Treatment for Children with HIV & AIDS

HIV develops very rapidly among infants and children, and, without treatment, a third of children with HIV will die of AIDS before their first birthday, with half dying before they are two.1 In 2010, there were 250,000 AIDS-related deaths in under-15s, most of which could have been prevented through early diagnosis and effective treatment.2 Though the number of children receiving antiretroviral therapy (ART) has increased significantly in recent years, at the end of 2010 only 23 percent of the 2.02 million children in need of ART in low- and middle-income countries were receiving it.3

back to top Identifying and testing children living with HIV

Providing treatment for children with HIV/AIDS essentially involves three stages: finding a child, testing a child and treating a child. 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 infected with the virus. If a child living with HIV is only diagnosed once they are ill, it may be too late for antiretroviral treatment to be effective.

An infant being tested for HIV Collection of dried blood spots from an infant

In high-income countries, children can be tested soon after birth using polymerase chain reaction (PCR) tests and other specialist techniques.4 Where this technology is available, the longest a mother will have to wait for an accurate result is usually around six weeks.

In resource-poor countries, where PCR testing is generally unaffordable or unavailable, 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.

In some resource-poor countries, ‘dried blood spot’ testing has been introduced. 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. However, dried blood spot testing can be expensive and it can take a long time for test results to return. There is 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.5 6

Problems with testing

In 2010, only 28 percent of children born to women living with HIV were tested within two months of birth among 65 reporting low- and middle-income countries. Whilst this remains low, it is an improvement compared to the 6 percent coverage in 2009.7

A number of factors may prevent children from being tested. Health authorities’ lack of technical ability, poor systems for laboratory analysis, problems with transportation of specimens and results, and little confidence in caring for children are all significant factors.8

Furthermore, parents may be unwilling to take their child for an HIV test for fear that the child will face prejudice once diagnosed. A lack of knowledge about testing and the fact HIV can be effectively treated could also lead to poor testing rates. Mothers who have not yet been tested may too be fearful of discovering their child is infected as this would likely mean they are infected also. Hospitals or clinics that provide testing may not be accessible and will lose contact with HIV-exposed children for follow-up tests. 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.9

back to top Starting antiretroviral treatment in children with HIV

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 antiretroviral drug side effects if treatment is started too early.

Measuring the stage of HIV infection in children

CD4 counts in children

To judge whether an HIV-positive person requires treatment, a CD4 test is usually carried out. This 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. However, it is difficult to judge the health of a child's immune system based on CD4 count. Absolute CD4 counts vary with age, and younger children usually have a much higher CD4 count than adults. Percentage CD4 count on the other hand does not vary in the same way as absolute CD4 count, and is therefore recommended for children under five.

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.

Clinical symptoms

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 sometimes have to make a presumption that a child should begin treatment based on their stage of HIV infection as defined by a range of cancers and infections that are present.

When to start treatment

The World Health Organization (WHO) now recommends that all diagnosed infants and children less than two years of age should begin antiretroviral therapy regardless of the child's clinical or immunological stage.10 (Children under 12-months with clinically diagnosed presumptive severe HIV should also begin treatment, but confirmation of infection should be obtained as soon as possible.)

The Children with HIV Early Antiretroviral Therapy (CHER) study of infants (aged six-to-twelve weeks) in South Africa compared the outcomes of those starting limited treatment immediately with those deferring treatment until CD4 percentage dropped below certain levels or if symptomatic and severe disease occurred. (The study's criteria for deferred treatment were only slightly different from South African or WHO guidelines.) It found the risk of death for infants who began treatment immediately was 76 percent lower than the deferred treatment group.11

Doctors at a clinic in Tintswalo treat an ill HIV positive child Doctors at the Rixile HIV clinic treat an ill HIV positive child, Tintswalo, South Africa

The United States recommends treatment for all infants with HIV, regardless of CD4 percentage, clinical status or viral load.12 The 2009 guidelines produced by the Paediatric European Network for Treatment of AIDS (PENTA) also advocate treatment for all infected children under 12 months regardless of clinical or immunological stage.13 Other countries’ guidelines may be revised to reflect WHO recommendations and the CHER study’s findings.

