All [HIV-exposed] infants should receive oral antiretroviral prophylaxis for the entire duration of breastfeeding - CON

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1 All [HIV-exposed] infants should receive oral antiretroviral prophylaxis for the entire duration of breastfeeding - CON Amy Slogrove Stellenbosch University 10 th International HIV Pediatrics Workshop 21 st July 2018, Amsterdam, Netherlands

2 No conflicts of interest to declare

3 Abbreviations Mother-to-Child Transmission (MTCT) Peri and postnatal HIV transmission (PPT) Infant Pre-exposure Prophylaxis (iprep) = prolonged infant postnatal prophylaxis for the duration of breastfeeding Maternal lifelong antiretroviral therapy (mart)

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5 Yes!

6 Should all HIV-exposed infants receive oral ARV prophylaxis for the entire duration of breastfeeding? NO

7 Should all HIV-exposed infants receive oral ARV prophylaxis for the entire duration of breastfeeding? 1 Is it safe? 2 Is it more effective than current standard of care? 3 What is the opportunity cost (indirect harm)? 4 Reality check

8 Safety of Infant PrEP Study Intervention Safety comparison Duration Safe* BAN Nevirapine No nevirapine 28 weeks (max) Yes HPTN046 Nevirapine Placebo 28 weeks (max) Yes PROMISE (IMPAACT 1077BF) Nevirapine No drug 18 months (max) Yes ANRS Lopinavir/ritonavir Lamivudine 50 weeks (max) Yes ANRS Lamivudine Lopinavir/ritonavir 50 weeks (max) Yes * No difference in serious adverse events between intervention and safety comparison groups BUT 1. We really don t know about ARVs in breastmilk and less about combined ARV exposure (Catriona Waitt CROI 2018) 2. Psychological harm of the daily fight to get medication into small children underestimated how much this shapes the maternal-child relationship

9 Safety of Infant PrEP FIRST *Pregnancy and infant pharmacovigilance systems in Low and Middle Income Countries*

10 Should all HIV-exposed infants receive oral ARV prophylaxis for the entire duration of breastfeeding? 1 Is it safe?? 2 Is it more effective than current standard of care? 3 What is the opportunity cost (indirect harm)? 4 Reality check

11 Prevention of Postnatal HIV Transmission Maternal ART Postnatal transmission at 6 months [Bispo, JAIDS 2017] Infant postnatal prophylaxis HPTN 046 [Coovadia, Lancet 2012]: Postnatal transmission at 6 months 1.1% (95% CI 0.3, 1.8) with extended invp; 2.4% (95% CI 1.3, 3.6) with placebo 1.1% (95% CI 0.3, 1.9) ANRS [Nagot, Lancet 2016]: Postnatal transmission at 12 months 1.4% (95% CI 0.4, 2.5) with extended ilpv/r; 1.5% (95% CI 0.7, 2.5) with extended i3tc PROMISE (IMPAACT1077BF) [Flynn, JAIDS 2018]: postnatal transmission at 24 months 0.7% (95% CI 0.3, 1.4) with mart; 0.9% (95% CI 0.4, 2.3) with invp mart as effective as prolonged invp With a potent ARV drug postnatal transmission still not ZERO

12 Prevention of Postnatal HIV Transmission mart + iprep < mart?

13 Prevention of Postnatal HIV Transmission mart + iprep < mart? HPTN 046 [Coovadia, Lancet 2012]: Infants born to mothers on ART at randomization had low rates of postnatal transmission, no different by extended invp (0.5%, 95% CI [1/210]) or placebo (0% [0/203]) during breastfeeding Ready to expose 1.4 million infants every year to extended infant prophylaxis on that evidence base?

14 Should all HIV-exposed infants receive oral ARV prophylaxis for the entire duration of breastfeeding? 1 Is it safe?? 2 Is it more effective than current standard of care? 3 What is the opportunity cost (indirect harm)? 4 Reality check

15 Peri- and Postnatal HIV Transmission in Focus Countries UNAIDS 2018 Estimates (courtesy of Mary Mahy)

16 PERCENTAGE (%) Pregnant Women Living with HIV Receiving ARVs for Perinatal Transmission Prevention in Focus Countries Countries that have not reached >95 % coverage of pregnant WLHIV account for >80% 66 of transmissions in Indonesia Nigeria Angola India Ethiopia DR Congo Ghana Chad Cote divoire Kenya Cameroon UR Tanzania Burundi Mozambique Botswana Swaziland Lesotho Malawi Zambia Namibia South Africa Uganda Zimbabwe UNAIDS 2018 Estimates (courtesy of Mary Mahy)

17 Engagement in Care (Retention + Adherence) Maternal postpartum retention in B-plus era [Knettel, JAIDS 2018] 76% of postpartum WLHIV retained in care at 12 months Malawi [Haas, CID 2016]: 30% of WLHIV in care had adequate adherence to 2 years post ART initiation in pregnancy South Africa [Myer, CID 2017]: 70% of WLHIV in care had sustained viral suppression to 12 months postpartum Factors associated with disengagement from care Younger age Same-day ART initiation Initiation late in pregnancy Post-partum period Fear of disclosure, stigma, social discrimination (emotional stresses) Logistical barriers to care finances, transportation, time commitment Postpartum life is complex for women living with HIV Women living with HIV deserve more than a quick-fix

18 Engagement in Care (Retention + Adherence) Infant loss to follow-up by age 3 months [Sibanda, AIDS 2013] Isoniazid Preventive Therapy for tuberculosis exposure Risk of developing TB disease is 50% following exposure in infancy Only 20-30% of TB-exposed infants complete 6 months of IPT [Marais, ADC 2006; van Zyl, IJTLD 2006] 66% of HIV-exposed infants retained in care at 3 months of age Infants at risk of HIV infection deserve more than a quick-fix

19 Should all HIV-exposed infants receive oral ARV prophylaxis for the entire duration of breastfeeding? 1 Is it safe?? 2 Is it more effective than current standard of care? 3 What is the opportunity cost (indirect harm)? 4 Reality check

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21 Should all HIV-exposed infants receive oral ARV prophylaxis for the entire duration of breastfeeding? 1 Is it safe?? 2 Is it more effective than current standard of care? 3 What is the opportunity cost (indirect harm)? 4 Reality check

22 We can do better than another quick-fix 1. Work harder at scaling up maternal ART where there are still gains to be made maximize the effect of maternal ART through longterm health system investments 2. Work harder to understand how to support WLHIV through the antenatal and postnatal periods differentiated models of postpartum care and targeted interventions 3. Advocate for structural, systemic changes congruent with the Sustainable Developmental Goal aspirations Benefits for families living with HIV

23 Should all HIV-exposed infants receive oral ARV prophylaxis for the entire duration of breastfeeding? NO

24 Acknowledgments Elaine Abrams Mark Cotton Mary Mahy Kate Powis Helena Rabie Elrie du Plooy

25 Should all HIV-exposed infants receive oral ARV prophylaxis for the entire duration of breastfeeding? 1 Is it safe?? 2 Is it more effective than current standard of care? 3 What is the opportunity cost (indirect harm)? 4 Reality check

26 Children are not continuing to become HIV infected because we are failing to give them infant PrEP, children are continuing to become HIV infected because we are failing their mothers Helena Rabie