HIV-exposed, uninfected infants: new global challenges in the era of paediatric HIV elimination

The Lancet Infectious Diseases

Volumn 16, Issue 6, 2016, Pages e92-e107

  Evans, Ceri ^a,b   Jones, Christine E ^c   Prendergast, Andrew J ^a,b,d  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^b Zvitambo Institute for Maternal and Child Health Research   (Zimbabwe)

^c ST GEORGE S HOSPITAL   (United Kingdom)

^d JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COTRIMOXAZOLE; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; NEVIRAPINE; ZIDOVUDINE; ANTIVIRUS AGENT;

CHILD GROWTH; CHILD HOSPITALIZATION; DEVELOPED COUNTRY; DIARRHEA; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HIV TEST; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HUMORAL IMMUNITY; INFANT; INFANT FEEDING; INFANT MORTALITY; MIXED INFECTION; MORTALITY RATE; OPPORTUNISTIC INFECTION; PNEUMOCYSTIS PNEUMONIA; PRIORITY JOURNAL; REVIEW; SUSCEPTIBLE POPULATION; SUSTAINABLE DEVELOPMENT; TUBERCULOSIS; VACCINATION; VERTICAL TRANSMISSION; VIRAL CLEARANCE; AFRICA; DRUG EFFECTS; FEMALE; HIV INFECTIONS; IMMUNE SYSTEM; IMMUNOLOGY; NEWBORN; PREGNANCY; PREGNANCY COMPLICATIONS, INFECTIOUS; PREVENTION AND CONTROL; RISK FACTOR; STATISTICS AND NUMERICAL DATA; TRANSMISSION;

AFRICA; ANTIVIRAL AGENTS; FEMALE; HIV INFECTIONS; HUMANS; IMMUNE SYSTEM; INFANT; INFANT, NEWBORN; INFECTIOUS DISEASE TRANSMISSION, VERTICAL; PREGNANCY; PREGNANCY COMPLICATIONS, INFECTIOUS; RISK FACTORS;

EID: 84961914011     PISSN: 14733099     EISSN: 14744457     Source Type: Journal    
DOI: 10.1016/S1473-3099(16)00055-4     Document Type: Review

References (161)

1. 1 Datta, P, Embree, JE, Kreiss, JK, et al. Mother-to-child transmission of human immunodeficiency virus type 1: report from the Nairobi Study. J Infect Dis 170 (1994), 1134–1140.
2. 2 Shapiro, RL, Kitch, D, Ogwu, A, et al. HIV transmission and 24-month survival in a randomized trial of HAART to prevent MTCT during pregnancy and breastfeeding in Botswana. AIDS 27 (2013), 1911–1920.
3. 3 Forbes, JC, Alimenti, AM, Singer, J, et al. A national review of vertical HIV transmission. AIDS 26 (2012), 757–763.
4. 4 WHO. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach, 2013, World Health Organization, Geneva http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf (accessed July 28, 2015).
5. 5 UNAIDS. Global plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive, 2011, Joint United Nations Programme on HIV/AIDS (UNAIDS), Geneva http://www.unaids.org/sites/default/files/media_asset/20110609_JC2137_Global-Plan-Elimination-HIV-Children_en_1.pdf (accessed July 28, 2015).
6. 6 Embree, JE, Datta, P, Stackiw, W, et al. Increased risk of early measles in infants of human immunodeficiency virus type 1-seropositive mothers. J Infect Dis 165 (1992), 262–267.
7. 7 Thea, DM, St Louis, ME, Atido, U, et al. A prospective study of diarrhea and HIV-1 infection among 429 Zairian infants. N Engl J Med 329 (1993), 1696–1702.
8. 8 Marinda, E, Humphrey, JH, Iliff, PJ, et al. Child mortality according to maternal and infant HIV status in Zimbabwe. Pediatr Infect Dis J 26 (2007), 519–526.
9. 9 Koyanagi, A, Humphrey, JH, Ntozini, R, et al. Morbidity among human immunodeficiency virus-exposed but uninfected, human immunodeficiency virus-infected, and human immunodeficiency virus-unexposed infants in Zimbabwe before availability of highly active antiretroviral therapy. Pediatr Infect Dis J 30 (2011), 45–51.
10. 10 Brahmbhatt, H, Kigozi, G, Wabwire-Mangen, F, et al. Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda. J Acquir Immune Defic Syndr 41 (2006), 504–508.
11. 11 Sutcliffe, CG, Scott, S, Mugala, N, et al. Survival from 9 months of age among HIV-infected and uninfected Zambian children prior to the availability of antiretroviral therapy. Clin Infect Dis 47 (2008), 837–844.
12. 12 Spira, R, Lepage, P, Msellati, P, et al. Natural history of human immunodeficiency virus type 1 infection in children: a five-year prospective study in Rwanda. Mother-to-Child HIV-1 Transmission Study Group. Pediatrics, 104, 1999, e56.
13. 13 Schim van der Loeff, MF, Hansmann, A, Awasana, AA, et al. Survival of HIV-1 and HIV-2 perinatally infected children in The Gambia. AIDS 17 (2003), 2389–2394.
