- Over the last several years, virologic assays for the detection and measurement of HIV-1 RNA have become important in the diagnosis and management of perinatal HIV infection. Since AIDS Clinical Trials Group 076, a number of prospective and retrospective analyses have investigated the role of viral load in perinatal transmission. Although no universal virologic threshold for perinatal HIV transmission has been established, much has been learned about the timing of perinatal transmission and the relationship between maternal viral load and disease progression in HIV-infected neonates. Virologic assays have become accepted as standards of care in monitoring viral load during pregnancy, diagnosing neonatal infection, and establishing prognosis and response to therapy in infected infants.
- Since their implementation in the mid-1990s, virologic assays for the detection and measurement of HIV-1 DNA and RNA (viral load) have rapidly become vital tools in the diagnosis and management of HIV infection. In HIV-infected adults, measurement of HIV-1 RNA levels has been most useful in monitoring response to antiretroviral therapy and predicting the risk of disease progression and death. In the obstetric setting, maternal HIV-1 RNA levels are most useful in predicting the risk of perinatal HIV transmission. Also, the detection and measurement of HIV-1 DNA or RNA in an infant may be helpful in diagnosing early perinatal infection, establishing the timing of transmission (in utero, intrapartum, postpartum), and monitoring response to antiretroviral therapy.Types of Virologic Assays
- Virologic assays can be either qualitative or quantitative. Qualitative testing is useful in cases of acute HIV infection and neonatal HIV exposure, in evaluation of patients in the window period following viral exposure, and in patients with indeterminate serologic results. Qualitative methods include detection of HIV antigen, viral culture (of peripheral blood mononuclear cells), and HIV DNA polymerase chain reaction (PCR). The sensitivity of these tests is from 8% to 32%, from 95% to 100%, and greater than 99%, respectively, with the PCR assay being the most cost-effective.
- Quantitative testing of HIV-1 RNA is useful in diagnosing acute HIV infection, in predicting progression in infected persons, and in therapeutic monitoring. There are currently 3 commercial assays available in the United States for quantitative HIV-1 RNA testing (Table 1).
- Pathogenesis of Perinatal HIV Transmission
The pathogenesis of mother-to-child transmission of HIV is not well understood. The protective effects of cesarean delivery and topical antiseptic therapies suggest that most mother-to-child transmission of HIV likely occurs during the birth, while the fetus is exposed to infected maternal genital secretions. The increased incidence of HIV infection among firstborn twins and the correlation of perinatal transmission with HIV-1 levels in maternal secretions also suggest intrapartum acquisition of HIV as a result of mucosal factors.
- Factors influencing perinatal transmission may include viral, maternal, obstetric, and fetal characteristics. Advanced maternal HIV disease, high maternal HIV-1 RNA levels, low maternal CD4 lymphocyte count, maternal genital shedding of HIV, and presence of maternal chorioamnionitis or sexually transmitted disease have all been associated with increased perinatal transmission. Increased time to delivery after membrane rupture has been associated with increased vertical transmission. Neonatal factors such as prematurity and low birth weight may also enhance perinatal transmission, but they may occur secondary to infection. Breast-feeding is also a risk factor for transmission, with mastitis during breast-feeding further increasing transmission risk. Viral factors such as viral subtype, the presence of drug resistance mutations, and syncytia-inducing virus may also affect transmission of HIV from mother to child.Timing of Perinatal HIV Transmission
- Although it is not precisely known when perinatal HIV transmission occurs, use of virologic assays has suggested that most transmission happens in very late pregnancy or intrapartum.[4,5] HIV detection by DNA PCR has indicated that approximately one third of infected infants can be identified within 48 hours of birth. Presumably, these infants have been infected in utero. The remaining two thirds of perinatal transmission most likely occurs during labor and delivery; HIV DNA may be detected approximately 2 weeks later in these infants.[6,7] Low rates (less than 5%) of midtrimester transmission were found when HIV-1 RNA levels were measured in the fetuses of HIV- infected women terminating their pregnancies between 17 and 24 weeks of gestation.
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