Drug-Resistance Testing

For Antiretroviral Therapy-Naive Persons:

• HIV drug-resistance testing is recommended at entry into care for persons with HIV to guide selection of the initial antiretroviral therapy (ART) regimen (AII). If therapy is deferred, repeat testing may be considered at the time of ART initiation (CIII).
• Genotypic, rather than phenotypic, testing is the preferred resistance testing to guide therapy in antiretroviral (ARV)-naive patients (AIII).
• In persons with acute or recent (early) HIV infection, in pregnant people with HIV, or in people who will initiate ART on the day of or soon after HIV diagnosis, ART initiation should not be delayed while awaiting resistance testing results; the regimen can be modified once results are reported (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 should ensure that genotypic resistance testing also includes the integrase gene (AIII).

For Antiretroviral Therapy-Experienced Persons:

• HIV drug-resistance testing should be performed to assist the selection of active drugs when changing ART regimens in the following patients:
  • Persons with virologic failure and HIV RNA levels >1,000 copies/mL (AI)
  • Persons with HIV RNA levels >500 copies/mL but <1,000 copies/mL, drug-resistance testing may be unsuccessful but should still be considered (BII)
  • Persons with suboptimal viral load reduction (AII)
• When a person with HIV experiences virologic failure while receiving an INSTI-based regimen, genotypic testing for INSTI resistance (which may need to be ordered separately) should be performed to determine whether to include a drug from this class in subsequent regimens (AII).
• Drug-resistance testing in the setting of virologic failure should be performed while the person is taking prescribed ARV drugs or, if that is not possible, within 4 weeks after discontinuing therapy (AII). If more than 4 weeks have elapsed since the ARVs were discontinued, resistance testing may still provide useful information to guide therapy; however, it is important to recognize that previously selected resistance mutations can be missed due to lack of drug-selective pressure (CIII).
• Genotypic testing is preferred over phenotypic resistance testing to guide therapy in persons with suboptimal virologic response or virologic failure while on first- or second-line regimens and in individuals in whom resistance mutation patterns are known or not expected to be complex (AII).
• The addition of phenotypic to genotypic resistance testing is recommended for persons with known or suspected complex drug-resistance mutation patterns (BIII).
• All prior and current drug-resistance test results, if available, should be considered when constructing a new regimen for a patient (AIII).