14. 14 Rollins, NC, Ndirangu, J, Bland, RM, Coutsoudis, A, Coovadia, HM, Newell, ML, Exclusive breastfeeding, diarrhoeal morbidity and all-cause mortality in infants of HIV-infected and HIV uninfected mothers: an intervention cohort study in KwaZulu Natal, South Africa. PLoS One, 8, 2013, e81307.
15. 15 Chopra, M, Doherty, T, Goga, A, Jackson, D, Persson, LA, Survival of infants in the context of prevention of mother to child HIV transmission in South Africa. Acta Paediatr 99 (2010), 694–698.
16. 16 Shapiro, RL, Lockman, S, Kim, S, et al. Infant morbidity, mortality, and breast milk immunologic profiles among breast-feeding HIV-infected and HIV-uninfected women in Botswana. J Infect Dis 196 (2007), 562–569.
17. 17 Chilongozi, D, Wang, L, Brown, L, et al. Morbidity and mortality among a cohort of human immunodeficiency virus type 1-infected and uninfected pregnant women and their infants from Malawi, Zambia, and Tanzania. Pediatr Infect Dis J 27 (2008), 808–814.
18. 18 Moraleda, C, de Deus, N, Serna-Bolea, C, et al. Impact of HIV exposure on health outcomes in HIV-negative infants born to HIV-positive mothers in Sub-Saharan Africa. J Acquir Immune Defic Syndr 65 (2014), 182–189.
19. 19 Marquez, C, Okiring, J, Chamie, G, et al. Increased morbidity in early childhood among HIV-exposed uninfected children in Uganda is associated with breastfeeding duration. J Trop Pediatr 60 (2014), 434–441.
20. 20 Cutland, CL, Schrag, SJ, Zell, ER, et al. Maternal HIV infection and vertical transmission of pathogenic bacteria. Pediatrics 130 (2012), e581–e590.
21. 21 Landes, M, van Lettow, M, Chan, AK, Mayuni, I, Schouten, EJ, Bedell, RA, Mortality and health outcomes of HIV-exposed and unexposed children in a PMTCT cohort in Malawi. PLoS One, 7, 2012, e47337.
22. 22 Slogrove, A, Reikie, B, Naidoo, S, et al. HIV-exposed uninfected infants are at increased risk for severe infections in the first year of life. J Trop Pediatr 58 (2012), 505–508.
23. 23 Mussi-Pinhata, MM, Freimanis, L, Yamamoto, AY, et al. Infectious disease morbidity among young HIV-1-exposed but uninfected infants in Latin American and Caribbean countries: the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study. Pediatrics 119 (2007), e694–e704.
24. 24 Slogrove, AL, Cotton, MF, Esser, MM, Severe infections in HIV-exposed uninfected infants: clinical evidence of immunodeficiency. J Trop Pediatr 56 (2010), 75–81.
25. 25 Hoffmann, KS, Green, RJ, Candida perforation of the intestine in an HIV-exposed but uninfected infant. SAJCH 8 (2014), 119–121.
26. 26 Izadnegahdar, R, Fox, MP, Jeena, P, Qazi, SA, Thea, DM, Revisiting pneumonia and exposure status in infants born to HIV-infected mothers. Pediatr Infect Dis J 33 (2014), 70–72.
27. 27 McNally, LM, Jeena, PM, Gajee, K, et al. Effect of age, polymicrobial disease, and maternal HIV status on treatment response and cause of severe pneumonia in South African children: a prospective descriptive study. Lancet 369 (2007), 1440–1451.
28. 28 Kelly, MS, Wirth, KE, Steenhoff, AP, et al. Treatment failures and excess mortality among HIV-exposed, uninfected children with pneumonia. J Pediatric Infect Dis Soc 4 (2015), e117–e126.
29. 29 Karpelowsky, JS, Millar, AJ, van der Graaf, N, van Bogerijen, G, Zar, HJ, Outcome of HIV-exposed uninfected children undergoing surgery. BMC Pediatr, 11, 2011, 69.
30. 30 von Mollendorf, C, Cohen, C, de Gouveia, L, et al. Risk factors for invasive pneumococcal disease among children less than 5 years of age in a high HIV prevalence setting, South Africa, 2010 to 2012. Pediatr Infect Dis J 34 (2015), 27–34.
31. 31 von Mollendorf, C, von Gottberg, A, Tempia, S, et al. Increased risk for and mortality from invasive pneumococcal disease in HIV-exposed but uninfected infants aged <1 year in South Africa, 2009–13. Clin Infect Dis 60 (2015), 1346–1356.
32. 32 Zash, R, Shapiro, RL, Leidner, J, et al. The aetiology of diarrhoea, pneumonia and respiratory colonization of HIV-exposed infants randomized to breast- or formula-feeding. Paediatr Int Child Health, 2015, 10.1179/2046905515Y.0000000038 published online June 8.
33. 33 Hsiao, NY, Zampoli, M, Morrow, B, Zar, HJ, Hardie, D, Cytomegalovirus viraemia in HIV exposed and infected infants: prevalence and clinical utility for diagnosing CMV pneumonia. J Clin Virol 58 (2013), 74–78.
34. 34 Heresi, GP, Caceres, E, Atkins, JT, Reuben, J, Doyle, M, Pneumocystis carinii pneumonia in infants who were exposed to human immunodeficiency virus but were not infected: an exception to the AIDS surveillance case definition. Clin Infect Dis 25 (1997), 739–740.
