A proportion of HIV-positive people develop unusual manifestations of opportunistic or other infections soon after starting effective antiretroviral therapy, usually within three months. While these flare-ups may look like a recurrence or worsening of disease, they are thought to actually reflect improvement in the body's ability to control infection. Researchers believe these reactions happen as the recovering immune system mounts an excessive response against organisms that were already present in the body.

This ‘immune restoration syndrome’ can have various manifestations, including lymph node inflammation associated with Mycobacterium avium intracellulare (MAI), eye inflammation (uveitis or vitritis) associated with cytomegalovirus (CMV), worsening of tuberculosis, cryptococcosis, or toxoplasmosis symptoms, and elevated liver enzymes in people with hepatitis B or C coinfection. There have also been case reports of temporary worsening of Pneumocystis pneumonia (PCP), progressive multifocal lymphadenopathy (PML), herpes simplex and varicella zoster (shingles), warts due to human papillomavirus (HPV) and other skin conditions.

Although estimates vary, studies have found that immune restoration syndrome occurs in a minority of people starting antiretroviral therapy, usually around 10% to 30%. Research shows that these manifestations occur most often in patients who previously had advanced immune suppression, for example those with a CD4 cell count below 100 cells/mm³ or a CD4 cell percentage below 15% ^[1] [2].

One recent study found that the people most likely to develop immune restoration syndrome were those who started antiretroviral therapy closest to the time the associated infection was first treated. Immune restoration reactions have also been linked to larger viral load reductions or CD4 cell increases after starting HAART ^[3]. Other researchers, however, have found that none of these factors predicted the likelihood of immune restoration syndrome ^[4].

The best approach to managing immune reconstitution syndrome is unsettled, and treatment will differ depending on the original infection associated with each reaction. Since flare-ups indicate improvement in immune function, antiretroviral therapy is usually continued in all but the most serious cases. Even then, HAART is usually stopped only temporarily until the patient's condition has stabilised.

Anti-inflammatory medications may help decrease symptoms during the intense inflammatory phase, but routine use of corticosteroid therapy is general discouraged. There have been anecdotal reports of successful management of reactions using pentoxifylline (Trental), thalidomide, and the asthma medication montelukast ^[5] [6]. In many cases, immune reconstitution reactions resolve on their own without any additional treatment.