Vaccines

Be The Generation To End The AIDS Epidemic

Vaccines

More than 1.2 million people in the United States are living with HIV, and more than 650,000 U.S. lives have been lost as a result of HIV/AIDS-related illness. Treatment can slow disease, but there is no cure for HIV/AIDS. Prevention is essential.

A vaccine teaches the body how to fight infections and control diseases by helping the body to produce antibodies and T-cells against a disease. No major epidemic caused by a virus has ever been stopped without a vaccine. An HIV vaccine could help to prevent a person from acquiring HIV. Vaccines could also help the body control the disease for people living with HIV. Right now, there is no vaccine to prevent HIV, and there is still no cure for HIV. The vaccines being tested are only being used in research studies.

Even though there still is no HIV vaccine, each new research discovery helps guide future efforts. In 2009, a vaccine tested in Thailand was able to lower the number of new HIV infections by almost a third. This gives us hope that one day researchers will find a vaccine that is safe and effective for everyone.


HIV Vaccine FAQ

Why do we need a preventive HIV vaccine?

There is no cure for HIV. Although the availability of antiretroviral therapy has dramatically reduced AIDS-related deaths in the United States, these treatment regimens can be complex and costly, and some people experience side effects. In addition, HIV can develop resistance to antiretroviral drugs, particularly if individuals do not take the drugs on a regular and continuous basis. Effective treatment is dependent on long-term patient adherence; a vaccine could provide protection with minimal action on the patient's part.

A preventive HIV vaccine could help save millions of lives and billions of dollars each year in treatment costs. Safe, effective, and affordable vaccines that can prevent HIV are the best long-term hope for controlling and/or ending the HIV/AIDS epidemic.¹  ²

1 Ending AIDS — Is an HIV Vaccine Necessary? Anthony S. Fauci, M.D., and Hilary D. Marston, M.D., M.P.H. N Engl J Med 2014; 370:495-498February 6, 2014DOI: 10.1056/NEJMp1313771

2 Interview with Dr. Anthony Fauci on the need for an HIV vaccine and the advances that will help fulfill that need. Supplement to the N Engl J Med 2014; 370:495-498

Why isn’t there already an HIV vaccine available?

Most vaccines that are in use today have taken at least 30 years to develop.The polio vaccine took almost 50 years to develop! On top of that, HIV presents additional scientific challenges to vaccine development:

  • HIV evades neutralization and clearance by antibodies.
  • There are many different strains of HIV around the world, and the virus mutates over time. The diversity of HIV within a single person living with HIV is greater than the diversity of influenza viruses worldwide.
  • Animal models have not yet been shown to reliably predict vaccine efficacy, making selection of "promising" products for human trials difficult.

3 College of Physicians of Philadelphia. The History of Vaccines: A Project of the College of Physicians of Philadelphia.

What is happening in preventive HIV vaccine research?

Many agencies and organizations are working together to develop and test preventive HIV vaccines. These include U.S. government agencies, such as the National Institutes of Health (NIH), foreign governments, universities, charitable foundations, nonprofit organizations, and biotech and drug companies.

HIV vaccine clinical trials require large numbers of participants, both those who are highly vulnerable and those who are less vulnerable to contracting HIV. Approximately 35,000 volunteers have participated in HIV vaccine research sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), a part of the NIH (NIAID, January 2017).

Most recently, in 2009, a vaccine regimen tested in Thailand cut new HIV infections by about one third. This gives us hope that we can eventually find a vaccine that works well for everyone.4

Although efforts have not yet produced an HIV vaccine that is ready for licensure, each new research discovery brings scientists closer to that goal.

4 New England Journal of Medicine. Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand. (December 3, 2009).

How do vaccines work?

B and T cells are two types of immune cells that have the ability to specifically recognize molecular targets. They identify invaders (e.g. bacteria and viruses), mark them for destruction, block them from infecting cells, or kill cells after they have been infected.

After the initial immune response to an infection, the immune system develops memory B and T cells. These memory cells remember specific molecules in the bacteria and viruses and recognize them the next time they enter the body.

