189 results on '"Hellmuth, Joanna"'
Search Results
2. Autoantigen profiling reveals a shared post-COVID signature in fully recovered and long COVID patients.
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Bodansky, Aaron, Wang, Chung-Yu, Saxena, Aditi, Mitchell, Anthea, Kung, Andrew, Takahashi, Saki, Anglin, Khamal, Hoh, Rebecca, Lu, Scott, Goldberg, Sarah, Romero, Justin, Tran, Brandon, Kirtikar, Raushun, Grebe, Halle, So, Matthew, Hsue, Priscilla, Hellmuth, Joanna, Kelly, J, Henrich, Timothy, Greenhouse, Bryan, Martin, Jeffrey, Anderson, Mark, Deeks, Steven, Derisi, Joseph, Peluso, Michael, Durstenfeld, Matthew, and Huang, Beatrice
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Autoimmune diseases ,COVID-19 ,Humans ,Post-Acute COVID-19 Syndrome ,COVID-19 ,SARS-CoV-2 ,Autoantibodies ,Autoantigens - Abstract
Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as long COVID. The underlying pathophysiology of long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of SARS-CoV-2 infection and certain other post-COVID sequelae, their potential role in long COVID is important to investigate. Here, we apply a well-established, unbiased, proteome-wide autoantibody detection technology (T7 phage-display assay with immunoprecipitation and next-generation sequencing, PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected that separated individuals with prior SARS-CoV-2 infection from those never exposed to SARS-CoV-2, we did not detect patterns of autoreactivity that separated individuals with long COVID from individuals fully recovered from COVID-19. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and long COVID was apparent by this assay.
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- 2023
3. Impact of pre-existing chronic viral infection and reactivation on the development of long COVID
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Peluso, Michael J, Deveau, Tyler-Marie, Munter, Sadie E, Ryder, Dylan M, Buck, Amanda M, Beck-Engeser, Gabriele, Chan, Fay, Lu, Scott, Goldberg, Sarah A, Hoh, Rebecca, Tai, Viva, Torres, Leonel, Iyer, Nikita S, Deswal, Monika, Ngo, Lynn H, Buitrago, Melissa, Rodriguez, Antonio E, Chen, Jessica Y, Yee, Brandon C, Chenna, Ahmed, Winslow, John W, Petropoulos, Christos J, Deitchman, Amelia N, Hellmuth, Joanna, Spinelli, Matthew A, Durstenfeld, Matthew S, Hsue, Priscilla Y, Kelly, John Daniel, Martin, Jeffrey N, Deeks, Steven G, Hunt, Peter W, and Henrich, Timothy J
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Sexually Transmitted Infections ,Infectious Diseases ,Coronaviruses ,Clinical Research ,Emerging Infectious Diseases ,Infection ,Good Health and Well Being ,Adult ,Humans ,COVID-19 ,SARS-CoV-2 ,Post-Acute COVID-19 Syndrome ,HIV Infections ,Coinfection ,Fatigue ,Cytomegalovirus Infections ,Immunoglobulin G ,Antibodies ,Viral ,Adaptive immunity ,Cytokines ,Medical and Health Sciences ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BACKGROUNDThe presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.METHODSIn a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.RESULTSWe observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).CONCLUSIONOverall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.TRIAL REGISTRATIONLong-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150.FUNDINGThis work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763).
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- 2023
4. Plasma Markers of Neurologic Injury and Inflammation in People With Self-Reported Neurologic Postacute Sequelae of SARS-CoV-2 Infection
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Peluso, Michael J, Sans, Hannah M, Forman, Carrie A, Nylander, Alyssa N, Ho, Hsi-en, Lu, Scott, Goldberg, Sarah A, Hoh, Rebecca, Tai, Viva, Munter, Sadie E, Chenna, Ahmed, Yee, Brandon C, Winslow, John W, Petropoulos, Christos J, Martin, Jeffrey N, Kelly, JD, Durstenfeld, Matthew S, Hsue, Priscilla Y, Hunt, Peter W, Greene, Meredith, Chow, Felicia C, Hellmuth, Joanna, Henrich, Timothy J, Glidden, David V, and Deeks, Steven G
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Infectious Diseases ,Prevention ,Clinical Research ,Neurosciences ,Biomarkers ,COVID-19 ,Humans ,Inflammation ,SARS-CoV-2 ,Self Report - Abstract
Background and objectivesThe biologic mechanisms underlying neurologic postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are incompletely understood.MethodsWe measured markers of neurologic injury (glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and soluble markers of inflammation among a cohort of people with prior confirmed SARS-CoV-2 infection at early and late recovery after the initial illness (defined as less than and greater than 90 days, respectively). The primary clinical outcome was the presence of self-reported CNS PASC symptoms during the late recovery time point. We compared fold changes in marker values between those with and without CNS PASC symptoms using linear mixed-effects models and examined relationships between neurologic and immunologic markers using rank linear correlations.ResultsOf 121 individuals, 52 reported CNS PASC symptoms. During early recovery, those who went on to report CNS PASC symptoms had elevations in GFAP (1.3-fold higher mean ratio, 95% CI 1.04-1.63, p = 0.02), but not NfL (1.06-fold higher mean ratio, 95% CI 0.89-1.26, p = 0.54). During late recovery, neither GFAP nor NfL levels were elevated among those with CNS PASC symptoms. Although absolute levels of NfL did not differ, those who reported CNS PASC symptoms demonstrated a stronger downward trend over time in comparison with those who did not report CNS PASC symptoms (p = 0.041). Those who went on to report CNS PASC also exhibited elevations in interleukin 6 (48% higher during early recovery and 38% higher during late recovery), monocyte chemoattractant protein 1 (19% higher during early recovery), and tumor necrosis factor α (19% higher during early recovery and 13% higher during late recovery). GFAP and NfL correlated with levels of several immune activation markers during early recovery; these correlations were attenuated during late recovery.DiscussionSelf-reported neurologic symptoms present approximately 4 months after SARS-CoV-2 infection are associated with elevations in markers of neurologic injury and inflammation at earlier time points. Some inflammatory pathways seem to be involved months after acute infection. Additional work will be needed to better characterize these processes and to identify interventions to prevent or treat this condition.
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- 2022
5. Risk factors and abnormal cerebrospinal fluid associate with cognitive symptoms after mild COVID-19.
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Apple, Alexandra C, Oddi, Alexis, Peluso, Michael J, Asken, Breton M, Henrich, Timothy J, Kelly, J Daniel, Pleasure, Samuel J, Deeks, Steven G, Allen, Isabel Elaine, Martin, Jeffrey N, Ndhlovu, Lishomwa C, Miller, Bruce L, Stephens, Melanie L, and Hellmuth, Joanna
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Cerebrospinal Fluid ,Humans ,Disease Progression ,Risk Factors ,Cognition ,Adult ,Aged ,Middle Aged ,Research Personnel ,Female ,Male ,Young Adult ,COVID-19 ,SARS-CoV-2 ,Clinical Research ,Lung ,Infectious Diseases ,Neurosciences ,Brain Disorders ,Clinical Sciences - Abstract
Cognitive post-acute sequelae of SARS-CoV-2 (PASC) can occur after mild COVID-19. Detailed clinical characterizations may inform pathogenesis. We evaluated 22 adults reporting cognitive PASC and 10 not reporting cognitive symptoms after mild SARS-CoV-2 infection through structured interviews, neuropsychological testing, and optional cerebrospinal fluid (CSF) evaluations (53%). Delayed onset of cognitive PASC occurred in 43% and associated with younger age. Cognitive PASC participants had a higher number of pre-existing cognitive risk factors (2.5 vs. 0; p = 0.03) and higher proportion with abnormal CSF findings (77% vs. 0%; p = 0.01) versus controls. Cognitive risk factors and immunologic mechanisms may contribute to cognitive PASC pathogenesis.
