Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome in a Rural Area of Mozambique

Abstract

BackgroundThere is limited data on the epidemiology of Immune Reconstitution Inflammatory Syndrome (IRIS) in rural sub-Saharan Africa. A prospective observational cohort study was conducted to assess the incidence, clinical characteristics, outcome and predictors of IRIS in rural Mozambique.MethodsOne hundred and thirty-six consecutive antiretroviral treatment (ART)-naïve HIV-1-infected patients initiating ART at the Manhiça district hospital were prospectively followed for development of IRIS over 16 months. Survival analysis by Cox regression was performed to identify pre-ART predictors of IRIS development.ResultsThirty-six patients developed IRIS [26.5%, incidence rate 3.1 cases/100 persons-month of ART (95% CI 2.2–4.3)]. Median time to IRIS onset was 62 days from ART initiation (IQR 35.5–93.5). Twenty-five cases (69.4%) were “unmasking”, 10 (27.8%) were “paradoxical”, and 1 (2.8%) developed a paradoxical worsening followed by the unmasking of another condition. Systemic OI (OI-IRIS) accounted for 47% (17/36) of IRIS cases, predominantly of KS (8 cases) and TB (6 cases) IRIS. Mucocutaneous IRIS manifestations (MC-IRIS) accounted for 53% (19/36) of IRIS events, mostly tinea (9 cases) and herpes simplex infection (3 cases). Multivariate analysis identified two independent predictors of IRIS development: pre-ART CD4 count <50 cells/µl (HR 2.3, 95% CI 1.19–4.44, p = 0.01) and body mass index (BMI) <18.5 (HR 2.15, 95% CI 1.07–4.3, p = 0.03). The pre-cART proportion of activated T-cells, as well as the immunologic and virologic response to ART were not associated with IRIS development. All patients continued on ART, 7 (19.4%) required hospitalization and there were 3 deaths (8.3%) attributable to IRIS.ConclusionsIRIS is common in patients initiating ART in rural Mozambique. Pre-ART CD4 counts and BMI can easily be assessed at ART initiation in rural sub-Saharan Africa to identify patients at high risk of IRIS, for whom close supervision is warranted.

New insights into immune reconstitution inflammatory syndrome of the central nervous system

“…Retrospective studies from Mexico (22) and Mozambique (23) of 390 and 136 patients respectively initiating ART indicate that the incidence of IRIS is approximately 27%. The vast majority of IRIS cases are associated with opportunistic infections (OI) either recognized prior to initiation of ART but worsening after therapy (paradoxical IRIS) or recognized after therapy initiation due to the restoration of the immune system (unmasking IRIS) (Figure 1).…”

Selective expansion of polyfunctional pathogen-specific CD4+ T cells in HIV-1–infected patients with immune reconstitution inflammatory syndrome

“…14 Severely immunocompromised patients who are ART-naive at OI diagnosis 1 and those with low CD4 counts appear to be most susceptible to IRIS. 2,15,16 Other risk factors include high HIV-1 RNA levels before ART, 2 a more rapid initial HIV-1 RNA suppression, 1,17 a high OI-derived antigen load at the time of ART initiation, 3,18 a short time interval between diagnosis and/or treatment start of an OI and ART initiation, 1,3,16 and a low body mass index. 15 Nonetheless, reports are not consistent, and it has been suggested that risk factors might differ by mode of IRIS presentation and etiology.…”

“…2,15,16 Other risk factors include high HIV-1 RNA levels before ART, 2 a more rapid initial HIV-1 RNA suppression, 1,17 a high OI-derived antigen load at the time of ART initiation, 3,18 a short time interval between diagnosis and/or treatment start of an OI and ART initiation, 1,3,16 and a low body mass index. 15 Nonetheless, reports are not consistent, and it has been suggested that risk factors might differ by mode of IRIS presentation and etiology. 13,15 Most studies to date trying to elucidate potentially diagnostic risk factors and/or biomarkers of IRIS have focused on patient groups with a particular opportunistic infection, such as Mycobacterium tuberculosis (TB), 16,[19][20][21] Mycobacterium avium, and intracellulare complex (MAC), 22 Cryptococcus neoformans, 3,14,18 or CMV.…”

“…15 Nonetheless, reports are not consistent, and it has been suggested that risk factors might differ by mode of IRIS presentation and etiology. 13,15 Most studies to date trying to elucidate potentially diagnostic risk factors and/or biomarkers of IRIS have focused on patient groups with a particular opportunistic infection, such as Mycobacterium tuberculosis (TB), 16,[19][20][21] Mycobacterium avium, and intracellulare complex (MAC), 22 Cryptococcus neoformans, 3,14,18 or CMV. 12 However, we hypothesized that there might be some common mechanisms underlying the development of IRIS in HIV-1 patients on ART, despite the highly variable clinical manifestations and variety of agents that can be associated with the syndrome.…”

Immunotherapies and Vaccines

“…One of the complications that an individual can experience on HAART is immune reconstitution inflammatory syndrome (IRIS) (Letang, Miro et al 2011). IRIS is seen in individuals recovering from immunodeficiency.…”