Cerebrospinal fluid pleocytosis as a predictive factor for CSF and plasma HIV RNA discordance and escape

Almeida, Sérgio Monteiro de; Rotta, Indianara; Pereira, Ana Paula de; Tang, Bin; Umlauf, Anya; Ribeiro, Cléa Elisa Lopes; Letendre, Scott; Ellis, Ronald J.

doi:10.1007/s13365-020-00828-1

Cited by 18 publications

(18 citation statements)

References 54 publications

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“…This infection is largely “equilibrated” with CSF HIV RNA concentrations maintained at levels near 10 percent of those in blood ( 37 , 74 , 75 ), and CSF and blood populations are genetically similar ( 76 ), presumably because of continuous and fresh virus traffic from blood to CSF. When CD4 cells fall below 50/μl, the ratio of CSF to blood virus deceases to near 1% blood HIV RNA levels as CSF pleocytosis also diminishes, consistent with a relation between CSF WBCs and viral load ( 77 – 80 ). The extent of penetration of infection into the brain parenchyma at this stage is uncertain, but if present it is largely clinically silent.…”

Section: Clinical Backgroundsupporting

confidence: 56%

Neuroimmunology of CNS HIV Infection: A Narrative Review

Meyer

Njamnshi²,

Gisslén³

et al. 2022

Front. Neurol.

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This short review provides an overview of the interactions of human immunodeficiency virus type 1 (HIV), immune and inflammatory reactions, and CNS injury over the course of infection. Systemic infection is the overall driver of disease and serves as the “platform” for eventual CNS injury, setting the level of immune dysfunction and providing both the HIV seeding and immune-inflammatory responses to the CNS. These systemic processes determine the timing of and vulnerability to HIV-related neuronal injury which occurs in a separate “compartment” with features that parallel their systemic counterparts but also evolve independently. Direct CNS HIV infection, along with opportunistic infections, can have profound neurological consequences for the infected individual. HIV-related CNS morbidities are of worldwide importance but are enhanced by the particular epidemiological, socioeconomic and environmental factors that heighten the impact of HIV infection in Africa.

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Section: Clinical Backgroundsupporting

confidence: 56%

Neuroimmunology of CNS HIV Infection: A Narrative Review

Meyer

Njamnshi²,

Gisslén³

et al. 2022

Front. Neurol.

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“…]51 copies/mL; b) detectable plasma VL with concurrent CSF VL of at least 0.5 Log10 cp/mL higher than plasma 10 . PWH with any active inflammatory and/or infectious CNS disorder that could transiently increase CSF HIV RNA (such as CNS infections, autoimmune diseases or conditions increasing cells trafficking across the blood-brain barrier, as previously associated with secondary CVE [23][24][25][26] ) were excluded to focus on etiologic mechanisms underlying primary CVE. In case of availability of multiple CSF/plasma pairs per participant, the first pair only was included unless collected on different ART regimens at least one year apart.…”

Section: Study Design and Participantsmentioning

confidence: 99%

The Presence of Resistance-associated Mutations in Reverse Transcriptase Gene is Associated with Cerebrospinal Fluid HIV-1 Escape: a multicentric retrospective analysis

Trunfio

Pinnetti

Arsuffi

et al. 2022

Preprint

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Background: We assessed whether the association between the risk of cerebrospinal fluid escape (CVE) and specific antiretroviral (ARV) classes, such as protease inhibitors, is due to suboptimal pharmacological profile generated by archived resistance-associated mutations (RAMs). Methods: A retrospective multicentric study on 300 adult people with HIV on antiretroviral therapy (ART) and available historical plasma genotype resistance testing (HGRT) for reverse transcriptase (RT) and protease genes between 2001 and 2021. The odds ratio for demographic, clinic-, and ART-related variables and CVE was estimated by multivariable modelling. HGRT-adjusted central nervous system effectiveness penetration (CPE) score was computed in modelling the risk. Results: Median age, plasma VL, and CD4 count were 49 years, <50 copies/mL, and 310 cells/μL. CVE was detected in 51 participants (17.0%). No difference in CVE prevalence was observed according to ART type, number of ARVs or ARV classes. Participants with CVE had more frequently plasma (52.9% vs 32.1%, p=0.005) and CSF RAMs in RT (n=63, 57.1% vs 28.6%, p=0.029), but not in protease gene. The presence of plasma RAMs in RT associated with increased odds of CVE in adjusted analyses (aOR 3.9, p<0.001) and in models restricted to plasma viral load ≤50 copies/mL (n=202; aOR 4.3 , p=0.003). CVE risk decreased by 40% per each point increase in HGRT-adjusted CPE score in multivariable models (p<0.001). Conclusions: Viruses harboring mutations appear to favor CVE and the impact of single ARV classes or type of ART regimens may lose significance when adjusted for the presence and effect of specific RAMs.

