- Oral presentation
- Open Access
O123. Short-term variation of HIV tropism readouts in the absence of CCR5 antagonists
© Brumme et al; licensee BioMed Central Ltd. 2010
Published: 8 November 2010
Spontaneous tropism changes (from R5 to non-R5 or vice-versa) were observed in approximately 10% of patients between screening and study baseline in the maraviroc (MVC) clinical trials. Little is known of the biology of these apparent short-term tropism fluctuations.
Population-based and "deep" V3-loop sequencing were performed in 53 MVC recipients in the MERIT, MOTIVATE and A4001029 studies who spontaneously changed tropism readout by the original Trofile assay between screening and baseline (~4-8 weeks) and 72 randomly sampled patients who did not change. Tropism was inferred by "geno2pheno" with previously defined cutoffs: 2% X4 prevalence with a 3.5% false-positive rate (fpr) for "deep" sequencing; 5.75% fpr for population-based sequencing.
Screening X4% [IQR]
Baseline X4% [IQR]
In most cases, the prevalence of non-CCR5 usage inferred from "deep" sequencing was stable over the short term between screening and baseline. Where apparent phenotypic tropism changes from R5 to non-R5 occurred, non-R5 virus was generally detectable at the screening timepoint by genotype, coupled with relatively small increases in non-R5 virus by baseline. Small variations in CXCR4-using HIV populations around the phenotypic assay detection limit, rather than coreceptor switch, contributed to apparent tropism switching from R5 to non-R5.
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