1. OVERVIEW OF PREVENTING MOTHER TO CHILD TRANSMISSION OF HIV
Frederick Morfaw (Regional Hospital Bamenda Cameroon) and Jason Brophy (CHEO, University of Ottawa)
19 July 2016

2. INTRODUCTION: Global Burden of HIV in pregnancy
In 2013, about 16 million of the total 35 million individuals living with HIV globally were women aged 15 years and older, and 3.2 million were children under 15 years of age (UNAIDS 2014).
More than 90% of HIV-positive pregnant women reside in sub-Saharan Africa (Kendall, 2014).
In 2013, 1.5 million HIV-infected women gave birth globally and there were new paediatric infections
amounting to one new child infected every two minutes (UNAIDS 2014).
HIV is the leading cause of death in women of reproductive age globally; responsible for 1/4 of deaths during pregnancy and postpartum period in sub- Saharan Africa (Kendall 2014)
HIV infection is a pandemic disease. Globally, about 35 million individuals were living with HIV in Of these, 24.7 million were in sub-Saharan Africa and 4.8 million in Asia and the Pacific (UNAIDS 2014).

3. INTRODUCTION
HIV can be transmitted from mothers to their infants during pregnancy, delivery and breastfeeding.
Without intervention, the risk of transmission is:
15−30% in non-breastfeeding populations
20−45% in breastfeeding mothers (WHO 2010).
Combination antiretroviral therapy (ART) and antiretroviral drug (ARV) prophylaxis interventions through prevention of mother-to-child transmission of HIV (PMTCT) programmes can prevent almost all of these infections.
PMTCT can reduce the risk of mother-to-child transmission of HIV (MTCT) to:
less than 5% in breastfeeding populations
less than 2% in non-breastfeeding populations (WHO 2010).

4. WHAT IS PMTCT????
Mother-to-child transmission (MTCT) accounts for over 90% of new HIV infections among children.
PMTCT includes all interventions to prevent transmission of HIV from a mother living with HIV to her infant during pregnancy, labour and delivery or during breastfeeding. It also improves mother’s health through early initiation of ART (WHO 2013)

5. TENETS OF PMTCT
There are four approaches to a comprehensive PMTCT strategy:
Primary prevention of HIV infection among women of childbearing age
Prevention of unintended pregnancies among women living with HIV
Prevention of HIV transmission from women living with HIV to their infants
Provision of appropriate treatment, care, and support to mothers living with HIV, their children and families.

6. HISTORY OF PMTCT DRUG REGIMENS
“Option A” – AZT for the mother during pregnancy, and single-dose NVP (sd-NVP) plus AZT and 3TC at delivery and for a week postpartum RECOMMENDED IN WHO 2010 GUIDELINES, REMOVED IN 2013
“Option B” – ART to mother only during the period of risk of mother-to- child transmission, with continuing lifelong ART only for those women meeting eligibility criteria for the treatment of non-pregnant adults
RECOMMENDED IN 2010, REMOVED IN 2015
“Option B+” – Lifelong ART to all pregnant and breastfeeding women, INTRODUCED IN MALAWI 2011, RECOMMENDED BY WHO IN 2012, PREFERRED IN 2015 [NO MORE “OPTIONs” MENTIONED]
Years of introduction

7. HISTORY OF PMTCT DRUG REGIMENS
“Option A” – AZT for the mother during pregnancy, and single-dose NVP (sd-NVP) plus AZT and 3TC at delivery and for a week postpartum RECOMMENDED IN WHO 2010 GUIDELINES, REMOVED IN 2013
“Option B” – ART to mother only during the period of risk of mother-to- child transmission, with continuing lifelong ART only for those women meeting eligibility criteria for the treatment of non-pregnant adults
RECOMMENDED IN 2010, REMOVED IN 2015
“Option B+” – Lifelong ART to all pregnant and breastfeeding women, INTRODUCED IN MALAWI 2011, RECOMMENDED BY WHO IN 2012, PREFERRED IN 2015 [NO MORE “OPTIONs” MENTIONED]
Years of introduction

8. GUIDELINES FOR PREGNANT AND BREASTFEEDING WOMEN LIVING WITH HIV
The 2015 guidelines recommend:
Lifelong antiretroviral treatment be provided to all pregnant and breastfeeding women living with HIV regardless of CD4 count or WHO clinical stage.
Treatment should be maintained after delivery and completion of breastfeeding for life.
[previously called Option B+, now the only recommendation]

9. WHY “OPTION B+”????
Providing ART to all pregnant and breastfeeding women living with HIV serves three synergistic purposes:
(1) improving individual health outcomes for mother
(2) preventing mother-to-child transmission of HIV (with maximum HIV-free survival of infants)
(3) preventing the horizontal transmission of HIV from the mother to an uninfected sexual partner
BONUS: program simplification
no special recommendations for pregnant women different from other adults
not reliant on CD4 measurement
clear messaging that ART is a lifelong treatment once started)

10. WHY “OPTION B+”????
Providing ART to all pregnant and breastfeeding women living with HIV serves three synergistic purposes:
(1) improving individual health outcomes for mother
(2) preventing mother-to-child transmission of HIV (with maximum HIV-free survival of infants)
(3) preventing the horizontal transmission of HIV from the mother to an uninfected sexual partner
BONUS: program simplification
no special recommendations for pregnant women different from other adults
not reliant on CD4 measurement
clear messaging that ART is a lifelong treatment once started)

