HIV resistance to therapy develops in 78% of patients.
- Reasons for failure include:
- Lack of access to care
- Patient noncompliance
- Drug pharmacology issues (absorption, elimination, interactions)
- Development of antiretroviral resistance
- Highest resistance is to nucleoside RT inhibitors
- Role of resistance testing in primary infection
- Identify mutations present
- Identify the etiology of treatment failures
- Role of resistance testing in established infections that are currently treated
- Failure of current therapy (decreasing CD4 count, increasing viral load)
- Patient noncompliance with HAART regimen
- Increased risk of resistance to newly resumed therapy
- HIV-1 testing for drug resistance may be useful in guiding therapy in HIV-1 infected individuals
Diagnosis
- Indications for testing - HIV patients in whom therapy is to be initiated; patients on HAART therapy and treatment failure
- Laboratory testing
- Baseline genotypic testing in countries with evidence of HIV drug resistance
- Determine etiology of treatment failure - phenotyping and genotyping may help with determining etiology of treatment failure
- Test only if patient is highly adherent to anti-retroviral therapy
- Trofile Co-Receptor Tropism Assay
- Identify patients infected with R5 virus to guide the use of Maraviroc therapy in adults infected with only CCR5-tropic HIV-1 who have evidence of viral replication and have HIV-1 strains resistant to multiple antiretroviral agents to guide the use of receptor inhibitors (Maraviroc)
| HIV Retroviral Drugs | ||
| Generic Name | Trade Name | Code |
| Nucleoside Reverse Transcriptase Inhibitors | ||
| Zidovudine Didanosine Lamivudine Stavudine Abacavir Tenofovir Emtricitabine | Retrovir® Videx® Epivir® Zerit® Ziagen® Viread® Emtriva® | AZT, ZDV DDI 3TC D4T ABC TDF FTC |
| Protease Inhibitors | ||
| Saquinavir Ritonovir Indinavir Nelfinavir Lopinavir/Ritonavir Amprenavir Fosamprenavir Atazanavir Tipranavir Darunavir | Fortovase® Norvir® Crixivan® Viracept® Kaletra® Agenerase® Lexiva® Reyataz® Aptivus® Prezista® | SQV RTV IDV NFV LPV APV FOS ATV TPV DRV |
| Non-Nucleoside Reverse Transcriptase Inhibitor | ||
| Nevirapine Delavirdine Etravirine Efavirenz | Viramune® Rescriptor® Intelence™ Sustiva® | NVP DLV TMC125 EFV |
| Integrase Inhibitors | ||
| Raltegravir | Isentress™ | MK-0518 |
| Receptor Inhibitors - CCR5 | ||
| Maraviroc | Selzentry® | |
| Tests |
| Test name: Human Immunodeficiency Virus 1, Genotyping |
| ARUP #: 0055670 |
| Methodology: Reverse Transcription Polymerase Chain Reaction/DNA Sequencing |
| Use: Detect changes in the viral genome that are associated with drug resistance Use in conjunction with CD4 measurement to monitor treatment efficacy Test requires specimens with HIV-1 RNA plasma levels of greater than 1,000 copies/mL |
| Limitations: Treatment failure can be caused by factors other than drug resistance; therefore, the interpretation of resistance genotyping results must be done in conjunction with other clinical and laboratory information Comparisons between assays performed in different laboratories are not recommended since no method standardization exists among HIV-1 drug resistance testing Results from different test methods/algorithms may provide different resistance interpretation The absence of resistance mutations does not rule out the presence of reservoirs of resistant viruses that cannot be detected by these tests Some specimens with HIV-1 RNA plasma levels greater than 1,000 copies/mL may not provide adequate data due to polymorphisms in the priming areas of the genome This test does not detect minor HIV-1 populations that are less than approximately 20 percent of the total population |
| Test name: HIV Phenosense GT |
| ARUP #: 0092399 |
| Methodology: Phenotyping and Genotyping |
| Use: Estimate the ability of a cloned copy of the patient’s virus to replicate in cell culture in the presence of a drug Determine the amount of drug needed to inhibit viral replication in vitro and generally report the concentration of drug required to inhibit viral replication by 50%, or the IC50 Determine the cause of treatment failure Clarify and confirm results from HIV genotyping tests Test requires specimens with HIV-1 RNA plasma levels of greater than 1,000 copies/mL |
