Antiretroviral drugs for preventing mother-to-child transmission of HIV in sub-Saharan Africa: Balancing efficacy and infant toxicity

AIDS

Volumn 22, Issue 17, 2008, Pages 2359-2369

  Ciaranello, Andrea L ^a   Seage III, George R ^d   Freedberg, Kenneth A ^a,c,d   Weinstein, Milton C ^d   Lockman, Shahin ^b,d   Walensky, Rochelle P ^a,b,c  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

Antiretroviral therapy; Decision analysis; HIV AIDS; Mitochondrial toxicity; Pediatric HIV; PMTCT; Sub Saharan Africa

Indexed keywords

ANTIRETROVIRUS AGENT; LAMIVUDINE PLUS ZIDOVUDINE; NEVIRAPINE; ZIDOVUDINE;

AFRICA; ARTICLE; ARTIFICIAL MILK; BREAST FEEDING; CONTROLLED STUDY; DISABILITY; DRUG EFFICACY; DRUG SAFETY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MITOCHONDRIAL TOXICITY; NEUROTOXICITY; PERINATAL INFECTION; PRIORITY JOURNAL; PROPHYLAXIS; RISK BENEFIT ANALYSIS; SENSITIVITY ANALYSIS; SINGLE DRUG DOSE; TREATMENT DURATION; VIRUS TRANSMISSION;

ADOLESCENT; ADULT; AFRICA SOUTH OF THE SAHARA; ANTI-HIV AGENTS; ANTI-RETROVIRAL AGENTS; BOTTLE FEEDING; BREAST FEEDING; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; INFANT, NEWBORN; INFECTIOUS DISEASE TRANSMISSION, VERTICAL; PREGNANCY; PREGNANCY COMPLICATIONS, INFECTIOUS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 56549097803     PISSN: 02699370     EISSN: None     Source Type: Journal    
DOI: 10.1097/QAD.0b013e3283189bd7     Document Type: Article

References (95)

1. Connor EM, Sperling RS, Gelber R, Kiselev P, Scott C, O'Sullivan MJ, et al. 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 1994; 331:1173-1180.
2. Dominguez K, Bertolli J, Fowler M, Peters V, Ortiz I, Melville S, et al. Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children < or = 5 years of age, Pediatric Spectrum of HIV Disease project (PSD), USA. Ann N Y Acad Sci 2000; 918:236-246.
3. Leroy V, Karon JM, Alioum A, Ekpini ER, Meda N, Creenberg AE, et al. Twenty-four month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission of HIV-1 in West Africa. AIDS 2002; 16:631-641.
4. Cooper ER, Charurat M, Mofenson L, Hanson IC, Pitt J, Diaz C, et al. Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr 2002; 29:484-494.
5. Petra Study Team. Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial. Lancet 2002; 359:1178-1186.
6. McIntyre JA, Martinson N, Gray GE, Hopley M, Kimura T, Robinson P, Mayers D. Addition of short course Combivir (CBV) to single dose Viramune (sdNVP) for the prevention of mother to child transmission (pMTCT) of HIV-1 can significantly decrease the subsequent development of maternal and paediatric NNRTI-resistant virus [Abstract no. TuFo0204]. International AIDS Society. Rio de Janeiro; 2005.
7. Guay LA, Musoke P, Fleming T, Bagenda D, Allen M, Nakabiito C, et al. 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 1999; 354:795-802.
8. Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Huong N, Koetsawang S, et al. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med 2004; 351:217-228.
9. Lallemant M, Jourdain G, Le Coeur S, Kim S, Koetsawang S, Comeau AM, et al. A trial of shortened zidovudine regimens to prevent mother-to-child transmission of human immunodeficiency virus type 1. Perinatal HIV Prevention Trial (Thailand) Investigators. N Engl J Med 2000; 343:982-991.
10. Mandelbrot L, Landreau-Mascaro A, Rekacewicz C, Berrebi A, Benifla JL, Burgard M, et al. Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1. JAMA 2001; 285:2083-2093.
11. Dabis F, Bequet L, Ekouevi DK, Viho I, Rouet F, Horo A, et al. Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission. AIDS 2005; 19:309-318.
