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Developed by JHPIEGO’s Training in Reproductive Health Project with funding from USAID.

Lesson 8: Prevention of Mother-to-Child Transmission of HIV
Instructor: Jean Anderson, MD

Objectives

In this lesson, we will be discussing prevention of mother-to-child transmission (PMTCT) of HIV infection in limited-resource settings. By the end of this lesson, participants will be able to:

1. Describe the significance of MTCT
2. Discuss the timing and rates of MTCT
3. Explain to clients the factors that may increase or decrease MTCT
4. Describe interventions that have been shown to reduce the likelihood of MTCT
5. Talk to clients about breastfeeding and MTCT

Significance of MTCT

Why is it important to talk about MTCT of HIV? An estimated 200 million women around the world become pregnant each year, of whom about 2.5 million are HIV-positive. The majority of women with HIV throughout the world are young and of childbearing age. They may or may not know that they have HIV infection or they may become infected while trying to get pregnant. The prevalence of HIV-1 among pregnant women varies widely by geographic location, but in several African countries, HIV affects at least 20 to 30% of pregnant women. MTCT is responsible for more than 90% of pediatric HIV infections globally. During the year 2002, approximately 800,000 new infections have occurred in children, with more than 80% occurring in Sub-Saharan Africa.

Timing and Rates of MTCT

The rates of MTCT observed in published studies are lowest in nonbreastfeeding women, with a total risk of 15 to 30% transmission, about two-thirds of which occurs around the time of childbirth. Among those breastfeeding through the first 6 months of the newborn’s life, the rate of MTCT is estimated to be 25-35%. If breastfeeding goes through 18-24 months of the infant’s life, MTCT occurs in approximately 30-45% of cases. It is thought that breastfeeding may be responsible for up to one half of the MTCT that occurs throughout the world. 

Factors That Increase or Decrease MTCT

There are many factors that appear to increase or decrease the risk of MTCT. Some of these factors are related to the woman herself, some are related to pregnancy, and some are related to the virus. These factors include:

Plasma viral load Genital tract viral load Low CD4 cell count Advanced HIV disease Primary or acute HIV infection Antiretroviral (ARV) agents  Mode of childbirth Duration of membrane rupture Preterm childbirth Placental disruption (chorioamnionitis, placental abruption)

Invasive fetal monitoring Breastfeeding Sexually transmitted infections (STIs) Unprotected sex with multiple partners Smoking cigarettes Other substance abuse Vitamin A deficiency

Perhaps the most important factor is plasma viral load or HIV-RNA level. There is a direct correlation between HIV-RNA level and risk of MTCT. However, there is no level below which transmission never occurs and no level above which transmission always occurs. Viral load in the genital tract, which appears to be a separate viral compartment, is an independent predictor of MTCT. Risk of transmission is increased when women have low CD4 counts or either advanced disease or acute infections. This is probably due to high viral load in both early and late HIV infection. Sexually transmitted infections and other co-infections also increase HIV viral load in the genital tract. 

Interventions to Reduce MTCT During Pregnancy and Childbirth

Prevention of New Infections

What can be done to prevent MTCT in low-resource settings? First of all, it is important to prevent new infections in women. There should be special education and counseling about safer sexual and drug-using practices during pregnancy and breastfeeding. Women and their healthcare providers may forget that condoms should be used even when prevention of pregnancy is not an issue. 

Furthermore, women who are newly infected during pregnancy or breastfeeding are at increased risk for mother-to-child transmission. It is important to emphasize that a negative HIV test in pregnancy does not mean that the woman cannot become infected! Because of what we know about MTCT and because of interventions available to reduce the risk of MTCT, it is important to identify HIV infection in women who are pregnant or considering pregnancy. HIV testing should be done in the context of counseling and should be voluntary. 

