Immune Recovery Syndrome
Unmasking infection.
For some people taking potent HIV therapies, getting well may mean feeling sicker for a little while. Researchers are reporting that some people on potent HIV cocktails experience a transient recurrence of symptoms of opportunistic infections (OIs) they had in the past. This relatively uncommon phenomenon is being called immune recovery syndrome (IRS) and is mostly seen in people who are quite sick when they begin taking HIV combination therapies, or HAART. Symptoms appear to occur when the immune system begins to bounce back and launches an attack on antigens (foreign proteins) from healed infections. Increased immune activity can also "unmask" previously undiagnosed infections.

Immune-mediated illnesses take different forms depending on the OI that's being attacked. Cases have been connected to MAC, TB, CMV retinitis, herpes, and hepatitis. Cancers appear to be unaffected. CMV-related symptoms include "floaters," blurry vision, and swelling of the fovea area of the retina, also known as cystoid macular edema. These eye problems should not confused with uveitis associated with injections of anti-CMV medication. Post-HAART MAC symptoms include fever and inflamed lymph nodes, or lymphadenitis. Looking at TB, there has been only one published case of HAART-induced intracranial tuberculoma. Researchers have also found an alarming correlation between increases in CD4 and CD8 immune cell counts and hepatitis C viral activity. In some cases, these flare-ups are the first sign of a previously undetected hepatitis infection. It's crucial to test for hepatitis C before starting HAART so that symptoms can be anticipated and treated. It's also important to test for hepatitis A and B, which can occur in people on HAART.

Reports to date suggest that these transient symptoms can last anywhere from a few months to more than a year and that they can be treated with OI therapies, as well as steroids in some cases, to reduce swelling. The good news is that these problems, while scary, may not mean that the illness will return in full force. In fact, symptoms like lymph-node inflammation can be signs that the immune system is regaining its strength. Recurrence of herpes zoster (shingles) correlates with a high initial rebound in levels of CD8 T-cells (a key part of the first arm of our immune response). At the University of California in San Diego, Dr. Francesca Torriani found that CMV symptoms were linked to CD4 T-cell increases. "What we're seeing is good restoration of immune response to a specific antigen," she explains.

Immune-mediated illnesses can be prevented by starting anti-HIV therapy before the body becomes vulnerable to opportunistic infections-or in other words, before T-cell counts drop below 200. IRS "really only occurs in advanced patients who get treated" with HAART therapy, says UCLA opportunistic infections expert Dr. Judith Currier. "As people are treated earlier, we may see the problem disappear." Right now, researchers don't know whether OI prophylaxis and maintenance therapies will prevent immune-mediated illnesses. A warning: Decisions about TB treatment should be carefully discussed with a doctor because anti-TB drugs like rifabutin and rifampin can't be combined with many HIV drugs. All patients who do decide to stop OI prophylaxis or maintenance therapy should monitor their health and include specific screenings for past OIs (such as regular eye exams for CMV) in order to catch signs of recurrence or immune-mediated response.

Emily Bass