While there is an emerging consensus on initiating therapy immediately in infected infants, there is ongoing debate as to when treatment should begin in young children. According to US and PENTA guidelines treatment is recommended if significant symptoms are evident or percentage CD4 count has decreased to below 20-25 percent for children aged between one and five years.14 15 WHO 2010 recommendations suggest the initiation of ART for all HIV-infected children between two and five years with either a CD4 count of 750 or below, or a CD4 percentage of 25 or below, whichever is lower, irrespective of clinical status.16

Arguments for earlier treatment include: evidence that disease progression is faster in young children; that there is an association between severe HIV disease and persistent neurocognitive deficits in adolescent long-term survivors of perinatally acquired HIV;17 and that ART can reduce tuberculosis, encephalopathy and bacterial infections that occur even at high CD4 levels, as well as improve physical growth. Advocates for earlier treatment also point to studies showing that the risk of disease progression is identical between adults and over-5s so it follows that any argument for earlier initiation in adults should also apply to older children. Arguments for deferring treatment include a lack of information on the long term effect of doing so, and the additional cost and burden of adherence due to a longer overall period of treatment.18

Which antiretroviral drugs should be used?

As with adults, antiretroviral therapy with at least three drugs is recommended for children as 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).19 If a child has been exposed to NNRTIs during treatment to prevent mother-to-child transmission (common in most PMTCT interventions in developing countries) then his or her treatment should contain PIs. However, this not really feasible in most countries where the need for this treatment is greatest as most PIs are more expensive and may have special storage requirements such as refrigeration.

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 breastfeeding, all need to be taken into account when choosing a regimen.

back to top How effective is antiretroviral treatment for children with HIV?

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

Antiretroviral treatment reduces illness and mortality among children living with HIV in much the same way that it does among adults. In one study in Brazil, three-quarters of HIV-positive children receiving ART were alive after a four-year follow-up period.20 Positive outcomes have also been seen in paediatric ART programmes in Thailand, Kenya, and Ukraine.21 22 23 A study released in 2007, which monitored 586 HIV-positive children receiving antiretroviral treatment in 14 countries in Africa and Asia, found that 82 percent were still alive after two years.24

Some of the most compelling evidence that treatment works in children does not come from studies or statistics, but rather the stories 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 HIV25

However, one of the greatest challenges for children living with HIV is maintaining effective antiretroviral treatment for life. A European study which looked at more than a thousand children on antiretroviral treatment found that 12 percent of children experienced treatment failure of three classes of drugs after 5 years, over two times the rate of adults.26 Some of the reasons that lead to earlier treatment failure in children include a lack of choice of antiretroviral drugs for children, difficulties with adherence which may be linked to side effects and inadequate dosing.

Side effects of paediatric HIV treatment

Children receiving ARVs can suffer from the same drug 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 complications.27 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 them may be given. If side effects are regarded as life threatening, all ARVs should be stopped until the child has stabilised.28

Adherence

Children on HIV treatment 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.

You need to install Adobe Flash player to view AVERT's videos. Click on the logo below to install Flash player.

INVISIBLE: Children living with HIV/AIDS

A review of 17 studies regarding paediatric HIV treatment adherence found adherence ranging from 49 percent to 100 percent.29 Three-quarters of the studies showed adherence rates of 75 percent. Most of the studies in lower and middle-income countries revealed adherence rates above 75 percent, whereas adherence in higher-income countries was generally below 75 percent. However, there are variations in treatment adherence across and even within countries.30 31 32

Many factors can lead to adherence problems: inadequate dosing; high pill burden; reluctance among young infants to take syrups and powders due to their unpleasant taste; dietary restrictions; and toxic side effects of drugs. The socioeconomic status of the child, whether or not a child's status has been disclosed or not, and user fees may also affect whether a child is adherent to his or her treatment.33 34

Adherence issues 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. As well as the unavailability of appropriate drugs, stigma surrounding HIV can also lead to adherence problems if parents and caregivers are unwilling to make it publicly known that the child in their care is HIV-positive. 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.35 36 They may also hesitate to administer ARVs if other people are present when a child is due to receive them.

