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Viruses
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Acute HIV Infections
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Acute HIV Infections

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 13308

Special Issue Editor

Dr. Jean-Pierre Routy

E-Mail Website
Guest Editor
Chronic Viral Illness Service and Division of Hematology, McGill University Health Centre, Glen Site, Montreal, QC H4A 3J1, Canada
Interests: AIDS/HIV; vaccines; lymphoma; Immunotherapy; tryptophan metabolism; immunometabolism

Special Issue Information

Dear Colleagues,

Described in 1985 by David A. Cooper, different terms, including acute, recent, primary, and early HIV infection, have been coined to refer to variable periods following an initial infection with HIV.

The term "acute HIV infection" refers to symptomatic early infection, while "early HIV infection" refers to the approximate six-month period following HIV acquisition.

This short period of time represents a turning point for the life of the infected person, and a time to understand the virus–host interactions for the development of novel immunotherapies.

The diagnosis of acute or early HIV infection is of paramount importance since prompt initiation of ART reduces symptoms of acute infection, blocks AIDS development, abrogates secondary HIV transmission (U=U), reduces HIV reservoir size, and preserves anti-HIV immune functions.

Diagnostics can be difficult during cabotegravir long-action PrEP, leading to the recognition of a new syndrome called long-acting early viral inhibition (LEVI) syndrome. For persons infected while on suboptimal long-acting Prep such as cabotegravir, HIV rapid tests and Ag/Ab tests often fail to detect smoldering infection and HIV can persist undiagnosed for months after infection, even after cabotegravir injections are discontinued.

Failure to diagnose and rapidly treat individuals with early infection has significant individual and public health implications. We must acknowledge that recognition of recent HIV acquisition reveals the limits of prevention strategies including education, the perception of high-risk behaviours, and, more importantly, PrEP and PEP programs.

More recently, persons living with HIV and treated early have been identified as potentially eligible for investigative HIV eradication strategies. 

Identification of recent HIV infection by self-testing, medical or community setting remains a priority for research, care, and prevention to build a HIV/AIDS free era. 

This Special Issue of Viruses will encompass articles and reviews discussing the implications of acute HIV infection prevention and care, as well as host–virus interactions, both in people living with HIV and animal models, including SIV infected monkeys.

Dr. Jean-Pierre Routy
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • acute HIV infection
  • primary HIV infection
  • HIV acquisition prevention (PreP, PEP)
  • acute HIV pathogenesis
  • HIV reservoirs
  • anti-HIV immunity

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Published Papers (6 papers)

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Research

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21 pages, 7364 KiB  
Article
Double-Negative T-Cells during Acute Human Immunodeficiency Virus and Simian Immunodeficiency Virus Infections and Following Early Antiretroviral Therapy Initiation
by Alexis Yero, Tao Shi, Julien A. Clain, Ouafa Zghidi-Abouzid, Gina Racine, Cecilia T. Costiniuk, Jean-Pierre Routy, Jérôme Estaquier and Mohammad-Ali Jenabian
Viruses 2024, 16(10), 1609; https://doi.org/10.3390/v16101609 - 14 Oct 2024
Viewed by 1669
Abstract
HIV infection significantly affects the frequencies and functions of immunoregulatory CD3+CD4−CD8− double-negative (DN) T-cells, while the effect of early antiretroviral therapy (ART) initiation on these cells remains understudied. DN T-cell subsets were analyzed prospectively in 10 HIV+ individuals [...] Read more.
HIV infection significantly affects the frequencies and functions of immunoregulatory CD3+CD4−CD8− double-negative (DN) T-cells, while the effect of early antiretroviral therapy (ART) initiation on these cells remains understudied. DN T-cell subsets were analyzed prospectively in 10 HIV+ individuals during acute infection and following early ART initiation compared to 20 HIV-uninfected controls. In this study, 21 Rhesus macaques (RMs) were SIV-infected, of which 13 were assessed during acute infection and 8 following ART initiation four days post-infection. DN T-cells and FoxP3+ DN Treg frequencies increased during acute HIV infection, which was not restored by ART. The expression of activation (HLA-DR/CD38), immune checkpoints (PD-1/CTLA-4), and senescence (CD28−CD57+) markers by DN T-cells and DN Tregs increased during acute infection and was not normalized by ART. In SIV-infected RMs, DN T-cells remained unchanged despite infection or ART, whereas DN Treg frequencies increased during acute SIV infection and were not restored by ART. Finally, frequencies of CD39+ DN Tregs increased during acute HIV and SIV infections and remained elevated despite ART. Altogether, acute HIV/SIV infections significantly changed DN T-cell and DN Treg frequencies and altered their immune phenotype, while these changes were not fully normalized by early ART, suggesting persistent HIV/SIV-induced immune dysregulation despite early ART initiation. Full article
(This article belongs to the Special Issue Acute HIV Infections)
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14 pages, 2009 KiB  
Article
Human and Viral microRNA Expression in Acute and Chronic HIV Infections
by Elisabetta Lazzari, Gabriella Rozera, Roberta Gagliardini, Rozenn Esvan, Annalisa Mondi, Valentina Mazzotta, Marta Camici, Enrico Girardi, Andrea Antinori, Fabrizio Maggi and Isabella Abbate
Viruses 2024, 16(4), 496; https://doi.org/10.3390/v16040496 - 23 Mar 2024
Cited by 2 | Viewed by 1788
Abstract
Human and viral microRNAs (miRNAs) are involved in the regulation of gene transcription, and the establishment of their profiles in acute (AHI) and chronic (CHI) HIV infections may shed light on the pathogenetic events related to different phases of HIV disease. Next-generation sequencing [...] Read more.
Human and viral microRNAs (miRNAs) are involved in the regulation of gene transcription, and the establishment of their profiles in acute (AHI) and chronic (CHI) HIV infections may shed light on the pathogenetic events related to different phases of HIV disease. Next-generation sequencing (NGS) of miRNA libraries was performed, and the reads were used to analyze miRNA differential expression in the plasma with AHI and CHI. Functional analysis was then undertaken to investigate the biological processes characterizing the two phases of HIV infection. Except for hsa-miR-122-5p, which was found in 3.39% AHI vs. 0.18% CHI, the most represented human miRNAs were similarly represented in AHI and CHI. However, when considering the overall detected miRNAs in AHI and CHI, 15 displayed differential expression (FDR p < 0.05). Functional analysis identified 163 target mRNAs involved in promoting angiogenesis activation in AHI versus CHI through the action of hsa-miR10b-5p, hsa-miR1290, hsa-miR1-3p, and hsa-miR296-5p. The viral miRNAs detected, all belonging to herpesviruses, accounted for only 0.014% of total reads. The present data suggest that AHI patients exhibit strong innate immune activation through the upregulation of hsa-miR-122-5p and early activation of angiogenesis. More specific investigations are needed to study the role of viral miRNAs in HIV pathogenesis. Full article
(This article belongs to the Special Issue Acute HIV Infections)
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Review

