Neuropsychiatric problems related to HIV infection and antiretroviral therapy in Cape Town

神经精神问题在艾滋病毒感染者（PLWH）中很常见。认知障碍(即：思维和记忆问题)会影响大约四分之一的PLWH，并且通常与抑郁和其他心理健康症状有关。这些问题会对患者产生重大影响，造成日常运作和决策困难，减少就业，整体生活质量下降。此外，患有神经精神疾病的人不太可能定期服用艾滋病毒药物，这意味着治疗有可能无效。不定期服药的艾滋病毒感染者（称为不良依从性）更有可能因艾滋病毒而不适，并且他们将病毒传染给其他人的风险也会增加。在一些PLWH患者中，神经精神问题可能与大脑损伤有关，可能是HIV病毒本身造成的，也可能是为对抗HIV而服用的抗逆转录病毒药物造成的。人们对这个问题在南非的严重程度、如何检测以及如何帮助受影响的人知之甚少。这是一个重要的研究领域，因为这些因素是可以治疗的。为了调查这个问题，我们将在开普敦的诊所进行一个简短的认知问题筛查测试。在此基础上，我们将邀请178人参与我们的研究——一半有认知问题，一半没有。这些人将接受更详细的神经精神分析，包括基于计算机的认知功能测试和一系列与心理健康症状相关的问卷调查。我们将通过观察他们拿起药片的频率以及他们血液中的药物含量来评估他们对药物的依从性。然后我们将进行腰椎穿刺（LP）；这包括将一根针插入脊柱下部，提取位于大脑和脊髓周围的液体样本，称为脑脊液或CSF。我们将测试脑脊液，看看是否有比血液中更高水平的HIV病毒；这可能发生在约5-10%的患者中，可能是由于在脑和脑脊液中发现的抗逆转录病毒药物浓度较低。它会引起大脑炎症，从而引发神经精神问题。然后，我们将把他们的艾滋病毒治疗从依非韦伦（目前南非最常见的治疗方法）改为多替格拉韦（一种更新、更有效的治疗方法）。我们将在6个月后重复测试和LP。这将使我们看到艾滋病毒在大脑中引起神经精神问题的程度，以及多替格拉韦是否是一种有效的治疗方法。依非韦伦可能对大脑有毒，可能导致认知问题和/或抑郁。虽然多替格拉韦的副作用较小，但它也可能对大脑有毒，导致一些患者焦虑和失眠。除了评估症状我们还会测量血液和脑脊液中的药物浓度这将使我们能够研究这些药物对大脑的毒性作用。我们还将测试患者的DNA，看看遗传差异是否在决定哪些患者受影响最大方面发挥了作用。ODA依从性：我们对这些因素感兴趣的原因是，大脑中的HIV和药物毒性都有可能得到治疗，这为帮助PLWH解决神经精神问题提供了一种方法，也许还能为解决药物依从性差的问题提供新的方法。这种治疗将改善艾滋病患者的福利，增加他们谋生、养家和为社会做贡献的潜力。欧洲和北美制定的指南建议，应定期对PLWH进行认知障碍检测，并在排除其他原因后进行LP检查。我们不知道这个建议是否适合南非，因为南非面临的挑战不同，资源也更有限。这项研究将提供有用的信息，指导这一领域的公共卫生政策决定，确保最有效地分配资金。

Neuropsychiatric problems are common in people living with HIV (PLWH). Cognitive impairment (ie. problems with thinking and memory) can affect around a quarter of PLWH and is often associated with depression and other mental health symptoms. These problems can have a major impact on the person involved, causing difficulties with daily functioning and decision-making, reduced employment and overall poorer quality of life. In addition, people with neuropsychiatric problems are less likely to take their HIV medication regularly, meaning that there is a risk that the treatment could become ineffective. PLWH who do not take their medication regularly (called poor adherence) are more likely to become unwell from HIV, and there is an increased risk they will pass the virus to someone else. In some PLWH neuropsychiatric problems can be related to damage to the brain, either from the HIV virus itself or from the antiretroviral medication taken to combat HIV. There is little known about the extent of this problem in South Africa, how to test for it and what to do to help those affected. This is an important area of research as these factors are potentially treatable. To investigate this we will perform a brief screening test for cognitive problems in Cape Town clinics. Based on this we will ask 178 people to be involved in our study - half with cognitive problems and half without. These will undergo more detailed neuropsychiatric profiling involving a computer based test of cognitive function and a series of questionnaires related to mental health symptoms. We will assess their adherence to medication by looking at how often they pick up their tablets and how much medication can be measured in their blood. We will then perform a lumbar puncture (LP); this involves putting a needle into the lower spine to take a sample of the fluid that sits around the brain and spinal cord, called cerebrospinal fluid or CSF. We will test the CSF to see if there is HIV virus at greater levels than in blood; this can occur in around 5-10% of patients and may be due to the lower concentrations of antiretroviral drugs found in the brain and CSF. It can cause inflammation to the brain and hence neuropsychiatric problems. We will then change their HIV treatment from efavirenz (current most common treatment in South Africa) to dolutegravir (a newer, more effective treatment). We will repeat testing and LP 6 months later. This will allow us to see to what extent HIV in the brain is causing neuropsychiatric problems, and whether dolutegravir is an effective treatment for this. Efavirenz can be toxic to the brain potentially leading to cognitive problems and/or depression. Although dolutegravir has fewer side effects it can also be toxic to the brain, causing anxiety and insomnia in some patients. As well as assessing symptoms we will measure drug concentrations in blood and CSF. This will allow us to investigate the toxic effects of these drugs on the brain. We will also test patients DNA to see whether genetic differences play a role in determining which patients are most affected. ODA compliance: The reason we are interested in these factors is that both HIV in the brain and drug toxicity can potentially be treated, offering a way to help PLWH with neuropsychiatric problems, and perhaps offer new ways to tackle poor adherence to medication. Such treatments would improve the welfare of PLWH and increase their potential to earn a living, support their family and contribute to society. Guidelines developed in Europe and North America suggest that PLWH should be routinely tested for cognitive impairment, and a LP performed if other causes have been excluded. We don't know whether this advice is appropriate for South Africa where the challenges are different and resources are more limited. This study will provide useful information to guide public health policy decisions in this area, ensuring funds are allocated most effectively.