Immune reconstitution inflammatory syndrome in HIV

Lipman, Marc; Breen, Ronan

doi:10.1097/01.qco.0000200543.80712.01

Cited by 139 publications

(105 citation statements)

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“…This receptor is an important transcription factor in lipid and cytokine metabolism and provides an antiinflammatory effect in the lungs and airways; therefore, decreased levels might contribute to development of airway obstruction after ARV initiation (38)(39)(40)(41). Abnormal immune restoration similar to that in the immune reconstitution inflammatory syndrome may result in response to occult infection or colonization in the respiratory tract and lead to airway obstruction (12,42,43). Individuals with HIV infection are noted to have organ-specific autoimmune complications with ARV therapy, and another possibility is that autoimmunity may occur in response to lung antigens after ARV treatment (43)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Function Abnormalities in HIV-Infected Patients during the Current Antiretroviral Therapy Era

Gingo¹,

George²,

Kessinger³

et al. 2010

Am J Respir Crit Care Med

187

232

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Rationale: Before the introduction of combination antiretroviral (ARV) therapy, patients infected with HIV had an increased prevalence of respiratory symptoms and lung function abnormalities. The prevalence and exact phenotype of pulmonary abnormalities in the current era are unknown. In addition, these abnormalities may be underdiagnosed. Objectives: Our objective was to determine the current burden of respiratory symptoms, pulmonary function abnormalities, and associated risk factors in individuals infected with HIV. Methods: Cross-sectional analysis of 167 participants infected with HIV who underwent pulmonary function testing. Measurements and Main Results: Respiratory symptoms were present in 47.3% of participants and associated with intravenous drug use (odds ratio [OR] 3.64; 95% confidence interval [CI], 1.32-10.046; P 5 0.01). Only 15% had previous pulmonary testing. Pulmonary function abnormalities were common with 64.1% of participants having diffusion impairment and 21% having irreversible airway obstruction. Diffusion impairment was independently associated with ever smoking (OR 2.46; 95% CI, 1.16-5.21; P 5 0.02) and Pneumocystis pneumonia prophylaxis (OR 2.94; 95% CI, 1.10-7.86; P 5 0.01), whereas irreversible airway obstruction was independently associated with pack-years smoked (OR 1.03 per pack-year; 95% CI, 1.01-1.05; P , 0.01), intravenous drug use (OR 2.87; 95% CI, 1.15-7.09; P 5 0.02), and the use of ARV therapy (OR 6.22; 95% CI, 1.19-32.43; P 5 0.03). Conclusions: Respiratory symptoms and pulmonary function abnormalities remain common in individuals infected with HIV. Smoking and intravenous drug use are still important risk factors for pulmonary abnormalities, but ARV may be a novel risk factor for irreversible airway obstruction. Obstructive lung disease is likely underdiagnosed in this population.Keywords: HIV; respiratory function tests; smoking; antiretroviral therapy, highly active; AIDS Pulmonary complications have been a major cause of morbidity and mortality in patients with HIV infection (1, 2). With the development of combination antiretroviral (ARV) therapy and improvements in prophylaxis for Pneumocystis pneumonia (PCP) and other opportunistic infections, the incidence of infectious pulmonary complications has decreased drastically in patients with HIV infection (1, 3, 4). Changes in noninfectious pulmonary complications, such as chronic obstructive pulmonary disease (COPD) and asthma, are less clear, and these diseases may actually be increasing. Studies before the introduction of combination ARV demonstrated that persons with HIV infection had a higher prevalence of impaired diffusing capacity for carbon monoxide (DL CO ), increased emphysema, accelerated airway obstruction and small airways disease, and more frequent respiratory symptoms than subjects not infected with HIV (2, 5-8).Limited data exist regarding the extent and types of pulmonary function abnormalities in the current era. In one recent study, veterans with HIV infection had an increased risk of COPD compared wi...

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Section: Discussionmentioning

confidence: 99%

Pulmonary Function Abnormalities in HIV-Infected Patients during the Current Antiretroviral Therapy Era

Gingo¹,

George²,

Kessinger³

et al. 2010

Am J Respir Crit Care Med

187

232

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“…Dilution of T reg cell populations caused by antigen-nonspecific homeostatic proliferation could further bias the T cell compartment toward selfreactivity. In HIV patients, repopulation of the T cell pool has been associated with severe and diffuse tissue inflammation, a condition named immune reconstitution inflammatory syndrome (42). Obviously, repertoire diversity maintains dilution of individual T cells and may well serve as a tolerance mecha-Flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

