Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Clinical trial evaluates first-line approaches for treating HIV

15.08.2006
Results of first trial to compare two standard therapies and 'nuke'-sparing approach presented at AIDS 2006

In the first head-to-head comparison between two commonly used HIV treatments, researchers found one triple-drug therapy was significantly more effective at reducing HIV viral load in the blood when used as a first-line treatment.

Results of the clinical trial, which sought to determine from among three different therapies the optimal approach for patients beginning HIV treatment for the first time, will be reported at the XVI International AIDS Conference (AIDS 2006).

Of the two triple-drug approaches evaluated in the randomized trial, the therapy consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) with efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), suppressed the virus to undetectable levels in more participants than the three-drug combination of two NRTIs and a protease inhibitor called lopinavir/ritonavir. Moreover, a third regimen, efavirenz and lopinavir/ritonavir, performed nearly as well as the three-drug cocktail with efavirenz, suggesting initial therapy need not include NRTIs, a class of drugs that can produce intolerable side effects in some patients.

"Our findings suggest that the efavirenz plus two-NRTI regimen was the best of the three approaches as initial therapy, even in patients with relatively advanced HIV disease," said Sharon Riddler, M.D., M.P.H., assistant professor of medicine in the division of infectious diseases at the University of Pittsburgh School of Medicine, who will present the findings at AIDS 2006.

"Also, we found that the NRTI-sparing two-drug combination of efavirenz and lopinavir had a similar level of effectiveness to the efavirenz plus two-NRTI regimen. When we started this study, we heard from physicians with concerns about using efavirenz in the absence of NRTIs. Now that we've completed the trial, there should be little doubt that patients can benefit from this 'nuke'-sparing treatment regimen when NRTI side effects are a problem," she added.

The NRTI-sparing combination of lopinavir/ritonavir and efavirenz had never before been studied as first-line therapy in a large randomized clinical trial, in part because a general belief that combining an NNRTI with a protease inhibitor could result in resistance to two important classes of drugs. But earlier studies with other drug combinations suggested the approach would be safe. Thus, in designing the trial, Dr. Riddler and her national co-chair, Richard Haubrich, M.D., at the University of California, San Diego (UCSD) School of Medicine, felt it important to include this less conventional regimen so it could be evaluated under the rigors of a clinical trial.

The study included 753 participants at 55 centers and was conducted under the auspices of the AIDS Clinical Trials Group (ACTG), considered the world's largest HIV clinical trials organization. ACTG receives its funding from the National Institute of Allergy and Infectious Diseases.

At the start of the study, just more than half of the participants had viral loads greater than 100,000 copies of HIV RNA per milliliter of blood. The median CD4+ T cell count was just 182 cells per cubic milliliter. Each participant was randomly assigned to one of the three treatment arms: 250 were selected to receive the efavirenz-based triple drug therapy, 253 the lopinavir/ritonavir-based triple drug therapy, and 250 were assigned to the group receiving the NRTI-sparing regimen of efavirenz and lopinavir/ritonavir. Participants in the triple-drug therapy groups each received two NRTIs: lamivudine, plus their choice of stavudine, zidovudine or tenofovir disoproxil fumarate.

The researchers found all three of the treatment regimens were potent, producing substantial increases in CD4+ T cell counts and decreases in HIV viral load. After 96 weeks of treatment, 89 percent of the participants randomized to the efavirenz arm had "undetectable" levels of HIV, meaning viral load was less than 50 copies per milliliter; 77 percent of the lopinavir/ritonavir arm participants and 83 percent of the participants on the NRTI-sparing regimen had low viral loads. Interestingly, the CD4+ T cell count increase was greater in the two study arms containing lopinavir/ritonavir as compared to the efavirenz regimen. At week 96, the CD4+ T cells increased from baseline to 285 cells in the lopinavir/ritonavir group, 268 cells in the nucleoside-sparing group and 241 cells for the efavirenz regimen.

More participants in the lopinavir/ritonavir group experienced virologic failure – a rebound in the HIV virus load to detectable levels – during the study compared to the efavirenz group. After 96 weeks of treatment, 33 percent of participants in the lopinavir/ritonavir group had virologic failure compared to 24 percent of the participants receiving the efavirenz-based therapy and 27 percent of those in the NRTI-sparing group.

It was no mistake that the two particular triple-drug therapies were selected for the study. Both are listed as "preferred" options in the U.S. Department of Health and Human Service's treatment guidelines for HIV infection.

"We were surprised that the lopinavir plus two-NRTI regimen did not perform as well as the efavirenz-based treatment because lopinavir/ritonavir is considered one of the most potent drugs that we have available for HIV treatment at this time. It may be that the lopinavir/ritonavir regimen, which was dosed twice daily using the soft gel capsule form, was less convenient or less well tolerated by patients. We will continue to evaluate our study data to try to assess the reasons for these findings," noted Dr. Haubrich, professor of medicine in the division of infectious diseases at UCSD School of Medicine.

All of the drugs used in the clinical trial are approved for the treatment of HIV. Nucleoside reverse transcriptase inhibitors, or NRTIs, prevent healthy T cells from being infected by blocking a process called reverse transcription that HIV uses to convert its RNA into DNA. By inserting faulty building blocks, HIV can't copy its DNA. NNRTIs, the non-nucleoside reverse transcriptase inhibitors, target the same mechanism but block the reverse transcriptase enzyme by attaching to a different site than NRTIs. The class of drugs known as protease inhibitors blocks the maturation of proteins that HIV needs to assemble itself into an infectious virus.

Lisa Rossi | EurekAlert!
Further information:
http://www.upmc.edu

More articles from Health and Medicine:

nachricht The genes are not to blame
20.07.2018 | Technische Universität München

nachricht Targeting headaches and tumors with nano-submarines
20.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>