That's because human cells mutate at much slower rates than does HIV, so the virus would have much less chance of mutating around the drug, scientists explained.

The research is still in its early stages, but it "provides a very nice model that you can inhibit a cellular protein and affect HIV replication," explained co-senior author Dr. Pamela Schwartzberg, a senior investigator at the U.S. National Human Genome Research Institute.

Her team published the findings in this week's edition of the Proceedings of the National Academy of Sciences.

Almost all antiretroviral drugs work by targeting a viral protein. But HIV replicates continually, raising the odds for drug-resistant mutations. For this reason, HIV-positive patients must often take two or three different medications, so that if one drug fails, the others will still fend off the virus.

But there's another player in HIV infection: the human immune system T-cell, the virus' preferred host. T-cells carry their own surface proteins, but because humans replicate much less often than HIV, the odds of developing drug-resistant genetic mutations are much lower.

"If you are looking to affect a human protein, it's going to be much less susceptible to the process of developing resistance," explained Rowena Johnston, vice president of research at The Foundation for AIDS Research (amfAR) in New York City.

In their research, Schwartzberg and co-senior author Andrew Henderson, of Boston University, decided to focus on a T-cell protein called interleukin-2-inducible T-cell kinase (ITK). ITK is a "signaling" protein that works in a variety of ways to activate T-cells.

An activated T-cell is the ideal host for HIV, Schwartzberg pointed out, and ITK appears to be crucial to HIV's invasion and spread.

"We found that there were several cellular processes in T-cells that HIV needs to use and that ITK was important to," she said. "In fact, it seems to affect three stages in the HIV life cycle. That was a real surprise to us."

But would inhibiting ITK inhibit HIV? The researchers got help in answering that question from the pharmaceutical industry, which has been developing ITK inhibitor drugs as possible anti-asthma medications.

In laboratory experiments, Schwartzberg and Henderson used these experimental ITK inhibitors -- as well as another technique, called RNA interference -- to reduce ITK activity in HIV-infected T-cells.

"We could see rather dramatic effects on HIV replication in T-cells," Schwartzberg said.

Without active ITK in host T-cells, HIV found it much harder to enter the cell and to transcribe its genetic material into new viral particles, the team found. "The effect was quite strong over the course of a week, which was the length of time that we looked at," Schwartzberg said.

Of course, ITK is important to the proper function of immune T-cells, so questions remain as to whether its suppression might have unwanted side effects, such as a weakening of immune function. But experiments in mice suggest these effects might be minimal.

ITK-suppressed mice did have impaired immune function, but it was mostly confined to a specific type of response -- the defense the body mounts against allergies and asthma, Schwartzberg said. In other respects, ITK-suppressed cells appeared to "function in many circumstances, and they can fight off many infections," she noted.

Still, it's a long way from research in the test tube and in mice to human clinical trials. But the promise of a human cell-based HIV medication that attacks the virus at three different spots in its life cycle is hugely attractive, Johnston said.

"The virus would have to mutate in three different ways at once to overcome this ITK effect," she said. "It's not impossible, the virus can do it, but it would take a very long time."

Dampening down T-cell activity might not be such a bad idea, either, Johnston added, since HIV thrives on fully activated T-cells.

Schwartzberg said her team will continue to investigate the biological mechanisms underpinning the ITK-HIV relationship. In the meantime, she is optimistic that the drug industry will take up the gauntlet, in terms of clinical research.

"We hope that one of these companies that have developed ITK inhibitors will try and pursue this -- that would be wonderful," Schwartzberg said.

More information

For more on the fight against HIV/AIDS, head to amFAR.

But a new study shows that survival is only slightly affected if these decisions are based instead on the appearance of clinical symptoms.

Researchers still need to develop less expensive versions of laboratory tests currently used, but lack of test availability shouldn't affect access to highly effective drugs in poorer nations, said the authors of a study in this week's issue of The Lancet.

"I hope that the findings will reassure health policy makers and clinicians that they should continue to make every effort to widen access to ART and not allow any concerns over lack of laboratory monitoring to inhibit this," said study author Andrew Phillips, a professor of epidemiology at Royal Free and University Medical School in London.

The World Health Organization (WHO) recommends that, in lower-income areas, decisions regarding drug treatment for HIV be based on symptoms and, when available, CD4 cell count, rather than viral load.

With viral load, switches to second-line treatment occur when the viral load exceeds 500 copies per millileter.

CD4 cells are a type of immune system cell. Patients generally switch to the second-line drugs when CD4 counts in the blood drop 50 percent from their highest.

WHO-recommended first-line treatment consists of the antiretroviral drugs Zerit (stavudine), Epivir (lamivudine) and Viramune (nevirapine).

Using a computer simulation model to analyze how antiretroviral therapy influences HIV infection, the researchers compared survival rates, switch of second-line medication regimens and development of resistance for three different strategies: monitoring viral load and CD4 cell count or clinical observation.

