1. HIV/AIDS DEPARTMENT 2013 Consolidated ARV Guidelines Treatment Recommendations for Pregnant and Breastfeeding Women: Critical Issues Dr. Nathan Shaffer

2. Objectives of Presentation o Background o Overview of Key Recommendations: When to Start ART Breastfeeding What ART to Start o Issues and challenges

3. Progress and Barriers o Limited coverage and implementation of PMTCT and ART for pregnant women in many high burden countries ~ 1.4 million HIV+ pregnant women 65% PMTCT ARV coverage Limited ART in those eligible for treatment High loss to follow-up along PMTCT cascade Low ARV coverage during breastfeeding o Complexity of Option A Different treatment and prophylaxis regimens through pregnancy and breastfeeding Difficulty of long-term NVP dosing for infants Requirement for CD4 to determine eligibility Follow up along the PMTCT cascade is very low o Current approach needs to be optimized to achieve universal access and elimination 0 100 200 300 400 500 600 2009: ~430,000 infant infections 2012: ~290,000 infant infections 2015: Global Plan target <40,000 Steady progress reducing infant infections

4. Evolution of WHO PMTCT ARV Recommendations 20012006 2010 2004 Launch July 2013 PMTCT 4 weeks AZT; AZT+ 3TC, or SD NVP AZT from 28 wks + SD NVP AZT from 28wks + sdNVP +AZT/3TC 7days Option A (AZT +infant NVP) Option B (triple ARVs) Option B or B+ Moving to ART for all PW/BF ART No recommendation CD4 <200 CD4 <350CD4 <500 Move towards: more effective ARV drugs, extending coverage throughout MTCT risk period, and ART for the mother’s health

5. When to Start ART

6. Summary of Changes in Recommendations: When to Start in Adults

7. “Option B+” “Option B” “Option B+” “Option B” For programmatic and operational reasons, particularly in generalized epidemics, all pregnant and breastfeeding women infected with HIV should initiate ART as lifelong treatment. (conditional recommendation, low- quality evidence) For programmatic and operational reasons, particularly in generalized epidemics, all pregnant and breastfeeding women infected with HIV should initiate ART as lifelong treatment. (conditional recommendation, low- quality evidence) All pregnant and breastfeeding women infected with HIV should initiate triple ARVs (ART), which should be maintained at least for the duration of mother-to-child transmission risk. Women meeting treatment eligibility criteria should continue lifelong ART. (strong recommendation, moderate-quality evidence) In some countries, for women who are not eligible for ART for their own health, consideration can be given to stopping the ARV regimen after the period of mother-to-child transmission risk has ceased. (conditional recommendation, low- quality evidence) In some countries, for women who are not eligible for ART for their own health, consideration can be given to stopping the ARV regimen after the period of mother-to-child transmission risk has ceased. (conditional recommendation, low- quality evidence) Recommendations

8. Algorithms “Option B+” “Option B” “Option B+” “Option B”

9. Rationale: Shift from Option A to B+ or B Major issue now is not “when to start” or “what to start” but “whether to stop”

10. Programmatic considerations for B+ Initiate all HIV+ pregnant and breastfeeding women on ART Operational and programmatic advantages to lifelong ART for pregnant and breastfeeding women (“B+”), particularly in settings with: – Generalized epidemics – High fertility (though need to strengthen FP) – Long duration of breastfeeding – Limited access to CD4 to determine ART eligibility – High partner serodiscordance rates National programmes need to decide B or B+

