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 PET imaging tracks Zika virus infection, disease progression in mouse model
20.09.2017 | US Army Medical Research Institute of Infectious Diseases

nachricht 'Exciting' discovery on path to develop new type of vaccine to treat global viruses
18.09.2017 | University of Southampton

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: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Molecular Force Sensors

20.09.2017 | Life Sciences

Producing electricity during flight

20.09.2017 | Power and Electrical Engineering

Tiny lasers from a gallery of whispers

20.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>