Current HIV Research, 2003, 1, 447-462 447 1570-162X/03 $35.00+.00 © 2003 Bentham Science Publishers Ltd. Mother-to-Child Transmission of HIV Infection and its Prevention Claire Thorne * and Marie-Louise Newell Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, UK Abstract: An estimated 800,000 children acquired HIV-infection in 2002, most as a result of mother-to-child transmission (MTCT), and vertically-acquired HIV infection continues to be of major public health importance. Prevention of MTCT is possible with a combination of interventions including antiretroviral therapy (ART) (usually in highly active combinations), elective caesarean section and avoidance of breastfeeding, and where infected women are identified before or in pregnancy and have access to these interventions, risk of MTCT is now below 1-2%. However, prompt identification of pregnant women with HIV infection remains pressing in many developed countries; additionally, concerns have arisen regarding adherence to complex treatment regimens in pregnancy and the potential impact of HIV drug resistance. More disturbingly, most HIV-infected women live in developing countries where many pregnant women even when tested do not return for their HIV results for a variety of reasons including stigma, and where most, if not all, strategies for prevention of MTCT have been of limited accessibility and/or feasibility. However, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and other initiatives including pharmaceutical companies’ donation programmes and generic antiretroviral drug production have made prevention of MTCT in resource-poor settings an increasingly realistic goal, coupled with new evidence from clinical trials on the efficacy of abbreviated regimens of antiretroviral prophylaxis, including combination therapy, to prevent MTCT. Research is additionally focussing on reducing the risk of postnatal transmission through breastfeeding, with exclusive breastfeeding, early cessation and antiretroviral prophylaxis to breastfeeding women or breastfed infants under investigation. However, the key to prevention of paediatric HIV infections is adequate prevention of infection in women of reproductive age. Key words: mother-to-child transmission, vertical transmission, risk factors, interventions, prevention, antiretroviral prophylaxis, pregnancy. INTRODUCTION By the end of 2002, an estimated 42 million people were living with HIV/AIDS globally, of whom 19.2 million were women and 3.2 children aged less than 15 years [1]. During 2002, at least 2 million women became infected with HIV, mainly as a result of heterosexual transmission, and 800 000 children acquired HIV infection, the majority vertically from their mothers. As the epidemic has progressed, the relative proportion of women has increased and it is now estimated that half the adults living with HIV/AIDS worldwide are female; these women are concentrated in those parts of the world where the HIV epidemic has become generalised, with heterosexual contact the main route of transmission, mainly Africa (particularly sub-Saharan Africa), the Caribbean and South and South-East Asia [1]. As expected of an infection primarily acquired by women through sexual intercourse and injecting drug use, most infected women are of child-bearing age and in resource-poor settings, with limited availability of interventions to reduce mother-to-child transmission (MTCT), the HIV epidemic among children mirrors that among women, as the vast majority of children acquire infection vertically from their mothers. The United Nations General Assembly incorporated a Declaration of Commitment on HIV/AIDS within their *Address correspondance to this author at the Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK; Tel: +44 20 7905 2105; Fax: +44 20 7813 8145; E-mail: c.thorne@ich.ucl.ac.uk Millenium Goals in 2000 [152]. The targets within this declaration include a 25% reduction in the percentage of pregnant women aged 15-24 who are HIV infected by 2010 and a 20% reduction in infant HIV infection by 2005, and 50% by 2010. RATES AND TIMING OF MOTHER-TO-CHILD TRANSMISSION Vertical transmission of HIV infection from mother to infant can occur during pregnancy, around the time of delivery or postnatally, through breastfeeding. Little was known about the risk of vertical transmission in the early years of the epidemic, when studies tended to overestimate the rate of transmission, as they were based on small selected groups with bias towards children or women with symptoms or mothers who already had an infected child [132]. Cohort studies in which children born to HIV-infected women identified in pregnancy or at delivery are prospectively followed up were set up in Europe, the USA, Africa and elsewhere to estimate vertical transmission rates, determine risk factors for transmission and describe the natural history of paediatric HIV infection. Prior to the introduction of interventions to reduce vertical transmission, reported rates of mother-to-child transmission from such prospective studies varied considerably and ranged from 15- 20% in Europe, 16-30% in the USA, 25-40% in Africa to 13-48% in South and South East Asia [34,71,163,90]. The initial variation in reported vertical transmission rates may have been caused by methodological differences between