11. ARVs and breastfeeding

12. WHAT ART REGIMEN TO START

13. Summary of Changes in Recommendations: What to Start in Adults

14. No increased risk of birth defects with EFV when compared with other ARVs Evidence Summary: Safety of EFV and TDF in Pregnancy o Systematic review (including Antiretroviral Pregnancy Registry), reported outcomes for 1502 live births to women receiving EFV in the first trimester and found no increase in overall birth defects o Excludes > 3 fold increased risk in overall birth defects o Systematic review (including Antiretroviral Pregnancy Registry), reported outcomes for 1502 live births to women receiving EFV in the first trimester and found no increase in overall birth defects o Excludes > 3 fold increased risk in overall birth defects Source: Ford N et al. AIDS, 2011. Ford N et al. AIDS, 2013. Ekouevi DK et al.J AIDS, 2011. WHO, Geneva Use of EFV during pregnancy. 2012. http://www.who.int/hiv/pub/treatment2/efavirenz/en Nightingale SL. JAMA, 1998. British HIV Association. Guidelines for the management of HIV infection in pregnant women. HIV Medicine. 2012. De Santis M et al. Arch of Int Medicine, 2002. Source: Antiretroviral Pregnancy Registry Steering Committee http://www.APRegistry.com Siberry GK et al. AIDS, 2012 EFV o Potential concerns include renal toxicity, adverse birth outcomes and effects on bone density o Systematic review assessed the toxicity of fetal exposure to TDF in pregnancy In Antiretroviral Pregnancy Registry, prevalence of all birth defects with TDF exposure in 1 st trimester was 2.4% (same as background) o Limited studies showed no difference in fetal growth between exposed/unexposed o No studies of TDF among lactating women, who normally have bone loss during breastfeeding o Current data reassuring o More extensive studies ongoing o Potential concerns include renal toxicity, adverse birth outcomes and effects on bone density o Systematic review assessed the toxicity of fetal exposure to TDF in pregnancy In Antiretroviral Pregnancy Registry, prevalence of all birth defects with TDF exposure in 1 st trimester was 2.4% (same as background) o Limited studies showed no difference in fetal growth between exposed/unexposed o No studies of TDF among lactating women, who normally have bone loss during breastfeeding o Current data reassuring o More extensive studies ongoing TDF

15. HOW TO MONITOR AND WHEN TO SWITCH

16. Recommendations: Monitoring ART Response Major challenge for PMTCT and MNCH settings: How to expand access to VL monitoring? How to utilize CD4 data, especially for women with high baseline CD4? Major challenge for PMTCT and MNCH settings: How to expand access to VL monitoring? How to utilize CD4 data, especially for women with high baseline CD4?

17. Implementation Issues Adequate planning for changes in guidelines Expansion and integration of ART into PMTCT sites —Supply chain for ARVs (avoidance of stock-outs) —Task-shifting for ART initiation —Adherence, retention, follow up, linkages with chronic ART —All MNCH sites become ART sites Access to ART monitoring Major challenge for PMTCT and MNCH settings: How to expand access to VL monitoring? How to utilize CD4 data, especially for women with high baseline CD4? Major challenge for PMTCT and MNCH settings: How to expand access to VL monitoring? How to utilize CD4 data, especially for women with high baseline CD4?

18. Key research questions: Pregnant Women

19. Transition in PMTCT Regimens in the 22 Global Plan Priority Countries After 2010 WHO PMTCT ARV guidelines As of June 2013 Rapid Change Towards B/B+

20. Summary Major paradigm shift; convergence of PMTCT and ART Simplified, harmonized approach for adults and pregnant women All pregnant and breastfeeding women with HIV should start first-line ART With Option B+, all pregnant women with HIV «eligible» for lifelong ART  1.4 million pregnant women with HIV annually Benefit for mother’s health, prevention of infant infections, prevention of partner infections

21. Acknowledgements Special thanks and acknowledgements to: Maternal and Child Health GDG Co-Chairs: Elaine Abrams (ICAP, Mailman School of Public Health, Columbia University, USA) and Denis Tindyebwa (ANECCA -- African Network for the Care of Children Affected by AIDS, Uganda) MCH GDG members, special contributors, peer reviewers Members of all the GDGs contributing to the consolidated guidelines WHO Secretariat