26498 HIV-1 Genotypic Drug Resistance To Reverse Transcriptase, Protease, and Integrase Inhibitors, Plasma (HIVDR)

​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)

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:

This assay uses next-generation sequencing to identify HIV-1 antiviral drug resistance-associated codon mutations in patients prior to or while receiving combination antiretroviral therapy. This test can be used to predict the likelihood of a favorable response to current FDA-approved antiviral drug combinations used for treatment of HIV-1 infection.

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.

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.

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. 

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).

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.