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Preventing mother-to-child transmission of HIV (PMTCT)

What is mother-to-child transmission?

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.¹

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.^{2 3}

How can MTCT be prevented (PMTCT)?

Effective prevention of mother-to-child transmission (PMTCT) requires a three-fold strategy.^{4 5}

• 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 infant feeding practices and other interventions.

Antiretroviral drugs

Treatment for the mother

Women who have reached the advanced stages of HIV disease require a combination of antiretroviral drugs for their own health. This treatment, which must be taken every day for the rest of a woman's life, is also highly effective at preventing mother-to-child transmission (PMTCT). Women who require treatment will usually be advised to take it, beginning either immediately or after the first trimester. Their newborn babies will usually be given a course of treatment for the first few days or weeks of life, to lower the risk even further.

Pregnant women who do not yet need treatment for their own HIV infection can take a short course of drugs to help protect their unborn babies. The main options are outlined below, in order of complexity and effectiveness.

Single dose nevirapine

The simplest of all PMTCT 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.^{6 7} 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 simple intervention, which has been the mainstay of many PMTCT programmes.

When is single dose nevirapine appropriate?

A significant concern about the use of single dose nevirapine is drug resistance. Around a third of women who take single dose nevirapine develop drug resistant HIV,⁸ which can make subsequent treatment involving nevirapine and efavirenz (a related drug) less effective.⁹ Studies have found that drug resistance resulting from single dose nevirapine tends to decrease over time; if a mother waits at least six months before beginning treatment then it may be less likely to fail.^10 11 Nevertheless, in some cases the drug resistant HIV persists for many months in some parts of the body, even if it cannot be detected in the blood, and this may undermine the longer term effectiveness of treatment.¹²

Among babies infected with HIV and exposed to single-dose nevirapine, around half have drug resistance at 6-8 weeks old.¹³ Other infants may become infected with drug resistant HIV through breastfeeding.¹⁴

Because of concerns about drug resistance and relatively low effectiveness, there is now general agreement that single dose nevirapine should be used only when no alternative PMTCT 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 nevirapine, which can be used with little or no medical supervision at all. So, for now, single dose nevirapine remains the only practical choice for PMTCT of HIV in areas with minimal medical resources.

Combining AZT with single dose nevirapine

According to World Health Organisation (WHO) guidelines, the regimen currently recommended for preventing mother-to-child transmission (PMTCT) in resource-limited settings uses a combination of AZT and single dose nevirapine. This approach is much more difficult to administer than single dose nevirapine on its own, but it is also significantly more effective, and is less likely to lead to drug resistance. AZT was first shown to reduce MTCT rates in 1994, and is the best-studied drug for this purpose.

The woman should begin taking AZT after 28 weeks of pregnancy (or as soon as possible thereafter). During labour she should take AZT and 3TC, as well as a single dose of nevirapine. Her baby should receive a single dose of nevirapine immediately after birth, followed by a seven-day course of AZT. The mother should continue taking AZT and 3TC for seven days after delivery, to cut the risk of drug resistance still further.

The WHO says that PMTCT programmes are "strongly encouraged" to implement the above regimen. However, they acknowledge that in some settings it may still be necessary to use simpler options, as shown in the table below.

WHO guidelines for PMTCT drug regimens in resource-limited settings

	Pregnancy	Labour	After birth: mother	After birth: infant
Recommended	AZT after 28 weeks	single dose nevirapine; AZT+3TC	AZT+3TC for seven days	single dose nevirapine; AZT for seven days
Alternative (higher risk of drug resistance)	AZT after 28 weeks	single dose nevirapine	-	single dose nevirapine; AZT for seven days
Minimum (less effective)	-	single dose nevirapine; AZT+3TC	AZT+3TC for seven days	single dose nevirapine
Minimum (less effective; higher risk of drug resistance)	-	single dose nevirapine	-	single dose nevirapine

If the woman receives at least four weeks of AZT during pregnancy, doctors may choose to omit her dose of nevirapine from the recommended regimen. In this case she will not have to take 3TC during labour, or to take any drugs after birth. However, her baby must still receive nevirapine, and should also receive AZT for four weeks instead of one.

If the woman receives less than four weeks of AZT during pregnancy then her baby should receive AZT for four weeks instead of one.

Triple combinations

The most effective PMTCT therapy involves a combination of three antiretroviral drugs taken during the later stages of pregnancy and during labour. This therapy is essentially identical to the treatment taken by HIV-positive people for their own health, except that it is taken only for a few months, and the choice of drugs may be slightly different. Triple therapy is usually recommended to women in developed countries, and is becoming more widespread in the rest of the world. AVERT.org has more information about HIV and pregnancy, including a discussion of these more sophisticated regimens.

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.¹⁵

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.^{14, 15, 16, 17} Numerous subsequent studies, including a large clinical trial in Thailand, have reaffirmed that nevirapine is safe and effective at preventing MTCT.¹⁶

HIV and safer infant feeding

A number of studies have shown that the protective benefit of drugs is diminished when babies continue to be exposed to HIV through breastfeeding.^{17 18}

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.¹⁹

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 resource 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.^{20 21}

Read more about HIV and breastfeeding.