Behavior Change

There are simple behavioral practices that should be emphasized to all HIV-positive women. Condoms should be used consistently during pregnancy and in the postpartum period. Drugs, alcohol and cigarettes should be avoided. This will help prevent transmission of infection to sexual partners and may help prevent MTCT from occurring with already established infections. Screening and treating STIs and other co-infections that are present is associated with reductions in viral load, especially in the genital tract, and should decrease the risk of MTCT. Drug and alcohol abuse should be treated if present. Although vitamin A deficiency was associated with an increased risk of MTCT in a cross-sectional study, a recent clinical trial of vitamin A supplementation did not demonstrate a decrease in risk with supplementation.

Limit Exposure of the Fetus and Newborn to the Virus

Another strategy to decrease MTCT is to limit exposure of the fetus and newborn to the virus as much as possible. This can be done in several ways. A recent study of more than 4500 mother-newborn pairs found that duration of membrane rupture has a dramatic effect on MTCT, with an approximate 2% increase in risk per each hour of rupture. Healthcare providers should avoid rupturing membranes and may consider shortening the duration of membrane rupture when possible with careful use of forceps or vacuum extractor or with stimulation of labor. Invasive procedures, such as amniocentesis, external cephalic version, use of fetal scalp electrodes and sampling of fetal scalp blood should be avoided. Transfusion of blood or blood products, particularly in areas where the blood supply is not safe, should be given only when necessary in the presence of life- threatening complications. 

The precise role of vaginal cleansing or bathing of the newborn remains unclear. Two clinical trials conducted in Malawi and in Kenya using vaginal cleansing or lavage with a dilute solution of chlorhexidine did not result in an overall decreased rate of MTCT. However, in each study, there was some evidence that this practice might be effective in some subgroups of women. More study is needed. It is reasonable to quickly remove maternal blood and other secretions from the newborn’s body by thoroughly wiping with a dry cloth, although this has not been shown to decrease risk of HIV transmission.

Use of Antiretroviral Agents

The most important intervention to reduce risk of MTCT is the use of antiretroviral (ARV) agents. ARV agents lower viral load both in the plasma and the genital tract. This is thought to be the primary way in which they reduce the risk of MTCT. There are now several short oral ARV regimens that have been found to be effective in lowering the risk of MTCT in limited-resource settings and in both breastfeeding and nonbreastfeeding populations. In Thailand, zidovudine or ZDV, (also known as AZT), reduced transmission by 50% in a nonbreastfeeding cohort when started at 36 weeks of gestation and continued orally through labor. Both ZDV alone or in combination with lamivudine (also known as 3TC), have been found to decrease transmission risk in breastfeeding populations. More recently, a clinical trial in Uganda that gave a single dose of nevirapine (also known as NVP), to the mother at the onset of labor and a single dose to the newborn within 48 to 72 hours after birth reported a decrease in MTCT by almost 50% at a 4- month followup and 39% at 18 months. These drugs also appear to be safe for both mother and infant in followup to date. The effectiveness of these regimens is less in breastfeeding women than in nonbreastfeeding women and new infections continue to occur with longer followup as breastfeeding continues.

Scheduled Cesarean Section

Cesarean section is associated with a 50-80% decrease in the risk of MTCT compared to other modes of childbirth in women who are either taking no ARV drugs or are taking ZDV alone. There is no evidence, however, that cesarean section reduces MTCT risk if performed after labor begins or membranes have ruptured. 

There are also special concerns about performing cesarean sections in limited-resource settings. First, there is an increased risk of maternal morbidity and possible mortality from peri-operative infections or from hemorrhage with cesarean section. Because of the amount of blood loss associated with cesarean section, a safe blood supply needs to be available when a transfusion is required. A baby may be unintentionally delivered prematurely from attempts to perform cesarean section before the onset of labor. Other limitations in these settings include availability of anesthetic agents, antibiotics, and other supplies and equipment. There are also limitations such as lack of enough time and qualified providers. Therefore, in most limited-resource settings, the risks in performing cesarean section for the purpose of reducing MTCT will likely outweigh potential benefits and vaginal childbirth will offer the safest form of delivery for both mother and child.