Deficiency of the DNA repair enzyme ATM in rheumatoid arthritis

Shao¹,

Fujii²,

Colmegna³

et al. 2009

J Cell Biol

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In rheumatoid arthritis (RA), dysfunctional T cells sustain chronic inflammatory immune responses in the synovium. Even unprimed T cells are under excessive replication pressure, suggesting an intrinsic defect in T cell regeneration. In naive CD4 CD45RA + T cells from RA patients, DNA damage load and apoptosis rates were markedly higher than in controls; repair of radiation-induced DNA breaks was blunted and delayed. DNA damage was highest in newly diagnosed untreated patients. RA T cells failed to produce sufficient transcripts and protein of the DNA repair kinase ataxia telangiectasia (AT) mutated (ATM). NBS1, RAD50, MRE11, and p53 were also repressed. ATM knockdown mimicked the biological effects characteristic for RA T cells. Conversely, ATM overexpression reconstituted DNA repair capabilities, response patterns to genotoxic stress, and production of MRE11 complex components and rescued RA T cells from apoptotic death. In conclusion, ATM deficiency in RA disrupts DNA repair and renders T cells sensitive to apoptosis. Apoptotic attrition of naive T cells imposes lymphopenia-induced proliferation, leading to premature immunosenescence and an autoimmune-biased T cell repertoire. Restoration of DNA repair mechanisms emerges as an important therapeutic target in RA.

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“…Nuestros resultados son semejantes a los observados por otros investigadores en países en desarrollo donde la mayoría de pacientes infectados con el VIH que acuden a los hospitales son varones jóvenes en estadíos avanzados de la enfermedad (6,8,9), ésto último un factor de riesgo conocido para toxicidad medicamentosa y para el síndrome de reconstitución inmune (2,10,11). Basados en la norma técnica (2), el 66% de nuestra población inició la TARGA por encontrarse sintomáticos y el tercio restante por valores de CD4 o carga viral.…”

Section: Discussionunclassified

Efecto de la terapia antiretroviral de gran actividad (TARGA) en pacientes enrolados en un hospital público en Lima-Perú.

Zárate¹,

Koster²,

Quilca³

et al. 2012

Rev Med Hered

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RESUMEN.Introducción: En mayo del 2004, el Ministerio de Salud (MINSA) en colaboración con el Fondo Global de lucha contra el SIDA, la tuberculosis y la malaria implementó el programa nacional (PN) para brindar terapia antiretroviral en forma gratuita a todos los pacientes infectados con el VIH con indicación de tratamiento de acuerdo a la guía del PN. Objetivos: Describir las características pre-tratamiento antiretroviral, respuesta a la terapia antiretroviral de gran actividad (TARGA), toxicidad y tasa de mortalidad de la población de pacientes que iniciaron TARGA a través del PN en un hospital general. Material y Métodos: Revisamos las historias clínicas, fichas médicas, resultados de laboratorio y tarjetas de TARGA de todos los pacientes enrolados en el PN en el Hospital Nacional Cayetano Heredia (HNCH) y describimos las características pre-tratamiento antiretroviral, respuesta a la TARGA, toxicidad y tasa de mortalidad. Los pacientes seleccionados para este estudio fueron sujetos infectados con el VIH que: (i) tenían 18 años o más; (ii) iniciaron TARGA en el PN entre mayo 2004 y abril 2006; y (iii) no habían recibido terapia antiretroviral anteriormente (naïve). Se consideró como éxito virológico a la presencia de por lo menos un valor de carga viral indetectable (VIH-1 ARN < 400 copias/mL) entre los 3-6 meses posteriores al inicio de la TARGA. Resultados: Se incluyeron en el estudio a 453 pacientes: 68% fueron varones, la edad promedio fue 35,7 ± 9,5 años y el peso fue 55,6 ± 10,8 Kg. El valor medio de CD4 pre-tratamiento fue 98 células/mm 3 y el de carga viral fue 278 438 VIH-1 ARN copias/mL. Descontinuaron el tratamiento 84 pacientes (22 abandonaron, 59 fallecieron y 3 fueron transferidos a otra institución). Aquellos que continuaron fueron seguidos en promedio 337 días; el 38% (142/369) interrumpió temporalmente la TARGA, principalmente debido a toxicidad medicamentosa (82%). Se obtuvo éxito virológico en 85% de los pacientes. La mortalidad fue 13% y el 74% de las muertes ocurrió antes de los 3 meses de tratamiento. Conclusión: A pesar de una elevada frecuencia de interrupción del tratamiento, nuestros resultados muestran que la respuesta a las medicinas distribuidas por el PN es comparable a la reportada por programas de otros países. Es necesario realizar más estudios que evalúen la respuesta al tratamiento antiretroviral a largo plazo en el Perú. (Rev Med

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Immune reconstitution inflammatory syndrome in HIV

Abstract: IRIS is common and will become more so as HAART is rolled out worldwide. Clear clinical definitions are required to avoid its over-diagnosis due to misclassification of other conditions.

Cited by 139 publications

References 50 publications

Pulmonary Function Abnormalities in HIV-Infected Patients during the Current Antiretroviral Therapy Era

Pulmonary Function Abnormalities in HIV-Infected Patients during the Current Antiretroviral Therapy Era

Deficiency of the DNA repair enzyme ATM in rheumatoid arthritis

Efecto de la terapia antiretroviral de gran actividad (TARGA) en pacientes enrolados en un hospital público en Lima-Perú.

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