento com HAART no momento do diagnóstico, levando a uma prevalência 9,3% em pacientes recebendo HAART, em comparação com 0% em pacientes não tratadas com HAART. DTAI, hipertireoidismo e hipotireoidismo foram detectados em 4,6%, 3,1% e 4,1% das pacientes tratadas com HAART. Não foram detectadas disfunção tiroidiana ...

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“…However, an acquired defect associated with tolerance induction may predispose some individuals to higher rates of autoimmune disease (12,16,(28)(29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of thyroid function and autoimmunity in HIV-infected women

Carvalho

Teixeira

Panico

et al. 2013

Arq Bras Endocrinol Metab

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“…Although evidence is limited, carriage of specific HLA alleles suggest associations with the development of IRIS and specific pathogens [39]. Increased levels of interleukin-6 (IL-6) in IRIS patients may explain the exuberant Th1 response to mycobacterial antigens in subjects with clinical IRIS [9,40].…”

Section: Pathogenesis Of Irismentioning

confidence: 99%

Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options

et al. 2007

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The immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients initiating antiretroviral therapy (ART) results from restored immunity to specific infectious or non-infectious antigens. A paradoxical clinical worsening of a known condition or the appearance of a new condition after initiating therapy characterizes the syndrome. Potential mechanisms for the syndrome include a partial recovery of the immune system or exuberant host immunological responses to antigenic stimuli. The overall incidence of IRIS is unknown, but is dependent on the population studied and its underlying opportunistic infectious burden. The infectious pathogens most frequently implicated in the syndrome are mycobacteria, varicella zoster, herpesviruses, and cytomegalovirus (CMV). No single treatment option exists and depends on the underlying infectious agent and its clinical presentation. Prospective cohort studies addressing the optimal screening and treatment of opportunistic infections in patients eligible for ART are currently being conducted. These studies will provide evidence for the development of treatment guidelines in order to reduce the burden of IRIS. We review the available literature on the pathogenesis and epidemiology of IRIS, and present treatment options for the more common infectious manifestations of this diverse syndrome and for manifestations associated with a high morbidity.

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“…The hypothesis that mechanisms other than active viral replication are involved in monocyte dysfunction is further reenforced by the evidence that the blocking of HIV-1 replication is not linked to their functional recovery. 2 Different HIV-1 proteins are known to promote an activated immunologic environment, 3,4 and a direct influence of HIV-1 viral gene products in triggering monocyte activation and migration has been long postulated. The HIV-1 matrix protein p17 is continuously released in the extracellular space from HIV-1-infected cells.…”

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confidence: 99%

HIV-1 matrix protein p17 binds to the IL-8 receptor CXCR1 and shows IL-8–like chemokine activity on monocytes through Rho/ROCK activation

Giagulli¹,

Magiera²,

Bugatti

et al. 2012

Blood

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AbstractExogenous HIV-1 matrix protein p17 was found to deregulate biologic activities of many different immune cells that are directly or indirectly involved in AIDS pathogenesis after binding to unknown cellular receptor(s). In particular, p17 was found to induce a functional program in monocytes related to activation and inflammation. In the present study, we demonstrate that CXCR1 is the receptor molecule responsible for p17 chemokine–like activity on monocytes. After CXCR1 binding, p17 was capable of triggering rapid adhesion and chemotaxis of monocytes through a pathway that involved Rho/ROCK. Moreover, CXCR1-silenced primary monocytes lost responsiveness to p17 chemoattraction, whereas CXCR1-transfected Jurkat cells acquired responsiveness. Surface plasmon resonance studies confirmed the capacity of p17 to bind CXCR1 and showed that the p17/CXCR1 interaction occurred with a low affinity compared with that measured for IL-8, the physiologic CXCR1 ligand. In all of its activities, p17 mimicked IL-8, the natural high-affinity ligand of CXCR1. Recent studies have highlighted the role of IL-8 and CXCR1 in HIV-1 replication and AIDS pathogenesis. Our findings herein call for an exploration of the therapeutic potential of blocking the p17/IL-8/CXCR1 axis in HIV-1 infection.

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Immune dysfunction and immune restoration disease in HIV patients given highly active antiretroviral therapy

Cited by 103 publications

References 45 publications

Evaluation of thyroid function and autoimmunity in HIV-infected women

Evaluation of thyroid function and autoimmunity in HIV-infected women

Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options

HIV-1 matrix protein p17 binds to the IL-8 receptor CXCR1 and shows IL-8–like chemokine activity on monocytes through Rho/ROCK activation

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