Test Catalog

Test Id : HIVDR

HIV-1 Genotypic Drug Resistance to Reverse Transcriptase, Protease, and Integrase Inhibitors, Plasma

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying HIV-1 genotypic mutations associated with resistance to nucleotide and non-nucleoside reverse-transcriptase inhibitors, protease inhibitors, and integrase strain transfer inhibitors

 

Guiding initiation or change of combination antiretroviral therapy in individuals, including children, with HIV-1 infection

Highlights

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For more information see HIV Treatment Monitoring Algorithm

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Reverse Transcription Polymerase Chain Reaction (RT-PCR) followed by Targeted Next-Generation Sequencing (NGS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

HIV-1 Genotypic Drug Resistance, P

Aliases
Lists additional common names for a test, as an aid in searching

AIDS (acquired immune deficiency syndrome)

HIV Genotyping

HIV Resistance

HIV-1 Drug Resistance Mutation Analysis

HIV-1 Genotyping for Drug Resistance

HIV-1 Mutation Analysis

Next Gen Sequencing test

Human Immunodeficiency Virus (HIV)

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For more information see HIV Treatment Monitoring Algorithm

Specimen Type
Describes the specimen type validated for testing

Plasma EDTA

Ordering Guidance

This test is intended for detection and identification of drug resistance-associated HIV-1 genotypic mutations in plasma specimens of individuals prior to or while receiving combination antiretroviral therapy.

 

Prior to requesting this test, patients must have a confirmed plasma HIV-1 RNA level (ie, viral load) of 1000 copies/mL or higher within the preceding 30 days. HIVQN / HIV-1 RNA Detection and Quantification, Plasma is available to provide this prerequisite test result. Alternately, if the patient's viral load is unknown, order HIQDR / HIV-1 RNA Quantification with Reflex to Genotypic Drug Resistance to Reverse Transcriptase, Protease, and Integrase Inhibitors, Plasma, which will perform viral load followed by genotype, if appropriate.

 

For initial diagnosis of HIV, order HIVDX / HIV-1 and HIV-2 Antigen and Antibody Diagnostic Evaluation, Plasma.

Shipping Instructions

If shipment will be delayed for more than 24 hours, freeze plasma specimen at -70 degrees C (up to 35 days) until shipment on dry ice.

Necessary Information

The following ask-at-order entry question must be answered at the time of test ordering (mark answer on the test request form if not ordering electronically):

 

HIV-1 RNA level copies/mL in last 30 days = (select answer option)

<1000

1000 to 1,000,000

1,000,001 to 10,000,000

>10,000,000

 

Note: Test requests for submitted specimens with less than 1000 copies/mL (not sufficient amount for testing), “No,” or no response entered will be canceled.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Supplies: Aliquot Tube, 5 mL (T465)

Collection Container/Tube: Lavender top (EDTA)

Submission Container/Tube: Plastic vial

Specimen Volume: 2.2 mL

Collection Instructions:

1. Centrifuge blood collection tube and aliquot plasma into plastic vial per collection tube manufacturer's instructions (eg, centrifuge and aliquot within 2 hours of collection for BD Vacutainer tubes).

2. Freeze aliquoted plasma for shipment.

Additional Information: Specimens submitted for HIV-1 genotyping must contain 1000 copies/mL or more of HIV-1 RNA.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.8 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Plasma EDTA Frozen (preferred) 60 days
Refrigerated 7 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying HIV-1 genotypic mutations associated with resistance to nucleotide and non-nucleoside reverse-transcriptase inhibitors, protease inhibitors, and integrase strain transfer inhibitors

 

Guiding initiation or change of combination antiretroviral therapy in individuals, including children, with HIV-1 infection

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For more information see HIV Treatment Monitoring Algorithm

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Antiviral resistance may compromise the efficacy of antiretroviral therapy (ART) in patients receiving such therapy for HIV1 infection. When combination therapy fails, detection and analysis of antiviral drug resistance-associated viral genotypic mutations can guide necessary changes to ART to suppress viral replication (ie, reduce viral load), thereby improving patient outcome.

 

HIV-1 is an RNA virus that infects cells and is then converted to complementary DNA by the action of the viral reverse transcriptase (RT) gene product. RT has little proofreading capacity and therefore, incorporates errors in the proviral DNA. These errors are transcribed into infectious viral particles when the proviral DNA is transcribed into RNA. Similarly, the enzyme protease catalyzes a polyprotein to produce peptides necessary for active viral replication. Although ART (combination of nucleoside and nonnucleoside reverse-transcriptase inhibitors, protease inhibitors, and/or integrase strain transfer inhibitors) may be effective in reducing the viral load, genotypic mutations arising in the drug-targeted HIV-1 genome due to selective pressure from antiviral therapy will result in antiviral resistance that may compromise such therapy.

