Test Catalog

Test ID: HIVPR    
HIV-1 Genotypic Drug Resistance to Protease and Reverse Transcriptase Inhibitors, Plasma

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

Identification of genotypic variants associated with viral resistance to HIV-1 nucleotide reverse-transcriptase inhibitors, non-nucleotide reverse-transcriptase inhibitors, and protease inhibitors


Guiding initiation or change of combination antiretroviral therapy in individuals, including children, living with HIV

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-infected patients receiving HAART. When combination therapy fails, detection and analysis of HIV genotypic variants 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 variants 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 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 variants 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 variants.

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 variants conferring resistance to an antiviral drug are reported as amino acid codon changes (eg, M184V) resulting from the alterations, according to the interpretative algorithm of the Stanford HIV Database program. Genotypic variant codons are categorized and interpreted in relation to previously performed phenotypic antiviral susceptibility tests. Each variant is assigned a drug penalty score and the total score generated from all of the variants 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 variants.


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


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


High-level Resistant (HR) indicates that genotypic variants 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 genotypic resistant variants in the patient's HIV 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, <500 copies/mL).


Inconclusive indicates inability of the assay to reliably determine antiviral resistance because of the presence of PCR 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 patient.


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 variants is poor and unreliable when the plasma HIV-1 viral load is less than 500 copies/mL. Specimens submitted for this test should contain greater or equal to 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 variants 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 variant interpretation for group M subtype B isolates apply to these other groups and subtypes of HIV-1.


The list of drug resistance-associated genotypic variant codons 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 variant codons 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. Gunthard HF, Calvez V, Paredes R, et al: Human immunodeficiency virus drug resistance: 2018 Recommendations of the International Antiviral Society-USA Panel. Clin Infect Dis. 2019 Jan 7;68(2):177-187

2. Wensing AM, Calvez V, Ceccherini-Silberstein F, et al: 2019 Update of the drug resistance mutations in HIV-1. Top Antivir Med. 2019 Sep;27(3):111-121

3. U.S. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents: Guidelines for the use of antiretroviral agents in adults and adolescents with HIV.. July 10, 2019. Updated August 16, 2021. Accessed October 6, 2021. Available at https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL.pdf

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