Test Summary
HIV-1 Genotype
Test code: 34949
Clinical use
- Guide selection of antiretroviral drugs
- Detect HIV-1 mutations in the reverse transcriptase (RT) and protease (PR) genes
Clinical background
Despite continuing advances in treatment for HIV-1 infection, highly active antiretroviral therapy (HAART) may fail to suppress viral replication. The high replication rate of HIV-1 coupled with its rapid mutation rate drives the accumulation of mutations,1 which may reduce susceptibility to antiretroviral agents. If viral replication is not adequately suppressed during HAART, HIV-1 variants containing resistance-associated mutations may emerge, increasing the likelihood of treatment failure.
The HIV-1 Genotype assay (test code 34949) identifies RT and PR mutations associated with current or evolving drug resistance. Current guidelines support the use of resistance testing to help guide therapy decisions in treatment-naive as well as treatment-experienced patients and to document transmission of resistant virus.2–4 Because of its generally lower cost, faster turnaround time, and sensitivity for detecting variants in mixed viral populations, genotypic testing is recommended in most clinical settings where resistance testing is indicated.2,3 The addition of phenotypic resistance testing is recommended for patients with complex resistance patterns.2,3
Because wild-type virus tends to outcompete resistant virus in the absence of selective pressure, resistance testing is most reliable for antiretroviral drugs in the patient’s regimen at the time of testing and should be performed within 4 weeks after discontinuing therapy.2,4
Individuals suitable for testing
- Individuals with acute or chronic HIV-1 infection at entry into care (before therapy is initiated)
- Individuals with chronic infection initiating their first antiretroviral regimen
- Individuals experiencing antiretroviral regimen failure
- Individuals experiencing suboptimal viral suppression
- Pregnant women with HIV-1 infection
Method
- Reverse transcription and polymerase chain reaction (PCR) amplification of plasma HIV-1 RNA followed by automated DNA sequencing
- Amplification of the entire sequence of the PR gene (to codon 99) and RT gene (to codon 319)
- Sequencing using an Applied Biosystems Model 3730 capillary automated sequencer
- Multiple control samples with known mutations included in each assay run
- Phylogenetic tree analysis and sequence searches of the Quest Diagnostics HIV sequence database provide quality control measures that confirm specimen integrity
- Associated drug resistance identified using the Quest Diagnostics rules-based algorithm
- Report includes detected mutations and predicted drug resistance
- Limit of detection (LOD95): approximately 600 copies/mL
- Limit of detection for minority mutations: mutations accounting for approximately 20% to 25% of the viral population can be detected
- Synonyms: HIV-1 drug resistance, HIV-1 gene sequencing, HIV-1 mutations
Interpretive information
The report form lists individual mutations in the RT and PR genes, along with associated drug resistance for each antiretroviral drug. The HIV-1 subtype is also reported. The interpretation algorithm used to associate mutations with drug resistance is updated regularly by a panel of HIV experts but is not reviewed by the FDA. Resistance may also be affected by as yet uncharacterized mutations and interactions among mutations. In addition, mutations in minor viral populations (20% to 25% of the viral population) may not be detected.
Therapeutic failure may be due to factors other than resistance, including poor adherence to the drug regimen, suboptimal therapy or drug bioavailability, and immunologic decline. Thus, in clinical practice, physicians select therapeutic regimens based on the patient's antiretroviral treatment history, viral load, clinical status, and potential metabolic toxicity as well as resistance information.
References
- Coffin JM. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science. 1995;267(5197):483-489. doi:10.1126/science.7824947
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. Published March 23, 2023. Accessed August 8, 2023. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf
- Günthard 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;68(2):177-187. doi:10.1093/cid/ciy463
- Gandhi RT, Bedimo R, Hoy JF, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults. JAMA. 2023;329(1):63-84. doi:10.1001/jama.2022.2224
Content reviewed 09/2023
34949 - HIV-1 Genotype
HIV: Laboratory Testing for Screening, Diagnosis, and Management
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