12. Dorenbaum A, Cunningham CK, Gelber RD, Culnane M, Mofenson L, Britto P, et al. Two-dose intrapartum/newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission: a randomized trial. JAMA 2002; 288: 189-198.
13. Thistle P, Gottesman M, Pilon R, Glazier RH, Arbess G, Phillips E, et al. A randomized control trial of an Ultra-Short zidovudine regimen in the prevention of perinatal HIV transmission in rural Zimbabwe. Cent Afr J Med 2004; 50:79-84.
14. Shaffer N, Chuachoowong R, Mock PA, Bhadrakom C, Siriwasin W, Young NL, et al. Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial. Bangkok Collaborative Perinatal HIV Transmission Study Group. Lancet 1999; 353:773-780.
15. Moodley D, Moodley J, Coovadia H, Gray G, McIntyre J, Hofmyer J, et al. 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 2003; 187:725-735.
16. Taha TE, Kumwenda NI, Hoover DR, Fiscus SA, Kafulafula G, Nkhoma C, et al. Nevirapine and zidovudine at birth to reduce perinatal transmission of HIV in an African setting: a randomized controlled trial. JAMA 2004; 292:202-209.
17. Nduati R, John G, Mbori-Ngacha D, Richardson B, Overbaugh J, Mwatha A, et al. Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial. JAMA 2000; 283:1167-1174.
18. Leroy V, Sakarovitch C, Cortina-Borja M, McIntyre J, Coovadia H, Dabis F, et al. Is there a difference in the efficacy of peripartum antiretroviral regimens in reducing mother-to-child transmission of HIV in Africa? AIDS 2005; 19:1865-1875.
19. Kumwenda NI, Hoover DR, Mofenson LM, Thigpen MC, Kafulafula G, Li Q, et al. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. N Engl J Med 2008; 359:119-129.
20. Sastry J, and The Six Week Extended Dose Nevirapine (SWEN) Study Team. Extended-dose nevirapine to 6 weeks of age for infants in Ethiopia, India, and Uganda: a randomized trial for prevention of HIV transmission through breastfeeding [Abstract 43]. Proceedings of the Conference on Retroviruses and Opportunistic Infections; Boston; 2008.
21. Bedri A, Gudetta B, Isehak A, Kumbi S, Lulseged S, Mengistu Y, et al. 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 randomised controlled trials. Lancet 2008; 372:300-313.
22. Thomas T, Masaba R, Ndivo R, Zeh C, Borkowf C, Thigpen M, et al., and Kisumu Breastfeeding Study Team. Prevention of mother-to-child transmission of HIV-1 among breastfeeding mothers using HAART: The Kisumu Breastfeeding Study, Kisumu, Kenya, 2003-2007 [Abstract 45aLB]. Proceedings of the Conference on Retroviruses and Opportunistic Infections; Boston; 2008.
23. Palombi L, Marazzi MC, Voetberg A, Magid NA. Treatment acceleration program and the experience of the DREAM program in prevention of mother-to-child transmission of HIV. AIDS 2007; 21 (Suppl 4):S65-S71.
24. Kilewo C, Karlsson K, Ngarina M, Massawe A, Lyamuya E, Lipyoga R, et al. Prevention of mother-to-child transmission of HIV-1 through breastfeeding by treating mothers prophylactically with triple antiretroviral therapy in Dar es Salaam, Tanzania - the MITRA PLUS study. International AIDS Society. Sydney, Australia; 2007.
25. Arendt V, Ndimubanzi P, Vyankandondera J, Ndayisaba G, Muganda J, Courteille O, et al. AMATA study: effectiveness of antiretroviral therapy in breastfeeding mothers to prevent postnatal vertical transmission in Rwanda. International AIDS Society. Sydney, Australia; 2007.
26. Thior I, Lockman S, Smeaton LM, Shapiro RL, Wester C, Heymann SJ, et al. Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding phis infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana: a randomized trial: the Mashi Study. JAMA 2006; 296:794-805.
27. Jackson JB, Musoke P, Fleming T, Guay LA, Bagenda D, Allen M, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet 2003; 362:859-868.