Upon subsequent exposure, memory cells produce a faster and stronger immune response to the same invader, protecting the body from infection or severe disease.

Vaccines mimic infection by stimulating the production of memory B and T cells that will recognize the actual infectious agent upon exposure. It can take a few weeks after vaccination for the immune system to develop memory cells.

When a safe and effective preventive HIV vaccine becomes available, at what age will vaccination start?

A preventive HIV vaccine would be effective in preventing people from contracting HIV only if given before exposure to HIV. A person can contract HIV the first time they have sexual contact with another person or engage in injecting drug use. Ideally, HIV vaccination would be recommended at an age before these behaviors typically start, such as during the pre-teen years or early adolescence. However, the vaccine could also be very useful at other ages, such as to protect adults or to protect infants born to mothers living with HIV who continue to breastfeed.

How many vaccinations will a person need to be protected?

The number of vaccinations needed for HIV protection can only be determined through clinical trials and will depend on the specific vaccine regimen being tested. The ultimate goal is to develop vaccines that require the fewest possible vaccinations. It is possible that first-generation HIV vaccines will require more vaccinations, and that improvements resulting from further research will allow for fewer vaccinations.

Could vaccines help people already living with HIV?

Researchers are also looking to see whether HIV vaccines could help people who are already living with HIV. Vaccines used in this way are called therapeutic vaccines. If effective, a therapeutic vaccine would teach the body to control HIV infection, so the progression from HIV to AIDS would happen much more slowly or maybe even be stopped. We don't know if a vaccine that is found effective at preventing HIV would also be therapeutic. It is possible that different types of vaccines might be needed for HIV prevention and HIV therapy. Researchers are working to develop and test both kinds of vaccines.

What might be in an HIV vaccine candidate?

Preventive HIV vaccines contain lab-made copies of genes or proteins that appear to the immune system like those in the real human immunodeficiency virus, but they don't contain all the elements required to cause infection. Preventive HIV vaccine candidates, like other viral vaccines such as the hepatitis B vaccine, are made with different approaches that may include one or a combination of the following:

  • Proteins, or pieces of proteins, such as those found on the outer coating of the virus.
  • Viral vector—A way to package HIV (or other) genes inside the shell of another virus, so that the proteins coded by the HIV genes are presented to the immune system. Viral vectors are disabled so that they do not cause disease; they can be non-replicating (they do not make copies of themselves) or replicating.
  • DNA vector—HIV genes or gene fragments, usually delivered in a circular DNA molecule called a "plasmid."
  • Pseudovirion—Virus-like particle that resembles a virus but does not contain its genetic information and cannot replicate.
  • Live bacterial vector—Bacteria engineered to carry HIV genetic material.

In addition, some HIV vaccines being studied also use adjuvants—"immune boosters" that are combined with vaccines to promote an earlier, more potent, and/or more persistent immune response to the vaccine. Adjuvants may allow for a lower vaccine dosage or fewer doses of vaccines to be given, or direct the immune system toward either a B-cell or T-cell response.

Some vaccines, like those for polio, contain whole, killed virus or live, attenuated (weakened) virus, but because of safety concerns, these types of HIV vaccines are not tested in HIV prevention trials.

Who/what organization will own the vaccine?

"Ownership" of a vaccine depends on the specific patents and licenses for any given vaccine being tested. Many agencies and organizations are working together to develop and test preventive HIV vaccines. These include U.S. government agencies, such as the National Institutes of Health (NIH), foreign governments, universities, charitable foundations, nonprofit organizations, and biotech and drug companies.

How can health care providers support preventive HIV vaccine research?

To help support HIV vaccine research in your community:

Learn all you can about HIV vaccine trials in your area so you can answer patients' questions accurately.

If any of your patients are current or former HIV vaccine trial volunteers and you wish to perform HIV testing as part of their routine health care, please instead ask them to provide you with their HIV test results from their clinical trial site, or encourage them to contact their clinical trial site to arrange for testing. This is because study vaccines can cause the immune system to produce antibodies that can be detected on common HIV diagnostic tests and can be misinterpreted as an indicator of HIV infection. The clinical trials sites use a multi-step algorithm of HIV testing to differentiate between vaccine-induced antibodies and true HIV infection. In NIAID-sponsored trials, this testing is provided free of charge to the volunteer.

Raise awareness about the potential public health benefits of HIV preventive vaccines among the individuals who come to you for care.

Know where to refer patients who want more in-depth information about HIV vaccine research.

If your patients have questions about joining an HIV vaccine study, encourage them to:

Ask the study investigator questions. A list of questions they may want answered can be found at www.clinicaltrials.gov. The clinical trial site can also provide a copy of the Informed Consent Form and a Frequently Asked Questions document describing the study.

Carefully review the consent information with your patient to ensure that they understand the purpose of the study, the risks of participation, and their responsibilities as a study participant.

Encourage the potential study participant to discuss the decision with family, friends, and others whom they trust. With the patient's permission, trial site staff can also talk to these people to help answer their questions.

Clinical Trial Participation

Who should participate in preventive HIV vaccine research?

To gather the best data about vaccine safety and efficacy, preventive HIV vaccines are tested among individuals from diverse populations—including those of different sexes, races, ethnicities, and socioeconomic backgrounds and with different environmental factors and potential routes of HIV transmission. The majority of studies (Phase I studies) enroll persons with low vulnerability to contracting HIV, whereas efficacy trials may be designed to enroll only persons who are highly vulnerable to contracting HIV. Individuals interested in joining a study do not necessarily need to be highly vulnerable to contracting HIV.

In addition, every trial is designed to answer specific research questions. Depending on the research questions, some trials may only enroll women, while others may be open to women, men, or transgender individuals. It is important to understand who is eligible for each study, and what research questions will be addressed in the study.

How are participants recruited?

Recruitment strategies for HIV vaccine clinical trials vary by trial purpose, location, and target population. Past recruitment strategies have included print ads, online ads, social media sites, outreach by community organizations, outreach in venues frequented by the target population, referral by friends or health care providers, and announcements in local news media. Individuals interested in participating in a clinical trial can search for studies in their area at ClinicalTrials.gov.

What is the age limit of research participants?

The age of HIV vaccine clinical trial participants varies, depending on the specific trial protocol. The usual range is 18-45 or 18-50 years of age. The age range of participants will be determined by the objectives of the study, combined with ethical and safety considerations.

What is the time commitment for participating in an HIV vaccine study?

Each study is different, but a typical study lasts 1 to 2 years and requires 10 to 20 clinic visits. Each visit usually takes between 30 minutes and 3 hours. In general, the first few visits are longer because you are learning about the study, going through the informed consent process, and having a physical exam and blood tests to see if you are eligible to join the study. Details about the study visits are part of the informed consent process.

What are the benefits of participating in an HIV vaccine trial?

The HIV/AIDS epidemic affects people from all walks of life, all around the world. It is in everyone's best interests that we find an effective vaccine to prevent HIV that has been tested in diverse populations. Participating in vaccine research—and encouraging others who do—helps further efforts to find an effective HIV vaccine and, ultimately, control or stop the HIV/AIDS epidemic. Though we do not know whether receiving a study vaccine would benefit a participant, we do know that being in a study might still help participants in some ways. The risk reduction counseling that participants get as part of the study may help them avoid HIV acquisition. Also, the lab tests and physical exams that participants get while in the study might detect health problems they don’t yet know about.

If I am in an HIV vaccine study, am I protected from contracting HIV?

We don’t know. You should never assume that you are protected from HIV because of your participation in a vaccine study. You should continue to practice safer sex and limit yourself to single-use, non-shared needles to reduce your risk of exposure to HIV. We do not know if a study vaccine will protect you from HIV, and you may have gotten a placebo, not the vaccine itself. (A placebo is a shot that looks just like the vaccine but does not have vaccine in it. Participants won’t know whether they got a placebo or the vaccine until the end of the trial.) In addition, some clinical trials are only designed to answer questions about product safety, and cannot answer the question of whether the vaccine is protective. If you think you might be vulnerable to contracting HIV, seek counseling to learn about ways you can protect yourself. If you decide to join a vaccine study, the clinic staff will talk with you be sure you know all of your options for HIV prevention.

