Call to action for an HIV/AIDS-free generation

October 2006

TORONTO — The most effective way to reduce the burden of pediatric HIV globally is to focus on the prevention of mother-to-child transmission, according to the World Health Organization. However, each day nearly 1,500 new cases occur in children younger than 15 years, more than 90% of which occur in developing countries.

“Currently, a global inequity exists between developed and resource constrained countries in standard of care for the prevention of HIV infection in infants and young children,” said Renè Ekpini, MD, medical officer with the prevention in the health sector department of HIV/AIDS at WHO. “In most resource-constrained countries, especially in high HIV burdened countries, access to … quality HIV prevention, care and treatment services remains very limited.”

Data from 2004 indicated that globally less than 15% of HIV-infected pregnant women were tested for HIV, less than 10% of HIV-infected pregnant were offered antiretroviral (ARV) prophylaxis and less than 5% of HIV-infected pregnant women in need of treatment were offered antiretroviral therapy (ART).

At the XVI International AIDS Conference, held here, WHO presented 2006 revised guidelines for treating pregnant women in infants in resource-limited settings.

The implementations of these guidelines are designed to achieve universal access to ARV for mothers by 2010, and requires that governments demonstrate political leadership and commitment by allocating adequate resources, officials said. They also present optimal ARV regimens that benefit both mothers and children.

“We hope that the current and new WHO guidelines will help public health decision makers to make the best choices of ARV regimens for pregnant women, appropriate to their specific country context” said Urbain Olanguena Awono, Cameroon’s Minister of Public Health.

Key evidence

In December 2005, UNICEF and WHO officials, in collaboration with members of the expanded interagency task team, convened a global partners forum on the prevention of mother-to-child transmission of HIV. Representatives from more than 25 countries, as well as donor and development prevention organizations, attended the forum and issued a call for action from national governments to commit to the elimination of HIV/AIDS in infants and young chidren by scaling up comprehensive HIV prevention, treatment, care and support services in the context of preventing mother-to-child transmission. To achieve this goal, the high level forum recommended that governments should improve the standards of care, strengthen quality assurance systems and develop strategies to increase service uptake.

The recommendations were based on evidence from randomized controlled trials, observational cohort data and expert opinion where evidence was lacking.

Studies in breast-fed and non-breast-fed infants have demonstrated reduction of HIV transmission with short-course zidovudine (Retrovir, GlaxoSmithKline) alone or zidovudine plus lamivudine (Epivir, GlaxoSmithKline). In contrast, the efficacy of single dose nevirapine (Viramune, Boehringer Ingelheim) is less effected by continued breast-feeding. Studies also indicate that a combination of zidovudine plus single dose nevirapine is more effective than single drug regimens in formula-fed as well as breast-feeding populations, according to Ekpini.

Low CD4 cell counts are associated with higher mother-to-child transmission rates in women, even when they receive short-course ARV prophylaxis. This transmission risk can be remarkedly reduced if these women are provided with antiretroviral treatment for their own health. About 20% to 30% of pregnant women living with HIV meet WHO’s criteria for initiating ART for their own heath. Studies in the Ivory Coast showed that the use of ARV treatment in breast-feeding populations could reduce the four- to five-week risk of transmission to level around 2%.

Updated recommendations

Recommendations for initiating ART for pregnant mothers are the same as for non-pregnant women, with the exception that pregnant woman in WHO HIV disease clinical stage III, who have a CD4 cell count less than 350 cells/mm³ could be initiated on ART. Where CD4 cell counts are not available, all women in stage III should be treated, according to Ekpini. As for non-pregnant women, WHO guidelines recommend not treating those with clinical stage I and II, unless their disease CD4 cell count is less than 200 cells/mm³.

“According to the revised guidelines, treatment should be started as soon as practical, even if they are in the first trimester of pregnancy, unless it is desirable for the women to delay treatment. Women who do not need ART should be offered ARV prophylaxis for mother-to-child transmission prevention.”

Single dose nevirapine for prevention is only the minimum standard of care for pregnant women living with HIV, when the conditions do not permit administration of more efficacious regimens, according to Ekpini. The recommended first line ART regimen is a combination of zidovudine plus lamivudine plus nevirapine for eligible women and zidovudine and single dose nevirapine for those not eligible for treatment. For the infant, the recommended regiment is single dose nevirapine soon after birth plus one week of zidovudine. If the mother received less than four weeks of antenatal zidovudine during pregnancy, then the infant should receive a four-week course of zidovudine.

There are special considerations based on the woman’s history of ARV treatment, gestation period and potential adverse events. Alternative prophylactic regimens for the woman consists of antepartum zidovudine starting at 28 weeks of pregnancy or as soon as thereafter, intrapartum single dose nevirapine and zidovudine/lamivudine started during labor and continued for one week postnatally. The guidelines also recommend the use of zidovudine/lamivudine for seven days postantenally in women receiving nevirapine whether alone or in combination with zidovudine to reduce resistance.

The guidelines state that “in view of current evidence and programmatic experiences, current UN recommendations on HIV and infant feeding remain valid respective of whether a woman is receiving ART. Women receiving ART who are breast-feeding should continue their regimen and the use of ARV drugs in the mother and/or infant to prevent mother-to-child transmission through breast-feeding is currently not recommended,” Ekpini said.

The revised guidelines also address issues of when to administer ART to pregnant women living with HIV who also have anemia or active tuberculosis, those who use injection drugs, those with HIV-2 and those with primary HIV during pregnancy.

In the late 1990s, 11 countries conducted the first pilot projects on preventing mother-to-child transmission of HIV, and now more than 100 countries have established programs, according to Alan Court, director of programs at UNICEF. In 2003, an estimated 3% of women living with HIV were receiving ART; however, by 2005 the rate increased to 9% and a few countries in Eastern Europe and Latin America exceeded 80% of coverage.

“It is high time, therefore, for a determined drive for scale up of this highly effective and eminently affordable intervention,” said Court. “We must unite for children, we must unite against AIDS and preventing mother-to-child transmission is the ideal place to demonstrate that we could make a difference in our collective efforts to mitigate the impact of HIV on children and on their families.”

WHO officials called for governments to demonstrate leadership and commitment by allocating greater resources to strengthening of health delivery services to build the necessary human resource capacity and develop strategies for reducing new infections in children.

“Achieving the goal of eliminating HIV infection in infants and young children … requires integrating prevention of mother-to-child transmission into basic health services in all our health facilities, adopting a good standard of care for all pregnant women and providing access to HAART for pregnant women,” Awono said. “This standard of care should be built around good quality reproductive and sexual health care, routine HIV testing and counseling in delivery care settings, ART with more efficacious ARV regimens for mother-to-child transmission prevention, access to a comprehensive global care of HIV infection for the mothers, their children and their spouses or partners.”

Ekpini believes that many factors need to be considered to scale up national prevention programs of HIV. These factors include: the government leadership and commitment to mobilize and allocate human and financial resources, strength of health services, adoption of standards of care and implications of service delivery approaches.

“Achieving the goal of elimination of HIV in infants and young children will require that all pregnant women with HIV in need of ART have access to it. National programs are strongly encouraged to develop capacities for delivering more efficacious regimens,” he said. “Despite difficulties and challenges, a glimmer of hope can arise for an HIV-free and AIDS-free generation.”

For more information:

• Awono UO, McDermott P, DeCock K, et al. PMTCT of HIV in the era of HAART: opportunities, challenges and experiences in implementing national programs. Satellite session SUSA07. Presented at: XVI International AIDS Conference; August 13-18, 2006; Toronto.
• The 2006 revised WHO guidelines can be viewed in its entirety at: www.who.int/hiv/pub/guidelines/WHOpaediatric.pdf