Among older children and adolescents, a variety of social factors such as fear of stigma and discrimination, stress and anxiety and peer relations impact treatment adherence.37 Side effects, and the need to take treatment at different times of the day, also explain why adolescents may find it difficult to adhere to their treatment regimens.38

“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 girl39

Nutritional support whilst on HIV treatment

An HIV-positive child, South Africa An HIV-positive child, South Africa

Malnutrition is common in children living with HIV in low and middle-income countries, and is a major cause of death.40 Ideally, children living with HIV who are asymptomatic need to consume 10 percent more calories than other children of their age and sex. Children who are symptomatic, or recovering from acute infections, need to consume 20-30 percent more calories than other children.41

If a child is suffering from malnutrition, it is recommended that they receive treatment to stabilise their condition before antiretroviral treatment 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 antiretroviral drugs should be administered 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.42

Dosing and drug formulations in children

The dose of antiretroviral drugs given to children is generally based on either weight or body surface area. Children have traditionally been thought of as being ‘mini adults’ but this is not the case. Children’s bodies are constantly changing and developing and often it is vital that drug doses are altered to ensure that a child is not given too much, or too little, of a drug. The study of how a child’s body reacts to medication is called pharmacokinetics (PK) but current paediatric PK studies mostly focus on 6-18 years old, which misses the early stages of development; a period when the human body changes the most. Pharmacokinetic properties such as absorption, distribution, metabolism and excretion of a drug all influence the efficacy, toxicity and dosing regimen required in a child. As such, information is limited on PK for infants 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.43

“Unfortunately, a lot of HIV medicine has an unpleasant taste, especially in syrups and powder form.”

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 drugs that are more child friendly such as syrups, powders, sprinkles or ‘melts’ but these formulations are not widely available and are expensive.44 45 Unfortunately, a lot of HIV medicine has an unpleasant taste, especially in syrups and powder form. This can make it difficult for children to take their ARVs daily. In addition, it is critical that children’s medicine has clear and concise labelling to ensure that caregivers are able to give an appropriate dosing and ensure adherence. Studies that have analysed the rate of failure of antiretroviral treatment in children often cite inadequate adherence due to poor dosing by caregivers as one of the reasons that drug resistance develops in young children.46 47

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 into measures appropriate for children. There is evidence that dividing tablets carries a risk of under- or over-dosing48 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.49 The World Health Organisation supports this practice in situations where no appropriate paediatric medications are available.50

“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, Malawi51

An encouraging development is the relatively recent availability of fixed-dose combination therapies (FDCs), which combine multiple ARVs into a single tablet, for children. Tablets consisting of lamivudine, stavudine and nevirapine have been supplied by the Clinton HIV/AIDS Initiative (CHAI), in conjunction with drug purchase facility, UNITAID, to children in 26 nations. In these countries CHAI’s monthly paediatric treatment formerly consisted of 12 bottles of liquid. For those children who can now access FDCs, only a small container of tablets is needed, making the therapy easier to store, transport and administer.52

If fixed-dose combinations (explanation) appropriate for use in children became more widely 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.

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.

Preventing opportunistic infections

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 one month after birth.53 For children who have no access to ARVs, treatment for opportunistic infections may delay the need for antiretroviral treatment.

Co-trimoxazole, 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 percent and hospital admission rates by 28 percent among children with HIV in a major trial in Zambia.54 Based on this trial and other evidence, experts agree that co-trimoxazole 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 co-trimoxazole until tests confirm that they are HIV-negative. Co-trimoxazole prophylaxis can be given to a child from 4 to 6 weeks of age.55 As well as being effective, co-trimoxazole is cheap, costing as little as US$0.03 a day to provide. However, provision is low; in 2010, only 23 percent of infants in reporting low and middle-income countries in need of co-trimoxazole received it within two months of birth.56

Even though many governments have increased efforts to distribute co-trimoxazole, financial and logistical barriers still stand in the way of its provision. Increasing the numbers of children receiving this relatively low-cost drug would save many lives.

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.57 58 However, it should be noted that ‘live vaccines’ are often not considered safe for use in HIV-positive children.

Treating opportunistic infections

Children are at particular risk of tuberculosis (TB), particularly if they are suffering from a weak immune system due to HIV infection and if their mother is infected.59 60 While the basic principles of TB treatment are the same in HIV-positive children and uninfected children, the situation is complicated by drug interactions between ARVs and drugs that are used to treat TB. Such interactions can lead to sub-therapeutic drug levels and an increased risk of toxic side effects. There are also drugs used for TB treatment specially formulated for children. For HIV-positive children who are not yet receiving ARVs, it is recommended that treatment for TB 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.61 In order to avoid late diagnosis of HIV, it has been suggested that all TB-infected children should be considered for an HIV test.62

Lack of appropriate treatment

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.63 Those that are available are often unaffordable in the areas where they are most needed. The paediatric formulations that are available can be significantly more expensive than adult equivalents and therefore an expansion of the development of cheap, fixed-dose combinations for children is greatly needed. A lack of appropriate treatment is one of the main reasons that treatment failures occurs in children.

