Mother to child transmission (MTCT) is when an HIV positive woman passes the virus to her baby. This can occur during pregnancy, labour and delivery, or breastfeeding. Without treatment, around 15–30% of babies born to HIV positive women will become infected with HIV during pregnancy and delivery. A further 5–20% will become infected through breastfeeding.
Is MTCT a major problem?
In 2005, around 700,000 children under 15 became infected with HIV, mainly through mother to child transmission. About 90% of these MTCT infections occurred in Africa where AIDS is beginning to reverse decades of steady progress in child survival.
In high income countries MTCT has been virtually eliminated thanks to effective voluntary testing and counselling, access to antiretroviral therapy, safe delivery practices, and the widespread availability and safe use of breast-milk substitutes. If these interventions were used worldwide, they could save the lives of thousands of children each year.
How can MTCT be prevented?
A three-fold strategy is needed to prevent babies from acquiring HIV from their infected mothers.
Preventing HIV infection among prospective parents
Avoiding unwanted pregnancies among HIV positive women
Preventing the transmission of HIV from HIV positive mothers to their infants during pregnancy, labour, delivery and breastfeeding.
The last of these can be achieved by the use of antiretroviral drugs, safer feeding practices and other interventions.
The first great breakthrough in the prevention of MTCT (PMTCT) came in November 1994. After a clinical trial lasting more than two and a half years, a team of scientists reported that pregnant women who received a course of the antiretroviral drug zidovudine (AZT) had a two-thirds lower risk of transmitting HIV than those who took a placebo. The study, which involved American women with mildly symptomatic HIV disease and no prior drug treatment, found no serious short-term side effects in the mothers or their infants.
For the first time there was real hope that drugs could save children from HIV infection. However, the treatment regimen used in the 1994 study, known as ACTG 076, did have certain drawbacks. Women were required to take five oral doses of AZT per day during pregnancy and AZT injections during labour, and their infants were given oral AZT every six hours for six weeks. Later studies showed that simpler courses of AZT were also effective, but they still required many doses of drugs taken over many weeks. Scientists therefore began investigating less intensive, lower cost options that could be used for PMTCT where resources were limited.
Single dose nevirapine
One of the simplest of all drug regimens was tested in the HIVNET 012 trial, which took place in Uganda between 1997 and 1999. This study found that a single dose of nevirapine given to the mother at the onset of labour and to the baby after delivery roughly halved the rate of HIV transmission. As it is given only once to the mother and baby, single dose nevirapine is relatively cheap and easy to administer. Since 2000, many thousands of babies in resource-poor countries have benefited from this intervention, which has been the mainstay of many PMTCT programmes.
When is single dose nevirapine appropriate?
A major concern about the use of single dose nevirapine is drug resistance. Studies have suggested that single dose nevirapine can make future treatment with nevirapine or efavirenz (a related drug) less effective. This could have serious consequences for mothers who wish to prevent MTCT during subsequent pregnancies, or who later use nevirapine or efavirenz as part of combination therapy to improve their own health. There is also some evidence to suggest that if a mother develops nevirapine resistant HIV, this may be passed through breast milk to her baby.
Because of these concerns, there is now general agreement that single dose nevirapine should be used only when no alternative MTCT drug regimen is available. Whenever possible, women should receive a combination of drugs to prevent HIV resistance problems and to decrease MTCT rates even further.
Nevirapine, however, is still the only single dose drug available to prevent MTCT. Other "short course" treatments require women to take drugs during and after pregnancy as well as during labour and delivery. This means they are much more expensive and more difficult to implement in resource poor settings than is nevirapine, which can be used with little or no medical supervision at all. So, for now, single dose nevirapine remains the best choice for preventing MTCT of HIV in areas where medical resources are limited.
HIVNET 012 controversies
In mid December 2004 a news story appeared alleging that side effects from single dose nevirapine during the HIVNET 012 study had been covered up. It claimed that US officials had been warned that nevirapine research "was flawed and may have underreported thousands of severe reactions including deaths".
By the time this news story appeared, a committee from the US Institute of Medicine was already engaged in a major independent review of the design, conduct, results and validity of the HIVNET 012 study. After evaluating extensive material from a variety of sources and reviewing primary source documents from Uganda, the investigation reported its findings in April 2005.
The committee found that the original report on the HIVNET 012 study was "sound, presented in a balanced manner, and can be relied upon for scientific and policy-making purposes". The allegations about unreported deaths were found to be completely untrue. Of the 306 mothers who received nevirapine, 16 experienced serious adverse events, and only one was thought possibly to be due to nevirapine.
The safety and effectiveness of single dose nevirapine has been confirmed by many other clinical trails. Although long-term use of nevirapine has been linked to liver damage, there is no evidence of any significant safety risk from a single dose to prevent MTCT. The December 2004 press story (which seems to have arisen from a personal feud between US officials) has been thoroughly discredited. Numerous subsequent studies, including a large clinical trial in Thailand, have reaffirmed that nevirapine is safe and effective at preventing MTCT.
