BACKGROUND: HIV is the human immunodeficiency virus. It can lead to acquired immune deficiency syndrome, or AIDS. Two types of HIV exist, HIV-1 and HIV-2. Usually, HIV will refer to HIV-1. However, both will damage a patient’s body by destroying certain blood cells, called CD4+T cells. These cells are vital for helping the body fight off diseases. People can develop flu-like symptoms within a few weeks of being infected with HIV; others will not have any symptoms at all. People living with HIV can appear healthy for several years, but the disease is still affecting their bodies. All people with HIV should be taking medications to treat the infection. They can limit the destruction of the immune system, improve their health, and can reduce their ability to transmit HIV. During the early stages of HIV, it can become dangerous if untreated because it could lead to cardiovascular disease, liver disease, kidney disease, and cancer. AIDS is the last stage of HIV infection. Currently, people can live a lot longer with HIV before they developed AIDS because of the many different combinations of medications that were introduced in the mid-1990s. (Source: www.cdc.gov/hiv)
HIV ORIGIN: Scientists believe that HIV originated in a chimpanzee in West Africa. The chimpanzee version of the infection is called simian immunodeficiency virus (SIV). SIV was transmitted to humans and mutated into HIV when they hunted them for meat and were in contact with the chimpanzee’s infected blood. The virus has existed in the United States since the middle to late 1970s. From 1979-1981, there were reports of cancer, pneumonia, and other illnesses in New York and Los Angeles among men who had sexual relations with other men. By 1982, public health officials were beginning to officially label the occurrences as AIDS; therefore, official tracking of AIDS began that year. In 1983, researchers discovered what was causing AIDS. At first they named the virus HTLV-III/LAV. They later changed it to HIV. (Source: www.cdc.gov/hiv)
TREATMENT: The recommended treatment for HIV is antiretroviral therapy (ART). It involves taking a combination of three or more anti-HIV medications daily. This therapy is designed to prevent HIV from multiplying and destroying infection-fighting CD4 cells. Treatment with anti-HIV medications prevents the virus from multiplying and destroying the immune system, which prevents HIV from advancing to AIDS. (Source: www.aidsinfo.nih.gov)
NEW TECHNOLOGY: Within the science community, health care professionals have been working on an HIV vaccine. In fact, a new vaccine is now being testing in humans. The HIV Vaccine Trials Network (HVTN) is an international effort to search for an effective and safe HIV vaccine. The organization’s HIV Vaccine Trial Units are located at leading research institutions in 27 cities on four continents. The National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, is examining whether a two-part vaccine regimen can decrease viral load (the amount of HIV in the blood) in study participants who later become infected with HIV. The study’s strategy is: a series of three immunizations with recombinant DNA-based vaccine (the primer vaccine) over the course of eight weeks followed by a single immunization with a recombinant vaccine (the boosting vaccine) based on a weakened adenovirus type 5 (Ad5) that carries the vaccine contents and helps stimulate the immune system. Ad5 is a common virus that causes colds, but it is disabled and can’t cause a cold or other illnesses. It encodes for HIV proteins that are found inside the virus and on its outer envelope. The study is designed to enroll 1,350 HIV-negative men who are between 18 and 45 years old who have sexual relations with other men. (Source: http://www.niaid.nih.gov/news/newsreleases/2009). Another possible vaccine comes from Texas Biomedical Research Institute. It is a single-dose vaccine that creates a coating, preventing the virus from finding entry to our bodies through any pore. The vaccine comes from a virus resistant layer of the skin that is constantly growing from our own stem cells. It is designed to last a lifetime. This vaccine is directed at mucosal layers of the epithelium in the genital and rectal areas where the virus enters the body. The vaccine has already been tested in the lab in mice and was successful. Now they are being tested in monkeys. (Source: www.txbiomed.org)
Dr. Kenneth Mayer, Medical Research Director at Fenway Health in Boston, talks about the latest HIV vaccine trial.
Are vaccines the most popular way to prevent HIV?
Dr. Mayer: We think vaccines are the Holy Grail for HIV prevention. We have been trying to find a perfect vaccine for more than twenty years now. Here at Fenway Health in Boston, we vaccinated the first volunteers in New England in 1994, but we still think we have got a ways to go.
What is the latest vaccine; is it HVT 10505?