28. Blanche S, Tardieu M, Rustin P, Slama A, Barret B, Firtion G, et al. Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues. Lancet 1999; 354:1084-1089.
29. Aldrovandi G, Moye J, Chu C, Ha B, Handelsman E, Shearer W, et al., for the WITS Study Group. Mitochondrial DNA content of peripheral blood mononuclear cells in uninfected infants born to HIV-infected women with or without ART exposure in the Women and Infants Transmission Study [Paper #695]. Conference on Retroviruses and Opportunistic Infections; Denver; 2006.
30. Vigano A, Bianchi R, Schneider L, Cafarelli L, Tornaghi R, Pinti M, et al. Lack of hyperlactatemia and impaired mitochondrial DNA content in CD4+ cells of HIV-uninfected infants exposed to perinatal antiretroviral therapy [Paper #942]. Proceedings of the Conference on Retroviruses and Opportunistic Infections; San Francisco; 2004.
31. Maagaard A, Holberg-Petersen M, Kollberg G, Oldfors A, Sandvik L, Bruun JN. Mitochondrial (mt)DNA changes in tissue may not be reflected by depletion of mtDNA in peripheral blood mononuclear cells in HIV-infected patients. Antivir Ther 2006; 11:601-608.
32. Barret B, Tardieu M, Rustin P, Lacroix C, Chabrol B, Desguerre I, et al. Persistent mitochondrial dysfunction in HIV-1-exposed but uninfected infants: clinical screening in a large prospective cohort. AIDS 2003; 17:1769-1785.
33. Culnane M, Fowler M, Lee SS, McSherry G, Brady M, O'Donnell K, et al. Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women. Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams. JAMA 1999; 281:151-157.
34. Le Chenadec J, Mayaux MJ, Guihenneuc-Jouyaux C, Blanche S. Perinatal antiretroviral treatment and hematopoiesis in HIV-uninfected infants. AIDS 2003; 17:2053-2061.
35. O'Meara M, Goode M, Hayes E, Butler K. Simplification of neonatal component of regimens to prevent perinatal HIV transmission [Abstract #853]. Proceedings of the Conference on Retroviruses and Opportunistic Infections; Boston; 2003.
36. Noguera A, Fortuny C, Munoz-Almagro C, Sanchez E, Vilaseca MA, Artuch R, et al. Hyperlactatemia in human immunodeficiency virus-uninfected infants who are exposed to antiretrovirals. Pediatrics 2004; 114:e598-e603.
37. Giaquinto C, De Romeo A, Giacomet V, Rampon O, Ruga E, Burlina A, et al. Lactic acid levels in children perinatally treated with antiretroviral agents to prevent HIV transmission. AIDS 2001; 15:1074-1075.
38. Ekouevi DK, Toure R, Becquet R, Viho I, Sakarovitch C, Rouet F, et al. Serum lactate levels in infants exposed peripartum to antiretroviral agents to prevent mother-to-child transmission of HIV: Agence Nationale de Recherches Sur le SIDA et les Hepatites Virales 1209 study, Abidjan. Ivory Coast Pediatrics 2006; 118:e1071-e1077.
39. Brogly S, Ylitalo N, Mofenson L, Oleskee J, Van Dyke R, Craing M, et al. In utero nucleoside reverse transcriptase inhibitor exposure and signs of possible mitochondrial dysfunction in HIV-uninfected children. AIDS 2007; 21:929-938.
40. European Collaborative Study. Exposure to antiretroviral therapy in utero or early life: the health of uninfected children born to HIV-infected women. J Acquir Immune Defic Syndr 2003; 32:380-387.
41. Benhammou V, Tardieu M, Warszawski J, Rustin P, Blanche S. Clinical mitochondrial dysfunction in uninfected children born to HIV-infected mothers following perinatal exposure to nucleoside analogues. Environ Mol Mutagen 2007; 48:173-178.
42. Hunink M, Glasziou PP, Siegel JE, Weeks JC, Pliskin JS, Elstein AS, Weinstein MC. Decision making in health and medicine: integrating evidence and values. Cambridge: Cambridge University Press; 2003.
