Immune reconstitution

Aiuti A, Vai S, MorteUaro A, Casorati G, Ficara F, Andolfi G, Ferrari G, Tabucchi A, Carlucci F, Ochs HD, Notarangelo LD, Roncarolo MG, Bordignon C (2002b) Immune reconstitution in ADA-SCID after PBL gene therapy and discontinuation of enzyme replacement. Nat Med 8 423 25... 

Immune reconstitution inflammatory syndrome AIDS on HAART Acute or subacute Worsening or new neurological symptoms in the setting of immune reconstitution Immune mediated... 

HAART has been associated with numerous neurological immune reconstitution illnesses, which generally occur within 6 months after its introduction and are thought to constitute an aberrant immune response to opportunistic pathogens (Shelburne and Hamill 2003 Riedel et al. 2006 Venkataramana et al. 2006). 

Overall, it appears that immune reconstitution is only rarely associated with peripheral neuropathies in HIV-infected individuals. 

Makela and colleagues described the occurrence of a probable recurrent GBS six weeks after initiation of HAART and after a striking increase in CD4 cell count in an HfV-infected individual (Makela et al. 2002). Piliero and colleagues described an HIV-infected patient with AIDS who developed GBS, 26 days after initiation of a 6-drug HAART regimen, which had led to an impressive immune reconstitution (a rise in CD4 cell count from 31 to 602 cells/pL) (Piliero et al. 2003). Puthanakit and colleagues identified a child who developed GBS, 3 weeks after initiation of efavirenz-based HAART in a cohort of HIV-infected Thai children (Puthanakit et al. 2006). 

Makela P, Howe L et al (2002) Recurrent GuiUain-Barre syndrome as a complication of immune reconstitution in HIV. J Infect 44(1) 47 9... 

Piliero PJ, Fish DG et al (2003) Guillain-Barre syndrome associated with immune reconstitution. Clin Infect Dis 36(9) el 11-el 14... 

Puthanakit T, Oberdorfer P et al (2006) Immune reconstitution syndrome after highly active antiretroviral therapy in human immunodeficiency virus-infected thai children. Pediatr Infect Dis J... 

Riedel DJ, Pardo CA et al (2006) Therapy Insight CNS manifestations of HIV-associated immune reconstitution inflammatory syndrome. Nat Clin Pract Neurol 2(10) 557-565 Rizzuto N, Cavallaro Tet al (1995) Role of HIV in the pathogenesis of distal symmetrical peripheral neuropathy. Acta Neuropathol 90(3) 244-250... 

Shelburne SA III, HamiU RJ (2003) The immune reconstitution inflammatory syndrome. AIDS Rev 5(2) 67-79... 

Venkataramana A, Pardo CA et al (2006) Immune reconstitution inflammatory syndrome in the CNS of HIV-infected patients. Neurology 67(3) 383-388 Verma A (2001) Epidemiology and clinical featmes of HIV-1 associated neuropathies. J Peripher Nerv Syst 6(1) 8-13... 

Immune reconstitution syndrome A syndrome characterized by fever and worsening of clinical symptoms of opportunistic infections or new symptoms occurring within weeks after starting antiretroviral therapy. This has been described for mycobacterial infections (Mycobacterium avium complex and Mycobacterium tuberculosis), Pneumocystis proved pneumonia, toxoplasmosis,... 

ADA deficiency is most commonly associated with these mutations of the ADA structural gene that result in either unstable or inactive enzyme protein. Immune reconstitution would be achieved by enzyme replacement therapy with polyethylene glycol-modified bovine ADA (PEG-AD A), alone or in combination with gene therapy (H3). 

Small, T.N. et al., Comparison of immune reconstitution after unrelated and related T-cell-depleted bone marrow transplantation effect of patient age and donor leukocyte infusions,... 

Singh N, Perfect JR Immune reconstitution syndrome associated with opportunistic mycoses. Lancet Infect Dis 2007 7 395-401. 

Zhan H, Sinclair J, Adams S, et al Immune reconstitution and recovery of FoxP3 (forkhead box P3)-expressing T cells after transplantation for IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-hnked) syndrome. Pediatrics 2008 121 e998-el002. 

Immune reconstitution syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including tipranavir. 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

The immune reconstitution inflammatory syndrome (IRIS) has emerged as an important clinical issue in the management of HIV-infected individuals on ART. IRIS is characterized by paradoxical worsening of symptoms and signs of inflammation in individual on ART (usually 2-6 months after ART initiation) related to the immunological gains of ART. 

The clinical trial was later expanded to include two more ADA-SCID patients, and included treatment follow-ups at 10, 15, 29 and 35 months after therapy [515038], [516040], [643376]. The results from the most recent follow-up matched those found in the initial study of two patients. PBL counts in all patients were 2.5 x 9 , 0.2 x 109/1, 1.3 x 109/1 and 0.7 x 109/1 for Ptl, Pt2, Pt3 and Pt4, respectively. The overall level of myeloid engraftment and the speed and degree of immune reconstitution correlated with both the dose of infused transduced CD34+ cells and the degree of myelosuppression [643376]. 

Not all patients experiencing immune reconstitution may discontinue CMV retinitis therapy due to a lack of restored CMV-spectfic T lymphocyte defenses, despite increases in the overall CD4-I- cell count. Additionally, patients who have experienced CD4-I- cell increases but later discontinue HAART run the risk of experiencing recurrence of CMV retinitis, if the CD4-I- count drops... 

The introduction of potent, combination ART and the use of prophylactic medications against opportunistic infections had a significant impact on the natural history of HIV (Palella et al., 1998). Morbidity and mortality have declined dramatically, and HIV has evolved from a fatal disease to a chronic, manageable condition. Immune reconstitution achieved with ART can be potent and sustained enough that primary and secondary prophylaxis against opportunistic infections can be safely discontinued (www.aidsinfo.nih.gov). 

In a study of compassionate use of intravenous cidofovir in AIDS patients with CMV retinitis, iritis developed in 21 of 51 individuals (7). The appearance of this inflammatory process did not fit the characteristics of the vitritis associated with immune reconstitution, or with HIV-induced vitritis. The high rate in this cohort (compared with a 5-7% incidence in randomized trials) was associated with severe CMV retinitis, and the authors suggested that breakdown of the blood-ocular barrier in these patients may promote higher intraocular concentrations of cidofovir and thus enhance local toxicity. Previous correlations of prior use of HIV protease inhibitors with iritis were not confirmed in this study, although patients with iritis had better immunological and virological status than those without the disease. 

Lawn SD, Wood C, Lockwood DN. Borderline tuberculoid leprosy an immune reconstitution phenomenon in a human immunodeficiency virus-infected person. Clin Infect Dis 2003 36(l) e5-6. 

Steingrimsdottir H. Gruber A. Bjorkholm M. et al. Immune reconstitution after autologous hematopoietic stem cell transplantation in relation to underlying disease, type of high-dose therapy and infectious complications. Haematologica 2000,85,832-838. 

---