The successes of the United States and other developed countries in the prevention and treatment of pediatric HIV/AIDS have not been replicated in the developing world, where children continue to become infected with HIV and die from HIV/AIDS at astounding rates. Children are underrepresented among recipients of antiretroviral therapy in almost every setting worldwide where treatment programs have been established. The barriers to scaling up HIV/AIDS care and treatment globally are substantial. Nevertheless, nearly a decade after the introduction of pediatric highly active antiretroviral therapy in the United States, the opportunity finally exists to provide treatment to huge numbers of HIV-infected children in the developing world, changing forever the way that pediatric HIV/AIDS is perceived and managed. We propose the creation of a Clinical Centers of Excellence Network and Pediatric AIDS Corps of US pediatric health professionals, increased support for pediatric research relevant to resource-poor settings, commitment of the US government and others to proportionate funding for pediatric HIV/AIDS care and treatment, expanded availability of pediatric antiretroviral drug formulations, and a renewed commitment to collaborative partnerships as practical steps that can be taken to dramatically expand access of HIV-infected children and families in the developing world to health-restoring, life-prolonging care and treatment.
The near elimination of new cases of HIV infection and AIDS among US children is 1 of a precious few public health success stories in the nearly 25-year history of the epidemic. The enormous success of efforts to prevent mother-to-child HIV transmission, as well as the advent of pediatric highly active antiretroviral therapy (HAART) in the mid-1990s, has led to a decrease in new US pediatric AIDS cases of >90%, from 945 in 1992 to just 48 in 2004.1 The annual death rate for HIV-infected children in care at Texas Children's Hospital declined from ∼13% in 1995 to ∼1% in 2004–2005 (unpublished data).
Unfortunately, the successes of the United States and other developed countries have not been replicated in the developing world, where children continue to become infected with HIV and die from HIV/AIDS at astounding rates. Until recently, public health authorities were questioning whether the kinds of treatments that had transformed HIV/AIDS in the United States from an invariably fatal condition to a chronic, manageable medical condition ever would be available, practical, or affordable for people who live in the world's poor countries. Now, nearly a decade after the introduction of pediatric HAART in the United States, the opportunity finally exists to provide treatment to huge numbers of HIV-infected children globally, changing forever the way that pediatric HIV/AIDS is perceived and managed.
IMPACT OF HIV/AIDS ON CHILDREN GLOBALLY
Approximately 1.9 million (80%) of the 2.3 million children (younger than 15 years) who were living with HIV/AIDS at the end of 2005 were African.2 Approximately 700000 children were newly infected with HIV in 2005 alone, and 570000 children died, 1 every minute of every hour of every day. Children account for 14% of all new HIV infections and 18% of all deaths from HIV/AIDS globally.
Approximately 4% of all deaths globally of children who are younger than 5 years are attributable to HIV/AIDS, but the disease is the dominant cause of death in some southern African countries, accounting for more deaths in this age group than all other causes combined (Fig 1). 3 Botswana, Zimbabwe, and Swaziland, which currently register the second, third, and fourth greatest rates, respectively, of increase in mortality of children who are younger than 5 years globally, also have the world's highest national HIV/AIDS prevalence rates: ∼37%, 25%, and 39%, respectively.
Deaths represent only 1 facet of the impact of HIV/AIDS on children in the developing world. Currently, 15 million children worldwide and 12 million children in sub-Saharan Africa have been orphaned by HIV/AIDS.4 The number of African children who are orphaned by HIV/AIDS is likely to exceed 18 million by 2010, when every fifth child in the most affected countries of southern Africa will be an orphan. Many of these children are destined for lives of poverty, illiteracy, disease, and early death.
CURRENT STATUS OF PEDIATRIC HIV/AIDS CARE AND TREATMENT IN THE DEVELOPING WORLD
In the instance of antiretroviral therapy, the scenario for children is, quite simply, doomsday.
United Nations Special Envoy for Africa
January 18, 2005
The World Health Organization (WHO) and the Joint United Nations Program on HIV/AIDS estimate that at least 6.5 million people (660 000 children) worldwide have advanced HIV/AIDS and are in urgent need of antiretroviral treatment. In September 2003, the WHO and the Joint United Nations Program on HIV/AIDS announced the “3 by 5” Initiative, an interim program to provide antiretroviral treatment to at least 3 million HIV-infected people in the developing world by the end of 2005. By the end of June 2005, the number of people who had received antiretroviral treatment in developing and transitional countries through this and other programs was only about 970 000.5 This figure includes 500000 Africans, or ∼11% of the 4.7 million Africans who are in need of antiretroviral treatment.
