Ultrasensitive Assessment of Residual Low-Level HIV Viremia in HAART-Treated Patients and Risk of Virological Failure

Maggiolo, Franco; Callegaro, Annapaola; Cologni, Giuliana; Bernardini, Claudia; Velenti, Daniela; Gregis, Giampietro; Quinzan, Giampaolo; Soavi, Laura; Iannotti, Nathalie; Malfatto, Emanuele; Leone, Sebastiano

doi:10.1097/qai.0b013e3182567a57

Cited by 82 publications

(97 citation statements)

References 33 publications

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“…when routine viral load (VL) is found between quantitation limit and detection limit) [16]. This also represents one of the suspected causes of virological failure [17,18], immunological suboptimal gain [18] or persistent immune activation [19], but this is also currently debated [20][21][22].…”

Section: Cd38mentioning

confidence: 99%

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Saison

Ferry

Demaret

et al. 2014

Clinical and Experimental Immunology

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SummaryThe mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (Tregs) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4 + T cell count (> or < 500/mm 3 ). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4 + lymphocytes, including Treg subsets, and CD8 + T cells was performed. Percentages of activated CD4 + T cells, Tregs, effector Tregs and terminal effector Tregs were found to be significantly elevated in iIR. Neither the percentage of activated CD8+ T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4 + T cell count and percentage of Tregs were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4 + and CD8+ T cells, Treg percentages and very low-level viraemia. Causative interactions between Tregs and CD4 + T cells should now be explored prospectively in a large patients cohort.

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Section: Cd38mentioning

confidence: 99%

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Saison

Ferry

Demaret

et al. 2014

Clinical and Experimental Immunology

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“…Therapy outcomes have been shown to be influenced by lowlevel viremia in some studies (16,(22)(23)(24)(25)(26)(27)(28) but not others (29)(30)(31)(32), in part reflecting differences in the measured outcomes. However, the overall clinical relevance of low-level viremia remains controversial.…”

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confidence: 99%

Comparative Performances of HIV-1 RNA Load Assays at Low Viral Load Levels: Results of an International Collaboration

et al. 2014

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Low-level viremia during antiretroviral therapy and its accurate measurement are increasingly relevant. Here, we present an international collaboration of 4,221 paired blood plasma viral load (pVL) results from four commercial assays, emphasizing the data with low pVL. The assays compared were the Abbott RealTime assay, the Roche Amplicor assay, and the Roche TaqMan version 1 and version 2 assays. The correlation between the assays was 0.90 to 0.97. However, at a low pVL, the correlation fell to 0.45 to 0.85. The observed interassay concordance was higher when detectability was defined as 200 copies/ml than when it was defined as 50 copies/ml. A pVL of ϳ100 to 125 copies/ml by the TaqMan version 1 and version 2 assays corresponded best to a 50-copies/ml threshold with the Amplicor assay. Correlation and concordance between the viral load assays were lower at a low pVL. Clear guidelines are needed on the clinical significance of low-level viremia.

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“…Furthermore, even HIV-RNA levels Ͻ50 copies/ml (residual viremia [RV]) are receiving increased attention, because this level may announce beforehand a viral rebound risk in a manner that is directly proportional to the extent of the RV (8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

Ability of Two Commercially Available Assays (Abbott RealTi m e HIV-1 and Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 Version 2.0) To Quantify Low HIV-1 RNA Levels (<1,000 Copies/Milliliter): Comparison with Clinical Samples and NIBSC Working Reagent for Nucleic Acid Testing Assays

et al. 2014

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Concordance between molecular assays may be suboptimal at low HIV-1 viremia levels (<1,000 copies/ml); therefore, it may be difficult to define and compare virologic endpoints for successful and failed therapy. We compared two commercial assays (the Abbott RealTime HIV-1 and the Roche Cobas AmpliPrep/TaqMan HIV-1 version 2.0) for their ability to detect and quantify low viral loads. A comparison was performed using 167 residual clinical samples (with values ranging from "not detected" to 1,000 copies/ml, as measured by the Abbott assay) and the National Institute and Biological Standards and Control (NIBSC) HIV-1 RNA working reagent 1 for nucleic acid amplification techniques (NAT) assays (serially diluted to a range from 1 to 1,000 copies/ ml). Quantitative results were compared using Lin's concordance correlation coefficient and a Bland-Altman plot. Concordance with the qualitative results was measured by Cohen's kappa statistic. With clinical samples, the degree of interassay concordance of the qualitative results at a 40-copies/ml HIV-1 RNA threshold was substantial ( ‫؍‬ 0.762); the correlation among the quantified samples was suboptimal (concordance correlation coefficient, 0.728; P < 0.0001); the mean difference of the values between the Roche and Abbott assays was 0.193 log 10 copies/ml. Using the HIV-1 RNA working reagent 1 for NAT assays, the results provided by the Roche assay were, on average, 3 times higher than expected, while the Abbott assay showed high accuracy. The Roche assay was highly sensitive, being able to detect a level as low as 3.5 copies/ml HIV-1 RNA with 95% probability. The performance characteristics of each molecular assay should be taken into account when HIV-1 RNA threshold values for "virologic suppression," "virologic failure," "persistent low viral loads," etc., are defined and indicated in the support of clinical decisions.

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Ultrasensitive Assessment of Residual Low-Level HIV Viremia in HAART-Treated Patients and Risk of Virological Failure

Cited by 82 publications

References 33 publications

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

Comparative Performances of HIV-1 RNA Load Assays at Low Viral Load Levels: Results of an International Collaboration

Ability of Two Commercially Available Assays (Abbott RealTi m e HIV-1 and Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 Version 2.0) To Quantify Low HIV-1 RNA Levels (<1,000 Copies/Milliliter): Comparison with Clinical Samples and NIBSC Working Reagent for Nucleic Acid Testing Assays

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