Greater economic incentives are needed for companies to accelerate development of vaccines against killers like AIDS and bird flu, according to the head of the International AIDS Vaccine Initiative.

Dr. Seth Berkley, president of the non-profit group, said the threat posed by bird flu highlights the folly of not taking a long-term approach toward vaccines.

The world is ill-prepared to make the large quantities of flu vaccine that will be needed if avian flu triggers a human pandemic, as many scientists fear, because few companies remain in the business and there has been no investment in modern production methods.

Flu vaccine is still made laboriously in chicken eggs, rather than in cell-based manufacturing systems that are widely used for producing other biotechnology products.

"The whole system for vaccines is not aligned properly," Berkley told Reuters. "We have to find better ways to accelerate research, to finance research and to create incentives for pharmaceutical companies."

He plans to lobby for such commitments in discussions with policymakers at the annual meeting of the World Economic Forum in Davos this week.

With 4.9 million new HIV infections in 2005 alone, scientists agree a vaccine is desperately needed to end the AIDS epidemic.

G-8 PROMISES

The G-8 group of industrialized nations noted AIDS vaccines as a priority area during its meeting in Gleneagles, Scotland, in 2005. But Berkley said it was the sixth time the group had expressed support, and implementing such promises remained a critical requirement.

Changes were needed both to push forward good scientific ideas and to pull big drug makers into the field, by offering them advanced purchase commitments that would guarantee a market for any products developed, he said.

Although more than 30 HIV/AIDS vaccines are now being tested in clinical trials around the world, Berkley said there would not be a useable product on the market until the next decade, even in a best-case scenario.

The first-ever large-scale AIDS vaccine trial was completed in 2003, but it failed to provide protection.

Since then, Merck & Co Inc has reported encouraging early-stage results with an experimental vaccine, called MRKAd5, prompting it to expand testing last year.

Doubts remain, however, as to how well Merck's vaccine, which uses a common-cold virus to carry HIV genes into human cells, would work in the developing world.

Another problem is that all the most advanced AIDS vaccine candidates use a similar approach, known as cell mediation, and Berkley said there is an urgent need to study other approaches as well, notably antibody-based vaccines.

That will require more money, and Berkley repeated his call for annual global investment in AIDS vaccines to be doubled to at least $1.2 billion a year.

The dietary supplement DHEA seems to relieve the symptoms of minor depression in patients infected with HIV, the virus that causes AIDS, according to a new report.

"Based on our trial and the handful of others in the literature, I don't think any of us would recommend DHEA as first-line treatment for depression," Dr. Judith G. Rabkin told Reuters Health. "DHEA is, however, attractive for patients who refuse to take antidepressants or for patients with mild chronic depression who are particularly enthusiastic about complementary-alternative medicine strategies."

DHEA, which stands for dehydroepiandrosterone, is an unregulated steroid-like supplement to treat a variety of conditions. People take DHEA to build muscles, reduce abdominal fat, improve blood sugar levels and as an antiaging remedy, among other reasons.

Rabkin from Columbia University College of Physicians and Surgeons, New York and colleagues assessed the effectiveness of DHEA in an eight-week trial involving 145 HIV-positive adults with mild depression. Two thirds had a diagnosis of AIDS, according to the report in the American Journal of Psychiatry.

Participants were randomly assigned to placebo or DHEA tablets, starting at 100 milligrams per day, and increased up to 400 milligrams per day over 4 weeks if symptoms did not improve and if there were no side effects.

The response rate was higher for DHEA patients (56 percent) than for placebo patients (31 percent), the researchers report, and women and men responded equally well to DHEA.

Blood levels of DHEA did not differ significantly between responders and nonresponders, the results indicate.

DHEA treatment was associated with a significant increase in testosterone levels in women, but not in men, the researchers note. DHEA did not significantly affect CD4+ cell levels, a standard measure of immune function, or HIV viral load.

Side effects during treatment were relatively uncommon and did not differ between treatment groups, the report indicates.

"In response to many requests, we added a four-month extension phase for patients who responded to DHEA," the investigators write. "Overall, the results of this intermediate-term eight-month follow-up suggest that mood response is maintained with minimal and possibly nonspecific side effects, although long-term effects remain unknown."

"It would be extremely useful if there is some federal regulation/oversight of the purity and contents of substances such as DHEA that are sold over-the-counter, Rabkin suggested. The amount of DHEA in several samples bought by the researchers at health food stores ranged from 0 to 150 percent of what was on the label.

Another problem is dosing. "DHEA in 100 milligram tablets is hard to find in health food stores, where tablets usually are 25 milligrams," Rabkin explained. "Also, because it is not classified as a drug, insurance won't pay for it, which was a hardship for some of our patients on disability with minimal income, even though it is inexpensive."

SOURCE: American Journal of Psychiatry, January 2006.

Vaginal application of the PRO 2000 gel exerts activity against HIV and herpes simplex virus (HSV), investigators report in The Journal of Infectious Diseases.

However, PRO 2000 and the many other microbicides being investigated to protect against HIV transmission face multiple challenges before they can made widely available, authors of a second Journal article note.

PRO 2000 gel (Indevus Pharmaceuticals) is a synthetic compound that prevents HIV entry into cells by interacting with the proteins on the surface of the virus. While this agent has demonstrated the ability to inhibit HIV and HSV in cell cultures and in animal models, it was not known if it would be active after application in the human vagina.

Dr. Betsy C. Herold, from Mount Sinai School of Medicine in New York, and colleagues recruited 20 HIV-infected women. Cell samples from the vagina and cervix were collected before and one hour after vaginal application of 2 milliliters of the PRO 2000 gel or an inactive placebo gel.

Upon exposure to HIV, there was a significant reduction in HIV levels in cell samples from subjects treated with PRO 2000 compared with cells treated with the placebo.

Herold's group conducted a similar experiment using a virus that had surface proteins cloned from a HIV type that predominates "after sexual transmission and may be more readily transmitted via mucosal routes." HIV infection was inhibited by greater than 99 percent in cervical and vaginal cells exposed to PRO 2000.

The authors also noted potent anti-HSV activity with PRO 2000 compared with placebo.

"This trial demonstrates for the first time that a candidate microbicide is sufficiently bioavailable and retains substantial anti-HIV and anti-HSV activity after intravaginal application," Herold and her team conclude.

In the second paper, Drs. Darpun Dhawan and Kenneth H. Mayer, from Brown Medical School in Providence, Rhode Island, report that more than 30 other microbicides are under investigation, including 15 that are being studied in clinical trials.

Strategies of candidate microbicides include disruption of the HIV membrane, alteration of the vaginal pH, inhibition of HIV receptors.

Major obstacles that remain are developing ways for preclinical testing to evaluate safety and potential microbicidal resistance in the genital tract.

Other challenges include the need to enroll thousands of HIV-uninfected, high-risk subjects in clinical trials that will last for several years and the development of agents to prevent transmission during anal intercourse.

SOURCE: The Journal of Infectious Diseases, January 1, 2006.