HIV-Affected but not Infected

Transcription

1 HIV-Affected but not Infected The Dilemma of HIV-Exposed Uninfected Infants and Children Kate Powis, MD, MPH, MBA

2 Disclosures No financial conflicts or disclosures

3 Objectives HIV-exposed uninfected (HEU) child population HEU selected infant/child outcomes Mortality Morbidity Review HEU child health surveillance challenges

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6 Objectives HIV-exposed uninfected (HEU) child population HEU selected infant/child outcomes Mortality Morbidity Review HEU child health surveillance challenges

7 HIV+ Women by ARV Access in Pregnancy Total Estimated # of Pregnant Women Living with HIV Pregnant Women Living with HIV Women without ARV Use in Pregnancy Pregnant Women Living with HIV with ARV Use in Pregnancy UNAIDS-SPECTRUM 2016

8 HIV+ Women by ARV Access in Pregnancy & New HIV Infections among Children Pregnant Women Living with HIV Women without ARV Use in Pregnancy Pregnant Women Living with HIV with ARV Use in Pregnancy Newly HIV-Infected Children UNAIDS-SPECTRUM 2016

9 After climbing a great hill, one only finds that there are many more great hills to climb Nelson Mandela

10 Infants Born to Women Living with HIV by Infant HIV Status HIV Exposed Uninfected Infants HIV-Infected Infants New Child HIV+ HIV-Exposed Uninfected Children UNAIDS-SPECTRUM 2016

11 Infant born to Women Living with HIVby HIV and ARV status HIV & ARV Exposed Uninfected Infants HIV Exposed ARV Unexposed Uninfected Infants HIV-Infected Infants New Child HIV+ New Child HEU ARV- New HIV/ARV Exposed Infant UNAIDS-SPECTRUM 2016

12 Prevalence of Infant HIV & ARV In Utero Exposure Number of children under age : 7.1 million HEU under 5 year olds ~ 5.6 million also ARV-exposed HIV+ HEU ARV- HEU ARV+ UNAIDS-SPECTRUM 2016

13 Objectives HIV-exposed uninfected (HEU) child population HEU selected infant/child outcomes Mortality Morbidity Review HEU child health surveillance challenges

14 Elevated HEU Mortality Source: le Roux et al TMIH 2016;21: Source: Brennan et al AIDS 2016;30:

15 Elevated HEU Mortality Source: le Roux et al TMIH 2016;21: Source: Brennan et al AIDS 2016;30:

16 Elevated HEU Mortality RR birth 12 months: 1.8 (1.1, 2.8) RR months: 1.6 (1.1, 2.3) RR > 24 months: 1.7 (1.1, 2.6) Source: le Roux et al TMIH 2016;21: Source: Brennan et al AIDS 2016;30:

17 Botswana Child Mortality Bending the Curve

18 Botswana Child Mortality Bending the Curve Maikaelelo Study HEU Mortality Maikaelelo Study HU Mortality Zash et al.. BMC Pediatrics 2016;16:103 Lockman et al. Lancet Global Health 2017;5:e

19 Botswana Child Mortality Bending the Curve Maikaelelo Study HEU Mortality 47.3 Mpepu Study HEU Mortality Maikaelelo Study HU Mortality Zash et al.. BMC Pediatrics 2016;16:103 Lockman et al. Lancet Global Health 2017;5:e

20 Complexity of HEU Child Health Outcomes Disparities HEU Risk Areas Morbidity Mortality Growth Cognition Behavioral NCDs Adapted from Slogrove et al Pediatr Infect Dis J 2017;36:e38-e44

21 The Tsepamo Study Preterm Delivery by ARV Regimen 30% 16% 22% 19% 25% 24% 3,7% 4,1% 5,2% 5,9% 5.2% 9,0% *Models adjusted for maternal age, educational attainment and gravida Zash CROI 2017 Oral Presentation

22 The Tsepamo Study Small-for-Gestational-Age 25% 29% 28% 15% 17% 21% 5.4% 7,3% 11% 13% 14% 13% HIV- Unexposed (N=34,616) SGA arr* (95% CI) Very SGA arr* (95% CI) TDF/FTC/EFV (N=2,503) TDF/FTC/NVP (N=775) ZDV/3TC/NVP (N=1,403) TDF/FTC/LPV-r (N=237) ZDV/3TC/ LPV-r (N=169) ref 1.4 (1.2,1.7) 1.7 (1.5,1.9) 1.6 (1.3,2.0) 1.1 (0.8,1.6) ref 1.5 (1.2,1.9) 1.8 (1.4,2.2) 1.8 (1.3,2.6) 1.7 (1.1,2.6) *Models adjusted for maternal age, educational attainment and gravida Zash CROI 2017 Oral Presentation

