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: 5.77). 10/2010; 16(10):1525-31. DOI: 10.1111/j.1469-0691.2010.03300.x
Source: PubMed


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.
    Full-text · Article · Jan 2014 · Journal of Medical Virology
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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.
    Full-text · Article · Dec 2012 · Journal of virological methods
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    • "The huge genetic variability of HIV-1 results in a complex and dynamic molecular classification of types (HIV-1 and 2), groups (M,N,O,P), and the pandemic group M could be divided into subtypes (A-D,F-H,J,K) and recombinant forms, such as circulating recombinant forms (CRF) and unique recombinant forms (URF). Such HIV-1 variation has an important impact on diagnosis, viral load measurement and the performance of HIV-1 genotyping systems [1-3]. Thus, HIV-1 subtypes also contribute to the capacity of HIV-1 to evade the host immune response, [4] which can affect the response to antiretroviral treatment and, consequently, to the emergence of drug resistance [5]. "
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    ABSTRACT: BACKGROUND: The city of Sao Paulo has the highest AIDS case rate, with nearly 60% in Brazil. Despite,several studies involving molecular epidemiology, lack of data regarding a large cohort studyhas not been published from this city.Objectives This study aimed to describe the HIV-1 subtypes, recombinant forms and drug resistancemutations, according to subtype, with emphasis on subtype C and BC recombinants in thecity of São Paulo, Brazil.Study designRNA was extracted from the plasma samples of 302 HIV-1-seropositive subjects, of which211 were drug-naive and 82 were exposed to ART. HIV-1 partial pol region sequences wereused in phylogenetic analyses for subtyping and identification of drug resistance mutations.The envelope gene of subtype C and BC samples was also sequenced. RESULTS: From partial pol gene analyses, 239 samples (79.1%) were assigned as subtype B, 23 (7.6%)were F1, 16 (5.3%) were subtype C and 24 (8%) were mosaics (3 CRF28/CRF29-like). Thesubtype C and BC recombinants were mainly identified in drug-naïve patients (72.7%) andthe heterosexual risk exposure category (86.3%), whereas for subtype B, these values were69.9% and 57.3%, respectively (p = 0.97 and p = 0.015, respectively). An increasing trend ofsubtype C and BC recombinants was observed (p < 0.01). CONCLUSION: The HIV-1 subtype C and CRFs seem to have emerged over the last few years in the city ofSão Paulo, principally among the heterosexual population. These findings may have animpact on preventive measures and vaccine development in Brazil.
    Full-text · Article · Aug 2012 · Virology Journal
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