February 1, 2002

Study finds cholesterol-lowering effect in investigational HIV drug

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Dr. David W. Haas, associate professor of Medicine, led the study at VUMC.

Study finds cholesterol-lowering effect in investigational HIV drug

Sometimes drug side effects can be good.

Dr. David W. Haas, associate professor of Medicine, presented data at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), indicating that the investigational anti-HIV protease inhibitor atazanavir has favorable effects on lipid profiles in patients with HIV infection.

Lipid abnormalities such as lipodystrophy, elevated cholesterol, elevated triglycerides, and even progression to arthrosclerotic disease are negative side effects experienced by some patients taking the various protease inhibitors currently available. Unfortunately for many patients, although benefits offered by protease inhibitors outweigh the risk, negative side effects can also cause additional health problems and distort physical appearance.

Haas studied patients who were already failing another multi-drug regimen. In about 90 percent of patients, the regimen included a protease inhibitor. These patients were unable to control the virus despite being on a protease inhibitor. Initially, the goal of the study was to determine if treatment with a new regimen that included atazanavir would be able to effectively control the virus. Investigators would soon discover that atazanavir produced other promising effects.

The discovery that atazanavir actually improves lipid profiles is one of the many encouraging benefits offered by the drug. Combination drug therapy including atazanavir did provide substantial virologic benefit as determined by the decrease in the amount of HIV in the patient’s blood.

Also, atazanavir inhibits some of the liver enzymes involved in drug metabolism, allowing levels of other drugs to increase at the same time.

Doctors providing care to HIV-positive patients often struggle to determine the best drug therapy for a patient’s individual needs. They must consider not only the drug’s benefits, but also the risks the drug carry.

“Developing effective antiretroviral agents that have favorable side effect profiles is one of the biggest challenges in the field of HIV therapy,” said Haas. “As it turns out, atazanavir was found to have very favorable effects on lipid profiles in patients with HIV infection.”

Atazanavir can also be given in conjunction with another protease inhibitor, such as saquinivir, once a day. In this study, atazanavir was given with saquinivir, providing the benefits of the atazanavir plus the benefits of the saquinivir at a much lower daily dosage. The combination allowed once daily dosing.

“One of the difficulties facing HIV providers and their patients is identifying regimens that are not only able to control the virus, but also do not have huge pill burdens,” Haas said. “This combination can be given once a day, which is a big plus.”

Ritonavir, another protease inhibitor that blocks the liver enzymes and allows other protease inhibitors to achieve much higher levels, often increases lipid levels considerably. Atazanavir is able to offer the same benefit but actually seems to improve the lipid levels.

The study was a comparison of patients who were on a combination of atazanavir-saquinivir or ritonavir-saquinivir and was performed at 36 centers in the United States, Europe, Canada, and South America. Haas served as lead investigator at Vanderbilt and was also involved in the data analysis and presentation.

Haas has been involved with Bristol Meyers Squibb, the manufacturer of atazanavir, to decide the best use of the agent. As part of an ongoing collaboration between industry and academia, Bristol Meyers Squibb is sponsoring one of their employees in the Masters of Science in Clinical Investigation program at Vanderbilt. The student, Dr. Mustafa Noor, is designing a research project studying the effects of atazanavir in healthy volunteers to better understand how it affects lipid metabolism. Haas is serving as his mentor.

Atazanavir is currently in phase 3 clinical trials, and Haas predicts that the drug may be approved later this year. For more information or to inquire about participating in HIV clinical trials, contact Victoria Harris at 467-0154 extension 109 or e-mail, victoria.harris@vanderbilt.edu.