11. ART REGIMENS First-line ART for pregnant and breastfeeding women
Two nucleoside reverse-transcriptase inhibitors (NRTIs) and a non- nucleoside reverse-transcriptase inhibitor (NNRTI).
Recommended: TDF + 3TC (or FTC) + EFV as a once-daily fixed-dose combination
Second-line ART should consist of two nucleoside reverse-transcriptase inhibitors (NRTIs) + a ritonavir-boosted protease inhibitor (PI).
That is : TDF + 3TC (or FTC) + ATV/r or LPV/r (If d4T or AZT was used in the first line regimen).  AZT + 3TC + ATV/r or LPV/r (if TDF was used in first-line ART)

12. GUIDELINES FOR HIV EXPOSED INFANTS
All infants born to HIV-positive mothers should receive ARV prophylaxis as soon as possible after birth.
The treatment should be linked to the mother's course of antiretroviral drugs and the infant feeding method.
Breastfeeding - the infant should receive once-daily nevirapine from birth for six weeks.
Replacement feeding - the infant should receive once-daily nevirapine (or twice-daily zidovudine) from birth for four to six weeks.

13. ADOPTION OF POLICY ON PMTCT IN LOW- AND MIDDLE-INCOME COUNTRIES, Global AIDS Response Progress Reporting (WHO, UNAIDS, UNICEF)

14. PMTCT COVERAGE BY REGION

15. PMTCT IN HIGH- vs LOW-RESOURCE COUNTRIES
WHO recommendations on use of ARVs in pregnant women follows a public health approach (WHO 2013), while in resource rich settings treatment is individualized (SOGC 2014)
The majority of cases of MTCT occur in sub-Saharan Africa, where high HIV prevalence among pregnant women combined with an under-resourced health-care infrastructure result in nearly 90% of the world’s children infected each year

16. SITUATION IN HIGH-RESOURCE COUNTRIES – EG. CANADA
Strong health-care infrastructure with universal HIV screening in pregnancy
Low HIV seroprevalence
Near-universal service coverage

17. SITUATION IN HIGH-RESOURCE COUNTRIES – EG. CANADA
Strong health-care infrastructure with universal HIV screening in pregnancy
Low HIV seroprevalence
Near-universal service coverage
The rate of transmission for mothers who received cART was 1% overall, and 0.4% if more than 4 weeks of cART was given
Canadian Perinatal HIV Surveillance Program, AIDS 2012

18. SITUATION IN LOW-RESOURCE COUNTRIES – EG. SUB-SAHARAN AFRICA
Fewer women have access to completely suppressive ARV regimens, elective Caesarean or safe alternatives to breastfeeding
Basic antenatal service access is far from universal
Breastfeeding remains an important route of transmission; however, benefits of replacement feeding in Africa are lost in the face of risks from not breastfeeding (diarrhea/pneumonia, malnutrition)

19. WHY THE DISPARITY BETWEEN HIGH- AND LOW-RESOURCE COUNTRIES IN PMTCT
Countries in general have good national-level policies on PMTCT, closely reflecting the guidelines provided by UNAIDS and the WHO
Yet the elimination of mother-to-child transmission is still lagging
The issue with PMTCT programs in sub-Saharan Africa is not one of convincing governments to pursue them, but rather of improving program effectiveness
Governments know that it is a priority focus area, but they do not necessarily have the resources to pursue PMTCT in the most effective way.!!!

20. KEY MESSAGE ON PMTCT IN LOW-RESOURCE COUNTRIES
How to improve PMTCT implementation to greater success?
By improving the ability of governments to measure their epidemics, track their patients, and promote the use of this data in revising program implementation.

21. RESEARCH AND PRAGMATIC QUESTIONS IN LOW-RESOURCE COUNTRIES
Research on the areas that improve governments’ capabilities to better implement context-specific interventions, ie, improving the monitoring and evaluation of programs.
How do we better collect and use data on mothers and children?
How do we encourage and enable women - especially pregnant women and new mothers – to engage with health services?
Any commitment to reducing infections in children and keeping them HIV free for their entire lives must start with a strong focus on the health, health-related knowledge, and empowerment of women
Pragmatic or Programmatic Questions?

22. RESEARCH AND PRAGMATIC QUESTIONS IN LOW- AND HIGH-RESOURCE COUNTRIES
What are the safest and most effective regimens for PMTCT?
PIs and prematurity; tenofovir and bone health; efavirenz and neurotoxicity
Long-term safety of in utero and breastfeeding ARV exposure in infants
Evidence of immunologic defects; questions about neurodevelopment, bone health, early aging
Safety of new drugs/formulations in pregnancy, and how to implement them on a population level including pregnant women?
TLE400 (reduced dose efavirenz), dolutegravir, TAF

23. CONCLUSION
The virtual elimination of MTCT of HIV is possible (Cuba, Belarus, Armenia!!)
“Option B+” is the recommended ART strategy
The burden of disease in far greater in low-resource than in high-resource countries
This has created different settings with different (but overlapping) pragmatic and research questions

24. THANKS !!!!!