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Virologic Determinants of Breast Milk Transmission of HIV-1

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Human Immunodeficiency Virus type 1 (HIV-1) and Breastfeeding

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 743))

Abstract

In 1985, the first report of presumed HIV breast milk transmission was described in an Australian infant whose mother received a postpartum transfusion from an apparently healthy male homosexual donor, who subsequently developed Kaposi’s sarcoma and Pneumocystis pneumonia [1]. Later that year, HIV was cultured from the cell-free fraction of breast milk of 3 HIV-infected women [2]. On the basis of these reports, guidelines in the USA were changed advising HIV-infected women not to breastfeed, but for the majority of HIV-infected women worldwide this was not and is not an option. In the intervening 25 years, much has been learned about breast milk transmission, including ways to reduce its occurrence. Some of this knowledge may appear “obvious”; e.g., avoidance of breast feeding prevents breast milk transmission [3]. Less obvious is the fact that breastfeeding behavior, i.e., exclusive breastfeeding, as opposed to mixed feeding, substantially reduces the risk of transmission [4]. However, despite these advances, there are still many questions regarding key pathogenic mechanisms of HIV breast milk transmission. Among these are whether cell-free or cell-associated virus is responsible for transmission; where and when transmission occurs; which virologic determinants predispose mother–infant pairs to transmission; and whether the breast is a separate virologic compartment? This chapter reviews the virologic factors that have been associated with breast milk transmission of HIV.

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References

  1. Ziegler JB, Cooper DA, Johnson RO, Gold J (1985) Postnatal transmission of AIDS-associated retrovirus from mother to infant. Lancet 1:896–898

    Article  PubMed  CAS  Google Scholar 

  2. Thiry L, Sprecher-Goldberger S, Jonckheer T et al (1985) Isolation of AIDS virus from cell-free breast milk of three healthy virus carriers. Lancet 2:891–892

    Article  PubMed  CAS  Google Scholar 

  3. Nduati R, John G, Mbori-Ngacha D et al (2000) Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial. JAMA 283:1167–1174

    Article  PubMed  CAS  Google Scholar 

  4. Kuhn L (2010) Milk mysteries: why are women who exclusively breast-feed less likely to transmit HIV during breast-feeding? Clin Infect Dis 50:770–772

    Article  PubMed  Google Scholar 

  5. Dunn DT, Newell ML, Ades AE, Peckham CS (1992) Risk of human immunodeficiency virus type 1 transmission through breastfeeding. Lancet 340:585–588

    Article  PubMed  CAS  Google Scholar 

  6. Richardson BA, John-Stewart GC, Hughes JP et al (2003) Breast-milk infectivity in human immunodeficiency virus type 1-infected mothers. J Infect Dis 187:736–740

    Article  PubMed  Google Scholar 

  7. Gray L, Fiscus S, Shugars D (2007) HIV-1 variants from a perinatal transmission pair demonstrate similar genetic and replicative properties in tonsillar tissues and peripheral blood mononuclear cells. AIDS Res Hum Retroviruses 23:1095–1104

    Article  PubMed  CAS  Google Scholar 

  8. Vogt MW, Witt DJ, Craven DE et al (1986) Isolation of HTLV-III/LAV from cervical secretions of women at risk for AIDS. Lancet 1:525–527

    Article  PubMed  CAS  Google Scholar 

  9. Southern SO (1998) Milk-borne transmission of HIV. Characterization of productively infected cells in breast milk and interactions between milk and saliva. J Hum Virol 1:328–337

    PubMed  CAS  Google Scholar 

  10. Toniolo A, Serra C, Conaldi PG, Basolo F, Falcone V, Dolei A (1995) Productive HIV-1 infection of normal human mammary epithelial cells. AIDS 9:859–866

    Article  PubMed  CAS  Google Scholar 

  11. Lyimo MA, Howell AL, Balandya E, Eszterhas SK, Connor RI (2009) Innate factors in human breast milk inhibit cell-free HIV-1 but not cell-associated HIV-1 infection of CD4+ cells. J Acquir Immune Defic Syndr 51:117–124

    Article  PubMed  Google Scholar 

  12. Habte HH, de Beer C, Lotz ZE, Tyler MG, Kahn D, Mall AS (2008) Inhibition of human immunodeficiency virus type 1 activity by purified human breast milk mucin (MUC1) in an inhibition assay. Neonatology 93:162–170

    Article  PubMed  CAS  Google Scholar 

  13. Habte HH, Kotwal GJ, Lotz ZE et al (2007) Antiviral activity of purified human breast milk mucin. Neonatology 92:96–104

