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Addressing pediatric AIDS in Africa requires multifaceted approach
There are tremendous barriers that will require new advances from the medical community to make a dent in the AIDS rate.
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The numbers are so enormous that they become almost meaningless.
At the conclusion of 2006, UNAIDS estimated that there were almost 40 million people living with HIV worldwide and that 2.3 million were children younger than aged 15. During this past year there were approximately 530,000 new HIV infections and 380,000 HIV-associated deaths in children worldwide, yet in the United States and other developed countries, new pediatric infections and/or deaths occur only rarely.
The treatment of patients with HIV treated with HAART became the standard of care in the United States in 1996. While developed countries have had access to these life-saving medicines for more than a decade, they did not become widely available in Africa until early in 2005. The distribution of antiretroviral medications for both prevention and treatment programs on the African continent have not been easy. Scale up has been especially strong in Botswana, Kenya, Malawi, Namibia, South Africa, Uganda and Zambia. But as strong as the efforts have been, the major focus of these programs has been on the care and treatment of adults. Currently, only about 5% of those receiving HAART are children younger than 15 years of age, despite the fact that children comprise approximately 15% of people living with HIV.
HIV alone would be devastating to many resource-limited countries on the African continent, but in combination with poverty, malnutrition, malaria, and tuberculosis, whole generations of people are dying. The governmental and social support systems of many African countries that were already being pushed to their limit prior to HIV now find themselves completely overwhelmed and in need of help. For Africa to survive this epidemic there needs to be substantial progress in six areas: 1) prevention of maternal-fetal transmission of HIV; 2) increased availability of virologic testing for all infants; 3) sustainable programs for infant feeding; 4) an increase of practitioners that are able to serve children; 5) antiretroviral formulations that can be given to children of all ages and 6) the ability of local governments to provide support for these programs.
Prevention of mother-to-child transmission (PMTCT) of HIV is of the utmost importance if this epidemic is ever going to be controlled. The use of prophylactic zidovudine in pregnant women and their infants became the standard of care in the United States in the mid-1990s. The use of this single agent dropped the perinatal transmission rate from approximately 26% to 8% (NEJM. 1994;331:1173-1180). Due to cost constraints and limited access to prenatal care in resource-limited areas, many countries have implemented HIV prevention protocols using a single dose of nevirapine (sdNVP) for the mother and infant. Well over 875,000 women/infant pairs to date have used this regimen. Although not as effective as other antiretroviral regimens that provide medications during pregnancy, labor and delivery, the use of sdNVP has had a significant effect on mother to child transmission of HIV (Lancet. 1999;354:795-802). But in Sub-Saharan Africa only about 10% of mothers with HIV actually have access to prophylactic antiretroviral therapy.
The reasons for the poor uptake include: 1) limited prenatal screening; 2) the lack of women’s rights; 3) rural living conditions; 4) society and cultural lack of acceptance and 5) limited availability of medications. WHO currently recommends sdNVP as the third option for women who have HIV but are not yet in need for HAART. The recommended regimen includes starting zidovudine at 28 weeks, zidovudine and lamivudine and sdNVP during labor, followed by zidovudine plus lamivudine for seven days after delivery. The infant receives sdNVP plus zidovudine for seven additional days. But if sdNVP can only reach 10% of the women with HIV that require prophylactic treatment during pregnancy and delivery, attempting to roll out a more involved regimen will fail unless significant improvements are made in reaching mothers and infants living outside of large urban areas. An additional problem with the PMTCT programs is that most are stand-alone programs and are not integrated into both the pediatric or adult care and treatment programs. Therefore, once these mothers deliver, the linkage of the post-partum women that require HAART and their HIV-exposed infants to care and treatment providers continues to be problematic. Women that are eligible for HAART never find their way to the adult care and treatment programs and their HIV-exposed infants are also lost to follow-up. These infants therefore, will not have access to early testing nor trimethoprim-sulfamethoxazole prophylaxis.
In many African countries, only antibody tests (eg, ELISA, Western blot, rapid tests) are available for diagnosing HIV infections. These tests are not helpful in confirming infection in children younger than 18 months due to the transplacental passage of maternal antibody. Although the detection of HIV DNA by polymerase chain reaction (PCR) testing of dried blood spots has been a great advance in establishing a diagnosis in infants and children younger than 18 months, these tests are not widely available. In many countries, samples must be sent to regional centers that are often located in a neighboring country leading to delays of four to eight weeks before results become available. There is an urgent need for new technology in the area of virologic testing for infants in resource-limited areas such as Africa. The next generation of virologic tests should: 1) allow people with very limited training to perform these tests; 2) be highly accurate in infants and children younger than 18 months of age; 3) be compact and extremely portable; 4) require a limited power source and be able to run without a large water requirement and 5) be economical for all parties involved.
In developed countries, mothers with HIV are instructed not to breast-feed due to the possibility of transferring their infection to the newborn infant via the consumption of infected breast milk. But in areas of the world that have no access to formula or clean water, breast-feeding is the only source of nutrition for most infants. Even though breast-feeding accounts for 5% to 20% of all HIV infections in children younger than 1 year of age, WHO officials currently support exclusive breast-feeding (no additional water or foods, only liquid medications are acceptable) of all infants for the first 6 months of life with a transition to other options once there is an Acceptable, Feasible, Affordable, Sustainable and Safe alternative (AFASS) to breast milk. If however the children are known to have HIV, they are instructed to continue to breast-feed until 2 years of age so that malnutrition becomes less of an issue. The AFASS solution to breast-feeding is not as easy as providing formula to all mothers. Breast-feeding is the cultural norm in most countries and women who do not breast-feed are the source of suspicion and ridicule. In addition, it has been shown that infants that are bottle-fed are more likely to have diarrheal illnesses resulting in death as compared to those that are breast-fed (JAMA. 2006;296:794-805). Many women are eager to quit breast-feeding as soon as possible since they understand the risk to the infant but they do so without a sustainable nutritional substitute. Infants are then at risk of developing moderate-to-severe malnutrition that have mortality rates of between 30% and 80%. Although there have been advances in “ready to use therapeutic foods (RUTF)” for the treatment of malnutrition, data are lacking on the use of these products in the prevention of moderate to severe malnutrition. In addition, most RUTF currently available are costly and are not produced locally, thus requiring importation. New technologies are needed that can enable people to produce new RUTF using locally available products for sources of carbohydrate, protein, fat, and essential minerals.
