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Disease Categories > Infectious Disease > Viruses

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Human Immunodeficiency Virus 1, Antiretroviral Drug Resistance Testing - HIV Drug Resistance

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 infection, currently treated
- Failure of current therapy (decreasing CD4 count, increasing viral load)
- Patient noncompliance with HAART regimen, increasing risk of resistance to newly resumed therapy
HIV-1 testing for drug resistance may be useful in guiding therapy in HIV-1 infected individuals

Recommendations – baseline genotypic testing in countries with evidence of HIV drug resistance

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®

Indications for Ordering

Tests generally appear in the order most useful for common clinical situations
Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Recommended Use	Limitations
Human Immunodeficiency Virus 1, Genotyping 0055670 Method: Reverse Transcription Polymerase Chain Reaction/DNA Sequencing	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	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
HIV Phenosense GT 0092399 Method: Phenotyping and Genotyping	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	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
Human Immunodeficiency Virus (HIV) Phenotype Comprehensive 0092050 Method: Drug Susceptibility using HIV Culture	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	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
Human Immunodeficiency Virus 1, virco®TYPE 0051186 Method: Reverse Transcription Polymerase Chain Reaction and DNA Sequencing with interpretation using a phenotypic database	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	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
Trofile Co-Receptor Tropism Assay 0093370 Method: Recombinant virus, single replication	Predict HIV-1 drug resistance to CCR5 inhibitors (prototype is Selzentry®) Test requires specimens with HIV-1 RNA plasma levels of greater than 1,000 HIV-1 copies/mL

Guidelines

Diagnostic, monitoring, and resistance tests for HIV. New York State Department of Health - State/Local Government Agency [U.S.]. 2004 (revised 2005 May). 12 pages. NGC:004378 (Link to NGC)

HIV infection: detection, counseling, and referral. Sexually transmitted diseases treatment guidelines 2006. Centers for Disease Control and Prevention - Federal Government Agency [U.S.]. 1993 (revised 2006 Aug 4). 5 pages. NGC:005183 (Link to NGC)

Pilcher CD, Eron JJ Jr, Galvin S, Gay C, Cohen MS. Acute HIV revisited: new opportunities for treatment and prevention. J Clin Invest. 2004;113(7):937-945. (Link to PubMed)

Primary care guidelines for the management of persons infected with human immunodeficiency virus: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Infectious Diseases Society of America - Medical Specialty Society. 2004 Sep 1. 21 pages. NGC:003793 (Link to NGC)

Revised guidelines for HIV counseling, testing, and referral. MMWR Recomm Rep. 2001;50(RR-19):1-57. (Link to PubMed)

General References

Bartlett JA, Buda JJ, von Scheele B, Mauskopf JA, Davis EA, Elston R, King MS, Lanier ER. Minimizing resistance consequences after virologic failure on initial combination therapy: a systematic overview. J Acquir Immune Defic Syndr. 2006;41(3):323-331. (Link to PubMed)

Booth CL, Geretti AM. Prevalence and determinants of transmitted antiretroviral drug resistance in HIV-1 infection. J Antimicrob Chemother. 2007;59(6):1047-1056. (Link to PubMed)

Geretti AM. Clinical implications of HIV drug resistance to nucleoside and nucleotide reverse transcriptase inhibitors. AIDS Rev. 2006;8(4):210-220. (Link to PubMed)

Geretti AM. Epidemiology of antiretroviral drug resistance in drug-naive persons. Curr Opin Infect Dis. 2007;20(1):22-32. (Link to PubMed)

Hirsch MS, Brun-Vezinet F, Clotet B, Conway B, Kuritzkes DR, D'Aquila RT, Demeter LM, Hammer SM, Johnson VA, Loveday C, Mellors JW, Jacobsen DM, Richman DD. Antiretroviral drug resistance testing in adults infected with human immunodeficiency virus type 1: 2003 recommendations of an International AIDS Society-USA Panel. Clin Infect Dis. 2003;37(1):113-128. (Link to PubMed)

Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. January 29, 2008. (Accessed 21 Feb 2008) (Link to resource)

Richman DD. Antiviral drug resistance. Antiviral Res. 2006;71(2-3):117-121. (Link to PubMed)

Scosyrev E. An overview of the human immunodeficiency virus featuring laboratory testing for drug resistance. Clin Lab Sci. 2006;19(4):231-245. (Link to PubMed)

Sen S, Tripathy SP, Paranjape RS. Antiretroviral drug resistance testing. J Postgrad Med. 2006;52(3):187-193. (Link to PubMed)

Stanford University HIV Drug Resistance Database. (Accessed 1 Feb 2008) (Link to resource)

Vercauteren J, Vandamme AM. Algorithms for the interpretation of HIV-1 genotypic drug resistance information. Antiviral Res. 2006;71(2-3):335-342. (Link to PubMed)

Reviewed by

Hillyard, David R., M.D. Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Associate Professor, Pathology, University of Utah

Reimer, Larry G., M.D. Medical Director, Microbiology, Veteran's Affair Hospital; Professor of Pathology and Associate Dean for Curriculum and GME, University of Utah School of Medicine

Comprehensive Review: March 2008
Last Update: July 2008