Toxicity of ART

8/11/2019 Toxicity of ART

1/10

Dr F Amod FCP, FCPath

Toxicity of ART

SA Aids ConferenceJune 2013

Dr Farida AmodInfectious Disease Physician

Durban Clinical Trials Unit


2/10


Case 1

31 year old male on Aluvia and efavirenz for12 weeks presents with epigastric pain and

nausea for 2 weeks.

Clinical examination normal apart from mild

weight loss (+/- 2 kg)


3/10


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 2weeks later with severe nausea, deep jaundice andbleeding gums.

At week 14:LFT: AST 4390IU/L, TB 342umol/l

INR: 3.09

Developed fulminant hepatitis, went into liver failureand died.


4/10


Hep B IRIS

Visit AST CD4 HIV VL Px Hep B

VL

(c/ml)

scr 35 65 >750000

nil 10 000

12 56 199 3 mill


5/10


Hepatotoxicity vs IRIS

30 yr old male (on TDF/FTC/ boosted atazanavir)

Hep BsAg +/ eAg -/ cIgM

-/ cIgG+

All ARVs stopped (week20)

Hepatitis resolved byweek 24

Visit CD4 VL ALT

scr 54 >750000 58

20 174 513 1048

24 73 450 000 146


6/10


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 -


7/10


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


8/10


Diagnostic criteria continued

Clin manifestation consistent with an

inflammatory syndrome

Absence of drug resistant infection, drug

adverse reaction, noncompliance or drug

malabsorption


9/10


Epidemiology of IRIS

15-25% incidence within first 3 months ofinitiating 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 Chemo2006 57:167-70


10/10


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

Toxicity of ART

Documents

Transcript of Toxicity of ART