35. 35 Jeena, PM, Bobat, B, Thula, SA, Adhikari, M, Children with Pneumocystis jiroveci pneumonia and acute hypoxaemic respiratory failure admitted to a PICU, Durban, South Africa. Arch Dis Child, 93, 2008, 545.
36. 36 Morrow, BM, Hsaio, NY, Zampoli, M, Whitelaw, A, Zar, HJ, Pneumocystis pneumonia in South African children with and without human immunodeficiency virus infection in the era of highly active antiretroviral therapy. Pediatr Infect Dis J 29 (2010), 535–539.
37. 37 Morrow, BM, Samuel, CM, Zampoli, M, Whitelaw, A, Zar, HJ, Pneumocystis pneumonia in South African children diagnosed by molecular methods. BMC Res Notes, 7, 2014, 26.
38. 38 Paul, ME, Chantry, CJ, Read, JS, et al. Morbidity and mortality during the first two years of life among uninfected children born to human immunodeficiency virus type 1-infected women: the women and infants transmission study. Pediatr Infect Dis J 24 (2005), 46–56.
39. 39 Bekker, A, Du Preez, K, Schaaf, HS, Cotton, MF, Hesseling, AC, High tuberculosis exposure among neonates in a high tuberculosis and human immunodeficiency virus burden setting. Int J Tuberc Lung Dis 16 (2012), 1040–1046.
40. 40 Carina M, Chamie G, Achan J, et al. Tuberculosis infection in early childhood in Uganda and the influence of HIV exposure. Conference on Retroviruses and Opportunistic Infections; Boston, MA; March 3–6, 2014.
41. 41 van Eijk, A, Brooks, JT, Adcock, PM, et al. Diarrhea in children less than two years of age with known HIV status in Kisumu, Kenya. Int J Infect Dis 14 (2010), e220–e225.
42. 42 Taron-Brocard, C, Le Chenadec, J, Faye, A, et al. Increased risk of serious bacterial infections due to maternal immunosuppression in HIV-exposed uninfected infants in a European country. Clin Infect Dis 59 (2014), 1332–1345.
43. 43 Epalza, C, Goetghebuer, T, Hainaut, M, et al. High incidence of invasive group B streptococcal infections in HIV-exposed uninfected infants. Pediatrics 126 (2010), e631–e638.
44. 44 Adler, C, Haelterman, E, Barlow, P, Marchant, A, Levy, J, Goetghebuer, T, Severe infections in HIV-exposed uninfected infants born in a European country. PLoS One, 10, 2015, e0135375.
45. 45 Larsen E, Lunding S, Helleberg M, et al. Hospitalizations among uninfected children exposed or unexposed to HIV—a nationwide cohort study. Conference on Retroviruses and Opportunistic Infections; Seattle, WA, Feb 23–26, 2015.
46. 46 McNally, LM, Jeena, PM, Lalloo, U, et al. Probable mother to infant transmission of Pneumocystis jiroveci from an HIV-infected woman to her HIV-uninfected infant. AIDS 19 (2005), 1548–1549.
47. 47 Kuhn, L, Kasonde, P, Sinkala, M, et al. Does severity of HIV disease in HIV-infected mothers affect mortality and morbidity among their uninfected infants?. Clin Infect Dis 41 (2005), 1654–1661.
48. 48 Fox, MP, Brooks, DR, Kuhn, L, et al. Role of breastfeeding cessation in mediating the relationship between maternal HIV disease stage and increased child mortality among HIV-exposed uninfected children. Int J Epidemiol 38 (2009), 569–576.
49. 49 Gray, KJ, Kafulafula, G, Matemba, M, Kamdolozi, M, Membe, G, French, N, Group B Streptococcus and HIV infection in pregnant women, Malawi, 2008–2010. Emerg Infect Dis 17 (2011), 1932–1935.
50. 50 Chatterjee, A, Bosch, RJ, Hunter, DJ, Fataki, MR, Msamanga, GI, Fawzi, WW, Maternal disease stage and child undernutrition in relation to mortality among children born to HIV-infected women in Tanzania. J Acquir Immune Defic Syndr 46 (2007), 599–606.
51. 51 Kuhn, L, Sinkala, M, Semrau, K, et al. Elevations in mortality associated with weaning persist into the second year of life among uninfected children born to HIV-infected mothers. Clin Infect Dis 50 (2010), 437–444.
52. 52 Newell, ML, Coovadia, H, Cortina-Borja, M, et al. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet 364 (2004), 1236–1243.
53. 53 Slyker, JA, Patterson, J, Ambler, G, et al. Correlates and outcomes of preterm birth, low birth weight, and small for gestational age in HIV-exposed uninfected infants. BMC Pregnancy Childbirth, 14, 2014, 7.
54. 54 Mussi-Pinhata, MM, Motta, F, Freimanis-Hance, L, et al. Lower respiratory tract infections among human immunodeficiency virus-exposed, uninfected infants. Int J Infect Dis 14:suppl 3 (2010), e176–e182.
55. 55 Mwiru, R, Spiegelman, D, Hertzmark, E, et al. Nutritional predictors of acute respiratory infections among children born to HIV-infected women in Tanzania. J Trop Pediatr 59 (2013), 203–208.
56. 56 Afran, L, Garcia Knight, M, Nduati, E, Urban, BC, Heyderman, RS, Rowland-Jones, SL, HIV-exposed uninfected children: a growing population with a vulnerable immune system?. Clin Exp Immunol 176 (2014), 11–22.