    Article  PubMed  CAS  Google Scholar 

  14. Villamor E, Koulinska IN, Furtado J et al (2007) Long-chain n-6 polyunsaturated fatty acids in breast milk decrease the risk of HIV transmission through breastfeeding. Am J Clin Nutr 86:682–689

    PubMed  CAS  Google Scholar 

  15. Viveros-Rogel M, Soto-Ramirez L, Chaturvedi P, Newburg DS, Ruiz-Palacios GM (2004) Inhibition of HIV-1 infection in vitro by human milk sulfated glycolipids and glycosaminoglycans. Adv Exp Med Biol 554:481–487

    PubMed  CAS  Google Scholar 

  16. Baron S, Poast J, Richardson CJ, Nguyen D, Cloyd M (2000) Oral transmission of human immunodeficiency virus by infected seminal fluid and milk: a novel mechanism. J Infect Dis 181:498–504

    Article  PubMed  CAS  Google Scholar 

  17. Martin V, Maldonado A, Fernandez L, Rodriguez JM, Connor RI (2010) Inhibition of human immunodeficiency virus type 1 by lactic acid bacteria from human breastmilk. Breastfeed Med 5:153–158

    Article  PubMed  Google Scholar 

  18. Buransin P, Kunakorn M, Petchlai B et al (1993) Detection of human immunodeficiency virus type 1 (HIV-1) proviral DNA in breast milk and colostrum of seropositive mothers. J Med Assoc Thai 76:41–44

    Google Scholar 

  19. Guay LA, Hom DL, Mmiro F et al (1996) Detection of human immunodeficiency virus type 1 (HIV-1) DNA and p24 antigen in breast milk of HIV-1-infected Ugandan women and vertical transmission. Pediatrics 98:438–444

    PubMed  CAS  Google Scholar 

  20. Nduati RW, John GC, Richardson BA et al (1995) Human immunodeficiency virus type 1-infected cells in breast milk: association with immunosuppression and vitamin A deficiency. J Infect Dis 172:1461–1468

    Article  PubMed  CAS  Google Scholar 

  21. Ruff AJ, Coberly J, Halsey NA et al (1994) Prevalence of HIV-1 DNA and p24 antigen in breast milk and correlation with maternal factors. J Acquir Immune Defic Syndr 7:68–73

    PubMed  CAS  Google Scholar 

  22. Van de Perre P, Simonon A, Hitimana DG et al (1993) Infective and anti-infective properties of breastmilk from HIV-1-infected women. Lancet 341:914–918

    Article  PubMed  Google Scholar 

  23. Gantt S, Shetty AK, Seidel KD et al (2007) Laboratory indicators of mastitis are not associated with elevated HIV-1 DNA loads or predictive of HIV-1 RNA loads in breast milk. J Infect Dis 196:570–576

    Article  PubMed  Google Scholar 

  24. Koulinska IN, Villamor E, Chaplin B et al (2006) Transmission of cell-free and cell-associated HIV-1 through breast-feeding. J Acquir Immune Defic Syndr 41:93–99

    Article  PubMed  Google Scholar 

  25. Rousseau CM, Nduati RW, Richardson BA et al (2004) Association of levels of HIV-1-infected breast milk cells and risk of mother-to-child transmission. J Infect Dis 190:1880–1888

    Article  PubMed  Google Scholar 

  26. Kantarci S, Koulinska IN, Aboud S, Fawzi WW, Villamor E (2007) Subclinical mastitis, cell-associated HIV-1 shedding in breast milk, and breast-feeding transmission of HIV-1. J Acquir Immune Defic Syndr 46:651–654

    Article  PubMed  Google Scholar 

  27. Villamor E, Koulinska IN, Aboud S et al (2010) Effect of vitamin supplements on HIV shedding in breast milk. Am J Clin Nutr 92:881–886

    Article  PubMed  CAS  Google Scholar 

  28. Vonesch N, Sturchio E, Humani AC, Fei PC, Coszena D, Caprilli F, Pezzella M (1992) Detection of HIV-1 genome in leukocytes of human colostrum from anti-HIV-1 seropositive mothers. AIDS Res Hum Retroviruses 8:1283–1287

    Article  PubMed  CAS  Google Scholar 

  29. John GC, Nduati RW, Mbori-Ngacha DA et al (2001) Correlates of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission: association with maternal plasma HIV-1 RNA load, genital HIV-1 DNA shedding, and breast infections. J Infect Dis 183:206–212

    Article  PubMed  CAS  Google Scholar 

  30. Hoffman IF, Martinson FE, Stewart PW et al (2003) Human immunodeficiency virus type 1 RNA in breast-milk components. J Infect Dis 188:1209–1212