Breastfeeding and MTCT

The benefits of breastfeeding have been well established. Breastfeeding provides complete nutrition for the newborn for at least 4-6 months and can provide a significant proportion of nutritional needs up to 1 year of life. Breastfeeding also provides significant protection against infectious morbidity and mortality from gastrointestinal infections, lower respiratory infections, otitis media and meningitis. Newborn mortality in general is increased 3-5 fold in the absence of breastfeeding. For the mother, breastfeeding delays the return of fertility. This delay helps space pregnancies and allows the mother to recover from blood loss associated with childbirth. Breastfeeding also promotes mother-newborn bonding and is the least expensive type of newborn feeding.

Maternal Factors Affecting Transmission

The magnitude of the risk of mother-to-child transmission through breastfeeding ranges from 3.2 to 6.9 per 100 child-years of breastfeeding. A number of factors may affect the risk of transmission with breastmilk. Women who have acute or primary HIV infection are estimated to have a MTCT rate of approximately 29%, significantly higher than women with chronic or established infection. Advanced HIV infection in the mother also increases risk of transmission. High plasma viral load, found in both acute and advanced infection, and low CD4 cell counts seen in advanced HIV increase the risk for transmission with breastmilk. Breastmilk viral load has also been identified as a risk factor. Although higher viral loads in breastmilk are usually found when plasma viral load is also increased, levels of HIV in breastmilk may also be increased in the presence of breast inflammation. This may occur with mastitis or breast abscess, both of which have been associated with increased risk of transmission. The presence of cracked nipples during breastfeeding also increases risk. Although data are limited, increased HIV viral load in breastmilk has been associated with vitamin A deficiency in the mother. This suggests that vitamin A deficiency may also increase risk of transmission with breastfeeding.

Newborn Factors Affecting Transmission

There is less information about the influence of newborn factors on the risk of breastmilk transmission. Lesions in the mouth or in the gastrointestinal tract from thrush, trauma or other infections may result in mucosal sores that could provide entry for the virus. The presence of preterm birth and low birth weight as well as certain nutritional deficiencies may affect immune system development and the strength of the lining of the mouth and the entire intestinal tract. Therefore, these conditions may also increase risk of breastmilk transmission.

Breastfeeding Characteristics Affecting Transmission

There is also evidence that breastfeeding characteristics related to the duration and pattern of breastfeeding affect transmission risk. The risk of transmission appears to be highest in the first months of breastfeeding, but continues throughout the entire breastfeeding period. Exclusive breastfeeding is defined as the use of breastmilk alone for newborn nutrition. Mixed feeding involves the use of breastmilk along with other foods or liquids, which include water or a glucose water solution, weak tea, formula, cereal or porridge, fruits and vegetables. Exclusive breastfeeding has been associated with reduced incidence of diarrhea, respiratory illness and allergy, as well as reduced neonatal mortality, as compared to mixed feeding.

A prospective cohort study conducted in Durban, South Africa, examined the risk of HIV transmission by type and pattern of newborn feeding. HIV transmission was compared among women who never breastfed their newborns, those who breastfed their newborns exclusively for 3 months or more and those who gave their newborns a mixture of breastmilk and other liquids or solids or had exclusively breastfed for periods of less than 3 months. Newborns who were exclusively breastfed had no excess risk of HIV infection over the first 6 months as compared to those newborns who were never breastfed. Newborns who were fed with a mixture of breastmilk and other foods or liquids were at the greatest risk of HIV transmission. Newborns in the exclusive breastfeeding group began to develop new infections after being fed other foods or liquids in addition to breastmilk. It may be that contaminated fluids and foods may cause damage to the bowel in newborns, thereby assisting the entry of HIV in breastmilk into newborn tissues. Exclusive breastfeeding also reduces exposure to waterborne pathogens in areas where the water supply is unsafe.

A randomized clinical trial of breastfeeding versus formula feeding was conducted in Nairobi, Kenya. Women in the formula group had access to safe water, were given free formula and taught how to prepare it correctly. After 24 months followup, the total MTCT rate was 36.7% in those assigned to breastfeeding as compared to 20.5% in those assigned to formula, a significant difference. This difference means that the estimated breastmilk transmission rate was 16.2% in the first 2 years of life. Breastmilk accounted for 44% of all newborn infections among those exposed to breastmilk. Only 58% of women in the breastfeeding group had an infant who was alive at 2 years and free from HIV infection, as compared to 70% of women in the formula group. More than one quarter of the women assigned to the formula group also breastfed to some degree. Therefore, this study probably represents an underestimate of the MTCT rate from breastmilk. 

