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Test Catalog

Test ID: HIVI    
HIV-1 Genotypic Integrase Inhibitor Drug Resistance, Plasma

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

Identification of HIV-1 genotypic mutations in the integrase region of HIV-1 to predict antiretroviral drug resistance in HIV-1-infected patients receiving integrase strand transfer inhibitors (ie, bictegravir, dolutegravir, elvitegravir, raltegravir)

 

Guiding initiation or change of drug combinations for the treatment of HIV-1 infection

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

See HIV Treatment Monitoring Algorithm in Special Instructions.

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

Antiviral resistance may compromise highly active antiretroviral therapy (HAART) in HIV-1-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-1 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). 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 (PR) catalyzes a polyprotein to produce peptides necessary for active viral replication. Although HAART (combinations of nucleoside analogs, nonnucleoside agents, protease inhibitors and/or integrase strand transfer inhibitors) may be effective in reducing viral load, genotypic mutations arising in drug-targeted HIV loci due to selective pressure from antiviral therapy can result in antiviral resistance that may compromise such therapy.

 

Amplification and analysis of drug-targeted HIV-1 sequences allows identification of changes in nucleotide sequence and associated amino acid codons that may cause antiviral drug resistance. Such genotypic changes are identified by comparing the sequence data of the patient's HIV-1 strain to that of a wild-type HIV-1 strain. The significance of these genotypic mutations in relation to antiviral resistance is then determined by a set of interpretive rules developed and used by the Stanford HIVdb Program Genotypic Resistance Interpretation Algorithm (http://sierra2.stanford.edu/sierra/servlet/JSierra) for final interpretation.

 

In the Stanford HIVdb program, genotypic mutations are categorized and interpreted according to phenotypic antiviral susceptibility tests performed using the ViroLogic PhenoSense assay (Monogram Biosciences Inc, San Francisco, US) or a HeLa-CD4 reporter gene assay. Each 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 HIVdb Team 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.

Not applicable

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, N155H), along with associated resistance interpretations for the current FDA-approved integrase strand transfer inhibitors (bictegravir, dolutegravir, elvitegravir, and raltegravir).

 

Susceptible (SUSC) indicates that the genotypic 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 genotypic 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 genotypic mutations detected have been associated with reduction in susceptibility to the specific drug (Stanford HIVdb score 15 to 29).

 

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

 

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

 

Unable to Genotype indicates that viral target sequences are of poor quality to reliably determine antiviral resistance. This result may be due to low viral load, ambiguous or incomplete viral target sequences, presence of PCR inhibitors, and/or mutations in the PCR or sequencing primer binding regions.

 

Inconclusive indicates inability of the assay to reliably determine antiviral resistance because of the presence of PCR inhibitors, mutations in the PCR or sequencing primer binding regions, or ambiguous or incomplete viral target sequences that did not allow reliable analysis to determine antiviral resistance.

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 Antiviral 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 a patient's viral population 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 less than 500 copies/mL. Specimens submitted for this test should contain at least 500 copies/mL of HIV-1 RNA.

 

This assay has been optimized for genotypic analysis of HIV-1 group M, subtype B, which includes the majority of HIV-1 strains infecting patients in the United States and Europe. HIV-1 groups N and O, and some group M, non-B subtypes may not be detected using this assay, and the significance of mutations and drug resistance mutation interpretation for these other groups and subtypes of HIV-1 is unknown.

 

The genotypic mutation database and interpretive rules used by the Stanford HIVdb Program Genotypic Resistance Interpretation Algorithm for final interpretation are updated periodically. Therefore, the test results may 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 include 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. Ceccherini-Silberstein F, Cento V, Calvez V, Perno CF: The use of human immunodeficiency virus resistance tests in clinical practice. Clin Microbiol Infect 2010;16:1511-1517

2. Gunthard HF, Saag MS, Benson CA, et al: Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2016 Recommendations of the International Antiviral Society-USA Panel. JAMA 2016;316(2):191-210

3. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Accessed 9/12/16. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf

4. Taylor BS, Olender SA, Tieu HV, Wilkin TJ: CROI 2016: Advances in antiretroviral therapy. Top Antivir Med 2016;24(1):59-81

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