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HIV & AIDS Treatment in Children: The Problems

Of the 780,000 children living with HIV in low and middle-income countries who could be benefiting from HIV & AIDS antiretroviral treatment, it is estimated that only 15% were receiving it at the end of 2006. ¹ Providing treatment for children with HIV/AIDS essentially involves three stages: finding a child, testing a child and treating a child. Each of these stages can bring major problems, especially in resource-poor countries. In these countries, where health services are often weak and few facilities are available, most HIV-positive children are not even being identified, yet alone tested or treated.

Identifying and testing children living with HIV

If a child living with HIV is only identified clinically once they are ill, it may be too late for antiretroviral treatment to be effective. Children therefore need to be identified as HIV-positive as early as possible, before they become sick, so that appropriate medical care can be provided.

Most children living with HIV become infected through mother to child transmission, and these children need to be tested as soon as possible after birth to find out if they are HIV positive.

In developed countries, children can be tested soon after birth (sometimes within 48 hours) using polymerase chain reaction (PCR) tests and other specialist techniques. Where this technology is available, the longest a mother will have to wait for an accurate result is usually around 6 weeks.

In resource-poor countries, where PCR testing is generally unaffordable, a mother may have to wait up to 18 months after giving birth before antibody tests (which are used in adults, and are more commonly available) can be used to accurately diagnose her child. During this time the antenatal clinic, where the mother was probably diagnosed, is likely to lose contact with her. Without help from the clinic, parents and carers must use their own initiative to take their child for a HIV test but a number of different things may stop this from ever happening:

• A child’s mother/father/carers may not be willing to take them for an HIV test, even if they know that there is a risk of infection. The stigma surrounding AIDS can play a big role in this, as carers are sometimes afraid that their child – and their family as a whole – will face prejudice once diagnosed. For mothers who have not yet been tested for HIV, an HIV-positive test result for their child is likely to mean that they too are infected, and fear of finding this out can be a major deterrent. Carers may not appreciate the importance of testing, and may not even be aware that HIV is a treatable condition. ²
• Hospitals or clinics that provide testing may not be accessible. A mother may have to travel long distances to reach the nearest health service that can test her child, and this may be impractical and expensive. ³
• A child may become sick or die before they reach the age of 18 months.

If PCR is available, and a child is tested soon after birth at the same location where they are born, these problems can often be avoided. But with most mothers having to wait 18 months before their child can be accurately diagnosed, most HIV-positive children simply aren’t being identified fast enough.

In some resource-poor countries, ‘dried-blood spot’ testing has been introduced in recent years. This is where a small sample of blood is taken from a child, dropped onto paper, and sent to a laboratory where it can be tested. Since these samples do not need to be refrigerated and are easy to transport, they can potentially be sent miles away to places where PCR is available. This means that even children living in resource-poor areas can be tested relatively quickly. Dried blood spot testing can be expensive though, and it can take a long time for test results to return. There's also evidence that when the drug nevirapine is used to prevent mother-to-child transmission of HIV, dried blood spot testing doesn't always detect HIV in the first few days of the child's life. ^{4 5}

Providing the antiretroviral drugs

As well as the general problems surrounding the provision of aids drugs, there are a number of problems specific to providing treatment to children.

Suitable drug formulations are expensive

Younger children cannot swallow tablets, so ARVs ideally need to be administered to them in the form of syrups or powders. Since most innovative pharmaceutical companies are based in developed countries where there are few children living with HIV, research and development of such formulations receives little attention, and many appropriate drugs are only available in tablets suitable for adults. ⁶ The paediatric formulations that are available can be up to four times more expensive than adult equivalents. ⁷

“Since there are still no available, easy-to-use triple drug combinations for children, I do what most doctors are doing: I try to show caregivers such as grandparents how to break adult tablets, hoping that the children will get the doses they need.”

- Dr Fasineh Samura, Malawi

As more groups speak out about the unacceptably high cost of these formulations, some progress is being made. In December 2006, The Clinton Foundation (founded by ex-U.S. President Bill Clinton) announced that it had negotiated price-reductions in paediatric drug formulations made by two Indian pharmaceutical companies. Under this agreement, 19 different ARVs that can be used in children will be produced, and made available at the low price of 19 U.S. cents per day. This will make them 45% cheaper than previously available drugs. As a result of this agreement, the number of children receiving treatment is likely to rise significantly in the 62 developing countries where the drugs are being made available. ⁸

Suitable drug formulations are impractical

In addition to their high cost, there are also a range of practical problems associated with the storage and use of paediatric formulations. Drugs that come in a powdered form need to be mixed with water, so they cannot be used unless clean drinking water is readily available. Syrups generally have a short shelf-life, and often need to be refrigerated after opening, which depends on a reliable electricity supply.

