HIV can damage your immune system and decrease your body’s natural ability to fight infections. Immune reconstitution or restoration refers to:

• Improving the body’s immune function
• Repairing the damage done by HIV

Right now the main way to control HIV is by taking powerful, and sometimes toxic, HIV drugs. Successful immune reconstitution strategies might allow the body to fight HIV more effectively onits own. This could result in HIV+ people being less dependent on HIV drugs.

While many different methods of immune reconstitution are under investigation, there are no FDA-approved immune-based therapies for HIV disease available.

HIV Reduces the Number of CD4 Cells

HIV attacks the immune system’s soldiers – the CD4 cells. When the immune system loses too many CD4 cells, you are less able to fight off infection and can develop serious, often deadly, infections. These are called opportunistic infections (OIs) because they take advantage of the body's weakened defenses.

HIV Reduces the Type of CD4 Cells

In a healthy immune system, there are different types of CD4 cells that fight different diseases. As HIV progresses and kills off CD4 cells, some types of CD4 cells can disappear, leaving gaps in the immune system’s defenses.

One way to find out if you have damage to your immune system is to have a CD4 cell count done. This is a routine blood test. If you have fewer then 200 CD4 cells you are at increased risk for OIs, and your doctor will probably recommend that you receive preventative therapy for certain OIs. If your CD4 cells are below 350, and you have not started HIV treatment, you should probably talk to your doctor about starting treatment at that point.

A viral load test can help predict how quickly HIV may damage your immune system. An increasing and/or high viral load may mean that you are at greater risk for immune damage.

A simple test for hemoglobin or hematocrit can determine if you are anemic.  Anemia can have a bad effect on your immune system, so if you are anemic, it is important to discuss with your doctor options for treatment of your anemia.

Other immune function tests are in development.

Many HIV + people have experienced restored immunity (increases in CD4 cell counts) and a delay in disease progression with the use of HIV drugs. By keeping HIV under control, these drugs protect the immune system from further damage and allow it to repair itself instead of constantly fighting off HIV.

One sign that the immune system is getting stronger is an increase in CD4 cells. At first, the new CD4 cells are probably copies of existing types of CD4 cells. If some types of CD4 cells were lost, they won't come back right away. This could leave some gaps in the body's immune defenses.

However, if HIV stays under control for a few years, the immune system might make new CD4 cells that could fill in these gaps and more completely restore immune function.

Most people go on prophylaxis (medications to prevent OIs) when their CD4 cell counts go below 200. However, if you take HIV drugs and your CD4 cell count goes back over 200, it is usually safe to stop the prophylaxis. (Speak to your doctor before you stop taking any medication.)

Several experimental strategies are being studied to restore immune function. These methods focus on improving the function of various parts of the immune system:

Thymus

The thymus is a small gland that turns certain white blood cells into CD4 cells, also called t-cells. In fact, the “t” in t-cell stands for thymus. Scientists have studied transplanting a human or animal thymus into an HIV+ person. They have also tried to stimulate the thymus with hormones. To date these methods have not proven to be particularly successful.

CD4 Cells

Various methods are being studied to increase and improve CD4 cell function:

• Cell Expansion – A person's cells are multiplied outside the body, and then infused back in.
• Cell Transfer – A person is given immune cells from their twin or an HIV- relative.
• Cytokines or Immune Modulators – These are proteins that our body naturally makes whenever there is an infection. The most work has been done on a cytokine called interleukin-2 (IL-2). To date, trials have shown that IL-2 significantly increases CD4 cells in HIV+ people; however the long-term benefits are still unknown.
• Gene Therapy – This approach attempts to modify cells so that they are resistant to HIV infection.

Immune Response

Therapeutic HIV vaccines may help the immune system to better recognize HIV. Many scientists believe that this should improve and stimulate the body's response to the virus. Although data released so far have been disappointing, several new types of therapeutic vaccines are being studied in clinical trials.

Although an increase in CD4 cell counts is a good sign, it has led to a flare up of certain types of infections or a worsening of these infections in some HIV+ people. This is referred to as immune restoration inflammatory syndrome (IRIS). The reported infections include Mycobacterium avium complex (MAC), cytomegalovirus (CMV), herpes simplex virus, hepatitis B and C, tuberculosis (TB), and herpes zoster (or shingles).

IRIS occurs in 15%-25% of people who are starting therapy for HIV for the first time. IRIS can occur when people with very weak immune systems (e. g. people who have low CD4 cell counts, high CD8 cell counts, or anemia) start HIV treatment or in people who start HIV treatment when they already have an OI. If the immune system recovers quickly after starting HIV treatment, it might have a strong response to some germs that were already in the body or new germs with which it might come into contact.

Although the outlook for most HIV+ people with IRIS is good, IRIS has been associated with some serious illnesses, so it is important for you to discuss IRIS with your doctor before you start HIV treatment.

Research into ways to enhance immune reconstitution is ongoing. But for now, the only way to improve and support the immune system is with general health maintenance like good nutrition, exercise, and stress management, and, when necessary, the use of HIV drugs to help control the virus.

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