| Limitations: Treatment failure can be caused by factors other than drug resistance; therefore, the interpretation of resistance genotyping results must be done in conjunction with other clinical and laboratory information Comparisons between assays performed in different laboratories are not recommended since no method standardization exists among HIV-1 drug resistance testing The absence of resistance mutations does not rule out the presence of reservoirs of resistant viruses that cannot be detected by these tests Some specimens with HIV-1 RNA plasma levels greater than 1,000 copies/mL may not provide adequate data due to polymorphisms in the priming areas of the genome |
| Follow-up: |
| Test name: Human Immunodeficiency Virus (HIV) Phenotype Comprehensive |
| ARUP #: 0092050 |
| Methodology: Drug Susceptibility using HIV Culture |
| Use: Measure the ability of a patient’s virus to replicate in cell culture in the presence of a drug Determine the amount of drug needed to inhibit viral replication in vitro and generally report the concentration of drug required to inhibit viral replication by 50%, or the IC50 Determine the cause of treatment failure When used in conjunction with genotyping, can provide a complete picture of antiretroviral susceptibility to HIV Test requires specimens with HIV-1 RNA plasma levels of greater than 1,000 copies/mL |
| Limitations: Treatment failure can be caused by factors other than drug resistance; therefore, the interpretation of resistance genotyping results must be done in conjunction with other clinical and laboratory information Comparisons between assays performed in different laboratories are not recommended since no method standardization exists among HIV-1 drug resistance testing The absence of resistance mutations does not rule out the presence of reservoirs of resistant viruses that cannot be detected by these tests Some specimens with HIV-1 RNA plasma levels greater than 1,000 copies/mL may not provide adequate data due to polymorphisms in the priming areas of the genome |
| Follow-up: |
| Test name: Human Immunodeficiency Virus 1, virco®TYPE |
| ARUP #: 0051186 |
| Methodology: Reverse Transcription Polymerase Chain Reaction and DNA Sequencing with interpretation using a phenotypic database |
| Use: Predict HIV-1 drug resistance from the nucleic acid sequence of the human immunodeficiency virus Test requires specimens with HIV-1 RNA plasma levels of greater than 1,000 HIV-1 copies/mL |
| Limitations: Treatment failure can be caused by factors other than drug resistance; therefore, the interpretation of resistance genotyping results must be done in conjunction with other clinical and laboratory information Comparisons between assays performed in different laboratories are not recommended since no method standardization exists among HIV-1 drug resistance testing The absence of resistance mutations does not rule out the presence of reservoirs of resistant viruses that cannot be detected by these tests Some specimens with HIV-1 RNA plasma levels greater than 1,000 copies/mL may not provide adequate data due to polymorphisms in the priming areas of the genome |
| Follow-up: |
| Test name: Trofile Co-Receptor Tropism Assay |
| ARUP #: 0093370 |
| Methodology: Recombinant virus, single replication |
| Use: Identify patients infected with R5 virus to guide the use of maraviroc therapy Note: Maraviroc therapy has been approved by the FDA for combination antiretroviral treatment of adults infected with only CCR5-tropic HIV-1 who have evidence of viral replication and have HIV-1 strains resistant to multiple antiretroviral agents |
| Limitations: Test requires specimens with HIV-1 RNA plasma levels of greater than 1,000 HIV-1 copies/mL |
Guidelines
General References
Comprehensive Review: March 2008
Last Update: September 2008