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- 2022
6. Central Nervous System Effects of COVID-19 in People with HIV Infection
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Peluso, Michael J, Hellmuth, Joanna, and Chow, Felicia C
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Medical Microbiology ,Biomedical and Clinical Sciences ,HIV/AIDS ,Lung ,Neurosciences ,Infectious Diseases ,Sexually Transmitted Infections ,Coronaviruses ,Coronaviruses Disparities and At-Risk Populations ,Emerging Infectious Diseases ,Infection ,Good Health and Well Being ,COVID-19 ,Central Nervous System ,HIV Infections ,Humans ,Pandemics ,SARS-CoV-2 ,HIV ,Central nervous system ,Immunology ,Virology ,Clinical sciences - Abstract
The convergence of the HIV and SARS-CoV-2 pandemics is an emerging field of interest. In this review, we outline the central nervous system (CNS) effects of COVID-19 in the general population and how these effects may manifest in people with HIV (PWH). We discuss the hypothetical mechanisms through which SARS-CoV-2 could impact the CNS during both the acute and recovery phases of infection and the potential selective vulnerability of PWH to these effects as a result of epidemiologic, clinical, and biologic factors. Finally, we define key research questions and considerations for the investigation of CNS sequelae of COVID-19 in PWH.
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- 2021
7. Persistent COVID-19-associated neurocognitive symptoms in non-hospitalized patients.
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Hellmuth, Joanna, Barnett, T Allen, Asken, Breton M, Kelly, J Daniel, Torres, Leonel, Stephens, Melanie L, Greenhouse, Bryan, Martin, Jeffrey N, Chow, Felicia C, Deeks, Steven G, Greene, Meredith, Miller, Bruce L, Annan, Wesley, Henrich, Timothy J, and Peluso, Michael J
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Humans ,Memory ,Short-Term ,Neuropsychological Tests ,Time Factors ,Adult ,Middle Aged ,Outpatients ,Female ,Executive Function ,Cognitive Dysfunction ,COVID-19 ,SARS-CoV-2 ,Brain fog ,Cognitive changes ,Outpatient COVID-19 ,Infectious Diseases ,Neurosciences ,Clinical Research ,Basic Behavioral and Social Science ,Brain Disorders ,Behavioral and Social Science ,Mental Health ,Neurodegenerative ,2.1 Biological and endogenous factors ,Mental health ,Virology ,Clinical Sciences ,Medical Microbiology - Abstract
As cases of coronavirus disease 2019 (COVID-19) mount worldwide, attention is needed on potential long-term neurologic impacts for the majority of patients who experience mild to moderate illness managed as outpatients. To date, there has not been discussion of persistent neurocognitive deficits in patients with milder COVID-19. We present two cases of non-hospitalized patients recovering from COVID-19 with persistent neurocognitive symptoms. Commonly used cognitive screens were normal, while more detailed testing revealed working memory and executive functioning deficits. An observational cohort study of individuals recovering from COVID-19 (14 or more days following symptom onset) identified that among the first 100 individuals enrolled, 14 were non-hospitalized patients reporting persistent cognitive issues. These 14 participants had a median age of 39 years (interquartile range: 35-56), and cognitive symptoms were present for at least a median of 98 days (interquartile range: 71-120 following acute COVID-19 symptoms); no participants with follow-up evaluation reported symptom resolution. We discuss potential mechanisms to be explored in future studies, including direct viral effects, indirect consequences of immune activation, and immune dysregulation causing auto-antibody production.
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- 2021
8. Bilateral basal ganglia infarcts presenting as rapid onset cognitive and behavioral disturbance
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Hellmuth, Joanna, Casaletto, Kaitlin, Cuneo, Richard, Possin, Katherine L, Dillon, William, and Geschwind, Michael D
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Biological Psychology ,Clinical and Health Psychology ,Biomedical and Clinical Sciences ,Psychology ,Behavioral and Social Science ,Brain Disorders ,Mental Health ,Dementia ,Acquired Cognitive Impairment ,Clinical Research ,Neurosciences ,Neurological ,Aged ,80 and over ,Basal Ganglia Diseases ,Behavioral Symptoms ,Caudate Nucleus ,Cerebral Infarction ,Cognitive Dysfunction ,Executive Function ,Humans ,Male ,Memory ,Short-Term ,Space Perception ,Bilateral basal ganglia ,caudate head ,frontal lobe syndrome ,executive function ,spatial working memory ,Clinical Sciences ,Cognitive Sciences ,Experimental Psychology ,Biological psychology ,Clinical and health psychology - Abstract
We describe a rare case of a patient with rapid onset, prominent cognitive and behavioral changes who presented to our rapidly progressive dementia program with symptoms ultimately attributed to bilateral basal ganglia infarcts involving the caudate heads. We review the longitudinal clinical presentation and neuropsychological testing for this patient, and discuss the implicated basal ganglia and frontal lobe neuroanatomy.
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- 2020
9. Plasma inflammatory biomarkers link to diffusion tensor imaging metrics in virally suppressed HIV-infected individuals.
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Chang, Kevin, Premeaux, Thomas A, Cobigo, Yann, Milanini, Benedetta, Hellmuth, Joanna, Rubin, Leah H, Javandel, Shireen, Allen, Isabel, Ndhlovu, Lishomwa C, Paul, Robert, and Valcour, Victor
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Biomedical Imaging ,Neurosciences ,Sexually Transmitted Infections ,Behavioral and Social Science ,Mental Health ,Infectious Diseases ,Clinical Research ,Brain Disorders ,Basic Behavioral and Social Science ,HIV/AIDS ,Aged ,Anisotropy ,Anti-Retroviral Agents ,Biomarkers ,CD4 Lymphocyte Count ,Corpus Callosum ,Diffusion Tensor Imaging ,Female ,HIV Infections ,Humans ,Lipopolysaccharide Receptors ,Male ,Middle Aged ,Neuropsychological Tests ,Retrospective Studies ,White Matter ,diffusion tensor imaging ,inflammation ,MRI ,neurocognitive disorders ,neuroimaging ,white matter ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveInflammation may contribute to brain white matter health in people living with HIV who report cognitive symptoms despite adherence to combination antiretroviral therapy and viral suppression. We explored relationships between diffusion tensor imaging (DTI) metrics of white matter, plasma biomarkers of immune activation, and cognitive function in the HIV-infected population.DesignRetrospective study of older adults living with HIV who are combination antiretroviral therapy adherent, virally suppressed, and self-report cognitive symptoms.MethodsMRI, blood draws, and standardized neuropsychological test scores were collected from HIV-infected individuals. DTI metrics (fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity) and plasma biomarkers (soluble CD163, soluble CD14, neopterin, IFN γ-induced protein 10, monocyte chemoattractant protein 1) were quantified. Statistical analysis explored associations between biomarker levels or neuropsychological test scores and DTI metrics using region of interest analyses and a voxelwise approach.ResultsA total of 43 participants with median (interquartile range) age of 64 (62-66 years), CD4 cell count of 600 (400-760 cell/μl) who were all virally suppressed (
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- 2020
10. Very Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma
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Hellmuth, Joanna, Slike, Bonnie M, Sacdalan, Carlo, Best, John, Kroon, Eugene, Phanuphak, Nittaya, Fletcher, James LK, Prueksakaew, Peeriya, Jagodzinski, Linda L, Valcour, Victor, Robb, Merlin, Ananworanich, Jintanat, Allen, Isabel E, Krebs, Shelly J, and Spudich, Serena
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,HIV/AIDS ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Infection ,Acute Disease ,Adult ,Anti-Retroviral Agents ,Antiretroviral Therapy ,Highly Active ,Biomarkers ,CD4 Lymphocyte Count ,CD4-CD8 Ratio ,Cohort Studies ,Female ,HIV Infections ,HIV-1 ,Host-Pathogen Interactions ,Humans ,Lymphocyte Activation ,Male ,RNA ,Viral ,Time-to-Treatment ,Viral Load ,Young Adult ,CSF ,immune activation ,acute HIV ,inflammation ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundChronic immune activation in the blood and central nervous system is a consequence of human immunodeficiency virus (HIV) infection that contributes to disease morbidity and can occur despite virally suppressive antiretroviral therapy (ART). The trajectory of HIV-related inflammation may vary with the timing of ART initiation. We examined immune activation markers in cerebrospinal fluid (CSF) and blood specimens collected over 96 weeks from participants who initiated ART during acute HIV infection (AHI).MethodsRV254/SEARCH010 study participants with AHI underwent CSF (n = 89) and plasma (n = 146) sampling before initiating ART and at weeks 24 and 96 of treatment. A majority participants (64.4%) received a standard ART regimen (hereafter, "standard ART"), with some (34.7%) also receiving maraviroc and raltegravir for the first 24 weeks (hereafter, "ART plus"). We compared neopterin, CXCL10, CCL2, and interleukin 6 (IL-6) levels in the AHI group to those in 18 healthy, uninfected controls.ResultsFollowing 24 and 96 weeks of treatment, levels of all CSF markers normalized while levels of several plasma markers remained elevated in the AHI group (P < .001). Participants receiving the ART-plus regimen had lower median plasma CCL2 levels at week 24 and lower plasma neopterin levels at week 96.ConclusionsART initiation during AHI differentially impacts the brain compartment, with markers of inflammation returning to normal levels in the CSF, where they were sustained at week 96, but not in plasma.
