Predictors of ART-associated TB in a prospective study:Results of the Kericho IRIS Study

The Rainbow of IRIS in HIV InfectionJuly 26, 2012 

Fredrick Kirui, MBChB, MMEDKenya Medical Research Institute/Walter Reed Project HIV Program

Kericho, Kenya

IRIS-Kericho

A Cohort Observational Study Evaluating Predictors, Incidence and Immunopathogenesis of Immune Reconstitution Syndrome (IRIS) in HIV-1 Infected Patients with CD4 Count <100 Cells/µL

who are Initiating Antiretroviral Therapy

Primary Objectives: To identify baseline predictors of IRIS within 6 months of

ART initiation. To evaluate the immunopathogenesis of IRIS with the

goal to identify more appropriate therapeutic targets and interventions.

200 volunteers enrolled between February 2009 and June 2010 and followed for 2 years

Participant Characteristics at Baseline

Characteristic Value [mean (SD) or %] Age (yrs) 36.5 (8.2) Female 53 BMI (kg/m2) 18.6 (3.6) HgB (g/dL) 11.2 (2.1) Cr (mmol/L) 66.6 (21.0) ALT (U/L) 34.3 (31.5) CD4 (T cells/mm3) 43.2 (35.8) HIV-1 RNA (copies/ml) 347,327 (266,135)

TB in the IRIS Study

• IRIS Events (37) Majority of IRIS cases observed were TB related (17, 46%) Approximately 2/3 were unmasking TB

• ART associated TB (within 6 months of ART initiation - considered unmasking TB-IRIS per ACTG definition)

31 cases (19%) of participants Mean age=37 years, 59% F At an average of 6 weeks after ART initiation PTB (63%) > extra-pulmonary (25%) > disseminated (12%)

Comparison of ART-associated TB cases with non-TB study participants

• Compared to controls TB cases at baseline had: - Lower Hgb (9.4 vs. 11.3 gm/dL, p=<0.0001) and BMI

(17.7 vs. 18.9, p=0.015) - Higher ESR (74.6 vs. 38.56 mm/hr, p=0.002) - Higher proportion of CD8+/PD1+ T cells (39.9 vs. 29.%,

p=0.007) *remained significant in regression analysis (p=0.005)• - Higher mortality (28% vs 9% p=0.0066)• Screening of patients with low CD4 counts and BMI and

anemia and high ESR may facilitate earlier TB diagnosis and treatment.

Asanteni Sana!IDCRP NIAID USMHRP KEMRI/WRPBrian AganIrini Sereti Nelson Michael Fred SaweGreg Martin Alice Pau Deline Glover Kibet Shikuku

Gregg Roby Jun Tan Deborah LangatJoAnn Mican Hellen NgenoVirginia Sheikh Argwings Miruka

Lazarus Momanyi

Doug ShafferIRIS Endpoint Committee: Martyn French, Chair

IRIS Study Volunteers