1. Mitchell J. Besser, MD Founder and Medical Director mothers 2 mothers 14 December 2010 mothers 2 mothers: Preventing Mother-to-Child HIV Transmission in Africa Using New Paradigms in Health Care Delivery

2. Population HIV Prevalence Zimbabwe South Africa Botswana Senegal Mali

3. Life Expectancy: 1950-2005 with high HIV prevalence : Zimbabwe South Africa Botswana with low HIV prevalence: Madagascar Senegal Mali Source: UN Department of Economic and Social Affairs (2001) World Population Prospects, the 2000 Revision . 1950– 1955 1955- 1960 1960- 1965 1965- 1970 1970- 1975 1975- 1980 1980- 1985 1985- 1990 1990- 1995 1995- 2000 2000- 2005 30 35 40 45 50 55 60 65 Life expectancy (years)

5. Global HIV Prevalence 33.3 million living with HIV in 2010 Sub-Saharan Africa 22.4 million

6. 90% of HIV-positive pregnant women are in Sub-Saharan Africa 1.4 million pregnant women in low- and middle-income countries are infected with HIV

7. Towards Universal Access, WHO, 2009 Grim Inequities Prevalence in Pregnancy Nigeria 2.4 - 4% South Africa 29% US and UK 0.6% Adult Prevalence Nigeria 3% South Africa 18% US and UK 0.3 - 0.6% PMTCT Coverage Nigeria 10% South Africa 73% US and UK > 95% ARV Coverage (children) Nigeria 12% South Africa 61% US and UK > 95%

8. Pediatric HIV infections in U.S. 80% decline CDC PACTG 076 – AZT treatment starts

9. Siripon Kanshana, 2007 Pediatric HIV infections in Thailand 80% decline HIV testing PMTCT ARVs National PMTCT program

10. UNAIDS estimates 2008 Pediatric HIV infections in World

11. 1100 children infected per day in 2008

12. ≈ 1000 in Africa <1 in the US 1 in Europe 100 in Asia & the Pacific

13. Annual pregnancies in HIV-positive women United States (7000) Rwanda (8000) South Africa (300,000) Baragwanath Hospital (8000) (Soweto)

14. PMTCT Cascade Gap = Missed Opportunities

15. Reducing the Risk: Treatment PMTCT Treatment Transmission Rate at 6 Weeks No Treatment 25% Single-dose Nevirapine (sdNVP) 12% AZT (28 weeks) + sdNVP 3% HAART 1%

18. HIV Infected Babies Myth of the 80s Reality of the 80s NVP: 12% 183 146 AZT+NVP: 3% 137 73 HAART: 1% 127 57

19. HIV Infected Babies Myth of the 80s Reality of the 80s NVP: 12% 183 146 AZT+NVP: 3% 137 73 HAART: 1% 127 57

20. Four Prongs of PMTCT Prevention of unintended pregnancies among HIV infected women Preventing mother to child transmission of HIV Primary prevention of HIV infection in women Provision of care and support for HIV infected mothers, their infants, partners and families

21. Incident HIV Challenges and Responses

22. Discordant /concordant Couple Status – Discordance Predominates Country Ratio Data Source Ethiopia 6 :1 DHS-05 Tanzania 3 :1 AIS 03/04 Kenya 2 :1 DHS-03 Uganda 2 :1 AIS-04/5

23. If man is HIV+ and in a couple… Couple Status – Discordance Predominates Country … % Woman HIV + Data Source Ethiopia 27% DHS-05 Tanzania 37% AIS 03/04 Uganda 55% AIS-04/5 Kenya 57% DHS-03

25. T Creek, personal communication 2008 Impact of Incident HIV Infection in Pregnancy A study in Botswana showed: Among women testing negative in early pregnancy: Botswana National PMTCT program transmission data show: Extrapolating incident HIV to the national Botswana figures : Incident HIV is thus estimated to account for 470/1090 (43%) of all infant infections in 2007 1.3% were infected in 17 weeks before delivery 1.8% were infected in the first year after delivery 13,900 HIV+ women infected estimated 620 infants (4.7%) Estimate 950 women acquired HIV during pregnancy or first postpartum year, and infected 470 infants

26. Feeding the Baby

28. Am J Epidem 1995 Timing of HIV Transmission (non Breastfeeding cohort)

29. Months 0 5 10 15 20 25 30 35 1 12 18 % HIV infected Transmission Cumulative 4% Transmission of HIV for every 6 months of breast-feeding 6 -3 Delivery Timing of HIV Transmission Delivery

30. Infant Feeding and HIV Transmission Infant Age Coutsoudis,13th AIDS Conf, 2000 8% 7% 7% 19% 19% 26% 0 10 20 30 % Transmission 1 Day 6 Mos Never Breastfed (N=157) Exclusive Breastfed (N=118) Mixed Feeding (N=276)

