IRIS common in patients with cryptococcal meningitis who start HIV treatment, but benefits of therapy outweigh risks

A large proportion of HIV-positive patients with cryptococcal meningitis develop an immune reconstitution inflammatory syndrome (IRIS) illness after starting HIV treatment, an international team of investigators report in the September 15^th edition of Clinical Infectious Diseases (now online). The timing of the initiation of HIV treatment did not affect the risk of an IRIS illness, but the investigators found clear evidence that the benefits of starting antiretroviral therapy outweighed any risks that may arise from an immune reconstitution illness.

Antiretroviral treatment reduces the risk of illness and death in HIV-positive patients who have developed opportunistic infections. After starting HIV treatment, some patients developed an immune reconstitution illness. Earlier research suggests that the proportion of patients with cryptococcal meningitis who develop this syndrome after starting HIV treatment varies between 8 and 50%.

Existing information on the incidence of IRIS in patients with cryptococcal disease comes from retrospective studies and may therefore have limitations.

Investigators from the Bacteriology and Mycology Study Group therefore performed a prospective study involving 101 HIV-infected patients with crytococcal meningitis who started HIV treatment. The study was originally designed to compare different treatment strategies for cryptococcal meningitis in HIV-positive patients.

A total of 13 of these patients developed an immune reconstitution illness. The overall incidence such illnesses was 47 per 100 person years. Such an incidence was in line with the findings of the earlier retrospective research.

The median interval between the initiation of antiretroviral therapy and the developed of immune reconstitution illness was 63 days, and headache was the most frequently reported symptom.

No association was identified between the timing of HIV treatment and the onset of IRIS, and delaying HIV treatment for 42 days after the commencement of therapy for cryptococcal meningitis did not reduce the risk of developing immune reconstitution illness. This finding was in contrast to the earlier retrospective research.

Patients who developed IRIS did not have an increased risk of death compared to those who did not (8% vs 15%). However, they were significantly more likely than non-IRIS patients to develop neurological complications including papilledema (swelling of the optic nerve caused by intracranial pressure) (15% vs 1%, p = 0.04) and depressed levels of consciousness (23% vs 3%, p = 0. 03).

The only factor significantly associated with an increased risk of developing immune reconstitution illness was a higher cryptococcal antigen level (p < 0.05).

“Cryptococcal IRIS after HAART [highly active antiretroviral therapy] initiation is common in AIDS patients with cryptococcal meningitis. There is no association between the timing of HAART initiation and IRIS”, write the investigators.

They note that outcomes in their main study were significantly better amongst patients who started antiretroviral therapy than those who did not (p < 0.01). The investigators therefore comment “it seems probable that the increased likelihood of successful outcome when using HAART could outweigh the risks of developing IRIS in these patients.”