CLINICAL OUTCOMES IN ELDERLY HIV PATIENTS

描述（由申请人提供）：高效抗逆转录病毒疗法（HAART）改善了艾滋病毒感染者的寿命，并使50岁以上人群中艾滋病毒感染的流行率不断上升。一些初步数据表明，老年患者对HAART的反应可能不如年轻患者。具体来说，免疫恢复可能不太好，老年患者的发病率和死亡率可能更高。随着艾滋病毒感染人口的老龄化，越来越需要更好地确定疾病的自然史、治疗的有效性以及与年龄相关的合并症对疾病进展的影响。我们建议在美国的5个HIV初级保健点对3600名HIV感染者进行观察性队列研究（1800名年龄在50岁及以上，1800名年龄在50岁以下，匹配HAART开始的年份、HAART前CD4和护理地点）。具体目标1：评估50岁以上接受HAART治疗的患者与接受HAART治疗的年轻患者的病毒学和免疫反应、HIV疾病进展和死亡率。我们假设老年患者将获得更高的病毒学抑制率，但免疫反应较少，并且比年轻患者有更严重的HIV疾病进展和死亡率。我们的主要研究结果将是HIV疾病进展。次要结果包括CD4+细胞计数的变化、病毒载量抑制和死亡。具体目标2：评估药物不良反应（adr）的发生率，特别是肝毒性、肾毒性、胰腺炎、糖尿病和脂质异常的老年hiv感染患者，按HAART分类分层。我们假设基于PI的HAART的老年患者比基于NNRTI的HAART的HIV+老年患者有更多的ADR需要停止HAART。具体目标3：确定50岁以上艾滋病毒感染患者合并症的发病率、流行率和死亡率，特别关注(a)终末期肾病，(b)与艾滋病毒无关的恶性肿瘤，(c)贫血和(d)心血管疾病。我们假设老年患者将比年龄匹配的HIV血清阴性对照者有更大的这些合并症发生率。我们的主要结局是这些合并症的发生率和流行率。次要结果包括死因特异性死亡率。我们的研究团队在艾滋病毒和老龄化方面有着悠久的合作历史，并汇集了丰富的研究专业知识，包括艾滋病毒治疗结果，老年人合并症，以及艾滋病毒疾病和艾滋病的队列研究和纵向分析的新型生物统计和流行病学方法。

DESCRIPTION (provided by applicant): Highly active antiretroviral therapy (HAART) has resulted in improved longevity in HIV-infected patients and a growing prevalence of HIV infection in people over the age of 50. Some preliminary data suggest that older patients may not respond as well to HAART as younger patients. Specifically, immune recovery may be less good, and both morbidity and mortality rates may be higher in older patients. As the HIV-infected population ages, there is a growing need to better define the natural history of the disease, the effectiveness of therapy, and the effect of age-related comorbidities on disease progression. We propose to conduct an observational cohort study of 3,600 HIV-infected individuals (1,800 aged 50 years and over and 1,800 under age 50 years, matched on year of HAART initiation, pre-HAART CD4, and site of care) followed at 5 HIV primary care sites in the United States. Specific aim 1: evaluate virologic and immunologic response, HIV disease progression, and mortality in patients over 50 on HAART compared to younger patients on HAART. We hypothesize that older patients will achieve greater rates of virologic suppression, but less immunologic response and have worse HIV disease progression and mortality than younger patients. Our primary study outcome will be HIV disease progression. Secondary outcomes will include changes in CD4+ cell counts, viral load suppression, and death. Specific Aim 2: evaluate the incidence of adverse drug reactions (ADRs), particularly hepatotoxicity, nephrotoxicity, pancreatitis, diabetes, and lipid abnormalities in older HIV-infected patients, stratified by HAART class. We hypothesize that older patients on PI based HAART will have more ADR's requiring cessation of HAART than HIV+ older patients on NNRTI based HAART. Specific Aim 3: define incidence, prevalence, and mortality from comorbidities in HIV-infected patients over age 50 with a particular focus on (a) end-stage renal disease, (b) non-HIV related malignancies, (c) anemia and (d) cardiovascular disease. We hypothesize that older patients will have a greater incidence of these comorbidities than age matched HIV seronegative controls. Our primary outcomes will be incidence and prevalence of these comorbidities. Secondary outcomes will include cause-specific mortality. Our research team has an established history of collaboration in HIV and aging, and brings together a wealth of research expertise in HIV treatment outcomes, co-morbidities in the elderly, and novel biostatistical and epidemiological methodologies in cohort studies and longitudinal analyses of HIV disease and AIDS.