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Article ; Online: CROI 2023: Neuropsychiatric Complications in People With HIV.

Anderson, Albert M / Ances, Beau M / Letendre, Scott L

2023 Volume 31, Issue 4, Page(s) 543–555

Abstract: The 2023 Conference on Retroviruses and Opportunistic Infections (CROI) featured new and impactful findings about neuropsychiatric complications in people with HIV and other infections. Reports included new evidence of (a) the importance of myeloid cells ...

Abstract	The 2023 Conference on Retroviruses and Opportunistic Infections (CROI) featured new and impactful findings about neuropsychiatric complications in people with HIV and other infections. Reports included new evidence of (a) the importance of myeloid cells in the pathogenesis of HIV disease in the central nervous system, including as an HIV reservoir; (b) eukaryotic and prokaryotic viruses in cerebrospinal fluid during suppressive antiretroviral therapy; (c) the influence of sex on pathogenesis, including in novel neuropsychiatric biotypes identified by machine learning and other methods;(d) premature aging in people with HIV, including the brain-age gap observed on magnetic resonance imaging; (e) cellular and soluble biomarkers of neuropsychiatric complications in people with HIV; and (f) the neurotoxicity of certain antiretroviral drugs. This review summarizes these and other new findings and highlights new research directions for the neuro-HIV field.
MeSH term(s)	Humans ; HIV Infections/complications ; HIV Infections/drug therapy ; Retroviridae Infections ; Aging, Premature ; Anti-Retroviral Agents/adverse effects ; Brain/diagnostic imaging
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2023-07-31
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2656632-1
ISSN	2161-5853 ; 2161-5853
ISSN (online)	2161-5853
ISSN	2161-5853
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Time of Day Influences Concentrations of Total Protein and Albumin in Cerebrospinal Fluid in HIV.

Kakarla, Visesha / Letendre, Scott L / Ellis, Ronald J

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: The accumulation of soluble proteins and metabolites during wakefulness and their clearance during sleep via the glymphatic system occurs in healthy adults and is disturbed in some neurological conditions. Such diurnal variations in the cerebrospinal ... ...

Abstract	The accumulation of soluble proteins and metabolites during wakefulness and their clearance during sleep via the glymphatic system occurs in healthy adults and is disturbed in some neurological conditions. Such diurnal variations in the cerebrospinal fluid (CSF) proteins produced outside the central nervous system and entering via the blood-brain barrier (BBB) have not been evaluated in people with HIV (PWH). CSF and blood were collected in 165 PWH at six US centers between 2003 and 2007. The time of collection was compared to CSF albumin, globulin, and total protein concentrations using bivariate and multivariate regression. Participants all took antiretroviral therapy (ART) and were mostly middle-aged (median age 44.0 years) men (78.8%), with AIDS (77.0%), plasma HIV RNA ≤ 200 copies/mL (75.8%), and immune recovery (median CD4+ T-cell count 414/µL). CSF was collected at median 1:10 p.m. (range 9:00 a.m. to 5:20 p.m.) and within a median of 15 min of blood collection. A later time of CSF collection was associated with higher total protein (
MeSH term(s)	Male ; Adult ; Middle Aged ; Humans ; HIV-1/metabolism ; HIV Infections/drug therapy ; HIV Infections/complications ; Central Nervous System/metabolism ; Blood-Brain Barrier/metabolism ; Albumins/metabolism ; RNA, Viral/metabolism ; Viral Load
Chemical Substances	Albumins ; RNA, Viral
Language	English
Publishing date	2023-02-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032832
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Article ; Online: Time of Day Influences Concentrations of Total Protein and Albumin in Cerebrospinal Fluid in HIV

Visesha Kakarla / Scott L. Letendre / Ronald J. Ellis

International Journal of Molecular Sciences, Vol 24, Iss 2832, p

2023 Volume 2832

Abstract	The accumulation of soluble proteins and metabolites during wakefulness and their clearance during sleep via the glymphatic system occurs in healthy adults and is disturbed in some neurological conditions. Such diurnal variations in the cerebrospinal fluid (CSF) proteins produced outside the central nervous system and entering via the blood–brain barrier (BBB) have not been evaluated in people with HIV (PWH). CSF and blood were collected in 165 PWH at six US centers between 2003 and 2007. The time of collection was compared to CSF albumin, globulin, and total protein concentrations using bivariate and multivariate regression. Participants all took antiretroviral therapy (ART) and were mostly middle-aged (median age 44.0 years) men (78.8%), with AIDS (77.0%), plasma HIV RNA ≤ 200 copies/mL (75.8%), and immune recovery (median CD4+ T-cell count 414/µL). CSF was collected at median 1:10 p.m. (range 9:00 a.m. to 5:20 p.m.) and within a median of 15 min of blood collection. A later time of CSF collection was associated with higher total protein ( p = 0.0077) and albumin ( p = 0.057) in CSF but not in serum, and was additionally associated with higher CSF globulin ( p = 0.013). The glymphatic clearance of albumin, globulin, and total protein is preserved in PWH. The analyses of soluble biomarkers in CSF should account for the time of collection.
Keywords	HIV ; cerebrospinal fluid ; glymphatic ; biomarker ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CROI 2022: neurologic complications of HIV-1, SARS-CoV-2, and other pathogens.

