By Megan Rauscher

NEW YORK (Reuters Health) - Among HIV-infected adults who have not been previously treated with HIV drugs who start on highly active antiretroviral therapy (HAART), less than perfect adherence to medication schedules and high levels of HIV in the blood before therapy are two major predictors of drug resistance.

These are the results of a study presented in New York City on Thursday at the American Medical Association Media Briefing "HIV/AIDS: The Drug Resistance Epidemic." The findings are also published in The Journal of Infectious Diseases.

Dr. P. Richard Harrigan from the British Columbia Center for Excellence in HIV/AIDS in Vancouver and colleagues evaluated drug resistance in all 1191 HIV-infected adults beginning HAART in British Columbia between August 1, 1996 and September 30, 1999.

Two hundred ninety-eight subjects (25 percent) developed drug-resistant virus mutations during follow-up, which is in line with previous reports.

"If one looks systematically, approximately one third of patients starting HAART will have developed some degree of HIV drug resistance over the first 2.5 years of therapy," Harrigan told Reuters Health.

There was little difference in time to resistance whether one started with a protease inhibitor-based regimen or a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen, he reported.

Of all the factors studied, adherence to medication had the greatest impact on the development of drug resistance.

The findings revealed that "people who are doing what is actually a pretty reasonable job of adhering to therapy -- they are taking most of their medication -- have the highest risk of developing resistance," Harrigan noted.

Patients with prescription refill rates between 80 and 90 percent were more than four times more likely to develop drug resistance than patients who refilled less than 20 percent of their prescriptions. Those with medication refill percentages of 95 percent or higher did not develop resistance during the study period.

"The lowest risk was in those who religiously picked up their medication and consistently had good levels of the drugs in their bloodstream, managed to suppress their virus well," he added.

Another important predictor of the development of drug-resistance was blood levels of HIV at the start of therapy. Patients with high blood levels of HIV at the start of therapy had a 59-percent increased risk of developing drug resistance.

"This implies that the HIV drugs were not sufficient to completely shut down virus replication in these individuals who had very high amounts of virus, and that one should be most wary of potential resistance problems in those with high viral loads," Harrigan said.

SOURCE: The Journal of Infectious Diseases, February 1, 2005.

By Patricia Reaney

LONDON (Reuters) - A single change in a human gene may hold the key to preventing people living with HIV from progressing to full-blown AIDS, researchers said on Monday.

They found a crucial difference between a gene in humans and one in rhesus monkeys that blocks infection of the virus in the animals -- a finding that offers new insights into the origins of AIDS and gene therapy.

Had the gene been the same in humans, scientists at the National Institute of Medical Research in London believe, there may not have been the AIDS epidemic that now affects 40 million people worldwide.

"If it had recognized HIV, we probably would never have had AIDS. I believe it is a key change," said Dr Jonathan Stoye, head of virology at the institute.

Scientists had been aware that it was much more difficult to infect monkey cells with HIV than human cells in laboratory experiments, which suggested there was something different in the animal cells that blocked infection.

A gene called Trim 5 alpha was later found to be the reason why. In monkeys, but not in humans, it stops the virus from replicating.

Stoye and his team studied differences in the gene products of the monkey and human Trim 5 alpha genes. They pinpointed one specific change in a protein that was important in blocking HIV. By substituting a human protein with a monkey-derived protein they found they could make the human cells resistant to HIV.

"The discovery has significant implications for the development of effective gene therapy to combat AIDS," Stoye, who reported the findings in the journal Current Biology, told Reuters.

He and his team believe introducing the gene carrying that single change back into human cells would make those cells resistant to HIV infection.

Gene therapy is an experimental technique which introduces genetic material into cells to fight disease. The technique has been used for Parkinson's disease and in trials for illnesses such as cystic fibrosis and cancer.

Two French boys with severe immune deficiency were cured with gene therapy but they later developed leukemia.   

The resistant cells might be sufficient to prevent the progression to AIDS, he added.

But Stoye stressed that more laboratory research, followed by animal tests and human trials will be needed.

"If this were the equivalent of adding a drug with a new target to the repertoire of drugs that we have for the treatment of AIDS, I think it would be of value."

© Reuters 2005. All Rights Reserved.

Thursday January 13, 9:22 PM

Study: AIDS Problem Growing in Russia

HIV/AIDS is spreading at a devastating pace in Russia, with a new study showing an estimated 1 million people infected _ three times the number officially reported _ U.S. and Russian experts said Wednesday.

A recently released 90-page report by Murray Feshbach and Cristina Galvin of the Woodrow Wilson International Center for Scholars urged Russian authorities to take aggressive steps to fight the epidemic. The study was sponsored by U.S. Agency for International Development.

According to official statistics, Russia has some 300,000 HIV-positive people. But Feshbach, as well as Russian experts, said the true number is closer to 1 million. The study estimated the number of AIDS deaths in Russia at 13,000, almost three times the official figure of 4,800.

If officials ignore the problem, "the consequences will be devastating to the society, family formation, to the military, labor productivity" within two to three years, Feshbach said by telephone from Washington.

Local experts say authorities are not getting the message.

"Despite all that we have been saying and what international organizations have been saying, funding for HIV/AIDS is not being increased, but is actually being reduced because of inflation," said Vadim Pokrovsky, the head of the Federal AIDS Center.

Pokrovsky said that the 2005 national budget envisages $4.3 million for HIV/AIDS, whereas the amount needed is nearly 40 times higher _ $161.7 million.

The study also found HIV testing has dropped significantly in recent years, after the financial burden for tests was transferred from the federal to the regional budget.

The study showed that more than 80 percent of HIV/AIDS-infected Russians are under 30, compared with 70 percent in North America and Western Europe.

Pokrovsky also said the epidemic is shifting from mainly intravenous drug users to transmission through heterosexual activity.

"This past year has seen a major shift from drug users to heterosexual sex _ in some regions as many as half of new infections were the result of heterosexual intercourse," Pokrovsky said.

Human Genome: FDA approves trials for AIDS drug

LONDON (AFX) -- Human Genome Sciences Inc. said it has received clearance from the U.S. Food and Drug Administration of its application to begin clinical trials of its monoclonal antibody CCR5 mAb for the treatment of HIV/AIDS. It now plans to proceed with a Phase 1 clinical trial.
This story was supplied by CBSMarketWatch. For further information see www.cbsmarketwatch.com.

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