Could a “therapeutic” AIDS vaccine help people who are already infected with HIV?

The primary goal of most AIDS vaccine trials is to identify a preventive vaccine that could protect HIV-uninfected people from HIV infection or disease. However, many people would also like to know whether the experimental vaccines that are currently being tested as preventive candidates could also be tested as “therapeutic vaccines.”

The goal of a therapeutic vaccine would be to strengthen HIV-specific immune responses in people who are already infected with HIV. These strengthened defenses would be very unlikely to control HIV by themselves, if a therapeutic vaccine was to be found. This is why a therapeutic vaccine would almost certainly not be used on its own. However, when used in combination with antiretroviral (ARV) drugs, a therapeutic vaccine might be an additional way to control HIV and help HIV-infected people remain healthier for longer.

At present, there are no therapeutic vaccines for HIV infection—or for any diseases at all. All of the licensed vaccines that are used to prevent other diseases such as measles, mumps or polio are preventive vaccines; none of them can treat or cure people who already have a particular disease. Vaccines against rabies and tetanus may prevent disease if they are given immediately after exposure—such as a dog bite. But these are not true therapeutic vaccines since they are only effective within a very short time period after exposure. This is similar to post-exposure prophylaxis (PEP), which uses ARVs to reduce the risk of HIV infection when given to people within hours of high risk contact.

None of the AIDS vaccine candidates tested in HIV-infected people has been effective. The challenge is that HIV attacks the immune system and specifically targets CD4+ T cells (see Primer), crucial immune defenses that also play a key role in responding to vaccines. Developing a vaccine to boost CD4+ T cells and other immune responses against HIV in people who are already infected will most likely be very difficult—especially in people who have been infected with HIV for many years and have severely weakened immune systems. Most scientists think that it will be much more difficult to make a therapeutic AIDS vaccine than a preventive AIDS vaccine. It may even be impossible.

However, with around 42 million people worldwide currently infected with HIV, a therapeutic AIDS vaccine that strengthened the body’s immune defenses against HIV would be a valuable weapon in fighting the virus. This is one reason why some scientists feel that it is important to evaluate the current preventive AIDS vaccine candidates to see if they have any therapeutic benefit for people already infected with HIV.

What would an effective therapeutic AIDS vaccine do?

The goal of a therapeutic AIDS vaccine would be to strengthen the body’s ability to fight HIV. A vaccine might be able to do this by producing or strengthening defenses, including immune cells and neutralizing antibodies that reduce the harm that HIV does to the immune system.

When a person becomes infected with HIV, the immune system responds with defenses that can control HIV for some time. This is why most people with HIV feel healthy for several years after they become infected. However, eventually the virus begins to win the battle. If a therapeutic AIDS vaccine was able to cause the production of additional HIV-specific immune responses they could potentially work alongside these naturally-occurring immune defenses.

Even if it was effective, a therapeutic vaccine would not be able to cure HIV. Also, a therapeutic vaccine would not be a replacement for ARVs. But it is possible that a therapeutic vaccine could strengthen the body’s ability to fight HIV when used in combination with ARVs and other treatments for HIV-related illnesses.

HIV can change or “mutate” itself so that it becomes “drug-resistant” to one or more of the ARVs that a person is taking. When this happens, ARVs can no longer control the virus. If an effective therapeutic vaccine was available, the immune defenses it produced might improve control of the virus and delay the development of drug-resistant virus. This would allow HIV-infected people to take the same combination of ARVs for longer periods of time without developing resistance.

HIV might also be able to mutate to avoid the immune defenses produced by an effective therapeutic vaccine. This is an additional reason that these vaccines would only be used in combination with ARVs, which would help control the virus and serve as an additional barrier to the emergence of drug-resistant virus. An effective therapeutic vaccine might also be used as part of a “structured treatment interruption” (STI) strategy in which people infected with HIV stopped taking ARVs for weeks or months, while under close medical supervision to monitor the amount of HIV (viral load) in the blood. STIs are being studied as a way to give people with HIV short breaks from lifelong ARV treatment, which can be complex and can cause severe side effects.

STI strategies are still highly experimental and carry risks, including the possibility that drug resistant forms of HIV will emerge during the period when treatment has been stopped. In some of these STI studies, half of the volunteers receive experimental therapeutic vaccines prior to stopping ARVs, while the other half do not. Scientists are looking to see if people given the therapeutic vaccine can wait longer before their viral load begins to increase and they have to resume treatment. If this group can wait longer before re-starting ARVs it may be because the immune defenses created by the therapeutic vaccine are helping to control the virus.

However, none of the AIDS vaccine candidates that have been tested so far for therapeutic effects have shown these types of benefits.

Research to date

Therapeutic AIDS vaccine research started in the early 1990s when several trials in the US and Europe tested therapeutic vaccines in people taking ARVs. Researchers studied blood samples from these volunteers and found that some vaccines caused very small improvements in some immune responses against HIV. However, none of these vaccines was found to improve the health of patients or slow the rate of HIV disease progression.

Today new vaccine candidates are being tested for therapeutic effects in small Phase I safety studies. These include vaccines which are also being tested in preventive AIDS vaccine trials. It is important to note that all of these therapeutic vaccine trials are enrolling volunteers who are taking ARVs that effectively control their HIV infection. Without ARVs, the immune system is very vulnerable to the effects of HIV and it is highly unlikely that a therapeutic vaccine could provide any benefits in this situation. Used without ARVs, a therapeutic vaccine might even cause some harm by creating more targets (CD4+ T cells) for HIV infection.

Scientists are continuing with therapeutic vaccine research in spite of the challenges because there is still a need for strategies other than ARVs to control the virus. Therapeutic vaccines are just one example of immune-based therapies that could be used to build immune defenses in HIV-infected people. Even if it proves impossible to develop a therapeutic AIDS vaccine, trials of therapeutic vaccine candidates could provide clues about the types of immune defenses that are—and are not—effective in fighting HIV. These clues could be used to guide the design of future AIDS vaccines.

------------
All articles written by Emily Bass