HIV-1 DNA decay dynamics in early treated individuals: practical considerations for clinical trial design.
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
01 08 2020
01 08 2020
Historique:
received:
08
11
2019
revised:
17
03
2020
accepted:
18
03
2020
pubmed:
27
4
2020
medline:
25
6
2021
entrez:
27
4
2020
Statut:
ppublish
Résumé
Initiation of combination antiretroviral therapy (cART) soon after HIV-1 infection limits the establishment of viral reservoirs. Thus, early treated individuals are preferred candidates to evaluate novel viral remission strategies. However, their cART-dependent HIV-1 DNA decay dynamics are still poorly defined. This can hamper the design and interpretation of results from clinical trials intended to further reduce viral reservoirs. To clarify the duration of cART needed for the HIV-1 reservoir to be stabilized in early treated individuals. We characterized the longitudinal decline of total HIV-1 DNA levels by droplet digital PCR in 21 individuals initiating cART within 6 months after estimated HIV-1 acquisition. Measurements were taken at cART initiation, after 6 months and annually until Year 4. Correlations between virological and clinical parameters were statistically analysed. Statistical modelling was performed applying a mixed-effects model. Total HIV-1 DNA experienced a median overall decrease of 1.43 log10 units (IQR = 1.17-1.69) throughout the 4 years of follow-up. Baseline levels for total HIV-1 DNA, viral load, absolute CD4+ T cell count and CD4+/CD8+ ratio correlate with final HIV-1 DNA measurements (R2 = 0.68, P < 0.001; R2 = 0.54, P = 0.012; R2 = -0.47, P = 0.031; and R2 = -0.59, P = 0.0046, respectively). Statistical modelling shows that after 2 years on cART the viral reservoir had reached a set point. A waiting period of 2 years on cART should be considered when designing interventions aiming to impact latent HIV-1 reservoir levels and viral rebound kinetics after cART discontinuation, in order to facilitate interpretation of results and enhance the chance of viral control.
Sections du résumé
BACKGROUND
Initiation of combination antiretroviral therapy (cART) soon after HIV-1 infection limits the establishment of viral reservoirs. Thus, early treated individuals are preferred candidates to evaluate novel viral remission strategies. However, their cART-dependent HIV-1 DNA decay dynamics are still poorly defined. This can hamper the design and interpretation of results from clinical trials intended to further reduce viral reservoirs.
OBJECTIVES
To clarify the duration of cART needed for the HIV-1 reservoir to be stabilized in early treated individuals.
METHODS
We characterized the longitudinal decline of total HIV-1 DNA levels by droplet digital PCR in 21 individuals initiating cART within 6 months after estimated HIV-1 acquisition. Measurements were taken at cART initiation, after 6 months and annually until Year 4. Correlations between virological and clinical parameters were statistically analysed. Statistical modelling was performed applying a mixed-effects model.
RESULTS
Total HIV-1 DNA experienced a median overall decrease of 1.43 log10 units (IQR = 1.17-1.69) throughout the 4 years of follow-up. Baseline levels for total HIV-1 DNA, viral load, absolute CD4+ T cell count and CD4+/CD8+ ratio correlate with final HIV-1 DNA measurements (R2 = 0.68, P < 0.001; R2 = 0.54, P = 0.012; R2 = -0.47, P = 0.031; and R2 = -0.59, P = 0.0046, respectively). Statistical modelling shows that after 2 years on cART the viral reservoir had reached a set point.
CONCLUSIONS
A waiting period of 2 years on cART should be considered when designing interventions aiming to impact latent HIV-1 reservoir levels and viral rebound kinetics after cART discontinuation, in order to facilitate interpretation of results and enhance the chance of viral control.
Identifiants
pubmed: 32335675
pii: 5825343
doi: 10.1093/jac/dkaa139
pmc: PMC7366202
doi:
Substances chimiques
Anti-Retroviral Agents
0
DNA, Viral
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2258-2263Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
Références
Retrovirology. 2018 Feb 02;15(1):18
pubmed: 29394935
J Infect Dis. 2013 Oct 15;208(8):1202-11
pubmed: 23852127
AIDS. 2003 Sep 5;17(13):1871-9
pubmed: 12960819
Open Forum Infect Dis. 2015 Sep 22;2(4):ofv138
pubmed: 26512359
Biometrics. 1999 Jun;55(2):410-8
pubmed: 11318194
J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):140-7
pubmed: 24457632
J Intern Med. 2011 Dec;270(6):550-60
pubmed: 21929712
EBioMedicine. 2016 Sep;11:68-72
pubmed: 27460436
Nat Commun. 2015 Oct 09;6:8495
pubmed: 26449164
Lancet HIV. 2016 Oct;3(10):e463-72
pubmed: 27658863
Nat Med. 2016 Sep;22(9):1043-9
pubmed: 27500724
PLoS One. 2012;7(3):e33948
pubmed: 22479485
Clin Infect Dis. 2015 Jun 1;60(11):1715-21
pubmed: 25737374
J Virol. 2014 Sep 1;88(17):10056-65
pubmed: 24965451
PLoS One. 2017 Apr 17;12(4):e0175899
pubmed: 28414780
AIDS. 2018 Sep 24;32(15):2113-2118
pubmed: 30005008
Nature. 2019 Feb;566(7742):120-125
pubmed: 30700913
AIDS. 2011 Nov 13;25(17):2069-78
pubmed: 21860347
Elife. 2014 Sep 12;3:e03821
pubmed: 25217531
Clin Infect Dis. 2014 Nov 1;59(9):1312-21
pubmed: 25073894
Trends Microbiol. 2015 Apr;23(4):192-203
pubmed: 25747663
J Antimicrob Chemother. 2013 May;68(5):1169-78
pubmed: 23335199