Abstract
ObjectiveThe false-positive rate (FPR) is a percentage-score provided by Geno2Pheno-algorithm indicating the likelihood that a V3-sequence is falsely predicted as CXCR4-using. We evaluated the correlation between FPR obtained by V3 population-sequencing and the burden of CXCR4-using variants detected by V3 ultra-deep sequencing (UDPS) and Enhanced-Sensitivity Trofile assay (ESTA).Methods54 HIV-1 B-subtype infected-patients (all maraviroc-naïve), with viremia >10,000copies/ml, were analyzed. HIV-tropism was assessed by V3 population-sequencing, UDPS (considering variants with >0.5% prevalence), and ESTA.ResultsBy UDPS, CCR5-using variants were detected in 53/54 patients, irrespective of FPR values, and their intra-patient prevalence progressively increased by increasing the FPR obtained by V3 population-sequencing (rho = 0.75, p = 5.0e-8). Conversely, the intra-patient prevalence of CXCR4-using variants in the 54 patients analyzed progressively decreased by increasing the FPR (rho = −0.61; p = 9.3e-6). Indeed, no CXCR4-using variants were detected in 13/13 patients with FPR>60. They were present in 7/18 (38.8%) patients with FPR 20–60 (intra-patient prevalence range: 2.1%–18.4%), in 5/7 (71.4%) with FPR 10–20, in 4/6 (66.7%) with FPR 5–10, and in 10/10(100%) with FPR<5 (intra-patient prevalence range: 12.1%–98.1%).ConclusionsFPR by V3 population-sequencing can predict the burden of CXCR4-using variants. This information can be used to optimize the management of tropism determination in clinical practice. Due to its low cost and short turnaround time, V3 population-sequencing may represent the most feasible test for HIV-1 tropism determination. More sensitive methodologies (as UDPS) might be useful when V3 population-sequencing provides a FPR >20 (particularly in the range 20–60), allowing a more careful identification of patients harboring CXCR4-using variants.
Highlights
Human immunodeficiency virus type 1 (HIV-1) entry into host cells requires coordinated interactions of the envelope glycoprotein gp120 with the CD4 receptor and with one of the chemokine receptors, CCR5 or CXCR4
Determining HIV-1 co-receptor usage is critical since the CCR5 co-receptor has become the target of a new class of antiHIV-1 drugs that inhibit the entry of CCR5-tropic
Using a false-positive rate (FPR) of 10, the sensitivity and specificity of ultra-deep sequencing (UDPS) raised to 94.7% and dropped to 50%, respectively
Summary
Human immunodeficiency virus type 1 (HIV-1) entry into host cells requires coordinated interactions of the envelope glycoprotein gp120 with the CD4 receptor and with one of the chemokine receptors, CCR5 or CXCR4. Pure CCR5-tropic and pure CXCR4-tropic virus use only the CCR5 and CXCR4 coreceptors to enter target-cells, respectively, while dual-tropic virus can use both co-receptors [1]. Determining HIV-1 co-receptor usage is critical since the CCR5 co-receptor has become the target of a new class of antiHIV-1 drugs that inhibit the entry of CCR5-tropic. HIV-1 strains into the target cells by allosteric inhibition of the CCR5 co-receptor [5]. Assessment of HIV-1 co-receptor usage is mandatory for the clinical use of this drug (http://www.aidsinfo.nih.gov/ ContentFiles/AdultandAdolescentGL.pdf) [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
