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Maternal-Fetal Transmission of Human Immunodeficiency Virus
1Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson, Ariz., USA.
Insights
Human immunodeficiency virus type 1 (HIV-1) transmission from mothers to infants is a major concern. Research suggests specific HIV-1 variants transmitted to infants possess distinct molecular properties, crucial for developing prevention strategies.
Area of Science:
- Virology
- Immunology
- Pediatrics
Background:
- Perinatal human immunodeficiency virus type 1 (HIV-1) infection accounts for most pediatric HIV-1 cases, with transmission rates exceeding 30%.
- Factors influencing mother-to-infant HIV-1 transmission include maternal health status, viral load, and co-infections, but molecular mechanisms remain unclear.
- Zidovudine (ZDV) has shown potential in reducing transmission, though its efficacy is influenced by various factors not fully understood.
Purpose of the Study:
- To investigate the molecular and biological properties of HIV-1 variants involved in mother-to-infant transmission.
- To identify differences between transmitted and non-transmitted HIV-1 variants from infected mothers.
- To lay the groundwork for targeted prevention and treatment strategies against pediatric HIV-1 infection.
Main Methods:
- Analysis of HIV-1 genotypes and subtypes in infected mothers and their infants.
- Comparison of minor and major HIV-1 variants present in maternal and infant viral populations.
- Investigating the initial predominance and subsequent diversification of transmitted HIV-1 genotypes in infants.
Main Results:
- Minor HIV-1 genotypes from mothers often predominate in infants initially, forming a homogeneous population that diversifies over time.
- Transmission of major or multiple HIV-1 genotypes from mother to infant has also been observed.
- Evidence suggests distinct molecular and biological characteristics differentiate HIV-1 variants transmitted from those not transmitted.
Conclusions:
- The molecular and biological properties of transmitted HIV-1 variants differ from non-transmitted ones.
- Understanding these properties is key to developing targeted interventions to prevent mother-to-infant HIV-1 transmission.
- Further research into viral variant characteristics will enable precise targeting for effective prevention strategies.
Abstract:
The World Health Organization estimates that by year 2000, 10 million children will be infected with human immunodeficiency virus type 1 (HIV-1) at birth and will subsequently develop AIDS. Perinatally acquired infections account for the majority of all HIV-1 cases in children, with an estimated mother-to-infant transmission rate of more than 30%. It is not clear why more than half of the children born to HIV-1-infected mothers are uninfected. Maternal transmission of HIV-1 occurs at three levels: prepartum, intrapartum, and postpartum. Several maternal parameters including advanced clinical stages of the mother, low CD4+ lymphocyte counts, maternal immune response to HIV-1, recent infection, high level of circulating HIV-1, and maternal disease progression have been implicated in an increased risk of mother-to-infant transmission of HIV-1. Viral factors influencing mother-to-infant transmission are not known. Furthermore, several other factors such as acute infection during pregnancy, presence of other sexually transmitted diseases (STD) or other chronic infections, vaginal bleeding, disruption of placental integrity, premature rupture of membrane (PROM), and preterm PROM have been associated with mother-to-infant transmission of HIV-1. In addition, tobacco and cigarette smoking during pregnancy have been shown to triple the rate of maternal transmission of HIV-1. The AIDS Clinical Trial Group (ACTG) suggested that zidovudine (ZDV) can reduce therate of mother-to-infant transmission of HIV-1 if administered to HIV-1-infected pregnant women with CD4 counts greater than 200. Moreover, this study failed to take into consideration several factors that may influence maternal transmission of HIV-1. However, the molecular mechanisms involved in mother-to-infant transmission of HIV-1 are not understood, which makes it more difficult to define strategies for effective treatment and prevention of HIV-1 infection in children. Several groups are engaged in the understanding of the molecular and biological properties of HIV-1 influencing mother-to-infant transmission. Results from my and several other laboratories suggest that the minor genotypes, subtypes, or variants of HIV-1 found in a genetically heterogeneous virus population of infected mothers are transmitted to their infants. The minor HIV-1 genotype predominates initially as a homogeneous population in the infant and then becomes diverse as the infant matures. Furthermore, transmission of a major or multiple HIV-1 genotypes from mother to infant has been reported. Taken together, these results strongly suggest that there are differences among the molecular and biological properties of the maternal variants that are transmitted to the infants and the maternal variants that are not transmitted to the infants. The understanding of the molecular and biological properties of the transmitted viruses will enable researchers to target a particular subtype in the mothers that is transmitted to the infants. Copyright 1996 S. Karger AG, Basel