Recommendation for Pre-treatment Genotype Drug Resistance Testing

Human immunodeficiency virus (HIV) treatment guidelines, from the United States Department of Health and Human Services (DHHS), recommend conducting drug-resistance testing before starting anti-retroviral treatment for HIV.* As is recommended for tuberculosis, testing for drug-resistant HIV allows selection of treatment regimens (HAART) with a higher probability of success. When multi-drug resistance is found, partner counseling and referral services (PCRS) efforts can be enhanced to find additional people infected with hard-to-treat virus in order to tailor their treatment regimens accordingly, and to try to block further spread of a virus that may be more difficult to treat.

The first primary HIV drug resistance genotype surveillance project in King County was carried out from 1998 to 2000. The second project began in 2003 and is ongoing. Surveillance is not yet population-based because only two labs are participating; however, these two labs account for over half of all new HIV diagnoses in King County. For the current project, participating labs set aside aliquots of sera from positive diagnostic HIV tests for resistance testing. These aliquots are sent to the genotype laboratory if they are eligible for the project; eligibility requires a new HIV diagnosis and that the patient had not yet used antiretroviral therapy. HIV Surveillance Program staff and members at the Washington State Department of Health are currently exploring the possibility of consolidating HIV confirmatory testing in centralized public health labs, in part to facilitate true population-based primary HIV-resistance surveillance.

Local Surveillance Unveils 12 Cases of Multi-drug Resistant HIV

Over the course of conducting local resistance surveillance, the proportion of people with high level resistance to one or more antiretroviral drug has remained steady at about 11 percent. About 3 percent of individuals have been infected with multi-drug resistant HIV (MDR HIV). Multi-drug resistance is defined as a high level of resistance to one or more drug in each of two or more of the three major drug classes. These drug classes are protease inhibitors, nucleoside or nucleotide reverse transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors.

Since 2000, Public Health has investigated 12 cases of MDR HIV. These cases were identified in 2000 (1 case), 2003 (4 cases), 2004 (3 cases), 2005 (3 cases), and 2006 (1 case so far). The patterns of resistance break down as follows:

• 2 cases had HIV infections resistant to both protease inhibitors and non-nucleoside reverse transcriptase inhibitors
• 2 cases had HIV infections resistant to both protease inhibitors and nucleoside/nucleotide reverse transcriptase inhibitors
• 4 cases had HIV infections resistant to non-nucleoside reverse transcriptase inhibitors and nucleoside/nucleotide reverse transcriptase inhibitors, and
• 4 cases had HIV infections resistant to all 3 drug classes.

Notably, the two most recent cases identified were infected with very similar viruses with 97.7% homology. Follow-up investigation confirmed that the specimens were from different individuals, and both genotype test results were confirmed by a second laboratory on new specimens. Both individuals were men who had sex with multiple, mostly anonymous, male partners. PCRS investigations found a few partners -- including a couple with longstanding HIV already treated with HAART. The investigations have not yielded any additional primary MDR HIV nor did we find acquired drug resistance in the HAART-treated partners.

Antiretroviral drug resistance surveillance is essential to monitor potential community-wide loss of effective treatments. Community resistance levels are needed to inform treatment decisions and guide prevention efforts. For example, community resistance levels are needed to guide post-exposure prophylactic treatment, and to guide treatment to prevent vertical transmission when a woman in labor is diagnosed with HIV and there isn’t time to test for resistance.

Primary resistance is a marker for inadequately treated HIV, often due to failure to adhere to antiretroviral treatment regimens, combined with viral replication, persistence of drug resistant virus, and ongoing behaviors promoting HIV transmission. In sum, morbidity and mortality due to HIV may be reduced with population-based drug resistance surveillance to identify unusual strains of HIV and, when resistance is present, to adjust treatments accordingly and promote prevention activities to limit the spread of resistant virus.

* DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescent (May 4, 2006) can be found at:
http://aidsinfo.nih.gov/contentfiles/adultandadolescentgl.pdf

For more information about the Public Health-Seattle & King County HIV/AIDS Surveillance and Epidemiologic Research Program, please call (206) 205-1470 or see: www.metrokc.gov/health/apu/epi/epiproj.htm