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HIV-1 Resistance to Antiretroviral Agents: Relevance to Mothers and Infants in the Breastfeeding Setting

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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))

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Abstract

HIV is a retrovirus whose genetic material is comprised of RNA. It is a decidedly adaptable virus with properties of high replication rates in association with an RNA copying enzyme—reverse transcriptase—which possesses a relatively high copying error rate, in the order of 1 error or mutation for every 10,000 nucleotides copied. This translates to a single mutation for every viral replication event on average in the setting of a billion viral copies produced daily in an infected individual. As such, the viral quasispecies (the pool of viral variants present at a given time) can and does adapt rapidly to environmental pressures such as the immune response or antiretroviral agents. It should not be surprising, therefore, that as antiretroviral agents have been developed and deployed, mutations in HIV genes associated with ARV resistance have rapidly been detected, underscoring the strategy of multiple agent and multiple class ARV therapy known as highly active antiretroviral therapy (HAART).

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References

  1. Connor EM, Sperling RS, Gelber R et al (2004) Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 331(18):1173–1180

    Article  Google Scholar 

  2. Guay LA, Musoke P, Fleming T et al (1999) Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 354:795–802

    PubMed  CAS  Google Scholar 

  3. Dorenbaum A, Cunningham CK, Gelber RD et al (2003) Two-dose nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission: a randomized trial. JAMA 288:189–198

    Article  Google Scholar 

  4. Cooper ER, Charurat M, Mofenson LM et al (2002) Combination antiretroviral strategies for the treatment of HIV-1 infected pregnant women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr 29:484–494

    PubMed  CAS  Google Scholar 

  5. Chou R, Smits AK, Huffman LH et al (2005) Prenatal screening for HIV: a review of the evidence for the US Preventive Services Task Force. Ann Intern Med 143:38–54

    PubMed  Google Scholar 

  6. Huang DD, Bremer JW, Brambilla DJ et al (2005) Model for assessment of proficiency of human immunodeficiency virus type 1 sequencing-based genotypic antiretroviral assays. J Clin Microbiol 43:3963–3970

    Article  PubMed  Google Scholar 

  7. Halvas EK, Wiegand A, Boltz VF et al (2010) Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment-experienced patients. J Infect Dis 201(5):672–680

    PubMed  CAS  Google Scholar 

  8. Paredes R, Lalama CM, Ribaudo HJ et al (2010) Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. J Infect Dis 201(5):662–671

    PubMed  CAS  Google Scholar 

  9. 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(3):1170–1176

    Article  PubMed  CAS  Google Scholar 

  10. Spencer L, Neely M, Mordwinkin N et al Intensive PK of zidovudine (AZT), lamivudine (3TC), and atazanavir (ATV) and HIV-1 viral load in breast milk and plasma in HIV+ women receiving HAART Therapy. 16th CROI 2009; Abstract #942

    Google Scholar 

  11. Corbett A, Martinson F, Rezk N et al Antiretroviral drug concentrations in breast milk and breastfeeding infants. 15th CROI 2008; Abstract #648

    Google Scholar 

  12. Kunz A, Frank M, Mugenyi K et al (2009) Persistence of nevirapine in breast milk and plasma of mothers and their children after single-dose administration. J Antimicrob Chemother 63(1):170–177

    Article  PubMed  CAS  Google Scholar 

  13. Corbett A, Martinson F, Rezk N et al Lopinavir/ritonavir concentrations in breast milk and breast-feeding infants. 16th CROI 2009; Abstract #947

    Google Scholar 

  14. Andreotti M, Galluzzo CM, Guidotti G, Germano P, Doro Altan A, Pirillo MF (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 Research and Human Retroviruses, 25

    Google Scholar 

  15. 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(17):2360–2362

    Article  PubMed  Google Scholar 

  16. Salazar-Gonzalez JF, Salazar MG et al (2011) Origin and evolution of HIV-1 in breast milk determined by single genome amplification and sequencing. J Virol 85(6):2751–63, Mar 2011

    Google Scholar 

  17. 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(6):819–825, 15 Mar 2011

    Google Scholar 

  18. 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 5:1–11

    Article  Google Scholar 

  19. Gray RR, Salemi M, Lowe A et al (2011) Multiple independent lineages of HIV-1 persist in breast milk and plasma. AIDS 25(2):143–152

    Article  PubMed  Google Scholar 

  20. 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 

  21. WHO. Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. http://www.who.int/hiv/pub/mtct/antiretroviral/en/index.html. Accessed 17 Feb 2011

  22. 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 

  23. Aizire J, Mudiope P, Matovu F et al (2010) Impact of systemic and mucosal nevirapine levels on serial HIV RNA levels in maternal plasma and breast milk after perinatal single dose nevirapine. 17th Conference on Retroviruses and Opportunistic Infections. http://www.retroconference.org/2010/Abstracts/37126.htm. Accessed 17 Feb 2011

  24. 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. JID 192:1260–1264

    Article  PubMed  CAS  Google Scholar 

  25. Chasela CS, Hudgens MG, Jamieson DJ et al (2010) Maternal or infant antiretroviral drugs to reduce HIV-1 transmission. N Engl J Med 362(24):2271–2281

