The dual-target approach in viral HIV-1 viremia testing: An added value to virological monitoring?
Adult
Anti-Retroviral Agents
/ therapeutic use
CD4 Lymphocyte Count
DNA, Viral
/ blood
Drug Resistance, Viral
Female
Gene Products, pol
/ genetics
Genotype
HIV Infections
/ drug therapy
HIV Long Terminal Repeat
/ genetics
HIV-1
/ genetics
Humans
Leukocytes, Mononuclear
/ cytology
Logistic Models
Male
Middle Aged
Proviruses
/ genetics
RNA, Viral
/ blood
Viral Load
Viremia
/ pathology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
04
06
2019
accepted:
10
01
2020
entrez:
6
2
2020
pubmed:
6
2
2020
medline:
28
4
2020
Statut:
epublish
Résumé
New methods of HIV-1 RNA quantification based on dual-target detection are increasingly used in HIV viral load monitoring, but clinical implications and impact of dual-target detection on HIV-1 infection management are not established. Aptima HIV-1 Quant Dx assay is a last generation HIV viral load method, that uses pol and LTR as simultaneous target, providing quantitative results based mainly on pol target, while LTR target is used to report the results when pol signal is absent. In our laboratory, about 6% of results of all HIV-1 viral load tests performed with this platform in one year period resulted from LTR signal. Interestingly, LTR-based viremia (sometimes exceeding 1,000 copies/mL) was observed in a small proportion (up to 1%) of patients under ART, considered for long time virologically suppressed on the basis of a single target (pol-based) assay. Male gender, >700 vs <200 CD4 cell/mL and dual therapy including NRTI plus either NNRTI, or PI/b or INSTI were independently associated with increased risk of LTR-based HIV-1 viral load detection by multivariable logistic regression. A significant linear correlation was observed between LTR-based HIV-1 RNA levels and PBMC-associated proviral DNA. Moreover, in a small group of patients with HIV-1 RNA levels >200 copies/mL, longitudinal assessments showed parallel kinetics between plasma viremia and proviral DNA. Sequencing of pol region for drug resistance assessment in patients with LTR-based viremia failed on plasma HIV-1 RNA, while it was successful on proviral DNA. The detection/quantification of HIV-1 viremia based only on LTR signal with a dual target assay in samples resulting undetectable with the more conventional target pol needs accurate evaluation; unravelling the biological basis of this phenomenon, here described for the first time, is mandatory to establish relevance and implication by both pathogenetic (i.e. infectivity of LTR-detected viruses, reservoir turnover, immune activation, etc.) and clinical standpoint.
Identifiants
pubmed: 32023284
doi: 10.1371/journal.pone.0228192
pii: PONE-D-19-15804
pmc: PMC7001951
doi:
Substances chimiques
Anti-Retroviral Agents
0
DNA, Viral
0
Gene Products, pol
0
RNA, Viral
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0228192Commentaires et corrections
Type : ErratumIn
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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