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HIV-associated infections are infections which are common in HIV-infected people. They may be caused by a wide range of organisms such as bacteria, viruses, fungi or protozoa. These infections occur when the immune system becomes damaged. The first clinical sign to suggest that a child has a weakened immune system is often the appearance of an HIV-associated infection.
HIV-associated infections are common in people with a weakened immune system.
No, as some HIV-associated infections such as pulmonary TB or shingles may also be found in HIV-negative children and children with stage 1 to 3 HIV infection. These infections, however, should always alert one to the fact that the child may be HIV infected. HIV-associated infections are therefore an important indicator for HIV screening.
These are clinical infections which only occur in children who have a severely damaged immune system due to HIV infection. Therefore they are called ‘AIDS-defining infections’. They include conditions which are rare in HIV-negative children, such as oesophageal candidiasis and Pneumocystis pneumonia.
The term ‘AIDS-defining illnesses’ also includes conditions such as unexplained wasting, stunting or severe malnutrition, HIV encephalopathy, non-Hodgkin’s lymphoma, and Kaposi’s sarcoma.
Children with an AIDS-defining illness are classified as having stage 4 HIV infection.
Both infections and malignancies can be AIDS-defining illnesses.
Opportunistic infections or ‘OIs’ are infections which should not occur in children with a healthy immune system. These organisms ‘take the opportunity’ of infecting and causing illness in children with a weakened immune system. Unfortunately this is a confusing term as some experts use the term opportunistic infections only for AIDS-defining infections while others use the term for all infections seen in HIV-infected children.
The lower the CD4 percentage or count the higher the risk of an HIV-associated infection.
The best way of preventing most severe HIV-associated infections is to start antiretroviral treatment in HIV patients. The risk of HIV-associated infections can also be reduced by:
Severe or repeated bacterial infections as these are very common and can be fatal in HIV-positive children. Important bacterial infections include pneumonia, septicaemia, meningitis, urinary tract infection, osteitis, skin sepsis and otitis media. They often run a complicated course and respond slowly to treatment.
Severe or repeated bacterial infections are common in children with HIV infection.
Many common skin infections occur in children who are HIV-infected. However, they are more severe, and often take longer to respond to treatment, than in children who are not immunosuppressed. Common skin infections in children with HIV infection are:
Any of these severe skin conditions, especially shingles, suggests that the child is infected with HIV. Shingles is a very painful vesicular rash which usually only affects one part of the body. Molluscum contagiosum and warts are often extensive and do not recover spontaneously. Severe tinea capitis and impetigo often need systemic therapy and do not respond to local treatment.
Except for children with mild, acute diarrhoea, most of these children should be referred to hospital for further investigation and management.
Oesophageal candidiasis presents with painful swallowing.
Oral candidiasis (thrush) can usually be successfully treated with mycostatin drops 1 ml or miconazole gel six-hourly after a feed or meal. If the response is poor, oral fluconazole 3 mg/kg daily can be used for seven days.
Oesophageal candidiasis is treated with oral fluconazole 6 mg/kg daily for 2 to 4 weeks depending on the clinical response. Intravenous treatment may be needed for a few days if the child cannot swallow. Local treatment with topical drugs is not adequate. These patients must be referred to hospital as they may need intravenous rehydration or nasogastric feeding. Analgesia should be given as this condition is painful.
It is important that children with a sore mouth take adequate amounts of fluids and do not become dehydrated. Intravenous or nasogastric fluids may be required.
Pneumocystis pneumonia is a severe lung infection caused by a fungus called Pneumocystis jiroveci. This fungus does not cause pneumonia in children with a healthy immune system. Therefore, a diagnosis of Pneumocystis pneumonia usually indicates that the child has AIDS. Pneumocystis pneumonia commonly presents in the first year of life with high fever, a cough and marked respiratory distress often with hypoxia. The onset of illness is sudden. It is a fatal infection if not treated.
The risk of Pneumocystis pneumonia can be greatly reduced with co-trimoxazole prophylaxis from four to six weeks in all HIV-exposed infants (i.e. infants born to HIV-positive women).
Chest X-ray shows non-specific changes.
Pneumocystis pneumonia is an important cause of respiratory distress in infants with HIV infection.
Infants with suspected Pneumocystis pneumonia must be urgently referred to hospital for treatment with an intravenous loading dose of co-trimoxazole 20 mg/kg followed by 5 mg/kg intravenously every six hours for 21 days. If intravenous access becomes difficult, change to oral co-trimoxazole 5 mg/kg six-hourly to complete 21 days of treatment. Usually the child is clinically improved after three days of treatment.
