Page 26 - HIV/AIDS Guidelines

Drug-Resistance Testing (Last updated January 10, 2011; last reviewed January 10, 2011)

Panel’s Recommendations
• HIV drug-resistance testing is recommended for persons with HIV infection when they enter into care regardless of
whether antiretroviral therapy (ART) will be initiated immediately or deferred (AIII). If therapy is deferred, repeat testing at
the time of ART initiation should be considered (CIII).
• Genotypic testing is recommended as the preferred resistance testing to guide therapy in antiretroviral (ARV)-naive
patients (AIII).
• Standard genotypic drug-resistance testing in ARV-naive persons involves testing for mutations in the reverse
transcriptase (RT) and protease (PR) genes. If transmitted integrase strand transfer inhibitor (INSTI) resistance is a
concern, providers may wish to supplement standard genotypic resistance testing with genotypic testing for resistance to
this class of drug (CIII).
• HIV drug-resistance testing should be performed to assist in the selection of active drugs when changing ARV regimens in
persons with virologic failure and HIV RNA levels >1,000 copies/mL (AI). In persons with HIV RNA levels >500 but <1,000
copies/mL, testing may be unsuccessful but should still be considered (BII).
• Drug-resistance testing should also be performed when managing suboptimal viral load reduction (AII).
• In persons failing INSTI-based regimens, genotypic testing for INSTI resistance should be considered to determine
whether to include a drug from this class in subsequent regimens (BIII).
• Drug-resistance testing in the setting of virologic failure should be performed while the person is taking prescribed ARV
drugs or, if not possible, within 4 weeks after discontinuing therapy (AII).
• Genotypic testing is recommended as the preferred resistance testing to guide therapy in patients with suboptimal
virologic responses or virologic failure while on first or second regimens (AIII).
• Addition of phenotypic to genotypic testing is generally preferred for persons with known or suspected complex drug-
resistance mutation patterns, particularly to protease inhibitors (PIs) (BIII).
• Genotypic resistance testing is recommended for all pregnant women prior to initiation of therapy (AIII) and for those
entering pregnancy with detectable HIV RNA levels while on therapy (AI).

Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = data from randomized controlled trials; II = data from well-designed nonrandomized trials or observational
cohort studies with long-term clinical outcomes; III = expert opinion

Genotypic and Phenotypic Resistance Assays
Genotypic and phenotypic resistance assays are used to assess viral strains and inform selection of treatment
strategies. Standard assays provide information on resistance to nucleoside reverse transcriptase inhibitors
(NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). Testing for
integrase and fusion inhibitor resistance can also be ordered separately from several commercial laboratories.
No genotypic assays for assessing resistance to CCR5 antagonists are currently commercially available for
clinical use in the United States. (See Coreceptor Tropism Assays.)

Genotypic Assays
Genotypic assays detect drug-resistance mutations present in relevant viral genes. Most genotypic assays
involve sequencing of the RT and PR genes to detect mutations that are known to confer drug resistance.
Genotypic assays that assess mutations in the integrase and gp41 (envelope) genes are also commercially
available. Genotypic assays can be performed rapidly with results available within 1–2 weeks of sample
collection. Interpretation of test results requires knowledge of the mutations that different ARV drugs select for
and of the potential for cross resistance to other drugs conferred by certain mutations. The International AIDS
Society-USA (IAS-USA) maintains a list of updated significant resistance-associated mutations in the RT, PR,
integrase, and envelope genes (see also http://www.iasusa.org/resistance_mutations). The Stanford University
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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents C-8

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