57. 57 Klatt, NR, Chomont, N, Douek, DC, Deeks, SG, Immune activation and HIV persistence: implications for curative approaches to HIV infection. Immunol Rev 254 (2013), 326–342.
58. 58 Brenchley, JM, Price, DA, Schacker, TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12 (2006), 1365–1371.
59. 59 Bunders, MJ, van Hamme, JL, Jansen, MH, Boer, K, Kootstra, NA, Kuijpers, TW, Fetal exposure to HIV-1 alters chemokine receptor expression by CD4+T cells and increases susceptibility to HIV-1. Sci Rep, 4, 2014, 6690.
60. 60 Reikie, BA, Adams, RC, Leligdowicz, A, et al. Altered innate immune development in HIV-exposed uninfected infants. J Acquir Immune Defic Syndr 66 (2014), 245–255.
61. 61 Velilla, PA, Montoya, CJ, Hoyos, A, Moreno, ME, Chougnet, C, Rugeles, MT, Effect of intrauterine HIV-1 exposure on the frequency and function of uninfected newborns' dendritic cells. Clin Immunol 126 (2008), 243–250.
62. 62 Slyker, JA, Lohman-Payne, B, John-Stewart, GC, et al. The impact of HIV-1 infection and exposure on natural killer (NK) cell phenotype in Kenyan infants during the first year of life. Front Immunol, 3, 2012, 399.
63. 63 Miles, DJ, Gadama, L, Gumbi, A, Nyalo, F, Makanani, B, Heyderman, RS, Human immunodeficiency virus (HIV) infection during pregnancy induces CD4 T-cell differentiation and modulates responses to Bacille Calmette-Guérin (BCG) vaccine in HIV-uninfected infants. Immunology 129 (2010), 446–454.
64. 64 Rich, KC, Siegel, JN, Jennings, C, Rydman, RJ, Landay, AL, Function and phenotype of immature CD4+ lymphocytes in healthy infants and early lymphocyte activation in uninfected infants of human immunodeficiency virus-infected mothers. Clin Diagn Lab Immunol 4 (1997), 358–361.
65. 65 Ono, E, Nunes dos Santos, AM, de Menezes Succi, RC, et al. Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART. Braz J Med Biol Res 41 (2008), 700–708.
66. 66 Clerici, M, Saresella, M, Colombo, F, et al. T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV. Blood 96 (2000), 3866–3871.
67. 67 Romano, MF, Buffolano, W, Bisogni, R, et al. Increased CD154 expression in uninfected infants born to HIV-positive mothers exposed to antiretroviral prophylaxis. Viral Immunol 19 (2006), 363–372.
68. 68 Kidzeru, EB, Hesseling, AC, Passmore, J-A, et al. In-utero exposure to maternal HIV infection alters T-cell immune responses to vaccination in HIV-uninfected infants. AIDS 28 (2014), 1421–1430.
69. 69 Jones, CE, Hesseling, AC, Tena-Coki, NG, et al. The impact of HIV exposure and maternal Mycobacterium tuberculosis infection on infant immune responses to bacille Calmette-Guérin vaccination. AIDS 29 (2015), 155–165.
70. 70 Economides, A, Schmid, I, Anisman-Posner, DJ, Plaeger, S, Bryson, YJ, Uittenbogaart, CH, Apoptosis in cord blood T lymphocytes from infants of human immunodeficiency virus-infected mothers. Clin Diagn Lab Immunol 5 (1998), 230–234.
71. 71 Nielsen, SD, Jeppesen, DL, Kolte, L, et al. Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts. Blood 98 (2001), 398–404.
72. 72 Liu, AY, Lohman-Payne, B, Chung, MH, et al. Maternal plasma and breastmilk viral loads are associated with HIV-1-specific cellular immune responses among HIV-1-exposed, uninfected infants in Kenya. Clin Exp Immunol 180 (2015), 509–519.
73. 73 Gaensbauer, JT, Rakhola, JT, Onyango-Makumbi, C, et al. Impaired Haemophilus influenzae type b transplacental antibody transmission and declining antibody avidity through the first year of life represent potential vulnerabilities for HIV-exposed but -uninfected infants. Clin Vaccine Immunol 21 (2014), 1661–1667.
74. 74 Jones, CE, Naidoo, S, De Beer, C, Esser, M, Kampmann, B, Hesseling, AC, Maternal HIV infection and antibody responses against vaccine-preventable diseases in uninfected infants. JAMA 305 (2011), 576–584.
75. 75 Jones, C, Pollock, L, Barnett, SM, Battersby, A, Kampmann, B, Specific antibodies against vaccine-preventable infections: a mother-infant cohort study. BMJ Open, 3, 2013, e002473.
76. 76 Madhi, SA, Izu, A, Violari, A, et al. Immunogenicity following the first and second doses of 7-valent pneumococcal conjugate vaccine in HIV-infected and -uninfected infants. Vaccine 31 (2013), 777–783.
77. 77 Simani, OE, Izu, A, Violari, A, et al. Effect of HIV-1 exposure and antiretroviral treatment strategies in HIV-infected children on immunogenicity of vaccines during infancy. AIDS 28 (2014), 531–541.
