Louise Kuhn Gertrude H. Sergievsky Center & Department of Epidemiology,

1. HIV prevention is not enough: Update on protecting the health of children born to HIV-infected mothers in low resource settings Louise Kuhn Gertrude H. Sergievsky Center & Department of Epidemiology, Mailman School of Public Health Columbia University New York, NY

2. 100 Infants born to HIV positive Mothers 32 of these babies will become infected with HIV if mothers do not receive any PMTCT intervention • 20 of the 100 babies will become infected during pregnancy or delivery (in utero and peripartum transmission) • 12 of the 100 babies will become infected through breastfeeding (postnatal transmission) • 68 babies will remain uninfected

3. Timing of transmission No ARVs With ARVs Total Among infected

4. To breastfeed or not to breastfeed? Diarrhea Pneumonia Malnutrition Poor child spacing Spillover Stigma Death $$$$$ No HIV HIV Improved growth/development Less ID morbidity Maternal child bonding Child spacing Affordable

5. Bringing some “refinement” to thinking about breastfeeding All vs. Nothing Something vs. Something else Some vs. All

6. Benefits of exclusive breastfeeding on early postnatal transmission through 4 months 10.1% Non-exclusive BF 4.0% Exclusive BF P=0.002 Increased transmission due to non-exclusive BF: (as time-dependent) Relative Hazard 3.5 (95% CI: 1.7–7.2) PLOS ONE 2007; 2(12):e1363

7. Tell your friends … Breastfeeding can be made safer by breastfeeding exclusively in the first 6 months Tell your bosses …. Benefits of EBF are as big as benefits of short course ARVs. Put programs in place to add them together

8. Age-specific hazard rates of postnatal HIV transmission per month of breastfeeding in control group Non-EBF BF w CF (Non-EBF) EBF

9. Assumptions • It is safe to stop breastfeeding when the child is older “…breastfeeding should be discontinued as soon as is feasible.” • Replacement feeding can be made safe through providing formula, education, and cotrimoxazole • Abrupt cessation of breast feeding at the end of the period of exclusive breastfeeding is best because it avoids any period of mixed feeding • Advising women to end breastfeeding early will substantially reduce transmission

10. No benefit of early, abrupt cessation of breast feeding for HIV-free survival of children in Zambia N Engl J Med 2008; 359:130-41

11. Show me the data!

12. Overall HIV-free Survival among Children without HIV & still Breastfeeding at 4 Months of Age by Group Assignment No Benefit to Early Cessation of breastfeeding vs. Continued Breastfeeding Group A Group B P = 0.21

13. Observational study results are not always confirmed in clinical trials

14. Viral Load in Breast milk Obtained 2 wks after Cessation of Breastfeeding vs. Postpartum-matched Controls • Longitudinal analysis among • 29/31 “weaners” • Median VL copies: • Before – 353 • 2 wk after – 15,822 Thea et al. AIDS. 2006

15. Abrupt Weaning: No no no no pleeeeze do not recommend Elevations of breast milk viral load Mastitis occurs Breast milk exposures may still occur Breastfeeding is a behavior and an interaction

16. Benefits of continued breastfeeding after 4-6 months of exclusive breastfeeding Reductions in severe pneumonia Reductions in severe diarrhea Nutritious complement to generally poor family foods Child spacing Convenience Improved cognitive development

17. Predictors of uninfected infant mortality <4 months Adjusted Hazard ratio** (95% CI) ____________________________________________________________________________________________ Maternal CD4 count <350 vs. >350 2.87 (1.03 – 8.03) Maternal hemoglobin <10 vs. > 10 g/dL 2.37 (1.04 – 5.41) Mother died<4 month vs. survived 6.84 (2.65 –17.70) Birth weight <2,500g vs. >2,500g 2.43 (1.05 – 5.65) ____________________________________________________________________________________________ ** Calculated from Cox-Proportional Hazards model with all of the above factors in the model simultaneously Kuhn et al. Clin Infect Dis 2005 Dec 1;41:1654-61

18. Increased mortality among uninfected children 4-24 months if not breastfed

19. Risk factors for mortality among uninfected children 4-24 months

20. HIV-free Survival by feeding behaviors Better outcomes if breastfeeding was prolonged among healthier mothers (i.e. not meet criteria for ARVs) Continued BF P = 0.03 Stopped BF < 4 m

21. Survival of HIV-infected Children with Positive Results before 4 Months of Age by Group Assignment Early cessation of BF was Harmful to HIV-infected Children Group B Group A P = 0.01

22. Infant diagnosis offers opportunities to improve infant feeding counseling • For the uninfected child • Opportunity to encourage and support EBF • 8 weeks MUCH too early to stop breastfeeding • For the infected child • Strongly encourage continued breastfeeding well into the 2nd year • Relactation

23. Would you want to implement an expensive intervention that … Does not reduce the outcome of interest Is harmful in subgroups Is poorly accepted in the community where it was tested ? ?

24. What about keeping moms healthy to protect their babies? • Multiple studies have demonstrated that women with advanced HIV disease are at highest risk for transmitting HIV to their babies

25. Postnatal HIV transmission is strongly related to maternal CD4 count RR=12.8 RR=7.7 RR=3.3 < 200: 45% of postnatal infections < 350: 83% of postnatal infections

26. Prioritizing Pregnant and Lactating Women for HIV Treatmentto Enhance Exposed Infant HIV Free Survival Women with advanced disease are at highest risk for transmitting HIV to their infants during breastfeeding. Treating women with advanced disease with HAART should protect their babies from acquiring the virus. Need to ensure that women with advanced disease are retained in HIV care Keep lactating women not on HAART in postnatal care services and ensure regular monitoring of HIV disease stage

27. ART for Prevention of PMTCT during Breast Feeding • Studies are currently underway evaluating the efficacy of ART for prevention of postnatal transmission • HAART to women who do not qualify for treatment • NVP or other drugs to infant during breastfeeding • None evaluating regimens that extend for the full duration of breastfeeding

28. HIV prevention is not nearly enough Healthy children (HIV-free survival) Healthy mothers (prevent orphans)