1. Immune dysregulation in HIV patients following successful ART Dino Tan, Yean Kong Yong, Hong Yien Tan, Adeeba Kamarulzaman, Lian Huat Tan, Andrew Lim, Martyn French, Patricia Price
Hypothesis:
Immune restoration disease (IRD) in ART-treated HIV patients is caused by immune dysregulation which may involve:
- Excessive antigen-specific IFNγ responses
- High proportions of activated CD4+ T-cells
- Deficiency of regulatory CD4+ T-cells (T-regs)
Objectives:
To investigate the immunological characteristics of IRD from a cohort of HIV patients (n=47) commencing ART at the Infectious Disease Outpatient Clinics in University Malaya Medical Centre, Kuala Lumpur, Malaysia

2. Study design 2 Cryptococcal IRD & 3 TB IRD patients 8 Non-IRD patients
17 HIV-negative
Healthy controls
Matched by ethnicity (Chinese), gender (male) and age
All HIV patients selected:
Started ART with <100 CD4+ T-cells/μl
Suppressed viral replication & recovered CD4+ T-cells on ART
PBMC were collected at 0, 6, 12, 24 and 48 weeks
ELISpot
IFNγ responses to Cryptococcus neoformans
PPD, ESAT-6 & CMV
Flow cytometry
Activated (HLA-DRhi) CD4+ T-cells (CD25+CD127lo) CD4+ T-regs (CTLA-4+) CD4+ T-regs

3. Increased IFNγ responses & proportions of activated CD4+ T-cells during IRD are not associated with reduced CD4+ T-regs
IFNγ response peaks during IRD
IFNγ response peaks at IRD
Activated CD4+ T-cells high during IRD
Activated CD4+ T-cells increased during IRD
Cryptocoocus neoformans specific IFNγ producing cells
(% of CD4+ T-cells)
HLA-DRhi
Weeks on ART
Weeks on ART
CTLA (% of CD4+ T-cells)
CD25+CD127lo (% of CD4+ T-cells)
CD4+ T-regs high during IRD
Weeks on ART
Cryptococcal IRD patients
Non-IRD patients
Healthy controls (median)
Healthy controls (interquartile range)