Featured Research

from universities, journals, and other organizations

Persistent HIV replication associated with lower drug concentrations in lymphatic tissues

Date:
January 22, 2014
Source:
University of Minnesota Academic Health Center
Summary:
Drugs used to treat HIV penetrate poorly into lymphatic tissues where most HIV replication takes place and there is persistent low-level virus replication in these tissues according to research.

Drugs used to treat HIV penetrate poorly into lymphatic tissues where most HIV replication takes place and there is persistent HIV replication in these tissuesaccording to research from the University of Minnesota and University of Nebraska Medical Center.

The results appear in the latest issue of the Proceedings of the National Academy of Sciences (PNAS).

"We know the drugs we use today are effective because our patients are doing better and living longer, but these drugs cannot cure the infection," said Timothy Schacker, M.D., director of the Program in HIV Medicine at the University of Minnesota. "We wanted to know why and thought that maybe the drugs were not getting into the tissues where most virus replication is happening."

Schacker teamed up with Ashley Haase, M.D., Regents' Professor and Head of Microbiology, and Courtney Fletcher, Pharm.D., dean of the College of Pharmacy at the University of Nebraska Medical Center to measure drug levels and find the impact on HIV-1 replication in those tissues.

"These are very complex questions requiring expertise from many disciplines to get the data required to understand what is going on," said Schacker. "This is a great example of the kind of team science we need to make progress in curing this disease."

Schacker, the principal investigator of the project, assembled a cohort of patients and started them on antiretroviral therapy. He collected lymph nodes and gut samples from these patients at frequent intervals.

Fletcher used highly specialized and sensitive methods, developed in his laboratory, for measuring drug levels inside cells obtained from lymph nodes and gut tissues.

"The common approach of looking at drug concentrations in plasma may provide misleading information. What is most important to understand is the concentration of a drug actually inside an HIV-infected cell in the compartments where most of the virus is actually produced," said Fletcher. "What we found, in studies conducted during six months of therapy in 12 HIV-infected persons receiving combinations of five of the most commonly used drugs to treat HIV infection was that concentrations inside the cells from lymph tissues were surprisingly low compared with blood."

Haase then used sensitive methods to precisely measure the amount and location of virus in the lymph node and gut tissues and found the virus continued to replicate in the tissues, even when it was undetectable in blood.

"Most HIV replicates in the lymph and gut tissues and that's where we need to look to understand the efficacy of these drugs. The ongoing replication we found in the lymph and gut tissues we tested directly correlated with the drug levels found there," said Haase. "This persistent low-level replication may be one cause of the chronic immune activation we find in these patients, and is likely an important factor in accelerated aging, increased cardiovascular events and early mortality common in these patients."

Schacker, Fletcher, Haase and their collaborators are now working on a comprehensive survey of all available anti-retroviral drugs in an effort to identify a combination of drugs with that will provide maximum penetration into lymph nodes and more effectively stop virus replication.

"We will not cure this disease until we can completely suppress virus replication," said Schacker.


Story Source:

The above story is based on materials provided by University of Minnesota Academic Health Center. The original article was written by Caroline Marin. Note: Materials may be edited for content and length.


Journal Reference:

  1. Courtney V. Fletcher, Kathryn Staskus, Stephen W. Wietgrefe, Meghan Rothenberger, Cavan Reilly, Jeffrey G. Chipman, Greg J. Beilman, Alexander Khoruts, Ann Thorkelson, Thomas E. Schmidt, Jodi Anderson, Katherine Perkey, Mario Stevenson, Alan S. Perelson, Daniel C. Douek, Ashley T. Haase, and Timothy W. Schacker. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. PNAS, January 2014

Cite This Page:

University of Minnesota Academic Health Center. "Persistent HIV replication associated with lower drug concentrations in lymphatic tissues." ScienceDaily. ScienceDaily, 22 January 2014. <www.sciencedaily.com/releases/2014/01/140122153917.htm>.
University of Minnesota Academic Health Center. (2014, January 22). Persistent HIV replication associated with lower drug concentrations in lymphatic tissues. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2014/01/140122153917.htm
University of Minnesota Academic Health Center. "Persistent HIV replication associated with lower drug concentrations in lymphatic tissues." ScienceDaily. www.sciencedaily.com/releases/2014/01/140122153917.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins