HIV/AIDS Vaccines: Defining What Works

Designing an effective HIV/AIDS vaccine is something of a paradox: a good vaccine would be safe and look enough like HIV to kick-start the immune system into neutralizing the virus -- but the problem is that this is exactly what the human immune system has trouble doing even when it's exposed to the real thing.

Now a team of researchers led by scientists at The Scripps Research Institute in La Jolla, CA has developed a strategy for inducing a key part of an effective immune response to HIV. By tracing the evolution of HIV-recognizing molecules called antibodies taken from the blood of rare individuals whose immune systems are naturally able to target and neutralize the virus, they may have found a way to replicate this for everybody.
At a talk next week at the American Crystallographic Association meeting in Hawaii, the team will present multiple crystal structures, which like detailed architectural blueprints show how the virus interacts with components of the immune system. Examining these structures has allowed them to reverse engineer molecules that specifically activate the precursors of effective, neutralizing antibodies against the virus -- molecules that may be components of a future vaccine against HIV.
"What we tried to do was to learn how those [effective] antibodies developed over the course of natural infection and attempt to guide the immune response in the direction of what we know works in certain HIV-infected individuals," said structural biologist Jean-Philippe Julien, who is presenting the work in Hawaii.
He conducted the research under the direction of Professors Ian Wilson and William Schief of The Scripps Research Institute. The work was funded by the International AIDS Vaccine Initiative Neutralizing Antibody Center, the Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery and the National Institute of Allergy and Infectious Diseases (one of the National Institutes of Health). Additional support was provided through a Canadian Institutes of Health Research fellowship.
Julien cautioned that the work might not, by itself, be the final answer that shows how to make an effective HIV/AIDS vaccine -- but it is a step in the right direction. Most likely, Julien said, any future HIV/AIDS vaccine would combine multiple biological components in order to give the broadest possible protection against the virus.
He added that their candidate molecule was able to achieve the desired immune reactions in the test tube, and they are currently testing it in animals to see if it is able to kick start the desired immune response. If those experiments go well, he said, further studies will examine whether it can protect animals against infection, and human trials for safety and vaccine efficacy would be next -- though it may be years before those results are known.
While designing a vaccine against any pathogen is a long, hard process, HIV has been particularly difficult, and despite decades of efforts and hundreds of millions of dollars spent in the process, we still do not yet have an effective vaccine that can prevent infection.

Marital Status Reduces Risk of Death

At the height of the AIDS epidemic in the 1980s men who were married were significantly less likely to die of HIV/AIDS than their divorced or otherwise single counterparts

 For women, marital status had little impact on who was more likely to die of the disease. But race proved to be a significant risk factor, with African-American women nine times more likely to die of HIV/AIDS and Latinas seven times more likely to die of the disease than white women. Those mortality rates were considerably higher than those for men of color compared to white men.
The study by UCR sociology professor Augustine Kposowa -- "Marital status and HIV/AIDS mortality: evidence from the U.S. National Longitudinal Mortality Study" -- is the first to examine the effects of marital status on deaths of individuals with HIV/AIDS.

Using data from a recent release of the U.S. National Longitudinal Mortality Study and the National Death Index, Kposowa tracked nearly 763,000 individuals age 15 and older between 1983 and 1994. A total of 410 of those individuals died of HIV/AIDS in that period of time.

"These data capture when HIV/AIDS was approaching pandemic level," Kposowa explained. "People were very afraid. The perception was that only men who had sex with men were getting infected, so no one was looking at risk factors for people who were married, widowed or separated."

Kposowa's analysis of 11 years of mortality data found that marital status was a significant risk factor for men, but not women. Divorced and separated men were more than six times more likely to die of AIDS than married men, and those who had never married were 13.5 times more likely to die of the disease than those who were married. African-American men were 2.7 times as likely to die of HIV/AIDS as white men, and Hispanic men were more than twice as likely to die of the disease as white men.

"It turns out that the big story for women is race, particularly for African-Americans and Latinos," Kposowa said. "The question is, why would Latino and African-American women have been more at risk of HIV?"
The most logical explanation, Kposowa believes, relates to how little was known in the 1980s about how the HIV virus was transmitted, and a health care system that historically disadvantages the poor.

"Those without care are more likely to be minority women," he said. "It's really a function of the health care system, who has access, and how soon people seek care. So in the 1980s, poor people and minorities, who often lack information about health care, were at greater risk of death from HIV/AIDS. By the time they presented themselves for health care, the disease would have progressed."

Kposowa said his assertion is supported by other studies showing that women of color typically receive less aggressive treatment for diseases such as cancer, and that African-Americans and Hispanics are less likely to be prescribed narcotic pain medications for back pain than whites even when one takes into account pain severity. He noted that in the US, post diagnosis cancer survival rates are much lower for people of color than whites.

"The elephant in the room is the health care system and the value we put on different people because of their color and background," the sociologist added. "We don't say that consciously, but it is why the Obama administration has put so much emphasis on reducing health disparities in this country."

Pregnancy and HIV Testing

HIV, or human immunodeficiency virus, is the virus that causes AIDS (acquired immune deficiency syndrome). HIV weakens a person's immune system reducing their ability to fight infections and cancers. A person can get HIV by coming into contact with an infected person's body fluids (blood, semen, vaginal fluids, breast milk), and HIV can be spread through:

• Vaginal, oral, or anal sex
• Sharing unclean needles to take drugs
• Pregnancy (from an infected mother to baby)
• Blood transfusions (since 1985, blood donations have been routinely tested for HIV, so infection from blood transfusions is rare)

You cannot get HIV from:

• Touching or hugging someone who has HIV or AIDS
• Public bathrooms or swimming pools
• Sharing cups, utensils, telephones, or other personal items
• Bug bites

Doctors recommend all pregnant women get tested for HIV. Medications are available to prevent the spread of the virus to your unborn baby. In addition, steps can be taken during delivery to prevent spreading the infection. Some studies show a woman can further reduce the risk of spreading the virus to her baby by having a cesarean section before her water breaks. Moreover, your health care provider can take steps to help you stay healthy longer.

HIV testing is voluntary. Anyone is free to decline testing. Your decision to not get tested, or the test result itself, will not prevent you from getting health care during pregnancy.

What Do the HIV Test Results Mean?

A confirmed, positive test result means you have been infected with HIV. Being infected with HIV does not necessarily mean that you have AIDS. It can take many years for people with HIV to develop AIDS.

A negative test result means that no signs of HIV infection were found in your blood. A negative test does not always mean that you do not have HIV. Signs of HIV may not show up in the blood for several months after infection. For this reason, you should be tested again if you could have been exposed to HIV or are at risk for HIV infection.

Though HIV tests performed at most doctors offices become part of the patient's medical record, there are places you can go that provide confidential HIV testing. These places will perform HIV tests without even taking your name (anonymous testing). An anonymous HIV test does not become part of your medical record.

Should you discover that you have HIV, inform you medical providers so that you can receive proper care.

When AIDS Viruses Are Transmitted Despite Treatment

While antiretroviral drugs offer an efficient means of preventing the replication of HIV in the blood, shedding of HIV may occur in semen, so that other persons can become infected during unprotected sexual intercourse. This occurs in particular if the male genital tract also has other viral infections.

That is the conclusion reached by a scientist who is supported by the Swiss National Science Foundation (SNSF).
In principle, modern combination therapies are very effective at keeping AIDS causative agents in check. The treatment usually leads to a situation in which there is no longer any evidence of Human-Immunodeficiency Viruses (HIV) in the body. In this way, the drugs can also reduce the disease transmission rate to just one tenth. So why do new infections occur despite treatment?

Sperm containing a cocktail of viruses

The answer, according to findings recently published by the Swiss researcher Sara Gianella Weibel and her American colleagues, is that other viruses also play a role. Working at the University of California in San Diego, the SNSF-funded scientist studied the semen of 114 HIV-infected men undergoing treatment who have sex with men. She found that the seminal fluid of 11 of the men contained a considerable quantity of HI viruses, even though the viral load of the blood of all of the men was very low. In eight of these 11 cases, Gianella Weibel also found evidence of various forms of herpes.

Locally activated immune system

Some of these herpes viruses, such as cytomegalovirus, often remain unnoticed. However, if the viruses infect the male genital tract, they locally activate the immune system. As a result, there is a build-up of immune cells, including those in which HIV replicate, in the genital area. "Our data suggests that we must also direct our focus towards other viruses, if we really want to interrupt the transmission of AIDS," explains Gianella Weibel.