If it is not possible to achieve intravenous access, oral co-trimoxazole can be used. A single oral loading dose of 20 mg/kg should be given followed by 5 mg/kg every six hours for 21 days.
All children with cyanosis or a low oxygen saturation must be given oxygen. When hypoxia is present, oral steroids are given routinely (i.e. prednisone 2 mg/kg daily for seven days and then tapered off and discontinued over seven days).
Further episodes of Pneumocystis pneumonia can be prevented with prophylactic oral co-trimoxazole.
Lymphoid interstitial pneumonitis (LIP) is a common type of chronic lung disease in children with HIV infection, especially children older than two years. While rare in HIV-infected adults, it occurs in at least 30% of African children with stage 3 or 4 HIV infection. The cause of LIP remains uncertain but it may be caused by a viral infection.
LIP is a slowly progressive condition which usually presents with a chronic cough and shortness of breath (dyspnoea). These children are usually not generally ill other than their respiratory symptoms. They may even have no symptoms at all. However, enlarged parotid glands, lymph nodes, liver and spleen with finger clubbing are common. Advanced LIP causes central cyanosis and severe respiratory distress. It can be fatal. An oxygen saturation of less than 90% confirms hypoxia.
Lymphoid interstitial pneumonitis is an important cause of respiratory distress in older children with HIV infection.
By taking an X-ray of the child’s chest. This looks like miliary tuberculosis. It is important to exclude other pulmonary conditions such as bacterial or viral pneumonia, tuberculosis and bronchiectasis.
If the condition is symptomatic (respiratory distress or hypoxia) these children should be admitted to hospital. Oxygen should be given for hypoxia if cyanosis is present or the oxygen saturation is low. A course of antibiotics is often given to treat a suspected bacterial infection. LIP does not respond to antibiotics, but improves with antiretroviral treatment. Children with severe respiratory distress improve dramatically with oral steroids. LIP can be prevented by providing early antiretroviral treatment when indicated.
Tuberculosis is one of the commonest serious bacterial infections seen in children with HIV infection. The clinical pattern of tuberculosis is similar in both HIV-positive and negative children. The risk of tuberculosis is increased even in children with stage 1 and 2 HIV disease.
Tuberculosis is common in children with HIV infection. In one South African study of children under one year of age, the risk of acquiring culture-confirmed tuberculosis was 24-fold higher in HIV-infected infants compared to uninfected children of the same age.
Pulmonary TB due to Mycobacterium tuberculosis is the commonest form of TB in both HIV-infected and non-infected children. However, tuberculosis of other organs (extra-pulmonary TB, i.e. lymph node TB, TB meningitis, abdominal TB, TB osteitis, TB arthritis and miliary TB) is far more common in children who are infected with HIV.
A combination of HIV and TB infection leads to rapid immunosuppression with progression of both diseases. As a result, TB is more common and more severe in children with HIV infection.
TB in HIV-infected children usually responds well to treatment. However, multi-drug-resistant TB (MDR TB) and extensively drug resistant TB (XDR TB) are becoming a problem with HIV-infected children in South Africa. It is often the result of inadequate or incomplete TB treatment or spread from adults with multi-drug-resistant TB.
A persistent cough lasting longer than two weeks is an important symptom of pulmonary tuberculosis.
The clinical diagnosis of TB may be difficult in a child with HIV infection. Always consider TB if the clinical signs do not respond to a course of antibiotics.
If TB is diagnosed at the time that antiretroviral treatment is being considered the TB treatment should be started as soon as possible and antiretroviral treatment started two to eight weeks later. However, in some children with advanced HIV disease it may be necessary to start antiretroviral treatment soon after starting the TB treatment. It is no longer necessary to wait until the TB treatment is completed before starting antiretroviral treatment. When using TB and antiretroviral treatments together, ALT should be monitored monthly, as drug-induced hepatitis is common.
If possible tuberculosis should be diagnosed and treatment started for 2 to 8 weeks before starting antiretroviral treatment.
Treatment of HIV is difficult if TB treatment is also being given at the same time. Therefore, children with a co-infection of TB and HIV should be managed by an experienced clinician.
Drugs used in TB therapy and antiretroviral treatment may interact with each other.
Children with HIV and TB co-infection should be treated with 4 drugs, i.e. rifampicin, INH, pyrazinamide and ethambutol for 2 months (intensive phase) followed by rifampicin and INH only for the remaining four months (maintenance phase). Therefore the full course is for six months. However if there has been insufficient improvement on X-ray after six months the two drug maintenance should be continued for a further three months to give a nine month course. The anti-TB drugs are given daily. Compliance is better with daily treatment than only five days a week.