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24 HEU Child and Lung Health Slogrove; Pediatric Respiratory Reviews 2017

25 HEU Child and Lung Health Slogrove; Pediatric Respiratory Reviews 2017

26 HEU Child and Lung Health Slogrove; Pediatric Respiratory Reviews 2017

27 HEU Child and Lung Health Slogrove; Pediatric Respiratory Reviews 2017

28 Passive Immunity to Respiratory Pathogens - Brazil Geometric mean (95% CI) antibody concentration (EU/ml) against Respiratory Viruses and Pneumococcus at Birth HIV Exposed Uninfected Infants HIV-Unexposed Infants Respiratory Infection Type N Concentration N Concentration P Value Influenza A (44, 63) (175, 222) < Respiratory Syncytial Virus (67, 90) (42, 59) Parainfluenza Virus (3, 6) (10, 13) < Parainfluenza Virus (6, 11) (22, 30) < Parainfluenza Virus (9, 15) (24, 29) < Pneumococcus (0.8, 0.9) (1.0, 1.2) < Pneumococcus 6B (0.6, 0.7) (0.7, 1.0) Pneumococcus (2.6, 3.1) (3.3, 4.4) Weinberg et al AIDS 2017;31:

29 HEU Children and Immune Abnormalities Afran et al; Clinical and Experimental Immunology 2013 doi: /cei.12251

30 Infant Viral Respiratory Infections and Outcomes South Africa Incidents Rates of Viral Lower Respiratory Tract Infections per 100,000 Population of Hospitalized Infants > 2 Days of Life but 6 Months of Life Viral Infection Type HIV Exposed Uninfected Infants Incident Rates (95% CI) HIV-Unexposed Infants Incident Rates (95% CI) Incidence RR All LRTIs 14,097 (13,252-14,982) 10,313 (9,858-10,784) 1.4 ( ) RSV 5003 (4,505-5,541) 3,507 (3,244-3,787) 1.4 ( ) Rhinovirus 4,581 (4,105-5,097) 3,074 (2,827-3,357) 1.5 ( ) Adenovirus 1,563 (1,291-1,8770 1,253 (1,097-1,424) 1.2 ( ) Enterovirus 1,196 (959-1,474) 680 ( ) 1.8 ( ) hmpv 816 (622-1,050) 573 ( ) 1.4 ( ) Influenza 503 ( ) 434 ( ) 1.2 ( ) Cohen et al Pediatrics 2016;e

31 Infant Viral Respiratory Infections and Outcomes South Africa Incidents Rates of Viral Lower Respiratory Tract Infections per 100,000 Population of Hospitalized Infants > 2 Days of Life but 6 Months of Life Viral Infection Type HIV Exposed Uninfected Infants Incident Rates (95% CI) HIV-Unexposed Infants Incident Rates (95% CI) Incidence RR All LRTIs Mortality 14,097 from (13,252-14,982) Viral Respiratory Infections in 10,313 the First (9,858-10,784) Six Months of Life 1.4 ( ) by Infant HIV-Exposure Status RSV 5003 (4,505-5,541) 3,507 (3,244-3,787) 1.4 ( ) HEU HUU Rhinovirus Infection Type 4,581 (4,105-5,097) Case Fatality Ratio Case Fatality 3,074 Ratio (2,827-3,357) OR (95% CI) 1.5 ( ) Adenovirus RSV 1,563 (1,291-1,8770 5/592 (2%) 0/5231,253 (0%) (1,097-1,424) 12.2 (1.7- ) 1.2 ( ) Enterovirus Influenza 1,196 (959-1,474) 2/28 (7%) 1/54 (2%) 680 ( ) 4.1 ( ) 1.8 ( ) hmpv Rhinovirus 816 (622-1,050) 7/288 (2%) 9/477 (2%) 573 ( ) 1.3 ( ) 1.4 ( ) Influenza Adenovirus 503 ( ) 3/119 (3%) 2/228 (1%) 434 ( ) 2.9 ( ) 1.2 ( ) hmpv 0/9 (0%) 1/86 (1%) 1.7 (0-64.5) Enterovirus 0/59 (0%) 2/76 (3%) 0.5 (0.6.9) Cohen et al Pediatrics 2016;e