    Article  PubMed  CAS  Google Scholar 

  31. Lewis P, Nduati R, Kreiss JK et al (1998) Cell-free human immunodeficiency virus type 1 in breast milk. J Infect Dis 177:34–39

    Article  PubMed  CAS  Google Scholar 

  32. Pillay K, Coutsoudis A, York D, Kuhn L, Coovadia HM (2000) Cell-free virus in breast milk of HIV-1-seropositive women. J Acquir Immune Defic Syndr 24:330–336

    PubMed  CAS  Google Scholar 

  33. Rousseau CM, Nduati RW, Richardson BA et al (2003) Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease. J Infect Dis 187:741–747

    Article  PubMed  Google Scholar 

  34. Semba RD, Kumwenda N, Hoover DR et al (1999) Human immunodeficiency virus load in breast milk, mastitis, and mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis 180:93–98

    Article  PubMed  CAS  Google Scholar 

  35. Willumsen JF, Filteau SM, Coutsoudis A et al (2003) Breastmilk RNA viral load in HIV-infected South African women: effects of subclinical mastitis and infant feeding. AIDS 17:407–414

    Article  PubMed  Google Scholar 

  36. Lunney KM, Iliff P, Mutasa K et al (2010) Associations between breast milk viral load, mastitis, exclusive breast-feeding, and postnatal transmission of HIV. Clin Infect Dis 50:762–769

    PubMed  Google Scholar 

  37. Phiri W, Kasonka L, Collin S et al (2006) Factors influencing breast milk HIV RNA viral load among Zambian women. AIDS Res Hum Retroviruses 22:607–614

    Article  PubMed  CAS  Google Scholar 

  38. Semrau K, Ghosh M, Kankasa C et al (2008) Temporal and lateral dynamics of HIV shedding and elevated sodium in breast milk among HIV-positive mothers during the first 4 months of breast-feeding. J Acquir Immune Defic Syndr 47:320–328

    Article  PubMed  Google Scholar 

  39. Petitjean G, Becquart P, Tuaillon E et al (2007) Isolation and characterization of HIV-1-infected resting CD4+ T lymphocytes in breast milk. J Clin Virol 39:1–8

    Article  PubMed  CAS  Google Scholar 

  40. Neveu D, Viljoen J, Bland RM et al (2011) Cumulative exposure to cell-free HIV in breast milk, rather than feeding pattern per se, identifies postnatally infected infants. Clin Infect Dis 52:819–825

    Article  PubMed  CAS  Google Scholar 

  41. Chung MH, Kiarie JN, Richardson BA et al (2007) Independent effects of nevirapine prophylaxis and HIV-1 RNA suppression in breast milk on early perinatal HIV-1 transmission. J Acquir Immune Defic Syndr 46:472–478

    Article  PubMed  CAS  Google Scholar 

  42. Willumsen JF, Newell ML, Filteau SM et al (2001) Variation in breastmilk HIV-1 viral load in left and right breasts during the first 3 months of lactation. AIDS 15:1896–1898

    Article  PubMed  CAS  Google Scholar 

  43. Thea DM, Aldrovandi G, Kankasa C et al (2006) Post-weaning breast milk HIV-1 viral load, blood prolactin levels and breast milk volume. AIDS 20:1539–1547

    Article  PubMed  CAS  Google Scholar 

  44. Benaboud S, Pruvost A, Coffie PA et al (2011) Concentrations of tenofovir and emtricitabine in breast milk of HIV-1-infected women in Abidjan, Cote d’Ivoire, in the ANRS 12109 TEmAA Study, step 2. Antimicrob Agents Chemother 55:1315–1317

    Article  PubMed  CAS  Google Scholar 

  45. Schneider S, Peltier A, Gras A et al (2008) Efavirenz in human breast milk, mothers’, and newborns’ plasma. J Acquir Immune Defic Syndr 48:450–454

    Article  PubMed  CAS  Google Scholar 

  46. Shapiro RL, Holland DT, Capparelli E et al (2005) Antiretroviral concentrations in breast-feeding infants of women in Botswana receiving antiretroviral treatment. J Infect Dis 192:720–727

    Article  PubMed  CAS  Google Scholar 

  47. Colebunders R, Hodossy B, Burger D et al (2005) The effect of highly active antiretroviral treatment on viral load and antiretroviral drug levels in breast milk. AIDS 19:1912–1915

    Article  PubMed  CAS  Google Scholar 

  48. Manigart O, Crepin M, Leroy V et al (2004) Effect of perinatal zidovudine prophylaxis on the evolution of cell-free HIV-1 RNA in breast milk and on postnatal transmission. J Infect Dis 190:1422–1428

