Revised Guidelines for PMTCT and Infant Feeding in the Context of HIV Dr. A.K.GUPTA, MD (PEDIATRICS) OFICER ON SPECIAL DUTY DELHI STATE AIDS CONTROL SOCIETY

“We have effective drugs. There is no reason why any mother should die of AIDS. There is no cause for any child to be born with HIV If we work hard enough we can virtually eliminate mother-to-child transmission.” Ban Ki Moon UN Secretary-General

Risk of Mother-to-Child HIV Transmission Background transmission risk: 15-45% 15-30% Risk during pregnancy and delivery 10-20% Additional risk postpartum via breastfeeding Transmission risk with interventions: 20-30%No breastfeeding 15-25% Short-course ARV + breastfeeding 5-15% Short-course ARV, no BF <5% 2010 interventions, BF <2%2010 interventions, no BF

Duration, timing and complexity of ARV regimens to reduce MTCT Maternal triple ARV prophylaxis sd-NVP sc AZT + sd-NVPDaily Infant NVP Maternal therapeutic ART sc AZT + sd-NVP

Estimated number of new pediatric infections with and without PMTCT prophylaxis globally, UNAIDS, AIDS Epidemic Update ,000 infections averted in 2008

Rationale for Development of New 2010 PMTCT Recommendations New evidence on: Optimal timing and eligibility for ART initiation in HIV positive pregnant women Benefits of earlier initiation of ARV prophylaxis for PMTCT during pregnancy Effectiveness of different ARV prophylaxis strategies Effectiveness of ARV prophylaxis to mother or infants in reducing risk of HIV transmission during breastfeeding

Antiretroviral in Pregnancy- Key approaches Life-long ART for HIV-infected pregnant women in need of treatment ARV Prophylaxis to prevent HIV transmission from mother to child, for women who don’t require treatment for their own health

8 Benefit and Impact of Providing ART to Eligible Pregnant Women Pregnant women with CD4 <350: About 40% of HIV+ pregnant women Account for >75% of MTCT risk Account for >80% of postpartum transmission Account for 85% of maternal deaths within 2 years of delivery Strong benefit from initiating ART for maternal health and PMTCT during pregnancy, labour and delivery and breastfeeding

High MTCT Risk with CD4 <350 ZEBS study, Thea et al % of maternal deaths 82% of postnatal infections

ART Regimens 1 st Line2nd Line PreferredAZT+3TC+NVP(orEFV)TDF+3TC+LPV/r AlternativeTDF+3TC+NVP(orEFV)AZT+3TC+LPV/r If anemic (Hb<7Gm/L), replace the AZT-containing regimen with TDF (10% cases). If 1st trimester, do not use EFV-containing regimen: Use NVP Should be initiated on lifelong ART as soon as possible 1. Pregnant Women Eligible for ART (CD4<350) Baby receives daily NVP for 6 weeks after birth (breastfeeding or replacement feeding)

ARV prophylaxis to the mother or the baby from 1-6 weeks until 6-7 months post partum prevents HIV breastfeeding transmission Maternal Postpartum ARTInfant Postpartum ARV Mom AZT/3TC Mom AZT/ddI Adapted from Lynne Mofenson Mom AZT/3TC sdNVP

ARTRegimensforEligiblePregnantWomen st 1Line nd 2Line PreferredAZT+3TC+NVP(orEFV)TDF+3TC+LPV/r AlternativeTDF+3TC+NVP(orEFV)AZT+3TC+LPV/r If anemic (Hb<8.0g/L), replace the AZT-containing regimen with TDF If 1st trimester, do not use EFV-containing regimen: Use NVP If a pregnant women has CD4 ≤ 350, or is Stage III or IV, she should be initiated on lifelong ART as soon as possible 1. PMTCT Regimens for pregnant women eligible for ART Baby receives daily NVP for 6 weeks after birth (breastfeeding or replacement feeding) Note: It is generally better to use NVP instead of EFV in pregnant women (unless there are toxicities). These women are on ART for life and most will become pregnant again---if on EFV in 1 st trimester there is a risk of birth defects