What are the short-and long-term risks of HIV vaccine research?

All clinical trial participation has both known and unknown risks. Like most licensed and approved vaccines, the HIV vaccines used in clinical trials may cause side effects such as soreness and redness at the injection site, low-grade fever, and body aches. These side effects tend to go away quickly. Other potential risks will vary according to the specific vaccine product. Before volunteering for a trial, potential participants should be sure they understand the risks, which are described in the informed consent process. Any questions can be directed to the study site staff.

Can a trial participant get HIV from the vaccine?

No. There is NO risk of getting HIV from the preventive vaccines being tested because they do not contain HIV. They contain only lab-made, synthetic copies that look like pieces of HIV. These synthetic copies are not able to cause infection.We do not know if study vaccines will decrease, increase, or not change a participant's chance of contracting HIV if they are exposed to the virus.

Several studies have tested whether HIV vaccines can reduce the risk of getting HIV from another person. In some studies, people who got the vaccine seemed to have the same risk of contracting HIV as people who did not get the vaccine. In one study, people who got the vaccine were at lower risk of contracting HIV than people who did not get the vaccine. In another study, some men who got the vaccine had a higher risk of contracting HIV than men who did not get the vaccine. As soon as researchers noticed this trend, they stopped giving the vaccine. The vaccine in that trial, however, did not cause people to contract HIV; participants in the study who contracted HIV got the virus from another person who had HIV.

5 Cooper, C. J., Metch, B., Dragavon, J., Coombs, R.W., Baden, L. R. (2010). Vaccine-induced HIV seropositivity/reactivity in noninfected HIV vaccine recipients. JAMA, 304.

How will you know if an HIV vaccine works?

Studies that test whether an experimental vaccine works are called efficacy studies. Not all vaccine studies are efficacy studies. Early vaccine studies test if the study vaccine is safe to give to people, and whether people are able to take the study vaccine without becoming too uncomfortable. Another important goal of early studies is to test if people’s immune systems respond to the study vaccines. Efficacy studies are done after these smaller, early studies show the vaccine is safe and the immune system reacts to it in the desired ways.

When you go through the informed consent process, you will find out if the study you want to join is an early study or an efficacy study. With all studies, it may take several years before the results are known. Efficacy studies can last as long as 5 years.

Regardless of what the study is looking for (whether it is safety or efficacy), all HIV vaccine studies teach us something important and bring us closer to finding a vaccine that works.

How will HIV vaccine trial participation affect pregnancies?

Until vaccine candidates are more advanced in their development, pregnant women will not be accepted as volunteers in HIV vaccine clinical trials. Women who plan to become pregnant should postpone becoming pregnant until after the trial. Pregnancy tests are done as part of the screening process and before each immunization. Women of childbearing age must agree to use an adequate method of birth control before and during the immunization period. Women who become pregnant during a trial continue to be monitored for safety, but are no longer vaccinated.

If I decide to participate, can I change my mind later?

Yes, you can leave the study at any time without any negative consequences. You are encouraged to take your time in deciding whether to join a vaccine study, so that you feel comfortable and fully informed before you sign up. You may want to speak with your doctor, family, and friends before you decide to join.

Research Safety and Ethics

How is an HIV vaccine candidate developed and evaluated?

Vaccine candidates are first tested for safety and activity in the laboratory and then in animals. Human clinical trials of preventive HIV vaccines then occur in three phases:

Phase I — 12 to 18 months, about 20 to 100 participants—A small group of healthy, HIV-negative participants with low vulnerability to contracting HIV and who do not have other medical problems that interfere with evaluation of the safety of the vaccine are selected to participate in trials that evaluate vaccine safety and immune responses elicited by the vaccine.

Phase II — 2+ years, 100–400 participants—If a vaccine has promising safety and early immune response data, HIV-negative participants are enrolled in Phase II studies to continue to test safety and immune responses. Participants in these studies can be highly vulnerable or less vulnerable to contracting HIV, but the study is not intended to prove efficacy.