78. 78 Cumberland, P, Shulman, CE, Maple, PA, et al. Maternal HIV infection and placental malaria reduce transplacental antibody transfer and tetanus antibody levels in newborns in Kenya. J Infect Dis 196 (2007), 550–557.
79. 79 de Moraes-Pinto, MI, Almeida, AC, Kenj, G, et al. Placental transfer and maternally acquired neonatal IgG immunity in human immunodeficiency virus infection. J Infect Dis 173 (1996), 1077–1084.
80. 80 de Moraes-Pinto, MI, Verhoeff, F, Chimsuku, L, et al. Placental antibody transfer: influence of maternal HIV infection and placental malaria. Arch Dis Child Fetal Neonatal Ed 79 (1998), F202–F205.
81. 81 Le Doare, K, Allen, L, Kampmann, B, et al. Anti-group B Streptococcus antibody in infants born to mothers with human immunodeficiency virus (HIV) infection. Vaccine 33 (2015), 621–627.
82. 82 Reikie, BA, Naidoo, S, Ruck, CE, et al. Antibody responses to vaccination among South African HIV-exposed and unexposed uninfected infants during the first 2 years of life. Clin Vaccine Immunol 20 (2013), 33–38.
83. 83 Hesseling AC, Jones CE, Blakney AK, et al. Delayed BCG immunization does not alter antibody responses to EPI vaccines in HIV-exposed and HIV-unexposed South African infants. Vaccine (in press).
84. 84 Kolte, L, Rosenfeldt, V, Vang, L, et al. Reduced thymic size but no evidence of impaired thymic function in uninfected children born to human immunodeficiency virus-infected mothers. Pediatr Infect Dis J 30 (2011), 325–330.
85. 85 Madhi, SA, Adrian, P, Cotton, MF, et al. Effect of HIV infection status and anti-retroviral treatment on quantitative and qualitative antibody responses to pneumococcal conjugate vaccine in infants. J Infect Dis 202 (2010), 355–361.
86. 86 Simani, OE, Adrian, PV, Violari, A, et al. Effect of in-utero HIV exposure and antiretroviral treatment strategies on measles susceptibility and immunogenicity of measles vaccine. AIDS 27 (2013), 1583–1591.
87. 87 Abramczuk, BM, Mazzola, TN, Moreno, YMF, et al. Impaired humoral response to vaccines among HIV-exposed uninfected infants. Clin Vaccine Immunol 18 (2011), 1406–1409.
88. 88 Elliott, AM, Mawa, PA, Webb, EL, et al. Effects of maternal and infant co-infections, and of maternal immunisation, on the infant response to BCG and tetanus immunisation. Vaccine 29 (2010), 247–255.
89. 89 Garcia-Knight, MA, Nduati, E, Hassan, AS, et al. Altered memory T-Cell responses to Bacillus Calmette-Guerin and tetanus toxoid vaccination and altered cytokine responses to polyclonal stimulation in HIV-exposed uninfected Kenyan infants. PLoS One, 10, 2015, e0143043.
90. 90 Sanz-Ramos, M, Manno, D, Kapambwe, M, et al. Reduced poliovirus vaccine neutralising-antibody titres in infants with maternal HIV-exposure. Vaccine 31 (2013), 2042–2049.
91. 91 Hesseling, AC, Jaspan, HB, Black, GF, Nene, N, Walzl, G, Immunogenicity of BCG in HIV-exposed and non-exposed infants following routine birth or delayed vaccination. Int J Tuberc Lung Dis 19 (2015), 454–462.
92. 92 Van Rie, A, Madhi, SA, Heera, JR, et al. Gamma interferon production in response to Mycobacterium bovis BCG and Mycobacterium tuberculosis antigens in infants born to human immunodeficiency virus-infected mothers. Clin Vaccine Immunol 13 (2006), 246–252.
93. 93 Mansoor, N, Scriba, TJ, de Kock, M, et al. HIV-1 infection in infants severely impairs the immune response induced by Bacille Calmette-Guérin vaccine. J Infect Dis 199 (2009), 982–990.
94. 94 Mazzola, TN, da Silva, MT, Abramczuk, BM, et al. Impaired Bacillus Calmette-Guérin cellular immune response in HIV-exposed, uninfected infants. AIDS 25 (2011), 2079–2087.
95. 95 Siberry, GK, Patel, K, Bellini, WJ, et al. Immunity to measles, mumps, and rubella in US children with Perinatal HIV infection or perinatal HIV exposure without infection. Clin Infect Dis 61 (2015), 988–995.
96. 96 Kim, D, Huey, D, Oglesbee, M, Niewiesk, S, Insights into the regulatory mechanism controlling the inhibition of vaccine-induced seroconversion by maternal antibodies. Blood 117 (2011), 6143–6151.
97. 97 Henderson, RA, Miotti, PG, Saavedra, JM, et al. Longitudinal growth during the first 2 years of life in children born to HIV-infected mothers in Malawi, Africa. Pediatr AIDS HIV Infect 7 (1996), 91–97.
98. 98 Bailey, RC, Kamenga, MC, Nsuami, MJ, Nieburg, P, St Louis, ME, Growth of children according to maternal and child HIV, immunological and disease characteristics: a prospective cohort study in Kinshasa, Democratic Republic of Congo. Int J Epidemiol 28 (1999), 532–540.
