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 Vanishing capillaries
23.03.2017 | Technische Universität München

nachricht How prenatal maternal infections may affect genetic factors in Autism spectrum disorder
22.03.2017 | University of California - San Diego

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: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

Inactivate vaccines faster and more effectively using electron beams

23.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>