Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1

AbstractIntegrase strand transfer inhibitors (INSTI) are a main component of the current antiretroviral regimens recommended for treatment of HIV infection. However, little is known about the impact of INSTI on neurocognition and neuroimaging. We developed a prospective observational trial to evaluate the effects of INSTI-based antiretroviral therapy on comprehensive brain outcomes (cognitive, functional, and imaging) according to the time since HIV-1 acquisition. We recruited men living with HIV who initiated antiretroviral therapy with INSTI < 3 months since the estimated date of HIV-1 acquisition (n = 12) and > 6 months since estimated date of HIV-1 acquisition (n = 15). We also recruited a group of matched seronegative individuals (n = 15). Assessments were performed at baseline (before initiation of therapy in HIV arms) and at weeks 4 and 48. Baseline cognitive functioning was comparable between the arms. At week 48, we did not find cognitive differences between starting therapy with INSTI earlier than 3 months or later than 6 months after acquisition of HIV-1 infection. Functional status was poorer in individuals diagnosed earlier. This effect recovered 48 weeks after initiation of therapy. Regarding brain imaging, we found that men living with HIV initiating antiretroviral therapy later experienced a greater decrease in medial orbitofrontal cortex over time, with expected negative repercussions for decision-making tasks.

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Increasing Cerebrospinal Fluid Chemokine Concentrations Despite Undetectable Cerebrospinal Fluid HIV RNA in HIV-1???Infected Patients Receiving Antiretroviral Therapy

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/00042560-200012150-00007 ◽

2000 ◽

pp. 426-433 ◽

Cited By ~ 5

Author(s):

Elisabeth H. Gisolf ◽

Rieneke M. E. van Praag ◽

Suzanne Jurriaans ◽

Peter Portegies ◽

Jaap Goudsmit ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Antiretroviral Therapy ◽

Hiv Rna ◽

Hiv 1

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First-line antiretroviral therapy and dyslipidemia in people living with HIV-1 in Cameroon: a cross-sectional study

AIDS Research and Therapy ◽

10.1186/1742-6405-8-33 ◽

2011 ◽

Vol 8 (1) ◽

pp. 33 ◽

Cited By ~ 24

Author(s):

Eric Pefura Yone ◽

Awa Betyoumin ◽

André Kengne ◽

François Kaze Folefack ◽

Jeanne Ngogang

Keyword(s):

Antiretroviral Therapy ◽

Cross Sectional Study ◽

People Living With Hiv ◽

Sectional Study ◽

First Line ◽

Cross Sectional ◽

Living With Hiv ◽

Hiv 1

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Recurrent cerebrospinal fluid escape in an HIV-1-infected patient receiving antiretroviral therapy

AIDS ◽

10.1097/qad.0000000000001037 ◽

2016 ◽

Vol 30 (7) ◽

pp. 1143-1144 ◽

Cited By ~ 3

Author(s):

Joana Martins ◽

Ernestina Santos ◽

Paula Salgado ◽

Luís Maia ◽

Daniel Dias ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Antiretroviral Therapy ◽

Infected Patient ◽

Hiv 1

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Comment on “Higher CNS Penetration-Effectiveness of Long-Term Combination Antiretroviral Therapy is Associated With Better HIV-1 Viral Suppression in Cerebrospinal Fluid”

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/qai.0b013e3182809d9f ◽

2013 ◽

Vol 62 (4) ◽

pp. e118-e119 ◽

Cited By ~ 1

Author(s):

Andrea Calcagno ◽

Antonio DʼAvolio ◽

Giovanni Di Perri ◽

Stefano Bonora

Keyword(s):

Cerebrospinal Fluid ◽

Antiretroviral Therapy ◽

Viral Suppression ◽

Combination Antiretroviral Therapy ◽

Cns Penetration ◽

Cns Penetration Effectiveness ◽

Hiv 1

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Early ART-initiation Reduces HIV-1 Proviral DNA Levels in Children from the CHER Trial

10.21203/rs.3.rs-389348/v1 ◽

2021 ◽

Author(s):

Helen Payne ◽

Man Chan ◽

Sarah Watters ◽

Kennedy Otwombe ◽

Yuan Hsiao ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Factors Associated ◽

Proviral Dna ◽

Art Initiation ◽

Latent Hiv ◽

Dna Reduction ◽

Living With Hiv ◽

Hiv 1

Abstract BACKGROUND: Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial. METHODS: Infants with HIV <12 weeks old with CD4% ≥25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40W, ART-96W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40W/ART-96W, ART was started/re-started for clinical progression or CD4% <25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received ≥24 weeks ART and two consecutive undetectable HIV-1 RNA 12-24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression.FINDINGS: Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p=0.0003) and 248 weeks (p=0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p=0.0225) and 248 weeks (p=0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p=0.0042).INTEPRETATION: Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of “immune-attenuation” through early HIV-1 exposure.FUNDING: Wellcome Trust, National Institutes of Health, Medical Research Council.

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