Sensitivity of seven HIV subtyping tools differs among subtypes/recombinants in the Spanish cohort of naïve HIV-infected patients (CoRIS).
BACKGROUND
HIV-1 group M is classified into 9 subtypes and recombinants (CRFs/URFs). Variants other than subtype B (non-B) cause 90% of infections worldwide. HIV is often subtyped using automated tools instead of the gold-standard phylogenetic analysis. We evaluated the reliability of subtyping tools vs. phylogeny in a panel of HIV-1 pol sequences from the cohort of naïve patients of the HIV/AIDS Spanish Research Network (CoRIS).


METHODS
HIV-1 subtyping was performed using seven automated subtyping tools (Stanford, Geno2pheno, Rega, NCBI, EuResist, STAR, TherapyEdge) in HIV-1 pol sequences from 670 CoRIS patients previously subtyped by phylogeny (587 subtype B/83 non-B). Sensitivity with respect to phylogeny was assessed.


RESULTS
Most tools correctly classified subtype B, although up to 15% of non-B sequences were wrongly identified as B depending on the tool. For subtype B and CRF02_AG identification, Stanford/NCBI and Geno2pheno/Rega presented the highest/lowest sensitivities, respectively. EuResist and Geno2pheno correctly classified all 13 non-B "pure"subtypes at pol. The efficacy of all subtyping tools dropped clearly when identifying recombinants different from CRF02_AG. Only NCBI05, Rega and STAR identified URF, but with very low sensitivities. NCBI classified the highest number of subtypes B as non-B, and overestimated recombinants, especially when including references of 2009.


CONCLUSIONS
Automated tools are useful for subtype B identification, although they present serious limitations in classifying variants uncommon in developed regions, especially recombinants. Their sensitivity depends on the prevalence of non-B variants in the population, and decreases drastically when the frequency of recombinants increases. Furthermore, HIV-1 variant distribution differs according to the tool used.
FiBIO-IRYCIS (Hospital Ramón y Cajal) and CIBER-ESP, Madrid, Spain.
Gonzalo
G
Yebra
Miguel
M
de Mulder
Leticia
L
Martín
Santiago
S
Pérez-Cachafeiro
Carmen
C
Rodríguez
Pablo
P
Labarga
Federico
F
García
Cristina
C
Tural
Angels
A
Jaén
Gemma
G
Navarro
A
A
Holguín
D001331:Automation / Q000379:methods; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D058889:Molecular Typing; D010802:Phylogeny; D012680:Sensitivity and Specificity; D013030:Spain; D014773:Virology / Q000379:methods*; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D054302:pol Gene Products, Human Immunodeficiency Virus