    Article  PubMed  CAS  Google Scholar 

  49. Mirochnick M, Thomas T, Capparelli E et al (2009) Antiretroviral concentrations in breast-feeding infants of mothers receiving highly active antiretroviral therapy. Antimicrob Agents Chemother 53:1170–1176

    Article  PubMed  CAS  Google Scholar 

  50. Corbett A, Martinson F, Rezk N, Kashuba A, Jamieson D, Chasela C, Kayira D, Tegha G, Kamwendo D, van der Horst C, BAN Study Team. (2009) Lopinavir/ritonavir concentrations in breast milk and breast-feeding infants 16th CROI. Montreal, Canada

    Google Scholar 

  51. Corbett A, Kashuba A, Rezk N, Jamieson D, Chasela C, Hyde L, Tegha G, Joaki G, Kamwendo D, van der Horst C, BAN Study Team (2008) Antiretroviral drug concentrations in breast milk and breastfeeding infants. 15th CROI. Boston, MA

    Google Scholar 

  52. Rossenkhan R, Ndung’u T, Sebunya TK et al (2009) Temporal reduction of HIV type 1 viral load in breast milk by single-dose nevirapine during prevention of MTCT. AIDS Res Hum Retroviruses 25:1261–1264

    Article  PubMed  CAS  Google Scholar 

  53. Chung MH, Kiarie JN, Richardson BA, Lehman DA, Overbaugh J, John-Stewart GC (2005) Breast milk HIV-1 suppression and decreased transmission: a randomized trial comparing HIVNET 012 nevirapine versus short-course zidovudine. AIDS 19:1415–1422

    Article  PubMed  CAS  Google Scholar 

  54. Lehman DA, Chung MH, John-Stewart GC et al (2008) HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent mother-to-child transmission. AIDS 22:1475–1485

    Article  PubMed  CAS  Google Scholar 

  55. Giuliano M, Guidotti G, Andreotti M et al (2007) Triple antiretroviral prophylaxis administered during pregnancy and after delivery significantly reduces breast milk viral load: a study within the Drug Resource Enhancement Against AIDS and Malnutrition Program. J Acquir Immune Defic Syndr 44:286–291

    Article  PubMed  CAS  Google Scholar 

  56. Shapiro RL, Ndung’u T, Lockman S et al (2005) Highly active antiretroviral therapy started during pregnancy or postpartum suppresses HIV-1 RNA, but not DNA, in breast milk. J Infect Dis 192:713–719

    Article  PubMed  CAS  Google Scholar 

  57. Alfsen A, Yu H, Magerus-Chatinet A, Schmitt A, Bomsel M (2005) HIV-1-infected blood mononuclear cells form an integrin- and agrin-dependent viral synapse to induce efficient HIV-1 transcytosis across epithelial cell monolayer. Mol Biol Cell 16:4267–4279

    Article  PubMed  CAS  Google Scholar 

  58. Lagaye S, Derrien M, Menu E et al (2001) Cell-to-cell contact results in a selective translocation of maternal human immunodeficiency virus type 1 quasispecies across a trophoblastic barrier by both transcytosis and infection. J Virol 75:4780–4791

    Article  PubMed  CAS  Google Scholar 

  59. Lehman DA, Farquhar C (2007) Biological mechanisms of vertical human immunodeficiency virus (HIV-1) transmission. Rev Med Virol 17:381–403

    Article  PubMed  Google Scholar 

  60. Phillips DM (1994) The role of cell-to-cell transmission in HIV infection. AIDS 8:719–731

    Article  PubMed  CAS  Google Scholar 

  61. Becquart P, Hocini H, Levy M, Sepou A, Kazatchkine MD, Belec L (2000) Secretory anti-human immunodeficiency virus (HIV) antibodies in colostrum and breast milk are not a major determinant of the protection of early postnatal transmission of HIV. J Infect Dis 181:532–539

    Article  PubMed  CAS  Google Scholar 

  62. Bomsel M, Alfsen A (2003) Entry of viruses through the epithelial barrier: pathogenic trickery. Nat Rev Mol Cell Biol 4:57–68

    Article  PubMed  CAS  Google Scholar 

  63. Bosire R, John-Stewart GC, Mabuka JM et al (2007) Breast milk alpha-defensins are associated with HIV type 1 RNA and CC chemokines in breast milk but not vertical HIV type 1 transmission. AIDS Res Hum Retroviruses 23:198–203