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23 pages, 1120 KiB  
Review
Acute HIV-1 Infection: Paradigm and Singularity
by Antoine Chéret
Viruses 2025, 17(3), 366; https://doi.org/10.3390/v17030366 - 3 Mar 2025
Viewed by 2171
Abstract
Acute HIV-1 infection (AHI) is a transient period where the virus causes evident damage to the immune system, including an extensive apoptosis of CD4+ T cells associated with a high level of activation and a major cytokine storm to fight the invading virus. [...] Read more.
Acute HIV-1 infection (AHI) is a transient period where the virus causes evident damage to the immune system, including an extensive apoptosis of CD4+ T cells associated with a high level of activation and a major cytokine storm to fight the invading virus. HIV infection establishes persistence by integrating the viral genome into host cell DNA in both replicating and non-replicating forms, effectively hiding from immune surveillance within infected lymphocytes as cellular reservoirs. The measurement of total HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) is a reliable reflection of this reservoir. Initiating treatments during AHI with nucleoside reverse transcriptase inhibitors (NRTIs) and/or integrase strand transfer inhibitors (INSTIs) is essential to alter the dynamics of the global reservoir expansion, and to reduce the establishment of long-lived cellular and tissue reservoirs, while preserving and enhancing specific and non-specific immune responses. Furthermore, some of the patients treated at the AHI stage may become post-treatment controllers and should be informative regarding the mechanism of viral control, so patients treated during AHI are undoubtedly the best candidates to test innovative remission strategies toward a functional cure that could play a pivotal role in long-term HIV control. AHI is characterized by high levels of viral replication, with a significant increase in the risk of HIV transmission. Detecting AHI and initiating early treatment following diagnosis provides a window of opportunity to control the epidemic, particularly in high-risk populations. Full article
(This article belongs to the Special Issue Acute HIV Infections)
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26 pages, 2734 KiB  
Review
Interventions during Early Infection: Opening a Window for an HIV Cure?
by Christopher R. Hiner, April L. Mueller, Hang Su and Harris Goldstein
Viruses 2024, 16(10), 1588; https://doi.org/10.3390/v16101588 - 9 Oct 2024
Cited by 3 | Viewed by 2698
Abstract
Although combination antiretroviral therapy (ART) has been a landmark achievement for the treatment of human immunodeficiency virus (HIV), an HIV cure has remained elusive. Elimination of latent HIV reservoirs that persist throughout HIV infection is the most challenging barrier to an HIV cure. [...] Read more.
Although combination antiretroviral therapy (ART) has been a landmark achievement for the treatment of human immunodeficiency virus (HIV), an HIV cure has remained elusive. Elimination of latent HIV reservoirs that persist throughout HIV infection is the most challenging barrier to an HIV cure. The progressive HIV infection is marked by the increasing size and diversity of latent HIV reservoirs until an effective immune response is mobilized, which can control but not eliminate HIV infection. The stalemate between HIV replication and the immune response is manifested by the establishment of a viral set point. ART initiation during the early stage limits HIV reservoir development, preserves immune function, improves the quality of life, and may lead to ART-free viral remission in a few people living with HIV (PLWH). However, for the overwhelming majority of PLWH, early ART initiation alone does not cure HIV, and lifelong ART is needed to sustain viral suppression. A critical area of research is focused on determining whether HIV could be functionally cured if additional treatments are provided alongside early ART. Several HIV interventions including Block and Lock, Shock and Kill, broadly neutralizing antibody (bNAb) therapy, adoptive CD8+ T cell therapy, and gene therapy have demonstrated delayed viral rebound and/or viral remission in animal models and/or some PLWH. Whether or not their application during early infection can improve the success of HIV remission is less studied. Herein, we review the current state of clinical and investigative HIV interventions and discuss their potential to improve the likelihood of post-treatment remission if initiated during early infection. Full article
(This article belongs to the Special Issue Acute HIV Infections)
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13 pages, 1462 KiB  
Review
Central Nervous System Effects of Early HIV Infection and Consequences of Antiretroviral Therapy Initiation during Acute HIV
by Phillip Chan and Serena Spudich
Viruses 2024, 16(7), 1082; https://doi.org/10.3390/v16071082 - 5 Jul 2024
Cited by 5 | Viewed by 2254
Abstract
HIV infection is a multi-organ disease that involves the central nervous system (CNS). While devastating CNS complications such as HIV-associated dementia and CNS opportunistic infection typically manifest years after HIV acquisition, HIV RNA is readily detected in the cerebrospinal fluid in untreated neuroasymptomatic [...] Read more.
HIV infection is a multi-organ disease that involves the central nervous system (CNS). While devastating CNS complications such as HIV-associated dementia and CNS opportunistic infection typically manifest years after HIV acquisition, HIV RNA is readily detected in the cerebrospinal fluid in untreated neuroasymptomatic people with HIV, highlighting that HIV neuroinvasion predates overt clinical manifestations. Over the past two decades, increased awareness of HIV infection within the at-risk population, coupled with the accessibility of nucleic acid testing and modern HIV immunoassays, has made the detection of acute and early HIV infection readily achievable. This review aims to summarize research findings on CNS involvement during acute and early HIV infection, as well as the outcomes following the immediate initiation of antiretroviral therapy during this early stage of infection. The knowledge gap in long-term neuroprotection through early ART within the first year of infection will be discussed. Full article
(This article belongs to the Special Issue Acute HIV Infections)
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19 pages, 1527 KiB  
Review
Breakthrough Acute HIV Infections among Pre-Exposure Prophylaxis Users with High Adherence: A Narrative Review
by Davide Moschese, Samuel Lazzarin, Martina Laura Colombo, Francesco Caruso, Andrea Giacomelli, Spinello Antinori and Andrea Gori
Viruses 2024, 16(6), 951; https://doi.org/10.3390/v16060951 - 12 Jun 2024
Cited by 1 | Viewed by 1975
Abstract
Pre-exposure prophylaxis (PrEP) is a pivotal intervention among HIV prevention strategies. We aimed to narratively revise the topic of HIV acute infection in the setting of PrEP exposure with a focus on diagnostic options, clinical features, and future PrEP perspectives, with a particular [...] Read more.
Pre-exposure prophylaxis (PrEP) is a pivotal intervention among HIV prevention strategies. We aimed to narratively revise the topic of HIV acute infection in the setting of PrEP exposure with a focus on diagnostic options, clinical features, and future PrEP perspectives, with a particular focus on users with high adherence to PrEP. We searched the main databases (PubMed, Embase, and Scopus) with the keywords “PrEP” or “Pre-Exposure Prophylaxis” and “HIV” or “PLWH” and “breakthrough” or “acute infection” or “primary infection”. We included all randomized clinical trials and non-experimental studies (both case reports and observational studies) ever published. In the present narrative review, we revise the diagnostic challenges related to HIV diagnosis in the setting of PrEP and the clinical characteristics and symptoms of breakthrough infections. We discuss the management of acute HIV infection during PrEP and the new challenges that arise from the use of long-acting drugs for PrEP. Our review underlines that although extremely rare, HIV seroconversions are still possible during PrEP, even in a context of high adherence. Efforts to promptly identify these events must be included in the PrEP follow-up in order to minimize the chance of overlooked HIV breakthrough infections and thus exposure to suboptimal concentrations of antiretrovirals. Full article
(This article belongs to the Special Issue Acute HIV Infections)
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