DIAGNOSIS AND TREATMENT OF AIDS-RELATED OCULAR DISEASE

该项目的目标是开发诊断和治疗获得性免疫缺陷综合征(艾滋病)眼部并发症的改进方法。该项目包括评估艾滋病相关眼病患者的新诊断和治疗方法的临床试验，以及对巨细胞病毒(CMV)视网膜炎患者的自然病史研究。巨细胞病毒(CMV)视网膜炎是艾滋病患者最常见的眼内感染，往往发生在CD4+细胞计数降至每微升低于50个细胞后。虽然使用更昔洛韦、磷甲酸钠或西多福韦的抗CMV治疗最初会导致视网膜炎失活，但由于对复制病毒的控制不充分，尽管继续治疗，几乎所有患者的疾病都会发展。最近的研究表明，使用由蛋白酶抑制剂和核苷类似物组成的高效联合抗逆转录病毒疗法，可以降低人类免疫缺陷病毒(HIV)的载量，增加CD4+计数。我们一直在研究联合抗HIV治疗对CMV视网膜炎免疫恢复的影响。我们之前报告了4例艾滋病患者，并发现高效联合抗逆转录病毒化疗引起的CD4+细胞计数增加，尽管没有特效的抗CMV药物，但他们的CMV视网膜炎持续无效。在过去的一年里，我们报告了8名患者，在停用维持性抗CMV药物后，CD4+细胞计数超过每微升100个细胞，并出现稳定的CMV视网膜炎。NEI目前正在进行一项前瞻性临床试验，以确定稳定性视网膜炎患者是否可以安全地停止使用维持性抗CMV药物。这项研究还旨在确定停止抗CMV治疗是否会增加HIV载量或导致眼内炎症。初步试验阶段的征聘工作已经完成，应在明年对数据进行分析。在试验的第二阶段，我们将继续停止对稳定性视网膜炎患者使用维持性抗CMV药物。此外，我们将进行白细胞透析术，并检查淋巴细胞的体外研究是否可以预测视网膜炎的复发。作为这项研究的一部分，异源双链分析将分析T细胞受体谱系。最后，许多治疗艾滋病的药物都有眼部副作用。我们首次报道了抗逆转录病毒药物二磷酸核苷引起视网膜毒性。我们一直在使用眼电图仪(EOG)，它测量来自视网膜的电信号，以监测二磷酸核苷对艾滋病毒感染儿童视网膜的潜在毒性作用。目前，我们正在监测艾滋病毒相关疾病患者服用氟化二磷酸核苷类似物的第一阶段方案中的儿童。其他有眼部副作用的药物包括利福汀和西多福韦。我们继续对成人和儿童艾滋病患者进行定期眼科检查，以监测患者在机会性感染之外的眼部副作用的发展情况。-艾滋病、艾滋病毒、巨细胞病毒视网膜炎、眼部毒性--人类受试者

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 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 per microliter 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 heteroduplex 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. - AIDS, HIV, cytomegalovirus retinitis, ocular toxicity - Human Subjects