 

Amplification and analysis of drug-targeted HIV-gene sequence allows identification of changes in nucleotide bases and associated amino acid codons that may cause antiviral drug resistance. Such genotypic changes are deemed as variants by comparing the sequence data of the patient's HIV strain to those of a wild-type HIV strain. The significance of these genotypic mutations in relation to antiviral resistance is then determined by a set of interpretive rules developed by a consensus panel of leading experts in the field of HIV-1 resistance. Relevant data presented at a recognized scientific conference or published in peer-reviewed journals are considered by the consensus panel in developing these rules. When necessary, reliable unpublished drug resistance data known to consensus panel members may be considered in the process. The interpretive rules are updated by the consensus panel annually after reviewing newly published data on HIV-1 genotypic drug resistance mutations.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

Detectable HIV-1 genotypic mutations conferring resistance to an antiviral drug are reported as amino acid codon changes (eg, M184V) resulting from the nucleic acid base alterations, according to the interpretative algorithm of the Stanford HIV Database program. The codon mutations are categorized and interpreted in relation to previously published data of phenotypic antiviral susceptibility tests on virus that harbor such mutations. Each codon mutation is assigned a drug penalty score and the total score generated from all of the mutations relevant to the specific antiviral drug is used to estimate the level of resistance to that drug. These interpretive rules may be updated periodically by the Stanford HIV Database Team after reviewing newly published data on HIV-1 genotypic drug resistance-associated codon mutations.

 

Susceptible (SUSC) indicates that the codon mutations present in patient's HIV-1 strain have not been associated with resistance to the specific drug (Stanford HIVdb total score 0 to 9).

 

Potential Low-Level Resistance (PLR) indicates that codon mutations detected have been associated with possible reduction in susceptibility to the specific drug (Stanford HIVdb score 10 to 14).

 

Low-Level Resistance (LR) indicates that codon mutations detected have been associated with reduction in susceptibility to the specific drug (Stanford HIVdb score 15 to 29).

 

Intermediate Resistance (IR) indicates that codon mutations detected have been associated with reduction in susceptibility to the specific drug (Stanford HIVdb score 30 to 59).

 

High-level Resistant (HR) indicates that codon mutations detected have been associated with maximum reduction in susceptibility to the specific drug (Stanford HIVdb > or = 60).

 

Unable to genotype indicates that the sequence data obtained are of poor quality to determine the presence or absence of resistance-associated codon mutations in the patient's HIV-1 strain. Probable causes of such poor sequence data include polymorphism in the region of the sequencing primers interfering with primer binding and subsequent sequencing reaction, or low viral load (ie, <1000 copies/mL).

 

Inconclusive indicates inability of the assay to reliably determine antiviral resistance because of the presence of polymerase chain reaction inhibitors or ambiguous or incomplete viral target sequences generated from the assay.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Due to the complexity of the results generated, the International AIDS Society-USA Panel recommends expert interpretation of genotyping and phenotype test results for patient care management. A patient's response to antiviral therapy depends on multiple factors, including the percentage of patient's viral populations that is drug resistant, patient compliance with the prescribed drug therapy, patient access to adequate care, drug pharmacokinetics, and drug interactions. Drug resistance test results should be interpreted only in conjunction with clinical presentation and other laboratory markers when making therapeutic decisions.

 

Absence of resistance to a drug does not rule out the presence of reservoirs of drug-resistant virus in the infected individual.

 

The HIV-1 genotypic test is not a direct measure of drug resistance. Although genotypic testing can detect variants in the relevant HIV-1 genome, the significance of these variants requires careful interpretation to predict drug susceptibility. This assay's ability to amplify the target and detect genotypic mutation is poor and unreliable when the plasma HIV-1 viral load (VL) is less than 1000 copies/mL. Specimens submitted for this test should contain greater than or equal to 1000 copies/mL of HIV-1 RNA. Per assay manufacturer claims, the assay’s ability to detect minor drug-resistant HIV-1 variants among 90% or more of HIV-1 group M strains varies depending on the VL in the tested plasma specimen; 20% or higher at VL of 1000 copies/mL, 10% or higher at VL of 5000 copies/mL, and 5% or higher at VL of 15,000 copies/mL.

 

The list of drug resistance-associated codon mutations and interpretive rules used by the Stanford HIV database are updated periodically by the Stanford HIV Database team. Therefore, the test results do not necessarily include all of the resistance-associated codon mutations described in the current medical literature.

