SAFETY OF ISONIAZID PREVENTIVE THERAPY AMONG HIV-INFECTED PREGNANT WOMEN IN HIGH TB INCIDENCE SETTINGS: STUDY UPDATE OF IMPAACT P1078 (APPRISE) Dr B Kusakara

OUTLINE

Background Study Schema Status

BACKGROUND

Tuberculosis (TB) is the most important cause of morbidity and mortality among HIV infected persons

50% of HIV-related TB deaths are in women TB accounts for 25% of non-obstetric deaths Peak incidence in reproductive age 15-45 yrs

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Age, yearsWHO Global TB Report 2013; Deluca JAIDS 2009

Pregnancy and postpartum may increase risk of LTBI reactivation

TB is difficult to diagnose in infants most cases of infant TB due to martenal TB disease

Prevention of active TB in mother = prevention of TB in children

Isoniazid (IPT) can prevent TB in the in HIV positive people by 33%. HAART +IPT (not concurrent) can reduce incident TB by up to 89%

Pregnancy excluded in all trials of TB prevention therapy

“TB APPRISE” TB ANTE VS. POSTPARTUM PREVENTION WITH INH IN HIV SEROPOSITIVE MOTHERS AND THEIR EXPOSED INFANTS

A Phase IV Randomized Double-Blind Placebo-Controlled Trial to Evaluate the Safety of Immediate (Antepartum-Initiated) Versus Deferred (Postpartum-Initiated) Isoniazid Preventive Therapy Among HIV-Infected Women in High TB Incidence Settings

P1078 OBJECTIVES

Primary To compare safety (Grade 3 or 4 adverse events

or permanent discontinuation of INH/placebo related to INH in women) of immediate antepartum vs. deferred postpartum INH preventive therapy in era of HAART

SECONDARY OBJECTIVES

1. To compare safety and toxicity of INH on fetus and infants on study.

2. To compare TB incidence and all-cause mortality in HIV-infected women and their infants enrolled on study.

3. To evaluate for INH resistance among M.tb. isolates from HIV-infected women and infants who develop TB while on study.

4. To evaluate the intensive pharmacokinetics of INH and ART in a subset of HIV infected pregnant and postpartum women receiving HAART.

5. To evaluate and compare the performance characteristics of IGRA (TB ELISPOT and QGIT) with TST in HIV-infected women and their infants.

6. To compare adherence in women initiating immediate versus deferred INH preventive therapy.

7. To compare hepatotoxicity rates and evaluate risk factors for hepatotoxicity in immediate versus deferred INH therapy.

ENROLMENT AND RANDOMISATION

Study population- 950 mother infant pairs 12 sites in India , Bostwana Uganda ,

Tanzania,South Africa,Zambia and Zimbabwe. Zim - 300 mother infant pairs 31,6% of study population

HIV-infected pregnant women ≥ 14weeks through ≤ 34 weeks (34 weeks, 6 days) gestation with a NEGATIVE TB symptom screen.

At study entry, randomization will be in a 1:1 ratio to Arm A or B.

Arm A (immediate INH treatment) INH 300 mg - initiated at study entry and continued for 28 weeks. Placebo for INH initiated after 28 weeks of INH treatment and continued until 40 weeks postpartum.

Arm B (deferred INH treatment) Placebo for INH - initiated at study entry and continued until 12 weeks postpartum.THEN· INH 300 mg initiated at 12 weeks postpartum and continued until 40 weeks postpartum.

STUDY STATUS

Engaged MOHCC AIDS and TB Unit who are in the process of rolling out a programme for Isoniazid Preventive Therapy following a pilot programme completed in 2014

Protocol Approvals MRCZ -12 Apr 2013 JREC -17 Apr 2012 MCAZ- 16 Oct 2013Funding released February 2014 First participant enrolled on 16 Dec 2014

ACCRUAL AND RETENTION

Good response and support from the community

88 participants enrolled to date Retention 100%

THANK YOU

ACKNOWLEDGEMENTS