    Article  PubMed  CAS  Google Scholar 

  64. Farquhar C, Mbori-Ngacha DA, Redman MW et al (2005) CC and CXC chemokines in breastmilk are associated with mother-to-child HIV-1 transmission. Curr HIV Res 3:361–369

    Article  PubMed  CAS  Google Scholar 

  65. Kuhn L, Trabattoni D, Kankasa C et al (2006) HIV-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants. J Pediatr 149:611–616

    Article  PubMed  CAS  Google Scholar 

  66. Moore JS, Rahemtulla F, Kent LW et al (2003) Oral epithelial cells are susceptible to cell-free and cell-associated HIV-1 infection in vitro. Virology 313:343–353

    Article  PubMed  CAS  Google Scholar 

  67. Burkhard MJ, Dean GA (2003) Transmission and immunopathogenesis of FIV in cats as a model for HIV. Curr HIV Res 1:15–29

    Article  PubMed  CAS  Google Scholar 

  68. Ruprecht RM, Baba TW, Liska V et al (1999) Oral transmission of primate lentiviruses. J Infect Dis 179(Suppl 3):S408–S412

    Article  PubMed  Google Scholar 

  69. Otsyula MG, Miller CJ, Tarantal AF et al (1996) Fetal or neonatal infection with attenuated simian immunodeficiency virus results in protective immunity against oral challenge with pathogenic SIVmac251. Virology 222:275–278

    Article  PubMed  CAS  Google Scholar 

  70. Burkhard MJ, Obert LA, O’Neil LL, Diehl LJ, Hoover EA (1997) Mucosal transmission of cell-associated and cell-free feline immunodeficiency virus. AIDS Res Hum Retroviruses 13:347–355

    Article  PubMed  CAS  Google Scholar 

  71. O’Neil LL, Burkhard MJ, Hoover EA (1996) Frequent perinatal transmission of feline immunodeficiency virus by chronically infected cats. J Virol 70:2894–2901

    PubMed  Google Scholar 

  72. Obert LA, Hoover EA (2000) Feline immunodeficiency virus clade C mucosal transmission and disease courses. AIDS Res Hum Retroviruses 16:677–688

    Article  PubMed  CAS  Google Scholar 

  73. Howard KE, Burkhard MJ (2007) Mucosal challenge with cell-associated or cell-free feline immunodeficiency virus induces rapid and distinctly different patterns of phenotypic change in the mucosal and systemic immune systems. Immunology 122:571–583

    Article  PubMed  CAS  Google Scholar 

  74. Anderson DJ (2010) Finally, a macaque model for cell-associated SIV/HIV vaginal transmission. J Infect Dis 202:333–336

    Article  PubMed  Google Scholar 

  75. Sellon RK, Jordan HL, Kennedy-Stoskopf S, Tompkins MB, Tompkins WA (1994) Feline immunodeficiency virus can be experimentally transmitted via milk during acute maternal infection. J Virol 68:3380–3385

    PubMed  CAS  Google Scholar 

  76. Van Rompay KK, Abel K, Lawson JR et al (2005) Attenuated poxvirus-based simian immunodeficiency virus (SIV) vaccines given in infancy partially protect infant and juvenile macaques against repeated oral challenge with virulent SIV. J Acquir Immune Defic Syndr 38:124–134

    Article  PubMed  Google Scholar 

  77. Van Rompay KK, Greenier JL, Cole KS et al (2003) Immunization of newborn rhesus macaques with simian immunodeficiency virus (SIV) vaccines prolongs survival after oral challenge with virulent SIVmac251. J Virol 77:179–190

    Article  PubMed  CAS  Google Scholar 

  78. Van Rompay KK, Schmidt KA, Lawson JR, Singh R, Bischofberger N, Marthas ML (2002) Topical administration of low-dose tenofovir disoproxil fumarate to protect infant macaques against multiple oral exposures of low doses of simian immunodeficiency virus. J Infect Dis 186:1508–1513

    Article  PubMed  Google Scholar 

  79. Kourtis AP, Bulterys M (2010) Mother-to-child transmission of HIV: pathogenesis, mechanisms and pathways. Clin Perinatol 37:721–737, vii

    Article  PubMed  Google Scholar 

  80. Yamaguchi K, Sugiyama T, Takizawa M, Yamamoto N, Honda M, Natori M (2007) Viability of infectious viral particles of HIV and BMCs in breast milk. J Clin Virol 39:222–225

    Article  PubMed  CAS  Google Scholar 

  81. Walter J, Kuhn L, Aldrovandi GM (2008) Advances in basic science understanding of mother-to-child HIV-1 transmission. Curr Opin HIV AIDS 3:146–150

