HIV Neurology

Why, in 2014, should an entire issue of a neurology journal be dedicated to issues relating to HIV and its complications? Since the mid-1990s, major scientific advances in the diagnosis and treatment of HIV infection have transformed this condition from a uniformly fatal disease to a chronic treatable illness. Despite these successes, HIV remains highly prevalent, has an enormous global impact, and has the potential to affect the nervous system in virtually all infected persons.

Serena Spudich, MD, MA

Ana-Claire Meyer, MD, MSHS

Although the impact of HIV on the central nervous system (CNS) through infection and local immunopathogenesis has been long recognized, new efforts to eradicate or “cure” HIV has led to a re-examination of our understanding of CNS infection and HIV neuropathogenesis, specifically in understanding the establishment and maintenance of potential reservoirs for HIV infection.

Additionally, the emergence of widespread use of combination antiretroviral therapy in the past two decades has changed the clinical character of neurologic disease observed in HIV-infected individuals. As described in this issue, the incidence of severe dementia associated with HIV has reduced dramatically with the advent of effective HIV treatments, though a milder form of impairment of cognitive and motor functions is frequently identified in patients on apparently suppressive antiretroviral therapy. How do we diagnose and monitor the ongoing neurologic disease and effects of therapies targeted to ameliorate it, either using clinical, laboratory, or neuroimaging measures? Although antiretroviral treatment seems to prevent onset of new severe neurologic disorders in most HIV-infected persons, in some cases patients may have ongoing perturbation of the CNS while on therapy, and rarely patients present with new progressive severe neurologic diseases and evidence of CNS “escape” from therapy. Importantly, the availability of multiple options for HIV treatment have led to new questions about the optimization of therapies for treatment of the neurologic complications associated with HIV. Should antiretroviral regimens be selected based on their ability to target the brain or particular cells thought to harbor infection in this compartment? Are certain antiretroviral treatments toxic to the nervous system? Can regimens optimized for minimal systemic toxicity be safely used in the brain?

Furthermore, it is increasingly recognized that the alterations of the immune system attributable to HIV predispose patients to significant neurologic morbidity, not only from opportunistic infections in the case of advanced disease with immunosuppression, but also from metabolic and vascular complications such as stroke from heightened immune activation, even in the setting of treated HIV. Though in the 1980s and 1990s a striking feature of HIV was its concentration within young and middle-aged individuals, the beneficial effects of antiretroviral therapy have led to the emergence of a substantial new population of persons aging with HIV into the 60s and beyond. This confluence of HIV infection and aging brings up multiple issues of importance to CNS pathology and function. Finally, though most research on HIV and its associated nervous system complications has been conducted in resource-rich settings, the overwhelming majority of HIV-infected persons globally live in underresourced settings. There is an urgent need to understand the burden of HIV-associated neurologic disease in these contexts and to direct care and resources to these regions.

For this issue, colleagues from a diverse array of backgrounds including neurology, infectious disease, neuropsychology, immunology, neuroradiology, and medicine have contributed current reviews relevant to these most pressing questions relevant to the nervous system in the current era. We are pleased to have contributions from key clinicians and investigators who are dedicated to the care and understanding of neurologic complications related to HIV from throughout the international community. Potent antiretroviral treatment for HIV has changed the spectrum of issues relevant to HIV's effects on the CNS. We thank the authors for their valuable papers that we are confident will bring readers of Seminars in Neurology up to date on the new frontier of clinical issues facing HIV-infected persons and their providers worldwide.