Anderson, Albert M / Letendre, Scott L / Ances, Beau M

Topics in antiviral medicine

2022 Volume 30, Issue 3, Page(s) 475–489

Abstract: The 2022 Conference on Retroviruses and Opportunistic Infections featured new and important findings about the neurologic complications of HIV-1, COVID-19, and other infections. Long-term analyses identified that cognitive decline over time, phenotypic ... ...

Abstract	The 2022 Conference on Retroviruses and Opportunistic Infections featured new and important findings about the neurologic complications of HIV-1, COVID-19, and other infections. Long-term analyses identified that cognitive decline over time, phenotypic aging, and stroke are associated with various comorbidities in people with HIV. Neuroimaging studies showed greater neuroinflammation, white matter damage, demyelination, and overall brain aging in people with chronic HIV infection. Childhood trauma and exposure to environmental pollutants contribute to these neuroimaging findings. Studies of blood and cerebrospinal fluid biomarkers showed that systemic inflammation, neurodegeneration, endothelial activation, oxidative stress, and iron dysregulation are associated with worse cognition in people with HIV. Some animal studies focused on myeloid cells of the central nervous system, but other animal and human studies showed that lymphoid cells also contribute to HIV neuropathogenesis. The deleterious central nervous system effects of polypharmacy and anticholinergic drugs in people with HIV were demonstrated. In contrast, a large randomized controlled trial showed that integrase strand transfer inhibitor therapy was not associated with neurotoxicity. Studies of cryptococcal meningitis demonstrated he cost-effectiveness of single high-dose liposomal amphotericin and the prognostic value of the cryptococcal antigen lateral flow assay. People hospitalized with COVID-19 had more anxiety over time after discharge. The SARS-CoV-2 nucleocapsid antigen is present in cerebrospinal fluid in the absence of viral RNA. Systemic inflammation, astrocyte activation, and tryptophan metabolism pathways are associated with post-COVID-19 neurologic syndromes. Whether these processes are independent or intertwined during HIV-1 and COVID-19 infections requires further study.
MeSH term(s)	Male ; Humans ; HIV-1 ; HIV Infections/complications ; HIV Infections/drug therapy ; SARS-CoV-2 ; COVID-19/complications ; Nervous System Diseases ; Inflammation
Language	English
Publishing date	2022-11-05
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2656632-1
ISSN	2161-5853 ; 2161-5853
ISSN (online)	2161-5853
ISSN	2161-5853
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Article ; Online: The evolution of lifespan and ageing in response to dietary macronutrients in male and female decorated crickets.

Rios-Villamil, Alejandro / Letendre, Corinne / Williams, Alexandria / Rapkin, James / Sakaluk, Scott K / House, Clarissa M / Hunt, John

Evolution; international journal of organic evolution

2024

Abstract: Dietary macronutrients regulate lifespan and ageing, yet little is known about their evolutionary effects. Here, we examine the evolutionary response of these traits in decorated crickets (Gryllodes sigillatus) maintained on diets varying in caloric ... ...

Abstract	Dietary macronutrients regulate lifespan and ageing, yet little is known about their evolutionary effects. Here, we examine the evolutionary response of these traits in decorated crickets (Gryllodes sigillatus) maintained on diets varying in caloric content and protein-to-carbohydrate ratio. After 37 generations, each population was split: half remained on the evolution diet and half switched to a standardized diet. Crickets lived longed and aged slower when evolving on high calorie (both sexes) and carbohydrate-biased (females only) diets and had lower baseline mortality on high calorie (females only) diets. However, on the standardized diet, crickets lived longer when evolving on high calorie diets (both sexes), aged slower on high calorie (females only) and carbohydrate-biased (both sexes) diets and had lower baseline mortality on high-calorie (males only) and protein-biased (both sexes) diets. Lifespan was longer and baseline mortality lower when provided the evolution versus the standardized diet but ageing rate was comparable. Moreover, lifespan was longer, ageing slower (females only) and baseline mortality lower (males only) compared to our evolved baseline suggesting varying degrees of dietary adaptation. Collectively, we show dietary components influence the evolution of lifespan and ageing in different ways and highlight the value of combining experimental evolution with nutritional geometry.
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2036375-8
ISSN	1558-5646 ; 0014-3820
ISSN (online)	1558-5646
ISSN	0014-3820
DOI	10.1093/evolut/qpae024
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Article ; Online: Elevated Biomarkers of Inflammation and Vascular Dysfunction Are Associated with Distal Sensory Polyneuropathy in People with HIV.