32 Treatment Failure Mortality Pneumonia Treatment Failure/Mortality among HEUs Infants/Children in Botswana Botswana hospital based prospective cohort study of infants/children 1-23 months admitted for pneumonia 153 (64%) HIV-unexposed 64 (27%) HIV-exposed uninfected 8 (20%) HIV-infected Kelly et al. Journal of Pediatric Infectious Disease Society 2015;4:e

33 Treatment Failure Pneumonia Treatment Failure/Mortality among HEUs Infants/Children in Botswana HEU children experienced higher risk of treatment failure at 48 hours ALL [RR 1.83; 95% CI ; p=0.001] < 6 mos [RR 2.10; 95% CI ; p=0.001] Mortality HEU children experienced higher risk of inhospital mortality ALL [RR 4.31; 95% CI ; p=0.01] < 6 mos [RR 6.05; 95% CI ; p=0.0009] Kelly et al. Journal of Pediatric Infectious Disease Society 2015;4:e

34 HEU Children and Growth Botswana Studies In utero AZT Exposure Breastfed HEU Infants in the Mashi (n=303) and Mma Bana (n=516) studies In utero Triple ARV Exposure In utero exposure to triple ARVs compared with AZT monotherapy associated with lower mean length-for-age z-score at 24 months [-0.34; 95% CI to -0.15; p=0.0004] Powis et al AIDS 2016;30: Cross-sectional survey conducted in 5 health districts in Botswana enrolling caregiver-child pairs attending monthly under 5 well child clinics 67% of the excess risks of stunting in children 2 years of age attributable to birth weight < 2500 grams Sudfeld et al. JAIDS 2016;73: < 1 year HEU Children (n=100) HUU Children (n=283) 1 year to < 2 years HEU Children (n=109) HUU Children (n=282) 2 years to < 5 years HEU Children (n=187) HUU Children (n=544) Stunting Prevalence 20.0% 11.0% 22.9% 29.8% 31.0% 20.8% Multivariate Relative Risk of Stunting 1.91 ( ) REF 0.64 ( ) REF 1.42 ( ) REF P-value

35 HEU Children and Neurodevelopment AIDS PSYCHOLOGICAL CARE AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV 160 HEU and 167 HU children age and gender matched controls in the PREDICT Trial in Thailand and Cambodia age 2-15 years. HEU children with statistically lower scores in verbal IQ, full scale IQ, and Binet Bead Memory Conclusions: Small differences in some but not all neurodevelopmental outcomes among HEU children Unclear as to the immediate and long-term clinical significance Kerr et al AIDS Care 2014;26;

36 Objectives HIV-exposed uninfected (HEU) child population HIV-exposed uninfected infant/child outcomes Mortality Morbidity Review HEU child health surveillance challenges

37 Maternal ARV Use in Pregnancy over Time Canadian Perinatal HIV Surveillance Program Tenofovir Zidovudine Abacavir PIs NNRTIs INSTIs Courtesy of Dr. Jason Brophy

38 Zash CROI 2017 Oral Presentation Maternal ARV Use in Pregnancy over Time Botswana Research Data % of Women on ART from Conception Before 2012 PMTCT: WHO Option A - ZDV if CD4 >250 - ZDV/3TC/NVP if CD4 < PMTCT: WHO Option B -TDF/FTC/EFV (life-long if CD4 <350) TDF/FTC/EFV ZDV/3TC/NVP ZDV/3TC/LPV/r TDF/FTC/NVP TDF/FTC/LPV/r Other

39 HEU Health Disparities Etiology Matters

40 HEU Health Disparities Etiology Matters

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42 Establishing an HEU Child Outcomes Agenda Maternal-Child Health Care Infrastructure Bench Research Clinical Research Community Advocacy Ministry of Health & Public Health Policy

43 AIDS is clearly a disaster, effectively wiping out the development gains of the past decades and sabotaging the future. - President Nelson Mandela, South Africa

44 It always seems impossible until it is done Nelson Mandela FOR EVERY CHILD END AIDS Seventh Stocktaking Report, 2016

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46 Acknowledgements Elaine Abrams Jason Brophy Stanzi le Roux Lynne Mofenson Landon Myer Amy Slogrove