The Efficacy of Neuro-HAART in HIV Infected Individuals
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 19
- 试验地点
- 2
- 主要终点
- Change in Neurocognitive Functioning
研究概览
简要总结
Patients infected with Human Immunodeficiency Virus (HIV) are at risk of brain related complications despite the use of highly active antiretroviral therapy (HAART). Such complications are termed HIV neurocognitive disorders (HAND) and comprise a spectrum from asymptomatic neurocognitive impairment (ANI), through mild cognitive impairment (MCI) to severe HIV dementia (HAD).
Prior to HAART approximately 30% of patients with advanced HIV disease had cognitive impairment; with HAART the incidence of HAND has decreased but its prevalence increased. The reasons for the ongoing development of cognitive impairment in HAART treated patients are not clear. They might relate to virus induced brain injury prior to starting HAART, the onset of a separate neurological process, toxicity related to HAART, or ongoing viral infection in the brain.
It is clear that the ability of different antiretroviral drugs to penetrate the brain varies but what is not established is whether these differences between drugs lead to different neurological outcomes. The investigators propose to study HIV infected patients stable on HAART for 12 months; subdividing the groups according to the brain penetrance of their drug combination. Patients would undergo neuropsychological assessment and MRI brain scan at the start of the study and after 12 months.
Differences in neuropsychological tests and MRI would be sought between treatment groups to establish whether HAART with better CNS penetration is associated with better outcome and fewer MRI changes.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV positive with nadir cluster of differentiation 4 (CD4) count <350 /microlitre (uL)
- •Taking HAART with CNS Penetration Effectiveness (CPE) score of either ≤7.0 or ≥7.5 for 1 year or more. Changes in antiretrovirals (ARVs) within the last 12 months are allowed so long as the CPE score does not lead to a change groups
- •Plasma HIV viral load <50 copies / mL for preceding 12 months or longer
- •Informed consent given by participant or legally appointed guardian
排除标准
- •Non-HIV related neurological disorders and active CNS opportunistic infection as assessed by full blood count, electrolytes, creatinine, glucose, liver function tests, cryptococcal antigen, venereal disease reaction level (VDRL), MRI brain scan and cerebrospinal fluid analyses for cell count, protein, glucose, culture, VDRL and cryptococcal antigen.
- •Psychiatric disorders on the psychotic axis, current major depression, and current substance use disorder as assessed by the Study Enrolment Questionnaire for Eligibility
- •Severe substance use disorders (within 12 months of study entry)
- •Active Hepatitis C virus (HCV) (detectable HCV RNA because HCV per se can cause cognitive impairment)
- •History of loss of consciousness >1 hour
- •Non-proficient in English as assessed by the "English as a second language questionnaire"
- •Medications known pharmacologically to interact with ARVs
- •Pregnancy as assessed by the urinary pregnancy test
结局指标
主要结局
Change in Neurocognitive Functioning
时间窗: Change from baseline Neuropsychological testing at 6 and 12 months
Change in overall neurocognitive performance, defined as a global neurocognitive z-score, after a 12-month period of observation, between HIV positive patients taking antiretroviral regimens categorized as being either of high or low CNS penetration. To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, Standard Deviation=1) and 2) the set of individual subtest z-scores were averaged to generate a single composite (global) z-score for each subject. Lower (negative) scores therefore indicate greater levels of cognitive impairment.
次要结局
- Change in MRS Cerebral Metabolite Ratios in Basal Ganglia(Baseline and 12 months)
- Change in MRS Cerebral Metabolite Ratios in Frontal White Matter(Baseline and 12 months)
- Cerebrospinal Fluid(Baseline to 12 Months)
研究者
Bruce Brew
Professor
St Vincent's Hospital, Sydney