Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

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Laboratory Testing

Drug-Resistance Testing

Last Updated: October 25, 2018; Last Reviewed: October 25, 2018

Panel's Recommendations Regarding Drug-Resistance Testing
Panel's Recommendations

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).
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

Table 5. Recommendations for the Use of Drug-Resistance Assays
Clinical Setting and Recommendation Rationale
In Acute or Recent (Early) HIV Infection:
Drug-resistance testing is recommended (AII). A genotypic assay is generally preferred (AIII). Treatment should not be delayed while awaiting results of resistance testing (AIII).
Drug-resistance testing can determine whether drug-resistant virus was transmitted. The initial regimen can be modified, if necessary, once resistance test results are available. Genotypic testing is preferred to phenotypic testing because of lower cost, faster turnaround time, and greater sensitivity for detecting mixtures of wild-type and resistant virus.
If ART is deferred, repeat resistance testing may be considered when therapy is initiated (CIII). A genotypic assay is generally preferred (AIII). Repeat testing when ART is initiated may be considered because the patient may have acquired a drug-resistant virus (i.e., superinfection).
In ART-Naive Patients with Chronic HIV:
Drug-resistance testing is recommended at entry into HIV care to guide selection of initial ART (AII). A genotypic assay is generally preferred (AIII).
Transmitted HIV with baseline resistance to at least 1 drug is seen in 10% to 17% of patients, and suboptimal virologic responses may be seen in patients with baseline resistant mutations to ARVs in the prescribed regimen. Some drug-resistance mutations can remain detectable for years in untreated patients with chronic HIV.
For pregnant persons, or if ART will be initiated on the day of or soon after HIV diagnosis, treatment can be initiated prior to receiving resistance testing results. If necessary, the ART regimen can be modified once resistance test results are available.
If an INSTI is considered for an ART-naive patient and/or transmitted INSTI resistance is a concern, providers should supplement standard resistance testing with a specific INSTI genotypic resistance assay, which may need to be ordered separately (AIII). Genotypic assays provide information on resistance to NRTIs, NNRTIs, PIs, and INSTIs. In some circumstances, INSTI resistance tests need to be ordered separately (clinicians should check with the testing laboratory). Currently, transmitted INSTI resistance is infrequent, but the risk of a patient acquiring INSTI-resistant strains may be greater in certain known exposure settings.
If therapy is deferred, repeat resistance testing may be considered before initiation of ART (CIII). A genotypic assay is generally preferred (AIII). Repeat testing before initiation of ART may be considered because the patient may have acquired a drug-resistant virus (i.e., a superinfection).

Genotypic testing is preferred to phenotypic testing because of lower cost, faster turnaround time, and greater sensitivity for detecting mixtures of wild-type and resistant virus.
If use of a CCR5 antagonist is being considered, a co-receptor tropism assay should be performed (AI). See Co-Receptor Tropism Assays section.
In Patients with Virologic Failure:
Drug-resistance testing is recommended in patients on combination ART with HIV RNA levels >1,000 copies/mL (AI). In patients with HIV RNA levels >500 copies/mL but <1,000 copies/mL, testing may not be successful but should still be considered (BII).
Drug-resistance testing can help determine the role of resistance in drug failure and maximize the clinician’s ability to select active drugs for the new regimen.
Resistance testing should be done while the patient is taking ART or, if that is not possible, within 4 weeks after ART discontinuation (AII). If >4 weeks have elapsed, resistance testing may still be useful to guide therapy; however, previously-selected mutations can be missed due to lack of drug selective pressure (CIII). The absence of detectable resistance in such patients must be interpreted with caution when designing subsequent ARV regimens, as mutations may decay with time.
A standard genotypic resistance assay is generally preferred for patients experiencing virologic failure on their first or second regimens and for those with noncomplex resistance patterns (AII). Genotypic testing is preferred to phenotypic testing because of lower cost, faster turnaround time, and greater sensitivity for detecting mixtures of wild-type and resistant HIV.
All prior and current drug-resistance testing results should be reviewed and considered when designing a new regimen for a patient experiencing virologic failure (AIII). Drug resistance mutations may decay with time, and mutations detected in prior resistance tests may not be detected in current tests, though they remain clinically relevant.
When virologic failure occurs while a patient is on an INSTI-based regimen, genotypic testing for INSTI resistance should be performed to determine whether to include drugs from this class in subsequent regimens (AII). Genotypic assays provide information on resistance to NRTI-, NNRTI-, PI-, and INSTI-associated mutations. In some circumstances, INSTI resistance tests need to be ordered separately (clinicians should check with the testing laboratory).
Adding phenotypic testing to genotypic testing is generally preferred in patients with known or suspected complex drug-resistance patterns (BIII). Phenotypic testing can provide additional useful information in patients with complex drug resistance mutation patterns.
In Patients with Suboptimal Suppression of Viral Load:
Drug-resistance testing is recommended in patients with suboptimal viral load suppression after initiation of ART (AII).
Testing can determine the role of resistance in suboptimal viral suppression, and it can help the clinician identify the number of active drugs available in the current regimen and assess the need for a new regimen.
In Pregnant Persons with HIV:
Genotypic resistance testing is recommended for all pregnant persons before initiation of ART (AIII) and for those entering pregnancy with detectable HIV RNA levels while on therapy (AI).
The goals of ART in pregnant persons with HIV are to achieve maximal viral suppression for treatment of maternal HIV and to prevent perinatal transmission of HIV. Genotypic resistance testing will assist the clinician in selecting the optimal regimen for the patient. However, treatment should not be delayed while awaiting results of resistance testing. The initial regimen can be modified once resistance test results are available, if needed.
In Patients with Undetectable Viral Load or Low-Level Viremia:
HIV-1 proviral DNA resistance assays may be useful in patients with HIV RNA below the limit of detection or with low-level viremia, where a HIV RNA genotypic assay is unlikely to be successful (CIII).
This test may provide information about previously circulating resistant viral variants that are archived within proviral DNA. These assays may miss some or all prior resistance mutations that have occurred within the viral quasi-species, and therefore they should be interpreted with caution. The clinical utility of HIV-1 proviral DNA assays has not been fully determined.
Key to Acronyms: ART = antiretroviral therapy; ARV = antiretroviral; INSTI = integrase strand transfer inhibitors; NNRTI = non-nucleoside reverse-transcriptase inhibitors; NRTI = nucleoside reverse-transcriptase inhibitors; PI = protease inhibitor

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