Andalibi, Mohammadsobhan Sheikh / Fields, Jerel Adam / Iudicello, Jennifer E / Diaz, Monica M / Tang, Bin / Letendre, Scott L / Ellis, Ronald J

International journal of molecular sciences

2024 Volume 25, Issue 8

Abstract: Distal sensory polyneuropathy (DSP) is a disabling, chronic condition in people with HIV (PWH), even those with viral suppression of antiretroviral therapy (ART), and with a wide range of complications, such as reduced quality of life. Previous studies ... ...

Abstract	Distal sensory polyneuropathy (DSP) is a disabling, chronic condition in people with HIV (PWH), even those with viral suppression of antiretroviral therapy (ART), and with a wide range of complications, such as reduced quality of life. Previous studies demonstrated that DSP is associated with inflammatory cytokines in PWH. Adhesion molecules, essential for normal vascular function, are perturbed in HIV and other conditions linked to DSP, but the link between adhesion molecules and DSP in PWH is unknown. This study aimed to determine whether DSP signs and symptoms were associated with a panel of plasma biomarkers of inflammation (d-dimer, sTNFRII, MCP-1, IL-6, IL-8, IP-10, sCD14) and vascular I integrity (ICAM-1, VCAM-1, uPAR, MMP-2, VEGF, uPAR, TIMP-1, TIMP-2) and differed between PWH and people without HIV (PWoH). A cross-sectional study was conducted among 143 participants (69 PWH and 74 PWoH) assessed by studies at the UC San Diego HIV Neurobehavioral Research Program. DSP signs and symptoms were clinically assessed for all participants. DSP was defined as two or more DSP signs: bilateral symmetrically reduced distal vibration, sharp sensation, and ankle reflexes. Participant-reported symptoms were neuropathic pain, paresthesias, and loss of sensation. Factor analyses reduced the dimensionality of the 15 biomarkers among all participants, yielding six factors. Logistic regression was used to assess the associations between biomarkers and DSP signs and symptoms, controlling for relevant demographic and clinical covariates. The 143 participants were 48.3% PWH, 47 (32.9%) women, and 47 (33.6%) Hispanics, with a mean age of 44.3 ± 12.9 years. Among PWH, the median (IQR) nadir and current CD4+ T-cells were 300 (178-448) and 643 (502-839), respectively. Participants with DSP were older but had similar distributions of gender and ethnicity to those without DSP. Multiple logistic regression showed that Factor 2 (sTNFRII and VCAM-1) and Factor 4 (MMP-2) were independently associated with DSP signs in both PWH and PWoH (OR [95% CI]: 5.45 [1.42-21.00], and 15.16 [1.07-215.22]), respectively. These findings suggest that inflammation and vascular integrity alterations may contribute to DSP pathogenesis in PWH, but not PWoH, possibly through endothelial dysfunction and axonal degeneration.
MeSH term(s)	Humans ; Female ; Male ; HIV Infections/complications ; HIV Infections/blood ; HIV Infections/drug therapy ; Biomarkers/blood ; Middle Aged ; Adult ; Inflammation/blood ; Polyneuropathies/blood ; Polyneuropathies/etiology ; Cross-Sectional Studies ; Cytokines/blood
Chemical Substances	Biomarkers ; Cytokines
Language	English
Publishing date	2024-04-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25084245
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Article ; Online: CROI 2021: Neurologic Complications of HIV-1 Infection or COVID-19.

Ances, Beau M / Anderson, Albert M / Letendre, Scott L

Topics in antiviral medicine

2021 Volume 29, Issue 2, Page(s) 334–343

Abstract: The 2021 Conference on Retroviruses and Opportunistic Infections (CROI) featured a timely review of the neurologic complications of COVID-19 as well as new research findings on mechanisms by which SARS-CoV-2 may affect the brain. CROI included new and ... ...

