Alan Winston, MD, on HIV and Cognitive Disorders
An estimated 38 million people worldwide were living with HIV in 2019, according the Joint United Nations Programme on HIV/AIDS.1 Cognitive disorders have remained common among people with HIV, even in the era of antiretroviral therapy (ART).2
Infectious Diseases Consultant spoke with Alan Winston, MD, professor of HIV and Genitourinary Medicine at Imperial College London and consultant physician at St. Mary’s Hospital in London, about causes, management, and prevention of cognitive disorders among patients with HIV. Dr Winston recently co-authored “Cognitive Disorders in People Living With HIV,” which was published in The Lancet HIV.3
ID CON: Could you discuss potential causes of cognitive disorders among patients with HIV and the importance of addressing them in this patient population?
Dr Winston: Prior to the age of ART for HIV, about 20 to 30 years ago, the majority of cognitive disorders or dementia occurring among people with HIV were direct effects of HIV itself. Nowadays, we are still seeing cognitive disorders among people with HIV, even with effective, virologically suppressive ART. There may be several causes of this. First, it could be caused by a legacy effect of untreated HIV, such as damage to the nervous system before initiating ART. It could be caused by ongoing damage from HIV if viral suppression is not adequate in the blood or central nervous system. It could be caused by general aging, vascular dementia, or other age-related dementias. Lifestyle aspects, such as smoking cigarettes or using recreational drugs, can also contribute to the onset of cognitive disorders.
It is important to recognize this because, in many cases, there are some interventions or treatments that can improve these cognitive disorders. It is also crucial to recognize this because it substantially affects the quality of life for people with HIV. Several studies have shown that cognitive disorders affect quality of life, adherence to medication, and the actual success of treating HIV itself.
ID CON: What is considered standard-of-care for the management, as well as prevention, of cognitive disorders among patients with HIV?
Dr Winston: When managing cognitive disorders among people with HIV, the first aspects of prevention involve ensuring that people with HIV who are on ART commence ART at an early stage and are virologically suppressed. Studies, such as the START studie, have shown that there is reduced morbidity and mortality among people with HIV treated with ART, and this may also prevent the onset of cognitive disorders.
Other aspects of prevention include general lifestyle prevention measures and assessing for cardiovascular risks and other conditions, which can contribute to cognitive disorders. Management includes looking for viral suppression both in plasma and cerebrospinal fluid. Undertaking a lumbar puncture examination is key among people with HIV who have cognitive disorders in order to detect potential viral escape in cerebrospinal fluid. If this is found, it can be managed by looking for HIV viral resistance to antiviral drugs in plasma and cerebrospinal fluid, and then modifying the HIV treatment to ensure that patients are on a regimen that appropriately resolves any detected viral resistance.
ID CON: What other important considerations should clinicians keep in mind when it comes to managing cognitive disorders in HIV? What pitfalls are important to avoid?
Dr Winston: There are several pitfalls to avoid when assessing and managing people with HIV with cognitive disorders. The first is to consider non–HIV-related causes, including vascular dementia and other age-related diseases, such as Alzheimer disease. It is important for infectious disease and HIV specialists to work closely with neurology colleagues to avoid missing any neurological conditions. Clinicians must adequately investigate patients and rule out other disorders via magnetic resonance imaging of the brain.
Another pitfall is to avoid missing cerebrospinal fluid escape. Although cerebrospinal fluid escape is really pretty rare with modern ART, it does occur, especially among people with cognitive disorders.
One final pitfall is to not forget about potential antiretroviral toxicities from the HIV drugs themselves, which could manifest as a depressive illness or a cognitive disorder. Central nervous system manifestations have occurred with the use of newer antiretroviral drugs.
ID CON: What areas of future research are needed going forward in this area?
Dr Winston: Several areas of future research come to mind. Currently, many of the long-term toxicities of antiretroviral drugs and implications for the nervous system are not well understood. When drugs are developed in phase 3 programs, researchers frequently assess drug efficacy and toxicity among young individuals without many other medical issues. The toxicities that occur among these patients might be quite different from the toxicities that can be observed in older individuals or individuals with other neuropsychiatric disorders, such as depression or anxiety. Going forward, it will be important to understand toxicities in a wider population, including older patients and patients from different racial and ethnic groups. In addition, the incidence of cerebrospinal fluid escape has been described in cohort studies performed across the world, but its prevalence and risk factors are still poorly understood.
ID CON: What key takeaways do you hope to leave with infectious disease specialists and related clinicians treating HIV about this topic?
Dr Winston: First, do not forget that people with HIV can develop HIV-related cognitive disorders, despite treatment with modern ART. When assessing people with suspected cognitive disorders, always collaborate with colleagues in neurology and other specialties to rule out other potential causes of cognitive disorders. Finally, do not forget to examine patients for potential antiretroviral toxicity, and be sure to assess for cerebrospinal fluid escape by undertaking a lumbar puncture and examination among patients who consent to it.
—Christina Vogt
References:
- Global HIV & AIDS statistics — 2020 fact sheet. UNAIDS. Accessed July 30, 2020. https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics
- Alford K, Vera JH. Cognitive impairment in people living with HIV in the ART era: a review. Br Med Bull. 2018;127(1):55-68. doi:10.1093/bmb/ldy019
- Winston A, Spudich S. Cognitive disorders in people living with HIV. Lancet HIV. 2020;7(7):E504-E513. doi:10.1016/S2352-3018(20)30107-7