Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

GHIVR
88782
Reference Values:
Not applicable
Clinical References: 1. Cavert W, Balfour HH: Detection of antiretroviral resistance in HIV-1. Clin
Lab Med 2003;23:915-928 2. Hirsch MS, Gunthard HF, Schapiro JM, et al: Antiretroviral drug resistance
testing in adult HIV-1 infection: 2008 Recommendations of an International AIDS Society-USA Panel.
Clin Infect Dis 2008;47:266-285 3. Thompson MA, Aberg JA, Cahn P, et al: Antiretroviral treatment of
adult HIV infection: 2010 Recommendations of the International AIDS Society-USA Panel. JAMA
2010;304:321-333
HIV-1 Genotypic Drug Resistance Mutation Analysis, with
Reflex to Phenotypic Drug Resistance Prediction, Plasma
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 which infects cells and is then
converted to complementary DNA 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, non-nucleoside 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 genotypic drug resistance mutations. Phenotypic assays for
antiviral drug susceptibility determine the amount of drug needed to inhibit viral growth in cell culture.
The amount of drug needed to inhibit virus growth by 50% is called the 50% inhibitory concentration or
IC50. Similarly, the concentration of drug that inhibits virus growth by 95% is known as the IC95.
Testing a particular drug against a large number of isolates from patients who never received antiretroviral
therapy can determine the average IC50 for wild-type HIV-1 isolates. Viruses that are inhibited by the
same or lower concentrations of that drug are considered susceptible or sensitive, while those that are
inhibited only at higher drug concentrations are considered resistant. Results of phenotypic assays are
typically expressed as a fold change in IC50 of each drug against the patient's virus when compared to the
IC50 for the reference wild-type HIV-1 strain. For example, if the IC50 of zidovudine (AZT) for the
reference wild-type stain is 2 nM and the drug shows an IC50 of 20 nM for the patient's isolate, then the
patient's virus would be 10-fold more resistant than the wild-type strain to this drug. However, fold
changes in IC50 must be interpreted in relation to the concentration of drug that can be achieved in the
plasma and the clinical response to the drug in question.
Useful For: Identification of key HIV genotypic mutations associated with resistance to nucleotide
reverse-transcriptase inhibitors, nonnucleotide reverse-transcriptase inhibitors, and protease inhibitors
Interpretation: Detectable HIV-1 genotypic mutations conferring resistance to an antiviral drug are
reported as amino acid codon changes (eg M184V) resulting from the mutations. Genotypic drug
resistance: -"Susceptible" indicates that the genotypic mutations present in patient's HIV-1 strain have not
been associated with resistance to the specific drug in question. -"Resistant" indicates that genotypic
mutations (see specific list in corresponding result comment) detected have been associated with
maximum reduction in susceptibility to the specific drug. -"Possibly resistant" indicates that genotypic
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