HIV and Neurology: An Overview of Complications and Challenges

Global progress in addressing the HIV epidemic has been welcome and astounding in the last few years. Between 2014 and 2015, the number of people living with HIV (PLWH) who were taking antiretroviral therapy reached 17 million; this is an increase of one third over just a 1-year period.

The infection rate is also falling, although eliminating infection transmission is still a formidable challenge. A continuing concern is HIV-associated neurologic syndromes. People living with HIV are at elevated risk for neurologic syndromes due to opportunistic infection, immune reconstitution, and adverse events associated with antiretroviral treatment. And, HIV itself can affect the nervous system.

A multinational team of researchers has assembled a comprehensive review of HIV-associated neurologic complications. Published in the journal AIDS, the overview could be a go-to resource for questions about this topic.

The authors reported that increased global access to antiretroviral therapy has led to an aging HIV-positive population and the combination has revealed some cognitive, cerebrovascular, and peripheral neuropathy consequences. Patients who are most likely to be affected reside in resource-limited settings or are severely immunocompromised.

The authors indicated that mounting evidence supports the hypothesis that the central nervous system (CNS) is a reservoir for HIV virus and contributes to persistence of this deadly infection. HIV's tendency to hide in the CNS may be a major barrier to disease eradication.

The review highlights a number of different neurologic consequences:

• In the peripheral nervous system, PLWH are at increased risk for distal symmetric polyneuropathy, with up to half of patients with HIV affected.
• PLWH are up to 1.76 times more likely to have a stroke than people who are not infected. Females are at greatest risk.
• CNS opportunist infections also cause neurologic impairment, with progressive multifocal encephalopathy, cytomegalovirus, tuberculosis, cryptococcal meningitis, and cerebral toxoplasmosis all contributing. These opportunistic infections occur most often in patients whose CD4 cell counts fall below 200 cells/microliter.
• CNS-immune reconstitution syndrome is a concern also. Some patients who start antiretroviral therapy develop immune reconstitution inflammatory syndrome (IRIS). IRIS can occur during rapid restoration of immune function. Patients at highest risk have low CD4 cell counts or high viral load when they start treatment. Patients who have opportunistic infection are also at increased risk.
• The neurotoxic effects associated with antiretrovirals are many, and they contribute to nonadherence or treatment cessation. Newer antiretrovirals tend to be less toxic, but in resource-limited areas, they may be inaccessable.

The authors also addressed the mechanisms that may explain each of these neurologic consequences and examined comorbid conditions, seizure disorders, the impact of the aging population, and special concerns in children.

Overall, the authors concluded that acute and chronic effects of HIV on the nervous system are increasing, especially in aging populations, with synergistic effects on cognitive function and cerebrovascular disease. Additionally, barriers continue to limit the quality of life in patients with HIV with major neurological manifestations.

Reference

Thakur KT, Boubour A, Saylor D, Das M, Bearden DR, Birbeck GL. Global HIV neurology: a comprehensive review. AIDS. 2018 Mar 15. doi: 10.1097/QAD.0000000000001796. [Epub ahead of print]