Children performing a play about the benefits of antiretroviral medication Children in Uganda performing a play about the benefits of ARVs

As more groups speak out about the unacceptably high cost of child-friendly formulations, some progress is being made. In December 2006, the Clinton HIV/AIDS Initiative (CHAI), founded by former US president Bill Clinton, announced that it had negotiated reductions in paediatric drug prices made by two Indian pharmaceutical companies. Under this agreement, 19 different ARVs that can be used in children were scheduled to be made available for an average 16 cents per day. This is 45 percent cheaper than previously available drugs.64 This agreement has probably contributed considerably in increasing child access to ART in recent years. Since CHAI and UNITAID partnered in 2006, they claim to have reduced the cost of leading child treatments by 64 percent in low income countries.65

The wider provision of cheaper, simplified drug formulations, fixed-dose combination tablets and low-cost generic versions of paediatric drugs would all have immense benefits. Although developments in paediatric HIV drugs are urgently needed it has also been observed that "children are often a low priority when it comes to drug development and financing."66

back to top Improving testing and treatment for children

While stepping up efforts to prevent mother-to-child-transmission (PMTCT) would decrease the need for paediatric treatment, it is likely that HIV will continue to infect many thousands of children for years to come. Given this situation, 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.

As HIV-related stigma and discrimination can affect children's testing and treatment adherence due to the unwillingness of some caregivers to reveal a child's HIV status, negative attitudes towards those living with HIV need to be tackled. Efforts to maximise adherence should be strengthened and delivered before and alongside treatment.

General improvements in the health systems of low and middle-income countries would allow for greater resources to be allocated towards treating children. 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.

Just as with adults, antiretroviral treatment for children living with HIV is highly effective at reducing mortality and illness. In high resource countries, where access to testing and effective antiretroviral treatment for children living with HIV is more widespread than in developing countries, children living with HIV are expected to survive well into adulthood.67 However, children with HIV face a number of challenges with regards to treatment; maintaining long term adherence despite a lack of suitable paediatric ARVs and dosing formulations, the risk of running out of drug options sooner in case of drug resistance, and the need for psychosocial support - particularly during adolescence.68 69

If improvements in these areas were made, the problems of HIV and AIDS among children could potentially be minimised. At present, though, progress is not happening fast enough and hundreds of thousands of children with HIV continue to die every year. Greater advocacy, funding and effort on the part of governments, international organisations and donors are required if the challenges surrounding HIV treatment for children are to be overcome.