Caesarean sections

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.

International PMTCT initiatives

There are a number of large-scale international initiatives to prevent mother-to-child transmission of HIV. These include:

1. The President's Emergency Plan for AIDS Relief (PEPFAR)
2. The Call to Action Project
3. The UN Interagency Task Team on MTCT
4. MTCT-Plus
5. The Global Fund

The President's Emergency Plan for AIDS Relief (PEPFAR)

On June 19th 2002, US President Bush announced a new $500 million International Mother and Child HIV Prevention Initiative to prevent the transmission of HIV from mothers to infants and to improve health care delivery in Africa and the Caribbean. The Initiative was later integrated into the President's Emergency Plan for AIDS Relief (PEPFAR), which is a $15 billion, five-year programme to fight HIV/AIDS around the world.

The original Initiative had the aim of reaching one million women with HIV testing and counselling and providing preventive drugs to 80 per cent of HIV positive delivering women by 2007. It aimed to reduce mother-to-child transmission by 40 percent in its fourteen focus countries, twelve of which are in Africa. PEPFAR is building on what the Initiative has already achieved and is moving towards providing more long-term antiretroviral treatment for mothers and infected infants, instead of single dose nevirapine.²²

In Fiscal Year 2004, PEPFAR helped to provide 125,100 women with ARV therapy to prevent infection of their unborn child, and as a result an estimated 23,766 infant infections were averted.²³

AVERT.org has more information about the President's Emergency Plan for AIDS Relief in our PEPFAR page.

The Call to Action Project

The Elizabeth Glaser Paediatric AIDS Foundation initiated the Call to Action Project (CTA) in September 1999 to help reduce MTCT of HIV in resource poor countries. The CTA is a public-private partnership that receives funding from both private sources such as the Gates Foundation and government grants. CTA has worked or is now working at approximately 400 sites in nineteen countries worldwide, of which twelve are in Africa.

The Foundation joined up with USAID in 2002 to rapidly expand PMTCT programmes. Programmes that were funded by USAID are now part of PEPFAR, while other CTA sites are still supported with private funding. By the end of 2003, the Call to Action project had trained over 5,000 healthcare workers and provided voluntary counselling to more than 625,000 women. Of the women who received counselling, 80 percent of them also received HIV testing. In its first three years, the project reached over 60,000 mothers and babies with antiretroviral drugs to prevent MTCT.²⁴

The UN Interagency Task Team on MTCT

The UN Interagency Task Team on MTCT involves UNICEF, UNFPA, WHO, the World Bank and the UNAIDS Secretariat and works with the governments of various developing countries to set up PMTCT programmes.

During the Task Team's pilot phase in Botswana and Rwanda, from April 1999 to July 2001, counselling was provided to 220,000 pregnant women. Of these women, 138,000 were tested for HIV, and about 4,500 HIV positive women received antiretroviral therapy to prevent MTCT. As of mid-2005, support was being provided to 226 programme sites in sixteen countries, of which ten are in Africa.²⁵

MTCT-Plus

The MTCT-Plus Initiative was established in 2002, and is coordinated by the Mailman School of Public Health at Columbia University. The Initiative aims to move beyond interventions aimed only at preventing infant HIV infection. It does this by supporting the provision of specialised care to HIV-infected women, their partners and their children who are identified in MTCT programmes. Funding for the initiative is provided by a group of private foundations, including the Gates Foundation, the Kaiser Family Foundation and the Rockefeller Foundation, as well as by PEPFAR via USAID.

The MTCT-Plus Initiative provides operational funding, medications, training and technical assistance at 12 sites in sub-Saharan Africa and at one site in Thailand. By mid-2005 it had enrolled over 8,000 individuals in care and treatment.²⁶

The Global Fund

The Global Fund to Fight AIDS, Tuberculosis and Malaria is a public-private partnership that distributes grants worldwide to fund HIV/AIDS prevention and treatment programmes. Grants are distributed over two years and most countries receive some grants to fund PMTCT programmes. Targets set by Global Fund grant recipients include:

• In India to reduce the MTCT rate to less than 10 percent by 2008 - potentially averting 70,000 infant HIV infections.²⁷
• In Haiti to treat 12,100 HIV positive pregnant women per year, and to halve the number of infected babies born each year.²⁸
• In Malawi to ensure that 70 percent of HIV positive pregnant women receive nevirapine.²⁹

AVERT.org has more about The Global Fund.

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 tesing 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."³⁰

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.³¹

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 HIV testing and counselling 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.

Read more about the practicalities of PMTCT, or join AVERT's Stop AIDS in Children campaign to call for more effective action.

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AVERT.org has more about:

• HIV prevention
• PMTCT around the world
• HIV and pregnancy
• HIV and infant feeding