Risk Factors for In Utero and Intrapartum Transmission of HIV
Risk Factors for In Utero and Intrapartum Transmission of HIV
Objective: To identify predictors of in utero and intrapartum HIV-1 transmission in infants born in the Women and Infants Transmission Study between 1990 and 2000.
Methods: In utero HIV-1 infection was defined as an infant with the first positive HIV-1 peripheral blood mononuclear cell culture and/or DNA polymerase chain reaction assay at 7 days of age or younger; intrapartum infection was defined as having a negative HIV-1 culture and/or DNA polymerase chain reaction assay at 7 days of age or younger and the first positive assay after 7 days of age.
Results: Of 1709 first-born singleton children with defined HIV-1 infection status, 166 (9.7%) were found to be HIV-1 infected; transmission decreased from 18.1% in 1990-1992 to 1.6% in 1999-2000. Presumed in utero infection was observed in 34% of infected children, and presumed intrapartum infection, in 66%. Among infected children, the proportion with in utero infection increased over time from 27% in 1990-1992 to 80% (4 of 5) in 1999-2000 ( P = 0.072). Maternal antenatal viral load and antiretroviral therapy were associated with risk of both in utero and intrapartum transmission. Controlling for maternal antenatal viral load and antiretroviral therapy, low birth weight was significantly associated with in utero transmission, while age, antenatal CD4 cell percentage, year, birth weight, and duration of membrane rupture were associated with intrapartum transmission.
Conclusion: Although there have been significant declines in perinatal HIV-1 infection over time, there has been an increase in the proportion of infections transmitted in utero.
Mother-to-child HIV-1 transmission can occur in utero, intrapartum, or postnatally through breast-feeding. Different factors may influence HIV-1 transmission during each of these time periods, and hence interventions to reduce transmission during each of these periods may also require different preventive strategies. Many studies that have evaluated risk factors for transmission have pooled together all cases of transmission. If some of the risk factors do indeed differ, pooling in utero cases with intrapartum or postnatal cases could lead to an underestimate of the impact of some risk factors and perhaps a failure to identify others. Some studies have tried to distinguish risk factors for transmission occurring during these different time points.
One difficulty in distinguishing risk factors for transmission during different time periods is determining which children have acquired infection in utero and which have acquired it during delivery. The usual approach has been to base the classification on whether the child is positive or negative by HIV-1 culture or DNA polymerase chain reaction (PCR) assay during the first 48 hours of life. However, it is possible that this approach could lead to some misclassification, which could reduce the ability to distinguish risk factors for the 2 types of transmission. In addition, virologic testing during the first 48 hours of life may not always be available.
The Women and Infants Transmission Study (WITS) is an ongoing, prospective, multicenter, longitudinal study of maternal-infant HIV-1 transmission in non-breast-feeding infants in the United States that began enrollment in 1989. We used the WITS data and a definition of presumed in utero transmission based on the timing of the first positive HIV-1 culture or DNA PCR assay to identify distinct risk factors for in utero and intrapartum transmission. In addition, we used probabilistic approaches to allow for the possibility that some of the children were misclassified with respect to the timing of transmission using our definitions. Finally, we evaluated trends in the proportion of in utero and intrapartum transmission over time in the WITS.
Objective: To identify predictors of in utero and intrapartum HIV-1 transmission in infants born in the Women and Infants Transmission Study between 1990 and 2000.
Methods: In utero HIV-1 infection was defined as an infant with the first positive HIV-1 peripheral blood mononuclear cell culture and/or DNA polymerase chain reaction assay at 7 days of age or younger; intrapartum infection was defined as having a negative HIV-1 culture and/or DNA polymerase chain reaction assay at 7 days of age or younger and the first positive assay after 7 days of age.
Results: Of 1709 first-born singleton children with defined HIV-1 infection status, 166 (9.7%) were found to be HIV-1 infected; transmission decreased from 18.1% in 1990-1992 to 1.6% in 1999-2000. Presumed in utero infection was observed in 34% of infected children, and presumed intrapartum infection, in 66%. Among infected children, the proportion with in utero infection increased over time from 27% in 1990-1992 to 80% (4 of 5) in 1999-2000 ( P = 0.072). Maternal antenatal viral load and antiretroviral therapy were associated with risk of both in utero and intrapartum transmission. Controlling for maternal antenatal viral load and antiretroviral therapy, low birth weight was significantly associated with in utero transmission, while age, antenatal CD4 cell percentage, year, birth weight, and duration of membrane rupture were associated with intrapartum transmission.
Conclusion: Although there have been significant declines in perinatal HIV-1 infection over time, there has been an increase in the proportion of infections transmitted in utero.
Mother-to-child HIV-1 transmission can occur in utero, intrapartum, or postnatally through breast-feeding. Different factors may influence HIV-1 transmission during each of these time periods, and hence interventions to reduce transmission during each of these periods may also require different preventive strategies. Many studies that have evaluated risk factors for transmission have pooled together all cases of transmission. If some of the risk factors do indeed differ, pooling in utero cases with intrapartum or postnatal cases could lead to an underestimate of the impact of some risk factors and perhaps a failure to identify others. Some studies have tried to distinguish risk factors for transmission occurring during these different time points.
One difficulty in distinguishing risk factors for transmission during different time periods is determining which children have acquired infection in utero and which have acquired it during delivery. The usual approach has been to base the classification on whether the child is positive or negative by HIV-1 culture or DNA polymerase chain reaction (PCR) assay during the first 48 hours of life. However, it is possible that this approach could lead to some misclassification, which could reduce the ability to distinguish risk factors for the 2 types of transmission. In addition, virologic testing during the first 48 hours of life may not always be available.
The Women and Infants Transmission Study (WITS) is an ongoing, prospective, multicenter, longitudinal study of maternal-infant HIV-1 transmission in non-breast-feeding infants in the United States that began enrollment in 1989. We used the WITS data and a definition of presumed in utero transmission based on the timing of the first positive HIV-1 culture or DNA PCR assay to identify distinct risk factors for in utero and intrapartum transmission. In addition, we used probabilistic approaches to allow for the possibility that some of the children were misclassified with respect to the timing of transmission using our definitions. Finally, we evaluated trends in the proportion of in utero and intrapartum transmission over time in the WITS.