As a result of these problems, formulations suitable for use in children are not widely available in most resource-poor countries, where they are needed the most. In their absence, clinicians often have to resort to crushing or dividing adult tablets into smaller doses that children can swallow. This practice is commonplace in areas where paediatric formulations are not available, and studies suggest that it can work effectively when no other options are available. ⁹ Dividing tablets is far from ideal though, because it can be very difficult to determine the exact dose needed for a child. In most cases, there is simply no other choice:

“Since there are still no available, easy-to-use triple drug combinations for children, I do what most doctors are doing: I try to show caregivers such as grandparents how to break adult tablets, hoping that the children will get the doses they need.” - Dr Fasineh Samura, Malawi¹⁰

Fixed dose combinations are not available

Many adults being treated for HIV are given fixed dose combination (FDC) tablets as part of their drug regimen. These tablets combine two or three different ARVs into a single dose. There are several advantages to FDCs: as well as being easier to manage for the individuals receiving them, they are cheaper than separate tablets and easier to distribute on a national level. ¹¹

Despite the obvious advantages that FDCs designed for children would bring, there are currently none available. There are, however, signs of progress in this area: three drug companies based in India and Thailand have developed FDCs for children and are currently attempting to get them approved. ¹²

Few medical staff are trained to treat children

There are currently very few professionals trained to diagnose HIV in children, or to administer ARVs to those that need them. ¹³ While adults taking ARVs can often maintain their own treatment programme unassisted, children ideally require constant check-ups and advice from trained personnel. Most developing countries face a shortage of health-care workers in general.

Poor infrastructure

The drug formulations that are appropriate for children are not usually widely distributed or available through local suppliers. Few poorer countries have the resources or infrastructure to set up and maintain a system through which paediatric treatment can be supplied nationally. ¹⁴

The problems faced after a child has started treatment

Even when the necessary drugs, personnel and facilities are available, it can be very difficult to treat a child living with HIV. Once therapy has started, there are a whole new set of problems faced by parents and caregivers, healthcare workers, and children themselves, that have to be overcome if treatment is to work effectively. In some ways, these problems are separate from those that are making it difficult to provide ARVs to children in the first place. At the same time, these issues may in themselves stop people from starting a child on treatment.

Treating children is technically complicated

Children’s bodies are undeveloped, constantly growing, and vulnerable to illness and infections. As they grow, changes take place in the way that they absorb, metabolise, distribute and excrete drugs. HIV-positive children need to be monitored more regularly than adults, and while they are being monitored it needs to be taken into account that CD4 count and viral load – the two main markers used to judge the progression of HIV in an individual’s body – need to be judged differently in adults and children, so adult guidelines are often irrelevant. Drug doses need to be carefully calculated on the basis of either weight or body surface area. Because dosing is so complicated, there is a risk that children will be given too little or too much of a drug, which can lead to treatment failure. These problems are discussed in more detail on our HIV Treatment in Children page.

The majority of HIV-positive people are adults, and so medical research on ARVs has not generally focused on children. Guidelines on treating children have been strengthened in recent years, but there is still a lack of information on certain drugs, and a lack of consensus on issues such as when a child should start receiving ARVs.

Adherence issues

Children on HAART need to take three or more types of ARVs every day for the rest of their lives. If drugs are not taken routinely, at around the same time every day, HIV may become resistant to the therapy, causing it to stop working.

Adhering to treatment can be particularly challenging in children. Some paediatric drugs taste very unpleasant, and all of them can cause adverse side effects, so children are often reluctant to take their medications. This can put an enormous strain on the daily lives of parents and caregivers, who are usually responsible for administering treatment. Some ARVs need to be taken with food, so carers may have to perform the (often difficult) task of providing a meal and administering drugs simultaneously. This is assuming that an adequate supply of food is actually available.