    Article  PubMed  Google Scholar 

  82. Coutsoudis A, Dabis F, Fawzi W et al (2004) Late postnatal transmission of HIV-1 in breast-fed children: an individual patient data meta-analysis. J Infect Dis 189:2154–2166

    Article  PubMed  Google Scholar 

  83. Miotti PG, Taha TE, Kumwenda NI et al (1999) HIV transmission through breastfeeding: a study in Malawi. JAMA 282:744–749

    Article  PubMed  CAS  Google Scholar 

  84. Moodley D, Moodley J, Coovadia H et al (2003) A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis 187:725–735

    Article  PubMed  CAS  Google Scholar 

  85. Mandelbrot L, Burgard M, Teglas JP et al (1999) Frequent detection of HIV-1 in the gastric aspirates of neonates born to HIV-infected mothers. AIDS 13:2143–2149

    Article  PubMed  CAS  Google Scholar 

  86. Coovadia HM, Rollins NC, Bland RM et al (2007) Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. Lancet 369:1107–1116

    Article  PubMed  Google Scholar 

  87. Kuhn L, Sinkala M, Kankasa C et al (2007) High uptake of exclusive breastfeeding and reduced early post-natal HIV transmission. PLoS One 2:e1363

    Article  PubMed  Google Scholar 

  88. Olesen R, Wahl A, Denton PW, Garcia JV (2011) Immune reconstitution of the female reproductive tract of humanized BLT mice and their susceptibility to human immunodeficiency virus infection. J Reprod Immunol 88:195–203

    Article  PubMed  CAS  Google Scholar 

  89. Zhu T, Mo H, Wang N et al (1993) Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science 261:1179–1181

    Article  PubMed  CAS  Google Scholar 

  90. Zhang LQ, MacKenzie P, Cleland A, Holmes EC, Brown AJ, Simmonds P (1993) Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection. J Virol 67:3345–3356

    PubMed  CAS  Google Scholar 

  91. Wolinsky SM, Wike CM, Korber BT et al (1992) Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants. Science 255:1134–1137

    Article  PubMed  CAS  Google Scholar 

  92. Derdeyn CA, Decker JM, Bibollet-Ruche F et al (2004) Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science 303:2019–2022

    Article  PubMed  CAS  Google Scholar 

  93. Keele BF, Giorgi EE, Salazar-Gonzalez JF et al (2008) Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci USA 105:7552–7557

    Article  PubMed  CAS  Google Scholar 

  94. Zhang H, Tully DC, Hoffmann FG, He J, Kankasa C, Wood C (2010) Restricted genetic diversity of HIV-1 subtype C envelope glycoprotein from perinatally infected Zambian infants. PLoS One 5:e9294

    Article  PubMed  CAS  Google Scholar 

  95. Margolis L, Shattock R (2006) Selective transmission of CCR5-utilizing HIV-1: the ‘gatekeeper’ problem resolved? Nat Rev Microbiol 4:312–317

    Article  PubMed  CAS  Google Scholar 

  96. Salvatori F, Scarlatti G (2001) HIV type 1 chemokine receptor usage in mother-to-child transmission. AIDS Res Hum Retroviruses 17:925–935

    Article  PubMed  CAS  Google Scholar 

  97. Rainwater SM, Wu X, Nduati R et al (2007) Cloning and characterization of functional subtype A HIV-1 envelope variants transmitted through breastfeeding. Curr HIV Res 5:189–197

    Article  PubMed  CAS  Google Scholar 

  98. Mulder-Kampinga GA, Simonon A, Kuiken CL et al (1995) Similarity in env and gag genes between genomic RNAs of human immunodeficiency virus type 1 (HIV-1) from mother and infant is unrelated to time of HIV-1 RNA positivity in the child. J Virol 69:2285–2296

    PubMed  CAS  Google Scholar 

  99. Satomi M, Shimizu M, Shinya E et al (2005) Transmission of macrophage-tropic HIV-1 by breast-milk macrophages via DC-SIGN. J Infect Dis 191:174–181

    Article  PubMed  CAS  Google Scholar 

  100. Heath L, Conway S, Jones L et al (2010) Restriction of HIV-1 genotypes in breast milk does not account for the population transmission genetic bottleneck that occurs following transmission. PLoS One 5:e10213

    Article  PubMed  CAS  Google Scholar 

  101. Salazar-Gonzalez JF, Salazar MG, Learn GH et al (2011) Origin and evolution of HIV-1 in breast milk determined by single-genome amplification and sequencing. J Virol 85:2751–2763

    Article  PubMed  CAS  Google Scholar 

  102. Andreotti M, Galluzzo CM, Guidotti G et al (2009) Comparison of HIV type 1 sequences from plasma, cell-free breast milk, and cell-associated breast milk viral populations in treated and untreated women in Mozambique. AIDS Res Hum Retroviruses 25:707–711