The number of live TB bacilli drops by more than 95% within 48 hours of starting TB treatment. Once antiretroviral treatment is begun the child’s immune system will begin to recover and may start to respond to the remaining dead TB bacilli. This results in the immune reconstitution inflammatory syndrome (IRIS) with worsening of the signs of TB. Children with marked immune suppression are at greatest risk of this complication.
The antiretroviral treatment must be continued and anti-TB treatment started. However, the antiretroviral regimen may require modification e.g. if the child is on a lopinavir/ritonavir-containing regimen then it should be boosted with additional ritonavir. The child should be carefully monitored for signs of drug interactions and side effects. It is important to exclude TB before starting antiretroviral treatment.
Rifampicin is the usual cause of adverse drug interactions. Rifampicin affects the blood levels of many antiretroviral drugs, especially the ‘non-nucs’ and PIs. Rifampicin stimulates liver enzymes which, as a result, increase the rate of breakdown of these antiretroviral drugs. This leads to low blood levels of these antiretroviral drugs which may prevent them killing HIV. Therefore the choice of antiretroviral drugs and their doses may need to be changed.
The choice and dose of antiretroviral drugs may have to be changed if rifampicin is used to treat tuberculosis.
These decisions should be made by an experienced clinician. Not making these changes may lead to drug resistance and failure of antiretroviral treatment.
Table 6-1: Dose of ritonavir for boosting standard dose of lopinavir/ritonavir in children also receiving rifampicin.
|Body weight||3-4.9 kg||5-13.9 kg||14-19.9 kg||20-24.9 kg||25-39.9 kg||40 and above kg|
|Twice daily dose||1 ml||1.5 ml||2 ml||2.5 ml||3 ml||4 ml|
Nausea, rash, hepatitis and peripheral neuropathy. As a result these side effects are commoner and may be more serious if the two drug regimens are used together. This may result in a change in the choice of antiretroviral drugs. Careful monitoring is needed for these side effects.
Drug side effects are more frequent and may be severe if anti-tuberculous and antiretroviral treatments are given together.
Adherence may be poor when so many medicines need to be taken. There may also be confusion about the dosing instructions of the many different medicines. Patients should be told they will have to take a large number of medicines and be counselled about these possible problems. A clearly written plan for both anti-TB and antiretroviral treatment is essential. Additional support may be necessary to ensure adherence such as additional counselling and education sessions, more frequent clinic visits, or using a ‘treatment buddy’ or DOTS advocate.
All HIV-infected children, irrespective of age, who are exposed to TB through a household or close contact should be considered for TB prophylaxis, provided active TB is excluded.
All clinically well HIV infected children irrespective of age who have been in contact with someone who has smear-positive pulmonary TB should be given prophylactic treatment. These young children are at very high risk of developing TB.
Children under five years who are clinically well but have a positive Mantoux skin test (10 mm or more) should also be started on anti-TB treatment.
Currently, prophylaxis consists of isoniazid for six months. The treatment is given daily for seven days a week using the same dose as for short-course treatment. It is important to exclude active TB before starting prophylaxis.
These children present with delayed milestones and develop neurological signs such as weakness, brisk reflexes, increased tone and gait disturbance. The expected growth in head circumference may slow down. The diagnosis is confirmed by CT brain scan.
Delayed neurological milestones may be a sign of HIV encephalopathy.
Palliative care is the care of patients who have an incurable disease (such as AIDS). It also addresses the needs of the family. It aims at reducing suffering and improving the quality of life in these patients so that they can still have a good life for as long as possible. Palliative care starts at the time of the diagnosis and addresses all the patient’s physical, emotional, social and spiritual needs. Although HIV infection cannot be cured, most of the HIV-associated conditions can be prevented or adequately treated and controlled. HIV infection has now become a chronic, manageable condition.
Palliative care addresses the physical, emotional, social and spiritual needs of people with an incurable disease.
In contrast, terminal care (or end-of-life care) is the active care of patients whose disease no longer responds to treatment. Terminal care is not the same as no care or poor care. Patients who are dying of AIDS need terminal care. Care should never be withdrawn because there is no longer any hope for cure.
Terminal care is the supportive care of patients who have a serious illness that no longer responds to treatment.
Yes. As with adults dying of AIDS, there is an enormous need for terminal care for these children. Terminal care is most needed for children who are likely to die within months or weeks. Their families and carers also need support.
