Increased Frequency of HIV-1 Viral Load Blip Rate Observed After Switching From Roche Cobas Amplicor to Cobas Taqman Assay

Smit, Erasmus; Bhattacharya, Sanjay; Osman, Husam; Taylor, Steve

doi:10.1097/qai.0b013e3181aa13b3

Cited by 36 publications

(34 citation statements)

References 7 publications

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“…In vitro evidence and reports from our cohort and other sites have questioned the clinical implications of employing the TaqMan VL assay at the lower end of the dynamic range due to increased reports of detectable low-level viremia and ''blips'' in previously well-controlled individuals. [18][19][20][21] Because of concerns over the use of the TaqMan assay v.1.0 during the study period, VL <400 c/ml was utilized for the analysis of comparative effectiveness of 48-week virologic suppression. Primary viral load effectiveness analyses employed a missing is equal to missing approach, excluding patients who did not have a viral load measure within the 48-week assessment window.…”

Section: Willig Et Almentioning

confidence: 99%

Darunavir Outcomes Study: Comparative Effectiveness of Virologic Suppression, Regimen Durability, and Discontinuation Reasons for Three-Class Experienced Patients at 48 Weeks

Willig

Aban²,

Nevin³

et al. 2010

AIDS Research and Human Retroviruses

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Several new antiretroviral (ARV) agents for treatment experienced HIV-infected patients have been approved since June 2006, including darunavir (DRV) and raltegravir (RAL). While efficacious in clinical trials, the effectiveness, durability, and tolerability of these new ARVs remains understudied in the context of routine clinical care. The Darunavir Outcomes Study is a prospective cohort study of three-class ARV-experienced patients changing regimens at the 1917 Clinic after 1/7/2006. All treatment decisions were at the discretion of primary providers. Multivariate (MV) logistic regression for 48 week VL <400c/ml and Cox models for regimen durability were completed. Propensity score methods controlled for sociodemographics. Among 108 patients, mean age of 46, 48% were white, 80% male, with prior exposure to a mean 10.5 ARVs. Overall, 64% of patients achieved 48-week VL <400 c/ml. In MV modeling DRV/r (OR ¼5.77;95%CI ¼ 1.62-20.58) and RAL (OR ¼ 3.84;95%CI ¼ 1.23-11.95) use increased odds of 48-week suppression. Use of these agents exhibited a trend towards prolonged regimen durability in Cox models. Among those highly ARV-experienced, regimens containing DRV/r and/or RAL were more likely to achieve 48-week VL <400 c/ml and exhibited a trend towards prolonged durability. New agents have transformed the treatment landscape for ARV-experienced patients, with effectiveness in routine clinical care mirroring efficacy in clinical trials.

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Section: Willig Et Almentioning

confidence: 99%

Darunavir Outcomes Study: Comparative Effectiveness of Virologic Suppression, Regimen Durability, and Discontinuation Reasons for Three-Class Experienced Patients at 48 Weeks

Willig

Aban²,

Nevin³

et al. 2010

AIDS Research and Human Retroviruses

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“…The new real-time PCR methodologies offer a broad range of benefits over the traditional endpoint PCR, including higher precision, full automation with high throughput, expanded reportable range capabilities, and ever-decreasing lower limits of detection (20 to 40 copies/ml). However, with the improved sensitivity comes concern over an increased frequency of low-level viremia being detected (8,18,24) and the implications this may have for clinical management. assay.…”

mentioning

confidence: 99%

Cross-Platform Analysis of HIV-1 RNA Data Generated by a Multicenter Assay Validation Study with Wide Geographic Representation

et al. 2012

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HIV-1 RNA quantitation continues to be extremely important for monitoring patients infected with HIV-1, and a number of assays have been utilized for this purpose. Differences in assay performance with respect to log 10 recovery and HIV-1 subtype specificity have been well documented for commercially available assays, although comparisons are usually limited to one or two assay platforms. Two new FDA-approved assays, the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test (RT) and the Abbott RealTime HIV-1 assay (AR), that utilize real-time PCR have replaced previous HIV-1 RNA platforms. Inadequate detection of some strains of HIV-1 resulted in the addition of a new primer/probe set and the introduction of a second version of the RT assay. In this study, comparisons of assay performance between the different FDA-approved HIV-1 RNA assay platforms (both new and existing) were performed by using validation data that included both well-characterized virus stock and locally collected clinical samples. Laboratories across diverse geographical regions performed the validation testing and submitted data to the Virology Quality Assurance program (VQA) for analysis. Correlation values for clinical sample testing varied across the assay platforms ( r = 0.832 to 0.986), and average log 10 recoveries for HIV-1 RNA controls (compared to the nominal value) ranged from −0.215 to 0.181. These data demonstrate the need for use of one assay platform for longitudinal patient monitoring, but the data also reinforce the notion that no one assay is superior and that testing across platforms may be required for discordance reconciliation.

