Evolution in the sensitivity of quantitative HIV-1 viral load tests

https://doi.org/10.1016/j.jcv.2011.09.015Get rights and content

Abstract

Significant advancements in molecular diagnostics have been made since the inception and application of PCR-based technologies in clinical diagnostic laboratories and the management of HIV-1 infected patients. More recently, real-time PCR has improved the overall performance of assays used for detecting and quantifying HIV-1 RNA viral load in patients undergoing antiretroviral treatment. The effects of these changes and the interpretations of the HIV-1 viral load results are discussed in this review in the context of the different assays used, the viral dynamics of the HIV-1 virus, and the recent changes to HIV-1 treatment guidelines.

Section snippets

Background HIV-1 RNA viral load tests

Real-time PCR tests are capable of detecting and quantifying small amounts of nucleic acid. This is especially the case with HIV-1 viral load monitor tests, where the analytical sensitivity of commercial tests is currently as low as 20 copies/mL.1 Nearly two decades ago, Roche Molecular Systems (Pleasanton, CA) HIV-1 viral load tests, the AMPLICOR® HIV-1 MONITOR Test, version 1.5 (which used microwell plates) and later the semi-automated COBAS® AMPLICOR HIV-1 MONITOR Test, version 1.5 (CA-HIM

Analytical considerations

In a given plasma sample from an HIV-1-infected patient, the volume drawn will have various proportions of numbers, “X”, of HIV-1 RNA copies that generate three types of reported test results (Table 3 and Fig. 1). These proportions can be approximated using a Poisson probability distribution describing the probability of having X = 0, 1, 2,… copies in a test sample as a function of the mean number of copies per sample volume in the patient's blood. The random variation of the number of copies in

Conclusions

Advances in technologies will continue to bolster improvements in molecular diagnostics applications, potentially providing a diagnostic tool before it can be well understood clinically. This has been the case with more sensitive tests for HIV-1 RNA viral load monitoring and detecting low levels of HIV-1 RNA without a clear context or supporting data to determine clinical significance. However, more sensitive HIV-1 RNA tests have proved to be useful in research studies to help better understand

Funding source

None.

Ethical approval

Not required.

Conflict of interest

Bryan R. Cobb, Jeffrey E. Vaks, Tri Do, and Regis A. Vilchez are employees of Roche Molecular Systems.

References (48)

  • A. De Bel et al.

    Correction of underquantification of human immunodeficiency virus type 1 load with the second version of the Roche COBAS AmpliPrep/COBAS TaqMan assay

    J Clin Microbiol

    (2010)
  • M. Wirden et al.

    Upgraded COBAS Ampliprep-COBAS TaqMan Version 2.0 HIV-1 RNA quantification assay versus first version: correction of underestimations

    J Clin Microbiol

    (2011)
  • S.M. Hammer et al.

    Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel

    JAMA

    (2008)
  • T. Elbeik et al.

    Comparative analysis of HIV-1 viral load tests on subtype quantification: Bayer Versant HIV-1 RNA 3.0 versus Roche Amplicor HIV-1 Monitor version 1.5

    J Acquir Immune Defic Syndr

    (2002)
  • N. Taylor et al.

    Initial evaluation of the Roche COBAS TaqMan HIV-1 v2.0 assay for determining viral load in HIV-infected individuals

    Antivir Ther

    (2009)
  • S. Pas et al.

    Performance evaluation of the new Roche COBAS AmpliPrep COBAS TaqMan HIV-1 test version 2.0 for the quantification of HIV-1 RNA

    J Clin Microbiol

    (2010)
  • J.S. Montaner et al.

    International AIDS Society-USA Antiretroviral Guidelines Panel Poor agreement between 2 tests for measuring low levels of HIV-1 viral load

    Clin Infect Dis

    (2009)
  • V. Lima et al.

    Increased reporting of detectable plasma HIV-1 RNA levels at the critical threshold of 50 copies per milliliter with the Taqman assay in comparison to the Amplicor assay

    J Acquir Immune Defic Syndr

    (2009)
  • E. Smit et al.

    Increased frequency of HIV-1 viral load blip rate observed after switching from Roche COBAS Amplicor to COBAS TaqMan assay

    J Acquir Immune Defic Syndr

    (2009)
  • S. Szabo et al.

    Low-level viremia associated with the use of TaqMan assay

    J Int Assoc Physicians AIDS Care (Chic)

    (2010)
  • M.G. de Boer et al.

    Potential influence of more-sensitive HIV-1 load detection by the new Roche COBAS AmpliPrep/COBAS TaqMan version 2.0 assay on clinical management of HIV-positive pregnant women

    J Clin Microbiol

    (2010)
  • T. Bourlet et al.

    HIV-1 load comparison using four commercial real-time assays

    J Clin Microbiol

    (2011)
  • Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents

    (2011)
  • K. Sebire et al.

    Stability of human immunodeficiency virus RNA in blood specimens as measured by a commercial PCR-based assay

    J Clin Microbiol

    (1998)
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