Revised Guidelinesfor 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 HIVIf we work hard enough we can virtually eliminate mother-to-child transmission.”

Ban Ki MoonUN Secretary-General

Risk of Mother-to-Child HIV Transmission

Background transmission risk: 15-45%15-30% Risk during pregnancy and delivery10-20% Additional risk postpartum via breastfeeding

Transmission risk with interventions:20-30% No breastfeeding15-25% 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-NVP Daily Infant NVP

Maternal therapeutic ART

sc AZT + sd-NVP

Estimated number of new pediatric infections with and without PMTCT prophylaxis globally, 1996-2008

UNAIDS, AIDS Epidemic Update2009

70,000 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

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 <350ZEBS study, Thea et al. 2008

0% 10% 20% 30% 40% 50%

<200

200-350

350-500

>500

CD

4 C

ount

Percent Transmission

In Utero Intrapartum-Early Postpartum Postpartum

3.9 4.5 1.9

3.5

7.6

7.6 15.5

7.3

2.3

20.8

13.3

7.4

84% of maternal deaths82% of postnatal infections

ART Regimens1st Line 2nd Line

Preferred AZT+3TC+NVP(orEFV) TDF+3TC+LPV/rAlternative TDF+3TC+NVP(orEFV) AZT+3TC+LPV/rIf 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

0.9% 0.6% 1.1% 0.6%

3.0%

1.2% 0.8%1.8%

4.4%

2.3%

0%

2%

4%

6%

8%

10%

% M

TCT

6 M

onth

s

MitraPlus

Amata KIBS DREAM BAN Mitrainfant(3TC)

SIMBA(NVP)

BAN(NVP)

SWEN(NVP)

PEPI-Malawi(NVP)

Maternal Postpartum ART Infant Postpartum ARV

Mom AZT/3TC

Mom AZT/ddI

Adapted from Lynne MofensonMom

AZT/3TCsdNVP

ARTRegimensforEligiblePregnantWomenst1Line

nd2Line

Preferred AZT+3TC+NVP(orEFV) TDF+3TC+LPV/rAlternative TDF+3TC+NVP(orEFV) AZT+3TC+LPV/rIf anemic (Hb<8.0g/L), replace the AZT-containing regimen with TDFIf 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 beinitiated on lifelong ART as soon as possible

1. PMTCT Regimens for pregnant womeneligible 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 aretoxicities). These women are on ART for life and most will become pregnant again---if onEFV in 1st trimester there is a risk of birth defects

11

Why it is important to ensure that eligible pregnantwomen (<350) are initiated on ART

Pregnant women with CD4 ≤ 350 mayaccount for:Approximately 40% of all HIV+ pregnant womenContribute to greater than 75% of overall transmissionand greater than 80% of postpartum transmission85% 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 A Option B

MotherIf CD4 >350•Ante partum AZT (from 14weeks)•sdNVP+AZT/3TC* at delivery•AZT/3TC for 7days post partumIf CD4 ≤350: Lifelong ART

MotherIf CD4 >350•HAART from 14weeks of pregnancyUntil 1week after breast feeding hasstoppedIf CD4 ≤350:Lifelong ART

Infant•If breast feeding: daily NVP from birth untilOne wk after breast feeding has stopped•If not breast feeding or mother on ART:NVP for 6wks

Infant•NVP for 6 weeks (regardless ofWhether 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 A Option 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

InfantBreastfeeding population• Daily NVP (from birth until one

wk after all exposure to breast milk)

Non-breastfeeding population• AZT or NVP for 4-6 weeks

InfantFor 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 GuidelinesNew Guidance is based on new evidence on:

• Benefits of earlier initiation of ARV prophylaxis during pregnancy inreducing mother-to-child transmission

• Effectiveness of ARV prophylaxis provided during breastfeeding inreducing 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, whichthe NACO , Ministry of Health, GOI has adapted for 40 districts

Summary of new ChangesPrevention of Mother-to-Child Transmission (PMTCT):

1. ARV use for the HIV positive pregnant womenRecommend initiation of ARVs earlier during pregnancy from14 week of gestation

2. ARV use during Breast Feeding;Recommend ARV prophylaxis to either the baby or mother upto 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 reducesrates 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 aresult they never receive ARVs for PMTCT

Transmission through breastfeeding will decrease because thebaby or mother will receiving ARV prophylaxis dailyMothers can breastfeed for a longer time because the baby isreceiving NVP; hence contributing to “increased HIV freesurvival” through reduced HIV risk as well as morbidity andmortality from malnutrition

Infant Age NVP Daily Dose(10mg/ml formulation)

Birth to6 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 months 2ml once daily>6 months to 9 months 3ml once daily>9 months to end of breast feeding

4ml once daily

Dosing schedule for infant NVP prophylaxis

Acceptable Mother perceives no significant cultural or social barriers to replacement feeding

Feasible Mother has adequate knowledge, skills, resources, and support to correctly mix formula or milk, and feed the infant up to12 times in 24hours

Affordable 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.

Sustainable Mother has access to a continuous and uninterrupted supply of all ingredients Needed for safe replacement feeding as long as the infant needs it

Safe 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 amother is able to replacement feed

NOTE: Currently options for replacement feeding include commercial infantformula and modified animal milk

However, WHO recommended that animal milk should no longer be used forinfants below 6 months.

Current Feeding Guidelines (2006-2009)

In the current feeding guidelines, HIV-positive mothersstop breastfeeding exposed infants at 6 months

Mothersencouraged to EXCLUSIVELY BREASTFEED until 6 months of age ifreplacement feeding is not AFASS

Mothers should wean over the course of 2 weeksIf mothers cannot provide Sufficient animal milk at 6 months, they can continue tobreastfeed while also introducing complementary feeds

If mothers are able to meet the AFASS criteria at any time, encouragereplacement 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 whilethe 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 until12 months of age

If mothers cannot provide sufficient animal milk at 12 months, they can continue tobreastfeed until able

Exposed infants receive daily NVP prophylaxis until 1 week after cessation ofbreastfeeding

Breastfeeding is the preferred feeding method. However, if mothers stilldesire to replacement feed, they can, if able to meet the AFASS criteriaInfants 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 givetheir babies an adequate substitute

Challenges of the 2006-2009 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 breastmilk 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 exposureto HIV is increased

The counseling messages given to mothers during antenatal changes with the new

guidelines In the current guidelines (2006-2009):

Mothers are encouraged to breastfeed exclusively for 6 monthsand then stop; unless replacement feeding if AFASS

In the new guidelines (2010):HIV+ mothers are strongly encouraged to breastfeed theirexposed infants for 12 months while on ARV’s

Exclusive BF until 6 months, complementary from 6-12 monthsBreastfeeding is no longer Just “necessary” but “critical”because of the nutritional need and because ARV prophylaxisnow limits the risk of transmissionHowever, if the mother still prefers to replacement feed aftercounseling, she can do so if AFASS criteria is met

Comprehensive approach to virtual elimination

Childbearing Women

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, 1996-2008

UNAIDS, AIDS Epidemic Update2009

70,000 infections averted in 2008

3 Sets of Rapid Advice, Nov 2009

New 2010 WHO GuidelinesAdult ART; PMTCT; HIV and Infant Feeding

http://www.who.int/hiv/en/

Risk of Mother-to-Child HIV Transmission

Background transmission risk: 15-45%15-30% Risk during pregnancy and delivery10-20% Additional risk postpartum via breastfeeding

Transmission risk with interventions:20-30% No breastfeeding15-25% 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 QuestionsImportant 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:

http://www.who.int/hiv/en/