By Francesca Merico
The vast majority of the children who will die this year from AIDS-related illnesses would be alive if they could receive the treatment they needed.
Antiretroviral medications (ARVs) make the difference between life and death for 800,000 children under the age of 15 living with HIV. However, if children living with HIV cannot access treatment that is appropriate to their needs, they are subjected to unnecessary suffering and die faster than do adults living with this virus.
Despite evidence that treatment is very successful in children living with HIV, there remain significant obstacles to paediatric ARV scale-up, and 1,000 children below the age of 15 die of AIDS-related illnesses every day.
In order to identify HIV-positive children, it is crucial to identify and to take care of HIV-positive pregnant women. Ninety percent of the 2.5 million children now living with HIV became infected through mother-to-child transmission (MTCT).
MTCT can be reduced to less than 2 percent by a package of interventions comprising ARV treatment to HIV-positive pregnant women and to their children immediately after birth, combined with elective caesarean birth and avoidance of breastfeeding.
Coverage of programmes to prevent MTCT is still very low in many countries. According to the World Health Organization (WHO), coverage ranges from less than 1 percent to 54 percent in sub-Saharan Africa (where 85 percent of HIV-positive pregnant women live).
Also important are increased efforts to accelerate the diagnosis of HIV-positive children and to:
- Increase research and production of HIV diagnostic tests capable of identifying the HIV virus in children below 18 months;
- Simple, user-friendly, and rapid viral load tests that can be used in low-income settings, where highly skilled laboratory technicians and constant electric supply often are lacking;
- The high price of infant diagnostic methods;
- Train paediatricians and other healthccare workers to identify HIV in children and to use modern technologies that can detect HIV in children.
Even when HIV-positive mothers receive the drugs needed to avoid MTCT of HIV, and they undergo caesarean sections and avoid breastfeeding, their children need to be tested for HIV as soon as possible. HIV is usually diagnosed through a test which detects HIV-antibodies. These tests do not yield reliable results in children younger than 18 months because infants acquire their mothers’ antibodies.
Other challenges to infant diagnosis are stigma and discrimination, the lack of treatment availability and the lack of accessibility of hospitals or clinics.
Increased efforts to expand access to medicines to treat HIV in children include:
- Increasing research and development of new paediatric ARVs;
- Developing drug formulations better adapted to low-income settings;
- Conducting ethical trials to verify drug quality, efficacy and safety for treating HIV in children;
- Strengthening safety monitoring and vigilance of medicines for children;
- Decreasing the price of existing paediatric ARVs;
- Creating and distributing easy-to-follow dosing recommendations;
- Rapidly qualifying and approving paediatric ARVs and FDCs when safe, effective and of good quality;
- Registering and marketing paediatric FDCs in all countries;
- Forming and training medical personnel in the care of children living with HIV.
Once HIV is detected in the child, the viral load and the level of CD4 cells, the white blood cells that are attacked by HIV, must be monitored to establish when the antiretroviral treatment should be initiated. When treatment becomes necessary, the next challenge faced is that many antiretroviral drugs used to treat adults do not exist in formulations appropriate for use in children, particularly fixed dose combinations for children under the age of 12.
Paediatric ARVs and FDCs are needed because children absorb and metabolise drugs according to their age and their physical development. To be effective and safe, the appropriate dosage of antiretroviral drugs should be established in accordance with the child’s weight or body surface area, and it varies as the child grows. Side effects associated with ARVs have been reported to occur in 30 percent of HIV-positive children in antiretroviral therapy. According to WHO, most of these side effects could be reversed by modifying the dosage or changing to an alternative medicine. This often is unfeasible in poor settings.
The lack of paediatric ARVs suitable for use in low-income settings is indeed another major challenge to access to treatment for HIV-positive children.
Paediatric formulations in syrup or powder forms have significant disadvantages in resource-limited situations. Syrups are difficult to handle and to store; they have a short shelf life; they require refrigeration, which is often not possible in poor countries; they are difficult to transport; and they usually have a bad after-taste.
Powder formulations require clean water, often unavailable in areas where clean drinking water is not taken for granted. In addition, despite the high incidence of malnourishment and hunger in poor countries, few paediatric ARVs can be taken without food. For all but infants and very sick children, a tablet or capsule smaller than the adult version would be the preferable solution. However, babies and very sick children need FDCs for oral suspension and solutions.
FDCs, both in the form of three different drugs in one pill and of oral suspensions and solutions, could simplify the treatment regimen. Paediatric fixed-dose combinations are still very rare and those that do exist are awaiting regulatory approval. As a consequence, children in Highly Active Antiretroviral Therapy (HAART) must take three or more different antiretroviral drugs several times a day to avoid the development of resistance to a single drug and to prevent the virus from progressing into AIDS.
This makes it harder for caregivers to treat children and for children themselves to comply with the treatment. FDCs not only reduce the total pill burden and thus improve adherence, but they also simplify forecasting, procurement, storage and distribution logistics.
This situation is worsened by the lack of reliable clinical data on the way medicines affect children. This results in few medicines being developed, produced and marketed for children.
Another major consequence is the “off-label use” of medicines: children are given drugs that have only been tested in adults and are not officially approved for use in children. In addition, the majority of paediatric medicines lack evidence of long-term benefits and risks
Other obstacles that limit HIV-positive children’s access to the treatment they deserve include:
- High cost of paediatric medicines. UNICEF reports that the cost of ARVs for a child in a low-income country is US$200 per year; for an adult a typical ARV regimen costs US$130. In some places, the paediatric formulations can be up to four times more expensive than respective equivalent for adults. In many low-income countries, a one-year supply of HIV paediatric treatment may consume the equivalent of an adult’s income for 10 years. Access to second line regimen for children is more problematic also because they are more expensive.
- The length of time for approval and qualification of paediatric drugs by competent regulatory authorities also contributes to hinder access to treatment of HIV-positive children. Frequently, paediatric ARVs that exist are not registered or marketed in the countries where they are most needed and those that are registered and marketed may not be available through the local distributor.
- Once children are receiving ARVs, it is necessary to monitor treatment compliance in order to avoid treatment failure and the development of resistance. However, because of the shortage of medical personal trained in the care of children living with HIV, both the treatment of such children and their follow up often are inadequate and insufficient.
Source: AVERT; WHO; UNAIDS; EAA Briefing paper on Paediatric AIDS.