DIAGNOSIS AND TREATMENT OF AIDS-RELATED OCULAR DISEASE

该项目的目标是开发改进的 用于诊断和治疗眼并发症的方法 获得性免疫缺陷综合症（艾滋病）。这个项目 包括评估新诊断和 艾滋病相关眼病的治疗方法 疾病，以及患者的自然史研究， 巨细胞病毒（CMV）视网膜炎。 巨细胞病毒（CMV） 视网膜炎是最常见的眼内感染的患者， 艾滋病后往往发生CD 4+细胞计数减少到更少 超过50个细胞/？L.尽管使用更昔洛韦进行抗CMV治疗， 膦甲酸钠或西多福韦最初导致 视网膜炎，疾病进展，几乎所有的患者，尽管 由于对复制的控制不足， 病毒最近的研究表明，高活性的 由蛋白酶抑制剂组成的联合抗逆转录病毒疗法 和核苷类似物，导致人类 免疫缺陷病毒（HIV）载量和CD 4+计数增加。 我们一直在研究免疫恢复的效果 联合抗HIV治疗CMV视网膜炎后。我们 此前报道了四名艾滋病患者， 高效联合抗逆转录病毒诱导的细胞计数 化疗后持续无活动性CMV视网膜炎， 没有特定的抗CMV药物。去年，我们 报道了8例患者的CD 4+细胞计数超过100个细胞/？L 维持抗CMV药物治疗后稳定的CMV视网膜炎 已经停止了。NEI现在正在进行一项前瞻性的 临床试验，以确定是否维持抗CMV 在稳定的患者中可以安全地停用药物。 视网膜炎该研究还旨在确定是否 停止抗CMV治疗将增加HIV载量或导致 眼内炎症试验初始阶段的招募 已经完成，数据应在下一个 年在第二阶段的试验中，我们将继续 在以下患者中停止维持抗CMV药物治疗 稳定性视网膜炎此外，我们将进行白细胞分离术， 检查淋巴细胞的体外研究是否可以预测 视网膜炎复发。作为本研究的一部分， 将分析T细胞受体库。 最后，许多 用于治疗艾滋病的药物具有眼部副作用。我们首先 报告说，抗逆转录病毒药物去羟肌苷引起视网膜病变， 毒性我们一直在使用眼电图（EOG）， 测量来自视网膜的电信号， 去羟肌苷对HIV感染者视网膜的潜在毒性作用 孩子目前，我们正在监测儿童在第一阶段， 的氟化类似物的给药方案 去羟肌苷用于HIV相关疾病患者。其他 具有眼部副作用的药物包括利福韦和西多福韦。 我们继续对一个队列进行定期眼科检查， 成人和儿童艾滋病患者监测病人， 除了机会性的眼部副作用外， 感染.

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/?l. 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 studies have shown that treatment with highly active combination antiretroviral therapy, consisting of protease inhibitors and nucleoside analogs, has led to decreased human immunodeficiency virus (HIV) loads and increased CD4+ counts. We have been investigating the effect of immune restoration following combination anti-HIV therapy on CMV retinitis. We previously reported four patients with AIDS and increases in CD4+ cell counts induced by highly active combination antiretroviral chemotherapy who had persistently inactive CMV retinitis despite no specific anti-CMV medications. During the last year, we reported eight patients with CD4+ cell counts above 100 cells/?l and stable CMV retinitis after maintenance anti-CMV medications were discontinued. The NEI is now conducting a prospective clinical trial to determine whether maintenance anti-CMV medications can be safely discontinued in patients with stable retinitis. The study is 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, and data should be analyzed during the next year. In the second phase of the trial, we will continue to discontinue maintenance anti-CMV medications in patients with stable retinitis. In addition, we will perform leukopharesis and examine whether in vitro studies on lymphocytes can predict recurrence of retinitis. As part of this study, a heterodpulex assay will analyze the T cell receptor repertoire. Finally, many medications used to treat AIDS have ocular side effects. We first reported that the antiretroviral agent didanosine caused retinal toxicity. We have been using the electro-oculogram (EOG), which measures the electrical signal from the retina, to monitor the potentially toxic effect of didanosine on the retina in HIV-infected children. Currently, we are monitoring children in a Phase I protocol for the administration of a fluorinated analogue of didanosine in patients with HIV-associated diseases. Other medications with ocular side effects include rifabutin and cidofovir. We continue to perform periodic eye examinations on a cohort of both adults and children with AIDS to monitor patients for the development of ocular side effects in addition to opportunistic infections.