HIV and Infant Feeding:

1. HIV and Infant Feeding: Knowledge, Gaps, and Challenges for the Future by Ellen G. Piwoz Jay Ross Academy for Educational Development

2. Overview of the Presentation • Context of the presentation • Overview of HIV transmission during breastfeeding • risk factors • timing of transmission • feasibility of feeding alternatives • Challenges for the future

3. Timing of Mother-to-Child HIV Transmission with Breastfeeding and No ARV Early Postpartum (0-6 months) Late Postpartum (6-24 months) Early Antenatal (<36 wks) Laborand Delivery Late Antenatal (36 wks to labor) 5-10% 10-20% 10-20% Adapted from N Shaffer, CDC

4. MTCT in 100 HIV+ Mothers by Timing of Transmission 63 uninfected 15 15 7

5. Major causes of death among children under five, world, 2000 Deaths associated with undernutrition 60% EIP/WHO; Caulfield et al, forthcoming

6. Technical Overview of HIV Transmission during Breastfeeding

7. Mother Immune status Plasma viral load Breast milk virus Breast infection (mastitis, abscess, bleeding nipples) New HIV infection Viral Characteristics Infant Breastfeeding duration Non-exclusive BF Age (first months) Lesions in mouth, intestine Prematurity Infant immune response Risk Factors For Postnatal Transmission WHO, 1998; Bulterys et al, 2002; Newell et al, 2002

8. How does HIV transmission during breastfeeding occur? • Exact mechanisms unknown • HIV virus in blood passes to breast milk • cell-free, cell-associated virus observed • virus shed intermittently (undetectable ~ 25-35%) • levels vary between breasts in samples taken at same time (Willumsen et al, 2001) • Infant consumes HIV • enters/infects through permeable mucosal surfaces, lymphoid tissues, lesions in mouth, intestine • Although BF infant may consume >500,000 virons, >25,000 infected cells per day, majority don’t become infected (Lewis et al, 2001) • immune factors in BM may play a role (Sabbaj et al, 2002)

9. Risk factors for postnatal transmission: Maternal immune status Leroy et al 2002

10. Risk factors for postnatal transmission: Maternal viral load • Viral RNA is an important predictor of intra-partum MTCT(Leroy et al, 2001; Semba et al, 1999; Thea et al, 1997) • Plasma viral load may also be a risk factor during breastfeeding • 29% transmission risk among women infected postnatally (Dunn et al, 1992) • risk of infection after 2 months associated with plasma viral load > 43k copies/ml (John et al, 2001) (OR=2.6) • predicted MTCT by 12 months, after taking into account maternal immune status, Na+ in breast milk (Semba et al, 1999) (Adj OR=1.71 log HIV load)

11. Risk factors for postnatal transmission:Breast milk viral load BM viral load was consistently higher in women with low CD4 counts (p<0.01). BM RNA was associated with increased MTCT, after adjusting for maternal CD4 (OR=2.82) Pillay et al, 2000

12. Prevalence of breast pathologies in HIV+ women in Africa • Mastitis (clinical/sub-clinical): • Clinical exam: 7-11% (Embree, 2000; John et al, 2001) • Na+/K > 1.0: 11-12% at 6, 14 wk (Willumsen et al, 2000) • Na+ > 12 mmol/L: 16.4% at 6 wk (Semba et al, 1999) • Nipple lesions: • Clinical exam: 11-13% (Embree, 2000; John et al, 2001) • Clinical exam: 10% (Ekpini et al, 1997) • Hospitalized infants: 11% (Kambarami et al, 1997) • Breast abscesses: • Clinical exam: 12% (John et al, 2001) • Clinical exam: 3% (Ekpini et al, 1997)