    Article  PubMed  CAS  Google Scholar 

  103. Renjifo B, Gilbert P, Chaplin B et al (2004) Preferential in-utero transmission of HIV-1 subtype C as compared to HIV-1 subtype A or D. AIDS 18:1629–1636

    Article  PubMed  CAS  Google Scholar 

  104. Tapia N, Franco S, Puig-Basagoiti F et al (2003) Influence of human immunodeficiency virus type 1 subtype on mother-to-child transmission. J Gen Virol 84:607–613

    Article  PubMed  CAS  Google Scholar 

  105. Murray MC, Embree JE, Ramdahin SG, Anzala AO, Njenga S, Plummer FA (2000) Effect of human immunodeficiency virus (HIV) type 1 viral genotype on mother-to-child transmission of HIV-1. J Infect Dis 181:746–749

    Article  PubMed  CAS  Google Scholar 

  106. Yang C, Li M, Newman RD et al (2003) Genetic diversity of HIV-1 in western Kenya: subtype-specific differences in mother-to-child transmission. AIDS 17:1667–1674

    Article  PubMed  Google Scholar 

  107. Renjifo B, Fawzi W, Mwakagile D et al (2001) Differences in perinatal transmission among human immunodeficiency virus type 1 genotypes. J Hum Virol 4:16–25

    PubMed  CAS  Google Scholar 

  108. Blackard JT, Renjifo B, Fawzi W et al (2001) HIV-1 LTR subtype and perinatal transmission. Virology 287:261–265

    Article  PubMed  CAS  Google Scholar 

  109. Koulinska IN, Villamor E, Msamanga G et al (2006) Risk of HIV-1 transmission by breastfeeding among mothers infected with recombinant and non-recombinant HIV-1 genotypes. Virus Res 120:191–198

    Article  PubMed  CAS  Google Scholar 

  110. Eshleman SH, Lie Y, Hoover DR et al (2006) Association between the replication capacity and mother-to-child transmission of HIV-1, in antiretroviral drug-naive Malawian women. J Infect Dis 193:1512–1515

    Article  PubMed  Google Scholar 

  111. Becquart P, Chomont N, Roques P et al (2002) Compartmentalization of HIV-1 between breast milk and blood of HIV-infected mothers. Virology 300:109–117

    Article  PubMed  CAS  Google Scholar 

  112. Becquart P, Courgnaud V, Willumsen J, Van de Perre P (2007) Diversity of HIV-1 RNA and DNA in breast milk from HIV-1-infected mothers. Virology 363:256–260

    Article  PubMed  CAS  Google Scholar 

  113. Henderson GJ, Hoffman NG, Ping LH et al (2004) HIV-1 populations in blood and breast milk are similar. Virology 330:295–303

    Article  PubMed  CAS  Google Scholar 

  114. Gantt S, Carlsson J, Heath L et al (2010) Genetic analyses of HIV-1 env sequences demonstrate limited compartmentalization in breast milk and suggest viral replication within the breast that increases with mastitis. J Virol 84:10812–10819

    Article  PubMed  CAS  Google Scholar 

  115. Gray RR, Salemi M, Lowe A et al (2011) Multiple independent lineages of HIV-1 persist in breast milk and plasma. AIDS 25:143–152

    Article  PubMed  Google Scholar 

  116. Andreotti M, Guidotti G, Galluzzo CM et al (2007) Resistance mutation patterns in plasma and breast milk of HIV-infected women receiving highly-active antiretroviral therapy for mother-to-child transmission prevention. AIDS 21:2360–2362

    Article  PubMed  Google Scholar 

  117. Farr SL, Nelson JA, Ng’ombe TJ et al (2010) Addition of 7 days of zidovudine plus lamivudine to peripartum single-dose nevirapine effectively reduces nevirapine resistance postpartum in HIV-infected mothers in Malawi. J Acquir Immune Defic Syndr 54:515–523

    Article  PubMed  CAS  Google Scholar 

  118. Hudelson SE, McConnell MS, Bagenda D et al (2010) Emergence and persistence of nevirapine resistance in breast milk after single-dose nevirapine administration. AIDS 24:557–561

    Article  PubMed  CAS  Google Scholar 

  119. Kassaye S, Lee E, Kantor R et al (2007) Drug resistance in plasma and breast milk after single-dose nevirapine in subtype C HIV type 1: population and clonal sequence analysis. AIDS Res Hum Retroviruses 23:1055–1061

