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

点击翻译按钮获取中文摘要

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.