99. 99 Sherry, B, Embree, JE, Mei, Z, et al. Sociodemographic characteristics, care, feeding practices, and growth of cohorts of children born to HIV-1 seropositive and seronegative mothers in Nairobi, Kenya. Trop Med Int Health 5 (2000), 678–686.
100. 100 Lepage, P, Msellati, P, Hitimana, DG, et al. Growth of human immunodeficiency type 1-infected and uninfected children: a prospective cohort study in Kigali, Rwanda, 1988 to 1993. Pediatr Infect Dis J 15 (1996), 479–485.
101. 101 Osterbauer, B, Kapisi, J, Bigira, V, et al. Factors associated with malaria parasitaemia, malnutrition, and anaemia among HIV-exposed and unexposed Ugandan infants: a cross-sectional survey. Malar J, 11, 2012, 432.
102. 102 Wei, R, Msamanga, GI, Spiegelman, D, et al. Association between low birth weight and infant mortality in children born to human immunodeficiency virus 1-infected mothers in Tanzania. Pediatr Infect Dis J 23 (2004), 530–535.
103. 103 Kourtis, AP, Wiener, J, Kayira, D, et al. Health outcomes of HIV-exposed uninfected African infants. AIDS 27 (2013), 749–759.
104. 104 Venkatesh, KK, Lurie, MN, Triche, EW, et al. Growth of infants born to HIV-infected women in South Africa according to maternal and infant characteristics. Trop Med Int Health 15 (2010), 1364–1374.
105. 105 McGrath, CJ, Nduati, R, Richardson, BA, et al. The prevalence of stunting is high in HIV-1-exposed uninfected infants in Kenya. J Nutr 142 (2012), 757–763.
106. 106 Patel, D, Bland, R, Coovadia, H, Rollins, N, Coutsoudis, A, Newell, ML, Breastfeeding, HIV status and weights in South African children: a comparison of HIV-exposed and unexposed children. AIDS 24 (2010), 437–445.
107. 107 Arpadi, S, Fawzy, A, Aldrovandi, GM, et al. Growth faltering due to breastfeeding cessation in uninfected children born to HIV-infected mothers in Zambia. Am J Clin Nutr 90 (2009), 344–353.
108. 108 Ross, A, Raab, GM, Mok, J, Gilkison, S, Hamilton, B, Johnstone, FD, Maternal HIV infection, drug use, and growth of uninfected children in their first 3 years. Arch Dis Child 73 (1995), 490–495.
109. 109 Agostoni, C, Zuccotti, GV, Giovannini, M, et al. Growth in the first two years of uninfected children born to HIV-1 seropositive mothers. Arch Dis Child 79 (1998), 175–178.
110. 110 Neri, D, Somarriba, GA, Schaefer, NN, et al. Growth and body composition of uninfected children exposed to human immunodeficiency virus: comparison with a contemporary cohort and United States National Standards. J Pediatr 163 (2013), 249–254.
111. 111 Le Doaré, K, Bland, R, Newell, ML, Neurodevelopment in children born to HIV-infected mothers by infection and treatment status. Pediatrics 130 (2012), e1326–e1344.
112. 112 Gómez, C, Archila, ME, Rugeles, C, Carrizosa, J, Rugeles, MT, Cornejo, JW, A prospective study of neurodevelopment of uninfected children born to human immunodeficiency virus type 1 positive mothers. Rev Neurol 48 (2009), 287–291 (in Spanish).
113. 113 Kandawasvika, GQ, Kuona, P, Chandiwana, P, et al. The burden and predictors of cognitive impairment among 6- to 8-year-old children infected and uninfected with HIV from Harare, Zimbabwe: a cross-sectional study. Child Neuropsychol 21 (2015), 106–120.
114. 114 Nicholson, L, Chisenga, M, Siame, J, Kasonka, L, Filteau, S, Growth and health outcomes at school age in HIV-exposed, uninfected Zambian children: follow-up of two cohorts studied in infancy. BMC Pediatr, 15, 2015, 66.
115. 115 Kerr, SJ, Puthanakit, T, Vibol, U, et al. Neurodevelopmental outcomes in HIV-exposed-uninfected children versus those not exposed to HIV. AIDS Care 26 (2014), 1327–1335.
116. 116 Jahanshad, N, Couture, MC, Prasitsuebsai, W, et al. Brain imaging and neurodevelopment in HIV-uninfected Thai children born to HIV-infected mothers. Pediatr Infect Dis J 34 (2015), e211–e216.
117. 117 UNAIDS. Global report: UNAIDS report on the global AIDS epidemic 2013, 2013, Joint United Nations Programme on HIV/AIDS (UNAIDS), Geneva http://www.unaids.org/sites/default/files/media_asset/UNAIDS_Global_Report_2013_en_1.pdf (accessed July 28, 2015).
118. 118 Quinn, TC, Global burden of the HIV pandemic. Lancet 348 (1996), 99–106.
119. 119 Ronsmans, C, Chowdhury, ME, Dasgupta, SK, Ahmed, A, Koblinsky, M, Effect of parent's death on child survival in rural Bangladesh: a cohort study. Lancet 375 (2010), 2024–2031.
120. 120 Joint United Nations Programme on HIV/AIDS UNICEF, the United States Agency for International Development (USAID). Children on the brink 2004: a joint report of new orphan estimates and a framework for action, 2004, Joint United Nations Programme on HIV/AIDS, the United Nations Children's Fund, and the United States Agency for International Development, New York, NY http://www.unicef.org/publications/cob_layout6-013.pdf (accessed July 29, 2015).
