ArticlePLoS pathogens2017
Early Antiretroviral Therapy Is Associated with Lower HIV DNA Molecular Diversity and Lower Inflammation in Cerebrospinal Fluid but Does Not Prevent the Establishment of Compartmentalized HIV DNA Populations.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Implications and prospects of immunological and neuroimaging research in HIV-associated neurocognitive disorders.Frontiers in neurologyPooled it
- Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Trial
- HIV RNA Rebound in Seminal Plasma after Antiretroviral Treatment Interruption.Journal of virology · 2020Trial
- Pharmacokinetics and antiviral activity of cabotegravir and rilpivirine in cerebrospinal fluid following long-acting injectable administration in HIV-infected adults.The Journal of antimicrobial chemotherapy · 2020Trial
- Persistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance.The Journal of clinical investigation · 2019Trial
- Latent HIV Infection of BBB Pericytes Enhances Gap Junction-mediated Crosstalk with Endothelial Cells.Molecular neurobiology · 2026Article
- Review
- Latent HIV Infection of BBB Pericytes Disrupts Gap Junction-Mediated Crosstalk with Endothelial Cells.Research square · 2026Article
- HIV-1 latent infection modulates RNA sensors and innate immunity signaling in human brain pericytes.Research square · 2025Article
- Rapid Initiation of Antiretroviral Therapy Suppresses T Cell Pathological Proliferation and Improves Immune Recovery in People Living with HIV.Infection and drug resistance · 2025Article
- Genetic Variations in EIF2AK3 are Associated with Neurocognitive Impairment in People Living with HIV.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Differences in neuroinflammation in people who started antiretroviral treatment during primary versus chronic HIV infection: an 18kDa Translocator protein (TSPO) positron emission tomography (PET) study.Journal of neurovirology · 2024Observational
- Microglial- neuronal crosstalk in chronic viral infection through mTOR, SPP1/OPN and inflammasome pathway signaling.Frontiers in immunology · 2024Review
- Absence of Proviral Human Immunodeficiency Virus (HIV) Type 1 Evolution in Early-Treated Individuals With HIV Switching to Dolutegravir Monotherapy During 48 Weeks.The Journal of infectious diseases · 2023Article
- Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology.The Journal of infectious diseases · 2023Article
- Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related Neurological Dysfunction.Journal of virology · 2023Article
- Controversies in the Design of Strategies for the Cure of HIV Infection.Pathogens (Basel, Switzerland) · 2023Review
- Lessons for Understanding Central Nervous System HIV Reservoirs from the Last Gift Program.Current HIV/AIDS reports · 2022Review
- A Rationale and Approach to the Development of Specific Treatments for HIV Associated Neurocognitive Impairment.Microorganisms · 2022Review
- Shock and kill within the CNS: A promising HIV eradication approach?Journal of leukocyte biology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Even when antiretroviral therapy (ART) is started early after infection, HIV DNA might persist in the central nervous system (CNS), possibly contributing to inflammation, brain damage and neurocognitive impairment. Paired blood and cerebrospinal fluid (CSF) were collected from 16 HIV-infected individuals on suppressive ART: 9 participants started ART <4 months of the estimated date of infection (EDI) ("early ART"), and 7 participants started ART >14 months after EDI ("late ART"). For each participant, neurocognitive functioning was measured by Global Deficit Score (GDS). HIV DNA levels were measured in peripheral blood mononuclear cells (PBMCs) and CSF cell pellets by droplet digital (dd)PCR. Soluble markers of inflammation (sCD163, IL-6, MCP-1, TNF-α) and neuronal damage (neurofilament light [NFL]) were measured in blood and CSF supernatant by immunoassays. HIV-1 partial C2V3 env deep sequencing data (Roche 454) were obtained for 8 paired PBMC and CSF specimens and used for phylogenetic and compartmentalization analysis. Median exposure to ART at the time of sampling was 2.6 years (IQR: 2.2-3.7) and did not differ between groups. We observed that early ART was significantly associated with lower molecular diversity of HIV DNA in CSF (p<0.05), and lower IL-6 levels in CSF (p = 0.02), but no difference for GDS, NFL, or HIV DNA detectability compared to late ART. Compartmentalization of HIV DNA populations between CSF and blood was detected in 6 out of 8 participants with available paired HIV DNA sequences (2 from early and 4 from late ART group). Phylogenetic analysis confirmed the presence of monophyletic HIV DNA populations within the CSF in 7 participants, and the same population was repeatedly sampled over a 5 months period in one participant with longitudinal sampling. Such compartmentalized provirus in the CNS needs to be considered for the design of future eradication strategies and might contribute to the neuropathogenesis of HIV.
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Registered trials
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