Immunovirologic Control 24 Months After Interruption of Antiretroviral Therapy Initiated Close to HIV Seroconversion

Lodi, Sara; Meyer, Laurence; Kelleher, Anthony D.; Rosińska, Magdalena; Ghosn, Jade; Sannes, Mette; Porter, Kholoud

doi:10.1001/archinternmed.2012.2719

Cited by 107 publications

(83 citation statements)

References 10 publications

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“…Our results show that viral rebound generally occurs quickly after treatment interruption and confirm the rarity of post-treatment controllers, most of whom initiated ART during early infection [30][31][32]. A more in-depth analysis of participants with sustained post-treatment control within the ACTG ATI studies is needed.…”

Section: Discussionsupporting

confidence: 55%

The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption

2016

Aids

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Objectives-Therapies to achieve sustained antiretroviral therapy-free HIV remission will require validation in analytic treatment interruption (ATI) trials. Identifying biomarkers that predict time to viral rebound could accelerate the development of such therapeutics.Design-A pooled analysis of participants from 6 AIDS Clinical Trials Group ATI studies to identify predictors of viral rebound.Methods-Cell-associated DNA (CA-DNA) and CA-RNA were quantified in pre-ATI PBMC samples, and residual plasma viremia (RV) was measured using the single-copy assay.Results-Participants who initiated ART during acute/early HIV infection and those on an NNRTI-containing regimen had significantly delayed viral rebound. Participants who initiated ART during acute/early infection had lower levels of pre-ATI CA-RNA (acute/early vs. chronictreated: median <92 vs. 156 HIV-1 RNA copies/10 6 CD4+ cells, P<0.01). Higher pre-ATI CA-RNA levels were significantly associated with shorter time to viral rebound (≤4 wks vs. 5-8 wks vs. >8 wks: median 182 vs. 107 vs. <92 HIV-1 RNA copies/10 6 CD4+ cells, Kruskal-Wallis P<0.01). The proportion of participants with detectable RV prior to ATI was significantly higher among those with shorter time to viral rebound.Conclusions-Higher levels of HIV expression while on ART are associated with shorter time to HIV rebound after treatment interruption. Quantification of the active HIV reservoir may provide a biomarker of efficacy for therapies that aim to achieve ART-free HIV remission.

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Section: Discussionsupporting

confidence: 55%

The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption

2016

Aids

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“…If confirmed, the present characterization of transcriptionally and functionally distinctive NK cells may be exploited for the prospective identification of HIV patients with good chances of success for undergoing cART simplification to monotherapy (65) or cART interruption (e.g., PTCP) (58,66,67).…”

Section: Discussionmentioning

confidence: 75%

Control of the HIV-1 DNA Reservoir Is AssociatedIn VivoandIn Vitrowith NKp46/NKp30 (CD335 CD337) Inducibility and Interferon Gamma Production by Transcriptionally Unique NK Cells

Marras¹,

Casabianca

Bozzano

et al. 2017

J Virol

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“…In contrast to the SMART trial, there were no adverse effects on clinical outcomes 51, 210. Adult case series from prospective observational cohort studies and the results of the Agence Nationale de Recherche sur le SIDA (ANRS) Virological and Immunological Studies in Controllers after Treatment Interruption (VISCONTI) study suggest that some patients with different genetic characteristics and characteristic CD8 cell response to HIV, after prolonged treatment of primary HIV infection, can control HIV replication post treatment interruption for at least several years 211, 212. It appears that restricting the pool of HIV‐infected cells by very early treatment might decrease long‐lived viral reservoirs 213, which may be essential for successful control without therapy 212.…”

Section: Stopping Treatment and Treatment Interruptionsmentioning

confidence: 98%

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

et al. 2015

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The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV‐1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short‐term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long‐term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first‐ and second‐line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

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Immunovirologic Control 24 Months After Interruption of Antiretroviral Therapy Initiated Close to HIV Seroconversion

Abstract: Most patients experience virologic rebound soon after cART interruption; however, although PTCs are rare, the results of this study confirm their existence.

Cited by 107 publications

References 10 publications

The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption

The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption

Control of the HIV-1 DNA Reservoir Is AssociatedIn VivoandIn Vitrowith NKp46/NKp30 (CD335 CD337) Inducibility and Interferon Gamma Production by Transcriptionally Unique NK Cells

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

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