121. 121 Kakkar, F, Lamarre, V, Ducruet, T, et al. Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency. BMC Infect Dis, 14, 2014, 236.
122. 122 Gupta, RK, Lawn, SD, Bekker, LG, Caldwell, J, Kaplan, R, Wood, R, Impact of human immunodeficiency virus and CD4 count on tuberculosis diagnosis: analysis of city-wide data from Cape Town, South Africa. Int J Tuberc Lung Dis 17 (2013), 1014–1022.
123. 123 Slyker, JA, Rowland-Jones, SL, Dong, T, et al. Acute cytomegalovirus infection is associated with increased frequencies of activated and apoptosis-vulnerable T cells in HIV-1-infected infants. J Virol 86 (2012), 11373–11379.
124. 124 Schramm, DB, Kuhn, L, Gray, GE, Tiemessen, CT, In vivo effects of HIV-1 exposure in the presence and absence of single-dose nevirapine on cellular plasma activation markers of infants born to HIV-1-seropositive mothers. J Acquir Immune Defic Syndr 42 (2006), 545–553.
125. 125 Nazli, A, Chan, O, Dobson-Belaire, WN, et al. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathog, 6, 2010, e1000852.
126. 126 Townsend, CL, Tookey, PA, Newell, ML, Cortina-Borja, M, Antiretroviral therapy in pregnancy: balancing the risk of preterm delivery with prevention of mother-to-child HIV transmission. Antivir Ther 15 (2010), 775–783.
127. 127 Barret, B, Tardieu, M, Rustin, P, et al. Persistent mitochondrial dysfunction in HIV-1-exposed but uninfected infants: clinical screening in a large prospective cohort. AIDS 17 (2003), 1769–1785.
128. 128 Sibiude, J, Mandelbrot, L, Blanche, S, et al. Association between prenatal exposure to antiretroviral therapy and birth defects: an analysis of the ANRS CO1/CO11 French Perinatal Cohort Study. PLoS Med, 11, 2014, e1001635.
129. 129 Sibiude, J, Le Chenadec, J, Bonnet, D, et al. In utero exposure to zidovudine and heart anomalies in the ANRS French perinatal cohort and the nested PRIMEVA randomized trial. Clin Infect Dis 61 (2015), 270–280.
130. 130 Thorne, C, Newell, ML, Safety of agents used to prevent mother-to-child transmission of HIV: is there any cause for concern?. Drug Saf 30 (2007), 203–213.
131. 131 Wang, L, Kourtis, AP, Ellington, S, Legardy-Williams, J, Bulterys, M, Safety of tenofovir during pregnancy for the mother and fetus: a systematic review. Clin Infect Dis 57 (2013), 1773–1781.
132. 132 Siberry, GK, Williams, PL, Mendez, H, et al. Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants. AIDS 26 (2012), 1151–1159.
133. 133 Powis, KM, Smeaton, L, Hughes, MD, et al. In-utero triple antiretroviral exposure associated with decreased growth among HIV-exposed uninfected infants in Botswana. AIDS 30 (2016), 211–220.
134. 134 Mermin, J, Were, W, Ekwaru, JP, et al. Mortality in HIV-infected Ugandan adults receiving antiretroviral treatment and survival of their HIV-uninfected children: a prospective cohort study. Lancet 371 (2008), 752–759.
135. 135 WHO. Guidelines on co-trimoxazole prophylaxis for HIV-related infections among children, adolescents and adults: recommendations for a public health approach, 2006, World Health Organization, Geneva http://www.who.int/hiv/pub/guidelines/ctxguidelines.pdf?ua=1 (accessed July 29, 2015).
136. 136 Ford, N, Shubber, Z, Jao, J, Abrams, EJ, Frigati, L, Mofenson, L, Safety of cotrimoxazole in pregnancy: a systematic review and meta-analysis. J Acquir Immune Defic Syndr 66 (2014), 512–521.
137. 137 Dryden-Peterson, S, Jayeoba, O, Hughes, MD, et al. Cotrimoxazole prophylaxis and risk of severe anemia or severe neutropenia in HAART-exposed, HIV-uninfected infants. PLoS One, 8, 2013, e74171.
138. 138 Dow, A, Kayira, D, Hudgens, M, et al. Effects of cotrimoxazole prophylactic treatment on adverse health outcomes among HIV-exposed, uninfected infants. Pediatr Infect Dis J 31 (2012), 842–847.
139. 139 Davis, NL, Barnett, EJ, Miller, WC, et al. Impact of daily cotrimoxazole on clinical malaria and asymptomatic parasitemias in HIV-exposed, uninfected infants. Clin Infect Dis 61 (2015), 368–374.
140. 140 Sandison, T, Homsy, J, Arinaitwe, E, et al. Protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children in rural Uganda: a randomised clinical trial. BMJ, 342, 2011, d1617.
141. 141 Coutsoudis, A, Pillay, K, Spooner, E, Coovadia, HM, Pembrey, L, Newell, ML, Routinely available cotrimoxazole prophylaxis and occurrence of respiratory and diarrhoeal morbidity in infants born to HIV-infected mothers in South Africa. S Afr Med J 95 (2005), 339–345.
