Genotypic Prediction of Human Immunodeficiency Virus Type 1 Tropism by Use of Plasma and Peripheral Blood Mononuclear Cells in the Routine Clinical Laboratory

Paar, Christian; Geit, Maria; Stekel, Herbert; Berg, Jörg

doi:10.1128/jcm.00336-11

Cited by 23 publications

(12 citation statements)

References 26 publications

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“…We found a high level of concordance between the two compartments (ϳ84%), confirming findings described previously in other studies (2,11,17,18). With the FPR set at 10%, concordance was found mainly for R5-tropic viruses (83%).…”

Section: Discussionsupporting

confidence: 79%

“…Although the use of MVC after DNA tropism testing has potential, this strategy is not yet recommended in current guidelines, because of the lack of large studies on this topic (6). Several studies showed a high level of concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and pvDNA findings (2,11,(17)(18)(19), but the factors that might be associated with the discrepancies between the two compartments have not yet been clearly determined. Moreover, little is known about the tropism concordance between the two compartments in patients with virological suppression (viremia levels of Ͻ50 copies/ml).…”

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confidence: 99%

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Genotypic Tropism Testing in HIV-1 Proviral DNA Can Provide Useful Information at Low-Level Viremia

et al. 2015

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eThe possibility of performing genotypic tropism testing (GTT) with proviral DNA (pvDNA) even during suppressed viremia would facilitate the use of CCR5 inhibitors as part of switching, simplification, or intensification strategies. Thus, we aimed to evaluate the tropism concordance between plasma RNA and pvDNA samples and to assess which factors could affect possible discrepancies between the two compartments. GTT was performed using both plasma RNA and pvDNA from 55 sample pairs from drug-experienced patients. Potential differences between the two compartments were evaluated by analyzing coreceptor usage and genetic variability. Paired samples were also stratified in three levels of viremia (<50, 51 to 500, and >500 copies/ml). Overall, Geno2Pheno comparisons of false-positive rates in the two compartments showed good correlation (r ‫؍‬ 0.72). A high level of concordance in tropism predictions for the two compartments was found (46/55 sample pairs [83.6%]). Among the 9 sample pairs with discordant tropisms, a larger proportion of pvDNA samples harboring CXCR4/dual-mixed-tropic viruses was found, in comparison with plasma RNA samples (88.9% versus 11.1%; P ‫؍‬ 0.0034). Discordant samples were characterized by greater genetic variability than were concordant samples. With stratification of the paired samples according to viremia levels, the prevalence of discordant samples decreased with increasing viremia (<50 copies/ml, 21.4%; 51 to 500 copies/ml, 15.4%; >500 copies/ml, 6.7%; P ‫؍‬ 0.2). Our findings confirm that prediction of viral tropism using pvDNA is feasible even in low-level viremia and provides useful information for therapy optimization for patients with low or suppressed viremia.

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Section: Discussionsupporting

confidence: 79%

mentioning

confidence: 99%

Genotypic Tropism Testing in HIV-1 Proviral DNA Can Provide Useful Information at Low-Level Viremia

et al. 2015

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“…Although clinical evaluations have been generally based on plasma-based genotypic assays, cell-based assays are favored for patients whose viral load is suppressed by ART but for whom a drug change is being considered because of adverse effects or regimen simplification [3]. Although both assays were predictive of a virologic response, discrepancies between genotypic tropism predictions using viral RNA and those using proviral DNA have been reported in many studies [16, 18–21, 23]. …”

Section: Discussionmentioning

confidence: 99%

“…Studies comparing DNA and RNA tropism assays have reported concordance rates ranging from 78 to 100 % [12–23]. In general, X4-tropic sequences are more frequently drawn from proviral DNA than from viral RNA (clinical meanings) [12, 17, 18, 20, 23], but opposite results have been reported in some studies [16, 19, 21]. However, the causes of these discrepancies are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Possible involvement of distinct phylogenetic clusters of HIV-1 variants in the discrepancies between coreceptor tropism predictions based on viral RNA and proviral DNA

Kotani

Sumii

Hasegawa

et al. 2016

J Pharm Health Care Sci

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BackgroundThe coreceptor tropism testing should be conducted prior to commencing a regimen containing a CCR5 antagonist for treatment of HIV-1 infection. For aviremic patients on long antiretroviral therapy, proviral DNA is often used instead of viral RNA in genotypic tropism testing. However, the tropism predictions from RNA and DNA are sometimes different. We examined the cause of the discrepancies between HIV-1 tropism predictions based on viral RNA and proviral DNA.MethodsThe nucleotide sequence of the env C2V3C3 region was determined using pair samples of plasma RNA and peripheral blood mononuclear cell DNA from 50 HIV-1 subtype B-infected individuals using population-based sequencing. The samples with discrepant tropism assessments between RNA and DNA were further analyzed using deep sequencing, followed by phylogenetic analysis. The tropism was assessed using the algorithm geno2pheno with a false-positive rate cutoff of 10 %.ResultsIn population-based sequencing, five of 50 subjects showed discrepant tropism predictions between their RNA and DNA samples: four exhibited R5 tropism in RNA and X4 tropism in DNA, while one exhibited the opposite pattern. In the deep sequencing and phylogenetic analysis, three subjects had single clusters comprising of RNA- and DNA-derived sequences that were a mixture of R5 and X4 sequences. The other two subjects had two and three distinct phylogenetic clusters of sequences, respectively, each of which was dominated by R5 or X4 sequences; sequences of the R5-dominated cluster were mostly found in RNA, while sequences of the X4-dominated cluster were mostly in DNA.ConclusionsSome of HIV-1 tropism discrepancies between viral RNA and proviral DNA seem to be caused by phylogenetically distinct clusters which resides in plasma and cells in different frequencies. Our findings suggest that the tropism testing using PBMC DNA or deep sequencing may be required when the viral load is not suppressed or rebounds in the course of a CCR5 antagonist-containing regimen.

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“…4. Finally, in clinical genotypic testing of HIV-1 tropism, from proviral or plasma samples, the importance of testing in triplicates remains elusive and is not as clear-cut as the authors maintain (4,6). As testing in triplicates is tedious and costly and does not readily fit into the work flow of a routine clinical laboratory, it is paramount to scientifically justify this.…”

Section: A Further Principal Issue In Genotypic Testing Of Hiv-1 Tro-mentioning

confidence: 99%

Issues on Results of the External Quality Assessment for Proviral DNA Testing of HIV-1 Tropism in the Maraviroc Switch Collaborative Study

et al. 2013

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Genotypic Prediction of Human Immunodeficiency Virus Type 1 Tropism by Use of Plasma and Peripheral Blood Mononuclear Cells in the Routine Clinical Laboratory

Cited by 23 publications

References 26 publications

Genotypic Tropism Testing in HIV-1 Proviral DNA Can Provide Useful Information at Low-Level Viremia

Genotypic Tropism Testing in HIV-1 Proviral DNA Can Provide Useful Information at Low-Level Viremia

Possible involvement of distinct phylogenetic clusters of HIV-1 variants in the discrepancies between coreceptor tropism predictions based on viral RNA and proviral DNA

Issues on Results of the External Quality Assessment for Proviral DNA Testing of HIV-1 Tropism in the Maraviroc Switch Collaborative Study

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