Immune Reconstitution

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What is Immune Reconstitution?

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

While many different methods of immune reconstitution are under investigation, there are no FDA-approved immune-based therapies for HIV disease available. The good news is that advances in HIV treatment have led to the development of HIV drugs that are more effective and less toxic. Although HIV drugs cannot cure HIV, they can help you stay healthy by preventing the virus from reproducing (making copies of itself) and doing more damage to your immune system.

How Does HIV Damage the Immune System?

HIV attacks immune system cells called CD4 cells. HIV enters these cells and turns them into virus factories that produce thousands of copies of HIV. Viral load is the amount of HIV (number of copies) in your bloodstream. The higher the amount of HIV, the greater the chances of your immune system being damaged.

As the virus reproduces, it damages or kills CD4 cells. Over time, the virus decreases both the number and type of CD4 cells. As the immune system loses CD4 cells, your body is less able to fight off infection. Serious, even deadly infections can develop. These are called opportunistic infections (OIs) because they take advantage of the body's weakened defenses.

Using HIV Drugs to Restore Immune Function

HIV drugs work by stopping HIV from making copies of itself. When HIV cannot reproduce, it cannot infect new cells in your body and your viral load remains low. This allows your body’s immune system to repair itself instead of constantly fighting off HIV.

The sooner someone who is living with HIV (HIV+) starts taking HIV drugs, the less damaged her immune system will be and the sooner it can return to its healthy, germ-fighting status. Research studies have shown that starting treatment earlier, even when someone feels fine and has plenty of CD4 cells, can prevent unseen damage to the immune system and slow disease progression. As a result, the US Department of Health and Human Services now recommends treatment for all people living with HIV, no matter what their CD4 count.

Monitoring the Health of the Immune System

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 opportunistic infections, and your health care provider will probably recommend that you receive preventive medication for certain OIs.

An increase in the number of CD4 cells is one sign that your immune system is getting stronger. At first, the new CD4 cells are probably copies of existing types of CD4 cells. If some types of CD4 cells were lost, they may not 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 may make new types of CD4 cells that can fill in these gaps and more completely restore immune function.

A viral load test tells you how active HIV is in your body. When compared over time, viral load results show if the amount of HIV in your bloodstream is higher or lower than it was before. The higher your viral load, the more active HIV is and the more likely you are to lose CD4 cells in the future.

When a combination of HIV drugs (your drug regimen) is working, the viral load usually goes down within weeks of starting the drugs. One goal of HIV treatment is to keep viral load levels as low as possible for as long as possible.

Immune Reconstitution Inflammation Syndrome (IRIS)

Although an increase in CD4 cells and a decrease in viral load are good signs, some people experience a flare up of certain types of infections or a worsening of their HIV-related symptoms. This is referred to as immune reconstitution inflammatory syndrome (IRIS).

IRIS happens when your immune system acts so strongly and so quickly that it generates an inflammatory response that actually makes your symptoms worse. For most, these symptoms include fever, swollen lymph glands, and rash, and they go away in a few weeks. For others, the symptoms are more severe and should be brought to the attention of a health care provider.

The symptoms often depend on what germs were already in the body when the immune system begins its strong, inflammatory response. The infections that often flare up include Mycobacterium avium complex (MAC), cytomegalovirus (CMV), herpes simplex virus (HSV), hepatitis B and C, tuberculosis (TB), herpes zoster (or shingles), Kaposi sarcoma (KS), and PCP (pneumocystis pneumonia). IRIS can also worsen some pre-existing conditions, especially autoimmune conditions like Graves' disease, lupus, or rheumatoid arthritis.

IRIS usually occurs in the first six weeks of treatment. It can occur in anyone starting HIV drugs for the first time, starting HIV drugs after being off them for a while, or switching to new HIV drugs. Most cases of IRIS occur in people who have low CD4 counts and high viral loads at the time they begin or switch HIV drugs. However, IRIS can occur at any CD4 count. IRIS also tends to occur more often in those people who see a rapid increase in their CD4 count and/or a rapid decrease in their viral load after starting treatment.

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 health care provider before you start or switch HIV drugs.

Taking Care of Yourself

For women living with HIV, the best way to improve and support your immune system’s health is to take HIV drugs on schedule (adherence is key!), eat well, be physically active, do what you can to manage the stress in you life, and get the support and care you need to stay healthy.

Additional Resources

Select the links below for additional material related to immune reconstitution.

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