Volume 5 Supplement 1

Fourth Dominique International Conference. Maternal chronic viral infections transmitted to infants: from mechanisms to prevention and care

Open Access

Early vs deferred highly active antiretroviral therapy in HIV infected infants: a European Collaborative Cohort Study

  • Tessa Goetghebuer1,
  • Edwige Haelterman1,
  • Jerome Le Chenadec2,
  • Catherine Dollfus3,
  • Diana Gibb4,
  • Katherine Boyd4,
  • Ali Judd4,
  • Luisa Galli5,
  • Clara Gabiano5,
  • Jose Ramos6,
  • Claire Thorne7,
  • Magdalena Marczynska8,
  • Olivia Keiser9,
  • Luminita Ene10,
  • Marc Hainaut1,
  • Henriette Scherpbier11,
  • Uwe Wintergerst12,
  • Véronique Schmitz13,
  • Gwenda Verweel14,
  • Carlo Giaquinto15,
  • Josiane Warszawski2 and
  • Jack Levy1
Retrovirology20085(Suppl 1):O25


Published: 9 April 2008


Without antiretroviral therapy (ART), approximately 20% of HIV-1 vertically infected infants develop severe disease manifestations before the age of 1 year [1] and surrogate markers poorly predict infants at higher risk of rapid disease progression. Several small prospective and retrospective studies in developed countries have suggested that ART initiated early in life could prevent this rapid clinical and immunologic deterioration [26].

Because of the small number of HIV-infected infants delivered in industrialized countries where mother to child transmission prophylaxis is widely applied, a prospective study of early versus delayed ART is currently not feasible. Implementation of early ART has varied across countries and over time since 1996 in Europe. The objective of this collaborative study was to compare the outcome of infants who received ART early in life with the outcome of those with deferred treatment.

Materials and methods

Children born between 01/09/96 and 31/12/2004 to mothers with known HIV infection at birth, who received neonatal prophylaxis, and diagnosed with HIV before age 3 months were eligible. The children who were identified as HIV-infected at the same time or after being diagnosed with AIDS, and children who develop AIDS before the age of 3 months were excluded. Thirteen prospective and retrospective cohorts from 11 European countries participated, enrolling a total of 210 eligible infants. Data including general demographics and pregnancy data, details of prophylaxis and ART in early life, CDC events and death, immunological and virological measurements since birth, were collected and pooled. The risk of AIDS/death was estimated by Kaplan-Meier survival analysis, and compared between the groups of infant treated or not treated before 3 months of age. Cox regression was used to estimate hazard ratios.


Among the 210 children, 21 developed AIDS and 3 died. The exposure to treatment was heterogeneous among cohorts. Overall ART and Highly active ART were initiated in 59% and 48% of the infants before 3 months of age and in 87% and 76% by one year, respectively.

Treatment was initiated before the age of 3 months in 124 infants. There was no significant difference in demographic, pregnancy and delivery characteristics between the two groups. Moreover the proportion of infants with early treatment did not vary significantly over time. As shown in figure 1, we found that the risk of developing AIDS/death at one year was 1.6% in infants treated before the age of 3 months compared to 11.7% in infants who started treatment later (p<0.001). At 5 years the risks were 4.6% and 21.5% respectively. Deferred treatment was associated with a five-fold higher risk of AIDS has compared with treatment before 3 months of age (crude hazard ratio = 5.0; 95% CI: 2.0-12.6). Adjustment for ethnicity, birth weight, breast feeding, number and class of neonatal prophylaxis, number and class of drug in first treatment did not substantially affect the hazard ratio.
Figure 1

Time from birth to AIDS/death comparing children treated before 3 months of age and children not treated before 3 months of age.


The preliminary results of this retrospective collaborative study suggest a significant association between ART started before the age of 3 months and a lower subsequent incidence of AIDS/death in infancy.



The study was supported by Paediatric European Network for the Treatment of AIDS. We thank all collaborators of the European Infant Collaborative study.

Authors’ Affiliations

Paediatric Department, CHU St Pierre
Institut National de la Santé et de la Recherche Médicale
AP-HP, Hôpital Trousseau, Service d'Hématologie et d'oncologie pédiatrique
MRC Clinical Trials Unit
Italian Register, Department of Paediatrics, University of Florence
Hospital 12 Octubre
ECS, institute of Child Health
Infectious Disease Hospital, Medical University Warsaw
Data Center of the Swiss HIV Cohort Study, Lausanne, and Institute of Social and Preventive Medicine, University of Bern
Hospital for Infectious Diseases ”Dr. Victor Babes”
Emma Children's Hospital, Academic Medical Center
University Children's Hospital
Hôpital La Citadelle
Erasmus MC Sophia Children's Hospital
Department of Pediatrics, Università di Padova


  1. Blanche S, Newell ML, Mayaux MJ, et al: Morbidity and mortality in European children vertically infected by HIV-1. The French Pediatric HIV Infection Study Group and European Collaborative Study. J Acquir Immune Defic Syndr Hum Retrovirol. 1997, 14 (5): 442-450.View ArticlePubMedGoogle Scholar
  2. Luzuriaga K, McManus M, Mofenson L, Britto P, Graham B, Sullivan JL: A trial of three antiretroviral regimens in HIV-1-infected children. N Engl J Med. 2004, 350 (24): 2471-2480. 10.1056/NEJMoa032706.View ArticlePubMedGoogle Scholar
  3. Faye A, Le Chenadec J, Dollfus C, et al: Early versus deferred antiretroviral multidrug therapy in infants infected with HIV type 1. Clin Infect Dis. 2004, 39 (11): 1692-1698. 10.1086/425739.View ArticlePubMedGoogle Scholar
  4. Aboulker JP, Babiker A, Chaix ML, et al: Highly active antiretroviral therapy started in infants under 3 months of age: 72-week follow-up for CD4 cell count, viral load and drug resistance outcome. Aids. 2004, 18 (2): 237-245. 10.1097/00002030-200401230-00013.View ArticlePubMedGoogle Scholar
  5. Van der Linden D, Hainaut M, Goetghebuer T, et al: Effectiveness of early initiation of protease inhibitor-sparing antiretroviral regimen in human immunodeficiency virus-1 vertically infected infants. Pediatr Infect Dis J. 2007, 26 (4): 359-361. 10.1097/01.inf.0000258626.34984.eb.View ArticlePubMedGoogle Scholar
  6. Chiappini E, Galli L, Tovo PA, et al: Virologic, immunologic, and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection. Aids. 2006, 20 (2): 207-215. 10.1097/01.aids.0000200529.64113.3e.View ArticlePubMedGoogle Scholar


© Goetghebuer et al.; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.