References back to top

  1. Newell, M. et al (2004), ‘Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis’, The Lancet 364:9441
  2. WHO/UNAIDS/UNICEF (2011) ‚'Global HIV/AIDS Response: Epidemic update and health sector progress towards Universal Access 2011'
  3. WHO/UNAIDS/UNICEF (2011) ‚'Global HIV/AIDS Response: Epidemic update and health sector progress towards Universal Access 2011'
  4. Aidsmap (2010) 'Accurate testing for babies'
  5. Prendergast A. et al. (2007, July), ‘International perspectives, progress and future challenges of paediatric HIV infection’, The Lancet, vol. 370:9581
  6. Mphatswe et al. (2007), ‘High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis’, AIDS 21:10
  7. WHO/UNAIDS/UNICEF (2011) ‚'Global HIV/AIDS Response: Epidemic update and health sector progress towards Universal Access 2011'
  8. UNICEF/WHO (2008, November), ‘Scale up of HIV-related prevention, diagnosis, care and treatment for infants and children: A Programming Framework’
  9. Chime J. et al. (2004, July), ‘Challenges of testing children for HIV in community and University Teaching Hospital (UTH) and Lusaka Zambia’, 15th International AIDS Conference, abstract no. B12283
  10. World Health Organization (2010) 'Antiretroviral Therapy for HIV infection in infants and children'
  11. National Institute of Health website (2007, 25th July), ‘Q&A: Children with HIV Early Antiretroviral Therapy (CHER) Study: Treating HIV-Infected Infants Early Helps Them Live Longer’; and Violari A. et al (2008, 20th November), ‘Early Antiretroviral Therapy and Mortality among HIV-Infected Infants’, New England Journal of Medicine 359:21
  12. Working Group on Antiretroviral Therapy and Medical Management of HIV-infected Children (2009, 23rd February) ‘Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection’
  13. Paediatric European Network for Treatment of AIDS (2009), 'Penta 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection'
  14. AIDSinfo, U.S. Department of Health and Human Services (2008, 29th July), ‘Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection’,
  15. Paediatric European Network for Treatment of AIDS (2009), 'Penta 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection'
  16. World Health Organization (2010) 'Antiretroviral Therapy for HIV infection in infants and children'
  17. Wood, S.M et al (2009) 'The impact of AIDS diagnoses on long-term neurocognitive and psychiatric outcomes of survival adolescents with perinatally acquired HIV', AIDS 23(14):1859-1865
  18. Welch, S.B., Gibb, D., (2008), ‘When should children with HIV infection be started on antiretroviral therapy?’, PLoS Medicine 5:3
  19. FDA, (2009) 'FDA Guidelines for the Use of Antiretroviral Agents in Paediatric HIV Infection'
  20. Matida, L.H. et al (2004), ‘Improving survival among Brazilian children with perinatally acquired AIDS’, Brazilian Journal of Infectious Diseases 8:6
  21. Puthanakit, T. et al (2005), ‘Efficacy of highly active antiretroviral therapy in HIV-infected children participating in Thailand’s national access to antiretroviral program’, Clinical Infectious Diseases 41:1
  22. Wamalwa D.C. et al (2007), ‘Early response to highly active antiretroviral therapy in HIV-1 infected Kenyan children’ Clinical Infectious Diseases 45:3
  23. Mahdavi, S. et al (2010) 'Treatment and disease progression in a birth cohort of vertically HIV-1 infected children in Ukraine' BMC Paediatrics 10:85
  24. O'Brien D.P. et al. (2007), ‘Treatment outcomes stratified by baseline immunological status among young children receiving non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in resource-limited settings’, Clinical Infectious Diseases 44:1245
  25. The Guardian (2006, November 22nd), ‘It’s difficult to say whether parents or children cope better’
  26. PLATO II (2011, April) 'Risk of triple-class virological failure in children with HIV: a retrospective cohort study' The Lancet 377(9777):1580-1587
  27. McComsey G.A., Leonard E. (2004), ‘Metabolic complications of HIV therapy in children’, AIDS, 18:13
  28. World Health Organisation (2006), ‘Antiretroviral Therapy of HIV Infection in Infants and Children in Resource Limited Settings: Towards Universal Access (Recommendations for a Public Health Approach)’
  29. Vreeman R C et al (2008), 'A systematic review of pediatric adherence to antiretroviral therapy in low- and middle-income countries'
  30. KIDS-ART-LINC Collaboration (2008) 'Low risk of death, but substantial program attrition, in pediatric HIV treatment cohorts in Sub-Saharan Africa' J Acquir Immune Defic Syndr. 49(5):523-31.
  31. Fennel, L (2010) 'Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa' J Acquir Immune Defic Syndr. 2010 Aug 15;54(5):524-32
  32. Bakanda, Celestin (2011, April 29) Survival of HIV-Infected Adolescents on Antiretroviral Therapy in Uganda: Findings from a Nationally Representative Cohort in Uganda'
  33. KIDS-ART-LINC Collaboration (2008) 'Low risk of death, but substantial program attrition, in pediatric HIV treatment cohorts in Sub-Saharan Africa' J Acquir Immune Defic Syndr. 49(5):523-31
  34. Fennel, L (2010) 'Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa' J Acquir Immune Defic Syndr. 2010 Aug 15;54(5):524-32