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“…This is consistent both with other findings of assay variability at low pVL 14 and with the observation that switching from the Amplicor to the Taqman 1 assay (40 copy/ml LLOQ) led to increased observation of blips. 1 Of greater concern than issues of assay accuracy per se was that blip detection can imply that pVL is consistently high in the 50 to 300 copy/ml range (Fig. 1).…”

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confidence: 99%

“…A number of theories have been advanced to explain viral blips, but there are essentially two hypotheses: (1) differences in detection of pVL at or around the lower limits of assay quantification (LLOQ) occur through errors in the reproducibility of the assays and fluctuations of pVL around mean HIV RNA levels below the LLOQ [1][2][3] ; and (2) new rounds of viral replication arise through a variety of mechanisms resulting in rapid increases in pVL above the LLOQ from previously low levels. [4][5][6] An underlying assumption with the second hypothesis is that successful ART suppresses pVL much lower than 50 copies/ml and a blip represents a large change in pVL.…”

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confidence: 99%

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Short Communication: HIV Blips While on Antiretroviral Therapy Can Indicate Consistently Detectable Viral Levels Due to Assay Underreporting

Murray

Zaunders²,

Koelsch³

et al. 2013

AIDS Research and Human Retroviruses

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Viral blips, where HIV RNA plasma viral load (pVL) intermittently increases above the lower limit of assay detection, are a cause for concern. We investigated a number of hypotheses for their cause. We assessed HIV RNA, and total and episomal HIV DNA from 16 individuals commencing antiretroviral therapy (ART) consisting of raltegravir and tenofovir/emtricitabine for 3 years, using two assays: a single-copy assay [SCA; lower limit of quantification (LLOQ), < 1 copy/ml] and the Amplicor assay (LLOQ of 50 copies/ml). Two individuals exhibited viral blips. From week 20 onward, the period where ART had achieved its final suppressive levels, pVL ranged from < 1 to 330 copies/ml, except for one individual at the final time. Both assays were 98% consistent (108/110) in assessing pVL < 50 copies/ml, but the Amplicor assay registered 56% of samples (19/34) as below the LLOQ that were in the 50 to 1000 copy/ml range as quantified by SCA. pVL changes between successive time points did not correlate with changes in cellular infection as measured through either total or episomal HIV DNA. Changes in pVL were correlated (negatively) with changes in total CD4+ T cell numbersPatients receiving stable, seemingly suppressive ART can have pVL near the 50 copy LLOQ at multiple time points. The high Amplicor assay error rate around this level implies that viral blips underrepresent pVL being more consistently above the LLOQ. Activation of latently infected cells is less likely to contribute to this phenomenon. S uppression of HIV plasma viral load (pVL) to as low levels as possible and for as long as possible is the primary goal of antiretroviral therapy (ART). Sudden rises of pVL in a patient after extended periods in the undetectable range ( < 50 copies/ml for many assays) can be a cause for concern for both physician and patient. A consistent increase in pVL is often a sign of ART failure, most likely due to noncompliance, low plasma drug levels, or the outgrowth of a drug-resistant viral quasispecies. The clinical implications of viral "blips," where seemingly random detectable pVL levels occur amongst undetectable ones, are less clear.A number of theories have been advanced to explain viral blips, but there are essentially two hypotheses: (1) differences in detection of pVL at or around the lower limits of assay quantification (LLOQ) occur through errors in the reproducibility of the assays and fluctuations of pVL around mean HIV RNA levels below the LLOQ 1-3 ; and (2) new rounds of viral replication arise through a variety of mechanisms resulting in rapid increases in pVL above the LLOQ from previously low levels. [4][5][6] An underlying assumption with the second hypothesis is that successful ART suppresses pVL much lower than 50 copies/ml and a blip represents a large change in pVL.We investigated these questions using data from 16 HIVinfected, therapy-naive patients [eight primary (PHI) and eight chronic (CHI)] commencing raltegravir and Truvada (tenofovir/emtricitabine) who were followed for 3 years (the PINT Study 7...

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Increased Frequency of HIV-1 Viral Load Blip Rate Observed After Switching From Roche Cobas Amplicor to Cobas Taqman Assay

Cited by 36 publications

References 7 publications

Darunavir Outcomes Study: Comparative Effectiveness of Virologic Suppression, Regimen Durability, and Discontinuation Reasons for Three-Class Experienced Patients at 48 Weeks

Darunavir Outcomes Study: Comparative Effectiveness of Virologic Suppression, Regimen Durability, and Discontinuation Reasons for Three-Class Experienced Patients at 48 Weeks

Cross-Platform Analysis of HIV-1 RNA Data Generated by a Multicenter Assay Validation Study with Wide Geographic Representation

Short Communication: HIV Blips While on Antiretroviral Therapy Can Indicate Consistently Detectable Viral Levels Due to Assay Underreporting

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