Interests of the Non-Human Primate Models for HIV Cure Research

Terrade, Gauthier; Huot, Nicolas; Petitdemange, Caroline; Lazzerini, Marie; Orta-Resendiz, Aurelio; Jacquelin, Béatrice; Müller‐Trutwin, Michaela

doi:10.3390/vaccines9090958

Cited by 13 publications

(14 citation statements)

References 188 publications

(304 reference statements)

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“…ECs showed lower FoxP3 + CD8 T-cell frequencies than HIV-progressors and were comparable to uninfected individuals, which contrasts with a unique report of an increase in FoxP3 + CD8 T-cells in SIV controllers Indian RMs compared to SIV progressor monkeys (18). These differences could be associated with increased viral fitness and VL and faster disease progression in the Indian RM model (61). In our study, the EC group is significantly older and with a longer duration of the infection, which can also impact our observations.…”

Section: Discussionmentioning

confidence: 67%

FoxP3+ CD8 T-cells in acute HIV infection and following early antiretroviral therapy initiation

et al. 2022

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ObjectivesBesides CD4 regulatory T-cells (Tregs), immunosuppressor FoxP3+ CD8 T-cells are emerging as an important subset of Tregs, which contribute to immune dysfunction and disease progression in HIV infection. However, FoxP3+ CD8 T-cell dynamics in acute HIV infection and following early antiretroviral therapy (ART) initiation remain understudied.MethodsSubsets of FoxP3+ CD8 T-cells were characterized both prospectively and cross-sectionally in PBMCs from untreated acute (n=26) and chronic (n=10) HIV-infected individuals, early ART-treated in acute infection (n=10, median of ART initiation: 5.5 months post-infection), ART-treated in chronic infection (n=10), elite controllers (n=18), and HIV-uninfected controls (n=21).ResultsAcute and chronic infection were associated with increased total, effector memory, and terminally differentiated FoxP3+ CD8 T-cells, while early ART normalized only the frequencies of total FoxP3+ CD8 T-cells. We observed an increase in FoxP3+ CD8 T-cell immune activation (HLADR+/CD38+), senescence (CD57+/CD28-), and PD-1 expression during acute and chronic infection, which were not normalized by early ART. FoxP3+ CD8 T-cells in untreated participants expressed higher levels of immunosuppressive LAP(TGF-β1) and CD39 than uninfected controls, whereas early ART did not affect their expression. The expression of gut-homing markers CCR9 and Integrin-β7 by total FoxP3+ CD8 T-cells and CD39+ and LAP(TGF-β1)+ FoxP3+ CD8 T-cells increased in untreated individuals and remained higher than in uninfected controls despite early ART. Elite controllers share most of the FoxP3+ CD8 T-cell characteristics in uninfected individuals.ConclusionsAlthough early ART normalized total FoxP3+ CD8 T-cells frequencies, it did not affect the persistent elevation of the gut-homing potential of CD39+ and LAP(TGF-β1)+ FoxP3+ CD8 T-cell, which may contribute to immune dysfunction.

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Section: Discussionmentioning

confidence: 67%

FoxP3+ CD8 T-cells in acute HIV infection and following early antiretroviral therapy initiation

et al. 2022

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“…Non-human primates (NHPs) are the only other species that are naturally susceptible to HIV infection. There are different strains of Simian Immunodeficiency Virus (SIV) that causes different disease phenotypes depending on the species of NHPs, which have been reviewed recently [147].…”

Section: Non-human Primatesmentioning

confidence: 99%

“…In infectious SIV model, infection of NHP with SIV leads to disease progression and immunopathogenesis that bears close resemblance to HIV infection in humans. That includes CD4+ T cell depletion, viremia that can be controlled using ART and ATI resulting in viral rebound [147,148]. However, the use of cross species SIV is shown to be most effective in infection progressing to AIDS, i.e., infection with one strain of SIV will not cause severe disease in some NHP (natural host) but would cause AIDS in a different NHP (non-natural host) [149].…”