 

Possible causes of treatment failure other than the development of drug resistance are poor adherence to medication regimen, drug potency, and individual variation in pharmacokinetics (eg, inadequate phosphorylation of nucleosides).

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Weber J, Volkova I, Sahoo MK, Tzou PL, Shafer RW, Pinsky BA: Prospective evaluation of the Vela Diagnostics next-generation sequencing platform for HIV-1 genotypic resistance testing. J Mol Diagn. 2019 Nov;21(6): 961-970. doi: 10.1016/j.jmoldx.2019.06.003

2. Avila-Rios S, Parkin N, Swanstrom R, et al: Next-generation sequencing for HIV drug resistance testing: laboratory, clinical, and implementation considerations. Viruses. 2020 Jun 5;12(6):617.doi: 10.3390/v12060617

3. Raymond S, Nicot F, Abravanel F, et al: Performance evaluation of the Vela Dx Sentosa next-generation sequencing system for HIV-1 DNA genotypic resistance. J Clin Virol. 2020 Jan;122:104229. doi: 10.1016/j.jcv.2019.104229

4. Panel on Antiretroviral Guidelines for Adults and Adolescents: Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. US Department of Health and Human Services. Updated January 20, 2022. Accessed March 29, 2022. Available at https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/guidelines-adult-adolescent-arv.pdf

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

This test utilizes the FDA-approved, commercially available Sentosa SQ HIV-1 Genotyping Assay, which is a next-generation sequencing assay based on a "sequencing by synthesis" method. The assay is designed to generate 2 amplicons (approximately 1500 base pairs [bp] and approximately 1000 bp in length) spanning the PR / RT- and INT-coding regions, respectively, of the HIV-1 genome for sequencing. Codon positions 1 to 99, 1 to 387, and 1 to 288 in the PR-, RT-, and INT-coding regions, respectively, are subsequently analyzed by the assay software for clinically relevant codon substitutions.

 

Clinical plasma specimens are subjected to automated HIV-1 RNA extraction and purification, followed by reverse-transcription polymerase chain reaction of HIV-1 target sequences, with both a system control and a positive control included in each assay run for quality control purposes. Automated DNA library preparation is performed using the amplified products, including enzymatic shearing, adapter ligation, purification, and normalization, prior to DNA template preparation and sequencing. Sequencing reactions are conducted with the Sentosa SQ301 sequencer, and the assembled sequence data are analyzed using proprietary analysis and interpretive software applications. HIV-1 antiviral drug-resistance interpretations are based on algorithms implemented in the most current version of the Stanford University HIV Drug Resistance Database (HIVdb; Stanford University) using a 5% variant detection cutoff threshold set by the assay manufacturer.(Instruction manual: Sentosa SQ HIV-1 Genotyping Assay User Manual. Vela Diagnostics; version 1.0, 11/2020)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 10 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

60 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

0219U

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
HIVDR HIV-1 Genotypic Drug Resistance, P 90901-0
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
616052 HIV-1 Genotypic Drug Resistance, P 80689-3
616729 HIV-1 group M subtype 83325-1
616737 Nucleos(t)ide RT mutations 45175-7
616918 Reverse Transcriptase failed codons In Process
616738 Abacavir 30287-7
616739 Didanosine 30284-4
616740 Emtricitabine 41402-9
616741 Lamivudine 30283-6
616742 Stavudine 30286-9
616743 Tenofovir 41396-3
616744 Zidovudine 30282-8
616745 Nonnucleoside RT mutations 45176-5
616746 Doravirine 91897-9
616747 Efavirenz 30291-9
616748 Etravirine 52749-9
616749 Nevirapine 30289-3
616750 Rilpivirine 68463-9
616751 Protease Mutations 33630-5
616919 Protease failed codons In Process
616752 Atazanavir + Ritonavir 49618-2
616753 Darunavir + Ritonavir 49630-7
616754 Fosamprenavir + Ritonavir 51409-1
616755 Indinavir + Ritonavir 49619-0
616756 Lopinavir + Ritonavir 42000-0
616757 Nelfinavir 30294-3
616758 Saquinavir + Ritonavir 49621-6
616759 Tipranavir + Ritonavir 49622-4
616760 Integrase mutations 61199-6
616920 Integrase failed codons In Process
616761 Bictegravir 90080-3
616762 Cabotegravir 96566-5
616763 Dolutegravir 72857-6
616764 Elvitegravir 72526-7
616765 Raltegravir 72525-9
HIRVL HIV RNA level copies/mL <30 days = 89543-3
618206 HIVDR_PR-RT_SEQ: No LOINC Needed
618207 HIVDR_INT_SEQ: No LOINC Needed

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Create a PDF

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports