Virologic Failure Following Persistent Low-level Viremia in a Cohort of HIV-Positive Patients: Results From 12 Years of Observation

Laprise, Claudie; Pokomandy, Alexandra de; Baril, Jean-Guy; Dufresne, Simon-Frédéric; Trottier, Helen

doi:10.1093/cid/cit529

Cited by 147 publications

(115 citation statements)

References 13 publications

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“…Prolonged breaks in adherence may thus represent islands of infectivity where host infectiousness relates positively to pretreatment SPVL. Finally, viral “blips” (brief and intermittent periods of detectable viral load despite adherence to ART) are observed more often in hosts with high baseline SPVL (Havlir et al., 2001; Leierer et al., 2015), and infections with large or frequent blips are more likely to experience virologic failure (Easterbrook et al., 2002; Grennan et al., 2012; Laprise, De Pokomandy, Baril, Dufresne, & Trottier, 2013) and achieve higher viral rebound upon treatment interruption (Castro et al., 2013). These observations span drug types, host populations and viral clades, but collectively support the intuitive assumption that infections with high SPVL are more infectious than those with low SPVL when imperfectly treated.…”

Section: Discussionmentioning

confidence: 99%

Modelling the evolution of HIV‐1 virulence in response to imperfect therapy and prophylaxis

Mideo

2017

Evolutionary Applications

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Average HIV‐1 virulence appears to have evolved in different directions in different host populations since antiretroviral therapy first became available, and models predict that HIV drugs can select for either higher or lower virulence, depending on how treatment is administered. However, HIV virulence evolution in response to “leaky” therapy (treatment that imperfectly suppresses viral replication) and the use of preventive drugs (pre‐exposure prophylaxis) has not been explored. Using adaptive dynamics, we show that higher virulence can evolve when antiretroviral therapy is imperfectly effective and that this evolution erodes some of the long‐term clinical and epidemiological benefits of HIV treatment. The introduction of pre‐exposure prophylaxis greatly reduces infection prevalence, but can further amplify virulence evolution when it, too, is leaky. Increasing the uptake rate of these imperfect interventions increases selection for higher virulence and can lead to counterintuitive increases in infection prevalence in some scenarios. Although populations almost always fare better with access to interventions than without, untreated individuals could experience particularly poor clinical outcomes when virulence evolves. These findings predict that antiretroviral drugs may have underappreciated evolutionary consequences, but that maximizing drug efficacy can prevent this evolutionary response. We suggest that HIV virulence evolution should be closely monitored as access to interventions continues to improve.

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Section: Discussionmentioning

confidence: 99%

Modelling the evolution of HIV‐1 virulence in response to imperfect therapy and prophylaxis

Mideo

2017

Evolutionary Applications

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“…Accurate, sensitive measurement of viral load at regular intervals is required to monitor the effectiveness of therapy. Virologic failure as defined by the World Health Organization (WHO) or the U.S. Department of Health and Human Services (HHS) is an increase in plasma HIV RNA levels to Ͼ1,000 copies/ml (1) or Ն200 copies/ml (2) as measured at 3-month intervals on therapy, but even viral loads of Ͻ200 copies/ml can be predictive of viral rebound (5,6) and can be associated with the evolution of drug resistance (7). Initiation of antiretroviral therapy at diagnosis could lead to a significant decrease in HIV transmission rates and, ultimately, to reductions in HIV incidence rates (8).…”

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confidence: 99%

Evaluation of Hologic Aptima HIV-1 Quant Dx Assay on the Panther System on HIV Subtypes

et al. 2016

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“…In particular, in patients undergoing suppressive ART, single measurements of HIV-1 RNA between 500 and 1,000 copies/ml seem to be associated with higher rebound risk, with respect to lower values (i.e., Ͻ500 copies/ml). To rule out blip or laboratory artifacts, VL increases starting from Ͻ500 copies/ml would benefit from confirmation by repeated testing (6,7).…”

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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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Virologic Failure Following Persistent Low-level Viremia in a Cohort of HIV-Positive Patients: Results From 12 Years of Observation

Abstract: In this cohort, all categories of persistent LLV between 50 and 999 copies/mL were associated with an increased risk of virologic failure. The results shed new light for the management of patients with LLV, especially with regard to LLV of 50-199 copies/mL.

Cited by 147 publications

References 13 publications

Modelling the evolution of HIV‐1 virulence in response to imperfect therapy and prophylaxis

Modelling the evolution of HIV‐1 virulence in response to imperfect therapy and prophylaxis

Evaluation of Hologic Aptima HIV-1 Quant Dx Assay on the Panther System on HIV Subtypes

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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