Section: Non-human Primatesmentioning

confidence: 99%

HIV Latency in Myeloid Cells: Challenges for a Cure

et al. 2022

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The use of antiretroviral therapy (ART) for Human Immunodeficiency Virus (HIV) treatment has been highly successful in controlling plasma viremia to undetectable levels. However, a complete cure for HIV is hindered by the presence of replication-competent HIV, integrated in the host genome, that can persist long term in a resting state called viral latency. Resting memory CD4+ T cells are considered the biggest reservoir of persistent HIV infection and are often studied exclusively as the main target for an HIV cure. However, other cell types, such as circulating monocytes and tissue-resident macrophages, can harbor integrated, replication-competent HIV. To develop a cure for HIV, focus is needed not only on the T cell compartment, but also on these myeloid reservoirs of persistent HIV infection. In this review, we summarize their importance when designing HIV cure strategies and challenges associated to their identification and specific targeting by the “shock and kill” approach.

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“…suppressing the virus in the absence of antiretroviral therapy and allowing, therefore, "drug holidays". Therapeutic HIV vaccines and other immunotherapeutics, such as broadly neutralizing antibodies and/or innate-immune-enhancing agents, are options that are currently considered [Terrade et al, 2021]. In combination with early initiated ART, these new approaches have been shown to be successful in non-human primates with simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) infections by limiting the viral reservoir, virus persistence in tissue, and delaying viral rebounds during ART interruptions [Byrareddy et al, 2016;Whitney et al, 2018;Okoye et al, 2018].…”

Section: A Milestone In Paediatric Hiv Research: Early Art Initiation...mentioning

confidence: 99%

“…The EPIICAL (Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies, www.epiical.org) project has been formed as an international and interdisciplinary collaboration establishing novel immunotherapeutic strategies to achieve ART-free HIV remission in children [Palma et al, 2015[Palma et al, , 2019. Its greater purpose is to investigate in which terms novel strategies could be implemented in children who perinatally acquired HIV and who have started ART early, as curative strategies are often combined with early initiated ART [Palma et al, 2019;Terrade et al, 2021]. Furthermore, EPIICAL aims to figure out which children are ideal and potential candidates for additional or alternative curative strategies to ART.…”

Section: Using Cohort Data To Study Paediatric Art Response Dynamicsmentioning

confidence: 99%

Paediatric HIV infection from a mathematical perspective

Schröter¹

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Background: Interventions aiming for an HIV cure would benefit from rapid elimination of virus after the onset of antiretroviral treatment (ART), by keeping the latent HIV reservoir small. Setting: We investigated HIV suppression in 312 perinatally infected infants starting ART within 6 months after birth from the EPPICC (European Pregnancy and Paediatric HIV Cohort Collaboration). Methods: To better understand kinetic differences in HIV suppression among infants, we investigated their individual viral loads (VL) decay dynamics. We identified VL decay patterns and determined times to viral suppression (TTS). For infants with strictly declining VLs (n=188), we used parameter fitting methods to estimate baseline VLs, decay rates and TTS. We subsequently identified the parameters determining TTS by linear modelling. Results: The majority of infants suppress HIV VL after the onset of ART. Some children experienced a long TTS due to an "erratic" VL decay pattern. We cannot exclude that this is partly due to treatment complications and subsequent treatment changes, but these children were characterised by significantly lower CD4 percentages (CD4%) at start of treatment compared to those with a "clean" VL decline. Focusing on this "clean" subset, the TTS could be predicted by mathematical modelling, and we identified baseline VL and CD4% as the major factors determining the TTS. Conclusion: As VL steeply increases and CD4% constantly decreases in untreated HIV-infected infants, the progression of an HIV infection is largely determined by these 2 factors. To prevent a further disease progression, treatment should be initiated early after contracting HIV, which consequently shortens TTS.

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Interests of the Non-Human Primate Models for HIV Cure Research

Cited by 13 publications

References 188 publications

FoxP3+ CD8 T-cells in acute HIV infection and following early antiretroviral therapy initiation

FoxP3+ CD8 T-cells in acute HIV infection and following early antiretroviral therapy initiation

HIV Latency in Myeloid Cells: Challenges for a Cure

Paediatric HIV infection from a mathematical perspective

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