Key words : Mother-to-child transmission; HIV infection; paediatric; interventions; epidemiology
Project number: QLK2-2000-00002
EC contribution: € 627,441
Duration: 36 months
Starting date: 01/09/2001
Summary: The European Collaborative Study aims to investigate the consequences of HIV infection in pregnancy and its outcome in infected and uninfected children born to HIV infected mothers. Interventions to reduce the risk of mother-to-child transmission are now widely available, which has resulted in substantially reduced rates of transmission. However, these interventions may have potential long-term adverse effects, in particular for uninfected children exposed to antiretroviral therapy in utero or early in life. Monitoring of the rates of transmission and the occurrence of such adverse events is vital on a European basis.
Problem: By the end of 1998, nearly 40,000 women had been diagnosed with AIDS in Europe, and there were an estimated 400,000 women living with HIV infection, mostly of childbearing age, and the number of infants at risk of vertically acquired HIV infection continues to rise. Although interventions are now available to reduce the risk of vertical transmission, such as anti-retroviral therapy with zidovudine, elective caesarean section and refraining from breastfeeding, important new questions have emerged regarding the effect of such interventions on the health of HIV-infected women and their infected and uninfected children. The European Collaborative Study is a unique prospective cohort study which has over the past decade provided an epidemiological assessment of the issues relating to HIV infection in pregnancy and childhood.
Aim: To investigate the consequences of HIV infection in pregnancy and after delivery in women and their children, in the era of anti-retroviral therapy and other interventions for treatment and prophylaxis. This includes monitoring of demographic and biological characteristics of HIV- infected pregnant women in Europe and the extent and type of anti-retroviral treatment and other interventions to reduce mother-to-child transmission given before, during and after pregnancy; monitoring pregnancy outcome, such as prematurity and the association with anti-retroviral combination therapy; estimating the rate of vertical transmission in Europe; to evaluate further interventions to reduce the risk of vertical transmission, such as Nevirapine, in a randomised trial; to elucidate the progression of vertically acquired HIV infection, allowing for exposure to prophylactic and therapeutic anti-retroviral therapy; and to act as a public health resource on a European basis.
Expected results: Much of current knowledge about HIV infection in pregnancy and mother-to-child transmission of HIV infection was acquired prior to the widespread introduction of anti-retroviral therapy both to delay progression of disease and as prophylaxis to reduce the risk of vertical transmission. An increasing number of HIV-infected women receive combination anti-retroviral therapy before and during pregnancy, and it is recommended that HIV-infected women should be offered an elective caesarean section delivery and be given advice to refrain from breastfeeding. New questions have therefore arisen as to the medium and long term effect of these intervention strategies on the health and quality of life of HIV-infected women and their children. In particular, concerns have been recently expressed about the possible serious adverse effects of ART exposure for uninfected children.
HIV infection in women was initially mostly restricted to easily identifiable groups such as those with a history of injecting drug use or those from an area where HIV infection is highly prevalent. However, in recent years there has been a shift towards heterosexual acquisition of infection, which is less easily identifiable. In many European centres therefore, all pregnant women are now offered an HIV test, so that those identified as infected can benefit from the available interventions. The risk of vertical transmission may increase or decrease depending on the characteristics of the HIV-infected pregnant women and the uptake of interventions, which aim to prevent mother-to-child transmission. The aim and objectives of the ECS project proposed here focus on the further identification of factors that influence vertical transmission of HIV infection, and the progression of HIV disease in women and children in this changing environment. The evaluation of interventions to reduce the risk of mother-to-child transmission of disease will contribute to knowledge on interventions in general, and mechanisms and timing of mother-to-child transmission in particular.
Use of anti-retroviral therapy by women before and during pregnancy will be assessed and issues relating to quality of life will be explored. Possible adverse pregnancy outcomes associated with anti-retroviral therapy will be monitored. Little is known about the medium to long-term adverse effect of exposure to anti-retroviral drugs in intra-uterine or early life, an issue especially important for the large numbers of uninfected children born to infected mothers. It is extremely important therefore to develop systems to enable any events to be identified. Evaluation of the efficacy of alternative interventions to reduce or prevent mother-to-child transmission may aid the identification of safer or cheaper approaches. Infants born to mothers who received anti-retroviral therapy but who were nevertheless infected may have acquired a resistant virus. Options for the management of these children may thus be limited, and a standard clinical approach will be developed. The quality of life of infected children and factors that influence therapy adherence in infected children will be explored.
The proposed development of common and shared data bases across the network will enable individual centres to monitor in a standard fashion their case load and clinical burden of HIV in women and children and facilitate the management of HIV infection in pregnant women and their infected children in Europe. Findings from the ECS will provide the basis for public health guidelines for the management of HIV infection in women and children across Europe, and will be translated into a standard approach to clinical care.
