A Randomized Controlled Trial of the Value of Phenotypic Testing in Addition to Genotypic Testing for HIV Drug Resistance

Dunn, David; Green, H; Loveday, Clive; Rinehart, Alex; Pillay, Deenan; Fisher, MJ; McCormack, Sheena; Babiker, AG; Darbyshire, JH

doi:10.1097/01.qai.0000148533.12329.96

Cited by 14 publications

(4 citation statements)

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“…However, in the subgroup of patients with more than four previous failures patients with vPRT did have significantly prolonged time to treatment failure [29]. In another randomized controlled trial by Dunn et al there was no difference between GRT alone and GRT plus PRT [30]. Both trial groups worked with a less sensitive method of PRT compared to the one used in this study.…”

Section: Discussionmentioning

confidence: 88%

“…This study was designed to analyse whether the dissecting, sensitive format of PRT may provide a diagnostic benefit over GRT. Analyses comparing virtual PRT to GRT have thus far not been able to document a clear clinical advantage for PRT with a higher proportion of patients achieving a suppressed viral load [14,15,26-30]. Our first retrospective single centre analysis of GRT combined with a highly sensitive rPRT already suggested, although statistically underpowered, that patients being switched to new cART based on drug choice from a combination of both tests tended to have better virological response than those with only GRT-based resistance information [31].…”

Section: Introductionmentioning

confidence: 99%

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Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

et al. 2011

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BackgroundReplicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients.MethodsPatients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5log reduction).ResultsOf 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15).ConclusionsIn heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

et al. 2011

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“…We excluded 19 potentially relevant studies and summarized these in the Characteristics of excluded studies table. Five of these studies used genotypic guided therapy in both study arms (Bossi 2004; Clevenbergh 2000; Dunn 2005a; Gianotti 2006; Hales 2006); and four compared genotypic versus phenotypic testing and included no control arm (Mazzotta 2003; Perez‐Elias 2003; Saracino 2004; Torti 2005). One was a simulation study (Lorenzana 2012).…”

Section: Resultsmentioning

confidence: 99%

Antiretroviral resistance testing in HIV-positive people

Aves

Tambe

Siemieniuk

et al. 2018

Cochrane Database of Systematic Reviews

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Background Resistance to antiretroviral therapy (ART) among people living with human immunodeficiency virus (HIV) compromises treatment effectiveness, often leading to virological failure and mortality. Antiretroviral drug resistance tests may be used at the time of initiation of therapy, or when treatment failure occurs, to inform the choice of ART regimen. Resistance tests (genotypic or phenotypic) are widely used in high‐income countries, but not in resource‐limited settings. This systematic review summarizes the relative merits of resistance testing in treatment‐naive and treatment‐exposed people living with HIV. Objectives To evaluate the effectiveness of antiretroviral resistance testing (genotypic or phenotypic) in reducing mortality and morbidity in HIV‐positive people. Search methods We attempted to identify all relevant studies, regardless of language or publication status, through searches of electronic databases and conference proceedings up to 26 January 2018. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov to 26 January 2018. We searched Latin American and Caribbean Health Sciences Literature (LILACS) and the Web of Science for publications from 1996 to 26 January 2018. Selection criteria We included all randomized controlled trials (RCTs) and observational studies that compared resistance testing to no resistance testing in people with HIV irrespective of their exposure to ART. Primary outcomes of interest were mortality and virological failure. Secondary outcomes were change in mean CD4‐T‐lymphocyte count, clinical progression to AIDS, development of a second or new opportunistic infection, change in viral load, and quality of life. Data collection and analysis Two review authors independently assessed each reference for prespecified inclusion criteria. Two review authors then independently extracted data from each included study using a standardized data extraction form. We analysed data on an intention‐to‐treat basis using a random‐effects model. We performed subgroup analyses for the type of resistance test used (phenotypic or genotypic), use of expert advice to interpret resistance tests, and age (children and adolescents versus adults). We followed standard Cochrane methodological procedures. Main results Eleven RCTs (published between 1999 and 2006), which included 2531 participants, met our inclusion criteria. All of these trials exclusively enrolled patients who had previous exposure to ART. We found no observational studies. Length of follow‐up time, study settings, and types of resistance testing varied greatly. Follow‐up ranged from 12 to 150 weeks. All studies were conducted in Europe, USA, or South America. Seven ...

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“…The available literature indicates that resistance testing is valuable in guiding the selection of initial therapy and determining the optimal antiretroviral therapy (ART) regimen after treatment failure [ 119 ]. Numerous studies have shown the cost-effectiveness of genotypic resistance testing both before initiating ART and during instances of virologic failure [ 120 , 121 , 122 , 123 , 124 ]. However, it should be noted that pre-treatment integrase gene sequencing, particularly for individuals taking integrase strand transfer inhibitors (INSTIs), may increase costs and potentially lead to unfavourable clinical outcomes [ 125 ].…”

Section: Drivers Of Virologic Failurementioning

confidence: 99%

Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review

Foka

Mufhandu

2023

Viruses

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Antiretroviral therapies (ARTs) have revolutionized the management of human immunodeficiency virus (HIV) infection, significantly improved patient outcomes, and reduced the mortality rate and incidence of acquired immunodeficiency syndrome (AIDS). However, despite the remarkable efficacy of ART, virologic failure remains a challenge in the long-term management of HIV-infected individuals. Virologic failure refers to the persistent detectable viral load in patients receiving ART, indicating an incomplete suppression of HIV replication. It can occur due to various factors, including poor medication adherence, drug resistance, suboptimal drug concentrations, drug interactions, and viral factors such as the emergence of drug-resistant strains. In recent years, extensive efforts have been made to understand and address virologic failure in order to optimize treatment outcomes. Strategies to prevent and manage virologic failure include improving treatment adherence through patient education, counselling, and supportive interventions. In addition, the regular monitoring of viral load and resistance testing enables the early detection of treatment failure and facilitates timely adjustments in ART regimens. Thus, the development of novel antiretroviral agents with improved potency, tolerability, and resistance profiles offers new options for patients experiencing virologic failure. However, new treatment options would also face virologic failure if not managed appropriately. A solution to virologic failure requires a comprehensive approach that combines individualized patient care, robust monitoring, and access to a range of antiretroviral drugs.

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A Randomized Controlled Trial of the Value of Phenotypic Testing in Addition to Genotypic Testing for HIV Drug Resistance

Abstract: The study did not demonstrate added value of phenotypic resistance testing in conjunction with genotypic resistance testing in patients with limited therapeutic options.

Cited by 14 publications

References 16 publications

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

Antiretroviral resistance testing in HIV-positive people

Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review

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