OVC Support Toolkit  >  Health and nutrition  >  Children Living with HIV/AIDS 

Which Drugs?

This section looks at issues affecting the choice of antiretroviral drugs to treat children with HIV. Other sections look at general issues regarding access to treatment and provide practical treatment tips.

Key points about choosing antiretroviral drugs in children are:

1. WHO has guidelines about when to start antiretroviral treatment for children with HIV/AIDS. This depends on the age of the child, how severely ill the child is and whether or not laboratory tests are available.

2. There are very many different antiretroviral drugs available. They are in three main categories ? Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) and Protease Inhibitors (PIs).

3. All treatment plans now use a combination of at least three drugs. These usually include two NRTIs and one from another group.

4. A wide range of issues need to be considered when deciding which drugs to use. Some of these are general while others apply particularly to children. It is helpful if a country has one combination of drugs which it uses for first treating people with HIV. This is called the primary regime. Other drug combinations may be needed for people who experience side-effects or do not respond to the primary treatment. These combinations are called secondary regimes.

5. Dosages for children are calculated either based on the surface area of a child or its weight. Special formulations of drugs are needed for children. However, these are not available for all antiretrovirals.

6. Children who have TB can be given antiretroviral treatment at the same time as their TB treatment.

7. WHO and UNAIDS recommend that Cotrimoxazole should be given to all children born to HIV positive mothers from age of 6 weeks.

Differences between Adults and Children

There are many differences between children and adults regarding HIV infection and its treatment. Diagnosis of HIV infection is difficult in children under 18 months of age. This is because they still have antibodies from their mother in their blood. It may be more difficult to measure disease progress in children using laboratory tests. This is because levels of viral load and CD4 cells are very different in children as compared to adults. Percentages of CD4 cells are measured in children (particularly those under 6 years of age) because these are less different from adult levels when compared to absolute numbers.

When to Start Treatment

WHO has produced guidelines for antiretroviral treatment of children in developing countries. These are illustrated in the following flow chart:

In practice, this means that different approaches are needed depending on whether the child is over the age of 18 months. Under that age, it will probably not be possible to be sure that the child has HIV infection. In that case, treatment is only recommended for those who are very ill (stages II and III) and have evidence of damage to their immune system (CD4 percentage <20%). In situations where neither virological testing (e.g. PCR) nor CD4 counts are available, treatment with antiretroviral drugs is not recommended in children under the age of 18 months. If the child is over the age of 18 months, treatment should only be given to children who have had a positive antibody test. It can then be given to all those who are very ill (stage III) and those who are less ill (stage I and II) but have evidence of a damaged immune system (CD4 percentage <15%).

Drug Types and Names

There are so many different antiretroviral drugs available that it can be very difficult to understand articles which describe ways in which they are use. Antiretroviral drugs have a variety of names:

• Trade or Proprietary Name: This is the name given to a particular version of a drug produced by a particular company. These names should not be used when describing or prescribing drugs. Some tablets contain more than one active drug. These drugs are often known by their trade names but it is better to describe them using their generic names or abbreviations.
• Generic Name: This is the name of the drug which is used by everyone that makes it. This is the name that should be used when describing the drug.
• Abbreviations: The generic names of most antiretroviral drugs are very long. This makes them hard to remember and use. Most of them have been given abbreviations which are made up of three letters or numbers. Some have more than one abbreviation. For example, AZT and ZDV both refer to Zidovudine.

Antiretroviral drugs can be grouped into three main types according to how they work. There are Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) and Protease Inhibitors (PIs). A table showing the names of drugs in these categories is shown below:

Combination Therapies

All treatment plans now use a combination of at least three drugs. These usually include two NRTIs and one from another group. There is now no place for treatment with one or two drugs only. Countries should develop their own policies on which drugs to use in primary and secondary treatment regimes. Where these exist they should be followed.

Factors to be considered in choosing drugs for the primary treatment regime include:

• Potency - that is the effectiveness or power of the drugs. For example, NNRTIs are not effective against HIV2.
• Side-effects
• Interactions with other drugs - for example Zidovudine and Stavudine can not be used together. Many antiretroviral drugs interact with the TB drug Rifampicin
• Potential for future treatment options
• Adherence - some drugs require precise timings and large numbers of tablets to be taken
• Coexistent conditions - that is, other diseases which the child has at the same time. The most important of these is TB
• Risks in children and pregnant women ? for example, Efavirenz can not be taken in pregnancy or by children under the age of 3
• Risk of resistance
• Cost and other access issues
• Suitability of each drug for use in areas of limited health infrastructure
• Ease of transport - some drugs require storage in glass containers and/or refrigeration
• The existence of different groups and sub-types of HIV
• The availability of formulations suitable for small children, such as liquids. It is not recommended to break adult tablets for children. However, this may be the only way of giving a child the drug if a suitable formulation is not available
• In the case of children, whether or not mothers have received antiretrovirals during pregnancy. Current evidence suggests that this does not need to be taken into account when choosing drug regimes.
• The primary treatment regime recommended for adults. If a child is on the same drugs as a parent, they are more likely to take them correctly.

One primary treatment regime suggested by WHO is Zidovudine (or Stavudine), Lamivudine and Efavirenz (or Nevirapine in those under 3 years of age). Secondary treatment regimes usually use two different NRTIs and a drug from a different category. This would mean that if a PI is used in the primary treatment regime, an NNRTI would be used in the secondary regime. Secondary regimes are required for people whose disease does not respond to the primary regime (after at least 24 weeks of treatment) and those who experience side effects from the primary regime.

Dosage of Antiretroviral Drugs in Children

It is important to calculate the dose of antiretroviral drugs accurately for children. This means that dosages must be increased as the child grows. Many documents advise doing this on the basis of surface area. However, it is not possible to measure a child's surface area directly. This has to be calculated from measurements of height and weight using formulae or charts. In some cases, dosages can be calculated from a child's weight. 'Drug tables' can assist with these calculations and help to avoid errors.

Monitoring Antiretroviral Treatment in Children

Children receiving antiretroviral drugs can be monitored through clinical assessments and using simple tests, such as measuring height, weight and the achievement of developmental milestones. Children who are responding to treatment will grow, will have improvements in their neurological symptoms and will have infections less often.

Other Issues

A few general issues are considered here:

• Children who have TB can be treated with antiretroviral drugs at the same time. However, when a child has been recently diagnosed with TB it may be preferable to postpone use of antiretroviral drugs for the first two months of TB treatment. In addition, several antiretroviral drugs interact with the TB drug Rifampicin. Efavirenz is an ideal drug in this situation but it can not be used in children under the age of three.
• Children who are breastfeeding from an HIV positive mother who is receiving antiretroviral drugs should be treated according to the same rules and with the same dosages as other children.
• Cotrimoxazole can be used to prevent children with HIV becoming ill with pneumocystis pneumonia (PCP). This is called PCP prophylaxis. It is recommended in all children born to HIV positive mothers from 6 weeks of age. It should be continued, preferably, until the child is shown to be HIV negative. In many resource-poor settings, this would mean giving Cotrimoxazole to all children born to HIV positive mothers for fifteen months. It is particularly important in the first 6-12 months of life. WHO and UNAIDS also recommend that Cotrimoxazole is provided to children over the age of fifteen months who are known to be HIV positive and have been ill as a result of their HIV infection. In situations where CD4 counts are available, Cotrimoxazole is also recommended for children with HIV who are not ill but have a CD4 percentage less than 15%. Cotrimoxazole may be stopped in HIV positive children receiving antiretroviral drugs whose CD4 count rises above 500 cells/mm3.
• Work is currently being undertaken to integrate issues relating to HIV into the approach to childhood illness currently recommended by the World Health Organisation. This is called the integrated management of childhood illnesses (IMCI).

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