31. Exclusive Breastfeeding in HIV+ Women in Clinical Trials in Resource-Poor Countries

34. HIV Infection through Age 7 Months is Higher in Breast Fed than Formula Fed Infants p=0.04 Thior I et al. JAMA 2006;296:794-805 7 Months

35. Mortality through Age 7 Months is Higher in Formula Fed than Breast Fed Infants p=0.004 Predominant causes infant death: Diarrheal disease and pneumonia 7 Months

36. No Difference in 18-Month HIV-Free Survival Between Formula Fed and Breast Fed Infants p=0.41 Thior I et al. JAMA 2006;296:794-805 18 Months

37. No Difference in 18-Month HIV-Free Survival Between Formula Fed and Breast Fed Infants p=0.41 Thior I et al. JAMA 2006;296:794-805 18 Months FF: 33 infected, 46 deaths BF: 54 infected, 34 deaths

38. BAN: Probability HIV positive or death by week 28 visit in infants uninfected at birth BAN Study: Probability of HIV+ or Death by 28 week visit in infants uninfected at birth Age (weeks) Probability HIV positive or death 1 4 8 12 16 20 24 28 0.00 0.02 0.04 0.06 0.08 Control vs Maternal HAART: p= 0.03 7.6% 4.7% 2.9% Control – No ARVs Maternal HAART Infant NVP

39. BAN: Probability HIV positive or death by week 28 visit in infants uninfected at birth BAN Study: Probability of HIV+ or Death by 28 week visit in infants uninfected at birth 7.6% 4.7% Age (weeks) Probability HIV positive or death 1 4 8 12 16 20 24 28 0.00 0.02 0.04 0.06 0.08 Control vs Maternal HAART: p= 0.03 7.6% 4.7% 2.9% Control – No ARVs Maternal HAART Infant NVP

40. BAN: Probability HIV positive or death by week 28 visit in infants uninfected at birth BAN Study: Probability of HIV+ or Death by 28 week visit in infants uninfected at birth 7.6% 2.9% Age (weeks) Probability HIV positive or death 1 4 8 12 16 20 24 28 0.00 0.02 0.04 0.06 0.08 Control vs Infant NVP: p <0.0001 7.6% 4.7% 2.9% Control – No ARVs Maternal HAART Infant NVP

41. BAN: Probability HIV positive or death by week 28 visit in infants uninfected at birth BAN Study: Probability of HIV+ or Death by 28 week visit in infants uninfected at birth 4.7% 2.9% Age (weeks) Probability HIV positive or death 1 4 8 12 16 20 24 28 0.00 0.02 0.04 0.06 0.08 Maternal HAART vs Infant NVP: p= 0.07 7.6% 4.7% 2.9% Control – No ARVs Maternal HAART Infant NVP

42. Integrating HIV into the push for MDGs 4 & 5 GOAL 4: REDUCE CHILD MORTALITY GOAL 5: IMPROVE MATERNAL HEALTH GOAL 6: COMBAT HIV/AIDS, MALARIA & OTHER DISEASES Target 1: Have halted by 2015 and begun to reverse the spread of HIV/AIDS Target 2: Achieve, by 2010, universal access to treatment for HIV/AIDS for all those who need it Target 1: Reduce by two thirds, between 1990 and 2015, the under-five mortality rate Target 1: Reduce by three quarters the maternal mortality ratio Target 2: Achieve universal access to reproductive health HIV / AIDS

43. Magical Thinking Health Systems

44. Global HIV Prevalence

45. Doctors Working in the World Sub-Saharan Africa: 25% of global disease burden 3% of world ’s health workers

46. http://www.hst.org.za/uploads/files/cahp9_07.pdf Staffing Ratios Health care workers per 100,000 population (2007) Region/Country Physicians Nurses United States 256 937 South Africa 77 408 Botswana 40 265 Zambia 12 174 Zimbabwe 16 72 Lesotho 5 62 Mozambique 3 21

47. http://www.hst.org.za/uploads/files/cahp9_07.pdf Staffing Ratios Health care workers per 100,000 population (2007) Region/Country Physicians Nurses United States 256 937 South Africa 77 408 Botswana 40 265 Zambia 12 174 Zimbabwe 16 72 Lesotho 5 62 Mozambique 3 21

48. SA Population (2009): 49 million population dependent on public health sector health professionals in public sector 85% 44 % 10% vacant posts in public health sector Doctors Nurses 36% 34% 30%

49. Has only minutes per patient 1) Counsel for HIV test 2) Perform HIV test, explain results 3) Dispense single dose nevirapine, 4) Explain how to take 5) Discuss infant feeding options 6) Reinforce exclusive infant feeding 7) Perform infant HIV test at 12-months, 8) Explain results PMTCT Program Interventions: In 2001… Transmission Rates: 14-16% Nurse:

50. Still has only minutes per patient 1) Counsel for HIV test 2) Perform HIV test, explain results 3) Perform CD4 test, get and explain results. Refer for HAART if CD4<350 4) Dispense cotrimoxazole 5) Discuss infant feeding options 6) Dispense AZT (from 14 weeks), explain how to take 7) Dispense HAART (if eligible), explain how to take 8) Counsel on adherence to HAART 9) Screen for HAART related toxicity 10) Reinforce exclusive infant feeding 11) Where ARVS for breast feeding are available, explain how to use 12) Perform infant HIV test at 6 weeks, 13) Explain results 14) Refer mother to follow-up care, 15) Encourage her to attend 16) RH/FP PMTCT Program Interventions: In 2010 … Transmission Rates: 2-5% Nurse:

51. ...

52. mothers 2 mothers

54. Goal 3. Empowerment Goal 2. Healthy mothers and infants Three m 2 m goals: Goal 1. PMTCT

58. m 2 m services

59. task-shifting

61. Site Management Plan MM MM MM MM SC MM SC Tertiary Care Hospital Primary Health Center Site Systems Regional or District Program Manager SC = Site Coordinator MM = Mentor Mother

62. Community Outreach Community Outreach Community Outreach Satellite Health Centres Hospital or Major HC Site System

67. CD4 and HAART uptake among m 2 m antenatal clients (N=1246) Antenatal m2m clients CD4 Tests CD4 Results CD4 <350 HAART

68. CD4 and HAART uptake among m 2 m antenatal clients by number of visits (N=1246)

70. Baby HIV Testing Tool Baby HIV Test Card Resources Developed for Study

72. Cellphone Subscribers - 2009 North America: 276m Africa: 358m

73. Non-ACFU Sites n = 204 ACFU Sites n=214 Eligible 8 week call Yes =179 (84%), No =35 (16%) Eligible 10 week call & home visit Yes =53 (32%), No =114 (68%) * Of 167 consenting for home visit 10 week home visit Reached =24 (45%) Not Reached = 22 (42%) Excluded/too far = 7 (13%) Early Infant Diagnosis Study

74. Non-ACFU Sites n = 204 ACFU Sites n=214 Eligible 8 week call Yes =179 (84%), No =35 (16%) Eligible 10 week call & home visit Yes =53 (32%), No =114 (68%) * Of 167 consenting for home visit 10 week home visit Reached =24 (45%) Not Reached = 22 (42%) Excluded/too far = 7 (13%) 60% reached by phone (108) Early Infant Diagnosis Study

75. Non-ACFU Sites n = 204 ACFU Sites n=214 Eligible 8 week call Yes =179 (84%), No =35 (16%) Eligible 10 week call & home visit Yes =53 (32%), No =114 (68%) * Of 167 consenting for home visit 10 week home visit Reached =24 (45%) Not Reached = 22 (42%) Excluded/too far = 7 (13%) Early Infant Diagnosis Study

76. Non-ACFU Sites n = 204 ACFU Sites n=214 Eligible 8 week call Yes =179 (84%), No =35 (16%) Eligible 10 week call & home visit Yes =53 (32%), No =114 (68%) * Of 167 consenting for home visit 10 week home visit Reached =24 (45%) Not Reached = 22 (42%) Excluded/too far = 7 (13%) Early Infant Diagnosis Study

77. Non-ACFU Sites n = 204 ACFU Sites n=214 Eligible 8 week call Yes =179 (84%), No =35 (16%) Eligible 10 week call & home visit Yes =53 (32%), No =114 (68%) * Of 167 consenting for home visit 10 week home visit Reached =24 (45%) Not Reached = 22 (42%) Excluded/too far = 7 (13%) 11% of total (214) reached by home visit Early Infant Diagnosis Study

78. Early Infant Diagnosis Study (N = 55,13) (N = 115,167) p < 0.01

79. Early Infant Diagnosis Study (N = 55,13) (N = 115,167) p < 0.01

80. Early Infant Diagnosis Study (N = 55,13) (N = 115,167) * Of those with known test results

81. mothers & babies communities healthcare systems Demand and Supply Side:

82. South Africa M2M2B - 2001

83. South Africa Malawi Ethiopia Kenya Rwanda Zambia Swaziland Lesotho Botswana Uganda Mozambique ??? Tanzania m 2 m 2010

84. m 2 m Today

85. Total HIV-positive pregnant women enrolled: 20% of the global disease burden m 2 m Activities 2010 Current Date Nov-10 Sites 703 Field Staff 1766 Patient Encounters Per Month 267,103 New HIV-positive Women Per Month 22,111

86. Helping Mothers Saving Babies