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Updated: Apr 12, 2026
Prediction of HIV-1 Coreceptor Usage Tropism by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
X4 Tropic Virus Prediction Is Associated with a Nadir CD4 T-Cell Count below 100 Cells/mm
Matthieu Sechet1, Catherine Roussel, Jean-Luc Schmit
1EA4294 Unité de Virologie Clinique et Fondamentale, UPJV et Centre Hospitalo-Universitaire, Amiens, France.
Objective:
The aim of this study was to evaluate tropism prediction performances of three algorithms [geno2pheno false-positive rate 10% (G2P10), position-specific scoring matrix (PSSM) and a combination of the 11/25 and net charge rules] and to investigate the viral and host factors potentially involved in the X4 or R5 prediction in human immunodeficiency virus-1 (HIV-1) patients.
Methods:
Viral tropism was determined in 179 HIV-1-infected patients eligible for CCR5 antagonist therapy. HIV-1 RNA or DNA was extracted and amplified for env gp120 sequencing. In parallel, demographic, viral, immunological and clinical determinants were analyzed.
Results:
According to the G2P10 algorithm, 48 patients harbored X4 or X4R5 virus. The tropism prediction was concordant for 87.7 and 88.2% of samples when comparing G2P10 with PSSM or with a combination of the 11/25 and net charge rules, respectively. X4 prediction was significantly associated with more than 35 amino acids in the V3 domain (p < 0.0001) and loss of an N-linked glycosylation site (p < 0.0001). Of the factors studied, only the nadir CD4 T-cell count was significantly associated with X4 tropism (p = 0.01).
Conclusion:
We determined that the X4 virus detection is closely linked to the nadir CD4 T-cell count below 100 cells/mm(3) that must be taken into account when considering a CCR5 antagonist therapy switch.
