(introduction...)

Reported rates of transmission of HIV from mother to child range from around 15%-25% in Europe and the USA to 25% to 40% in some African and Asian studies^111,112. With the advent of routine antiretroviral [ARV] therapy in many developed countries, much lower transmission rates are now being described^113,114. The estimated annual incidence of perinatal infections declined by 27% in the USA between 1992 and 1995 after the widespread implementation of antiretroviral therapy in pregnancy¹⁸.

Transmission of HIV-1 can occur in-utero, at the time of labour and delivery, or postnatally through breastfeeding. Knowledge about the likely timing of transmission is important for the design of possible interventions. Evidence for in utero transmission (as early as 8 weeks gestation) comes from: the detection of HIV-1 and viral antigens (p24) in fetal specimens and placental tissue, viral isolation from some infected infants at the time of birth which implies that transmission occurred before birth; in addition, the observation that some infants get sick very early in life whilst others have a prognosis similar to adults suggests that the first ones (rapid progressors) have acquired infection in utero^{92,115,116,117}.The evidence for intrapartum transmission came first from observations from a register of twins¹¹⁸, which found that the first born twin had a two-fold higher risk of contracting HIV-1 than the second born twin. It is thought that vaginal delivery of the first twin reduces exposure of the second twin to the virus in cervico-vaginal secretions although the same phenomenon is observed for twins delivered by Caesarean section. In addition, recent reports have indicated that mode of delivery may affect the transmission rate. Caesarean section whether elective or emergency has been shown to decrease transmission in some studies¹¹⁹ and prolonged rupture of membranes [more than four hours] to increase the risk of transmission¹²⁰. Around half of the infected infants will have negative viral studies at the time of birth¹¹⁶ indicating that transmission occurred during labour/delivery at the soonest (it takes some days after infection for viral studies to become positive). The evidence for post-partum transmission came from recovery of HIV in both the cell-free and cellular portions of breast milk. In addition, postnatal transmission through breastfeeding is generally assumed to explain most of the differences in transmission rates between developed countries (no or short breastfeeding) and developing countries (prolonged breastfeeding).

The contribution of each of these routes to overall transmission has not been quantified exactly but it appears that in-utero transmission is less frequent and that a substantial proportion of infection occurs at the time of delivery or late in pregnancy^121,122,123. This conclusion is based on the absence of an HIV-1 dysmorphic syndrome, the lack of manifestations of HIV-1 infection at birth and the finding that HIV-1 is detected in the first week of life in only about 50% of children later proven to be infected^{111,113,122,123,124,125,126}. A working definition for the classification of the timing of transmission has been proposed, based on the time of detection of HIV in the infant. Where virus is detectable within 48 hours of birth, an infant is considered to have been infected in utero, while intrapartum infection is assumed if viral studies are negative during the first week of life, but become positive between 7 and 90 days¹²⁷. A Markov model of the time to p24 antigenaemia based on results from the French Collaborative Study group suggested that 65% of infants were infected around the time of labour and 35% in utero¹²⁸. A probability of 27% for in utero transmission was obtained in the Women and Infants Transmission Study (WITS) in the USA¹²⁹, while in Kinshasa, 23% of infants were thought to be infected in utero, 65% intrapartum or early postpartum and 12% in late postpartum¹³⁰.