2. Tolerability of Isoniazid Preventive Therapy (IPT) in an HIV infected cohort
T Mudzviti1,2, T Shamu1, C Kunzekwenyika1, C Chimbetete1, S. Bote1, M Pascoe1, R Luethy1
1Newlands Clinic, Harare, Zimbabwe
2School of Pharmacy, University of Zimbabwe, Harare, Zimbabwe

3. WHO Recommended Collaborative TB/HIV Activities
Decrease burden of TB among PLHIV (the "Three I's")
Establish intensified TB case finding
Introduce Isoniazid (INH) preventive therapy for LTBI
Ensure TB infection control in health care and congregate settings

4. Who Should Receive IPT in Zimbabwe?
People at high risk for TB such as:
Adults & adolescents (including pregnant mothers) living with HIV (Pre-ART & on ART)”
Children living with HIV (Pre-ART & on ART)
Children contacts of active TB cases

5. Isoniazid Prophylaxis (IPT) at NC
Criteria for IPT Commencement:
HIV +ve children <12 years who do not have active TB
Any patient who has a sputum +ve household contact
Patients >12 years with a CD4 <200 &/or confirmed VF
All 3rd line candidates

6. Isoniazid Prophylaxis (IPT) at NC
Exclusion Criteria for IPT
Symptoms & signs suggestive of TB
Patient on TB treatment
Patients who have been on ART for three months or less
Signs of active liver disease or history of INH-induced hepatitis or heavy alcohol use

7. INH alone is hepatotoxic INH is now being combined with nevirapine
Some thoughts
INH alone is hepatotoxic
INH is now being combined with nevirapine
INH is now being used without rifampicin

8. IPT Toxicities at Newlands Clinic
Determination of the incidence of adverse hepatic events after IPT commencement in a cohort of HIV infected patients
Retrospective cohort study
Data from 438 patients were analyzed
Patients commenced IPT between January 2014 and May 2015

9. Results

10. Patient Characteristics (N = 438)
Variable
Statistic
Sex
Female, n(%)
202 (46.1)
Age at IPT start (years)
Median (IQR)
10.0 (7 – 12)
Nevirapine use, n (%)
Yes No
229 (52.3)
209 (47.7)

11. Severity of ALT Elevations (N =132)
Variable
Statistic
Grade 1 and 2 ALT elevations, n (%)
Median ALT (IQR)
Median time to grade 1 or 2 elevation (weeks)
104 (79)
66.05 ( )
12 (8 – 19)
Grade 3 and 4 ALT elevations, n (%)
Median time to grade 3 or 4 elevation (weeks)
Incidence
28 (21)
335 (257 – 420)
12 (9 - 16)
31.5/100 person-years (CI: 20.9 – 45.5)

12. (p=0.313)

13. Characteristics of patients who discontinued INH
Variable
Statistic
Number of events, n(%)
32 (7.1)
Time to discontinuation, median (IQR)
12.1(10 – 16) weeks
Age of participants who discontinued
Median (IQR)
10 (7 – 12) years
Female, n(%)
17 (54.8)

14. Risk Factors
Concomitant use of NVP was the only factor significantly associated with hepatotoxicity (RR: 2.7, CI: 1.2 – 6.3, p=0.012) or stopping IPT for any reason (RR: 3.1, CI: 1.5 – 6.4, p<0.001)

15. Conclusion Median time to hepatotoxicity was 12 weeks
Concomitant use of INH with NVP increases the risk of hepatotoxicity

16. Thank you!        