Genetic diversity among human immunodeficiency virus-1 non-B subtypes in viral load and drug resistance assays

UMR 145 VIH et Maladies Associées Institut de Recherche pour le Développement (IRD) and University of Montpellier 1, Montpellier, France.
Clinical Microbiology and Infection (Impact Factor: 5.2). 10/2010; 16(10):1525-31. DOI: 10.1111/j.1469-0691.2010.03300.x
Source: PubMed

ABSTRACT Clin Microbiol Infect 2010; 16: 1525–1531
The tremendous diversity of human immunodeficiency virus (HIV)-1 strains circulating worldwide has an important impact on almost all aspects of the management of this infection, from the identification of infected persons, through treatment efficacy and monitoring, and prevention strategies such as vaccine design. The areas where HIV-1 genetic diversity is highest are those where the majority of patients in need of treatment and biological monitoring live. With increased access to treatment in these areas, it is expected that the demand for monitoring tools such as viral load assays and resistance tests will also increase, and their reliability will be critical. Regular updates of these assays during the last two decades have aimed at improving their performances in different ways that include their reliability with different HIV-1 strains. We here review to what extent HIV-1 genetic diversity still limits or not the use of currently available viral load and resistance tests.

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    • "Most of available HIV-1 RNA assays are expensive (>s20/test). Also, they are subjected to sequence variability constraints that may significantly affect their performance by spoiling the hybridization of the primers and/or probe [Peeters et al., 2010; Luft et al., 2011; Rouet et al., 2011]. Globally, large field performance evaluations of HIV-1 RNA assays are lacking in Central Africa where emerging HIV-1 genetic diversity is the highest. "
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    ABSTRACT: Evaluations of HIV-1 RNA viral load assays are lacking in Central Africa. The main objective of our study was to assess the reliability of HIV-1 RNA results obtained with three different assays for samples collected in Gabon. A total of 137 plasma specimens were assessed for HIV-1 RNA using the Abbott RealTime HIV-1® and Nuclisens HIV-1 EasyQ® version 2.0 assays. It included HIV-1 non-B samples (n = 113) representing six subtypes, 10 CRFs and 18 URFs from patients infected with HIV-1 and treated with antiretrovirals that were found HIV-1 RNA positive (≥300 copies/ml) with the Generic HIV viral load® assay; and samples (n = 24) from untreated individuals infected with HIV-1 but showing undetectable (<300 copies/ml) results with the Biocentric kit. For samples found positive with the Generic HIV viral load® test, correlation coefficients obtained between the three techniques were relatively low (R = 0.65 between Generic HIV viral load® and Abbott RealTime HIV-1®, 0.50 between Generic HIV viral load® and Nuclisens HIV-1 EasyQ®, and 0.66 between Abbott RealTime HIV-1® and Nuclisens HIV-1 EasyQ®). Discrepancies by at least one log10 were obtained for 19.6%, 33.7%, and 20% of samples, respectively, irrespective of genotype. Most of samples (22/24) from untreated study patients, found negative with the Biocentric kit, were also found negative with the two other techniques. In Central Africa, HIV-1 genetic diversity remains challenging for viral load testing. Further studies are required in the same area to confirm the presence of HIV-1 strains that are not amplified with at least two different viral load assays. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 01/2014; 86(1). DOI:10.1002/jmv.23770 · 2.22 Impact Factor
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    • "This study found a predominance of CRF02 AG (86/147, 58.5%) and found that there was the circulation of 11 subtypes/CRFs, 16 unique recombinant forms and one unclassified sample, which is representative of a very high genetic diversity. The predominance of CRF02 AG has been previously described, particularly in Senegal and generally in West Africa (Peeters et al., 2010). The prevalence of subtype C strains and unique recombinants was higher than previously described in the general population of Senegal (Toure-Kane et al., 2000). "
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    ABSTRACT: The objective of this study was to investigate the performance of the ViroSeq HIV-1 Genotyping System v2.0 on HIV-1 non-B strains identified in Senegalese patients. The study involved 150 patients, and genotyping was performed using the ViroSeq HIV-1 Genotyping System v2.0 or an in-house method developed by the French National Agency on AIDS Research AC11 when the ViroSeq HIV-1 Genotyping System v2.0 failed. The sequences were edited to assess the performance of sequencing primers at their presumed binding regions. The Polymorphism was studied in the regions between the sequences of Senegalese patients and the subtype B strains used as references. The phylogenetic analysis showed a predominance of CRF02_AG (88/150; 58.7%) and the circulation of 11 subtypes/CRFs, 16 unique recombinant forms (URFs) and one unclassified sample. The amplification and sequencing rates were 98% (147/150) and 96.6% (142/147), respectively. This study showed that only primer B exhibited 100% success, while the failure rate ranged from 1.4% to 71.4% for the other primers (D: 71.4%, A and H: 12.2%, F: 7.5%, G: 5.5% and C: 1.4%). These findings suggest the need for an alternative method or alternative primers for non-B strains that were not sequenced successfully using the ViroSeq HIV-1 Genotyping System v2.0.
    Journal of virological methods 12/2012; 188(1-2). DOI:10.1016/j.jviromet.2012.11.044 · 1.88 Impact Factor
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    • "There is currently no 42 assay able to quantify the whole spectrum of circulating HIV-1 43 strains. Differences in primers/probe design, target region, technol- 44 ogy used may be responsible for underestimation of the viral load 45 or failure of detection with direct implications for clinical manage- 46 ment and detection of treatment failure (Peeters et al., 2010). "
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    ABSTRACT: HIV-1 viral load determination is a crucial step for monitoring the efficacy of highly active antiretroviral therapy (HAART) and predicts disease progression. Real-time PCR based assays are available for monitoring the viral load. They differ in sensitivity, genomic target region and dynamic range. In this study, the performance of the Roche Cobas Taqman HIV-1 v2.0 was evaluated on plasma samples from HIV-1 positive patients in parallel with the Abbott RealTime HIV-1 assay in a routine diagnostic setting. Overall, there was a good agreement between the two assays. However, some samples detected by the Abbott RealTime HIV-1 assay but below the limit of quantitation of the assay were found negative result when tested with the Roche Cobas Taqman HIV-1 v2.0. It is conceivable that signal anomalies or background noise may affect the lower-end precision of the Abbott RealTime HIV-1 assay. Based on these results, it is concluded that it is not recommended to switch platform during longitudinal viral load monitoring of HIV-1 positive patients.
    Journal of virological methods 03/2011; 173(2):399-402. DOI:10.1016/j.jviromet.2011.03.014 · 1.88 Impact Factor
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