11 Why it is important to ensure that eligible pregnant women (<350) are initiated on ART Pregnant women with CD4 ≤ 350 may account for: Approximately 40% of all HIV+ pregnant women Contribute to greater than 75% of overall transmission and greater than 80% of postpartum transmission 85% of maternal deaths within 2 years of delivery Due the high viral loads

**sd-NVP and AZT+3TC can be omitted if mother receives > 4 wks AZT antepartum Option AOption B Mother If CD4 >350 Ante partum AZT (from 14weeks) sdNVP+AZT/3TC* at delivery AZT/3TC for 7days post partum If CD4 ≤350: Lifelong ART Mother If CD4 >350 HAART from 14weeks of pregnancy Until 1week after breast feeding has stopped If CD4 ≤350:Lifelong ART Infant If breast feeding: daily NVP from birth until One wk after breast feeding has stopped If not breast feeding or mother on ART: NVP for 6wks Infant NVP for 6 weeks (regardless of Whether mother is breast feeding) ARV Prophylaxis in Pregnant Women Not eligible for ART (CD4 > 350)

Option A or Option B?  Both recommended options A and B provide significant reduction of the MTCT risk  There are advantages and disadvantages of both options, in terms of feasibility, acceptability and safety for mothers and infants, as well as cost  The choice for a preferred option should be made at a country level, after considering these advantages and disadvantages

ARV Prophylaxis Options ( India will soon adopt Option B) Option AOption B Mother Antepartum AZT (from 14 weeks) sd-NVP at onset of labour* AZT + 3TC during labour & delivery* AZT + 3TC for 7 days postpartum* Mother Triple ARV (from 14 wks until one wk after all exposure to breast milk has ended) – AZT + 3TC + LPV-r – AZT + 3TC + ABC – AZT + 3TC + EFV – TDF + 3TC or FTC + EFV Infant Breastfeeding population Daily NVP (from birth until one wk after all exposure to breast milk) Non-breastfeeding population AZT or NVP for 4-6 weeks Infant For all exposed infants AZT or NVP for 4-6 weeks *sd-NVP and AZT+3TC can be omitted if mother receives > 4 wks AZT antepartum

Rationale of the new Guidelines New Guidance is based on new evidence on: Benefits of earlier initiation of ARV prophylaxis during pregnancy in reducing mother-to-child transmission Effectiveness of ARV prophylaxis provided during breastfeeding in reducing mother-to-child-transmission Effectiveness of different ART regimens for children and adults Optimal timing and criteria for ART initiation in children & adults In response to this evidence, the World Health Organization (WHO) released new guidance for PMTCT, EID, ART & Infant Feeding, which the NACO, Ministry of Health, GOI has adapted for 40 districts

Summary of new Changes Prevention of Mother-to-Child Transmission (PMTCT): 1. ARV use for the HIV positive pregnant women Recommend initiation of ARVs earlier during pregnancy from 14 week of gestation 2. ARV use during Breast Feeding; Recommend ARV prophylaxis to either the baby or mother up to the end of all breastfeeding 3. Infant and Young Child Feeding (IYCF): Recommend HIV positive mothers to breastfeed for at least 12 months as long as the baby or mother is receiving ARV’s

Benefits of the New PMTCT policy guidelines AZT now started earlier in pregnancy—significantly reduces rates of intrauterine transmission Women receive prophylaxis for more of the transmission period AZT can now be started at the woman’s first visit Currently many women come before 28 weeks but don’t ever come back as a result they never receive ARVs for PMTCT Transmission through breastfeeding will decrease because the baby or mother will receiving ARV prophylaxis daily Mothers can breastfeed for a longer time because the baby is receiving NVP; hence contributing to “increased HIV free survival” through reduced HIV risk as well as morbidity and mortality from malnutrition