Stigma

Women assigned to the formula group often experienced pressure from their families or from the community to breastfeed and were sometimes concerned about maintaining confidentiality of their HIV status. Not breastfeeding may be stigmatizing and may arouse suspicion or even violence. Furthermore, strong cultural pressures to breastfeed along with a desire to protect the newborn as much as possible by not breastfeeding may increase the practice of mixed feeding by HIV-positive mothers, therefore actually increasing the risk to their newborns.

Recommendations

Women who are HIV-negative or who do not know their HIV status should exclusively breastfeed for 6 months to give their newborn the greatest benefits from breastfeeding and limit the potential risk from unrecognized HIV in the women who have not been tested.

Women who are HIV-positive should avoid breastfeeding WHEN replacement feeding is acceptable, feasible, affordable, sustainable and safe. When these mothers choose not to breastfeed, they should be given specific guidance and support to ensure that their newborns receive adequate and appropriate nutrition.

HIV-positive women who choose to breastfeed or for whom breastfeeding is the safest and most appropriate alternative should be encouraged to breastfeed exclusively up to 6 months of the newborn’s life. This takes advantage of the benefits from breastfeeding which are greatest in the first 6 months of life and avoids the risks of replacement feeding, which are less as the newborn matures. Limiting breastfeeding to 6 months also avoids the risk of HIV transmission, which continues with increasing duration of breastfeeding. Women should be educated about proper breastfeeding techniques, including proper attachment of the newborn to the nipples and frequent breast emptying to promote good breast health. Breastfeeding mothers should be taught to prevent, recognize and promptly seek treatment for mastitis, breast abscess, cracked nipples or other breast lesions that might increase risk of transmission. Similarly, the newborn’s mouth and oral cavity should be checked for oral thrush or other oral lesions and these should be treated.

Good hygiene and food safety should be taught and encouraged both to maintain maternal health and to ensure the safety of replacement feeding when it occurs. Improving the nutritional status of pregnant and breastfeeding mothers can improve the mothers’ health and may help prevent transmission through breastmilk. Vitamin E supplements were found to reduce mastitis risk in a Tanzanian study.

Finally, when breastfeeding is practiced, the transition from exclusive breastfeeding to complete weaning should be kept as short as possible. Again, mothers will need guidance after stopping breastfeeding to ensure adequate newborn nutrition, as well as counseling and support to maintain breast health and decrease the psychological consequences of rapid weaning.

Orphans of HIV/AIDS Epidemic

It is important not to forget another side to the tragedy of HIV in pregnancy. Today there are approximately 14 million children globally who have been orphaned by the death from AIDS of their mother or both parents. About 80% of these orphans live in Sub-Saharan Africa. These children are at increased risk for early death and are less likely to receive education, more likely to go hungry and live in poverty and perhaps more at risk for becoming HIV-positive later in life. As ARV drugs become more available in low-resource countries, it is important to provide care not just to prevent MTCT but to help infected women live longer and healthier lives. The use of highly active antiretroviral therapy (HAART), usually a combination of three agents, has significantly reduced mortality and morbidity due to AIDS and can lower MTCT rates to as low as 1-2%.

Summary

MTCT is the major cause of pediatric HIV/AIDS. It occurs 15-30% of the time in the absence of breastfeeding and without access to ARV drugs. Breastfeeding increases the overall risk to 30-45%. Several factors have been found to increase the risk of MTCT. The most important of these appears to be the HIV viral load. Several short courses of one or two ARV drugs can significantly decrease risk of MTCT. All HIV-positive pregnant women should receive counseling that includes general information about the risks and benefits of different newborn feeding options and specific guidance to help the mother choose the most suitable option for her individual situation. She should be given support for the alternative she chooses.

Next Week's Lesson: 
Infection Prevention for Healthcare Workers

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