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- 2019
11. Longitudinal brain atrophy patterns and neuropsychological performance in older adults with HIV-associated neurocognitive disorder compared with early Alzheimer's disease
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Milanini, Benedetta, Samboju, Vishal, Cobigo, Yann, Paul, Robert, Javandel, Shireen, Hellmuth, Joanna, Allen, Isabel, Miller, Bruce, and Valcour, Victor
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Biological Psychology ,Clinical and Health Psychology ,Psychology ,Behavioral and Social Science ,HIV/AIDS ,Brain Disorders ,Mental Health ,Dementia ,Aging ,Neurodegenerative ,Acquired Cognitive Impairment ,Alzheimer's Disease ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Infectious Diseases ,Clinical Research ,Neurosciences ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Mental health ,AIDS Dementia Complex ,Aged ,Aged ,80 and over ,Alzheimer Disease ,Atrophy ,Brain ,Cohort Studies ,Female ,HIV Infections ,Humans ,Longitudinal Studies ,Male ,Middle Aged ,Neurocognitive Disorders ,Neuropsychological Tests ,HIV ,Mild cognitive impairment ,Alzheimer disease ,Neuroimaging ,Cognitive dysfunction ,Clinical Sciences ,Neurology & Neurosurgery ,Biological psychology - Abstract
Older HIV-infected patients are at risk for both HIV-associated neurocognitive disorder (HAND) and Alzheimer's disease. We investigated neuroimaging and neuropsychological performance of 61 virally suppressed older adults with HAND (mean (SD) age 64.3 (3.9) years), 53 demographically matched individuals with mild cognitive impairment of the Alzheimer's type (MCI-AD; 65.0 [4.8]), and 89 healthy controls (65.0 [4.3]) cross-sectionally and over 20 months. At the baseline, both disease groups exhibited lower volumes in multiple cortical and subcortical regions compared with controls. Hippocampal volume differentiated MCI-AD from HAND. Cognitively, MCI-AD performed worse on memory and language compared with HAND. Adjusted longitudinal models revealed greater diffuse brain atrophy in MCI-AD compared with controls, whereas HAND showed greater atrophy in frontal gray matter and cerebellum compared with controls. Comparing HAND with MCI-AD showed similar atrophy rates in all brain regions explored, with no significant findings. MCI-AD exhibited more pronounced language decline compared with HAND. These findings reveal the need for further work on unique cognitive phenotypes and neuroimaging signatures of HAND compared with early AD, providing preliminary clinical insight for differential diagnosis of age-related brain dysfunction in geriatric neuroHIV.
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- 2019
12. The Rise of Pseudomedicine for Dementia and Brain Health
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Hellmuth, Joanna, Rabinovici, Gil D, and Miller, Bruce L
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Health Services and Systems ,Health Sciences ,Acquired Cognitive Impairment ,Behavioral and Social Science ,Neurosciences ,Dementia ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Aging ,Neurodegenerative ,Alzheimer's Disease ,Brain Disorders ,Mental health ,Neurological ,Good Health and Well Being ,Brain ,Cognition ,Cognitive Dysfunction ,Complementary Therapies ,Dietary Supplements ,Ethics ,Medical ,Humans ,Physician's Role ,Quackery ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Published
- 2019
13. A neuropathologic diagnosis of Alzheimer's disease in an older adult with HIV-associated neurocognitive disorder.
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Hellmuth, Joanna, Milanini, Benedetta, Masliah, Eliezer, Tartaglia, Maria Carmela, Dunlop, Miranda B, Moore, David J, Javandel, Shireen, DeVaughn, Saskia, and Valcour, Victor
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Brain ,Humans ,AIDS Dementia Complex ,Alzheimer Disease ,Magnetic Resonance Imaging ,Neuropsychological Tests ,Aged ,80 and over ,Male ,Alzheimer’s disease ,HIV-associated neurocognitive disorder ,dementia ,neuropathology ,neuropsychological testing ,Alzheimer's disease ,Dementia ,Neurosciences ,Infectious Diseases ,Brain Disorders ,HIV/AIDS ,Neurodegenerative ,Alzheimer's Disease ,Mental Health ,Acquired Cognitive Impairment ,Aging ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,2.1 Biological and endogenous factors ,4.1 Discovery and preclinical testing of markers and technologies ,Neurological ,Experimental Psychology ,Clinical Sciences ,Psychology ,Cognitive Sciences - Abstract
We discuss the challenges associated with diagnosing neurodegenerative disorders in older adults living with HIV, illustrated through a case report where neurologic co-diagnosis of Alzheimer's disease (AD) and HIV-associated Neurocognitive Disorder (HAND) are considered. The patient was followed and evaluated for over 4 years and underwent post-mortem neuropathologic evaluation. Further work is needed to identify diagnostic tests that can adequately distinguish HAND from early stage neurodegenerative disorders among older adults living with HIV and cognitive changes.
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- 2018
14. Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation
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Hellmuth, Joanna, Colby, Donn, Valcour, Victor, Suttichom, Duanghathai, Spudich, Serena, Ananworanich, Jintanat, Prueksakaew, Peeriya, Sailasuta, Napapon, Allen, Isabel, Jagodzinski, Linda L, Slike, Bonnie, Ochi, Derek, Paul, Robert, and on behalf of the RV254/SEARCH 010 Study Group
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Public Health ,Health Sciences ,Clinical Trials and Supportive Activities ,Infectious Diseases ,HIV/AIDS ,Mental Health ,Depression ,Clinical Research ,Behavioral and Social Science ,Infection ,Good Health and Well Being ,Adult ,Anxiety ,Biomarkers ,CD4 Lymphocyte Count ,Female ,HIV Infections ,Humans ,Lymphocyte Activation ,Male ,RNA ,Viral ,Thailand ,Viral Load ,Young Adult ,Acute infection ,Neopterin ,Men who have sex with men ,RV254/SEARCH 010 Study Group ,Public Health and Health Services ,Social Work ,Public health - Abstract
This observational study of 123 Thai participants sought to determine the rate and severity of affective symptoms during acute HIV infection (AHI) and possible associations to disease mechanisms. At diagnosis, just prior to starting combination antiretroviral therapy (cART), AHI participants completed assessments of depression and anxiety symptoms that were repeated at 4, 12, and 24 weeks. Blood markers of HIV infection and immune activation were measured at study entry, with optional cerebrospinal fluid measures. A high frequency of participants reported symptoms that exceeded published thresholds supportive of depression (55.0%) and anxiety (65.8%) at diagnosis, with significant reductions after starting cART. Meeting a threshold for clinically relevant depressive symptoms at study entry was associated with higher baseline plasma HIV RNA (5.98 vs. 5.50, t = 2.46, p = 0.015), lower CD4 counts (328 vs. 436 cells/mm3, t = 3.46, p = 0.001), and higher plasma neopterin, a marker of macrophage activation (2694 vs. 1730 pg/mL, Mann-Whitney U = 152.5, p = 0.011). Controlling for plasma HIV RNA and CD4 count, higher baseline plasma neopterin correlated with worse initial depression and anxiety scores. Depression and anxiety symptoms are frequent in acute HIV infection, associate with plasma immune activation, and can improve concurrent with cART.