43. World Health Organization. Antiretroviral drugs for treating pregnant women and preventing HIV infections in infants in resource-limited settings: towards universal access: recommendations for a public health approach; 2006. http://www.who.int/hiv/pub/guidelines/en/. Accessed 15 October 2006. July 15, 2008.
44. US Public Health Service Task Force. Perinatal HIV Guidelines Working Group. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States; 2008. http://aidsinfo.nih.gov/ contentfiles/PerinatalGL.pdf.
45. Feeney ME, Tang Y, Pfafferott K, Roosevelt KA, Draenert R, Trocha A, et al. HIV-1 viral escape in infancy followed by emergence of a variant-specific CTL response. J Immunol 2005; 174:7524-7530.
46. Massad LS, Springer G, Jacobson L, Watts H, Anastos K, Korn A, et al. Pregnancy rates and predictors of conception, miscarriage and abortion in US women with HIV. AIDS 2004; 18:281-286.
47. Coutsoudis A, Pillay K, Kuhn L, Spooner E, Tsai WY, Coovadia HM. Method of feeding and transmission of HIV-1 from mothers to children by 15 months of age: prospective cohort study from Durban, South Africa. AIDS 2001; 15:379-387.
48. Kuhn L, Aldrovandi GM, Sinkala M, Kankasa C, Semrau K, Mwiya M, et al. Effects of early, abrupt weaning on HIV-free survival of children in Zambia. N Engl J Med 2008; 359:130-141.
49. Taha TE, Hoover DR, Kumwenda NI, Fiscus SA, Kafulafula G, Nkhoma C, et al. Late postnatal transmission of HIV-1 and associated factors. J Infect Dis 2007; 196:10-14.
50. Magder LS, Mofenson L, Paul ME, Zorrilla CD, Blattner WA, Tuomala RE, et al. Risk factors for in utero and intrapartum transmission of HIV. J Acquir Immune Defic Syndr 2005; 38:87-95.
51. Dabis F, Msellati P, Meda N, Welffens-Ekra C, You B, Manigart O, et al. 6-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Cote d'Ivoire and Burkina Faso: a double-blind placebo-controlled multicentre trial. DITRAME Study Group. Diminution de la Transmission Mere-Enfant. Lancet 1999; 353:786-792.
52. Coutsoudis A, Pillay K, Spooner E, Kuhn L, Coovadia HM. Influence of infant-feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa: a prospective cohort study. South African Vitamin A Study Group. Lancet 1999; 354:471-476.
53. Thistle P, Spitzer RF, Glazier RH, Pilon R, Arbess G, Simor A, et al. A randomized, double-blind, placebo-controlled trial of combined nevirapine and zidovudine compared with nevirapine alone in the prevention of perinatal transmission of HIV in Zimbabwe. Clin Infect Dis 2007; 44:111-119.
54. Fawzi W, Msamanga G, Spiegelman D, Renjifo B, Bang H, Kapiga S, et al. Transmission of HIV-1 through breastfeeding among women in Dar es Salaam, Tanzania. J Acquir Immune Defic Syndr 2002; 31:331-338.
55. Iliff PJ, Piwoz EG, Tavengwa NV, Zunguza CD, Marinda ET, Nathoo KJ, et al. Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 2005; 19:699-708.
56. Chi BH, Chintu N, Cantrell RA, Kankasa C, Kruse G, Mbewe F, et al. Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission. J Acquir Immune Defic Syndr 2008; 48:220-223.
57. Jamisse L, Balkus J, Farquhar C, Osman N, Djedje M, Hitti J. Perinatal HIV transmission with HAART during late pregnancy and postpartum [Abstract 756]. Proceedings of the Conference on Retroviruses and Opportunistic Infections; Los Angeles; 2007.
58. Palombi L, Germano P, Liotta G, Magnano san Lio M, Guidotti G, Assane A, et al. Safety and efficacy of maternal HAART in the prevention of early and late postnatal HIV-1 transmission in Mozambique [Paper #747]. Proceedings of the Conference on Retroviruses and Opponunistic Infections; Los Angeles; 2007.