In recent years, researchers have done "test-of-concept" trials—also called "Phase IIb" trials—in a few thousand HIV-negative, vulnerable individuals. While these studies are not intended to lead directly to licensure, they can provide important clues as to what may constitute a protective immune response.

Phase III — 3+ years, several thousand participants who are vulnerable to contracting HIV are enrolled to test a vaccine's safety and efficacy. If data are favorable, these studies can lead to licensure.

To date, only a few Phase IIb and III HIV vaccine trials have been completed, none of which has led to licensure of the vaccines tested. One of them, RV144, a Phase III study carried out in Thailand, demonstrated modest vaccine efficacy: the rate of new HIV infections were about one third lower among participants who received the vaccine regimen compared with participants who received the placebo.4 These results are helping to guide the future of HIV vaccine research.

How do I know that the research is following local and international cultural and ethical standards?

Because of the history of unethical research in some communities, people in minority populations may be distrustful of clinical trial participation. Today's research studies in people, however, have safeguards in place to protect the safety and well-being of research participants. Participant safety is of utmost importance. Clinical trial researchers have to follow strict ethical and legal standards such as the Belmont Report, the Code of Helsinki, and others. In addition, most clinical research must follow federal laws in the US Code of Federal Regulations that protect study participants.

Participants can leave the study at any time.

All of the known or anticipated risks as well as the possibility of unknown risks are fully described as part of the informed consent process. All participants must sign a consent form before they can join the clinical trial. Participants are encouraged to ask questions before signing the consent form and discuss their potential study participation with others prior to enrollment. They are also welcome to ask questions throughout their study participation.

A clinical trial follows a carefully designed protocol, a study plan that details what researchers will do. The protocol undergoes rigorous review by several regulatory bodies, including a local Ethics Committee or Institutional Review Board.

A local group of independent experts known as an Institutional Review Board or Ethics Committee regularly reviews the clinical trial to oversee patient safety and makes sure the researchers follow the protocol.

Researchers report the results of the trial at scientific meetings, to medical journals, and to various government agencies. Participants' names are not included in any of these reports.

Side effects are reported to the study investigator, who takes any medical action needed. Side effects are also reported to study reviewers who monitor the study closely for participant safety.

Any study conducted in the United States with a research product such as an experimental HIV vaccine must be reviewed by the U.S. Food and Drug Administration for the safety of the product and the soundness of the study questions and design. Similar regulatory agencies in other countries are also involved when trials will be conducted internationally.

Will an investigational vaccine make someone test positive for HIV antibodies, and what does that really mean?

Participants who receive an HIV vaccine in a preventive clinical trial may test positive for HIV antibodies on standard HIV tests, such as ELISA, Western blot, and "rapid tests," even if they do not have HIV.5 This is because the vaccine elicited measurable antibodies to HIV proteins, resulting in a study participant having a vaccine-induced seropositive (VISP) test result. This may also be referred to as vaccine-induced seroreactive test result. The HIV Vaccine Trials Network uses a multi-step algorithm of HIV testing to measure HIV presence directly to determine whether or not someone with VISP truly has HIV. To avoid confusion, please request that your patient provide HIV test results from the study site rather than conducting your own HIV testing. This testing is provided free of charge for study volunteers, and can be provided even after the study has ended, or if the patient no longer lives near the study site.

An antibody response may be needed for a vaccine to be effective. However, for a participant with VISP, an incorrect HIV diagnosis resulting from standard HIV antibody testing could have significant undesired impacts, including:

  • Unnecessary distress
  • Unwarranted HIV reporting to public health authorities.
  • Compromise of the participant's "blind" HIV vaccine study participation, which is needed for accurate analysis of the vaccine's effect on safety, immunogenicity, and efficacy.
  • Inability to donate blood, organs, or tissue.

Because of the possibility of VISP, patients who are current or former HIV vaccine trial participants are counseled not to submit to an HIV test outside of the clinical trial site (unless the trial is finished and the participant received the placebo). The clinical trial sites can test current and former trial participants for HIV using methods that distinguish true HIV from VISP. With the patient's permission, results on the individual's HIV status can be shared with health care providers.