Over a period of five years, 83 percent of patients using the viral load monitoring strategy, 82 percent using CD4 cell count monitoring, and 82 percent using clinical monitoring survived.

After a period of 20 years, survival rates were 67 percent, 64 percent and 64 percent, respectively. Viral load monitoring showed a slightly longer survival but was not the most cost-effective avenue (at a cost of around $3,500 per life-year gained).

Other experts were concerned that the results might be construed to mean viral load monitoring and CD4 cell count should be abandoned in the developed world.

"It's a great study, but it has no application to First World countries," said Dr. Michael Horberg, director of HIV/AIDS policy at Kaiser Permanente Health Plan in Santa Clara, Calif. "There is wide availability of these tests, and there should be funds to support such monitoring.

"Having said that, it has to be well-acknowledged that in resource-limited nations, CD4 count and viral load monitoring are expensive and have limited availability, and clinical decisions have to be made on the basis of clinical impressions," Horberg continued. "Health-care infrastructures must be sent to resource-limited nations. However, in the interim, clinicians should at least be reassured that their clinical practices are not doing undue harm.

"Infectivity seems to be increased with increased viral load. Not monitoring viral load could mean that highly infectious patients are passing the virus to new people and, indeed, a virus which is already resistant to drugs."

More information

The World Health Organization has more on antiretroviral therapy for HIV infection.

FRIDAY, April 11 (HealthDay News) -- Three-quarters of the 68 countries most in need of improving mother and child mortality rates have made little, if any, progress in meeting internationally set goals over the past three years, according to a series of new reports.

The Countdown to 2015 for Maternal, Newborn and Child Survival, an international group that monitors these goals, still holds hope that progress can be made quickly in these underachieving nations, according to reports this week in a special edition of The Lancet.

The medical journal looks at the group's efforts in 68 "priority" or "countdown" countries, where 97 percent of the maternal and child-under-5 deaths occur worldwide. The group has set goals to reduce child mortality rate by two-thirds and maternal deaths by three-quarters by 2015.

In a commentary, Lancet Editor Dr. Richard Horton calls the Countdown project's overall progress "strikingly inadequate" and concludes, "children and mothers are dying, because those who have the power to prevent their deaths choose not to act. This indifference -- by politicians, policy makers, donors, research funders and civil society -- is a betrayal of our collective hope for a stronger and more just society."

Of the priority countries, only 16 are on track to reach the goal of reducing the mortality rate in children. Three -- China, Haiti and Turkmenistan -- had made demonstrable progress to improve maternal, newborn and child survival since the countdown began in 2005. The others were either already on track when the countdown was launched or were added onto the list only recently.

Most of the countries that have made no progress, or even taken steps backward, are in sub-Saharan Africa.

Another report in The Lancet states that most of the countries being watched have made some progress since 1990 to reduce the coverage gap for four key interventions -- family planning, maternal and newborn care, immunization and treatment of sick children. Yet the study, by the Countdown 2008 Equity Analysis Group, said the pace needs to be more than doubled if they hope to meet goals for 2015.

While actual maternal mortality was still high or very high in 56 of 68 countries, one report suggests some key parts of the solution are in place. These include consensus on priority interventions (such as immunization and antenatal care), various health-care policies and funding increases.

For example, donor funding increases have nearly doubled funding per child in the 68 countries, according to one report in The Lancet. Child-related disbursements increased from a mean of $4 per child in 2003 to $7 in 2006. Those for maternal and neonatal health increased from $7 per live birth in 2003 to $12 per live birth in 2006.

However, the report noted that funding still dropped in several countries, stifling attempts for governments to make long-term commitments to health improvements.

"In the seven years until 2015, the next two years before the next Countdown Report will be the most crucial," the study's authors wrote. "With strategic decisions and investments, and a focus on partnerships for results, we have the opportunity to see unprecedented progress in these 68 countries. Or will the 2010 report show more of the same gaps and lives lost?"

Some of the other findings in the special edition include:

• Policy gaps in many of the countries are hindering their progress along with financing woes and human resources issues.
• Tanzania is one of the few African nations on track to meet the goal of reducing child mortality, showing a 24 percent decline from 2000 to 2004. The report credits good program funding and several initiatives such as insecticide-treated nets to prevent malaria, vitamin A supplementation, immunization and exclusive breast-feeding.
• South Africa is suffering major setbacks in meeting its goals because of pregnancy and childbirth complications, newborn illness, childhood illness, HIV and AIDS, and malnutrition. It is one of just 12 countries globally where the child mortality rate has risen since 1990.

More information

Here's more about Countdown to 2015.

Preexisting immunity is believed to be a major problem in developing nations.

There will be 48 healthy volunteers taking part in the trial of the vaccine, which consists of a replication-incompetent, recombinant adenovirus serotype 26 (rAd26) vector encoding an HIV-1 envelope gene.

Each volunteer will receive either two or three immunizations, and then be monitored to assess the safety of the vaccine and its ability to trigger an immune response.

The rAd26 vaccine was developed by the Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) program, sponsored by the U.S. National Institute of Allergy and Infectious Diseases. The program brings together academic and industry researchers to accelerate development of promising HIV/AIDS vaccine candidates.

The vaccine, the first HIV-1 vaccine candidate to emerge from the IPCAVD program, is made by Dutch biotechnology company Crucell Holland B.V.

The approach used in developing the rAd26 vaccine enables researchers to circumvent preexisting immunity to serotype 5, the virus responsible for the common cold. This virus has recently shown limitations as an HIV-1 vaccine vector.

"The rAd26 vector does not regularly occur in the human population, and human antibodies to this vector are rare. The rAd26 vector therefore is efficacious in eliciting good T and B (immune) cell responses," Jaap Goudsmit, chief scientific officer at Crucell, said in a prepared statement.

About 33.2 million people worldwide are living with HIV/AIDS, and there were 2.7 million new infections reported in 2007.

More information

Currently, there is no vaccine to protect against HIV/AIDS. The American Academy of Family Physicians offers tips for preventing HIV infection.

Based on that data, the U.S. Food and Drug Administration is now conducting a safety review of the potential risks of both drugs.

Many people with HIV take a combination of antiretroviral drugs, which include a protease inhibitor and a nucleoside reverse transcriptase inhibitor such as abacavir or didanosine. Concerns have been raised about the cardiovascular effects of long-term use of these drugs.

"We have investigated a number of drugs used to treat HIV patients for whether they are associated with an altered risk of having a heart attack," said lead researcher Dr. Jens D. Lundgren, from the University of Copenhagen in Denmark. "We have identified [that] two of those drugs were indeed associated with an increased risk of a heart attack."

The actual risk of having a heart attack when using these drugs varies with whether a patient already has underlying risk for heart attack, Lundgren added. For example, a patient who is at risk for having a heart attack will increase his or her risk by 38 percent by using either abacavir or didanosine, he said.

"However, if you have a very small underlying risk of heart attack, the risk will only be slightly increased," Lundgren said.

The report was published Wednesday in the online edition of The Lancet.

In the study, Lundgren's team collected data on 33,347 HIV patients who participated in the Data Collection on Adverse Events of Anti-HIV Drugs study (D:A:D). Specifically, the researchers looked for a connection between HIV medications and heart attack.

For commonly used drugs called nucleoside reverse transcriptase inhibitors such as zidovudine, stavudine or lamivudine, the researchers found no association with an increased risk for heart attack.

However, the nucleoside reverse transcriptase inhibitors abacavir and didanosine were associated with an increased rate of heart attack, the researchers found. For patients taking abacavir, there was a twofold increased risk for heart attack. For those taking didanosine, the increased risk was about 50 percent.

For patients who stopped using these drugs, their risk for heart attack decreased within six months, Lundgren's group found.

"For those patients who have an increased underlying cardiovascular risk, then our suggestion is that these patients should consider whether there are other safer alternatives to these drugs," Lundgren said. "If there are safer alternatives, then patients should consider switching to those."

In a letter published in the same journal issue, GlaxoSmithKline, the maker of abacavir, said that their own analysis of 54 studies found no increase in the risk of heart attack from the drug.

GlaxoSmithKline spokesman Dr. Didier Lapierre wrote, "We did not find a result consistent with that of D:A:D... GSK takes the D:A:D finding seriously and is committed to understanding these data more fully and to communicating openly with treating physicians and regulatory agencies globally."

Didanosine is manufactured by Bristol-Myers Squibb.

Based on the data from D:A:D, the FDA said last week that it was conducting a safety review of both drugs.

"FDA continues to evaluate the overall risks and benefits of abacavir and didanosine. This evaluation may result in the need to revise labeling for the products. Until this evaluation is complete, health-care providers should evaluate the potential risks and benefits of each HIV-1 antiretroviral drug their patients are taking, including abacavir and didanosine," the agency said in a statement.

One expert thinks it's more important for patients to have their HIV under control; then they can worry about potential cardiovascular side effects.

"This is a surprising and provocative finding," said Dr. James Sosman, an associate professor of medicine at the University of Wisconsin School of Medicine. "We have not seen cardiovascular problems associated with abacavir."

Sosman noted that the use of antiretroviral drugs has replaced concerns about serious opportunistic infections in HIV patients with concerns about less serious risks like cardiovascular disease and diabetes.

"The most important thing for HIV patient is to control their HIV," Sosman said. "If they have excellent control with abacavir or didanosine, then you look for options to limit other risk factors. Patients not on HIV therapy have a higher risk of developing heart disease than people on HIV therapy," he said.

More information

For more on HIV, visit the U.S. National Institute of Allergy and Infectious Diseases.