Schrier RD, Song MK, Karavellas M, Freeman WR, Durand D, Torriani FJ; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 52 (abstract no. 31).
Univ of California, San Diego.
Background: Successful control of HIV has literally provided a new lease on life for many infected patients who developed CMV retinitis prior to initiation of HAART. However, immune reconstitution in over half of treated retinitis patients has been accompanied at our institution by a debilitating ocular inflammation and macular edema termed immune recovery uveitis (IRU). Methods: To investigate the etiology of this syndrome, clinical characteristics and systemic and local ocular immune responses were examined. Results: Clinically, patients who developed IRU (N = 15) tended to have a shorter course of anti-CMV maintenance therapy following the initial episode of retinitis than those who had not developed IRU (18.7 versus 36.2 months). Also, IRU patients received HAART more rapidly after the initial CMV retinitis diagnosis than non IRU patients (5.0 versus 12.3 months). IRU patients were slightly more likely (40% versus 25%) to have been treated with intraocular cidofovir injections than those who did not develop IRU. With respect to immune responses, systemic T-cell lymphoproliferation responses to CMV were significantly higher in patients with IRU than in non IRU patients (p = 0.02). However, single cell cytokine expression of interferon gamma or TNF by peripheral T-cells cultured with CMV was not elevated in IRU patients compared to non IRU patients. Within inflamed eyes, (aqueous and vitreous humor) symptoms of IRU correlated with higher levels of IL-12 (p = 0.05) compared to control eyes or eyes with active CMV retinitis, which had higher levels of IL-6 (p = 0.04). Levels of interferon gamma, TNF, and beta chemokines were not significantly different in retinitis and uveitis eyes. Cellular infiltrates in epiretinal membranes removed from IRU patients were primarily mononuclear T-cells (CD3+) with few monocytes or B-cells. Conclusions: The development of IRU only in eyes with prior CMV retinitis and in patients who received a relatively shorter course of anti CMV therapy implies that remaining CMV antigen or protein expression may trigger the syndrome, even though CMV DNA has been not been detected by PCR of ocular fluids during active IRU. Detection of a T-cell infiltrate and T-cell produced cytokine (IL-12) in IRU afflicted eyes suggests an antigen specific immune etiology.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Antiretroviral Therapy, Highly Active
- CD4-Positive T-Lymphocytes
- Cytomegalovirus Retinitis
- Cytosine
- Epiretinal Membrane
- HIV Infections
- Humans
- Phosphonic Acids
- T-Lymphocytes
- Uveitis
- Vitreous Body
- cidofovir
Other ID:
UI: 102243810
From Meeting Abstracts