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 Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

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: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>