Update on Breastfeeding and HIV studies Anna Coutsoudis Dept Paediatrics and Child Health

Breastmilk substitutes? HIV infected mothers have for many years been faced with an infant feeding dilemma Increased mortality Formula feeding HIV transmission Breastfeeding Breast feeding? Breastmilk substitutes? 2

Over the last 30 years the pendulum has swung from avoiding all breastfeeding to now encouraging breastfeeding. 2 key factors:

1. Reaffirmation of the importance of breastfeeding not only for child survival, but for infant health & development and maternal health Scaling up breastfeeding to near universal levels could prevent annually 823,000 under 5 deaths and 20,000 deaths from breast cancer. Other effects; reduced infections, increased intelligence, and probably reductions in obesity. Victora CG et al, Lancet 2016; 387: 475-90

2. Evidence that using Anti-Retroviral (ARV) drug prophylaxis to mothers or infants reduces HIV transmission

2010 guideline change – breastfeeding - option A or B Based on the accumulating evidence of ARV protection and breastfeeding benefits guidelines were changed to encourage breastfeeding in resource limited settings and either the infant (option A) or mother (option B) should receive ARV prophylaxis for about 12 months

WHO guidelines continued to change In 2013 Option A no longer recommended –Option B (until brf cessation) or B+ (lifelong prophylaxis) 2015 - lifelong ART recommended not only for pregnant and breastfeeding women but also for ALL people diagnosed with HIV Therefore, “options” seemed no longer valid and option B+ was encouraged for all Note: rationale behind option B+ not based on evidence of reduced PMTCT but rather on value of universal ART.

Further evidence… At the time of development of guidelines, majority of ARV prophylaxis studies included women who mostly only breastfed for 6 months Subsequently studies with 12 months of breastfeeding have confirmed very low tx rates whether ARVs given to mothers (Cohan et al) or infants (Kaletra or 3TC – Nagot et al).

Further evidence PROMISE STUDY 1ST study powered to directly compare option A vs option B breastfeeding duration > 12 months approx 2400 mother/infant pairs

PROMISE Study -median breastfeeding duration, 15 mths No signifcant difference between the 2 options; Tx rates 0.3% (6 mths); 0.5% (9mths); 0.6% (12 mths) – 18 mth date still to be published R a n d o m i z e Mother: Triple ARV Prophylaxis PROMISE is a complex protocol with three randomizations: The antepartum component during pregnancy, the post partum component during breastfeeding and the Maternal Health component following breastfeeding Infant NVP Prophylaxis

What about women in the developed world? Historically HIV infected mothers in the developed world were discouraged from breastfeeding and in the UK and US mothers potentially faced prosecution for breastfeeding. Following the clinical evidence of reduced transmission of HIV when a mother was on ARVs, the British HIV Association (BHIVA) published a revised position. Recommending that a virally suppressed woman on effective ARVs may after careful consideration choose to exclusively breastfeed for the first 6 months provided that she is fully adherent to her antiretroviral therapy and remains virally suppressed (Taylor 2011).

What about women in the developed world? In 2013 the American Academy of Pediatrics (AAP) followed suit applying similar rationale and reversing its previous stance against breastfeeding. The revised AAP guidelines recommend formula-feeding by HIV-infected mothers but similar to the UK they encourage clinicians to support mothers if they express any interest in breastfeeding.

Recent answer to previous question? Can HIV infected mothers produce sufficient breastmilk?

without compromising their own health. HIV infected women do produce adequate volumes of breastmilk for their infants Mulol et al, Breastfeeding Medicine 2016 Using an objective, deuterium oxide dose-to-mother technique, which measured the amount of breastmilk given to infants in the first year of life, HIV-infected mothers: produced sufficient volumes and comparable amounts to uninfected mothers. without compromising their own health.

When the first data on the protective effect of EBF for HIV transmission was published – Kuhn and Smith published a paper speculating on mechanisms – some recent data confirm these postulates of reduced gut inflammation-

Mechanisms behind EBF reducing risk of transmission Moodley-Govender, E. et al, Breastfeeding Medicine 2015

Remaining Questions? Long term side effects of ARV prophylaxis in infants and/or mothers? what is the best ARV combination for long term prophylaxis? – Tenofovir is currently one of the drugs used in most LMIC countries - evidence emerging of resistance and bone toxicity.

Other important questions:BF are low How do we assist mothers to adhere to ARVs long-term especially when they are well. (note infant prophylaxis should be used to compensate for maternal non-adherence)

Conclusion Huge strides in reducing HIV transmission during breastfeeding, and normalising breastfeeding for HIV infected women resulting in more concerted efforts in universal breastfeeding promotion. However, we must not forget the foundational strategy of reducing BRF tx viz. primary prevention of HIV in young women, and prevention of unplanned pregnancies in HIV infected women.