Home care is the basis of terminal care. If at all possible these children should be cared for in their own home where they are comfortable in their own surroundings and with their family and friends. Only if this is impossible should they be given care in an institution, preferably in a hospice. Hospital admission should be avoided if possible. Community helpers can be trained to provide basic nursing and provide extra help in the home (shopping, cooking, cleaning).
Terminal care should be provided at home if possible.
This is a place where terminally ill patients can be cared for. Management is aimed at compassionate care and support rather than cure. Members of a hospice team also help to care for patients who are at home.
As there are so many aspects to terminal care, it is best provided by a team of people who are trained in this special type of care. A multidisciplinary approach is needed to meet the many different physical, psychosocial and spiritual needs of terminally ill children. Patients, family and friends also have a very important role in terminal care. However, they need professional support to enable them to play their role in helping the child.
To improve the quality of care of children, and their families, who are facing death. The goal of terminal care is not necessarily to prolong life, but to offer prevention and relief of suffering.
The goal of terminal care is to prevent and relieve suffering.
These children are often wasted and very underweight. They may also have a poor appetite, nausea and difficulty swallowing. As a result it is often difficult for them to eat or drink.
High calorie and protein foods are important. It is important that these children are able to choose whichever foods they prefer. If possible, intravenous fluids or nasogastric feeds should be avoided. Soft or liquid foods are best.
Yes, severe pain is very common in children who are dying of AIDS. It is likely to be underdiagnosed and undertreated. Pain significantly reduces the quality of life and results in fear and despair. Pain also causes distress to the family.
Severe pain is a major problem in children who are dying of AIDS.
The aim of pain management is to control pain by giving analgesia regularly so that pain can be prevented.
The aim of pain management is to prevent pain.
Older children can say when they have pain. The assessment of pain in young children is dependent on observing the child’s behaviour and looking at their facial expression. Family and carers are usually good at assessing the degree of pain.
Into mild, moderate and severe. This is important, as the choice of analgesic is dependent on the severity of the pain.
The choice of analgesics in an individual depends on their degree of pain. As pain increases one moves up the ‘treatment ladder’ from step 1 (non-opioids such as paracetamol and ibuprofen) to step 2 (weak opioids such as tilidine) to step 3 (strong opioids such as morphine).
If possible it should be given orally. A dose must be given every four hours as the action of morphine is short. Give an extra dose equivalent to the four-hourly dose if the pain is not controlled. Giving extra doses for ‘breakthrough’ pain is very important. The starting four-hourly dose is 2.5 to 5 mg for children of one to five years and 5 to 10 mg for older children. Add up the total amount of morphine given in 24 hours (four-hourly dose plus any extra doses) to calculate the four-hourly dose for the next day. There is no maximum dose. The correct dose is the dose which is effective in controlling the pain. Therefore the dose of morphine should be titrated against the degree of pain.
Morphine can also be given intravenously or intramuscularly, but preferably by continuous subcutaneous infusion with a syringe driver.
Frequent doses of oral morphine are the most effective form of pain relief.
Addiction is not of concern when morphine is used to control pain in terminally ill patients. Do not stop morphine suddenly, however, as this may result in withdrawal symptoms. Respiratory depression is uncommon when morphine is used to control pain.
A syndromic approach is often used in terminal care when the symptoms are managed even if the underlying cause cannot be treated. Help from hospice staff is very useful in preventing and managing most of these problems.
Nausea is a common problem, especially when treatment with morphine is started. Metoclopramide (Maxolon) 1 to 5 mg (for children of two to 10 years) orally eight-hourly is helpful.
Improving the symptoms caused by HIV-associated infections can greatly improve the quality of the last weeks of life. For example, treating painful mouth ulcers or improving painful swallowing by managing fungal oesophagitis.
Relief of symptoms is often best achieved by treating HIV-associated infections.
This is often a very difficult question to answer. Sometimes it may be realistic not to treat terminally ill children if the treatment will only prolong their suffering. However, pain, discomfort and distress must always be aggressively managed. Both children and their parents should never be allowed to feel abandoned by their health carers.
The question that must always be asked is: ‘Will this make a difference to the quality of the child’s life?’
Anxiety and depression are common in terminally ill children and are often not recognised. It is important to manage anxiety and depression as they both aggravate pain. Children need comfort and love and should never feel abandoned or isolated. Physical touch (holding, stroking, cuddling) and emotional closeness are very important.
Anxiety and depression make pain worse.
Young children think that dying is like falling asleep and do not understand that dead people do not wake up again. Older children are afraid of being separated from their parents. Children are often more accepting of death than adults and do not understand all that death means. Their questions should be answered simply and honestly.