Combination drug treatments
The most effective PMTCT treatments involve a combination of drugs. What is more, pregnant women with advanced HIV disease should ideally receive combined therapy for their own health, as well as to prevent MTCT. Even in the most poorly resourced countries, PMTCT programmes are increasingly aiming to address this need.
A number of studies have shown that the protective benefit of drugs is diminished when babies continue to be exposed to HIV through breastfeeding.
Mothers with HIV are advised not to breastfeed whenever the use of breast milk substitutes (formula) is acceptable, feasible, affordable, sustainable and safe. However if they live in a country where safe water is not available then the risk of life-threatening conditions from formula feeding may be higher than the risk from breastfeeding. An HIV positive mother should be counselled on the risks and benefits of different infant feeding options and should be helped to select the most suitable option for her situation.
A baby fed on infant formula does not receive the special vitamins, nutrients and protective agents found in breast milk. And the cost of infant formula often puts it beyond the reach of poor families in reource poor countries, even if the product is widely available. Many women also lack access to the knowledge, potable water and fuel needed to prepare replacement feeds safely, or simply have no time to prepare them. If used incorrectly – mixed with unsafe water, for example, or over-diluted – a breast milk substitute can cause infections, malnutrition and even death. Furthermore, if a mother chooses not to breastfeed in settings where breastfeeding is the norm then this may draw attention to her HIV status and invite discrimination, violence or abandonment by her family and community. Another factor worth noting is the contraceptive effect of breastfeeding, which can help to lengthen the interval between pregnancies.
For HIV positive women who choose to breastfeed, exclusive breastfeeding is recommended for the first months of an infant’s life, and should be discontinued once an alternative form of feeding becomes feasible. Mixed feeding (breastfeeding mixed with bottle feeding of water or formula, or providing other foods) is not recommended because studies suggest it carries a higher risk than exclusive breastfeeding. This may be because mixed feeding damages the lining of the baby’s stomach and intestines and thus makes it easier for HIV in breast milk to infect the baby. Indirect evidence suggests that keeping the period of transition from exclusive breastfeeding to alternative feeding as short as possible may reduce the risk of transmission. Unfortunately, the best duration for this is not yet known and may vary according to the infant’s age and/or the environment.
A caesarean section is an operation to deliver a baby through its mother’s abdominal wall. When a mother is HIV positive a caesarean section may be done to protect the baby from direct contact with her blood and other bodily fluids. However, as with formula feeding, there is a need to weigh the risk of HIV transmission against the risk of harm due to the intervention.
If the mother is taking combination antiretroviral therapy then a caesarean section will often not be recommended because the risk of HIV transmission will already be very low. Caesarean delivery may be recommended if the mother has a high level of HIV in her blood, but the procedure is seldom available and/or safe in resource poor settings.
Challenges faced by PMTCT programmes
Even where PMTCT services are available, not all women receive the full benefit. Reasons for HIV positive pregnant women not accessing drugs include:
Not being offered an HIV test
Refusing to take an HIV test
Not returning for follow up visits
Not adhering to self-administered drugs
HIV testing is critical because women who do not know they are HIV positive cannot benefit from interventions. However some women refuse to be tested because they fear learning that they have a life-threatening condition; because they distrust HIV tests; or because they do not expect their results to remain confidential, and fear stigma and discrimination following a positive result.
Some women who test HIV positive do not return to clinics for follow up visits, or fail to take the drugs they have been given. This can happen because they have had negative experiences interacting with clinic staff, or because they have been poorly informed about HIV transmission and how it can be prevented. Also, some women choose not to attend clinics because by doing so they might disclose their HIV positive status. In the words of a woman from Cote d’Ivoire:
"My husband might see me with the medicines, and he will want to know what they are for. That way he will find out about my [HIV positive test] result. Even the location bothers me, because everyone who comes to the clinic knows what goes on [at the programme]. As soon as a pregnant woman is seen coming here, it’s known right away that she is seropositive."
One study in Zambia’s capital city found that single dose nevirapine was successfully administered to only 30% of HIV-positive pregnant women who attended public-sector clinics. This low rate was partly due to many women not being tested, but it was also found that around one third of women who were issued a dose of nevirapine never swallowed it.
To achieve a high success rate, PMTCT programmes must have well-trained, supportive staff who take great care to ensure confidentiality. They must be backed up by effective voluntary testing programmes and by good quality HIV/AIDS education, which is essential to eliminate myths and misunderstandings among pregnant women, and to counter stigma and discrimination in the wider community. Under these conditions, antiretroviral drugs have the potential to save many thousands of babies’ lives.
Note: This information is cross-posted and slightly adapted from AVERT.org in order to emphasize some aspects refering particulary to Moldova. For more details, visual adds, updated information and primary sources, please visit AVERT.org web page.