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“…33 Moreover, CSF inflammation, investigated based on the increase in CSF WBC, β-chemokine, interleukin levels, IgG intrathecal synthesis, and the presence of oligoclonal bands and CSF discordance or CSF viral escape, occurred at comparable frequencies between HIV-1 subtypes C and B. 41–43 However, previously, we found subtype-dependent differences in amyloid pathway impairment. 44,45…”

Section: Discussionmentioning

confidence: 90%

“…33 Moreover, CSF inflammation, investigated based on the increase in CSF WBC, b-chemokine, interleukin levels, IgG intrathecal synthesis, and the presence of oligoclonal bands and CSF discordance or CSF viral escape, occurred at comparable frequencies between HIV-1 subtypes C and B. [41][42][43] However, previously, we found subtype-dependent differences in amyloid pathway impairment. 44,45 In this study, the increase in CSF and serum suPAR correlated with an increase in CSF WBC while the increase in serum suPAR correlated with an increase in CSF and plasma HIV RNA levels.…”

Section: Discussionmentioning

confidence: 90%

Higher Cerebrospinal Fluid Soluble Urokinase-type Plasminogen Activator Receptor, But Not Interferon γ-inducible Protein 10, Correlate With Higher Working Memory Deficits

Almeida

Rotta

Tang

et al. 2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: We hypothesized that the induction of monocyte activation biomarkers, especially soluble urokinase-type plasminogen activator receptor (suPAR) and interferon g-inducible protein 10 (IP-10), is lower in HIV-1C than HIV-1B, owing to a defective Tat cysteine dimotif (C30S).Methods: A total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH), free of CNS opportunistic infections, from a Southern Brazil outpatient HIV clinic were evaluated such as HIV-1B subtype (n = 27), HIV-1C (n = 26), other (n = 15), and 19 HIV-negative controls. The levels of suPAR, IP-10, neopterin, and b 2 microglobulin (b 2 m) in the CSF and serum were quantified using different immunoassays.Results: Overall, in PWH, increases in CSF suPAR, CSF/serum suPAR, and CSF/serum b2m correlated with worse working memory deficits (r = 0.303, 0.353, and 0.289, respectively, all P , 0.05). The medians of IP-10, suPAR, neopterin, and b2m in CSF and serum and the CSF/serum ratio and suPAR index were comparable between the HIV-1B and HIV-1C subtypes. CSF IP-10 and neopterin and serum IP-10 and suPAR levels were higher in PWH than the HIV-negative controls (P = 0.015, P = 0.001, P , 0.0001, and P , 0.001, respectively). The serum b2m level was higher in HIV-associated dementia than neuropsychologically normal or asymptomatic (P = 0.024). Discussion:We observed that higher levels of CSF suPAR and the suPAR quotient correlated with worse working memory deficit. Elevated levels of monocyte activation were similar in both HIV-1 B and C subtypes, providing no evidence of reduced neuropathogenicity of HIV-1 subtype C Tat compared with subtype B.

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Cerebrospinal fluid pleocytosis as a predictive factor for CSF and plasma HIV RNA discordance and escape

Cited by 18 publications

References 54 publications

Neuroimmunology of CNS HIV Infection: A Narrative Review

Neuroimmunology of CNS HIV Infection: A Narrative Review

The Presence of Resistance-associated Mutations in Reverse Transcriptase Gene is Associated with Cerebrospinal Fluid HIV-1 Escape: a multicentric retrospective analysis

Higher Cerebrospinal Fluid Soluble Urokinase-type Plasminogen Activator Receptor, But Not Interferon γ-inducible Protein 10, Correlate With Higher Working Memory Deficits

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