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HIV & AIDS Treatment in Children

Many children born with HIV need treatment if they are not going to rapidly develop AIDS and die.

What does AIDS & HIV treatment in children involve?

The most effective treatment for HIV positive children is antiretroviral treatment. This treatment requires several antiretroviral drugs (ARVs) be taken every day.

How effective is antiretroviral treatment in children?

Studies have shown that antiretroviral treatment reduces illness and mortality among children living with HIV in much the same way that it does among adults. A trial in the United States, for example, found that the mortality rate among a sample of infected children was reduced from 5.3% to 0.7% per year after antiretroviral treatment was made widely available. ¹ Similar results have been found in developing countries. A study released in 2007, which monitored 586 HIV-positive children receiving antiretroviral treatment in 14 different Asian and African countries, found that 82% were still alive after 2 years.²

Some of the most compelling evidence that treatment works in children does not come from studies or statistics, but rather the personal testimonies of those who have witnessed HIV-positive children returning to health after starting treatment:

“You see scrawny, rashy, tired, lethargic kids come in, you start them on treatment and within weeks you’ve got bounding, podgy, gorgeous growing children. People often don’t believe, they’re often quite sceptical of the medications, and then you see this transformation and parents are like ‘The child’s got so much energy!’” - Julie, UK nurse working with children living with HIV. ³

Starting antiretroviral treatment in children

As with adult treatment, there is ongoing debate about when it is best to start antiretroviral treatment in HIV-positive children. There is a complex balance between the immediate benefits of providing treatment to children who are not showing any symptoms of AIDS-related illness, and concerns about long-term resistance and drug side effects if treatment is started too early. The general view is that treatment should be started when there is a significant risk of progression from HIV to AIDS, although the definition of ‘significant’ is not always clear. Many experts feel that the risk of progression in HIV-positive children under the age of 1 year is so high that they always offer antiretroviral treatment.

To judge whether an HIV-positive person needs to start receiving treatment, a CD4 test is usually carried out. This test measures the number of T-helper cells – white blood cells that are attacked by HIV – in an individual’s blood. It can either measure the absolute number of CD4 cells, or the percentage of white blood cells that are CD4 cells, in a sample of blood.

A falling CD4 count is a sign that HIV is progressing, and that the immune system is becoming weaker. In healthy, uninfected adults, absolute CD4 count is usually between 400 and 1,600 cells per millimetre cubed of blood. When a HIV-positive adult’s CD4 count falls between 350 and 200, it is usually recommended that they start receiving antiretroviral treatment.

For children below the age of six, though, these adult guidelines are generally irrelevant. Children below this age generally have a much higher CD4 level than is usually present in adults, unless their immune system has been damaged by AIDS. The CD4 levels found in children therefore need to be judged in context of their age, which can make it difficult to know exactly when treatment should be started. Since percentage CD4 count generally varies less with age, this type of test is generally recommended in children under the age of five. It is generally agreed across guidelines that a child aged less than one year with a percentage CD4 count below 25% should be started on treatment, whether symptomatic or not. In Europe, it is recommended that asymptomatic HIV positive children be started on treatment if the risk that they will progress to AIDS is higher than 10%, and the risk of death is higher than 5%; this can be determined through an assessment of percentage CD4 count and age. In the U.S., it is recommended that treatment be at least considered for all HIV positive children under the age of one year. In some cases, viral load testing (which measures the amount of HIV in an individual’s blood) is used alongside CD4 testing to guide decisions about treatment.

In resource-poor communities, the technology needed for CD4 counts and viral load testing is not always available. In the absence of these facilities, healthcare workers looking after a HIV-positive child sometimes have to make a clinical presumption that treatment needs to be started. The World Health Organisation recommends that if a child has reached a stage of severe or advanced HIV infection, then they need to start treatment. A HIV-positive child may be assumed to have reached these stages if they are suffering from any condition that is strongly associated with AIDS, or if symptoms of oral thrush, severe pneumonia or severe sepsis are present.

Which antiretroviral drugs should be used?

Many of the drugs that are conventionally used to treat adults living with HIV are not available in an appropriate form, or licensed/approved for use in children. Those that are available are often unaffordable in the areas where they are most needed.

Where the correct drugs are available, there are a number of different combinations that can work effectively in children. As with adults, antiretroviral therapy with at least three drugs is recommended when treating children, because this prevents HIV from becoming resistant to any single drug. It is usually recommended that this therapy should consist of two nucleoside reverse transcriptase inhibitors (NRTIs) combined with either one non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).

