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. 2017 Sep;55(9):2827-2837.
doi: 10.1128/JCM.00656-17. Epub 2017 Jul 12.

Comparative Evaluation of Subtyping Tools for Surveillance of Newly Emerging HIV-1 Strains

Lavinia Fabeni  1 , Giulia Berno  2 , Joseph Fokam  3 , Ada Bertoli  4 , Claudia Alteri  4 , Caterina Gori  2 , Federica Forbici  2 , Desiré Takou  3 , Alessandra Vergori  2 , Mauro Zaccarelli  2 , Gaetano Maffongelli  5 , Vanni Borghi  6 , Alessandra Latini  7 , Alfredo Pennica  8 , Claudio Maria Mastroianni  9 , Francesco Montella  10 , Cristina Mussini  6 , Massimo Andreoni  5 , Andrea Antinori  2 , Carlo Federico Perno  2 , Maria Mercedes Santoro  4 ; Resistance Study Group
Collaborators, Affiliations

Comparative Evaluation of Subtyping Tools for Surveillance of Newly Emerging HIV-1 Strains

Lavinia Fabeni et al. J Clin Microbiol. 2017 Sep.

Abstract

HIV-1 non-B subtypes/circulating recombinant forms (CRFs) are increasing worldwide. Since subtype identification can be clinically relevant, we assessed the added value in HIV-1 subtyping using updated molecular phylogeny (Mphy) and the performance of routinely used automated tools. Updated Mphy (2015 updated reference sequences), used as a gold standard, was performed to subtype 13,116 HIV-1 protease/reverse transcriptase sequences and then compared with previous Mphy (reference sequences until 2014) and with COMET, REGA, SCUEAL, and Stanford subtyping tools. Updated Mphy classified subtype B as the most prevalent (73.4%), followed by CRF02_AG (7.9%), C (4.6%), F1 (3.4%), A1 (2.2%), G (1.6%), CRF12_BF (1.2%), and other subtypes (5.7%). A 2.3% proportion of sequences were reassigned as different subtypes or CRFs because of misclassification by previous Mphy. Overall, the tool most concordant with updated Mphy was Stanford-v8.1 (95.4%), followed by COMET (93.8%), REGA-v3 (92.5%), Stanford-old (91.1%), and SCUEAL (85.9%). All the tools had a high sensitivity (≥98.0%) and specificity (≥95.7%) for subtype B. Regarding non-B subtypes, Stanford-v8.1 was the best tool for C, D, and F subtypes and for CRFs 01, 02, 06, 11, and 36 (sensitivity, ≥92.6%; specificity, ≥99.1%). A1 and G subtypes were better classified by COMET (92.3%) and REGA-v3 (98.6%), respectively. Our findings confirm Mphy as the gold standard for accurate HIV-1 subtyping, although Stanford-v8.1, occasionally combined with COMET or REGA-v3, represents an effective subtyping approach in clinical settings. Periodic updating of HIV-1 reference sequences is fundamental to improving subtype characterization in the context of an effective epidemiological surveillance of non-B strains.

Keywords: HIV-1; circulating recombinant forms; genetic diversity; phylogeny; subtypes; subtyping automated tools.

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Figures

FIG 1
FIG 1
Concordance between HIV-1 automated subtyping tools and new Mphy in the overall population (A), for B subtype (B), and for non-B subtypes (C).
FIG 2
FIG 2
Flow chart of a practical HIV-1 subtyping approach. This flow chart represents the HIV-1 subtyping practical approach through online subtyping tools, proposed in the case that Mphy cannot be used in routine practice due to its complexity.
FIG 3
FIG 3
Flow chart of Mphy. Shown are the main steps of HIV molecular phylogeny (Mphy) used for subtype assignment.
See this image and copyright information in PMC

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