Children are underrepresented among recipients of antiretroviral therapy in almost every setting worldwide where treatment programs have been established. In May 2005, it was estimated that only between 15000 and 25000 HIV-infected children globally were receiving antiretroviral therapy,6 fewer than 1% of the estimated 2.3 million children who are living with HIV/AIDS, and only ∼3% of all recipients of antiretroviral treatment.
The barriers to scaling up HIV/AIDS care and treatment globally are substantial. Although global spending on HIV/AIDS increased 15-fold between 1996 and 2003, to just under $5 billion, it is less than half of that needed.7 According to newly revised estimates, $12 billion will be needed in 2006 and $20 billion by 2007 for HIV/AIDS prevention and care in low- and middle-income countries. This $20 billion in annual spending would provide antiretroviral treatment to ∼6 million people, >4 million in sub-Saharan Africa alone.
In many settings worldwide, clinical and laboratory facilities for diagnosing HIV infection and administering and monitoring treatment simply do not exist. Antibody-based assays for HIV diagnosis (eg, HIV enzyme-linked immunoassay and Western blot) are of little use in infants, and virologic assays for HIV diagnosis (eg, HIV DNA or RNA polymerase chain reaction) often are prohibitively expensive or unavailable. Children usually are identified as having HIV infection only when they become ill; the majority die without a chance at therapy. Programs to prevent mother-to-child HIV transmission often are not coordinated with care and treatment programs, resulting in lost opportunities for early treatment of HIV infection in infants and prevention of HIV-related complications, such as by administration of trimethoprim-sulfamethoxazole. This is true especially in sub-Saharan Africa, where the demands are greatest.
The human professional capacity for delivering HIV/AIDS care and treatment is severely constrained across sub-Saharan Africa, where per capita numbers of physicians and nurses are only 1% to 2% of those of the United States. The productive capacity of African professional schools is low, and there is an ongoing exodus of health professionals to the developed countries, as well as a loss of large numbers of professionals to death. In Africa, it is estimated that between 19% and 53% of all health professional deaths are caused by HIV/AIDS.8 A recent report of the Institute of Medicine recommends that the US federal government create and fund an umbrella organization to mobilize the nation's best health care professionals and other experts to help combat HIV/AIDS in hard-hit African, Caribbean, and Southeast Asian countries.8
Health professional expertise in pediatrics is in particularly short supply in Africa. The kingdoms of Swaziland and Lesotho, for example, 2 countries that are particularly hard hit by HIV/AIDS, are home to fewer than 5 pediatricians each. Very few African or developing world health professionals have training in the care and treatment of HIV-infected children or have experience in the use of antiretroviral drugs in children. As a result, pediatric HIV/AIDS treatment often is viewed erroneously as prohibitively difficult or complex and the drugs as too dangerous or ineffective.
The prices of antiretroviral drugs in the developing countries have fallen dramatically in the past 5 years, from as much as $12000 to as little as $140 per patient per year for a first-line WHO combination antiretroviral treatment regimen. However, even this price may be prohibitive in some of the poorest countries of Africa, where per capita expenditures on health are as little as $10 to $30 per year. Furthermore, in many settings, treatment is available only to individuals with the ability to pay for the medications and necessary laboratory testing. For HIV-infected children, lack of pediatric formulations of many of the commonly used generic or copy antiretroviral drugs, as well as a disparity in pricing between adult and available pediatric antiretroviral drugs, has limited access of children to HIV/AIDS treatment in many settings across Africa and globally.
Finally, in only a few settings around the world has there been the political leadership and advocacy to make the treatment of HIV-infected children a priority. Perhaps because an HIV-infected child who is restored to health does not return to work, pay taxes, or vote and because pediatric treatment is viewed as intrinsically difficult and more expensive than the treatment of adults, relatively little emphasis has been placed in most settings on the treatment of children.
EXPANDING ACCESS OF CHILDREN TO HIV/AIDS CARE AND TREATMENT
In the face of stifling pessimism surrounding the treatment of HIV-infected children in the developing world, the Baylor College of Medicine International Pediatric AIDS Initiative (BIPAI) was established in 1996 to catalyze access of children globally to HIV/AIDS care and treatment. BIPAI has constructed and operates the world's largest centers for the treatment of HIV-infected children. The Romanian-American Children's Center (Constanta, Romania),9 opened on April 6, 2001, provides care to ∼620 HIV-infected children, one third of whom are orphaned or abandoned. More than 450 children receive HAART in the center as 1 facet of a comprehensive HIV/AIDS medical and psychosocial care and support and community education program. The death rate for HIV-infected children in Constanta dropped in just 3 years from ∼15% (109 deaths) to just 1% (7 deaths) (unpublished data).
