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Antimicrobial Agents and Chemotherapy, April 2000, p. 920-928, Vol. 44, No. 4
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Novel Phenotypic Drug Susceptibility Assay for Human Immunodeficiency Virus Type 1

Christos J. Petropoulos,* Neil T. Parkin, Kay L. Limoli, Yolanda S. Lie, Terri Wrin, Wei Huang, Huan Tian, Douglas Smith, Genine A. Winslow, Daniel J. Capon,dagger and Jeannette M. Whitcomb

ViroLogic, Inc., South San Francisco, California 94080

Received 27 September 1999/Returned for modification 1 December 1999/Accepted 5 January 2000

Although combination antiretroviral therapy has resulted in a considerable improvement in the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection, the emergence of resistant virus is a significant obstacle to the effective management of HIV infection and AIDS. We have developed a novel phenotypic drug susceptibility assay that may be useful in guiding therapy and improving long-term suppression of HIV replication. Susceptibility to protease (PR) and reverse transcriptase (RT) inhibitors is measured by using resistance test vectors (RTVs) that contain a luciferase indicator gene and PR and RT sequences derived from HIV-1 in patient plasma. Cells are transfected with RTV DNA, resulting in the production of virus particles that are used to infect target cells. Since RTVs are replication defective, luciferase activity is measured following a single round of replication. The assay has been automated to increase throughput and is completed in 8 to 10 days. Test results may be useful in facilitating the selection of optimal treatment regimens for patients who have failed prior therapy or drug-naive patients infected with drug-resistant virus. In addition, the assay can be used to evaluate candidate drugs and assist in the development of new drugs that are active against resistant strains of HIV-1.

* Corresponding author. Mailing address: 270 East Grand Ave., South San Francisco, CA 94080. Phone: (650) 866-7439. Fax: (650) 635-1111. E-mail: cpetropoulos{at}virologic.com.

dagger Present address: Genetic Information Systems, Inc., Hillsborough, CA 94010.

Antimicrobial Agents and Chemotherapy, April 2000, p. 920-928, Vol. 44, No. 4
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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