Infant Age NVP Daily Dose (10mg/ml formulation) Birth to 6 weeks Birth weight 2.0 to 2.5 kg 1ml once daily Birth weight>2.5 kg 1.5ml once daily >6 weeks to 6 months2ml once daily >6 months to 9 months3ml once daily >9 months to end of breast feeding 4ml once daily Dosing schedule for infant NVP prophylaxis

A cceptable Mother perceives no significant cultural or social barriers to replacement feeding F easible Mother has adequate knowledge, skills, resources, and support to correctly mix formula or milk, and feed the infant up to12 times in 24hours A ffordable Mother and family can pay the costs of replacement feeding—fuel, clean water, and all ingredients—without compromising the health and nutrition of the family. S ustainable Mother has access to a continuous and uninterrupted supply of all ingredients Needed for safe replacement feeding as long as the infant needs it S afe Replacement feeds are correctly and hygienically stored, prepared, and fed in nutritionally adequate amounts. Infant is fed by clean hands and preferably by cup AFASS Criteria for Replacement Feeding “AFASS” criteria is used to determine whether a mother is able to replacement feed NOTE: Currently options for replacement feeding include commercial infant formula and modified animal milk However, WHO recommended that animal milk should no longer be used for infants below 6 months.

Current Feeding Guidelines ( ) In the current feeding guidelines, HIV-positive mothers stop breastfeeding exposed infants at 6 months Mothers encouraged to EXCLUSIVELY BREASTFEED until 6 months of age if replacement feeding is not AFASS Mothers should wean over the course of 2 weeks If mothers cannot provide Sufficient animal milk at 6 months, they can continue to breastfeed while also introducing complementary feeds If mothers are able to meet the AFASS criteria at any time, encourage replacement feeding Infants confirmed HIV-positive should breastfeed exclusively for 6 months, & complementary feed until 24 months

HIV+ mothers are now urged to breastfeed for 12 months while the exposed baby (unknown status) receives ARV prophylaxis New Feeding Guidelines (2010) Mothers strongly recommended to exclusively breastfeeding until 6 months of age, and continue breastfeeding while introducing complementary feeds until 12 months of age If mothers cannot provide sufficient animal milk at 12 months, they can continue to breastfeed until able Exposed infants receive daily NVP prophylaxis until 1 week after cessation of breastfeeding Breastfeeding is the preferred feeding method. However, if mothers still desire to replacement feed, they can, if able to meet the AFASS criteria Infants confirmed HIV-positive should breastfeed exclusively for 6 months, & continue breastfeeding while adding in complementary feeds until 24 months

Rationale for the new infant feeding guidelines When mothers breastfeed for 6 months, and without ARV prophylaxis: Risk of HIV transmission is high, especially since many mothers mixed feed. However, if mothers replacement feed it will lead to malnutrition since most cannot meet AFASS criteria Risk of malnutrition after 6 months is high because many mothers can’t give their babies an adequate substitute Challenges of the Guidelines When mothers breastfeed for 12 months and with ARV PROPHYLAXIS: Risk of HIV transmission is reduced because ARV prophylaxis is provided throughout the breastfeeding period Risk of malnutrition is greatly reduced because babies are receiving breast milk for 12 months—by that age the baby has grown and the malnutrition risk is less Benefits of 2010 Guidelines However, if mother continue breastfeeding beyond 6 months, length of exposure to HIV is increased

The counseling messages given to mothers during antenatal changes with the new guidelines In the current guidelines ( ): Mothers are encouraged to breastfeed exclusively for 6 months and then stop; unless replacement feeding if AFASS In the new guidelines (2010): HIV+ mothers are strongly encouraged to breastfeed their exposed infants for 12 months while on ARV’s Exclusive BF until 6 months, complementary from 6-12 months Breastfeeding is no longer Just “necessary” but “critical” because of the nutritional need and because ARV prophylaxis now limits the risk of transmission However, if the mother still prefers to replacement feed after counseling, she can do so if AFASS criteria is met