Abstract	The 2021 Conference on Retroviruses and Opportunistic Infections (CROI) featured a timely review of the neurologic complications of COVID-19 as well as new research findings on mechanisms by which SARS-CoV-2 may affect the brain. CROI included new and important findings about the neurologic complications of HIV-1, human polyomavirus 2 (also known as JC Virus), and cryptococcus. New long-term analyses of cognition in people with HIV-1 identified that cognitive decline over time is associated with multimorbidity, particularly diabetes, chronic lung disease, and vascular disease risk conditions. These conditions are associated with aging, and the question of whether people with HIV are at risk for premature aging was addressed by several reports. New findings from large analyses of resting state networks also provided valuable information on the structural and functional networks that are affected by HIV-1 infection and cognitive impairment. Several reports addressed changes after initiating or switching antiretroviral therapy (ART). Findings that will improve understanding of the biologic mechanisms of brain injury in people with HIV were also presented and included evidence that host (eg, myeloid activation, inflammation, and endothelial activation) and viral (eg, transcriptional activity and compartmentalization) factors adversely affect brain health. Other research focused on adjunctive therapies to treat HIV-1 and its complications in the central nervous system. This summary will review these and other findings in greater detail and identify key gaps and opportunities for researchers and clinicians.
MeSH term(s)	Aging/physiology ; Anti-Retroviral Agents/therapeutic use ; Brain/physiopathology ; COVID-19/complications ; Cognitive Dysfunction/physiopathology ; Cryptococcus/isolation & purification ; HIV Infections/complications ; HIV Infections/drug therapy ; HIV-1 ; Humans ; JC Virus/isolation & purification ; Nervous System Diseases/epidemiology ; Nervous System Diseases/pathology ; Neuroimaging ; Retroviridae Infections ; United States
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2021-06-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2656632-1
ISSN	2161-5853 ; 2161-5853
ISSN (online)	2161-5853
ISSN	2161-5853
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: CROI 2019: neurologic complications of HIV disease.

Ances, Beau M / Letendre, Scott L

Topics in antiviral medicine

2019 Volume 27, Issue 1, Page(s) 26–33

Abstract: Investigators reported many new neuroHIV research findings at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI). These findings included confirmation that HIV-associated neurocognitive disorder (HAND) remains common with an ... ...

Abstract	Investigators reported many new neuroHIV research findings at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI). These findings included confirmation that HIV-associated neurocognitive disorder (HAND) remains common with an increasingly recognized role for comorbidities (eg, obesity) and neurodegenerative conditions (eg, Alzheimer's disease), especially as persons living with HIV (PLWH) advance into their seventh decade of life and beyond. HAND is increasingly recognized as a heterogeneous disorder that differs between individuals (eg, by sex) in the trajectory of specific neurocognitive abilities (eg, executive functioning). A more recent focus at this year's conference was toxicity of combination antiretroviral therapy: neurocognitive performance and neuroimaging data from several studies were presented but did not consistently support that integrase strand transfer inhibitors are associated with worse neurologic outcomes. Neuroimaging studies found that white matter changes reflect a combination of the effects of HIV and comorbidities (including cerebrovascular small vessel disease) and best correlate with blood markers of inflammation. The pathogenesis of HIV in the central nervous system (CNS) was the focus of a plenary lecture and numerous presentations on HIV compartmentalization in the CNS and cerebrospinal fluid viral escape. Novel findings were also presented on associations between HIV-associated neurologic complications and glycomics, neuron-derived exosomes, and DNA methylation in monocytes. This summary will review findings from CROI and identify new research and clinical opportunities.
MeSH term(s)	AIDS Dementia Complex/chemically induced ; AIDS Dementia Complex/diagnostic imaging ; AIDS Dementia Complex/pathology ; AIDS Dementia Complex/physiopathology ; Anti-HIV Agents/adverse effects ; Anti-HIV Agents/therapeutic use ; Comorbidity ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Neuroimaging/methods
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2019-05-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2656632-1
ISSN	2161-5853 ; 2161-5861
ISSN (online)	2161-5853
ISSN	2161-5861
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Article ; Online: Editorial commentary: protease inhibitor monotherapy: safe for the CNS in durably suppressed patients?

Letendre, Scott L

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2014 Volume 59, Issue 11, Page(s) 1635–1637

MeSH term(s)	Cognition Disorders/virology ; Female ; HIV Infections/drug therapy ; HIV Protease Inhibitors/administration & dosage ; Humans ; Male
Chemical Substances	HIV Protease Inhibitors
Language	English
Publishing date	2014-08-11
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciu645
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Article ; Online: Efficacy and safety of two-drug regimens for treatment of HIV in the central nervous system.

Gabuzda, Dana / McArthur, Justin C / Letendre, Scott L

AIDS (London, England)

2020 Volume 34, Issue 13, Page(s) 1975–1977

MeSH term(s)	Anti-HIV Agents/adverse effects ; HIV Infections/drug therapy ; HIV-1 ; Humans ; Nervous System
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2020-09-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000002665
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