In Gaborone, Botswana, BIPAI constructed and opened the Botswana-Baylor College of Medicine Children's Clinical Center of Excellence (Fig 2) on June 20, 2003. Two years later, >4400 children have been brought to the center for HIV testing, and >1400 HIV-infected children are receiving HAART, more than in any other center worldwide. The center has become a focal point in Botswana and southern Africa for health professional training and community education on pediatric HIV/AIDS. In partnership with the government of Botswana, the center has catalyzed the establishment of Africa's first-ever national HIV/AIDS treatment program for children.
Today, BIPAI is active in pediatric HIV/AIDS care and treatment, health professional education and training, and clinical research in 14 countries in Africa, Romania, Ukraine, China, and Mexico. We have learned a great deal about how to deliver HIV/AIDS treatment in some of the world's poorest places, and we sit on the cusp of a new era of treatment access for HIV-infected children and families in Africa and the developing world. What follows is a 6-point plan, based in experience, that we believe will dramatically expand access of HIV-infected children and families in the developing world to health-restoring, life-prolonging care and treatment (Table 1).
Create a Children's Clinical Centers of Excellence Network
The Children's Clinical Centers of Excellence Network will serve the primary and HIV/AIDS specialty care needs of tens of thousands of children and families in Africa and elsewhere in the developing world. In addition, the network will help to build a critical mass of pediatric health professionals with the training and experience to manage HIV/AIDS and many other pediatric health problems. Already, new Children's Clinical Centers of Excellence modeled after BIPAI's centers in Romania and Botswana are open or under construction or in development in Swaziland, Lesotho, Malawi, Uganda, and Burkina Faso in Africa, with others to follow in Asia and Eastern Europe.
Centers of Excellence will catalyze access to pediatric HIV/AIDS care and treatment, health professional education and training, and clinical research in the developing world. Americans, working with local professional colleagues, will help to develop best practices for the care and treatment of HIV/AIDS in the developing world, conduct multicenter clinical trials of treatment regimens that are practical and affordable in resource-poor settings, and educate whole communities regarding HIV/AIDS prevention and treatment. Such centers will serve as ideal bases for American professionals who travel to Africa and elsewhere in the developing world as part of a Pediatric AIDS Corps. Centers of Excellence will be key to demystifying pediatric HIV/AIDS, communicating a message of hope and optimism to communities that are hard hit by HIV/AIDS, and destigmatizing HIV/AIDS and reducing the isolation of affected children and families.
Establish a Pediatric AIDS Corps
Care and treatment programs for HIV-infected children must address the critical shortage in almost every setting of professionals who are trained in pediatric care and treatment, with a clear recognition that children are not small adults. American professionals clearly have a role to play: a Pediatric AIDS Corps, if you will, of physicians, nurses, pharmacists and others who are willing to give 1 or 2 years to the fight against HIV/AIDS in Africa and the developing world.
The Bristol-Myers Squibb Foundation and BIPAI announced on June 27, 2005, the creation of a Pediatric AIDS Corps of American health professionals, based in and around the Children's Clinical Centers of Excellence Network. The elements of this Pediatric AIDS Corps include the following:
American graduates of approved residency training programs in pediatrics and family medicine are recruited.
Participants in the Pediatric AIDS Corps commit to a minimum 1-year assignment to a primary health care setting that is affiliated with 1 of BIPAI's Children's Clinical Centers of Excellence in Africa.
Participants in the Pediatric AIDS Corps train at Baylor in pediatric and family HIV/AIDS care and treatment and medicine in the tropics before departing for Africa.
Every participating physician remains linked to 1 of the Children's Clinical Centers of Excellence for purposes of professional development and training, continuing education, and professional consultation.
Participants provide primary and HIV/AIDS specialty care and treatment in collaboration with local health professionals.
Pediatric AIDS Corps members participate in training activities of the Children's Clinical Centers of Excellence to build local capacity for pediatric and family primary and HIV/AIDS specialty care and treatment.
Participants receive from the program a living stipend and student loan debt relief for each year of service in Africa.