    Article  PubMed  CAS  Google Scholar 

  120. Lee EJ, Kantor R, Zijenah L et al (2005) Breast-milk shedding of drug-resistant HIV-1 subtype C in women exposed to single-dose nevirapine. J Infect Dis 192:1260–1264

    Article  PubMed  CAS  Google Scholar 

  121. Pilger D, Hauser A, Kuecherer C et al (2011) Minor drug-resistant HIV type-1 variants in breast milk and plasma of HIV type-1-infected Ugandan women after nevirapine single-dose prophylaxis. Antivir Ther 16:109–113

    Article  PubMed  CAS  Google Scholar 

  122. Kroodsma KL, Kozal MJ, Hamed KA, Winters MA, Merigan TC (1994) Detection of drug resistance mutations in the human immunodeficiency virus type 1 (HIV-1) pol gene: differences in semen and blood HIV-1 RNA and proviral DNA. J Infect Dis 170:1292–1295

    Article  PubMed  CAS  Google Scholar 

  123. Eron JJ, Vernazza PL, Johnston DM et al (1998) Resistance of HIV-1 to antiretroviral agents in blood and seminal plasma: implications for transmission. AIDS 12:F181–F189

    Article  PubMed  CAS  Google Scholar 

  124. Kashuba AD, Dyer JR, Kramer LM, Raasch RH, Eron JJ, Cohen MS (1999) Antiretroviral-drug concentrations in semen: implications for sexual transmission of human immunodeficiency virus type 1. Antimicrob Agents Chemother 43:1817–1826

    PubMed  CAS  Google Scholar 

  125. Moorthy A, Gupta A, Bhosale R et al (2009) Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. PLoS One 4:e4096

    Article  PubMed  CAS  Google Scholar 

  126. Shetty AK, Coovadia HM, Mirochnick MM et al (2003) Safety and trough concentrations of nevirapine prophylaxis given daily, twice weekly, or weekly in breast-feeding infants from birth to 6 months. J Acquir Immune Defic Syndr 34:482–490

    Article  PubMed  CAS  Google Scholar 

  127. Richman D, Shih CK, Lowy I et al (1991) Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture. Proc Natl Acad Sci USA 88:11241–11245

    Article  PubMed  CAS  Google Scholar 

  128. Richman DD, Havlir D, Corbeil J et al (1994) Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy. J Virol 68:1660–1666

    PubMed  CAS  Google Scholar 

  129. Eshleman SH, Mracna M, Guay LA et al (2001) Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012). AIDS 15:1951–1957

    Article  PubMed  CAS  Google Scholar 

  130. Arrive E, Newell ML, Ekouevi DK et al (2007) Prevalence of resistance to nevirapine in mothers and children after single-dose exposure to prevent vertical transmission of HIV-1: a meta-analysis. Int J Epidemiol 36:1009–1021

    Article  PubMed  Google Scholar 

  131. Flys T, Nissley DV, Claasen CW et al (2005) Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. J Infect Dis 192:24–29

    Article  PubMed  CAS  Google Scholar 

  132. Church JD, Huang W, Parkin N et al (2009) Comparison of laboratory methods for analysis of non-nucleoside reverse transcriptase inhibitor resistance in Ugandan infants. AIDS Res Hum Retroviruses 25:657–663

    Article  PubMed  CAS  Google Scholar 

  133. Hammer SM (2005) Single-dose nevirapine and drug resistance: the more you look, the more you find. J Infect Dis 192:1–3

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Microbiology & Immunology and Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB# 7290, Chapel Hill, NC, 27599-7290, USA

    Susan A. Fiscus Ph.D.

  2. Departments of Pediatrics and Pathology and Laboratory Medicine, Children’s Hospital of Los Angeles, Los Angeles, CA, USA

    Grace M. Aldrovandi MD, CM

Authors
  1. Susan A. Fiscus Ph.D.
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  2. Grace M. Aldrovandi MD, CM
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Correspondence to Susan A. Fiscus Ph.D. .

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Editors and Affiliations

  1. School of Medicine, Emory University, Buford Highway 4770, Atlanta, 30341, Georgia, USA

    Athena P. Kourtis

  2. and Prevention, Global AIDS Program - China, Centers for Disease Control, Emory University School of Medicine, Beijing, 100600, China, People's Republic

    Marc Bulterys

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Fiscus, S.A., Aldrovandi, G.M. (2012). Virologic Determinants of Breast Milk Transmission of HIV-1. In: Kourtis, A., Bulterys, M. (eds) Human Immunodeficiency Virus type 1 (HIV-1) and Breastfeeding. Advances in Experimental Medicine and Biology, vol 743. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-2251-8_5

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