  35. World Health Organisation (2006), ‘Antiretroviral Therapy of HIV Infection in Infants and Children in Resource Limited Settings: Towards Universal Access (Recommendations for a Public Health Approach)’
  36. Mbori-Ngacha, Dorothy 'Follow-Up and Adherence Management for Children and Adolescents Living with HIV' From the Ground Up Volume 2: Establishing a Framework for Success, Accessed: 20/05/2011
  37. Murphy DA (2005) 'Longitudinal antiretroviral adherence among adolescents infected with human immunodeficiency virus' 159(8):764-70
  38. Reisner SL (2009, Feb-March) 'A review of HIV antiretroviral adherence and intervention studies among HIV-infected youth' Topics in HIV Medicine 17(1):14-25
  39. Chintu C., Mwaba P., (2005, May), ‘Tuberculosis in children with human immunodeficiency virus infection’, The International Journal of Tuberculosis and Lung Disease, 9:5(477)
  40. Taye B, et.al, (2010) 'The impact of malnutrition in survival of HIV infected children after initiation of antiretroviral treatment (ART)' Ethiop Med J 48(1): 1-10
  41. World Health Organisation (2006), ‘Antiretroviral Therapy of HIV Infection in Infants and Children in Resource Limited Settings: Towards Universal Access (Recommendations for a Public Health Approach)’
  42. World Health Organisation (2006), ‘Antiretroviral Therapy of HIV Infection in Infants and Children in Resource Limited Settings: Towards Universal Access (Recommendations for a Public Health Approach)’
  43. Menson E. N. et al. (2006), ‘Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997-2005: cohort study’, British Medical Journal 332(1183)
  44. UNICEF and WHO, (April 2010) ‘Sources and Prices of Selected Medicines for Children’
  45. The Global Price Reporting Mechanism (Nov. 2009) ‘Transaction prices for Antiretroviral Medicines and HIV Diagnostics from 2008 to October 2009’
  46. PLATO II (2011, April) 'Risk of triple-class virological failure in children with HIV: a retrospective cohort study' The Lancet 377(9777):1580-1587
  47. Biadgilign S, et. al (2009) 'Barriers and facilitators to antiretroviral medication adherence among HIV-infected paediatric patients in Ethiopia: A qualitative study' 6(4):148-154
  48. Corbett A et al. (2005), ‘Pharmacokinetics between trade and generic liquid and split tablet formulations of lamivudine, stavudine and nevirapine in HIV-infected Malawian children’, 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington DC, abstract H-1106
  49. O'Brien D. P., Sauvageot D., Zachariah R. and Humblet P. (2006, October), ‘In resource-limited settings good early outcomes can be achieved in children using adult fixed-dose combination antiretroviral therapy’, AIDS 20:15
  50. World Health Organisation (2006), ‘Antiretroviral Therapy of HIV Infection in Infants and Children in Resource Limited Settings: Towards Universal Access (Recommendations for a Public Health Approach)’
  51. Medicines Sans Frontiers (2006, July), ‘Children and HIV/AIDS’, fact sheet
  52. William J. Clinton Foundation (2008), ‘CHAI Pediatric Program Pamphlet’
  53. Paediatric European Network for Treatment of AIDS (PENTA) (2009), ‘PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection’
  54. Chintu C. et al. (2004), ‘Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial’, The Lancet, 364:9448
  55. World Health Organisation (2006), ‘Guidelines on Co-trimoxazole prophylaxis for HIV-related infections among children, adolescents and adults in resource-limited settings’
  56. WHO/UNAIDS/UNICEF (2011) ‚'Global HIV/AIDS Response: Epidemic update and health sector progress towards Universal Access 2011'
  57. Obaro S.K. et al. (2004), ‘Immunogenecity and efficacy of childhood vaccines in HIV-1-infected children’, The Lancet Infectious Diseases, 4:8
  58. UNAIDS (2006), ‘Report on the global AIDS epidemic’
  59. Chintu C., Mwaba P., (2005, May), ‘Tuberculosis in children with human immunodeficiency virus infection’, The International Journal of Tuberculosis and Lung Disease, 9:5(477)
  60. UNICEF/UNAIDS (2010) 'Children and AIDS: Fifth Stocktaking Report'
  61. Mofenson L.M. et al. (2004, December), ‘Treating Opportunistic Infections Among HIV-Exposed and Infected Children’, Recommendations from the CDC, the National Institute of Health, and the Infectious Diseases Society of America
  62. Cohen, J.M. et al (2008), ‘Presentation, diagnosis and management of tuberculosis in HIV-infected children in the UK’, HIV Medicine, Vol. 9, Issue 5: 277-284.
  63. UNICEF/UNAIDS (2010) 'Children and AIDS: Fifth Stocktaking Report'
  64. International Herald Tribune (2006, 30th November), ‘Cost of Treating Children with HIV/AIDS to Plummet’
  65. William J Clinton Foundation (2009), ‘UNITAID and the Clinton HIV/AIDS Initiative Announce New Price Reductions for Key AIDS Medicines’
  66. UNICEF/UNAIDS (2010) 'Children and AIDS: Fifth Stocktaking Report'
  67. Brady, Michael T MD, et. al, 'Declines in Mortality Rates and Changes in Causes of Death in HIV-1-Infected Children During the HAART Era' JAIDS 53(1):86-94
  68. Hazra, Rohan et. al, 'Growing Up with HIV: Children, Adolescents, and Young Adults with Perinatally Acquired HIV Infection' Annual Review of Medicine 61:169-185
  69. New York Times (2010) 'Growing Up With H.I.V.'