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. 2012 Feb 1;54(3):424-33.
doi: 10.1093/cid/cir802. Epub 2011 Nov 17.

Paradoxical immune reconstitution inflammatory syndrome in HIV-infected patients treated with combination antiretroviral therapy after AIDS-defining opportunistic infection

Chad J Achenbach  1 , Robert D Harrington, Shireesha Dhanireddy, Heidi M Crane, Corey Casper, Mari M Kitahata
Affiliations

Paradoxical immune reconstitution inflammatory syndrome in HIV-infected patients treated with combination antiretroviral therapy after AIDS-defining opportunistic infection

Chad J Achenbach et al. Clin Infect Dis. .

Abstract

Background: The incidence of immune reconstitution inflammatory syndrome (IRIS) when antiretroviral therapy (ART) is initiated after an AIDS-defining opportunistic infection (OI) is uncertain and understudied for the most common OIs.

Methods: We examined patients in the University of Washington Human Immunodeficiency Virus Cohort initiating potent ART subsequent to an AIDS-defining OI. IRIS was determined through retrospective medical record review and adjudication using a standardized data collection process and clinical case definition. We compared demographic and clinical characteristics, and immunologic changes in patients with and without IRIS.

Results: Among 196 patients with 260 OIs, 21 (11%; 95% confidence interval, 7%-16%) developed paradoxical IRIS in the first year on ART. The 3 most common OIs among study patients were Pneumocystis pneumonia (PCP, 28%), Candida esophagitis (23%), and Kaposi sarcoma (KS, 16%). Cumulative 1-year incidence of IRIS was 29% (12/41) for KS, 16% (4/25) for tuberculosis, 14% (1/7) for Cryptococcus, 10% (1/10) for Mycobacterium avium complex, and 4% (3/72) for PCP. Morbidity and mortality were highest in those with visceral KS-IRIS compared with other types of IRIS (100% [6/6] vs 7% [1/15], P < .01). Patients with mucocutaneous KS and tuberculosis-IRIS experienced greater median increase in CD4(+) cell count during the first 6 months of ART compared with those without IRIS (+158 vs +53 cells/μL, P = .04, mucocutaneous KS; +261 vs +113, P = .04, tuberculosis).

Conclusions: Cumulative incidence and features of IRIS varied depending on the OI. IRIS occurred in >10% of patients with KS, tuberculosis, or Cryptococcus. Visceral KS-IRIS led to considerable morbidity and mortality.

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Figures

Figure 1.
Figure 1.
Scheme of patient identification, review, and inclusion in the study analysis. Abbreviations: ART, antiretroviral therapy; HIV, human immunodeficiency virus; OI, opportunistic infection; IRIS, immune reconstitution inflammatory syndrome.
Figure 2.
Figure 2.
Proportion of patients developing immune reconstitution inflammatory syndrome over the first year of antiretroviral therapy, categorized by type of opportunistic infection. Abbreviations: ART, antiretroviral therapy; IRIS, Immune Reconstitution Inflammatory Syndrome; KS, Kaposi sarcoma; MC, mucocutaneous; PCP, Pneumocystis pneumonia; Visc, visceral.
Figure 3.
Figure 3.
CD4+ cell counts in the first 6 months of antiretroviral therapy (ART) for individual immune reconstitution inflammatory syndrome (IRIS) cases categorized by type of AIDS-defining opportunistic infection. Note: I, marks timing of the IRIS event; I*, IRIS event occurred after the first 6 months of ART. Abbreviations: KS, Kaposi sarcoma; MAC, Mycobacterium avium complex; PCP, Pneumocystis pneumonia.
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