Virological Outcome Measures During Analytical Treatment Interruptions in Chronic HIV-1-Infected Patients.

HIV-1 STI immune-based therapy vaccine viral load

Journal

Open forum infectious diseases
ISSN: 2328-8957
Titre abrégé: Open Forum Infect Dis
Pays: United States
ID NLM: 101637045

Informations de publication

Date de publication:
Dec 2019
Historique:
received: 27 05 2019
accepted: 11 11 2019
entrez: 5 3 2020
pubmed: 5 3 2020
medline: 5 3 2020
Statut: epublish

Résumé

Analytical treatment interruptions (ATIs) are essential in research on HIV cure. However, the heterogeneity of virological outcome measures used in different trials hinders the interpretation of the efficacy of different strategies. We conducted a retrospective analysis of viral load (VL) evolution in 334 ATI episodes in chronic HIV-1-infected patients collected from 11 prospective studies. Quantitative (baseline VL, set point, delta set point, VL, and delta VL at given weeks after ATI, peak VL, delta peak VL, and area under the rebound curve) and temporal parameters (time to rebound [TtR], set point, peak, and certain absolute and relative VL thresholds) were described. Pairwise correlations between parameters were analyzed, and potential confounding factors (sex, age, time of known HIV infection, time on ART, and immunological interventions) were evaluated. The set point was lower than baseline VL (median delta set point, -0.26; TtR could be an optimal surrogate marker of response in HIV cure strategies. Our results underline the importance of taking into account baseline VL and other confounding factors in the design and interpretation of these studies.

Sections du résumé

BACKGROUND BACKGROUND
Analytical treatment interruptions (ATIs) are essential in research on HIV cure. However, the heterogeneity of virological outcome measures used in different trials hinders the interpretation of the efficacy of different strategies.
METHODS METHODS
We conducted a retrospective analysis of viral load (VL) evolution in 334 ATI episodes in chronic HIV-1-infected patients collected from 11 prospective studies. Quantitative (baseline VL, set point, delta set point, VL, and delta VL at given weeks after ATI, peak VL, delta peak VL, and area under the rebound curve) and temporal parameters (time to rebound [TtR], set point, peak, and certain absolute and relative VL thresholds) were described. Pairwise correlations between parameters were analyzed, and potential confounding factors (sex, age, time of known HIV infection, time on ART, and immunological interventions) were evaluated.
RESULTS RESULTS
The set point was lower than baseline VL (median delta set point, -0.26;
CONCLUSIONS CONCLUSIONS
TtR could be an optimal surrogate marker of response in HIV cure strategies. Our results underline the importance of taking into account baseline VL and other confounding factors in the design and interpretation of these studies.

Identifiants

pubmed: 32128329
doi: 10.1093/ofid/ofz485
pii: ofz485
pmc: PMC7047957
doi:

Types de publication

Journal Article

Langues

eng

Pagination

ofz485

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Références

Open Forum Infect Dis. 2014 Dec 23;1(3):ofu112
pubmed: 25734180
J Acquir Immune Defic Syndr. 2009 Dec;52(5):531-7
pubmed: 19855285
Sci Transl Med. 2013 Jan 2;5(166):166ra2
pubmed: 23283367
Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):E1126-34
pubmed: 25713386
AIDS Res Hum Retroviruses. 2015 Jan;31(1):36-44
pubmed: 25257573
J Infect Dis. 2018 Nov 5;218(12):1954-1963
pubmed: 30085241
AIDS Res Hum Retroviruses. 2009 Dec;25(12):1249-59
pubmed: 19943787
Sci Transl Med. 2017 Dec 6;9(419):
pubmed: 29212716
J Acquir Immune Defic Syndr. 2017 Jul 1;75(3):364-369
pubmed: 28394856
J Int AIDS Soc. 2015 Nov 09;18:20497
pubmed: 26561337
PLoS Pathog. 2018 Jan 11;14(1):e1006792
pubmed: 29324842
AIDS. 2014 Jun 1;28(9):1351-6
pubmed: 24959963
AIDS Res Hum Retroviruses. 2010 Apr;26(4):379-87
pubmed: 20377419
J Infect Dis. 2005 May 15;191(10):1680-5
pubmed: 15838795
AIDS. 2004 Dec 3;18(18):2361-9
pubmed: 15622312
J Acquir Immune Defic Syndr. 2008 Oct 1;49(2):142-50
pubmed: 18769356
AIDS. 2017 Aug 24;31(13):1895-1897
pubmed: 28590333
Arch Intern Med. 2003 May 26;163(10):1220-6
pubmed: 12767960
AIDS. 2001 Jun 15;15(9):F29-40
pubmed: 11416735
J Acquir Immune Defic Syndr. 2004 Jul 1;36(3):823-30
pubmed: 15213566
J Infect Dis. 2011 Feb 15;203(4):442-51
pubmed: 21245157
AIDS. 2009 Sep 24;23(15):1987-95
pubmed: 19696651
J Antimicrob Chemother. 2015;70(6):1833-42
pubmed: 25724985
J Acquir Immune Defic Syndr. 2016 Jul 1;72(3):310-3
pubmed: 26910502
J Acquir Immune Defic Syndr. 2007 Sep 1;46(1):39-47
pubmed: 17972364
J Antimicrob Chemother. 2009 Jan;63(1):184-8
pubmed: 19001447
AIDS. 1999 Jul 30;13(11):F79-86
pubmed: 10449278
N Engl J Med. 2006 Nov 30;355(22):2283-96
pubmed: 17135583
Clin Infect Dis. 2005 Sep 15;41(6):883-90
pubmed: 16107990
AIDS. 2016 Jan 28;30(3):343-53
pubmed: 26588174
AIDS. 2004 Aug 20;18(12):1697-705
pubmed: 15280781
AIDS. 2016 Mar 13;30(5):761-9
pubmed: 26730568
PLoS One. 2013 Oct 25;8(10):e78287
pubmed: 24205183
AIDS Res Hum Retroviruses. 2018 Jan;34(1):67-79
pubmed: 28562069
AIDS. 2003 Jan 3;17(1):43-51
pubmed: 12478068
Curr Opin HIV AIDS. 2008 Mar;3(2):131-5
pubmed: 19372954
J Acquir Immune Defic Syndr. 2004 Jul 1;36(3):791-9
pubmed: 15213562
J Virus Erad. 2017 Apr 1;3(2):82-84
pubmed: 28435691
Lancet. 1998 Nov 7;352(9139):1510-4
pubmed: 9820299
Int J Mol Sci. 2016 Nov 26;17(12):
pubmed: 27898045

Auteurs

Csaba Fehér (C)

Institute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute for Science and Technology, Barcelona, Spain.
Infectious Diseases Department, Hospital Clinic of Barcelona - HIVACAT, University of Barcelona, Barcelona, Spain.
Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) - HIVACAT, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.

Lorna Leal (L)

Infectious Diseases Department, Hospital Clinic of Barcelona - HIVACAT, University of Barcelona, Barcelona, Spain.
Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) - HIVACAT, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.

Montserrat Plana (M)

Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) - HIVACAT, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.

Nuria Climent (N)

Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) - HIVACAT, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.

Alberto Crespo Guardo (A)

Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) - HIVACAT, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.

Esteban Martínez (E)

Infectious Diseases Department, Hospital Clinic of Barcelona - HIVACAT, University of Barcelona, Barcelona, Spain.
Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) - HIVACAT, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.

Pedro Castro (P)

Infectious Diseases Department, Hospital Clinic of Barcelona - HIVACAT, University of Barcelona, Barcelona, Spain.
Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) - HIVACAT, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.
Medical Intensive Care Unit, Hospital Clinic of Barcelona, Barcelona, Spain.

Vicens Díaz-Brito (V)

Infectious Diseases Department, Hospital Clinic of Barcelona - HIVACAT, University of Barcelona, Barcelona, Spain.

Beatriz Mothe (B)

IrsiCaixa AIDS Research Institute, Badalona, Spain.
Infectious Diseases Department, Hospital Germans Trias i Pujol, Badalona, Spain.
University of Vic - Central University of Catalonia, Vic, Spain.

Juan Carlos López Bernaldo De Quirós (JC)

HIV/Infectious Diseases Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.

Josep María Gatell (JM)

Infectious Diseases Department, Hospital Clinic of Barcelona - HIVACAT, University of Barcelona, Barcelona, Spain.
Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) - HIVACAT, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.
ViiV Healthcare, Tres Cantos, Spain.

Patrick Aloy (P)

Institute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute for Science and Technology, Barcelona, Spain.
Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.

Felipe García (F)

Infectious Diseases Department, Hospital Clinic of Barcelona - HIVACAT, University of Barcelona, Barcelona, Spain.
Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) - HIVACAT, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.

Classifications MeSH