Transcript 6-Gwanzura_C-UZ-UCSF

Safety Monitoring & Adverse Drug
Reactions to Efavirenz and INH
Dr Clorata Gwanzura
MBChB-UZ, MPH –FETP (UZ)
Background
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Isoniazid Preventive Therapy (IPT) is a key public health
intervention aimed at prevention of progression of latent TB
infection to active TB disease among people living with HIV
Recommended by WHO since 2004 as part of 3 I’s for
strengthening TB/HIV collaborative activities
In Zimbabwe, the IPT Programme was commissioned by the
MOHCC in Dec 2012
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Initially as a pilot in 10 sites across 5 provinces from Dec 2012 – Dec 2013
then
Scaled up in a phased approach from Jan 2014 to date
As at end of Dec 2015, approximately 70 000 clients had been
offered IPT
Rationale for implementing IPT in
Zimbabwe?
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Tuberculosis - most common cause of mortality and morbidity
among HIV infected people
 68% HIV co-infection in all TB cases (Global TB Report,
2015)
Multiple studies have shown that IPT reduces TB incidence in
HIV infected patients by 33% – 64%
ART reduces the likelihood of developing TB disease, however
TB incidence among HIV infected on ART is still greater than
in the general population
Suspected INH Toxicity
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Index case, Nov 2014 - Previously well 56 year old HIV +ve female HCW
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More suspected cases reported by physicians in Harare province (public &
private sector)
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Suspected severe INH fulminant liver failure, Harare Central hospital
Patient deteriorated & subsequently died on day 5 post admission into ICU
A total 23 suspected cases reported to the ministry as at end of April 2015
MOHCC’s response
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Meetings conducted with Physicians (PAZ) & Public Health Physicians (CPHP)
& representatives of PLHIV
Task team comprising of a physician representative, a programme manager, an
M&E officer & an MPH officer made to critically investigate cases
Eight out of total ‘reported’ 23 suspected case records successfully retrieved and
analysed
Characteristics of the 8 Reported
Suspected Cases
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All were female clients, median age 38 years (Q1 = 26.5, Q3 = 43.5)
Duration in HIV care 3 - 11 years, latest CD4 ranging from 460 – 987
cells/ml, average 620 c/ml
All had been initiated on INH and the duration on IPT up to time of
presentation ranged from 3 weeks - 4 months
Seven (7) of the cases were on a concurrent Tenolam – E regimen and
one (1) was on Tenolam – N
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No additional concurrent medications with hepatotoxic effects
No history of traditional medicines use
Presenting Complains and Management
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Presenting symptoms - early onset nausea & vomiting followed by yellowing
of eyes & skin (jaundice)
Duration from onset of symptoms to presentation for admission ranged from
6 days - 1 month
Three of the clients had been attended to by another HCW prior to
presentation for admission (initially managed as acute GE)
Three (3) of the suspected cases had death outcomes, 5 completely
recovered and were discharged
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Two (2)were on a concurrent Tenolam –E regimen while one (1) was on Tenolam –
N
Two of the 3 who dies had altered level of consciousness and confusion on
admission
Investigations Done on Admission and Patient
Outcomes
Patient
number
1
Peak
Bilirubin
421
Peak ALT
Peak AST
Peak INR
Outcome
1.60
Length of
hospital stay
7 days
644
776
2
355
1915
3370
1.76
9 days
Alive
3
242
1349
1264
1.86
8 days
Died
4
283
289
703
2.80
18 days
Died
5
446
1360
2500
2.98
7 days
Died
6
54
286
932
8.49
6 days
Died
7
501
399
1326
-
7 days
Alive
8
344
481
1415
-
14 days
Alive
Alive
• Five (5) had USS done, two were normal, 1 had duct pathology suggesting a medical
pathology and 1 queried liver cirrhosis
• All 8 patients were hepatitis A, B and C negative
Research Questions to be answered?
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What is the extent of the problem and is the reported incidence of
adverse events above what one would expect from INH exposure
in general?
What are the current IPT prescribing practices among clinicians?
Is there need to further re-stratify clients eligible for IPT?
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Who is most affected (sex, CD4, etc)?
Could this be pharmacovigilance issue related to the batch of
INH medicines in use or not?
Is there possibility of interactions with EFV?
Next Steps
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Consultations done & are currently ongoing with colleagues in
neighbouring countries implementing IPT (Botswana & SA)
Impact of IPT program on reduction of incidence of TB infection
 Analysis of data controlling for increased ART coverage rates
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Data reporting tool developed & disseminated to all provinces
MOHCC has commissioned studies which are currently
ongoing to answer some of the research questions ‘Determining the Prevalence and Risk Factors Associated
with the Development of Isoniazid Toxicity among
Patients on Antiretroviral Therapy at Parirenyatwa
Hospital’
Next Steps
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MOHCC working with MCAZ to strengthen pharmacovigilance
system for ADRs
Exploring innovative strategies to sensitize HCWs, clients
enrolled in care and communities on IPT on the following
To have a high index of suspicion for potential adverse events,
 Importance of early presentation to HFs
 Strengthen reporting of AEs through the MCAZ Adverse Events
Reporting System - regular trainings, emails, SMS, whatsapp
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Acknowledgements
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MOHCC AIDS & TB staff
Dr A Reid, Dr T Gede and other physicians
Partners – WHO regional country office, CDC Zimbabwe, the
Union
MSF
Thank you