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 Antenatal (<36 wks) Late Antenatal (36 wks to labor) Late Postpartum (6-24 months) Early Postpartum (0-6 months) Adapted from N Shaffer, CDC 5-10% 10-20% Labor and Delivery

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

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

6 Technical Overview of HIV Transmission during Breastfeeding

7 Risk Factors For Postnatal Transmission 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 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 Pillay et al, 2000 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)

12 Prevalence of breast pathologies in HIV+ women in Africa Mastitis (clinical or 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 ( ) Kenya (John; overall) RR=3.9 ( ) Kenya (John; >=2 mo) RR=21.8 ( ) Malawi (Semba; overall) OR=2.3 ( ) 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 % 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 Coutsoudis et al, 1999; 2001 Cumulative HIV transmission Durban, SA

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 for 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 ( ) (Embree et al, 2000) –Cote d’ Ivoire: RR=5.0 ( ) (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 WHO Collaborative Study Team, 2000 Pooled Odds Ratios