59. Coutsoudis A, Dabis F, Fawzi W, Gaillard P, Haverkamp G, Harris DR, et al. Late postnatal transmission of HIV-1 in breastfed children: an individual patient data meta-analysis. J Infect Dis 2004; 189:2154-2166.
60. Uusimaa J, Remes AM, Rantala H, Vainionpaa L, Herva R, Vuopala K, et al. Childhood encephalopathies and myopathies: a prospective study in a defined population to assess the frequency of mitochondrial disorders. Pediatrics 2000; 105:598-603.
61. Darin N, Oldfors A, Moslemi AR, Holme E, Tulinius M. The incidence of mitochondrial encephalomyopathies in childhood: clinical features and morphological, biochemical, and DNA anbormalities. Ann Neurol 2001; 49:377-383.
62. Poirier MC, Divi RL, Al-Harthi L, Olivero OA, Nguyen V, Walker B, et al. Long-term mitochondrial toxicity in HIV-uninfected infants born to HIV-infected mothers. J Acquir Immune Defic Syndr 2003; 33:175-183.
63. Eypasch E, Lefering R, Kum CK, Troidl H. Probability of adverse events that have not yet occurred: a statistical reminder. BMJ 1995; 311:619-620.
64. World Health Organization. Mother-to-child transmission of HIV; 2007. http://www.who.int/hiv/mtct/en/index.html. Accessed 23 May 2007.
65. Spector SA, Saitoh A. Mitochondrial dysfunction: prevention of HIV-1 mother-to-infant transmission outweighs fear. AIDS 2006; 20:1777-1778.
66. Blanche S, Tardieu M, Benhammou V, Warszawski J, Rustin P. Mitochondrial dysfunction following perinatal exposure to nucleoside analogues. AIDS 2006; 20:1685-1690.
67. Tonwe-Gold B, Ekouevi DK, Viho I, Amani-Bosse C, Toure S, Coffie PA, et al. Antiretroviral treatment and prevention of peripartum and postnatal HIV transmission in West Africa: evaluation of a two-tiered approach. PLoS Med 2007; 4:e257.
68. Coovadia HM, Rollins NC, Bland RM, Little K, Coutsoudis A, Bennish ML, Newell ML. Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. Lancet 2007; 369:1107-1116.
69. De Cock KM, Fowler MG, Mercier E, De Vincenzi I, Saba J, Hoff E, et al. Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. JAMA 2000; 283:1175-1182.
70. Chigwedere P, Seage GR, Lee TH, Essex M. Efficacy of antiretroviral drugs in reducing mother-to-child transmission of HIV in Africa: a meta-analysis of published clinical trials. AIDS Res Hum Retroviruses 2008; 24:827-837.
71. Kourtis AP, Lee FK, Abrams EJ, Jamieson DJ, Bulterys M. Mother-to-child transmission of HIV-1: timing and implications for prevention. Lancet Infect Dis 2006; 6:726-732.
72. Dunn DT, Newell ML, Ades AE, Peckham CS. Risk of human immunodeficiency virus type 1 transmission through breastfeeding. Lancet 1992; 340:585-588.
73. Bulterys M, Nesheim S, Abrams EJ, Palumbo P, Farley J, Lampe M, Fowler MG. Lack of evidence of mitochondrial dysfunction in the offspring of HIV-infected women. Retrospective review of perinatal exposure to antiretroviral drugs in the Perinatal AIDS Collaborative Transmission Study. Ann N Y Acad Sci 2000; 918:212-221.
74. Nucleoside exposure in the children of HIV-infected women receiving antiretroviral drugs: absence of clear evidence for mitochondrial disease in children who died before 5 years of age in five United States cohorts. J Acquir Immune Defic Syndr 2000; 25:261-268.
75. Tovo PA, Chiapello N, Gabiano C, Zeviani M, Spada M. Zidovudine administration during pregnancy and mitochondrial disease in the offspring. Antivir Ther 2005; 10:697-699.
76. Chotpitayasunondh T, Vanprapar N, Simonds RJ, Chokephaibulkit K, Waranawat N, Mock P, et al. Safety of late in utero exposure to zidovudine in infants born to human immunodeficiency virus-infected mothers: Bangkok. Bangkok Collaborative Perinatal HIV Transmission Study Group. Pediatrics 2001; 107:E5.