Medical assistance
The loss of medical practitioners in many countries in Africa has been well documented (NEJM. 2007;356:440-443). There can really be no meaningful response to the HIV/AIDS epidemic without sufficient health care workers, but currently educating and retaining an adequate number is a tremendous challenge for all involved. For instance, Sub-Saharan Africa contains 11% of the world’s population but 60% of the world’s HIV/AIDS cases and they are trying to manage this with only 3% of the world’s health workforce (www.who.int/bulletin/africanhealth/en/index.html). There are a limited number of physicians trained on the African continent and the majority of the graduates will leave their homes to seek better salaries and working conditions in Europe, the United Kingdom, Australia and the United States. Once these practitioners leave it is very difficult to get them to return to their home due to the lack of a working medical infrastructure, poor wages and working conditions and the constant death that surrounds their practices.
The loss of qualified practitioners has an especially profound effect on the health care of children. Many of the countries’ health care systems are run by clinical officers with a two-year clinical degree or medical officers who have medical school training without a specialization and who acquire little pediatric training during their schooling. There is a perception among many practitioners with little or no pediatric training that providing antiretroviral therapy for children is too difficult, too dangerous, or not effective.
Efforts then become concentrated on the adults in the community and children become therapeutic orphans. Recently the Institute of Medicine proposed the development of a global health service corps in a report titled: “Healers Abroad: Americans Responding to the Human Resource Crisis in HIV/AIDS” and in a separate publication, Dr. Fitzhugh Mullan encouraged the United States government to develop a blend of the Peace Corps and the National Health Service Corps (JAMA. 2007;297:744-746). This Peace Corps for Health would help mobilize U.S. health workers that are ready to commit to working abroad in the long-term battle against HIV/AIDS. Unfortunately, neither of these proposals has materialized. Because of this the Baylor International Pediatric AIDS Initiative has developed the Pediatric AIDS Corps (PAC). The PAC is made up of physicians with training in pediatrics, internal medicine-pediatrics, and family medicine that work in African settings where there are only a limited number of practitioners available. They help facilitate care and treatment to children with HIV and their families. In addition, the training of local practitioners in the care and treatment of children with HIV and their family is a major focus of this group. Initiatives such as the PAC are not intended to be long-term solutions to the current manpower issues, however they can be helpful in certain areas until the number of practitioners that deliver health care to children can be replenished. There are no short cuts available, the long-term success in stopping this epidemic will require the re-building and maintenance of medical infrastructure in many parts of Africa.
Although the availability of antiretroviral medications for the care and treatment of children in Africa has improved, the choices of medications that are available are limited. Most country protocols will start children on zidovudine or stavudine plus lamivudine plus nevirapine or efavirenz. Stavudine is preferred over zidovudine in areas with high concentrations of malaria due to the occurrence of anemia with zidovudine. Efavirenz does not come in a liquid preparation and is started in children older than 3 years of age and 10 kilograms of weight. Protease inhibitor (eg, nelfinavir, lopinavir/ritonavir) usage is limited due to the cost of the medications. Therefore there are limited options for children that have problems with medication adverse events or for those who are failing their primary regimen. In addition, because fixed dose combinations (eg, stavudine plus lamivudine plus nevirapine in one tablet) of medications are not readily available for infants and younger children, three doses of individual liquid preparations may be required twice daily. Multiple drugs given frequently during the day leads to poor adherence and increases the chance of medication errors. In addition, some of these liquid medications require a cold chain (eg, stavudine, lopinavir/ritonavir) that adds to the difficulty of their use in areas without refrigeration. Fixed dose combinations are widely available for adults but these preparations are often cut in halves or quarters and used for children. These altered medications will not contain reliable amounts of individual drug in the smaller sections and can lead to either over or under dosing of the children. Although there have been pediatric preparations of these fixed dose combinations developed, they have not yet been approved for widespread use by the WHO.
Involve local government
Lastly, any program that currently is working in Africa must have a plan that will make their interventions sustainable by the local government. Local governments should be the primary partner for anyone working in the field so that there is political and policy support for the long term. This is exceedingly difficult since many of the African countries have no tax base or significant product that can be marketed that will provide income to pay for these programs in the long term. Currently, the Global Fund and the President’s Emergency Plan for AIDS Relief (PEPFAR) are among the leaders in providing financial support to many of these countries. But these funds are of a limited duration and it is incumbent on each country to find a way to develop a long-term economic plan that will help support the fight against HIV/AIDS. This is especially difficult when most of the countries in Sub-Saharan Africa have falling life expectancies and are losing citizens in the prime of their working years.
There are no simple answers for the children of Africa regarding the HIV/AIDS epidemic. Although significant improvements have been made over the past two years, there are still tremendous barriers present that will require new advances from the global medical community if we are going to be successful. Many individuals, organizations and governments have decided that there is no hope for the children of Africa, but we will never know if we do not try.
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- Gordon E. Schutze, MD, is a professor of pediatrics at Baylor College of Medicine and vice-president of the Baylor International Pediatric AIDS Initiative at Texas Children’s Hospital.