Dr F Amod FCP, FCPath

Toxicity of ART
SA Aids Conference
June 2013
Dr Farida Amod
Infectious Disease Physician
Durban Clinical Trials Unit

Dr F Amod FCP, FCPath
Case 1
31 year old male on Aluvia and efavirenz for
12 weeks presents with epigastric pain and
nausea for 2 weeks.

Clinical examination normal apart from mild
weight loss (+/- 2 kg)
Dr F Amod FCP, FCPath
Lab results
At baseline: Hep B sAg +/ eAg -/ cIgM-/ cIgG+
LFT : normal
At week 12: LFT: AST: 56 IU/L, ALT: 76, TB: 23umol/l

Patient continued with his medication. Presented 2
weeks later with severe nausea, deep jaundice and
bleeding gums.
At week 14: LFT: AST 4390IU/L, TB 342umol/l
INR: 3.09
Developed fulminant hepatitis, went into liver failure
and died.
Dr F Amod FCP, FCPath
Hep B IRIS
Visit AST

CD4 HIV VL Px Hep B
VL
(c/ml)
scr 35 65 >750
000
nil 10 000
12 56 199 <50 Aluvia/E
FV
14 4390 ARVs
stopped
>3 mill
Dr F Amod FCP, FCPath
Hepatotoxicity vs IRIS
30 yr old male (on TDF/
FTC/ boosted atazanavir)

Hep BsAg +/ eAg -/ cIgM
-/ cIgG+

All ARVs stopped (week
20)

Hepatitis resolved by
week 24

Visit CD4 VL ALT
scr 54 >750000 58
20 174 513 1048
24 73 450 000 146
Dr F Amod FCP, FCPath
Hepatotoxicity vs IRIS
Diff diagnosis
Hep B IRIS

drug-induced
hepatotoxicity

Visit Hep B
Viral load
Hep B
serology
scr >1000000 sAg +/
eAg-
Wk 20 6 400 sAg +/
eAg-
cIgM -
Dr F Amod FCP, FCPath
Diagnostic Criteria for IRIS
No single definition

Most of the ff should be present:
Low pretreatment CD4
Positive virologic and immunologic
response to HAART
Temporal ass bet HAART initiation and
clinical illness
Dr F Amod FCP, FCPath
Diagnostic criteria continued
Clin manifestation consistent with an
inflammatory syndrome

Absence of drug resistant infection, drug
adverse reaction, noncompliance or drug
malabsorption
Dr F Amod FCP, FCPath
Epidemiology of IRIS
15-25% incidence within first 3 months of
initiating ART
with known underlying OI: 15-45%
Risk factors:
Underlying OI
Lower baseline CD4 count
Higher baseline HIV RNA
Rapidity of HIV RNA decline on ART
Probably not the rapidity of CD4 increase
Shelbourne, J Antimicrob Chemo
2006;57:167-70
Dr F Amod FCP, FCPath
How to manage IRS
May be possible to avoid in patients with known OIs by
treating OIs for 1-2 months prior to initiation of HAART

Treat the underlying infection

Consider steroids to diminish inflammatory response
Start at Prednisone 0.5-1mg/kg/d, then taper while
monitoring for recurrence of symptoms

Continue ART unless the condition is life threatening