title: Maternal antiretroviral therapy for the prevention of mother-to-child transmission of HIV in Malawi: maternal and infant outcomes two years after delivery.
abstract: BACKGROUND
  Optimized preventive strategies are needed to reach the objective of eliminating pediatric AIDS. This study aimed to define the determinants of residual HIV transmission in the context of maternal antiretroviral therapy (ART) administration to pregnant women, to assess infant safety of this strategy, and to evaluate its impact on maternal disease.
  
  
  RESULTS
  A total of 311 HIV-infected pregnant women were enrolled in Malawi in an observational study and received a nevirapine-based regimen from week 25 of gestation until 6 months after delivery (end of breastfeeding period) if their CD4+ count was > 350/mm(3) at baseline (n = 147), or indefinitely if they met the criteria for treatment (n. 164). Mother/child pairs were followed until 2 years after delivery. The Kaplan-Meier method was used to estimate HIV transmission, maternal disease progression, and survival at 24 months. The rate of HIV infant infection was 3.2% [95% confidence intervals (CI) 1.0-5.4]. Six of the 8 transmissions occurred among mothers with baseline CD4+ count > 350/mm(3). HIV-free survival of children was 85.8% (95% CI 81.4-90.1). Children born to mothers with baseline CD4+ count < 350/mm(3) were at increased risk of death (hazard ratio 2.6, 95% CI 1.1-6.1). Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm(3) was 20.6% (95% CI 9.2-31.9) by 18 months of drug discontinuation.
  
  
  CONCLUSIONS
  HIV transmission in this cohort was rare however, it occurred in a significative proportion among women with high CD4+ counts. Strategies to improve treatment adherence should be implemented to further reduce HIV transmission. Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage. Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy. marina.giuliano@iss.it
authors.forename: Marina
authors.initials: M
authors.lastname: Giuliano
authors.forename: Mauro
authors.initials: M
authors.lastname: Andreotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Liotta
authors.forename: Haswell
authors.initials: H
authors.lastname: Jere
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Sagno
authors.forename: Martin
authors.initials: M
authors.lastname: Maulidi
authors.forename: Sandro
authors.initials: S
authors.lastname: Mancinelli
authors.forename: Ersilia
authors.initials: E
authors.lastname: Buonomo
authors.forename: Paola
authors.initials: P
authors.lastname: Scarcella
authors.forename: Maria F
authors.initials: MF
authors.lastname: Pirillo
authors.forename: Roberta
authors.initials: R
authors.lastname: Amici
authors.forename: Susanna
authors.initials: S
authors.lastname: Ceffa
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
authors.forename: Leonardo
authors.initials: L
authors.lastname: Palombi
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Marazzi
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control / Q000635:transmission*; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008295:Malawi; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents
references.citation: Antivir Ther. 2012;17(8):1511-9
references.pmid: 22910456
references.citation: AIDS. 2013 May 15;27(8):1253-62
references.pmid: 23324656
references.citation: AIDS. 2007 Jul;21 Suppl 4:S65-71
references.pmid: 17620755
references.citation: PLoS Med. 2011 Mar;8(3):e1001015
references.pmid: 21468300
references.citation: JAMA. 2011 Feb 9;305(6):576-84
references.pmid: 21304083
references.citation: N Engl J Med. 2010 Jun 17;362(24):2271-81
references.pmid: 20554982
references.citation: Lancet Infect Dis. 2011 Mar;11(3):171-80
references.pmid: 21237718
references.citation: Antivir Ther. 2011;16(3):349-56
references.pmid: 21555817
references.citation: Clin Infect Dis. 2012 Aug;55(3):449-60
references.pmid: 22573845
references.citation: J Acquir Immune Defic Syndr. 2011 Aug 1;57(4):319-25
references.pmid: 21423025
references.citation: Clin Infect Dis. 2011 Aug;53(4):388-95
references.pmid: 21810754
references.citation: Clin Infect Dis. 2004 Oct 15;39(8):1155-60
references.pmid: 15486839
references.citation: Clin Infect Dis. 2005 Dec 1;41(11):1654-61
references.pmid: 16267740
references.citation: Pediatr Infect Dis J. 2008 Sep;27(9):808-14
references.pmid: 18679152
references.citation: J Acquir Immune Defic Syndr. 2012 Jun 1;60(2):e36-45
references.pmid: 22622076
references.citation: J Acquir Immune Defic Syndr. 2012 Oct 1;61(2):226-34
references.pmid: 22692091
references.citation: J Infect Dis. 2011 May 1;203(9):1222-30
references.pmid: 21459815
references.citation: J Acquir Immune Defic Syndr. 2009 Nov 1;52(3):406-16
references.pmid: 19730269
references.citation: AIDS. 2012 Oct 23;26(16):2039-52
references.pmid: 22951634
references.citation: PLoS One. 2012;7(2):e28510
references.pmid: 22383946
references.citation: N Engl J Med. 2010 Jun 17;362(24):2282-94
references.pmid: 20554983
references.citation: Paediatr Perinat Epidemiol. 2003 Oct;17(4):384-90
references.pmid: 14629321
references.citation: J Infect Dis. 1996 May;173(5):1077-84
references.pmid: 8627057
references.citation: J Acquir Immune Defic Syndr. 2011 Nov 1;58(3):353-7
references.pmid: 21792062
references.citation: Trans R Soc Trop Med Hyg. 2009 Aug;103(8):827-33
references.pmid: 19409590