An HIV-positive woman who decides to have a baby is faced with many difficult decisions about her treatment and ways to reduce the risk of transmitting HIV to her baby.

In the absence of any intervention, an HIV-positive woman has a 15 to 30% chance of transmitting the virus to her baby during pregnancy and delivery, and a 10 to 20% increased risk of transmitting HIV if she breastfeeds.

Certain factors may increase the chance of mother-to-baby HIV transmission:

• A high viral load.

• Advanced HIV disease.

• HIV-related wasting.

• A low CD4 cell count or CD4 percentage.

• Low maternal antibodies.

• Older age.

• Premature delivery.

• Vaginal delivery.

• Waters breaking more than four hours before delivery.

• Prolonged or difficult labour.

• Frequent unprotected sex with multiple partners.

• Smoking during pregnancy.

• Use of illicit drugs during pregnancy.

• Cervical or vaginal infections.

• Chorioamnionitis: inflammation of the membranes that cover the foetus (van Dyke 1998; Wabire-Mangen 1999).

• Genetic factors of the mother, child or virus.

• Breastfeeding, particularly when mixed with other types of feeding.

Data from the United States Women and Infants Transmission Study provided information about the outcomes of pregnancy in HIV-positive women, finding that infants were more likely to be small for their gestational age and of low birth weight and to be born pre-term. Low birth weight and pre-term birth were associated with low CD4 cell percentage, a history of adverse pregnancy outcomes and bleeding during pregnancy. Low birth weight was also linked to trichomonas infection in the mother. Small-for-gestational age babies were seen most often in women who had used 'hard drugs' during pregnancy (Stratton 1999).

These data offer insight into the normal course of pregnancy in women with HIV in the developed world. The authors conclude that if this study were to be repeated today, the picture presented would be much more positive.

Co-infection

Infection with HIV and other pathogens has been linked to increased rates of HIV transmission from mothers to their children. Chorioamniotitis is often related to genital tract infections, while sexually transmitted infections can increase viral load in the genital tract and the likelihood of exposure to HIV during childbirth. Another maternal factor linked to risk of transmission is a high rate of shedding of the Epstein-Barr virus (Pitt 1998).

Co-infection with hepatitis C is associated with a 63% increased risk of mother-to-baby transmission of HIV, which was dependent on hepatitis C viral load. This study's investigators suggested that hepatitis C infection may be a marker for other factors, such as maternal drug use (Hershow 1997).

Cytomegalovirus (CMV) has also been linked to HIV infection. A study of 440 women co-infected with HIV and CMV found that HIV-positive babies were as likely to contract CMV as babies who did not contract HIV, but that they were almost twice as likely to have persistent CMV infection and to have died by 18 months of age. Those who survived were more likely to have impaired brain growth and movement disorders (Kovacs 1999).

Interactions between co-infections can be complex and bi-directional. For example, HIV infection greatly increases the likelihood of placental malaria in women from malarial regions. However, women co-infected with HIV and malaria are more likely to transmit HIV if they have a high burden of placental malaria, but are less likely to do so if they have low parasite densities (Ayisi 2004).

Other factors

Other things that may play a role in transmission include viral characteristics, host-specific immune responses and genetic characteristics, but the data is far from conclusive on the role of these risk factors.

For example, HIV that is transmitted sexually or via childbirth tends to use the CCR5 receptor to enter cells (LaRussa 2002). However, babies with a variant of this receptor to which HIV cannot bind, called CCR5 delta 32, may not be at a lower risk of contracting HIV, according to a meta-analysis of eleven studies involving close to 4000 HIV-exposed children. The children were genotyped for the CCR5 mutation, but having one copy of this mutation was not associated with a decreased transmission (Contopoulos-Ioannidis 2003). However, another study found a significantly higher prevalence of another chemokine receptor variant (CCR2-64I) amongst uninfected children. In infected children who carried this polymorphism, disease progression was found to be slower (Mangano 2000).

Another mutation called 59356 has been linked to HIV transmission. This is more common in African Americans than in Caucasians. Another mutation, 59402, was more common amongst Caucasians and appeared to have a slight protective effect (John 2001). It should be noted, however, that studies have not found rates of mother-to-baby HIV transmission to differ between different racial groups in United States-based studies.

