Kathryn B Holroyd1, Anastasia Vishnevetsky1, Maahika Srinivasan2, Deanna Saylor3,4. 1. Department of Neurology, MGH-Brigham Neurology, Boston, MA. 2. Harvard Medical School, Boston, MA. 3. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD. 4. University of Zambia School of Medicine, Lusaka, Zambia.
Abstract
PURPOSE OF REVIEW: This review focuses on the pathophysiology of acute HIV infection (AHI) and related central nervous system (CNS) pathology, the clinical characteristics of neurologic complications of AHI, and the implications of the CNS reservoir and viral escape for HIV treatment and cure strategies. RECENT FINDINGS: Recent studies in newly seroconverted populations show a high prevalence of peripheral neuropathy and cognitive dysfunction in AHI, even though these findings have been classically associated with chronic HIV infection. HIV cure strategies such as the "shock and kill" strategy are currently being studied in vitro and even in small clinical trials, though the CNS as a reservoir for latent HIV poses unique barriers to these treatment strategies. SUMMARY: Limited point of care diagnostic testing for AHI and delayed recognition of infection continue to lead to under-recognition and under-reporting of neurologic manifestations of AHI. AHI should be on the differential for a broad range of neurological conditions, from Bell's palsy, peripheral neuropathy, and aseptic meningitis, to more rare manifestations such as ADEM, AIDP, meningo-radiculitis, transverse myelitis, and brachial neuritis. Treatment for these conditions involves early initiation of antiretroviral therapy (ART) and then standard presentation-specific treatments. Current HIV cure strategies under investigation include bone marrow transplant, viral reservoir re-activation and eradication, and genome and epigenetic viral targeting. However, CNS penetration by HIV-1 occurs early on in the disease course with the establishment of the CNS viral reservoir and is an important limiting factor for these therapies.
PURPOSE OF REVIEW: This review focuses on the pathophysiology of acute HIV infection (AHI) and related central nervous system (CNS) pathology, the clinical characteristics of neurologic complications of AHI, and the implications of the CNS reservoir and viral escape for HIV treatment and cure strategies. RECENT FINDINGS: Recent studies in newly seroconverted populations show a high prevalence of peripheral neuropathy and cognitive dysfunction in AHI, even though these findings have been classically associated with chronic HIV infection. HIV cure strategies such as the "shock and kill" strategy are currently being studied in vitro and even in small clinical trials, though the CNS as a reservoir for latent HIV poses unique barriers to these treatment strategies. SUMMARY: Limited point of care diagnostic testing for AHI and delayed recognition of infection continue to lead to under-recognition and under-reporting of neurologic manifestations of AHI. AHI should be on the differential for a broad range of neurological conditions, from Bell's palsy, peripheral neuropathy, and aseptic meningitis, to more rare manifestations such as ADEM, AIDP, meningo-radiculitis, transverse myelitis, and brachial neuritis. Treatment for these conditions involves early initiation of antiretroviral therapy (ART) and then standard presentation-specific treatments. Current HIV cure strategies under investigation include bone marrow transplant, viral reservoir re-activation and eradication, and genome and epigenetic viral targeting. However, CNS penetration by HIV-1 occurs early on in the disease course with the establishment of the CNS viral reservoir and is an important limiting factor for these therapies.
Entities:
Keywords:
HIV cure; HIV reservoir; HIV-associated neurocognitive impairment; acute HIV infection; neurological complications of HIV
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