Immune reconstitution inflammatory syndrome

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 reconstitution inflammatory syndrome (IRIS) 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 co-infection. 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 reconstitution inflammatory 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

The best approach to managing immune reconstitution inflammatory syndrome is unsettled –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, highly active antiretroviral therapy (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.3 4 In many cases, immune reconstitution reactions resolve on their own without any additional treatment.


  1. Jevtovic DJ et al. The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy. HIV Med 6: 140-143, 2005
  2. Ratnam I et al. Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type-1-infected cohort. Clin Infect Dis 42: 418-427, 2006
  3. French MA et al. Immune restoration disease after antiretroviral therapy. AIDS 18: 1615-1627, 2004
  4. Lipman MCI et al. Successful drug treatment of immune reconstitution disease with the leukotriene receptor antagonist, montelukast: a clue to pathogenesis? AIDS 21: 383 – 384, 2007
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

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