NRTIs form the ‘backbone’ of any treatment regimen for children, and a number of combinations of these drugs are approved for use in paediatric treatment. Equally, there are some combinations that are not recommended, and there are specific advantages and disadvantages attached to all dual NRTI combinations. In developed countries, the two NRTIs are either combined with an NNRTI or a protease inhibitor. In children under 3, the NNRTI used is usually nevirapine, since there is a lack of dosing information available for efavirenz (the only other widely used NNRTI).

In resource-poor communities, NRTI/NNRTI-based combinations are recommended over other combinations, due to their relatively low cost and the availability of appropriate generic drugs. World Health Organisation guidelines for resource-poor communities do not recommend the use of protease inhibitors for initial therapy, because it is felt that they should be saved for second-line treatment, if it is needed. The WHO recommends that in resource-poor communities, the two NRTIs should include 3TC (lamivudine), combined with AZT (zidovudine), d4t (stavudine), or ABC (abacavir). A triple NRTI regimen, which avoids the use of an NNRTI, can also be considered as an option for initial therapy in special circumstances. This would be AZT or d4T, combined with both 3TC and ABC.

There are many factors that can influence the choice of drugs for children. Considerations about medications that the mother may have received during pregnancy, the toxicity of certain drugs, and whether the child is still being breastfed, all need to be taken into account when choosing a regimen.

Dosing and drug formulations in children

The dose of antiretroviral drugs given to children is generally based on either weight or body surface area. As children’s bodies are constantly changing, drug doses need to be altered to make sure that a child is not given too much, or too little, of a drug. Healthcare workers also need to take into account that children under the age of six metabolise drugs faster than adults, so even after adjusting for body weight, they may need to be given higher quantities of ARVs to achieve the same effect that the drugs would have in adults. Information about specific drugs is often limited, and drug manufacturers and expert guidelines use a variety of ways to calculate doses of paediatric ARVs, so there is no uniform dosing system to follow. ⁴ Because of the complex nature of paediatric dosing, under- or over-dosing can be a serious risk.

Dosing is further complicated by the variety of forms that ARVs may take when provided to children, all of which require different measurements. Infants who are too young to swallow tablets ideally need to be provided with ARVs in the form of syrups or powders, but these formulations are expensive and often impractical. Some syrups need to be refrigerated after opening, which requires a reliable electricity supply, and powders need to be mixed with water, which may be unfeasible in areas where clean drinking water is not regularly available. In addition, the unpleasant taste of syrups and powders can make it difficult for children to take their ARVs every day.

In areas where there is a lack of affordable paediatric ARV formulations, clinicians often have no choice but to divide adult fixed-dose combination drugs (FDCs, which combine multiple ARVs into a single tablet) into measures appropriate for children. There is evidence that dividing tablets carries a risk of under- or over-dosing, ⁵ but equally, a significant 2006 study of eight countries concluded that the use of divided adult FDCs can achieve successful and satisfactory results in children. ⁶ The World Health Organisation supports this practice in situations where no appropriate paediatric medications are available. ⁷ Fixed-dose combinations designed specifically for children are in development, but are not yet available. ⁸

Adherence

Adherence is a major issue in paediatric treatment. Unless a child adheres to a strict treatment regimen, it is likely that treatment failure will occur, and they may become resistant to one or more of the ARVs that they are taking. ^{9 10}

There is evidence that adherence problems are common in children. In one U.S. study, for instance, 43% of people caring for a child receiving treatment reported at least one missed dose in the past week. ¹¹ In less developed countries, adherence is an even greater challenge. There are a number of factors that commonly cause adherence problems: inadequate dosing; high pill burden; reluctance among young infants to take syrups and powders due to their unpleasant taste; a lack of willingness among caregivers to inform schools and care-centres that their child is infected, which can lead to them missing out on doses during the day; dietary restrictions; and toxic side effects of drugs. If fixed-dose combinations appropriate for use in children became available, it is likely that adherence would generally improve, since it is much easier to take a single dose every day rather than multiple doses.

Side effects

Children receiving ARVs can suffer from the same side effects that adults experience. Because children’s bodies are still developing, and they are likely to be exposed to treatment for prolonged periods of time, they may be particularly vulnerable to some such complications. ¹² Side effects can occur at various stages of a child’s course of treatment, and may be acute (occurring directly after drug administration), sub-acute (within one or two days after administration), or late (after prolonged drug administration). It can be difficult to distinguish between adverse events caused by ARVs given to a child and complications caused by HIV itself, so care should be taken to exclude other possible causes of illnesses before it is concluded that they are a result of ARVs.

