The goal of this project is to develop improved methods for diagnosing and treating the ocular complications of the acquired immunodeficiency syndrome (AIDS). This project encompasses clinical trials evaluating new diagnostic and therapeutic approaches for patients with AIDS-related eye disorders, as well as natural history studies of patients with Cytomegalovirus (CMV) retinitis. Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with AIDS and tends to occur after CD4+ cell counts decrease to less than 50 cells per microliter. Although anti-CMV therapy with ganciclovir, foscarnet sodium, or cidofovir initially leads to inactivation of the retinitis, the disease progresses in almost all patients despite continued therapy because of inadequate control of the replicating virus. Recent case reports have shown that treatment with highly active antiretroviral therapy, commonly consisting of protease inhibitors and nucleoside analogs, has led to decreased human immunodeficiency virus (HIV) loads and increased CD4+ counts. The NEI has been conducting a prospective clinical trial to determine whether maintenance anti-CMV medications can be safely discontinued in patients with stable CMV retinitis. The study was also designed to determine whether discontinuing anti-CMV therapy will increase HIV load or cause intraocular inflammation. Recruitment of the initial phase of the trial has been completed. To date, no patient has experienced CMV progression or any other study endpoint and these results were published. Unexpectedly, the majority of the patients in this trial were observed to have ocular inflammation related to their immune recovery, a phenomenon termed immune recovery uveitis. The details of this syndrome observed in patients participating in this trial were recently published. The protocol will continue to examine the durability of highly active antiretroviral therapy in maintaining increased CD4+ counts and inactive CMV retinitis.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000317-06
Application #
6681746
Study Section
(LI)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2002
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Sklar, Peter A; Agyemang, Amma F; Monastra, Rachelle et al. (2004) Five-year follow-up of a cohort of profoundly immunosuppressed patients discontinuing therapy for cytomegalovirus retinitis. AIDS 18:567-9
Davis, Jennifer L; Gilger, Brian C; Robinson, Michael R (2004) Novel approaches to ocular drug delivery. Curr Opin Mol Ther 6:195-205
Lee, Susan S; Robinson, Michael R; Morris, John C et al. (2004) Conjunctival involvement with T-cell prolymphocytic leukemia: report of a case and review of the literature. Surv Ophthalmol 49:525-36
Robinson, Michael R; Csaky, Karl G; Lee, Susan S et al. (2004) Fibrovascular changes misdiagnosed as cytomegalovirus retinitis reactivation in a patient with immune recovery. Clin Infect Dis 38:139-41
Rodriguez-Coleman, Hanna; Yuan, Peng; Kim, Hyuncheol et al. (2004) Intravitreal injection of triamcinolone for diffuse macular edema. Arch Ophthalmol 122:1085-6; author reply 1086-8
Srivastava, Sunil; Taylor, Perdita; Wood, Lauren V et al. (2004) Post-surgical scleritis associated with the ganciclovir implant. Ophthalmic Surg Lasers Imaging 35:254-5
Wright, Mary E; Suzman, Daniel L; Csaky, Karl G et al. (2003) Extensive retinal neovascularization as a late finding in human immunodeficiency virus-infected patients with immune recovery uveitis. Clin Infect Dis 36:1063-6