13. Risk factors for postnatal transmission:Breast health -1 • Sub-clinical mastitis is associated with higher viral load in BM (Willumsen et al, 2000; Semba et al, 1999) • Mastitis is associated with increased risk of postnatal transmission: Kenya (Embree; > 3 mo) OR=2.3 (1.1-5.0) Kenya (John; overall) RR=3.9 (1.2-12.7) Kenya (John; >=2 mo) RR=21.8 (2.3-211) Malawi (Semba; overall) OR=2.3 (1.2-4.3) Malawi (Semba; > 6 wk) RR=3.7 (NS) • Nipple lesions and breast abscesses also associated with increased transmission

14. Risk factors for postnatal transmission:Breast health -2 • 18-20% of overall MTCT may be attributable to mastitis (estimated from mastitis prevalence and adjusted risk estimates): • 18% of all transmission in first year in Malawi (Semba et al, 1999) • 20% of transmission up to 2 years (John et al, 2001) • If BF accounts for 40% of all transmission, then mastitis (breast health problems) may be the cause of 50% all postnatal transmission (20/40)

15. Risk factor for postnatal transmission: Duration of breastfeeding • Risk of transmission persists for as long as breastfeeding is practiced • Some studies indicate that the risk of HIV transmission may be higher in the first 6 months of life(Miotti et al, 1999; Nduati et al, 2000; John et al, 2001) • Several possible explanations • higher prevalence of mastitis, breastfeeding problems • infant gut more immature, vulnerable/permeable • more breast milk consumed

16. Postnatal transmission of HIV:Duration of breastfeeding Ghent meta-analysis -2(Read et al, 2002) Cumulative rates of late postnatal HIV infection (> 4 wks)

17. What about HIV transmission during the first month of breastfeeding? Monthly Risk of MTCT during Early Breastfeeding (<2 months)

18. Postnatal transmission of HIV: Pattern of breastfeeding Cumulative HIV transmission Durban, SA Coutsoudis et al, 1999; 2001

19. Infant mortality among children born to HIV+ mothers by early feeding pattern (0-3 months) in Harare, Zimbabwe (n=2,892)Tavengwa et al, 2002 Adjusted HR: BM+NHM vs EBF = 5.97 (p < 0.001); Predominant BF vs EBF=2.52 (p=0.04); Partial BF vs EBF=2.84 (p=0.02)

20. Risk factors for postnatal transmission: Infant oral lesions • Disruption of the skin or mucous membranes in mouth and intestine believed to increase the risk of HIV transmission during breastfeeding • epithelial integrity affected by nutritional deficiencies, infection • feeding pattern, mastitis did not effect intestinal permeability (Rollins et al, 2001; Willumsen et al, 2000) • Infant oral thrush associated with increased risk of postnatal transmission • Kenya: OR=2.8 (1.3-6.2) (Embree et al, 2000) • Cote d’ Ivoire: RR=5.0 (0.5-39.8) (Ekpini et al, 1997)

21. Infant Feeding Options for HIV+ Mothers

22. WHO recommendations on infant feeding for HIV+ women “When replacement feeding is acceptable, feasible, affordable, sustainable and safe, avoidance of all breastfeeding by HIV-infected mothers is recommended. Otherwise, exclusive breastfeeding is recommended during the first months of life. To minimize HIV transmission risk, breastfeeding should be discontinued as soon as feasible, taking into account local circumstances, the individual woman’s situation and the risks of replacement feeding (including infections other than HIV and malnutrition).” New Data on the Prevention of Mother-to-Child Transmission of HIV and their Policy Implications: Conclusions and Recommendations (WHO 2001)

23. How Can Families Decide? -1 • What is meant by ACCEPTABLE? • There are social and cultural norms about infant feeding. • Concerns about stigma associated women who do not breastfeed, suspicion of HIV • What is meant by FEASIBLE? • There are economic, behavioral, psycho-social aspects for care-giver and infant • Resources and skills are required

24. How Can Families Decide? -2 • What is meant by SUSTAINABLE? • It must be practiced every day and night • Resources must be available throughout • It should be exclusive over first 6 months • What is meant by SAFE? • Free from contamination • Nutritious • Free from stigma • Does not spillover to general population