Potential applications: The ECS network provides a range of expertise in areas ranging from medical care to social services, with epidemiological expertise provided centrally. The ECS cohort provides a unique opportunity to address these new research and clinical questions for HIV-infected pregnant women and their children. It is fundamental to investigate more fully the occurrence of adverse events associated with exposure to ART in foetal and neonatal life in uninfected children born to HIV-infected women, using the ECS cohort, which follows up both infected and uninfected children, and in collaboration with other prospective studies. Collaborating clinicians make an important contribution to dissemination locally, in addition to their vital role in translating ECS research findings into evidence-based clinical management. ECS findings have informed the development of clinical guidelines.
The participants in the European Collaborative Study
- Prof ML Newell with C. Thorne, Prof CS Peckham, Centre for Paediatric Epidemiology, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, London, UK.
Tel +44 20 7905 2105 Fax +44 7813 8145 email: firstname.lastname@example.org
- Dr Carlo Giaquinto, Instituto di Clinica Pediatrica, Via Giustiniani
3, 35128 Padova, Italy.
Tel: (39-049) 8213585 - Fax: (39-049) 8753865 Email: email@example.com
- Dr I Grosch Wörner, Kinderklinik Medizinische Fakultat der Humboldt,
Mittelallee 8, Station 63, Augestenburger Platz 1, 13353 Berlin,
Tel (49 30) 45066501 Fax: (49 30) 45066956 Email: firstname.lastname@example.org
- Dr JYQ Mok, Paediatric HIV service, Edinburgh Sick Children’s
NHS Trust 10 Chalmers Crescent, Edinburgh EH9 1TS, UK.
Tel: (44 131) 5360971 - Fax: (44 131) 5360570 Email: email@example.com
- Dr MI de Jose, S Pediatria, Hospital Infantil ‘La Paz’, P Castellana
261, Madrid 28046, Spain.
Tel: (34 1) 358 4454 - Fax: +34 1 729 1179 - Email: firstname.lastname@example.org
- Prof F Asensi-Botet, Department Medicine Pediatria, Hospital
de la Seguridad Social ‘La Fe’, Avenida de Campanar 21, 46009
Tel/Fax: (34 96) 386 2791 - Email: email@example.com
- Dr H Scherpbier, Academisch Medisch Centrum, Meibergdreef 9,
1105 AZ Amsterdam Zuidoost, The Netherlands.
Tel: (31 20) 566 9111 Fax: (31 20) 566 4440 Email: H.J.Scherpbier@amc.uva.nl
- Dr AB Bohlin, Dept of Paediatrics, Huddinge Hospital, S - 141
86 Huddinge, Sweden.
Tel: (46 8) 58587308 Fax: (46 8) 58581410 Email: firstname.lastname@example.org
- Dr A Ferrazin, Dr A De Maria, Department of Internal Medicine,
Ospedale ‘S Martino’, Largo R Benzi 10, 16134 Genoa, Italy.
Tel: (39 10) 3538933 Fax: (39 10) 3538904 Email: email@example.com
- Dr Graham Taylor, Department of GU Medicine and communicable
Diseases St Mary’s Hospital, Norfolk Place, London W2 1PG, UK.
Tel: (44 20) 75946581 - Email: firstname.lastname@example.org
- Prof J Levy, Hospital St Pierre, Paediatric Infectious Diseases
Unit, 322 Rue Haute, 1000 Bruxelles, Belgium.
Tel: (32 2) 535354344 - Fax: (32 2) 5354563 Email: Jack.Levy@stpierre-bru.be
- Dr Brunella Guerra, Instituto Clinica Ginecologia e Ostetrica,
cattedra Fisiopatalogia Prenatala, Policlinico S. Orsola – Malpighi,
Via Massarenti 13 40138 Bologna, Italy.
Tel: (39 051) 397637 - Fax: (39 051) 6446508
- Prof Pasquale Martinelli, Istituto di Clinica Ostetrica, II
Policlinico, Via S Pansini 5, 80131 Napoli, Italy
Tel: (39 81) 74662966 - Fax: (39 81) 74662966 Email: Martinel@unina.it
- Dr A Mur, Departamento de Pediatria, Hospital Del Mar, Passeig
Maritim 25-29 08003 Barcelona, Spain
Tel: (34 93) 221 1010 - Fax: (34 93) 221 0541 Email: email@example.com
- Dr O Coll, Departamento de Obstetica-Ginecologia, Hospital Clinic,
University of Barcelona, Calle VillaRroel 170, 08028 Barcelona,
Tel: (34 93) 2275436 - Fax: (34 93) 4510332 Email: firstname.lastname@example.org