Antiretroviral syrups, which often have to be used in young children, can be difficult to store. They take up more room than tablets, are harder to transport, and may require refrigeration. Some households don’t have any sort of refrigeration, and even in those that do, there may not be enough space to store large quantities of these formulations.

Due to the stigma surrounding HIV, parents and caregivers are often unwilling to make it publicly known that the child in their care is HIV-positive, and this can sometimes lead to adherence problems. For instance, carers may be reluctant to fill out prescriptions in their local community, or may not make a child’s school aware of their condition, which can lead to them missing out on drug doses during the school day. ¹⁵ They may also hesitate to administer ARVs if other people are present when a child is due to receive them. For children who are old enough to administer their own ARVs, it can be hard to fit their treatment routine in with their increasingly active social and lives:

“There are days when I can't be bothered [to take my medications] like when I am tired or if I am at someone else's house and have to hide it or whatever, then it's hard.” - 13 year old HIV-positive girl ¹⁶

Adherence is one of the most significant challenges to children receiving ARVs. If a child does not manage to adhere to treatment, and is affected by drug resistance, they may need to start a second-line drug regimen (i.e. an alternative combination of ARVs). While children in developed countries may be able to access second-line therapy, the drugs required for this are generally too expensive to be provided in resource-poor countries. Without second-line therapy, children who become resistant to ARVs face a high-risk of illness and death.

Treating children for opportunistic infections

Opportunistic infections, which take advantage of weak immune systems, are a serious threat to children living with HIV. Tuberculosis and PCP (a form of pneumonia) in particular are major causes of illness and death among infected infants.

Medicines to prevent such infections are effective and can delay the need for HAART. The drug cotrimoxazole in particular has proven extremely effective in preventing opportunistic infections, and can generally decrease the risk illness and death in HIV-positive children. ¹⁷ As well as being effective, cotrimoxazole is cheap, costing as little as US$0.03 a day to provide. The World Health Organisation and international AIDS organisations such as UNAIDS have recommended that cotrimoxazole be provided to all children who have been exposed to HIV, especially in areas where no ARVs are available. Even though many governments have increased efforts to distribute cotrimoxazole, financial and logistical barriers still stand in the way of its provision – at the moment, it is estimated that 4 million children who could be benefiting from the drug are unable to obtain it. ¹⁸

What needs to be done?

Preventing infection amongst children

Most of the 2.3 million children currently living with HIV became infected through mother-to-child-transmission. Through the use of ARVs and other interventions, the risk of a HIV-positive mother passing infection on to her child can be minimised, but most HIV-positive mothers in developing countries are still not benefiting from such interventions. Reducing the rate of mother-to-child-transmission would decrease the global burden of children that need to be treated, and so efforts to improve paediatric treatment ideally need to run parallel with campaigns that address this issue. AVERT is calling for an increased global effort to prevent mother-to-child-transmission in our Stop AIDS in Children campaign. AVERT.org also has more detailed information about Preventing Mother to Child Transmission worldwide.

Improving testing and treatment for children

While a reduction in the rate of mother-to-child-transmission would decrease the need for paediatric treatment, there is not going to be a time in the foreseeable future when there are no children living with HIV. As long as this is the case, testing and treatment facilities for children need to be improved, and ARVs that can be used in children need to be made much more widely available.

Progress is partly dependent on general improvements in the health systems of developing countries. Many countries lack the resources and capacity needed to help children living with HIV, and suffer from a shortage of healthcare workers that are trained to test and treat children. Health systems are so poor that few children living with HIV are even being provided with cheap antibiotics such as cotrimoxazole, which could fend off illness and potentially save lives. Due to its low cost, the provision of cotrimoxazole is one of the most obvious and immediate ways in which illness and death could be reduced among children with HIV in resource-poor countries.

There is also a need for greater research into, and development of, ARVs that can be used in children. The development of cheaper, simplified drug formulations, fixed-dose combination tablets and low-cost generic versions of ARVs suitable for children would all have immense benefits. Even the paediatric drugs that are currently available are simply not reaching enough children, so governments, international organisations and donors need to focus on achieving much wider treatment coverage.

If these improvements are made, the problems of HIV and AIDS among children could potentially be minimised. At present, though, progress is not happening fast enough. Greater advocacy, funding and effort will be required if the challenges surrounding HIV treatment for children are to be overcome.

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