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Effect of Analytic Treatment Interruption of Antiretroviral Therapy on HIV Reservoirs and Immunological Parameters

ABSTRACT: We compared transcriptional profiles of CD4+ and CD8+ T lymphocytes from HIV infected individuals before and 1 year after interruption of antiretroviral therapy (ART).

ORGANISM(S): Homo sapiens

PROVIDER: GSE98902 | GEO | 2018/01/01

SECONDARY ACCESSION(S): PRJNA386870

REPOSITORIES: GEO

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Dominant CD4+ T cell receptors remain stable throughout antiretroviral therapymediated immune restoration in people with HIV

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HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue

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Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns.

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Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders

Project description:Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. We used microarray analysis in post-mortem brain tissues to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed microarray analysis using Affymetrix Arrays in portmortem brain tissues from seven treated and eight untreated HAND patients and six uninfected controls.

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Expression data from HAART interruption in HIV patients

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HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue

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Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an HiPSC tri-culture model of HIV infection [scRNA-seq]

Project description:HIV-Associated Neurocognitive Disorders (HAND) affect over half of HIV-infected individuals, despite antiretroviral therapy (ART). Therapeutically targetable mechanisms underlying HAND remain elusive, partly due to a lack of a proper model. We developed a human-induced pluripotent stem cell (HiPSC) based model, independently differentiating HiPSCs into neurons, astrocytes, and microglia, and systematically combining to generate a tri-culture with or without HIV-infection and ART. Single cell RNAseq analysis on tri-cultures with HIV-infected microglia revealed inflammatory signatures in the microglia and EIF2 signaling in all three cell types. Treatment with the antiretroviral compound EFZ mostly resolved these signatures. However, EFZ increased RhoGDI and CD40 signaling in the HIV-infected microglia. This activation was associated with a persistent increase in TNFa production by microglia. This work establishes a tri-culture that recapitulates key features of HIV infection in the CNS and provides a new model to examine the effects of infection, its treatment, and other co-morbid conditions.

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