HIV Neurology - Research

Dr. Justin McArthur

Dr. McArthur's research is focused in three areas of the neurological manifestations of HIV infection: 1) neuroepidemiology, 2) clinical trials, and 3) studies of pathogenesis.

Neuroepidemiology studies are designed to define the epidemiology of HIV-associated dementia and sensory neuropathy in three cohorts: a) the Multicenter AIDS Cohort Study which has included a neurological and neuropsychological component since 1986; b) a referral cohort of HIV-infected individuals through the JHU AIDS Service; and c) NEAD (NorthEastern AIDS Dementia cohort), through a program project grant awarded by NINDS. These cohort studies have shown that the frequency of cognitive impairment is low during the asymptomatic phase of HIV infection and have defined incidence rates and risk factors for HIV dementia and sensory neuropathy. Decline on neuropsychological assessments has been shown to be predictive for the subsequent development of HIV dementia and also to predict more rapid progression to AIDS and shorter survival.

Clinical trials have examined the utility of novel therapeutic agents for HIV-associated dementia, HIV-associated sensory neuropathy, and PML. Dr. McArthur served as Chairman of the Neurology Committee of the AIDS Clinical Trials Group and both he and Dr. Ned Sacktor continue to be actively involved with both ACTG and non-ACTG trials of neurologic therapeutics. Through an NINDS program project grant (PI: Dr. David Clifford, Washington University), we participate in a 22 site consortium of academic centers with HIV neurological expertise, the Neurological AIDS Research Consortium. This consortium has facilitated the planning, implementation and completion of a number of investigator-initiated clinical trails including a placebo-controlled trial of abacavir for HIV associated dementia (completed) and a trial of cytosine arabinoside for PML (completed).

Studies of pathogenesis are designed to explore the mechanisms and biology of HIV infection of the nervous system, both peripheral and central. For the past 10 years we have had a program project grant funded by NINDS. This grant has served as a very valuable resources to allow us to establish a repository of plasma, CSF, and brain tissue specimens from neurologically characterized patients. Many of the patients participate in our cohort studies and have detailed serial neurological and neuropsychological evaluations. Our cerebrospinal fluid bank includes over separate samples, and the autopsy tissue bank contains over 520 separate autopsies, including both AIDS and appropriate seronegative controls. Using these resources, we have completed a number of studies which have convincingly shown that HIV-associated neurological disease is associated with marked immune activation and release of a variety of macrophage secretory products in brain and cerebrospinal fluid. The severity of neurological disease has been shown to correlate with pathological evidence of immune activation, as well as local production of inducible nitric oxide synthase. Dr. Gartner has a large NINDS-funded sequencing project to examine sequence differences from HIV isolates and clones derived from plasma, CSF, and various brain regions. Dr. McArthur also has a separate project to examine the dynamics of HIV suppression within CSF after initiation of highly active antiretroviral therapy. In addition, this project will examine the effect of incomplete medication adherence on CNS penetration of commonly used antiretroviral regimes.

Dr. Adriana Andrade

Dr.Andrade is a primary care physician from Brazil trained in public health and HIV care. Her primary areas of interest are adherence and pharmacology of antiretrovirals. Her work in the adherence field focuses on the use of electronic devices to enhance adherence to antiretrovirals in HIV infected subjects. She is presently a co-investigator in a prospective trial testing a novel electronic device as a potential adherence enhancing tool. Her other major area of interest is in the clinical pharmacology field. She is currently a co-investigator in a project studying the molecular mechanisms of HIV-1 protease inhibitors-associated diarrhea.

Dr. Kathy Conant

Dr. Conant' s research interests are focused on the pathogenesis of immune activation within the CNS and even more, with the consequences of this phenomenon. Changes in the peripheral blood may lead to changes in cells of the immune system, including monocytes, so that these cells can more easily enter the CNS or cause inflammation once there. In addition, cytokines and other substances released into the blood by activated/HIV infected monocytes and lymphocytes may more directly affect cells of the blood brain barrier or CNS parenchyma. Once "activated", CNS resident cells including perivascular monocytes and parenchymal astrocytes will release factors including the matrix metalloproteases, a principal research interest, which could contribute to neuronal disfunction through the degradation of ligands important to neuronal survival and through effects on the blood brain barrier which may allow toxins and additional inflammatory cells to enter the CNS.

Dr. Henraya Davis

Dr. Henraya Davis is a postdoctoral fellow in the Department of Neurology, Johns Hopkins University School of Medicine. She is a trained neuropsychologist that administers and evaluates neuropsychological measures in HIV-infected populations for various research projects within the Department of Neurology. Her main research interest is examining the relationships between neurocognitive impairment and medication adherence. Currently, she is working on a randomized trail, which uses an electronic device to audibly remind patients to take their antiretroviral medications.

Dr. Suzanne Gartner

Dr. Gartner is Associate Professor. She received her PhD in cancer biology in 1984 from Stanford University School of Medicine. Her primary field of expertise is retrovirology

Current research interests:

HIV studies

We are attempting to identify the sequence of events and molecular mechanisms involved in the development of HIV-associated dementia. We have recently proposed a novel model suggesting that a critical first step in this disease process is activation of greater numbers of blood monocytes, which subsequently results in enhanced trafficking of these cells into the brain. This model links initiation of HIV dementia with systemic events associated with immune deficiency and suppression, and it may have relevance to other dementing diseases. To test our hypothesis, we are engaged in virological and immunological studies of patient blood and cerebrospinal fluid specimens. We are also using phylogenetic analyses of HIV genes, molecularly cloned from post-mortem material, to trace the movement of monocytes from their origin in bone marrow, to their entry into the brain and other tissues. Complementary studies include characterization of brain macrophage subpopulations and cerebral white matter changes in the setting of HIV dementia. In addition, we are beginning studies of HIV disease progression with a focus on HIV infection within the bone marrow.

Endogenous retroviruses studies

Endogenous retroviruses are inheritable genetic elements which structurally resemble retroviruses. Although most of those identified thus far in humans are defective and incapable of making virus particles, a few are completely replication competent. Others are able to produce only a portion of the viral proteins; these include functional proteases and reverse transcriptases. Using specimens from patients with chronic lymphopenia, we are examining the expression of these retroviruses in association with immune activation.

Dr. Carlos Pardo

Dr. Michael Polydefkis

Dr. Ola Selnes

Dr. Selnes is an Associate professor in the Division of Cognitive Neurology. His specialization is in the clinical evaluation of disorders of higher cortical functions. Dr. Selnes has been involved in research to characterize the neurocognitive manifestations of HIV dementia since the inception of the Multicenter AIDS Cohort study, and has published extensively on both the early and late cognitive changes associated with HIV infection.

Dr. Ned Sacktor

Dr. Ned Sacktor is an Assistant Professor of Neurology, Johns Hopkins University School of Medicine. He obtained his medical training at the University of Pennsylvania School of Medicine. He then completed a residency program in Neurology and Behavioral Neurology fellowship at Columbia University. He joined the faculty at Johns Hopkins University in 1994. Dr. Sacktor’s primary research interest is in the cognitive manifestations of HIV infection. These investigations include clinical, epidemiological, and neuroimaging studies, as well as trials of therapeutic agents for the treatment of HIV-associated dementia. To participate in one of these clinical studies, please call Deneen Esposito at 410-955-1853 between the hours of 9:00 am and 5:00 pm on weekdays.