Low CD4 cell count, big drop in viral load, and boosted PI are risk factors for IRIS

A low baseline CD4 cell count, a big drop in viral load, and taking a ritonavir-boosted protease inhibitor are risk factors for an immune restoration inflammatory syndrome (IRIS) illness in people patients starting potent anti-HIV therapy, according to a study published in the December 1^st edition of the Journal of Acquired Immune Deficiency Syndromes.

There has been a significant fall in the amount of illness and death seen in HIV-positive people and a general improvement in the quality of life since effective antiretroviral therapy first became available in 1996.

But improvements in the immune system may cause a small number of people starting anti-HIV treatment to develop an IRIS. An IRIS is characterised by the emergence, or worsening, of symptoms associated with an existing dormant infection. Most cases happen in the first three months after antiretroviral therapy is initiated, but cases of IRIS have been observed up to two years after anti-HIV therapy was first started.

Information on the risk factors for IRIS and optimal treatment options are needed. Investigators from Johns Hopkins University in Baltimore, a major provider of HIV treatment and care, therefore designed a retrospective case-controlled study to identify the “clinical, demographic, and laboratory predictors of IRIS.”

The investigators identified a total of 49 individuals who developed an IRIS between 1998 and 2006. Each patient was matched with four control HIV-positive control patients who started anti-HIV therapy but did not develop an IRIS (total control population, 196).

Patients presented with symptoms of an IRIS a median of 29 days (range nine – 109 days) after starting potent anti-HIV therapy. The median nadir (lowest ever) CD4 cell count was 20 cells/mm³ indicating very advanced immune suppression.

There were no demographic differences between cases and controls, however the investigators did find the following factors were independently associated with the development of an IRIS:

• Taking an antiretroviral regimen that included a ritonavir-boosted protease inhibitor (odds ratio [OR] = 7.41; 95% confidence interval [CI]: 1.76 – 31.29, p= 0.006) or a boosted protease inhibitor with an NNRT (p = 0.02). An NNRTI-based regimen was not associated with a significant risk of an IRIS (p = 0.06).
• A nadir CD4 cell count below 100 cells/mm³ (OR = 5.97; 95% CI: 2.33 – 15.31, p
• A viral load drop of 2.5 log₁₀ or greater after starting anti-HIV treatment (OR = 2.43; 95% CI: 1.00 – 5.96, p

Nineteen patients received corticosteroids for the management of their IRIS. Median duration of such therapy was 163 days, ranging from 21 to 551 days. The patient with the longest duration of therapy had tuberculous meningitis. He had nausea, vomiting, and headache when steroid therapy was tapered off and therefore remained on steroids until the conclusion of his tuberculosis treatment.

The investigators conclude, “further prospective study of IRIS and its treatment is important in defining patients at greatest risk and to optimize immunomodulatory therapies”.