New WHO guidelines on PMTCT and infant feeding

New recommendations from the World Health Organization (WHO) for preventing mother-to-child transmission (PMTCT) have the potential to improve child survival and the mother’s own health, to reduce mother-to-child transmission risk to 5% or lower and virtually eliminate paediatric HIV infection, WHO said today.

The recommendations represent significant shifts in practice in several areas. The key recommendations are:

• Antiretroviral therapy for all HIV-positive pregnant women with a CD4 count below 350 or WHO stage 3 or 4 HIV disease, with treatment to begin without delay using a backbone of AZT and 3TC or tenofovir and either 3TC or FTC.
• Longer provision of antiretroviral prophylaxis for HIV-positive pregnant women who are not in need of ART for their own health.
• Where mothers are receiving ART for their own health, infants should receive prophylaxis with nevirapine for six weeks after birth if the mother is breastfeeding, and prophylaxis with either nevirapine or AZT for six weeks if the mother is not breastfeeding.
• For the first time there is enough evidence for WHO to support giving antiretroviral therapy to the mother or child throughout the breastfeeding period, with the recommendation that breastfeeding and prophylaxis should continue until twelve months of age if the infant is either HIV-negative or of unknown status.
• Where mother and infant are both HIV-positive, breastfeeding should be encouraged for at least the first two years of life, in line with recommendations for the general population.

“In the new recommendations we are sending a clear message that breastfeeding is a good option for every baby, even those with HIV-positive mothers, when they have access to antiretrovirals,” said Daisy Mafubelu, WHO’s Assistant Director General for Family and Community Health.

The guidelines offer guidance to countries on how to reduce HIV transmission from mother-to-child through more effective treatment and prevention regimens.

First issued in 2000, and revised in 2004 and 2006, the PMTCT antiretroviral guidelines recommend the delivery of simple, standard and effective regimens on a large scale in all settings.

The 2006 guidelines highlighted the importance of lifelong antiretroviral treatment for eligible HIV-positive pregnant women for their own health and their children. In addition combination antiretroviral prophylaxis replaced single-dose nevirapine. These guidelines serve as the technical backbone for rapid PMTCT scale-up, in particular in sub-Saharan Africa where more than 90% of HIV-positive pregnant women live.

An estimated 21% of pregnant women received an HIV test in 2008 and 45% received drugs to prevent mother-to-child transmission, of whom around one-third received single-dose nevirapine (Viramune), the least effective form of preventive treatment. Only one-third of those who tested positive were assessed for eligibility for antiretroviral treatment for their own health.

With an estimated 1.4 million pregnant women in low- and middle-income countries living with HIV in 2008, much more needs to be done to scale up HIV testing and counselling and PMTCT including integration of these services into strengthened maternal and child health programmes.

The new guidelines recommend lifelong antiretroviral treatment for all pregnant women with serious or advanced disease or with a CD4 count at or below 350 regardless of symptoms. Evidence suggests that this could prevent 75% of all mother-to-child transmission while also providing the best available treatment for the mother’s health, says WHO, in addition to providing protection during the breastfeeding period. It is consistent with the new adult ART recommendations.

In women who do not need antiretroviral therapy for their own health (ie, with a CD4 count above 350), antiretroviral therapy is to start earlier in the pregnancy, at 14 weeks or as soon as possible thereafter, and should continue through to the end of the breastfeeding period. This change reflects evidence from clinical trials showing the efficacy of antiretrovirals in preventing transmission of HIV to the infant while breastfeeding. In 2006, guidelines recommended starting ART at 28 weeks with a basic daily regimen of zidovudine (AZT, Retrovir) and single-dose nevirapine during labour and delivery, as well as infant prophylaxis for one week after birth.

The 2009 guidelines offer two options:

• Daily AZT for the mother during pregnancy, single dose nevirapine at the onset of labour, AZT/3TC during labour and for seven days post-partum. If a mother has taken AZT for at least four weeks prior to delivery AZT/3TC and single-dose nevirapine can be ommitted. Infant prophylaxis with nevirapine or AZT should be continued until the end of the breastfeeding period or for six weeks after birth in non-breastfeeding infants.

Or

• A three-drug regimen for the mother taken during pregnancy and throughout the breastfeeding period, as well as infant prophylaxis as in option A. The recommended regimens are AZT/3TC plus efavirenz, abacavir (Ziagen) or lopinavir/ritonavir (Kaletra/Aluvia).

WHO’s international expert review panel decided that there is now enough evidence for WHO to recommend antiretroviral treatment during breastfeeding.

Breastfeeding is to continue until the infant is twelve months old in HIV-exposed but uninfected infants, and those of unknown HIV status, as long as the HIV-positive mother or baby is taking antiretrovirals during this time.

While most babies of HIV-positive women in resource-rich settings are given formula feed from birth in order to prevent transmission through breastfeeding after delivery, in resource-limited settings safe replacement feeding has not been a viable option.

Depending on available interventions to prevent HIV transmission through pregnancy and delivery, breastfeeding has been responsible for between 30 and 60% of all HIV infections in children. Yet children who do not breastfeed are up to six times more likely to die from diarrhoea, malnutrition or pneumonia.

Mothers are faced with choosing between the benefits of breastfeeding but exposing their children to the risk of HIV transmission or not breastfeeding and increasing the child’s risk of death from other diseases.

There are two choices for HIV-positive women who breastfeed and are not taking ART:

• If a woman received zidovudine during pregnancy, daily nevirapine is recommended for her child from birth until the end of the breastfeeding period.

Or

• If a woman received a three-drug regimen during pregnancy, a continued regimen of three-drug prophylaxis is recommended for the mother until the end of the breastfeeding period.

Recommendations for infant feeding practices in the first 24 months of life:

• Mothers known to be HIV-infected (and whose infants are HIV-uninfected or of unknown HIV status) should exclusively breastfeed their infants for the first six months of life, introducing appropriate complementary foods after that, and continue breastfeeding for the first twelve months of life. Breastfeeding should then only stop once a nutritionally adequate and safe diet without breast milk can be provided.
• If infants and young children are known to be HIV-infected, mothers are strongly encouraged to exclusively breastfeed for the first six months of life and continue breastfeeding as recommended for the general population, that is up to two years and beyond.

National authorities are advised to choose one national policy, based on local circumstances and health system capacity: either to counsel and support mothers infected with HIV to breastfeed and receive ART interventions or to avoid all breastfeeding, as the strategy that will give the best chance of remaining uninfected and alive. WHO is developing guidelines to assist countries in this decision-making process. As in 2006, the recommendations reaffirm the call for agencies to invest in improved infant and young child nutrition.

In countries not affected by HIV it is estimated that improved infant feeding practices can reduce child mortality by up to 19%. The reduction in child mortality could be significantly greater in populations affected by HIV if improved feeding practices can be promoted throughout the population, not just among HIV-positive mothers, WHO says.

Weak health infrastructure, lack of human resources and limited management capacity, as well as lack of funding and support for PMTCT, still challenge scale-up and guideline implementation.

WHO suggests that successful implementation of the new guidelines will depend on:

• Universal voluntary HIV testing and counselling for pregnant womens
• Availability of CD4 testing and ART at primary care level and antenatal facilities where most maternal-child health care takes place, and not just in specialised clinics.
• Improved follow-up of pregnant women antenatal and of mothers and HIV-exposed infants after birth.
• Ability to provide prophyaxis to the mother or baby throughout breastfeeding, as well as infant feeding counselling and support.
• Appropriately trained staff.

The full guidelines are due to be published early in 2010.