The Pediatric AIDS Corps began with a goal of recruiting 50 physicians. However, in the future, participants might come from a variety of professional disciplines, including nursing, pharmacy, and social work. The Pediatric AIDS Corps will expand existing professional capacity for pediatric and family HIV/AIDS care and treatment in a complementary way, consonant with the goals and objectives of partner governments. All of BIPAI's Children's Clinical Centers of Excellence operate under Memorandums of Agreement with government Ministries of Health. Participants will acquire knowledge and experience that will build capacity among American professionals for the care and treatment of a variety of tropical diseases that rarely are seen in the United States.
Support Pediatric Research That Is Relevant to Resource-Poor Settings
Funding agencies of the US government and others must provide expanded support for operational and scientific research that is relevant to research-poor settings. Such studies may have spin-off benefits for the care and treatment of HIV-infected children in a variety of relatively resource-rich and resource-poor settings globally, but first and foremost, they must have relevance locally. The Botswana-Baylor Antiretroviral Assessment Trial 2, currently under way at the Botswana-Baylor College of Medicine Children's Clinical Center of Excellence, is 1 such example. This is a randomized, comparative trial of continuous versus intermittent HAART among HIV-infected infants and children in Botswana. The hypothesis of the study is that intermittent, lopinavircontaining HAART will be as effective, better tolerated, and less expensive than continuous, lopinavir-containing HAART. For Botswana and similar settings, proving the hypothesis could mean expanded access of HIV-infected children to affordable treatment, but there are obvious implications for the treatment of HIV-infected children in the developed countries, as well. When it is fully enrolled (500 children), Botswana-Baylor Antiretroviral Assessment Trial 2 will be the largest pediatric antiretroviral trial ever conducted on the African Continent.
Commit to Proportionate Funding for Pediatric HIV/AIDS Care and Treatment
Unless HIV-infected children in the developing world are to remain therapeutic orphans forever, the US government and other funders must consider setting aside resources specifically for the care and treatment of children. Availability of resources (ie, funding) and care and treatment services are reciprocally catalytic. Pediatric HIV/AIDS treatment never just happens. Substantial numbers of HIV-infected children generally are receiving treatment only in those countries where resources have been allocated specifically for that purpose.
Expand Availability of Pediatric Antiretroviral Drug Formulations
Manufacturers and others must work together to ensure that pediatric formulations of antiretroviral medications are made available at price parity with comparable adult formulations. No matter the reasons, it is unacceptable that medications that are used to treat HIV-infected infants or toddlers sometimes are priced substantially higher than the equivalent medications that are used in the same settings to treat HIV-infected adults, thereby pricing children out of access to treatment.
Although most of the relevant branded antiretroviral drugs are available in both adult and pediatric formulations, this is not the case for many of the generic (copy) drugs. The WHO and other relevant agencies should consider in their registration processes for these drugs the incorporation of incentives for the development and manufacture of pediatric drug formulations.
Make a Commitment to Partnerships
Scaling up the care and treatment of tens or hundreds of thousands of HIV-infected children will take a commitment to partnerships; governments, academic and health care institutions, community and faith-based organizations, and business communities in both the developed and developing countries all have a role to play. We are stronger and better together than apart.
To date, the world's reaction to HIV/AIDS in Africa and the developing world largely has consisted of despair and a sense of hopelessness and inevitable devastation. Nevertheless, as HIV/AIDS care and treatment programs have been developed and successes have been achieved, hope has returned. Today, we are for the first time on the cusp of an era in which huge numbers of HIV-infected children and families will gain access to health-restoring, life-prolonging treatment. Pediatric health professionals in the developed and developing worlds have the unique challenge and opportunity to change forever the way pediatric HIV/AIDS is perceived and managed globally.
The Baylor College of Medicine International Pediatric AIDS Initiative is supported by the Bristol-Myers Squibb Foundation (for the Pediatric AIDS Corps and Children's Clinical Centers of Excellence in Botswana, Lesotho, Swaziland, Uganda, and Burkina Faso), the Abbott Fund (for the Children's Clinical Centers of Excellence Network and individual centers in Romania and Malawi), the US Centers for Disease Control and Prevention (grant U62/CCU622420), the Fogarty International Center of the US National Institutes of Health (grant 5 D43 TW01036), and the National Institute of Allergy and Infectious Diseases (grant AI36211).
- Accepted August 18, 2005.
- Address correspondence to Mark W. Kline, MD, 6621 Fannin St, CC1210, Houston, TX 77030. E-mail:
The author has indicated he has no financial relationships relevant to this article to disclose.
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- Copyright © 2006 by the American Academy of Pediatrics