The impact of side effects may vary from mild to severe and life-threatening. Some moderate or severe side effects may require drug substitution, or even the discontinuation of treatment. In general, mild side effects do not require such changes, and symptomatic treatment for the side effects may be given. If side effects are regarded as life threatening, all ARVs should be stopped until the child has stabilised. ¹³

Nutritional support whilst on HIV treatment

Malnutrition is common in children living with HIV in developing countries, and is a major cause of death. Ideally, children living with HIV who are asymptomatic need to consume 10% more calories than other children of their age and sex. Children who are symptomatic, or recovering from acute infections, need to consume 20-30% more calories than other children. ¹⁴

If a child is suffering from malnutrition, it is recommended that they receive treatment to stabilise their condition before HAART is started. In poorer areas, however, this is not always possible. Even where it is possible to treat malnutrition, recovery from this condition is likely to be slow and limited in HIV-positive children. If a child has not been cured of malnutrition after six to eight weeks of special feeding or appropriate treatment, it may be decided that HAART should be started despite their condition.

In the opposite situation, where a child experiences rapid weight gain as a result of ARVs, nutrition also needs to be monitored carefully. As a child’s weight changes, so does the recommended dosage of ARVs that they require, so drug doses need to be constantly reviewed. ¹⁵

Treating children co-infected with HIV and Tuberculosis

Tuberculosis presents a serious risk to children’s health, particularly if they are suffering from a weak immune system due to HIV infection. Co-infection with HIV and Tuberculosis in children is increasingly common in many areas. ¹⁶ While the basic principles of TB treatment are the same in HIV-positive children and HIV-uninfected children, the situation is complicated by drug interactions between ARVs and drugs that are used to treat TB. The drug rifampicin, which is commonly used to treat TB, can react negatively with NNRTIs such as nevirapine, as well as with protease inhibitors. Such interactions can lead to sub-therapeutic drug levels and an increased risk of toxic side effects. For HIV-positive children who are not yet receiving ARVs, it is recommended that Tuberculosis (TB) treatment should ideally be initiated some weeks before ARV treatment, allowing the child to stabilise on this therapy. For children who are diagnosed with TB while already receiving treatment, ARV regimens need to be carefully reviewed, and may need to be adjusted in accordance with official guidelines. ¹⁷

Important interventions other than antiretroviral treatment

Due to their weak immune systems, children living with HIV are very vulnerable to opportunistic infections, and need to be provided with drug prophylaxis to prevent such illnesses. For example, prophylaxis against PCP (one of the most common opportunistic infections in children living with HIV) is recommended for all children born to HIV-positive mothers, starting from about four to six weeks after birth. ¹⁸ For children who have no access to ARVs, treatment for opportunistic infections may delay the need for antiretroviral treatment.

Cotrimoxazole, an antibiotic that is included in PCP prophylaxis and can help to prevent other infections such as TB, was shown to reduce AIDS-related mortality by 43% and hospital admission rates by 28% among children with HIV in one major Zambian trial. ¹⁹ Based on this trial and other evidence, experts agree that cotrimoxazole should be widely provided to all children living with HIV, especially where ARVs are not available. It is also recommended that all children born to HIV-positive mothers should be provided with cotrimoxazole until tests confirm that they are HIV-negative. Cotrimoxazole prophylaxis can be given to a child from 4 to 6 weeks of age. ²⁰ Unfortunately, despite its low cost, few children currently have access to cotrimoxazole in developing countries.

Another important intervention is vaccination or immunisation against common infections. There are some risks associated with providing routine vaccines to children living with HIV, but these risks are far outweighed by the benefits of immunisation. In general, routine vaccines are safe to administer in HIV-positive children, and are recommended. ^{21 22} However, it should be noted that ‘live vaccines’ are often not considered safe for use of in HIV-positive children.

Wider considerations

There are psychological, as well as technical, issues that need to be considered when providing treatment to children. Children with HIV who have access to treatment can be expected to live longer, healthier lives, so there is a need for sustained emotional support as they carry out their course of treatment. ²³ Parents and caregivers need to understand how drugs are administered and stored, and the importance of life-long adherence.

When guidelines are followed carefully, and adequate resources are available, children living with HIV can be treated very effectively. In most cases, however, resources are lacking, and even where they are not, other social and practical barriers can stop them from being treated successfully. To read about these problems, see our HIV & AIDS Treatment in Children: the Problems page.

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