General FAQ

• Why is HIV resistance testing important?
• In practical terms, how do the tests work?
• Under what circumstances is HIV resistance testing recommended?
• How often should these resistance tests be conducted in patients undergoing antiretroviral therapy?
   

Why is HIV resistance testing important?

The selection of active antiretrovirals based on HIV drug resistance testing can lead to better virologic response. The Genotypic Antiretroviral Resistance Testing study (J.D. Baxter et al. 'A randomized study of Antiretroviral management based on Plasma Genotypic Antiretroviral resistance Testing in Patients failing Therapy', CPCRA 046 Study Team; AIDS 14 (2000), F83-F93) showed that patients whose treatment was guided by drug resistance testing with expert interpretation had a greater reduction in viral load than patients whose treatment was guided by past history. Using HIV drug resistance information can also save money by reducing the use of ineffectual drugs and reducing or delaying other health care costs such as inpatient care. (Weinstein et al., 'Use of genotypic resistance testing to guide HIV therapy: clinical impact and cost effectiveness', Ann. Intern. Med. 134 (2001), pp 440-450)
 

In practical terms, how do the tests work?

In the case of the virco® TYPE HIV-1, a blood plasma sample is collected from a patient and (in the United States) is usually sent to a commercial reference laboratory (one of Virco's distributors) where the plasma is separated and the patient's HIV genotype is determined. In Europe, Canada, Japan, Thailand, Hong Kong and India, Virco has partnerships with several large HIV clinical centers or core centers who do the genotyping. A genotype test examines the actual genetic structure of the HIV virus in a sample, in order to determine the mutations that are known to cause resistance to certain drugs. The genotype test takes on average 10 days to be completed although this time frame could vary among different laboratories. Then, via Virco's proprietary vircoNET software, the lab electronically submits the patient's genotype to Virco's laboratory in Belgium where the virco® TYPE HIV-1 analysis is conducted. Test results are sent back to the laboratory, which then distributes them to the clinic or physician by mail, electronic mail, fax, or secure Internet link. A virco® TYPE HIV-1 test takes about 5 minutes to complete after the genotype is received. Alternatively, the sample can be sent to Virco's laboratory for both genotyping and virco® TYPE HIV-1 analysis.

In the case of the Antivirogram, a plasma sample from the patient is almost always directly shipped to Virco's laboratory in Belgium where the whole testing procedure takes place. This test takes about three to four weeks to be completed after the sample is received in Belgium.
 

Under what circumstances is HIV resistance testing recommended?

DHHS Guidelines: The DHHS Guidelines (as of October 2006) for resistance testing include the following recommendations.

1) Specimen collection: Drug resistance testing is not advised for persons with viral load < 1,000 copies/mL, because amplification of the virus is unreliable and representative sampling of the viral quasispecies is unlikely.

2) Antiretroviral naïve patients:

• In acute or recent HIV infection: If the decision is made to initiate therapy in a person with acute HIV infection, resistance testing is recommended due to the potential for transmitted drug resistance to compromise response. If therapy is not started, resistance testing should still be considered because of the possibility of detecting transmitted strains which might be replaced in plasma by wild-type HIV over time but which could still compromise therapy in the future. In this case the resistance test results need to be retained until they become clinically useful.
• In chronically infected patients: Drug resistance testing at baseline in ARV-naïve, chronically infected patients is less straightforward due to the potential decay of resistant strains since the time of infection. However, on balance, data suggest that the presence of baseline mutations does compromise therapy and that baseline resistance testing in chronic infection is cost-effective. The DHHS guidelines therefore recommend testing in this situation. In addition, testing chronically infected patients even in cases where they are not soon starting therapy should be considered.
• In testing patients without prior ARV exposure, genotypic testing is recommended.

3) Patients with virological failure:

• HIV drug resistance testing should be performed to assist in selecting active drugs when changing ARV regimens in cases of virologic failure.
• Drug resistance testing should also be considered when managing suboptimal viral load reduction.
• Drug resistance testing in the setting of virologic failure should be performed while the patient is taking his/her ARV drugs, or immediately (i.e., within 4 weeks) after discontinuing therapy.

EuroGuidelines: The current EuroGuidelines for resistance testing, updated in October of 2007, make the following recommendations.

1) Patients with acute or recent infection: Recommended in all situations, regardless of initiating therapy.

2) Patients with established infection:

• In treatment naïve patients, testing is recommended at the time of HIV diagnosis, regardless of initiation of therapy. If not performed upon diagnosis, testing is recommended prior to initiation of therapy.
• In cases of virological rebound or failure to fully suppress virus after 6 months of therapy, resistance testing should be performed if viral load is above 500-1,000 copies/mL.
• For pregnant patients, test before starting or changing therapy when viral load is detectable.
• Pediatric patients should be tested before starting or changing therapy when viral load is detectable.

Post-exposure prophylaxis (PEP): Genotypic resistance testing should be performed on the source patient when possible, but do not delay PEP.

The guidelines are summarized as follows:

Additionally, the DHHS guidelines recommend against resistance testing when plasma viral load is less than 1000 HIV RNA copies/mL, and in cases of strategic treatment interruption.

Reference 1: Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents - December 1, 2007; Click here.

Reference 2: Hirsch MS, et al., 'Antiretroviral drug resistance testing in adult HIV-1 infection. Recommendations of an international AIDS Society-USA Panel. JAMA. 2000;283:2417-2426. Hirsch MS, et al., '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;37:113-128. Click here.

Reference 3: Hirsch MS, et al., 'Antiretroviral drug resistance testing in adult HIV-1 infection. Recommendations of an international AIDS Society-USA Panel. JAMA. 2000;283:2417-2426. Hirsch MS, et al., '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;37:113-128.

It is advisable that patients undergo resistance testing every time they experience confirmed virologic failure, provided that the viral load level is > = 1,000 copies/mL. In addition, resistance tests can be used to assess a patient's adherence (adherence means taking the medications exactly as prescribed). Virologic failure in the absence of resistance is an indication that the patient did not adhere to his medication regimen.
 

How often should these resistance tests be conducted in patients undergoing antiretroviral therapy?

It is advisable that patients undergo resistance testing every time they experience confirmed virologic failure, provided that the viral load level is > = 1,000 copies/mL. In addition, resistance tests can be used to assess a patient's adherence (adherence means taking the medications exactly as prescribed). Virologic failure in the absence of resistance is an indication that the patient did not adhere to his medication regimen.