DIAGNOSIS AND TREATMENT OF AIDS-RELATED OCULAR DISEASE

该项目的目标是发展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疾患者的新诊断和治疗方法的临床试验，以及巨细胞病毒（CMV）视网膜炎患者的自然史研究。巨细胞病毒（CMV）视网膜炎是艾滋病患者中最常见的眼内感染，通常发生在CD4+细胞计数下降到每微升低于50个细胞后。虽然用更昔洛韦、膦酸钠或西多福韦进行抗巨细胞病毒治疗最初会导致视网膜炎失活，但由于对复制病毒控制不足，尽管继续治疗，但几乎所有患者的疾病都会进展。最近的研究表明，采用由蛋白酶抑制剂和核苷类似物组成的高活性抗逆转录病毒联合疗法治疗，可导致人类免疫缺陷病毒（HIV）载量下降和CD4+计数增加。我们一直在研究联合抗hiv治疗后免疫恢复对巨细胞病毒性视网膜炎的影响。我们之前报道了4例艾滋病患者，尽管没有特异性的抗巨细胞病毒药物，但高活性联合抗逆转录病毒化疗诱导CD4+细胞计数增加，这些患者患有持续不活跃的巨细胞病毒视网膜炎。在过去的一年中，我们报道了8例CD4+细胞计数高于每微升100个细胞的患者，在停止抗CMV药物治疗后，出现了稳定的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用维护性抗巨细胞病毒药物。该研究还旨在确定停止抗巨细胞病毒治疗是否会增加HIV载量或引起眼内炎症。试验初期阶段的招募工作已经完成，明年将对数据进行分析。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巨细胞病毒药物。此外，我们将进行白细胞电泳，并检查体外淋巴细胞研究是否可以预测视网膜炎的复发。作为本研究的一部分，异双工试验将分析T细胞受体库。最后，许多用于治疗艾滋病的药物都有眼部副作用。我们首先报道了抗逆转录病毒药物二腺苷引起视网膜毒性。我们一直在使用眼电图（EOG）来测量来自视网膜的电信号，以监测二腺苷对艾滋病毒感染儿童视网膜的潜在毒性作用。目前，我们正在对患有艾滋病毒相关疾病的患者使用氟化二腺苷类似物的第一阶段方案中的儿童进行监测。其他有眼部副作用的药物包括利法布汀和西多福韦。我们继续对一组患有艾滋病的成人和儿童进行定期眼科检查，以监测患者眼部副作用的发展以及机会性感染。-艾滋病，艾滋病毒，巨细胞病毒视网膜炎，眼毒性-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