HIV Drug Resistance Genotyping

HIV Drug Resistance Genotyping
By Xiaotian Zheng, PhD, DLS Microbiology Director, June 2001

Introduction of new, more effective antiretroviral drugs significantly reduced death rates of human immunodeficiency virus (HIV) and improved patient management. However, the infection rates of this organism remain unchanged (Romanelli 2000). In addition, due to the HIV’s rapid and error-prone replication, drug resistance can easily develop and this affects efficacy of antiretroviral agents. Assays for HIV drug resistance testing are now available. When prior therapy has failed, a significant correlation between drug resistance and virologic response to a new treatment regimen has been observed. After controlling for plasma HIV RNA level, CD4+ cell count, and treatment history, the presence of drug resistance is an independent risk factor for a poor virologic response. At nucleic acid sequence level, this test detects mutations of viral genome encoding reverse transcriptase or protease enzyme to identify resistance. Therefore, it is an indirect measure of susceptibility and it does require expert interpretation. The International AIDS Society-USA updated their recommendations to provide guidance for clinicians about indications for HIV-1 resistance testing. The conclusions state that “Resistance testing is recommended to help guide the choice of new regimens after treatment failure and for guiding therapy for pregnant women. It should be considered in treatment-naive patients with established infection, but cannot be firmly recommended in this setting. Testing also should be considered prior to initiating therapy in patients with acute HIV infection, although therapy should not be delayed pending the results.” Currently various genotyping tests are available. Many institutions validate their own in-house developed tests. To achieve laboratory standardization, kits are also developed by several companies for HIV mutation analysis. To improve the test turn-around-time and to provide better patient care in Hawaii, our Molecular Diagnostic Laboratory now offers an HIV-1 drug resistance genotyping test. The test, also called TRUGENE™ HIV Assay which is developed by Visible Genetics (Toronto, Ontario, Canada), is based on mutation analysis with nucleic acid sequencing all relevant codons. To date, this is the only test being evaluated by the Food and Drug Administration (FDA) for approval. We hope the test results and easy to read test reports help to improve the quality of patient care.
Note:(1) At this time, the test is for research use only.
(2) Patient’s plasma HIV-1 RNA viral load should be greater than 1,000 copies/ml, preferably measured within the past 4 weeks.

References:

(1) Durant, J., P. Clevenbergh, P. Halfon, P. Delgiudice, S. Porsin, P. Simonet, N. Montagne, C. A. B. Boucher, J. M.Schapiro, and P. Dellamonica. 1999. Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial. Lancet. 353(9171):2195-2199.

(2) Ginocchio, C. C. 1999. HIV testing: the next step beyond viral load. Clin. Microbiol. Newsletter. 21(11):83-94.

(3) Hirsch, M. S., Brun-Vezinet, F. D’Aquila, R. T., et al. 2000. Antiretroviral drug resistance testing in adult HIV-1 infection. Recommendations of an International AIDS Society-USA panel. JAMA. 283(10):2417-2426.

(4) Romanelli, F. and C. Pomeroy. 2000. Human immunodeficiency virus drug resistance testing: state of art in genotypic and phenotypic testing of antiretrovirals. Pharmacotherapy. 20(2):151-157.