142. 142 Madhi, SA, Nachman, S, Violari, A, et al. Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children. N Engl J Med 365 (2011), 21–31.
143. 143 Groome, MJ, Page, N, Cortese, MM, et al. Effectiveness of monovalent human rotavirus vaccine against admission to hospital for acute rotavirus diarrhoea in South African children: a case-control study. Lancet Infect Dis 14 (2014), 1096–1104.
144. 144 Habib, NA, Daltveit, AK, Bergsjo, P, Shao, J, Oneko, O, Lie, RT, Maternal HIV status and pregnancy outcomes in northeastern Tanzania: a registry-based study. BJOG 115 (2008), 616–624.
145. 145 Nunes, MC, Cutland, CL, Dighero, B, et al. Kinetics of hemagglutination-inhibiting antibodies following maternal influenza vaccination among mothers with and those without HIV infection and their infants. J Infect Dis 212 (2015), 1976–1987.
146. 146 Baroncelli, S, Galluzzo, CM, Mancinelli, S, et al. Antibodies against pneumococcal capsular polysaccharide in Malawian HIV-positive mothers and their HIV-exposed uninfected children. Infect Dis 48 (2015), 317–321.
147. 147 Hesseling, AC, Johnson, LF, Jaspan, H, et al. Disseminated bacille Calmette-Guérin disease in HIV-infected South African infants. Bull World Health Organ 87 (2009), 505–511.
148. 148 Fawzy, A, Arpadi, S, Kankasa, C, et al. Early weaning increases diarrhea morbidity and mortality among uninfected children born to HIV-infected mothers in Zambia. J Infect Dis 203 (2011), 1222–1230.
149. 149 Kafulafula, G, Hoover, DR, Taha, TE, et al. Frequency of gastroenteritis and gastroenteritis-associated mortality with early weaning in HIV-1-uninfected children born to HIV-infected women in Malawi. J Acquir Immune Defic Syndr 53 (2010), 6–13.
150. 150 Onyango-Makumbi, C, Bagenda, D, Mwatha, A, et al. Early weaning of HIV-exposed uninfected infants and risk of serious gastroenteritis: findings from two perinatal HIV prevention trials in Kampala, Uganda. J Acquir Immune Defic Syndr 53 (2010), 20–27.
151. 151 Homsy, J, Moore, D, Barasa, A, et al. Breastfeeding, mother-to-child HIV transmission, and mortality among infants born to HIV-Infected women on highly active antiretroviral therapy in rural Uganda. J Acquir Immune Defic Syndr 53 (2010), 28–35.
152. 152 Taha, TE, Hoover, DR, Chen, S, et al. Effects of cessation of breastfeeding in HIV-1-exposed, uninfected children in Malawi. Clin Infect Dis 53 (2011), 388–395.
153. 153 Ásbjörnsdóttir, KH, Slyker, JA, Maleche-Obimbo, E, et al. Breastfeeding is associated with decreased risk of hospitalization among HIV-exposed, uninfected Kenyan infants. J Hum Lact, 2015, 10.1177/0890334415607854 published online Sept 30, 2015.
154. 154 Ásbjörnsdóttir, KH, Slyker, JA, Weiss, NS, et al. Breastfeeding is associated with decreased pneumonia incidence among HIV-exposed, uninfected Kenyan infants. AIDS 27 (2013), 2809–2815.
155. 155 Coutsoudis, A, Pillay, K, Spooner, E, Coovadia, HM, Pembrey, L, Newell, ML, Morbidity in children born to women infected with human immunodeficiency virus in South Africa: does mode of feeding matter?. Acta Paediatr 92 (2003), 890–895.
156. 156 Bork, KA, Cournil, A, Read, JS, et al. Morbidity in relation to feeding mode in African HIV-exposed, uninfected infants during the first 6 mo of life: the Kesho Bora study. Am J Clin Nutr 100 (2014), 1559–1568.
157. 157 WHO. Guidelines on HIV and infant feeding. Principles and recommendations for infant feeding in the context of HIV and a summary of evidence, 2010, World Health Organization, Geneva http://apps.who.int/iris/bitstream/10665/44345/1/9789241599535_eng.pdf (accessed Dec 23, 2015).
158. 158 Pedersen, SH, Wilkinson, AL, Andreasen, A, et al. Longitudinal analysis of mature breastmilk and serum immune composition among mixed HIV-status mothers and their infants. Clin Nutr, 2015, 10.1016/j.clnu.2015.05.016 published online June 3.
159. 159 Muhangi, L, Lule, SA, Mpairwe, H, et al. Maternal HIV infection and other factors associated with growth outcomes of HIV-uninfected infants in Entebbe, Uganda. Public Health Nutr 16 (2013), 1548–1557.
160. 160 Rollins, N, Mahy, M, Becquet, R, Kuhn, L, Creek, T, Mofenson, L, Estimates of peripartum and postnatal mother-to-child transmission probabilities of HIV for use in Spectrum and other population-based models. Sex Transm Infect 88:suppl 2 (2012), i44–i51.
161. 161 UNICEF. The Double Dividend: Action to improve survival of HIV ‘exposed’ children in the era of eMTT and renewed child survival campaigns, 2013, United Nations Children's Emergency Fund, Cape Town http://www.unicef.org/aids/files/Action_Framework_Final.pdf (accessed July 29, 2015).