Comprehensive approach to virtual elimination Childbearing Women living with HIV Pregnant women living with HIV HIV-infected children Prevent new infections Avoid unintended pregnancies Prevent MTCT

Estimated number of new pediatric infections with and without PMTCT prophylaxis globally, UNAIDS, AIDS Epidemic Update ,000 infections averted in 2008

3 Sets of Rapid Advice, Nov 2009

New 2010 WHO Guidelines Adult ART; PMTCT; HIV and Infant Feeding

Risk of Mother-to-Child HIV Transmission Background transmission risk: 15-45% 15-30% Risk during pregnancy and delivery 10-20% Additional risk postpartum via breastfeeding Transmission risk with interventions: 20-30%No breastfeeding 15-25% Short-course ARV + breastfeeding 5-15% Short-course ARV, no BF <5% 2010 interventions, BF <2%2010 interventions, no BF

PMTCT ARV Recommendations Refer to Two Key Approaches 1.Lifelong ART for HIV-positive pregnant women in need of treatment 2.Prophylaxis, or short-term provision of ARV's, to prevent HIV transmission from mother to child – During pregnancy – During breastfeeding (if breastfeeding is the best infant feeding option)

How long to breastfeed? In the presence of ARV interventions breastfeeding can continue to 12 months avoids many of the complexities associated with stopping breastfeeding provides a safe and adequate diet for infants 6-12 months of age

Research Questions Important operations research needed in the context of the new guidelines Safety of starting and stopping triple ARV prophylaxis Safety of extended prophylaxis during breastfeeding Comparison of Option A and Option B Improved access to CD4 testing Improved monitoring of regimens Assessment of proposed strategies to provide ART (lifelong) to all HIV-infected pregnant women Outcome measures, PMTCT impact at national level

Successful implementation of the new guidelines depends on: Universal HIV testing and counseling for pregnant women Availability of CD4 testing and ARVs at primary care level and in ANC where most maternal-child health care takes place, not just in specialized clinics Integration of PMTCT and MNCH; PMTCT and ART Improved follow-up of pregnant women antenatally and of mothers and HIV-exposed infants after birth Ability to provide prophylaxis to the mother or baby throughout breastfeeding Health systems strengthening Enhanced M&E, including impact assessment Implementation Challenges

Support for Country Implementation New guidelines need to be linked with active support for country adaptation, implementation and evaluation Regional workshops Support through Global Fund and PEPFAR Active IATT partner support at country level Tools for adaptation and implementation: Adaptation guide, FAQs, core slide set, M&E guide, monitoring of country progress, sharing of country guidelines, IMAI/IMPAC

Guiding Principles Women (including pregnant women) in need of ARV for their own health should get life-long ART Antenatal CD4 is critical for decision-making about ART eligibility Interventions should maximize reduction of vertical transmission, minimize side effects, and preserve future HIV treatment options Unify antepartum and postpartum approaches; strengthen mother and infant follow up Effective postpartum ARV-based interventions for all women will allow safer breastfeeding practices Different options may be appropriate in different settings

Summary: Benefits and Opportunities Revised 2010 guidelines – new norms and standards for highly effective interventions to: – Improve health of the mother – Decrease mother-child HIV transmission – Improve HIV-free survival Reduce transmission to <5% in breastfeeding populations and <2% in non-breastfeeding populations Make significant progress towards virtual elimination of paediatric HIV

THANK YOU WHO: Tin Tin Sint, Ying-Ru Lo, Nigel Rollins, Gottfried Hirnschall, MTCT Unit UN partner agencies: UNICEF, UNAIDS, UNFPA Expanded IATT partners: PEPFAR (CDC, USAID), GFATM, EGPAF, ICAP, FHI, CHAI, and many others New recommendations available at: