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Pediatric care and prevention of mother-to-child transmission (PMTCT): Establishing standards of care

Pediatrics

The treatment of children and adolescents is an essential part of HIV/AIDS care. MSF currently treats over 10,000 pediatric patients (<15 years of age) with ART in over 50 projects worldwide. These programs are situated in resource-poor settings and face complex challenges for effective pediatric HIV management.

Over the last 5 years throughout MSF, nearly 4,000 children <5 years of age have been started on ART in 48 programs in 20 countries. About 90% of these children are in Africa, with 10% in Asia and <1% in Latin America. An analysis of all children (<5 years old) started on ART from April 2002 to January 2008 in these MSF programs showed that 79% were still on treatment. Survival of children <12 months of age was found to be significantly lower compared with older age groups. Overall, ART in young children appears effective and well-tolerated within MSF programs, but comparatively poor survival in the youngest children suggests the need for earlier access to infants at risk.

In two MSF programs in Cambodia, a high early mortality rate (death within first 6 months after enrollment) was observed among children, with the rate 8-fold higher among those not yet started on ART compared with those placed on treatment. In a program in Homa Bay, Kenya, data analysis by Epicentre showed that survival in children (n=34) after 3 years of ART was similar to that reported elsewhere in adults. Despite this positive result, viral suppression was found to be absent in 50% of treated children.

Such results point to the need for adapted pediatric ARV formulations and child- and context-appropriate adherence strategies. Of the ARVs available in pediatric formulations, most are ill-adapted for use in resource-limited settings. The drugs exist either as powders needing to be mixed with water, or as syrups often requiring refrigeration and having a bitter taste. One positive development was the approval in August 2007 of pediatric-formulation fixed-dose combination (FDC) tablets for 3TC/d4T/NVP (Baby and Junior Triomune). Still, pediatric formulations for safer and newer ARVs are needed.

MSF’s largest cohort of pediatric patients on ART is in Bulawayo, Zimbabwe, where in conjunction with the MOH, provision of highly active antiretroviral therapy (HAART) for children was started in 2004. In Bulawayo, >1,400 pediatric patients are currently on ART. Substantial gains in CD4 cell counts have been seen in these pediatric patients at 6 and 12 months of ART (range 45-180%). After 4 years, pediatric clinical outcomes included a 6.3% mortality rate, 7.9% lost to follow-up, and 1.7% treatment failure (based on virological assessment). This program exemplifies the feasibility of scaling up pediatric HIV care in a setting with low resources and high prevalence.

Positive outcomes have also been seen in a nurse-based pediatric HIV program in two MSF-supported health centers in Kigali, Rwanda. In an analysis from late 2003 to mid 2007, a total of 315 children (<15 years old) started on ART. Median follow-up time after ART start was 2 years, and 84% of the children were still on treatment. Important features of the program included the availability of viral load testing (87% tested), adequate training and supervision of the ARV-administering nurses, and family-centered care with psychosocial and educational support for the children. The favorable patient results of this program demonstrate the feasibility and effectiveness of decentralized pediatric HIV care in a resource-limited setting.

Pediatric diagnostics also play a crucial role in HIV care since early initiation of ART in children reduces mortality. The WHO recently revised its pediatric guidelines to test infants at 4-6 weeks using DNA-based diagnostics (and to start all HIV-positive infants <12 months old on ART regardless of clinical or immunological stage). Despite such proactive strides for earlier treatment of children, implementation is a challenge because, for many national programs, the polymerase chain reaction (PCR) equipment required for DNA testing is expensive, requires trained personnel, and is logistically demanding.

Proper counseling and education for children living with HIV/AIDS, such as appropriately disclosing HIV status or making medical information understandable, are often insufficient in resource-poor settings. Children are often treated like small adults or, worse, excluded, where counseling is addressed only to the caregivers and not the children. To address this, MSF projects, such as those in Kompong Cham and Phnom Penh, Cambodia; Busia and Kibera, Kenya; Chiradzulu and Thyolo, Malawi; Arua, Uganda; and Bulawayo and Tsholotsho, Zimbabwe, have developed family and group-counseling education programs for children and their parents. These programs provide information in books, films, toys, and play sessions on how HIV attacks the body, how ARVs work against the virus, and why blood draws and CD4 cell counts are important. MSF has begun to look at the concept of a basic minimal support package for pediatric HIV patients, ie, a minimal set of specific measures for patient support, including health education, treatment literacy, ARV preparation, individual and group counseling, children’s “clubs”, and social support.

PMTCT

HIV-positive children largely become infected from their mothers, either during pregnancy, delivery, or the breastfeeding period. In developed countries, pediatric HIV infection has been nearly eliminated through successful prevention of mother-to-child transmission (PMTCT). Transmission rates in developed countries are typically below 2%. , However, in developing countries, PMTCT interventions have not been as successful, with an estimated 420,000 new pediatric (<15 years old) infections globally in 2007. In the US, fewer than 250 infected infants are born each year according to current estimates. Today nearly 90% of all HIV-positive children live in sub-Saharan Africa.

Treatment providers, including MSF, continue to struggle to prevent newborn infections, grappling with complex protocols and high numbers lost to follow-up. PMTCT is an increasingly important component of MSF’s projects, and from our field experience the need for simplified protocols is clear. MSF currently offers PMTCT interventions in 54 projects, with >10,000 women having started in a PMTCT intervention in 2007. Major emphasis is placed on integrating PMTCT into routine antenatal care (ANC) and maternal and child health (MCH) services, such as in Arua, Uganda; Chiradzulu and Thyolo, Malawi; and Nairobi (Mathare and Kibera), Homa Bay, and Busia, Kenya; as well as in Lesotho, Burkina Faso, and Liberia. Collection and analysis of data in MSF’s PMTCT programs are in the early stages.

In many developing countries, women have little access to ANC. All mothers should be informed of the need for HIV testing, so that if positive they can receive both treatment for themselves and interventions for preventing HIV transmission to their children. Today only an estimated 20% of HIV-positive pregnant women are receiving ARVs for PMTCT. Although reasons for this low coverage rate include financial barriers, human resource shortages, and weak health systems for MCH, one neglected but crucial factor is that of the protocols and formulations available. The protocols are complicated, and adapted ARV packaging, such as single-dose nevirapine (NVP) syrup or zidovudine (AZT) syrup for one week, are unavailable.

Also, protocols applied to developing countries differ from those used in developed countries. In developed countries, any pregnant woman who is HIV-positive has the option to receive full ART throughout pregnancy, followed by formula feeding for the infant. In most resource-limited contexts, this is not an option. To protect infants from infection, interventions are being explored to simplify the PMTCT protocol in resource-limited settings, including HAART for all HIV-positive pregnant women throughout pregnancy and the breastfeeding period. Preliminary studies under trial environments have shown some success, with HIV transmission rates as low as nearly 1%. Access to triple therapy for all pregnant women regardless of immunological status (CD4 count) has been shown to be the best way to prevent HIV transmission to the child. MSF is currently looking at implementing triple therapy in the last trimester of pregnancy and throughout breastfeeding in some pilot projects. Discussions continue on how best to approach the breastfeeding period.

Rolling out and implementing PMTCT interventions on a large scale would require the identification of the most appropriate ARV combination and the development of an adaptable FDC that is easy to administer, has favorable toxicity, and has minimal risk of resistance. Some national frameworks have already adapted simplified protocols for their PMTCT programs, and international and national guidelines should be adapted to reflect these realities. The need is evident for the international community to expediently examine new strategies for implementing simplified PMTCT protocols in resource-limited settings, all so that child HIV infections can be significantly reduced.

Optimizing pediatric HIV care in resource-limited settings requires:

• Earlier and improved access to at-risk infants, with active follow-up of PMTCT-born newborns and testing of enrolled patients’ children
• Integration of PMTCT into MCH services, including antenatal and postnatal care
• In high prevalence contexts, the offer of early infant diagnosis at vaccination sites
• Pediatric and PMTCT FDC drug regimens
• Reliable, easy-to-use, inexpensive, point-of-care diagnostic tools adapted for pediatric use, and routine diagnostic facilities in high-risk populations, such as malnourished children
• Proper management of opportunistic infections, such as TB in pediatric cohorts
• Improvement of adherence through patient and peer support measures for both mothers and their children, including support tools according to age group

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