Measuring HIV response to antivirals using ViroLogic's PheonSense assay
Table of Contents
Genotypic predictions not always accurate
NNRTI hypersusceptibility linked to improved treatment response
Measuring resistance to integrase inhibitors
At the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Toronto last week, a number of papers were presented concerning HIV response to antiviral drugs. Three of these studies involved ViroLogic Inc.'s (South San Francisco, CA) PhenoSense HIV assay, a phenotypic drug susceptibility assay for HIV-1 that directly measures the susceptibility, or resistance, of a patient's virus to currently available antiretroviral drugs.
Genotypic predictions not always accurate
Data collected by Neil Parkin and a team of scientists from ViroLogic revealed that several common HIV mutations do not always confer resistance to antiretroviral drugs, as previously thought. The study, titled "Discordance Between Genotype-Based Predictions of HIV-1 Protease Inhibitor Susceptibility and Actual Phenotype in HIV-1 Isolates Containing Mutations at Positions 82 or 90," was conducted using the company's PhenoSense HIV assay.
"Resistance to anti-HIV drugs often arises from the complex interaction of genetic mutations in HIV," said Christos Petropoulos, vice president of research and development at ViroLogic. "As this study demonstrates, the accuracy and reliability of genotypic predictions can be problematic since there is an incomplete understanding of the interaction of genetic mutations in HIV."
In the study, scientists used PhenoSense HIV to determine the resistance profiles of viruses with mutations at two key positions in their genetic codes, amino acids 82 and 90 in the protease protein. The researchers found that 73% of viruses with mutations at position 82 were still sensitive to at least one drug that genotyping had labeled ineffective, and 47% of viruses with the common mutation L90M were susceptible to at least one supposedly ineffective drug.
NNRTI hypersusceptibility linked to improved HIV treatment response
According to other data presented at ICAAC, hypersusceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is prevalent among patients with previous HIV treatment experience. The research, titled "NNRTI Hypersusceptibility is Common and Improves Short-Term Virologic Response," suggests that hypersusceptible HIV may be more vulnerable to treatment with antiviral drugs, as hypersusceptibility was associated with improved treatment response.
Scientists from the University of California-San Diego, ViroLogic, and six other academic research institutions examined HIV from 164 patients across the U.S. again using PhenoSense HIV.
Lead investigator Richard Haubrich of the University of California-San Diego stated, "Our study shows that information about increased drug susceptibility, as well as drug resistance, may be useful in optimizing patient therapy. Patients who have virus that is hypersusceptible to particular drugs may respond better to treatment with those drugs, at least in the short term."
Hypersusceptibility to at least one NNRTI was detected among 24% of the study population, and the phenomenon was particularly prevalent among patients whose virus had grown resistant to one or more nucleoside reverse transcriptase inhibitors (NRTIs). In patients with hypersusceptible virus, administration of NNRTIs also resulted in greater short-term viral load reduction and larger increases in CD4+ cell counts, compared to those patients without hypersusceptible virus.
Measuring resistance to integrase inhibitors
In another report presented at ICAAC, scientists used the PhenoSense HIV assay to measure HIV resistance to integrase inhibitors, the newest class of HIV/AIDS drugs. The study, titled "Measuring HIV-1 Integrase Inhibitor Susceptibility Using a Recombinant Virus-Based, Single Cycle Replication Assay," found no cross-resistance between integrase inhibitors and other drug classes, indicating that these drugs may be a useful for patients whose virus has grown resistant to most available antiretroviral drugs.
The research was conducted by scientists from ViroLogic and Merck Research Laboratories, who examined integrase inhibitor resistance among a wide range of virus types, including virus resistant to many of the available AIDS drugs.
ViroLogic is a biotechnology company developing and marketing products to guide and improve treatment of viral diseases. The company's proprietary technology, PhenoSense, tests for drug resistance and susceptibility in viruses that cause serious diseases such as AIDS, hepatitis B, and hepatitis C.
For more information: ViroLogic Inc., 270 E. Grand Ave., South San Francisco, CA 94080. Tel: 650-635-1100. Fax: 650-635-1111.
Edited by Jim Pomager
Assistant Editor, Bioresearch Online