77. Alimenti A, Forbes JC, Oberlander TF, Money DM, Grunau RE, Papsdorf MP, et al. A prospective controlled study of neurodevelopment in HIV-uninfected children exposed to combination antiretroviral drugs in pregnancy. Pediatrics 2006; 118: e1139-e1145.
78. Paul ME, Chantry CJ, Read JS, Frederick MM, Lu M, Pitt J, 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 2005; 24:46-56.
79. Divi RL, Haverkos KJ, Humsi JA, Shockley ME, Thamire C, Nagashima K, et al. Morphological and molecular course of mitochondrial pathology in cultured human cells exposed long-term to Zidovudine. Environ Mol Mutagen 2007; 48:179-189.
80. Divi RL, Leonard SL, Kuo MM, Nagashima K, Thamire C, St Claire MC, et al. Transplacentally exposed human and monkey newborn infants show similar evidence of nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity. Environ Mol Mutagen 2007; 48:201-209.
81. Venerosi A, Valanzano A, Alleva E, Calamandrei G. Prenatal exposure to anti-HIV drugs: neurobehavioral effects of zidovudine (AZT) + lamivudine (3TC) treatment in mice. Teratology 2001; 63:26-37.
82. Schapira AH. Mitochondrial disease. Lancet 2006; 368:70-82.
83. Haas R, Dietrich R. Neuroimaging of mitochondrial disorders. Mitochondrion 2004; 4:471-490.
84. National Institute of Child Health and Human Development. Pediatric HIV/AIDS Cohort Study Home Page; 2007. http://phacs.nichdclinicalstudies. org/overview.asp.
85. Newell ML, Coovadia H, Cortina-Borja M, Rollins N, Gaillard P, Dabis F. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet 2004; 364:1236-1243.
86. Fassinou P, Elenga N, Rouet F, Laguide R, Kouakoussui KA, Timite M, et al. Highly active antiretroviral therapies among HIV-1-infected children in Abidjan, Cote d'Ivoire. AIDS 2004; 18:1905-1913.
87. Violari A, Cotton M, Gibb D, Babiker A, Steyn J, Jean-Phillip P, McIntyre J. Antiretroviral therapy initiated before 12 weeks of age reduces early mortality in young HIV-infected infants: evidence from the Children with HIV Early Antiretroviral Therapy (CHER) Study. International AIDS Society; Sydney, Australia; 2007.
88. Bolton-Moore C, Mubiana-Mbewe M, Cantrell RA, Chintu N, Stringer EM, Chi BH, et al. Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary healthcare facilities in Zambia. JAMA 2007; 298:1888-1899.
89. Foster CJ, Biggs RL, Melvin D, Walters MD, Tudor-Williams G, Lyall EG. Neurodevelopmental outcomes in children with HIV infection under 3 years of age. Dev Med Child Neurol 2006; 48:677-682.
90. Hammer SM, Eron JJ Jr, Reiss P, Schooley RT, Thompson MA, Walmsley S, et al. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society - USA Panel. JAMA 2008; 300:555-570.
91. El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, Arduino RC, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006; 355:2283-2296.
92. Lundgren JD, Babiker A, El-Sadr W, Emery S, Grund B, Neaton JD, et al. Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ Cell counts and HIV RNA levels during follow-up. J Infect Dis 2008; 197:1145-1155.
93. Lockman S, Shapiro RL, Smeaton LM, Wester C, Thior I, Stevens L, et al. Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med 2007; 356:135-147.
94. Llorente A, Brouwers P, Charurat M, Magder L, Malee K, Mellins C, et al. Early neurodevelopmental markers predictive of mortality in infants infected with HIV-1. Dev Med Child Neurol 2003; 45:76-84.
95. Rouet F, Sakarovitch C, Msellati P, Elenga N, Montcho C, Viho I, et al. Pediatric viral human immunodeficiency virus type 1 RNA levels, timing of infection, and disease progression in African HIV-1-infected children. Pediatrics 2003; 112:e289.