25. Infants who do not breastfeed have an increased risk of dying in the first year of life Pooled Odds Ratios WHO Collaborative Study Team, 2000

26. Risk of mortality is greater among women without access to hygiene, sanitation,water RR of Infant Mortality by Feeding Mode and Health Environment Habicht et al., 1988

27. Percent of Total Population with Access to Safe Water UNICEF, 2002

28. Percent of Total Population with Access to Adequate Sanitation UNICEF, 2002

29. Breastfeeding exclusive breastfeeding heat-treated breast milk wet-nursing milks banks early cessation of breastfeeding (as soon as feasible) Replacement feeding commercial infant formula home prepared infant formula (modified, with additional nutrients) enriched family diet with BMS/MN supplements after 6 months Feeding Options Currently Recommended by WHO (1998)

30. What do we know about the feasibility of exclusive breastfeeding? (BFHI/MCH/IMCI) -1 % infants breastfed exclusively in previous 24 hours @ 3 months @ 5 months < 6 months < 4 months

31. EBF rates at 6 weeks - over time and after the introduction of an education and counseling program on safer breastfeeding practices in Harare, Zimbabwe (n=9,931) Education and counseling intervention began ZVITAMBO data

32. Exclusive breastfeeding rates in PMTCT programs with infant feeding counseling - Barcelona AIDS abstracts Methodologies and ages at measurement varied

33. Methods used for measuring exclusive breastfeeding produce different rate estimates n=970 mothers exposed to infant feeding counseling ZVITAMBO data

34. Potential risks for infant Dehydration Anorexia Later behavior problems Malnutrition Illness or death Potential risks for mother Engorgement Mastitis Increased risks of pregnancy Depression Stigma Possible reversion to breastfeeding What do we know about the feasibility of early/rapid breastfeeding cessation? -1 Piwoz et al, 2002

35. What do we know about the feasibility of early breastfeeding cessation?-2 Barcelona AIDS Conference • Early, rapid cessation is possible (Uganda, Zambia, Botswana) • Problems encountered • breast engorgement; mastitis; babies crying, trouble sleeping, appetite loss, diarrhea; financial constraints with replacement feeding; family objections • more problems when cessation < 6 months (Botswana) • Trained counselors were able to help mothers overcome problems • Provision of replacement feeds, family support facilitated process • Impact on HIV transmission, survival not yet known

36. Breast milk contributes > 50% of the nutrient intake of children > 6 months in developing countries and won’t be easy to replace Adapted from WHO, 1998; Dewey and Brown, 2002 using data from Bangladesh, Ghana, Guatemala, Peru

37. What do we know about the feasibility of other breastfeeding options? • Heat-treated breast milk • heating milk to 56-62.5 degrees C for 12-15 min inactivates HIV in human milk (Jeffreys et al 2001) • no data on feasibility of daily use from birth • may be practical during transition period with early cessation • Use of wet nurse - no data • monitoring HIV status of wet nurse a challenge • practice may be less common because of HIV • Milk banks - no data • may be feasible in some settings (Brazil, LA Region)

38. What do we know about the feasibility of commercial formula? • High acceptance/adherence in some countries with access to clean water, health care, subsidized cost • Thailand, Brazil, South Africa, Botswana • Adherence with exclusive use may be higher than for exclusive BF (Botswana) • Stigma associated with its use widely reported in Africa • Access to safe water, health care needed • Proper instruction on safe preparation, feeding • Cost - > 6 months supply

39. Formula use in selected programs where providedfree Barcelona AIDS Conference

40. Uptake of Infant Formula in PMTCT program sites in SA McCoy et al, 2002

41. Evidence of Spillover?Infant feeding patterns in PMTCT vs.non-PMTCT sites in Botswana (< 6 months, 24 hr recall) EBF is lower, mixed feeding is higher in PMTCT sites P< 0.001 MOH/UNICEF, 2002

