Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Changes in prevalence of mutations associated with HIV treatment failure

14.02.2003


The results from a longitudinal study of the relative frequency of various types of HIV mutations associated with the use of antiretroviral therapy (ART) were presented today at a meeting of leading AIDS researchers. The study showed that the prevalence of most key mutations associated with antiretroviral resistance have changed significantly from 1999-2002.

Specifically, the results showed that the prevalence of thymidine analog mutations (TAMs) and other key mutations associated with HIV drug resistance has decreased significantly as reported in the LabCorp Database in recent years, while mutations such as K65R and Y115F are on the rise.

"Although further studies are needed to determine the reasons behind these findings, the increased use of three drug regimens, the introduction of new drugs and/or drug combinations and changes in the submission of patient samples for genotyping may all be factors affecting the changing patterns of HIV mutations in this large sample," said Doug Manion, M.D., vice president of Clinical Development, GSK.



The results come from a longitudinal study of the relative frequency of all primary mutations and many combinations of mutations associated with ART from January 1, 1999, through July 1, 2002. The study involved nearly 38,000 genotypic tests performed between 1999 and mid-2002 to identify mutations associated with HIV resistance to antiretroviral drugs, including nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs).

Trends in the use of specific antiretroviral therapies in the United States during the same time period also were presented by the researchers.

Study investigators noted that the databases used are not linked, and the results show independent trends, not a direct correlation between drug usage and mutation incidence. However, the data show that the changes in prescribing patterns of antiretroviral therapy and in the mutations associated with specific drugs or drug combinations follow expected parallel trends. Further studies are warranted to directly show the relationship between mutations, antiretroviral therapy choices and clinical practices.

The following trends were seen in mutations associated with resistance to the three classes of drugs included in the study:

Wild-Type

  • Wild-type samples increased from 29 percent to 37 percent.

NRTIs

  • The greatest proportional increases were for K65R (from 0.64 percent to 1.69 percent) and for Y115F (0.59 percent to 1.42 percent).
  • TAMS decreased steadily, including: T215Y (32 percent to 23 percent); D67N, K70R and 219E/Q (13 percent to 8 percent); and M41L, L210W and T215Y (17 percent to 11 percent).
  • L74V also decreased (9.77 percent to 7.85 percent).
  • No significant changes were seen in M184V (44 percent to 42 percent), T69SXX (0.81 percent to 0.73 percent) or Q151M (1.79 percent to 1.39 percent).

NNRTIs

  • Y181C decreased from 19 percent to 12 percent.
  • K103N was stable (29 percent to 30 percent).

Protease Inhibitors

  • All PI-associated mutations decreased with the exception of a small increase in I50V.
  • The most pronounced decreases were seen for M461/L, V82A, 184V and L90M.

"Resistance to antiretroviral therapy is a major factor that limits the effectiveness of drug therapy. As specific drugs increase or decrease in usage, the prevalence of mutations associated with those drugs should also rise or fall, although many other factors may alter the rate of mutant selection," said Manion.

Resistance Data May Help Predict Best Options

In a related study, resistance data were used to evaluate the median phenotype for 30 mutational patterns associated with resistance to NRTIs. Although further study is needed to determine utility in clinical practice, study investigators believe the technique may be useful to minimize the potential for the rapid selection of mutations resistant to multiple NRTIs arising from specific drug combinations, and guide the selection of treatment options after virologic failure.

"For example, patterns involving 65R and/or 74V in conjunction with M184V are associated with resistance to multiple NRTIs, and require substantially fewer mutations than TAM patterns associated with resistance to multiple NRTIs. TAMs individually and in many combinations do not increase phenotypic resistance to the NRTIs as much as some individual NRTI-associated mutations," said Manion.

In the study, a major database was searched for paired genotypes and phenotypes, and 10,478 unique pairs were studied based on clinically determined phenotypic "breakpoints" associated with resistance to the various drugs in the NRTI class.

GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and healthcare companies and an industry leader in HIV research and therapies. The company is engaged in basic research programs designed to investigate new targets to treat HIV.



AT A GLANCE

The prevalence of most key mutations associated with antiretroviral resistance have changed significantly from 1999-2002.

The largest increase was seen in the K65R and Y115F mutations, while thymidine analog mutations (TAMs) and most mutations associated with protease inhibitors have decreased steadily.

Resistance data from mutational patterns associated with specific drug combinations may be useful in predicting potential treatment failure or choosing future treatment options.

Media contacts:
Mary Faye Dark, GlaxoSmithKline
Cell phone: 919-946-0190 — 2/10 through 2/14
Office: 919-483-2839

Beth Schlesinger, Public Communications Inc.
Pager: 800-759-8888, PIN 1050707 — 2/10 through 2/14 Office: 312-558-1770

Amy Kling | EurekAlert!
Further information:
http://www.pcipr.com/

More articles from Health and Medicine:

nachricht Purdue cancer identity technology makes it easier to find a tumor's 'address'
16.11.2018 | Purdue University

nachricht Microgel powder fights infection and helps wounds heal
14.11.2018 | Michigan Technological University

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: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Purdue cancer identity technology makes it easier to find a tumor's 'address'

16.11.2018 | Health and Medicine

Good preparation is half the digestion

16.11.2018 | Life Sciences

Microscope measures muscle weakness

16.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>