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AIDS Therapies: Phenotypic Resistance Testing Might Improve Response to Anti-HIV Therapy


- A new study has suggested that phenotypic testing improves HIV treatment choices by physicians and significantly improves the viral suppression seen with antiviral medications.

The study examined the role of using HIV phenotypes for medication susceptibility versus just treatment history when changing patients' HIV treatment regimens after a first protease inhibitor-containing regimen has failed. The study was presented at the 7th Conference on Retroviruses and Opportunistic Infections in San Francisco, California, January 30 - February 2, 2000, by Calvin J. Cohen, MD, MSc, Community Research Initiative of New England, located in Boston, Massachusetts.

"This study demonstrates the important role that phenotypic testing may play in reducing guess work in determining next treatment regimens if previous treatments have failed," said Cohen. "This technology may enable us, as clinicians, to more effectively establish which treatments will work for individual patients. This allows a simpler and more scientific process for both physicians and patients."

Phenotypic resistance tests measure the susceptibility of an individual's HIV strain to each of the currently available anti-HIV drugs. The tests provide information about an individual's likely responsiveness to different drugs.

The phenotypic tests, by measuring each drug's ability to actually block HIV growth, differ from genotypic tests which look for changes in HIV's gene sequence that have been linked with drug resistance. Genotypic tests may miss unknown gene mutations or resistance mechanisms unrelated to genes. Phenotypic tests are most useful to evaluate current or recent therapies. The longer someone has been off a prior treatment, the harder it is to evaluate susceptibility to it, although resistance can return quickly after restarting a drug.

The ongoing, open-label, randomized study involves 274 patients who have experienced treatment with at least two nucleoside reverse transcriptase inhibitors (NRTIs) and one protease inhibitor and have a plasma viral load greater than 2,000 copies/mL. Patients were randomized to receive treatment based on phenotypic testing or on treatment history (standard of care) and were followed for 16 weeks after treatment change.

An interim analysis of 218 patients showed that patients in the phenotypic testing arm had a median baseline CD4 cell count of 348 cells/mm3, and patients in the standard-of-care arm had a median baseline CD4 cell count of 338 cells/mm3.

At week 16, 58% (42/72) of patients in the phenotypic testing arm and 37% (25/68) of patients in the standard of care arm had viral loads less than 400 copies/mL. CD4 cell count increases were similar in the two arms.

In an observed analysis of the data, patients in the phenotypic arm (n=111) had a -1.27 mean log(10) decrease in viral load, while the patients in the standard of care arm (n=107) experienced a -0.75 mean log(10) decrease. In the last observation carried forward (LOCF) analysis (uses the last available value and carries it forward to the current time point), patients experienced a -0.93 mean log(10) decrease and a -0.60 mean log(10) decrease in viral load on the phenotypic testing arm (n=111) and standard of care arm (n=107), respectively.

The Antivirogram assay was used for all phenotypic resistance testing in this study and was developed by Virco (Vircolab, Inc., Baltimore, Maryland). The assay is also available through LabCorp in the U.S. The retail cost of performing the test is approximately $800. Glaxo Wellcome conducted this study in collaboration with 25 leading AIDS research and treatment centers in the U.S. and with Virco.

This article was prepared by AIDS Weekly editors from staff and other reports.

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Copyright © 2000 -AIDS Weekly Plus, Publisher. All rights reserved to Charles Henderson, Publisher. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA. Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633- 4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX:(205) 995-1588 Visit AIDS WEEKLY PLUS.

Information in this article was accurate in February 21, 2000. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.