International Guidelines

HIV Drug-Resistance Testing Guidelines

Currently, there are many national and international guidelines on the use of resistance testing. These guidelines are based on phenotypic and clinical outcome evidence, as well as expert opinion. The most widely referenced guidelines are:

• Department of Health and Human Services (DHHS) Guidelines for the Use of ARV Agents in HIV-1-Infected Adults and Adolescents- January 29, 2008, which is available online (http://aidsinfo.nih.gov/guidelines) and is updated regularly (1)
• The EuroGuidelines, published through the European AIDS Clinical Society and most recently updated in October, 2007; available online at http://www.eacs.eu/guide/index.htm (2)

In recent years, resistance testing has increasingly become a standard of care during treatment of HIV infection. This likely reflects increased utility due to the availability of more agents with activity against some resistant viruses, as well as increasingly strong evidence of a negative impact of even low levels of transmitted drug resistant viruses on individual treatment outcomes . (3)

The DHHS Guidelines (as of January 29, 2008) for resistance testing include the following recommendations.

• HIV drug resistance testing is recommended for persons with HIV infection when they enter into care regardless of whether therapy will be started immediately. If therapy is deferred, repeat testing should be considered when antiretroviral therapy is initiated.
• A genotypic assay is generally preferred for antiretroviral-naïve persons.
• HIV drug resistance testing should be performed to assist in selecting active drugs when changing antiretroviral regimens following virologic failure.
• Drug resistance testing should be performed when managing suboptimal viral load reduction.
• Drug resistance testing in patients experiencing virologic failure should be performed while the patient is taking his/her antiretroviral drugs, or immediately (i.e., within 4 weeks) after discontinuing therapy.
• Drug resistance testing is recommended for all pregnant women prior to initiation of therapy and on therapy in cases of detectable viral load.
• Drug resistance testing is not advised for persons with viral load < 1,000 copies/mL, since results may be unreliable.

In addition, the guidelines note that in the absence of available genotypic results for treatment naïve patients it may be preferable to initiate therapy with a PI-based regimen due to the greater potential for the compromise of currently recommended first-line NRTI regimens by transmitted drug resistance.

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

Patients with acute or recent infection: recommended in all situations, regardless of initiating therapy. For patients with established infection:

• In treatment naïve patients, testing is recommended at the time of 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 supress the virus after 6 months of therapy, resistance testing should be performed if the viral load is above 500-1000 copies/mL.
• For pregnant patients, test before starting or changing therapy when viral load is detectable.
• Paediatric 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.
 

References:

1. Department of Health and Human Services (DHHS) Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. January 29, 2008. Available at http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf Clumeck, N. et al., 2. Euroguidelines, European Guidelines for the Clnical Management and Treatment of HIV Infected Adults in Europe 2007, European Aids Clinical Society. Available at http://www.eacs.eu/guide/index.htm. 3. Kuritzkes DR. HIV resistance: frequency, testing, mechanisms. Top HIV Med. 2007 Nov-Dec;15(5):150-4.