5 Cooper, C. J., Metch, B., Dragavon, J., Coombs, R.W., Baden, L. R. (2010). Vaccine-induced HIV seropositivity/reactivity in noninfected HIV vaccine recipients. JAMA, 304.

How long does vaccine-induced seropositivity last?

HIV vaccine-induced seropositivity (VISP) in HIV-negative vaccine recipients varies substantially depending on the specific vaccine used and the participant's individual response to it. In trials conducted by the HIV Vaccine Trials Network over the last 10 years, the average chance of VISP occurring was about 42%.5 With a few vaccines, VISP has lasted for more than 15 years. For other vaccines, VISP did not occur at all. Because different types of diagnostic tests may be used, VISP can appear at any point after administration of a vaccine candidate, even after completion of the HIV vaccine study. Study volunteers in NIAID-sponsored trials are offered long-term monitoring to watch for VISP; providers should encourage their patients to ask what long-term monitoring/testing is available from the trial sponsors. 

5 Cooper, C. J., Metch, B., Dragavon, J., Coombs, R.W., Baden, L. R. (2010). Vaccine-induced HIV seropositivity/reactivity in noninfected HIV vaccine recipients. JAMA, 304.

Will a woman who participates in HIV vaccine research and later becomes pregnant pass the HIV antibodies to her children?

A woman living with HIV typically passes HIV antibodies to her baby. This could also apply to vaccine-induced HIV antibodies, which could persist in the baby for a limited time. This has not been shown to happen, and these antibodies would not be expected to pose any risk to the baby. But while present, they could result in a false HIV diagnosis. It is important for a women to know if she has VISP so that her obstetrician can become educated about it prior to delivery so that the woman and her newborn are not mistakenly given anti-retroviral medications.

Does participation in HIV vaccine research encourage or lead to high-risk behaviors?

There is no evidence that participation in HIV vaccine research leads individuals to engage in behaviors that increase their HIV risk.6 In fact, data from several trials completed to date show that risk behaviors usually decline overall, particularly during the vaccination period when study visits are more frequent. Participants in clinical trials are continually counseled on how to reduce their risk of being exposed to HIV.

It is important to remember that once there is a vaccine, it may not be 100% effective. Any HIV vaccine—even one that is highly effective in preventing HIV—should be offered along with other state-of-the-art prevention tools to increase protection against HIV.  

6 Bartholow, B. N., Buchbinder, S., Celum, C., Goli, V., Koblin, Beryl, Para, M., Marmor, M., Novak, R. M., Mayer, K., Creticos, C., Orozco-Cronin, P., Popovic, V., Mastro, T. D. (May 1, 2005). HIV sexual risk behavior over 36 months of follow-up in the world's first HIV vaccine efficacy trial. Journal of Acquired Immune Deficiency Syndromes, 39 (1).


What is the HIV Vaccine Trials Network (HVTN)?

The HIV Vaccine Trials Network (HVTN) is the world’s largest publicly funded multi-disciplinary international collaboration facilitating the development of vaccines to prevent HIV/AIDS. The HVTN conducts all phases of clinical trials, from evaluating experimental vaccines for safety and immunogenicity to testing vaccine efficacy.

The HVTN recognizes the importance of public support in finding a vaccine against HIV/AIDS. HVTN staff and volunteers from around the globe work actively to help community members understand the science of HIV/AIDS vaccines, as well as research methods and clinical trial processes. Through its efforts and in collaboration with projects like Be the Generation, the HVTN hopes to dispel some of the misconceptions that surround HIV/AIDS and studies involving human participants.

HVTN funding is provided by public and private sources. The National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes of Health, an agency of the US Department of Health and Human Services, is the main funder and sponsor of most HVTN trials. Another significant funding source is the Bill & Melinda Gates Foundation (BMGF). The HVTN, NIAID, and BMGF have a close, cooperative working relationship with shared attention to intellectual and scientific issues.

The HVTN’s clinical research sites are located at leading research institutions in over 30 cities on five continents. Internationally renowned researchers in HIV vaccines and prevention lead these units and contribute to the HVTN’s scientific agenda. The HVTN’s headquarters are at the Fred Hutchinson Cancer Research Center in Seattle, WA.