42. What do we know about the feasibility of home prepared formula? • Nutritional adequacy and cost studied in KwaZulu Natal, SA • Fresh and powdered full-cream milk • Findings: • intakes of vitamins E, C, folic acid, pantothenic acid < 33% of adequate intake (AI) • intakes of zinc, copper, selenium, vitamin A < 80% AI • intakes of EFA were < 20-60% AI • cost was $9.80/month or 20% of average monthly income • preparation time was 20-30 minutes for 120 ml Papathakis et al, 2002

43. Challenges for the Future • Policy issues: • Can we reframe the debate on breastfeeding versus replacement feeding? • What is the role of commercial infant formula? • Implementation: • How do we implement October 2000 guidance/scale up? • Research: • Risk analysis and counseling hampered by uncertainty • Can breastfeeding or replacement feeding be made safer for HIV+ women? • Learning from ALL our experience

44. Can we reframe our thinking and discussion on this issue? -1 • Let’s talk about improving HIV-free survival instead of reducing HIV transmission • reflects higher objective • resolves conflicting strategies • Let’s talk about reducing postnatal transmission instead of HIV transmission through breastfeeding • more accurate • less emotional • less burdened with the weight of history

45. Can we reframe our thinking and discussion on this issue? -2 • Focus on maternal health & nutrition • Keeping HIV+ mothers well may be among the most important things we can do to prevent P/N transmission • BF transmission was ~2% between 6 w-24 months in WA study among women with CD4 >500 (Leroy et al, 2002) • Nutrition depletion, weight loss during BF may increase risk of maternal mortality (Nduati et al, 2001) • Keeping mothers alive will improve child’s chances for survival (Nduati et al, 2001) • ARV use during BF now being studied

46. What is the role of commercial formula for replacement feeding? • It is the best option for RF if conditions can be met • formulated specially for humans, nutritionally fortified • safe water, access to health care, training in safe preparation, feeding required to make it safe • postnatal follow-up also required (monitor growth/other outcomes, ensure adequate access/availability) • cost will make it NOT affordable for poor families to purchase • cost may make it NOT sustainable for governments • Code of Marketing of BMS protects against misuse if enacted/enforced • But “spillover” may be unavoidable if BF support for HIV-negative and status unknown mothers is not adequate

47. Can we make breastfeeding safer for HIV+ women? -1 • Enhance health/nutrition care for all women • Provide adequate lactation counseling and support, involving families/communities • increase adherence to exclusive breastfeeding • promote good breastfeeding techniques • prevent cracked nipples, maintain breast health • Immediate treatment for mastitis, other systemic infections that could affect viral load in BM • could prevent a sizeable fraction of BF transmission • may be most important in early month(s)

48. Can we make breastfeeding safer for HIV+ women? -2 • Assist families with early breastfeeding cessation • assess health status of mother and infant • prepare for the process so that the transition is safe (cup-feeding, safe preparation/hygiene, stigma) • heat treat breast milk if weaning is gradual • could prevent sizeable fraction of BF transmission • Provide adequate nutrition after breastfeeding ends • appropriate breast milk substitutes and/or multi-nutrient supplements should be provided to prevent malnutrition

49. HIV and Infant Feeding Risk Analysis in Setting where IMR=89/1000: Improving maternal health & safer BF practices Assumptions: 1000 live births; 20% prevalence; 20% transmission before & during delivery, healthy mother, EBF, lactation management (SBF+HM) reduces postnatal transmission by 67%; IMR=89/1000

50. HIV and Infant Feeding Risk Analysis in Setting where IMR=100/1000: Improving maternal health & safer BF practices Assumptions: 1000 live births; 20% prevalence; 20% transmission before & during delivery, healthy mother, EBF, lactation management (SBF+HM) reduces postnatal transmission by 67%;