Dr. Mayer: Yes, HVT505 is an exciting study. It will enroll twenty five hundred at risk men, primarily in the United States. This vaccine takes a virus that can cause colds in people and eliminates the part of the virus that causes the colds. The reason they use a live virus is because it gets very strong immune response. We use pieces of genetic material that look like HIV, but not active HIV. We would never use HIV even if we thought we killed it just because of the risk. It tricks the immune system into thinking that it’s seeing certain parts of HIV and then people’s immune system mounts a response. This vaccine is also enhanced by taking genetic material that looks like HIV. The laboratory studies suggest that this combination gives very strong immune responses. The question is, will they at the right place at the right time? The good thing about this study is it is large enough to determine if the vaccine worked or it didn’t work. That is why were optimistic, but a recent vaccine study that was done in Thailand looked at two different vaccines and neither of the vaccines by themselves were very effective. However, the people were getting combinations of vaccines. That was the first vaccine trial that was mildly successful. It probably wasn’t a good enough response. It is probably good for proof for principal, but it’s not enough of a protective effect. When you do statistical analysis on the trials, you never know if you repeat the same trial in a different population you may get a slightly different result. When they did the statistical analysis for the study in Thailand, the effects at the lower were border-line. They would hate to vaccinate millions of people and give them something that may give them very little protection. On the other hand, when we do the statistics we know that there was some level of a protective benefit. That was the first glimmer of hope that we can get a vaccine against AIDS. The current study of HV10505 is the next biggest study since the Thailand trial and we think that the vaccines will continue to have to be tweaked for a while. We don’t think this is going be the last vaccine trial. If it shows a more protective affect than the last Thailand study, then we know we are on the right track, but there are a lot of plan B’s and a lot of plan C’s. So there are a number of other vaccine candidates that are being evaluated to protect people against HIV.
Do you think there will be added risk to the patients getting vaccinated? Will they feel like they do not need to wear condoms or take other preventative measures?
Dr. Mayer: These vaccine trials are very tricky. Ethically we know that condoms work. We also know that a lot of people who are risky may not have well regulated lives. They may not be the kind of person who wants to go into a trial because these trials are experimental. We have an ethical obligation to monitor people very carefully and provide them with the highest standards of safety monitoring and protection. People who come into the study have to be altruistic because they don’t know if they’re going to get the actual vaccine. They may be getting placebo. They have to be highly motivated because the schedules of visits for these trials often vary. We’re having people come in at least once a month for several hours to get there blood drawn and to answer questions that we will have. We will follow them very closely. We may not be getting the riskiest people coming into the trial. Ethically anybody who does this kind of research, whether it’s a university, a health center like Fenway, or a public health department, will have the volunteer sign an informed consent. The informant consent is a document that’s both ethical and legal. When people sign an informed consent form, they’re saying I’ve read all this information and I understand what I’m getting myself into. The document explains the possible side effects and that the vaccine may not work and that’s why we still recommend that they use condoms for further protection. So we are getting people who are not necessarily risky and telling them to be careful because they may be getting something that is worthless, either because they are getting the placebo or because the actual vaccine may not work. HIV is not really that easily transmitted. If the virus is present in ten percent of high risk people in the community, it means that if they have a hundred partners ninety of them are not going to transmit HIV. So it’s only that minority who are having sex that might transmit HIV. What it boils down to is that all of these studies are very large because the actual percentages of people who become HIV infected in the trial usually are very low, close to three percent. Three percent is bad if you’re one of the three percent, but it also means that ninety-seven out of a hundred people who start the study don’t become HIV infected by the end. For example, in this latest vaccine trial of HV10505 we enrolled twenty-five hundred people to show the possibility that this vaccine is protective. Some people say well that’s not a big enough study, you may have to do a larger study to really define it. There is a tradeoff between having few people exposed to the vaccine because we would like to move on if it’s not successful. However, if the numbers are too small, then the results may not be definitive. For example, the study I mentioned in Thailand enrolled eighteen thousand people in that study. If you start doing the math about how many nurses, research assistants, and people are processing lab specimens, then these studies end up being very expensive. None of the studies that we’ve talked about today are less than ten million dollars and many of them are upwards towards a hundred million dollars for a single study. That is again another reason why the field doesn’t move as fast as we’d like it to because money is tight these days. Whether it’s the National Institutes of Health, the Gates Foundation, or the US Army, all of whom have sponsored vaccine trials, none of them want to spend ten, twenty, fifty, or one hundred million dollars. So getting these studies underway is not an easy process.
Is it hard not to get your hopes up every time you start a vaccine trial?
Dr. Mayer: I think it’s important to be optimistic because you can burn out doing this work. It is also important to be realistic. As researchers we don’t consider a study unsuccessful if it’s not a home run. We’d like it to be a home run, but for us it’s a successful study if it’s done well and we can understand the result. So as long as enough specimens and information are obtained and we figure out the vaccine didn’t work because people had this kind of response and in the test tube that didn’t really do anything to HIV. So they respond to the vaccine, but this kind of response isn’t correlated with protection. Even some of the negative studies give you information that helps you come up with a better candidate for the next trial.
How long do you think we are from getting that vaccine right?