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- 2017
15. Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years
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Clifford, Katherine M, Samboju, Vishal, Cobigo, Yann, Milanini, Benedetta, Marx, Gabriel A, Hellmuth, Joanna M, Rosen, Howard J, Kramer, Joel H, Allen, Isabel E, and Valcour, Victor G
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Behavioral and Social Science ,Infectious Diseases ,Aging ,Neurosciences ,Brain Disorders ,Sexually Transmitted Infections ,HIV/AIDS ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Neurological ,Infection ,Good Health and Well Being ,AIDS Dementia Complex ,Aged ,Antiretroviral Therapy ,Highly Active ,Atrophy ,Brain ,Case-Control Studies ,Female ,HIV Infections ,Humans ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Sustained Virologic Response ,HIV ,magnetic resonance imaging ,atrophy ,antiretroviral agents ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundCurrent HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests that viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared with that of healthy aging participants.MethodsWe examined longitudinal structural brain magnetic resonance imaging atrophy rates using region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants older than 60 years (n = 38) compared with age-matched HIV-uninfected healthy and cognitively normal controls (n = 24).ResultsThe mean age of participants was 63 years, the mean estimated duration of infection was 21 years, and the median duration of documented viral suppression was 3.2 years. Average proximal and nadir CD4 counts were 550 and 166, respectively; 15/38 (39%) met criteria for HIV-associated neurocognitive disorder. In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, P = 0.016), caudate (0.74% vs. 0.03%, P = 0.012), frontal lobe (0.48% vs. 0.01%, P = 0.034), total cortical gray matter (0.65% vs. 0.16%, P = 0.027), brainstem (0.31% vs. 0.01%, P = 0.026), and pallidum (0.73% vs. 0.39%, P = 0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status.ConclusionsDespite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared with healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences.
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- 2017
16. Chronic viral coinfections differentially affect the likelihood of developing long COVID
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Peluso, Michael J., Deveau, Tyler-Marie, Munter, Sadie E., Ryder, Dylan, Buck, Amanda, Beck-Engeser, Gabriele, Chan, Fay, Lu, Scott, Goldberg, Sarah A., Hoh, Rebecca, Tai, Viva, Torres, Leonel, Iyer, Nikita S., Deswal, Monika, Ngo, Lynn H., Buitrago, Melissa, Rodriguez, Antonio, Chen, Jessica Y., Yee, Brandon C., Chenna, Ahmed, Winslow, John W., Petropoulos, Christos J., Deitchman, Amelia N., Hellmuth, Joanna, Spinelli, Matthew A., Durstenfeld, Matthew S., Hsue, Priscilla Y., Kelly, J. Daniel, Martin, Jeffrey N., Deeks, Steven G., Hunt, Peter W., and Henrich, Timothy J.
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Chronic diseases -- Complications and side effects ,Virus diseases -- Complications and side effects ,Health care industry - Abstract
BACKGROUND. The presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited. METHODS. In a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms. RESULTS. We observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52). CONCLUSION. Overall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted. TRIAL REGISTRATION. Long-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150. FUNDING. This work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003- 03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763)., Introduction Intense efforts are underway to understand the pathophysiologic mechanisms that drive long COVID (LC), a type of postacute sequelae of SARS-CoV-2 infection (PASC), characterized by persistent or recurrent symptoms [...]
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- 2023
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17. Neurologic signs and symptoms frequently manifest in acute HIV infection.
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Hellmuth, Joanna, Fletcher, James LK, Valcour, Victor, Kroon, Eugène, Ananworanich, Jintanat, Intasan, Jintana, Lerdlum, Sukalaya, Narvid, Jared, Pothisri, Mantana, Allen, Isabel, Krebs, Shelly J, Slike, Bonnie, Prueksakaew, Peeriya, Jagodzinski, Linda L, Puttamaswin, Suwanna, Phanuphak, Nittaya, Spudich, Serena, and SEARCH 010/RV254 Study Group
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SEARCH 010/RV254 Study Group ,Brain ,Humans ,HIV Infections ,Acute Disease ,Anti-Retroviral Agents ,Magnetic Resonance Imaging ,Severity of Illness Index ,Incidence ,Cohort Studies ,Follow-Up Studies ,Motor Activity ,Cognition ,Time Factors ,Adult ,Female ,Male ,Biomarkers ,Mental Health ,Pediatric ,Clinical Research ,HIV/AIDS ,Neurosciences ,Infectious Diseases ,Infection ,Clinical Sciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
ObjectiveTo determine the incidence, timing, and severity of neurologic findings in acute HIV infection (pre-antibody seroconversion), as well as persistence with combination antiretroviral therapy (cART).MethodsParticipants identified with acute HIV were enrolled, underwent structured neurologic evaluations, immediately initiated cART, and were followed with neurologic evaluations at 4 and 12 weeks. Concurrent brain MRIs and both viral and inflammatory markers in plasma and CSF were obtained.ResultsMedian estimated HIV infection duration was 19 days (range 3-56) at study entry for the 139 participants evaluated. Seventy-three participants (53%) experienced one or more neurologic findings in the 12 weeks after diagnosis, with one developing a fulminant neurologic manifestation (Guillain-Barré syndrome). A total of 245 neurologic findings were noted, reflecting cognitive symptoms (33%), motor findings (34%), and neuropathy (11%). Nearly half of the neurologic findings (n = 121, 49%) occurred at diagnosis, prior to cART initiation, and most of these (n = 110, 90%) remitted concurrent with 1 month on treatment. Only 9% of neurologic findings (n = 22) persisted at 24 weeks on cART. Nearly all neurologic findings (n = 236, 96%) were categorized as mild in severity. No structural neuroimaging abnormalities were observed. Participants with neurologic findings had a higher mean plasma log10 HIV RNA at diagnosis compared to those without neurologic findings (5.9 vs 5.4; p = 0.006).ConclusionsAcute HIV infection is commonly associated with mild neurologic findings that largely remit while on treatment, and may be mediated by direct viral factors. Severe neurologic manifestations are infrequent in treated acute HIV.
