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HIV-1 tropism: a comparison between RNA and proviral DNA in routine clinical samples from Chilean patients.

Ferrer P, Montecinos L, Tello M, Tordecilla R, Rodríguez C, Ferrés M, Pérez CM, Beltrán C, Guzmán MA, Afani A - Virol. J. (2013)

Bottom Line: With cutoff 5.75% a concordance of 88.4% in tropism prediction was found after a simultaneous comparison between HIV tropism assessment by RNA and DNA.In total, five discrepancies (11.6%) were found, 3 patients were RNA-R5/DNA-X4 and two were RNA-X4/DNA-R5.A high degree of concordance was found between tropism testing with RNA and testing with proviral DNA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratorio de Medicina Molecular, Hospital Clínico Universidad de Chile, Santiago, Chile. pferrer40@gmail.com.

ABSTRACT

Background: HIV in Chile has a notification rate of 0.01%. Coreceptor antagonists are a family of antiretroviral drugs that are used with the prior knowledge of patients HIV-1 tropism. Viral RNA-based tropism detection requires a plasma viral load ≥1000 copies/mL, while proviral DNA-based detection can be performed regardless of plasma viral load. This test is useful in patients with low or undetectable viral loads and would benefit with a proper therapy. The aim of this study was to determine the correlation between HIV RNA and proviral genotypic DNA tropism tests.

Findings: Forty three Chilean patients were examined using population-based V3 sequencing, and a geno2pheno false-positive rate (FPR) cutoff values of 5, 5.75, 10 and 20%. With cutoff 5.75% a concordance of 88.4% in tropism prediction was found after a simultaneous comparison between HIV tropism assessment by RNA and DNA. In total, five discrepancies (11.6%) were found, 3 patients were RNA-R5/DNA-X4 and two were RNA-X4/DNA-R5. Proviral DNA enabled the prediction of tropism in patients with a low or undetectable viral load. For cutoff 5 and 5.75% genotypic testing using proviral DNA showed a similar sensitivity for X4 as RNA. We found that the highest sensitivity for detecting the X4 strain occurred with proviral DNA and cutoff of 10 and 20%. Viral loads were higher among X4 strain carriers than among R5 strain carriers (p < 0.05).

Conclusions: A high degree of concordance was found between tropism testing with RNA and testing with proviral DNA. Our results suggest that proviral DNA-based genotypic tropism testing is a useful option for patients with low or undetectable viral load who require a different therapy.

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Related in: MedlinePlus

Dispersion graph for simultaneous comparison between results of RNA–based prediction of tropism (x axis) and proviral DNA–based prediction (y axis) for 43 paired RNA/DNA samples. Predictions were performed with the geno2pheno software and results were expressed as false positive rate (FPR;%). The correlation coefficient was ρ = 0.817 (P = 2.39 × 10-11).
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Figure 1: Dispersion graph for simultaneous comparison between results of RNA–based prediction of tropism (x axis) and proviral DNA–based prediction (y axis) for 43 paired RNA/DNA samples. Predictions were performed with the geno2pheno software and results were expressed as false positive rate (FPR;%). The correlation coefficient was ρ = 0.817 (P = 2.39 × 10-11).

Mentions: For each sample, the lowest FPR obtained through RNA was correlated with the lowest FPR obtained through proviral DNA (Figure 1). The correlation coefficient (ρ) between both determinations was 0.817 with a p value of 2.39 × 10-11. The concordance in prediction between RNA and proviral DNA was 88.4%. Such results are similar to those found in previous articles [5-7].


HIV-1 tropism: a comparison between RNA and proviral DNA in routine clinical samples from Chilean patients.

Ferrer P, Montecinos L, Tello M, Tordecilla R, Rodríguez C, Ferrés M, Pérez CM, Beltrán C, Guzmán MA, Afani A - Virol. J. (2013)

Dispersion graph for simultaneous comparison between results of RNA–based prediction of tropism (x axis) and proviral DNA–based prediction (y axis) for 43 paired RNA/DNA samples. Predictions were performed with the geno2pheno software and results were expressed as false positive rate (FPR;%). The correlation coefficient was ρ = 0.817 (P = 2.39 × 10-11).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231446&req=5

Figure 1: Dispersion graph for simultaneous comparison between results of RNA–based prediction of tropism (x axis) and proviral DNA–based prediction (y axis) for 43 paired RNA/DNA samples. Predictions were performed with the geno2pheno software and results were expressed as false positive rate (FPR;%). The correlation coefficient was ρ = 0.817 (P = 2.39 × 10-11).
Mentions: For each sample, the lowest FPR obtained through RNA was correlated with the lowest FPR obtained through proviral DNA (Figure 1). The correlation coefficient (ρ) between both determinations was 0.817 with a p value of 2.39 × 10-11. The concordance in prediction between RNA and proviral DNA was 88.4%. Such results are similar to those found in previous articles [5-7].

Bottom Line: With cutoff 5.75% a concordance of 88.4% in tropism prediction was found after a simultaneous comparison between HIV tropism assessment by RNA and DNA.In total, five discrepancies (11.6%) were found, 3 patients were RNA-R5/DNA-X4 and two were RNA-X4/DNA-R5.A high degree of concordance was found between tropism testing with RNA and testing with proviral DNA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratorio de Medicina Molecular, Hospital Clínico Universidad de Chile, Santiago, Chile. pferrer40@gmail.com.

ABSTRACT

Background: HIV in Chile has a notification rate of 0.01%. Coreceptor antagonists are a family of antiretroviral drugs that are used with the prior knowledge of patients HIV-1 tropism. Viral RNA-based tropism detection requires a plasma viral load ≥1000 copies/mL, while proviral DNA-based detection can be performed regardless of plasma viral load. This test is useful in patients with low or undetectable viral loads and would benefit with a proper therapy. The aim of this study was to determine the correlation between HIV RNA and proviral genotypic DNA tropism tests.

Findings: Forty three Chilean patients were examined using population-based V3 sequencing, and a geno2pheno false-positive rate (FPR) cutoff values of 5, 5.75, 10 and 20%. With cutoff 5.75% a concordance of 88.4% in tropism prediction was found after a simultaneous comparison between HIV tropism assessment by RNA and DNA. In total, five discrepancies (11.6%) were found, 3 patients were RNA-R5/DNA-X4 and two were RNA-X4/DNA-R5. Proviral DNA enabled the prediction of tropism in patients with a low or undetectable viral load. For cutoff 5 and 5.75% genotypic testing using proviral DNA showed a similar sensitivity for X4 as RNA. We found that the highest sensitivity for detecting the X4 strain occurred with proviral DNA and cutoff of 10 and 20%. Viral loads were higher among X4 strain carriers than among R5 strain carriers (p < 0.05).

Conclusions: A high degree of concordance was found between tropism testing with RNA and testing with proviral DNA. Our results suggest that proviral DNA-based genotypic tropism testing is a useful option for patients with low or undetectable viral load who require a different therapy.

Show MeSH
Related in: MedlinePlus