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HelpTest ID HIVPR HIV-1 Genotypic Protease and Reverse Transcriptase Inhibitor Drug Resistance, Plasma
Useful For
Identification of HIV-1 genotypic mutations associated with resistance to nucleotide reverse-transcriptase inhibitors, non-nucleotide reverse-transcriptase inhibitors, and protease inhibitors
Guiding initiation or change of drug combinations for the treatment of HIV-1 infection
Testing Algorithm
See HIV Treatment Monitoring Algorithm in Special Instructions.
Special Instructions
Method Name
Reverse Transcription-Polymerase Chain Reaction (RT-PCR), and DNA Sequencing
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name
HIV-1 Genotypic PR-RT Resistance, PSpecimen Type
Plasma EDTACollection Container/Tube: Lavender top (EDTA)
Submission Container/Tube: Plastic vial
Specimen Volume: 2.2 mL
Collection Instructions:
1. Spin down and remove plasma from cells within 6 hours of draw.
2. Freeze plasma specimen immediately, and ship specimen frozen on dry ice.
3. If shipment will be delayed for >24 hours, freeze plasma specimen at -70° C (up to 35 days) until shipment on dry ice.
Additional Information:
1. This test is intended to be used to monitor known HIV-positive infections. It is not intended for primary detection of HIV infections.
2. Specimens submitted for HIV-1 genotyping should contain ≥500 copies/mL of HIV-1 RNA.
Specimen Minimum Volume
1.2 mL
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Plasma EDTA | Frozen (preferred) | 35 days |
| Refrigerated | 24 hours |
Clinical Information
Antiviral resistance may compromise highly active antiretroviral therapy (HAART) in HIV-infected patients receiving HAART. When combination therapy fails, detection and analysis of HIV genotypic mutations can guide necessary changes to antiretroviral therapy and decrease HIV viral load, thereby improving patient outcome.
HIV-1 is an RNA virus that infects cells and is then converted to complementary DNA (cDNA) 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 HAART (combination of nucleoside analog, nonnucleoside agent and/or protease inhibitor) may be effective in reducing the viral load, genotypic mutations arising in the drug-targeted HIV gene loci due to selective pressure from antiviral therapy 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 mutations 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 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
Not applicable
Cautions
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 patient.
The HIV-1 genotypic test is not a direct measure of drug resistance. Although genotypic testing can detect mutations in the relevant HIV-1 genome, the significance of these mutations requires careful interpretation to predict drug susceptibility. This assay's ability to amplify the target and detect genotypic mutations is poor and unreliable when the plasma HIV-1 viral load is <500 copies/mL. Specimens submitted for this test should contain ≥500 copies/mL of HIV-1 RNA.
This assay has been optimized for genotypic analysis and interpretation of HIV-1 group M subtype B, which are the majority of HIV-1 isolates infecting patients in the United States and Europe. The protease and reverse transcriptase gene regions examined in this assay are not well correlated with the envelope gene, which is the defining gene sequence used for subtyping. Other subtypes of group M HIV-1 have been tested and validated to a limited extent by this assay. Therefore, genotypic mutations in groups N and O, and some group M non-B subtype HIV-1 isolates may or may not be detected using this assay, and it is not known whether drug resistance mutation interpretation for group M subtype B isolates apply to these other groups and subtypes of HIV-1.
The genotypic mutation database and interpretive rules used by this commercial assay are updated periodically by the assay manufacturer. Therefore, the test results do not necessarily include all of the drug-related 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).
Day(s) Performed
Varies; test will be performed in batches of 10
Report Available
Monday through Wednesday, 2 days; Thursday and Friday, 4 daysPerforming Laboratory
Mayo Medical Laboratories in Rochester
Test Classification
This test has been modified from the manufacturer's instructions. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.CPT Code Information
87901