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- 2016
18. Interactions between ageing and NeuroAIDS
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Hellmuth, Joanna, Milanini, Benedetta, and Valcour, Victor
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Acquired Cognitive Impairment ,Brain Disorders ,Neurosciences ,Infectious Diseases ,Peripheral Neuropathy ,Clinical Research ,Neurodegenerative ,Mental Health ,Behavioral and Social Science ,Mind and Body ,HIV/AIDS ,AIDS Dementia Complex ,Adult ,Age Factors ,Aged ,Anti-Retroviral Agents ,Cognition Disorders ,HIV Infections ,Humans ,Middle Aged ,Nervous System Diseases ,Young Adult ,ageing ,AIDS ,cognition ,HIV ,neurology ,Public Health and Health Services ,Virology - Abstract
Purpose of reviewThe purpose of this study is to summarize recent advances in ageing and neuroAIDS by reviewing relevant articles from the preceding 18 months from PubMed and PsycINFO databases.Recent findingsThe success of combination antiretroviral therapy (cART) has led to ageing of the HIV-infected population, which in turn contributes to the prevalence of HIV-associated neurocognitive disorder (HAND). Biomedical advances continue to clarify the pathophysiology of HAND despite effective cART, including chronic inflammatory and neurovascular causes. In recent months, associations between HAND and nonneurological medical diseases have been identified, as well as linkage to neuroimaging in those ageing with HIV. Developing effective screening tools to detect impairment remains an important scientific gap, although promoting factors associated with successful cognitive ageing is emerging as a possible means of enhancing quality of life.SummaryA greater understanding of HAND pathophysiology among treated individuals with suppressed virus will aid in explaining the high prevalence of HAND despite effective cART and allow for development of novel targeted interventions. Neuroimaging and other biomarkers show promise in discerning HAND from age-associated cognitive disorders. Effective screening tools remain critically needed. Together, this work will inform promising strategies needed to address issues pertinent to an expanding group of older patients living with HIV.
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- 2014
19. Cognitive trajectories after treatment in acute HIV infection
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Chan, Phillip, Kerr, Stephen J., Kroon, Eugène, Colby, Donn, Sacdalan, Carlo, Hellmuth, Joanna, Reiss, Peter, Vasan, Sandhya, Ananworanich, Jintanat, Valcour, Victor, Spudich, Serena, and Paul, Robert
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- 2021
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20. Distribution of Human Immunodeficiency Virus (HIV) Ribonucleic Acid in Cerebrospinal Fluid and Blood Is Linked to CD4/CD8 Ratio During Acute HIV
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RV254/SEARCH 010 Study Team, Chan, Phillip, Patel, Payal, Hellmuth, Joanna, Colby, Donn J., Kroon, Eugène, Sacdalan, Carlo, Pinyakorn, Suteeraporn, Jagodzinski, Linda, Krebs, Shelly, Ananworanich, Jintanat, Valcour, Victor, and Spudich, Serena
- Published
- 2018
21. Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer's disease
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Garbutt, Siobhan, Matlin, Alisa, Hellmuth, Joanna, Schenk, Ana K, Johnson, Julene K, Rosen, Howard, Dean, David, Kramer, Joel, Neuhaus, John, Miller, Bruce L, Lisberger, Stephen G, and Boxer, Adam L
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Biological Psychology ,Health Sciences ,Psychology ,Eye Disease and Disorders of Vision ,Neurosciences ,Acquired Cognitive Impairment ,Neurodegenerative ,Dementia ,Basic Behavioral and Social Science ,Frontotemporal Dementia (FTD) ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Clinical Research ,Brain Disorders ,Aging ,Alzheimer's Disease ,Rare Diseases ,Alzheimer's Disease Related Dementias (ADRD) ,Behavioral and Social Science ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Aged ,Alzheimer Disease ,Brain ,Diagnosis ,Differential ,Eye Movement Measurements ,Female ,Humans ,Language Disorders ,Male ,Memory Disorders ,Middle Aged ,Neuropsychological Tests ,Ocular Motility Disorders ,Pursuit ,Smooth ,Saccades ,Signal Processing ,Computer-Assisted ,Supranuclear Palsy ,Progressive ,oculomotor ,frontotemporal lobar degeneration ,corticobasal syndrome ,progressive supranuclear palsy ,Alzheimer's disease ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Neurology & Neurosurgery ,Biomedical and clinical sciences ,Health sciences - Abstract
Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimer's disease, CBS and PSP, saccades and smooth pursuit were measured in three FTLD subtypes, including 24 individuals with frontotemporal dementia (FTD), 19 with semantic dementia (SD) and six with progressive non-fluent aphasia (PA), as compared to 28 individuals with Alzheimer's disease, 15 with CBS, 10 with PSP and 27 control subjects. Different combinations of oculomotor abnormalities were identified in all clinical syndromes except for SD, which had oculomotor performance that was indistinguishable from age-matched controls. Only PSP patients displayed abnormalities in saccade velocity, whereas abnormalities in saccade gain were observed in PSP > CBS > Alzheimer's disease subjects. All patient groups except those with SD were impaired on the anti-saccade task, however only the FTLD subjects and not Alzheimer's disease, CBS or PSP groups, were able to spontaneously self-correct anti-saccade errors as well as controls. Receiver operating characteristic statistics demonstrated that oculomotor findings were superior to neuropsychological tests in differentiating PSP from other disorders, and comparable to neuropsychological tests in differentiating the other patient groups. These data suggest that oculomotor assessment may aid in the diagnosis of FTLD and related disorders.
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- 2008
22. Autoantigen profiling reveals a shared post-COVID signature in fully recovered and Long COVID patients
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Bodansky, Aaron, primary, Wang, Chung-Yu, additional, Saxena, Aditi, additional, Mitchell, Anthea, additional, Takahashi, Saki, additional, Anglin, Khamal, additional, Huang, Beatrice, additional, Hoh, Rebecca, additional, Lu, Scott, additional, Goldberg, Sarah A., additional, Romero, Justin, additional, Tran, Brandon, additional, Kirtikar, Raushun, additional, Grebe, Halle, additional, So, Matthew, additional, Greenhouse, Bryan, additional, Durstenfeld, Matthew S., additional, Hsue, Priscilla Y., additional, Hellmuth, Joanna, additional, Kelly, J. Daniel, additional, Martin, Jeffrey N., additional, Anderson, Mark S., additional, Deeks, Steven G., additional, Henrich, Timothy J., additional, DeRisi, Joseph L., additional, and Peluso, Michael J., additional
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- 2023
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23. Cognitive Impairment and Persistent CNS Injury in Treated HIV
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Chan, Phillip, Hellmuth, Joanna, Spudich, Serena, and Valcour, Victor
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- 2016
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24. Impact of Pre-Existing Chronic Viral Infection and Reactivation on the Development of Long COVID
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Peluso, Michael J., primary, Deveau, Tyler-Marie, additional, Munter, Sadie E., additional, Ryder, Dylan, additional, Buck, Amanda, additional, Beck-Engeser, Gabriele, additional, Chan, Fay, additional, Lu, Scott, additional, Goldberg, Sarah A., additional, Hoh, Rebecca, additional, Tai, Viva, additional, Torres, Leonel, additional, Iyer, Nikita S., additional, Deswal, Monika, additional, Ngo, Lynn H., additional, Buitrago, Melissa, additional, Rodriguez, Antonio, additional, Chen, Jessica Y., additional, Yee, Brandon C., additional, Chenna, Ahmed, additional, Winslow, John W., additional, Petropoulos, Christos J., additional, Deitchman, Amelia N., additional, Hellmuth, Joanna, additional, Spinelli, Matthew A., additional, Durstenfeld, Matthew S., additional, Hsue, Priscilla Y., additional, Kelly, J. Daniel, additional, Martin, Jeffrey N., additional, Deeks, Steven G., additional, Hunt, Peter W., additional, and Henrich, Timothy J., additional
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- 2022
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25. New evidence for biological basis of “COVID-19 brain fog”
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Hellmuth, Joanna, primary and Tent, Michiel, additional
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- 2022
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26. Oculomotor Function in Frontotemporal Lobar Degeneration, Related Disorders and Alzheimer's Disease
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Garbutt, Siobhan, Matlin, Alisa, and Hellmuth, Joanna
- Abstract
Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimer's disease, CBS and PSP, saccades and smooth pursuit were measured in three FTLD subtypes, including 24 individuals with frontotemporal dementia (FTD), 19 with semantic dementia (SD) and six with progressive non-fluent aphasia (PA), as compared to 28 individuals with Alzheimer's disease, 15 with CBS, 10 with PSP and 27 control subjects. Different combinations of oculomotor abnormalities were identified in all clinical syndromes except for SD, which had oculomotor performance that was indistinguishable from age-matched controls. Only PSP patients displayed abnormalities in saccade velocity, whereas abnormalities in saccade gain were observed in PSP greater than CBS greater than Alzheimer's disease subjects. All patient groups except those with SD were impaired on the anti-saccade task, however only the FTLD subjects and not Alzheimer's disease, CBS or PSP groups, were able to spontaneously self-correct anti-saccade errors as well as controls. Receiver operating characteristic statistics demonstrated that oculomotor findings were superior to neuropsychological tests in differentiating PSP from other disorders, and comparable to neuropsychological tests in differentiating the other patient groups. These data suggest that oculomotor assessment may aid in the diagnosis of FTLD and related disorders. (Contains 5 tables and 6 figures.)
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- 2008
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27. Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection
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Peluso, Michael J., Valcour, Victor, Phanuphak, Nittaya, Ananworanich, Jintanat, Fletcher, James L.K., Chalermchai, Thep, Krebs, Shelly J., Robb, Merlin L., Hellmuth, Joanna, Gisslén, Magnus, Zetterberg, Henrik, and Spudich, Serena
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- 2017
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28. Plasma markers of neurologic injury and systemic inflammation in individuals with self-reported neurologic post-acute sequelae of SARS-CoV-2 infection (PASC)
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Peluso, Michael J., primary, Sans, Hannah M., additional, Forman, Carrie A., additional, Nylander, Alyssa N., additional, Ho, Hsi-en, additional, Lu, Scott, additional, Goldberg, Sarah A., additional, Hoh, Rebecca, additional, Tai, Viva, additional, Munter, Sadie E., additional, Chenna, Ahmed, additional, Yee, Brandon C., additional, Winslow, John W., additional, Petropoulos, Christos J., additional, Martin, Jeffrey N., additional, Kelly, J. Daniel, additional, Durstenfeld, Matthew S., additional, Hsue, Priscilla Y., additional, Hunt, Peter W., additional, Greene, Meredith, additional, Chow, Felicia C., additional, Hellmuth, Joanna, additional, Henrich, Timothy J., additional, Glidden, David V., additional, and Deeks, Steven G., additional
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- 2021
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29. Rates of amyloid PET positivity in geriatric HIV
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Milanini, Benedetta, primary, Javandel, Shireen, additional, Hillis, Madeline, additional, Chen, Karen, additional, Hellmuth, Joanna, additional, Paul, Robert, additional, Pohl, Kilian M, additional, and Valcour, Victor, additional
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- 2020
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30. Saccade Abnormalities in Autopsy-Confirmed Frontotemporal Lobar Degeneration and Alzheimer Disease
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Boxer, Adam L., Garbutt, Siobhan, Seeley, William W., Jafari, Aria, Heuer, Hilary W., Mirsky, Jacob, Hellmuth, Joanna, Trojanowski, John Q., Huang, Erik, DeArmond, Steven, Neuhaus, John, and Miller, Bruce L.
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- 2012
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31. Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus
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Hellmuth, Joanna, primary, Muccini, Camilla, additional, Colby, Donn J, additional, Kroon, Eugène, additional, de Souza, Mark, additional, Crowell, Trevor A, additional, Chan, Phillip, additional, Sacdalan, Carlo, additional, Intasan, Jintana, additional, Benjapornpong, Khunthalee, additional, Tipsuk, Somporn, additional, Puttamaswin, Suwanna, additional, Chomchey, Nitiya, additional, Valcour, Victor, additional, Sarnecki, Michal, additional, Tomaka, Frank, additional, Krebs, Shelly J, additional, Slike, Bonnie M, additional, Jagodzinski, Linda L, additional, Dumrongpisutikul, Netsiri, additional, Sailasuta, Napapon, additional, Samboju, Vishal, additional, Michael, Nelson L, additional, Robb, Merlin L, additional, Vasan, Sandhya, additional, Ananworanich, Jintanat, additional, Phanuphak, Praphan, additional, Phanuphak, Nittaya, additional, Paul, Robert, additional, and Spudich, Serena, additional
- Published
- 2020
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32. Conserved CSF HIV Antibody Response in Central Nervous System Escape (1647)
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Hawes, Isobel, primary, Schubert, Ryan, additional, Ramesh, Akshaya, additional, Sowa, Gavin, additional, Hellmuth, Joanna, additional, Gisslen, Magnus, additional, Price, Richard, additional, and Wilson, Michael, additional
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- 2020
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33. Longitudinal brain atrophy patterns and neuropsychological performance in older adults with HIV-associated neurocognitive disorder compared with early Alzheimer's disease
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Milanini, Benedetta, primary, Samboju, Vishal, additional, Cobigo, Yann, additional, Paul, Robert, additional, Javandel, Shireen, additional, Hellmuth, Joanna, additional, Allen, Isabel, additional, Miller, Bruce, additional, and Valcour, Victor, additional
- Published
- 2019
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34. Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus.
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Hellmuth, Joanna, Muccini, Camilla, Colby, Donn J., Kroon, Eugène, de Souza, Mark, Crowell, Trevor A., Chan, Phillip, Sacdalan, Carlo, Intasan, Jintana, Benjapornpong, Khunthalee, Tipsuk, Somporn, Puttamaswin, Suwanna, Chomchey, Nitiya, Valcour, Victor, Sarnecki, Michal, Tomaka, Frank, Krebs, Shelly J., Slike, Bonnie M., Jagodzinski, Linda L., and Dumrongpisutikul, Netsiri
- Abstract
Background. The central nervous system (CNS) is a likely reservoir of human immunodeficiency virus (HIV), vulnerable to viral rebound, inflammation, and clinical changes upon stopping antiretroviral therapy (ART). It is critical to evaluate the CNS safety of studies using analytic treatment interruption (ATI) to assess HIV remission. Methods. Thirty participants who started ART during acute HIV infection underwent CNS assessments across 4 ATI remission trials. ART resumption occurred with plasma viral load >1000 copies/mL. CNS measures included paired pre- vs post-ATI measures of mood, cognitive performance, and neurologic examination, with elective cerebrospinal fluid (CSF) sampling, brain diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). Results. Median participant age was 30 years old and 29/30 were male. Participants’ median time on ART before ATI was 3 years, and ATI lasted a median of 35 days. Post-ATI, there were no differences in median mood scores or neurologic findings and cognitive performance improved modestly. During ATI, a low level of CSF HIV-1 RNA was detectable in 6 of 20 participants with plasma viremia, with no group changes in CSF immune activation markers or brain DTI measures. Mild worsening was identified in post-ATI basal ganglia total choline MRS, suggesting an alteration in neuronal membranes. Conclusion. No adverse CNS effects were observed with brief, closely monitored ATI in participants with acutely treated HIV, except an MRS alteration in basal ganglia choline. Further studies are needed to assess CNS ATI safety in HIV remission trials, particularly for studies using higher thresholds to restart ART and longer ATI durations. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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35. Dietary Supplements for Brain Health—Reply
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Hellmuth, Joanna, primary, Rabinovici, Gil D., additional, and Miller, Bruce L., additional
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- 2019
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36. Resting-state neural signatures of depressive symptoms in acute HIV.
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Philippi, Carissa L., Reyna, Leah, Nedderman, Laura, Chan, Phillip, Samboju, Vishal, Chang, Kevin, Phanuphak, Nittaya, Ratnaratorn, Nisakorn, Hellmuth, Joanna, Benjapornpong, Khunthalee, Dumrongpisutikul, Netsiri, Pothisri, Mantana, Robb, Merlin L., Ananworanich, Jintanat, Spudich, Serena, Valcour, Victor, and Paul, Robert
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FUNCTIONAL connectivity ,CINGULATE cortex ,HIV infections ,HIV ,PREFRONTAL cortex ,LONGITUDINAL method ,AMYGDALOID body - Abstract
Depressive symptoms are often elevated in acute and chronic HIV. Previous neuroimaging research identifies abnormalities in emotion-related brain regions in depression without HIV, including the anterior cingulate cortex (ACC) and amygdala. However, no studies have examined the neural signatures of depressive symptoms in acute HIV infection (AHI). Seed-based voxelwise resting-state functional connectivity (rsFC) for affective seed regions of interest (pregenual ACC, subgenual ACC [sgACC], bilateral amygdala) was computed for 74 Thai males with AHI and 30 Thai HIV-uninfected controls. Group analyses compared rsFC of ACC and amygdala seed regions between AHI and uninfected control groups. Within the AHI group, voxelwise regression analyses investigated the relationship between depressive symptoms and rsFC for these affective seed regions. Group analyses revealed alterations in rsFC of the amygdala in AHI versus uninfected controls. Depressive symptoms associated with decreased rsFC between ACC regions and posterior cingulate/precuneus, medial temporal, and lateral parietal regions in AHI. Symptoms of depression also correlated to increased rsFC between ACC regions and lateral prefrontal cortex, sgACC, and cerebellum in AHI. Similar to the ACC, depressive symptoms associated with decreased rsFC between amygdala and precuneus. Of blood biomarkers, only HIV RNA inversely correlated with rsFC between posterior sgACC and left uncus. We found that depressive symptoms in AHI associate with altered rsFC of ACC and amygdala regions previously implicated in depression. Longitudinal research in this cohort will be necessary to determine whether these early alterations in rsFC of affective network regions are related to persistent depressive symptoms after combination antiretroviral therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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37. Safety of lumbar puncture procedure in an international research setting during acute HIV infection
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Chan, Phillip, primary, Hellmuth, Joanna, additional, Colby, Donn, additional, Kroon, Eugene, additional, Sacdalan, Carlo, additional, Fletcher, James, additional, Patel, Payal, additional, Pinyakorn, Suteera, additional, Valcour, Victor, additional, Ananworanich, Jintanat, additional, and Spudich, Serena, additional
- Published
- 2018
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38. Structural and functional brain imaging in acute HIV
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Samboju, Vishal, primary, Philippi, Carissa L., additional, Chan, Phillip, additional, Cobigo, Yann, additional, Fletcher, James L.K., additional, Robb, Merlin, additional, Hellmuth, Joanna, additional, Benjapornpong, Khunthalee, additional, Dumrongpisutikul, Netsiri, additional, Pothisri, Mantana, additional, Paul, Robert, additional, Ananworanich, Jintanat, additional, Spudich, Serena, additional, and Valcour, Victor, additional
- Published
- 2018
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39. High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection
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Kessing, Cari F., primary, Spudich, Serena, additional, Valcour, Victor, additional, Cartwright, Pearline, additional, Chalermchai, Thep, additional, Fletcher, James L. K., additional, Takata, Hiroshi, additional, Nichols, Carmen, additional, Josey, Benjamin J., additional, Slike, Bonnie, additional, Krebs, Shelly J., additional, Sailsuta, Napapon, additional, Lerdlum, Sukalaya, additional, Jagodzinski, Linda, additional, Tipsuk, Somporn, additional, Suttichom, Duanghathai, additional, Rattanamanee, Somprartthana, additional, Zetterberg, Henrik, additional, Hellmuth, Joanna, additional, Phanuphak, Nittaya, additional, Robb, Merlin L., additional, Michael, Nelson L., additional, Ananworanich, Jintanat, additional, and Trautmann, Lydie, additional
- Published
- 2017
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40. Prominent motor abnormalities in Thai men and women with presumed subtype CRF01_AE HIV-1 infection improve with antiretroviral therapy (P2.304)
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Silverman, Andrew, primary, Chan, Phillip, additional, Paul, Robert, additional, Hellmuth, Joanna, additional, Sithinamsuwan, Pasiri, additional, Ananworanich, Jintanat, additional, Phanuphak, Nittaya, additional, Fletcher, James, additional, Chalermchai, Thep, additional, Tipsuk, Somporn, additional, Suttichom, Duanghathai, additional, Valcour, Victor, additional, and Spudich, Serena, additional
- Published
- 2017
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41. Neurologic signs and symptoms frequently manifest in acute HIV infectionAuthor Response
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Kamtchum-Tatuene, Joseph, primary, Hellmuth, Joanna, primary, Wan Sulaiman, Wan Aliaa, additional, Lekoubou, Alain, additional, Valcour, Victor, additional, and Spudich, Serena, additional
- Published
- 2016
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42. Distribution of Human Immunodeficiency Virus (HIV) Ribonucleic Acid in Cerebrospinal Fluid and Blood Is Linked to CD4/CD8 Ratio During Acute HIV.
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Chan, Phillip, Patel, Payal, Hellmuth, Joanna, Colby, Donn J, Kroon, Eugène, Sacdalan, Carlo, Pinyakorn, Suteeraporn, Jagodzinski, Linda, Krebs, Shelly, Ananworanich, Jintanat, Valcour, Victor, Spudich, Serena, and RV254/SEARCH 010 Study Team
- Subjects
HIV infections ,RNA-RNA interactions ,CEREBROSPINAL fluid ,PLASMA flow ,TRANSMIGRATION - Abstract
Background: Human immunodeficiency virus (HIV) ribonucleic acid (RNA) levels in the plasma and cerebrospinal fluid (CSF) are correlated in chronic HIV infection, but their dynamics have not been characterized during acute infection.Methods: This study analyzed predictors of CSF HIV RNA and relative degree of CNS viral transmigration expressed as plasma minus CSF HIV log10 RNA (PCratio) during untreated acute HIV infection. Cerebrospinal fluid immune markers were compared between groups with different PCratio.Results: One hundred seventeen mostly male (97%) participants in the RV254 cohort in Bangkok, Thailand, had a median age of 28 years and an estimated median 18 days duration of infection; 43 (37%) were Fiebig stages I/II. Twenty-seven (23%) had CSF HIV RNA <80 copies/mL. Those with quantifiable levels (n = 90) had median CSF HIV RNA and PCratio of 3.76 and 2.36 log10 copies/mL, respectively. Human immunodeficiency virus RNA peaked at Fiebig III in plasma and Fiebig IV in CSF. In multivariable analyses, plasma HIV RNA and CD4/CD8 ratio independently correlated with CSF HIV RNA (P < .001), whereas CD4/CD8 ratio predicted PCratio (P = .018). Participants with PCratio <1 had higher CSF neopterin, soluble (s)CD163, interleukin-6, and sCD14 levels (all P < .05).Conclusions: CD4/CD8 ratio independently correlated with CSF HIV RNA and PCratio, suggesting that immune responses modulate central nervous system viral entry at early infection. [ABSTRACT FROM AUTHOR]- Published
- 2018
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43. CNS reservoirs for HIV: implications for eradication
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Hellmuth, Joanna, primary, Valcour, Victor, additional, and Spudich, Serena, additional
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- 2015
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44. High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection.
- Author
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Kessing, Cari F., Spudich, Serena, Valcour, Victor, Cartwright, Pearline, Thep Chalermchai, Fletcher, James L. K., Hiroshi Takata, Nichols, Carmen, Josey, Benjamin J., Slike, Bonnie, Krebs, Shelly J., Sailsuta, Napapon, Sukalaya Lerdlum, Jagodzinski, Linda, Somporn Tipsuk, Duanghathai Suttichom, Somprartthana Rattanamanee, Zetterberg, Henrik, Hellmuth, Joanna, and Nittaya Phanuphak
- Published
- 2017
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45. Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV.
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Valcour, Victor G., Spudich, Serena S., Sailasuta, Napapon, Phanuphak, Nittaya, Lerdlum, Sukalaya, Fletcher, James L. K., Kroon, Eugene D. M. B., Jagodzinski, Linda L., Allen, Isabel E., Adams, Collin L., Prueksakaew, Peeriya, Slike, Bonnie M., Hellmuth, Joanna M., Kim, Jerome H., Ananworanich, Jintanat, and null, null
- Subjects
ANTIRETROVIRAL agents ,NEUROLOGY ,INTEGRASE inhibitors ,CENTRAL nervous system diseases ,HIV infections ,HEALTH outcome assessment ,COMPARATIVE studies - Abstract
Objective: To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+). Design: 24-week randomized open-label prospective evaluation. Method: Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls. Results: At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log
10 HIV RNA (5.4 vs. 5.6, p = 0.382), CSF log10 HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically significant differences were seen in CSF cytokines compared to controls, despite individual variability among the HIV-infected group. Conclusions: A 24-week course of cART+ improved CNS related outcomes, but was not associated with measurable differences compared to standard cART. [ABSTRACT FROM AUTHOR]- Published
- 2015
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46. P3-005: The antisaccade task is sensitive to attention network integrity in normal elderly and dementia
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Boxer, Adam L., primary, Matlin, Alisa, additional, Handwerker, Daniel, additional, Garbutt, Siobhan, additional, Hellmuth, Joanna, additional, Schenk, Ana, additional, Brambati, Simona, additional, Gorno-Tempini, Marilu, additional, Lisberger, Stephen G., additional, Miller, Bruce L., additional, and Henry, RolG, additional
- Published
- 2008
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47. Essential function of HIPK2 in TGFβ-dependent survival of midbrain dopamine neurons
- Author
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Zhang, Jiasheng, primary, Pho, Vanee, additional, Bonasera, Stephen J, additional, Holtzman, Jed, additional, Tang, Amy T, additional, Hellmuth, Joanna, additional, Tang, Siuwah, additional, Janak, Patricia H, additional, Tecott, Laurence H, additional, and Huang, Eric J, additional
- Published
- 2006
- Full Text
- View/download PDF
48. Essential function of HIPK2 in TGFβ-dependent survival of midbrain dopamine neurons.
- Author
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Zhang, Jiasheng, Pho, Vanee, Bonasera, Stephen J., Holzmann, Jed, Tang, Amy T., Hellmuth, Joanna, Tang, Siuwah, Janak, Patricia H., Tecott, Laurence H., and Huang, Eric J.
- Subjects
TRANSFORMING growth factors-beta ,DOPAMINERGIC neurons ,PROTEIN kinases ,DEVELOPMENTAL neurobiology ,APOPTOSIS ,PSYCHOMOTOR disorders - Abstract
Transforming growth factor beta (TGFβ) is a potent trophic factor for midbrain dopamine (DA) neurons, but its in vivo function and signaling mechanisms are not entirely understood. We show that the transcriptional cofactor homeodomain interacting protein kinase 2 (HIPK2) is required for the TGFβ-mediated survival of mouse DA neurons. The targeted deletion of Hipk2 has no deleterious effect on the neurogenesis of DA neurons, but leads to a selective loss of these neurons that is due to increased apoptosis during programmed cell death. As a consequence, Hipk2
−/− mutants show an array of psychomotor abnormalities. The function of HIPK2 depends on its interaction with receptor-regulated Smads to activate TGFβ target genes. In support of this notion, DA neurons from Hipk2−/− mutants fail to survive in the presence of TGFβ3 and Tgfβ3−/− mutants show DA neuron abnormalities similar to those seen in Hipk2−/− mutants. These data underscore the importance of the TGFβ-Smad-HIPK2 pathway in the survival of DA neurons and its potential as a therapeutic target for promoting DA neuron survival during neurodegeneration. [ABSTRACT FROM AUTHOR]- Published
- 2007
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49. Medial Versus Lateral Frontal Lobe Contributions to Voluntary Saccade Control as Revealed by the Study of Patients with Frontal Lobe Degeneration.
- Author
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Boxer, Adam L., Garbutt, Siobhan, Rankin, Katherine P., Hellmuth, Joanna, Neuhaus, John, Miller, Bruce L., and Lisberger, Stephen G.
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FRONTAL lobe ,CEREBRAL cortex ,RAPID eye movement sleep ,MAGNETIC resonance imaging ,MOTOR ability ,MAGNETIC resonance ,DIAGNOSTIC imaging - Abstract
Deficits in the ability to suppress automatic behaviors lead to impaired decision making, aberrant motor behavior, and impaired social function in humans with frontal lobe neurodegeneration. We have studied patients with different patterns of frontal lobe dysfunction resulting from frontotemporal lobar degeneration or Alzheimer's disease, investigating their ability to perform visually guided saccades and smooth pursuit eye movements and to suppress visually guided saccades on the antisaccade task. Patients with clinical syndromes associated with dorsal frontal lobe damage had normal visually guided saccades but were impaired relative to other patients and control subjects in smooth pursuit eye movements and on the antisaccade task. The percentage of correct antisaccade responses was correlated with neuropsychological measures of frontal lobe function and with estimates of frontal lobe gray matter volume based on analyses of structural magnetic resonance images. After controlling for age, gender, cognitive status, and potential interactions between disease group and oculomotor function, an unbiased voxel-based morphometric analysis identified the volume of a segment of the right frontal eye field (FEF) as positively correlated with antisaccade performance (less volume equaled lower percentage of correct responses) but not with either pursuit performance or antisaccade or visually guided saccade latency or gain. In contrast, the volume of the presupplementary motor area (pre-SMA) and a portion of the supplementary eye fields correlated with antisaccade latency (less volume equaled shorter latency) but not with the percentage of correct responses. These results suggest that integrity of the presupplementary motion area/supplementary eye fields is critical for supervisory processes that slow the onset of saccades, facilitating voluntary saccade targeting decisions that rely on the FEF. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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50. Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection.
- Author
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Tovanabutra, Sodsai, Sirijatuphat, Rujipas, Pham, Phuc T., Bonar, Lydia, Harbolick, Elizabeth A., Bose, Meera, Song, Hongshuo, Chang, David, Oropeza, Celina, O'Sullivan, Anne Marie, Balinang, Joyce, Kroon, Eugene, Colby, Donn J., Sacdalan, Carlo, Hellmuth, Joanna, Chan, Phillip, Prueksakaew, Peeriya, Pinyakorn, Suteeraporn, Jagodzinski, Linda L., and Sutthichom, Duanghathai
- Subjects
CENTRAL nervous system ,CENTRAL nervous system physiology ,CEREBROSPINAL fluid ,CEREBROSPINAL fluid examination ,INFECTION - Abstract
HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission strategies that target the HIV reservoir. CNS compartmentalization is a key feature of HIV-1 neuropathogenesis. Thus far, the timing of how early CNS compartmentalization develops after infection is unknown. We examined whether HIV-1 transmitted/founder (T/F) viruses differ between CNS and blood during AHI using single-genome sequencing of envelope gene and further examined subregions in pol and env using next-generation sequencing in paired plasma and cerebrospinal fluid (CSF) from 18 individuals. Different proportions of mostly minor variants were found in six of the eight multiple T/F-infected individuals, indicating enrichment of some variants in CSF that may lead to significant compartmentalization in the later stages of infection. This study provides evidence for the first time that HIV-1 compartmentalization in the CNS can occur within days of HIV-1 exposure in multiple T/F infections. Further understanding of factors that determine enrichment of T/F variants in the CNS, as well as potential long-term implications of these findings for persistence of HIV-1 reservoirs and neurological impairment in HIV, is needed. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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