    Article  PubMed  CAS  Google Scholar 

  26. Thomas TK, Masaba R, Borkowf CB et al and KiBS Study Team (2011) Triple-antiretroviral prophylaxis to prevent mother-to-child HIV transmission through breastfeeding–the Kisumu Breastfeeding Study, Kenya: a clinical trial. PLoS Med 8(3):e1001015. Epub 2011 Mar 29

    Google Scholar 

  27. Kilewo C, Karlsson K, Ngarina M et al (2009) Prevention of mother to child transmission of HIV-1 through breastfeeding by treating mothers with triple antiretroviral therapy in Dar es Salaam, Tanzania: The Mitra Plus Study. J Acquir Immune Defic Syndr 52:406–416

    Article  PubMed  Google Scholar 

  28. Palombi L, Marazzi MC, Voetberg A, Magid NA, The DREAM Program prevention of mother to child transmission team (2007) Treatment acceleration program and the experience of the DREAM program in prevention of mother to child transmission of HIV. AIDS 21(Suppl 4):S65–S71

    Article  PubMed  Google Scholar 

  29. Shapiro RL, Hughes MD, Ogwu A et al (2010) Antiretroviral regimens in pregnancy and breast-feeding in Botswana. N Engl J Med 362(24):2282–2294, 17 June 2010

    Google Scholar 

  30. Kesho Bora Study Group (2011) Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trial. Lancet Infect Dis. published online 14 Jan 2011, doi:10.1016/S1473-3099(10)70288-7

  31. Bedri A, Gudetta B, Isehak A et al (2008) Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomized controlled trials. Lancet 372:300–313

    Article  PubMed  Google Scholar 

  32. Kumwenda NI, Hoover DR, Jamieson D et al (2008) Extended antiretroviral prophylaxis to reduce breast milk HIV-1 transmission. N Engl J Med 359:119–129

    Article  PubMed  CAS  Google Scholar 

  33. Kilewo C, Karlsson K, Massawe A et al (2008) Prevention of mother-to-child transmission of HIV-1 through breast-feeding by treating infants prophylactically with lamivudine in Dar es Salaam, Tanzania: the Mitra study. J Acquir Immune Defic Syndr 48:315–323

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  35. 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 

  36. 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 

  37. 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 

  38. 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(17):2360–2362, 12 Nov 2007

    Google Scholar 

  39. 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(7):707–711, Jul 2009

    Google Scholar 

  40. 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 

  41. Bulterys M, Weidle PJ, Abrams EJ, Fowler MG (2005) Combination antiretroviral therapy in African nursing mothers and drug exposure in their infants: new pharmokinetic and virologic findings. J Infect Dis 192:709–712

    Article  PubMed  CAS  Google Scholar 

  42. 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 

  43. 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 

  44. 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. JID 192:1260–1264

    Article  PubMed  CAS  Google Scholar 

  45. 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 

  46. Giuliano M, Guidotti G, Andreotti M et al (2007) Resistance mutation patterns in plasma and breast milk of HIV-infected women receiving HAART for PMTCT: a study within the DREAM program. Abstract 135; 14th Conference on Retroviruses and Opportunistic Infections, 2007

    Google Scholar 

  47. 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 21:2360–2361

    Article  PubMed  Google Scholar 

  48. Persaud D, Bedri A, Ziemniak C et al and the Ethiopian SWEN Study Team (2011) Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission. AIDS Res Hum Retroviruses 27(8):823–829. Epub 2011 Feb 25, Aug 2011

    Google Scholar 

  49. 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  Google Scholar 

  50. Lidstrom J, Guay L, Musoke P et al (2010) Multi-class drug resistance arises frequently in HIV-infected breastfeeding infants whose mothers initiate HAART post-partum. Abstract 920; 17th Conference on Retroviruses and Opportunistic Infections, 2010

    Google Scholar 

  51. Thomas R, Masaba R, Ndivo R, et al. Kisumu breastfeeding study team (2008) Prevention of mother-to-child transmission of HIV-1 among breastfeeding mothers using HAART: the Kisumu breastfeeding study, Kisumu, Kenya 2003–2007 (45aLB). 15th Conference on Retroviruses and Opportunistic Infections, 2008, Boston, MA

    Google Scholar 

  52. Zeh C, Weidle PJ, Nafisa L et al (2011) HIV-1 drug resistance emergence among breastfeeding infants born to ­HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. PLoS Med. 8(3):e1000430. Epub 2011 Mar 29, Mar 2011

    Google Scholar 

  53. WHO. Guidelines on HIV and infant feeding 2010. http://www.who.int/child_adolescent_health/documents/9789241599535/en/index.html. Accessed 17 Feb 2011

  54. Mofenson L (2009) Prevention of breast milk transmission of HIV: the time is now. J Acquir Immune Defic Syndr 52:305–308

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. HCMC Office, US Centers for Disease Control and Prevention, Ho Chi Minh City, Vietnam

    Michelle S. McConnell MD

  2. Section of Infectious Diseases and International Health, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH, 03756, USA

    Paul Palumbo MD

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  1. Michelle S. McConnell MD
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  2. Paul Palumbo MD
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Correspondence to Paul Palumbo MD .

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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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McConnell, M.S., Palumbo, P. (2012). HIV-1 Resistance to Antiretroviral Agents: Relevance to Mothers and Infants in the Breastfeeding Setting. 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_6

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  • DOI: https://doi.org/10.1007/978-1-4614-2251-8_6

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