Dr. Mayer: We will probably have the result for the current study sometime next year; sometime in 2013 we’ll know whether HV10505 worked. I have no crystal ball, but I don’t know that it will be the definitive vaccine study. If we are really optimistic, we would say this will be a good result but it will need to be refined. Even that would still take another three year. If we have the definitive vaccine in 2016, the next year would be great. I’m hopeful that eventually we will have an AIDS vaccine, but it just doesn’t happen overnight.
The current trial is still enrolling?
Dr. Mayer: HV10505 is still enrolling, but it’s far along. There are almost twenty two hundred of the twenty five hundred participants enrolled in the study. How quickly the study ends is partially a function of how quickly people are getting infected. We don’t know that the vaccine is going to work and we don’t know if they’re getting placebo, so we give them safer sex counseling. If the safer sex counseling was a hundred percent effective, you’d never see any new infections and it would take forever to show that the vaccine did anything. Within the next year or so there may be enough people becoming infected where an independent body, called A Data Safety Monitoring Board, a DSMB, that they get no money for participating. It includes people who are ethicists, lawyers, clinical researchers, and community members. They are presented the data independently and have to sign an oath basically saying they are not going to share the information with anyone. So they start looking at the curves and at the line of the number of new infections per month in the placebo versus the number of new infections in the active arm. They can stop a trial early if they say the lines are flat. They’re encouraged to have a fairly high level of certainty before they stop a study early.
What do you think of the HIV tests? How do you think it could help people with prevention?
Dr. Mayer: Home HIV testing is an interesting idea. In general most people who do HIV research and prevention are in favor because we feel like one size will not fit all. Some people will not think it is a good idea for them to be tested at home because they may not have the technical capacity. People may be scared of HIV or they may be emotionally fragile, it might not be a good idea. There are, however, a large number of people who may not understand why they have to go to a doc or a clinic. They would rather find out their self and if they find out they are positive, then they will go to the clinic to have them confirm it. So we think that there’s a market for home testing, but like many of these new prevention approaches it is in its early stages. We don’t know how much the uptake will be. One thing right now is that the price for the test is expensive for some populations. It’s about forty dollars a pop for home tests. People have to be fairly motivated. In many states, the public health benefit of people knowing their status is that the Federal Government and many State Governments have grants to maintain testing sites. For example, here at Fenway we have a walk-in clinic. People can come during the long hours of operation. As long as they’re willing to wait, they’ll definitely get tested for free for HIV and socially transmitted infections. If they have insurance they’ll be asked for co-pays. It would be a lot cheaper to go into the clinic and get tested than paying forty dollars for a home test. So there will be tradeoffs. Some people don’t want to go to the clinic and wait. Some people will trust that a professional group that’s doing the testing will be more skilled and may not trust themselves with a home test. I think the home testing is a great new advance, but you know there’s not one single thing that is the magic bullet yet. Eventually we may have a cure and have a perfect vaccine, but in the meantime I think trying to optimize the tools that we do have is really what it’s all about.
What is your reaction to the latest advances?
Dr. Mayer: It’s been exciting over the last few decades to see some of the improvements and the innovations. Certainly in the bad old days it was just so awful, people getting sick and dying. In the beginning, we didn’t know what the tests meant. We actually did some of the first testing in the U.S. at the clinic here at Fenway. Because the test was not commercially available, it was only being developed by one of the discoverers of the virus Robert Gallo. You had to send specimens down to his laboratory in Bethesda, Maryland at the National Institutes of Health, The National Cancer Institute, and then you’d get the report back. We were doing studies of couples where one partner was sick and the other partner was healthy. We wanted to see how many of those partners were exposed to the same virus. So we get the results back and about a fifth of the men had these antibodies. Their body was reacting to the virus, but we really didn’t know what that meant because there’s some infections where having antibodies are correlated with having protection against the infection. For example, if we test somebody for Hepatitis B and they have surface antibodies, they either got the vaccine or they developed natural infection. They cured the infection on their own. In other infections, like Hepatitis C, the antibody isn’t protective so that’s a marker that somebody is now at risk to get serious liver disease. Not everybody with Hepatitis C antibody gets bad liver disease, but certainly a large percentage does. In the early eighties, when we first had these tests for HIV we weren’t sure what the test mean. We gave the people the option of not knowing their test results. Now we are at a different era where we know, in addition to testing them for antibody, that we can look at their immune function with one simple test, called a CD4T helper test, and we can look at much of the virus they have in the body by looking for the viral genetic material in the blood now. If we have those three measures, then we know somebody is infected because they are antibody positive. We know the amount of virus in their blood and we know their immune function. We can make determination about whether they’ll get treatment. We can say if you don’t take treatment this is what your odds are of being asymptomatic for the next year or next five years. So we know so much more now than we did thirty years ago.