TY - JOUR
T1 - HIV-associated neurocognitive disorder - Pathogenesis and prospects for treatment
AU - Saylor, Deanna
AU - Dickens, Alex M.
AU - Sacktor, Ned
AU - Haughey, Norman
AU - Slusher, Barbara
AU - Pletnikov, Mikhail
AU - Mankowski, Joseph L.
AU - Brown, Amanda
AU - Volsky, David J.
AU - McArthur, Justin C.
N1 - Funding Information:
The authors of this manuscript have been supported by NIH grants: 2P30MH075673 (to J.C.M, B.S., N.H., A.B., N.S.); 1P01MH105280 (J.C.M, N.H., N.S.); 271201000036C-5-0-1, MH22005 and R21MH083465 (J.C.M., A.B.); 5R01MH099733, U01AI035042, NS081196 and MH107345 (N.S.); 5R01DA040390, 2R01MH077542, 1R01MH096636 and R03MH103985 (N.H.); DA037611, DA017618 and MH105145 (D.V.); AG034852, R21NS07062 and R03DA032470 (B.S.); R01MH083728 (M.P. ) ; P50MH-094268 (M.H.), P01 MH070306 (J.M.); R01NS077869 and R01NS089482 (J.M.). J.C.M. and A.B. are supported by Johns Hopkins University Center for AIDS Research (P30AI094189). M.P. is supported by the Stanley Medical Research Institute, Chevy Chase, Maryland, USA.
Publisher Copyright:
© 2016 Macmillan Publishers Limited. All rights reserved.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies - treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism - are needed to reverse or improve HAND-related neurological dysfunction.
AB - In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies - treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism - are needed to reverse or improve HAND-related neurological dysfunction.
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U2 - 10.1038/nrneurol.2016.27
DO - 10.1038/nrneurol.2016.27
M3 - Review article
C2 - 26965674
AN - SCOPUS:84960364100
VL - 12
SP - 234
EP - 248
JO - Nature Clinical Practice Neurology
JF - Nature Clinical Practice Neurology
SN - 1759-4758
IS - 4
ER -