Human leukocyte antigen (HLA) type I markers may also play a role in the risk of infection in infants. These are cell-surface proteins that play a key role in the immune systems ability to distinguish between the bodys own healthy cells and invasive organisms or diseased cells. HLA types are also genetically determined and vary in different populations. Concordance of HLA types among mother-child pairs in the Ariel Project was associated with an increased risk of transmission (Polycarpou 2002). The HLA type may differ if the infant inherits different HLA characteristics from her or his father. HLA types may also play a role in increased susceptibility to different sub-types of HIV-1 that are prevalent among different populations.

Several studies also suggest that some HIV-1 sub-types may be more easily transmitted from mother to child, and some even suggest that some sub-types may be more readily transmitted in the womb or via breastfeeding than others. For example, studies from Zimbabwe and Tanzania showed that HIV-1 sub-type C was more readily transmitted than other subtypes (Katzenstein 1999; Renjifo 2004). Sub-type C is prevalent in many parts of Africa and Asia, whereas sub-type B is the strain most commonly found in people who become infected with HIV in Europe and the United States. The results of these studies suggest that in regions with a predominantly HIV-1 subtype C epidemic, treatment may need to begin earlier in order to achieve the same degree of reduction in mother-to-child transmission.

References

Ayisi JG et al. Maternal malaria and perinatal HIV transmission, Western Kenya. Emerg Infect Dis 10: 643-652, 2004.

Contopoulos-Ioannidis DG et al. Effect of CCR5-delta32 heterozygosity on the risk of perinatal HIV-1 infection: a meta-analysis. J Acquir Immune Defic Syndr 32: 70-76, 2003.

Hershow RC et al. Increased vertical transmission of human immunodeficiency virus from hepatitis C virus-coinfected mothers. Women and Infants Transmission Study. J Infect Dis 176: 414-420, 1997.

John GC et al. CCR5 promoter polymorphisms in a Kenyan perinatal human immunodeficiency virus type 1 cohort: association with increased 2-year maternal mortality. J Infect Dis 184: 89-92, 2001.

Katzenstein D et al. Maternal HIV-1 RNA and V3 antibodies predict risks for vertical transmission and mortality in subtype C virus infection. Sixth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 235, 1999.

Kovacs A et al. Cytomegalovirus infection and HIV-1 disease progression in infants born to HIV-1-infected women. N Engl J Med 341: 77-84, 1999.

LaRussa P et al. Association of HIV-1 viral phenotype in the MT-2 assay with perinatal HIV transmission. J Acquir Immune Defic Syndr 30: 88-94, 2002.

Mangano A et al. Protective effect of CCR2-64I and not of CCR5-delta32 and SDF1-3'A in pediatric HIV-1 infection. J Acquir Immune Defic Syndr 23: 52-57, 2000.

Mwanyumba F et al. Placental inflammation and perinatal transmission of HIV-1. J Acquir Immune Defic Syndr 29: 262-269, 2002.

Pitt J et al. Maternal and perinatal factors related to maternal-infant transmission of HIV-1 in the P2C2 HIV study: the role of EBV shedding. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV-1 Infection (P2C2 HIV) Study Group. J Acquir Immune Defic Syndr 19: 462-470, 2002.

Polycarpou A et al. Association between maternal and infant class I and II HLA alleles and of their concordance with the risk of perinatal HIV type 1 transmission. AIDS Res Hum Retroviruses 18: 741-746, 2002.

Renjifo B et al. Preferential in-utero transmission of HIV-1 subtype C as compared to HIV-1 subtype A or D. AIDS 18: 1629-1636, 2004.

Shey WI et al. Vaginal disinfection during labour for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev 3: CD003651, 2002.

Stratton P et al. Obstetric and newborn outcomes in a cohort of HIV-infected pregnant women: a report of the women and infants transmission study. J Acquir Immune Defic Syndr Hum Retrovirol 20: 179-186, 1999.

van Dyke RB et al. The Ariel Project: A prospective cohort study of maternal-child transmission of human immunodeficiency virus type 1 in the era of maternal anti-retroviral therapy. J Infect Dis 179: 319-328, 1998.

Wabwire-Mangen F et al. Placental membrane inflammation and risks of maternal-to-child transmission of HIV-1 in Uganda. J Acquir Immune Defic Syndr 22: 379-385, 1999.