Unfortunately many children are losing parents to AIDS. They may even lose both parents. This is very traumatic and these children need an enormous amount of help and support. This is best provided by family and close friends. Siblings of dying children must not be forgotten as they also need help to talk about and accept the death. Dying parents need help to say farewell to their children.
This is a simple box that parents can store mementos in for their children. Photographs, letters and cards are kept in the box which is given to the children when they are older, to help them remember a parent who has died of AIDS. A memory box is one of the many ways that a parent can prepare themselves before death separates them from their children.
Yes. This is often forgotten or not realised. Care of the carers (both family and health workers) is a very important part of terminal care. It is physically and emotionally exhausting to care for a terminally ill patient. Signs of depression are often missed.
A three year old child is brought to a primary-care clinic with failure to thrive, dehydration, oral candidiasis and a one-week history of pain and difficulty in swallowing. It is noted that she has extensive severe scabies. A rapid HIV test is positive.
Yes. It is one of the first presentations in children with HIV infection. It is uncommon to get oral candidiasis (thrush) in children older than two months who have a healthy immune system. Oral candidiasis can usually be successfully treated with mycostatin drops 1 ml or miconazole gel six-hourly after a feed or meal.
This is any infection which is more common in children who have a suppressed immune system due to HIV infection. Therefore, oral candidiasis is an HIV-associated infection.
She almost certainly has oesophageal candidiasis. These children have pain and difficulty with swallowing and may drool saliva. They are hungry and thirsty but unable to swallow liquids or food. It is very important to look for signs of dehydration.
This child must be given fluids intravenously or via a nasogastric tube. Usually oesophageal candidiasis is treated with oral fluconazole for 2 to 3 weeks, depending on the clinical response. It may be necessary to give intravenous fluconazole for a few days until the child can swallow the medication. Treating the oral candidiasis alone will not help. Analgesia should be given as the condition is painful.
Yes, as it would be graded as stage 4 HIV infection.
Extensive scabies is common in HIV-infected children because of their weakened immune system. Many other skin infections, such as molluscum, warts, chickenpox, herpes, tinea and impetigo may also be severe and respond poorly to standard treatment.
A nine-month-old child is brought to a local hospital with an acute onset of cough, high fever and shortness of breath. The mother was found to be HIV-positive when screened during pregnancy but was not given prophylactic antiretroviral treatment. On clinical examination the child had clinical signs of pneumonia. There were also many small, painful ulcers on his mouth.
He may have a viral or bacterial pneumonia. However, he is most likely to have Pneumocystis pneumonia which is common in young infants who are HIV infected. TB pneumonia usually does not have an acute onset while lymphoid interstitial pneumonia is usually seen in older children. A chest X-ray will confirm the pneumonia but often does not help to identify the cause.
Pneumocystis pneumonia is usually treated with intravenous co-trimoxazole for 21 days. If drip access becomes difficult the antibiotic course may be completed with oral co-trimoxazole. Oral treatment can be used from the start if intravenous co-trimoxazole cannot be started. Additional antibiotics may be added to treat bacterial pneumonia (e.g. ampicillin plus gentimicin). The selection of antibiotics is dependent on the suspected organism. Steroids are given for presumed Pneumocystis pneumonia.
Children with stage 4 disease as Pneumocystis pneumonia is an AIDS-defining infection.
By starting all HIV-exposed children on prophylactic co-trimoxazole from six weeks of life. It should be continued unless the diagnosis of HIV infection is excluded.
Probably Herpes simplex causing severe stomatitis. Severe aphthous ulcers, necrotising ulcerative gingivitis and oral candidiasis can also cause a sore mouth.
Topical gentian violet or 0.1% povidone-iodine (Betadine mouth wash) may be used while oral acyclovir is indicated for large ulcers. Paracetamol can be given for pain. It is important to make sure that these children take enough liquids and do not become dehydrated.
While being prepared for antiretroviral treatment, a 5 year old child has a positive Mantoux skin test and signs of TB on his chest X-ray. The sputum is negative for TB on GeneXpert MTB/RIF but sputum is sent off for culture. The CD4 count is 20%. His mother asked when antiretroviral treatment will be started.
TB treatment should be started as soon as possible and antiretroviral treatment started 2 to 8 weeks later. In children with advanced HIV infection it may be necessary to start antiretroviral treatment soon after starting TB treatment. It is important to screen all children for TB before starting antiretroviral treatment.
Because of the risk of immune reconstruction inflammatory syndrome (IRIS). When the immune system starts to recover with antiretroviral treatment, there may be a severe inflammatory response to TB bacilli. The risk of IRIS is much less after two months of anti-TB treatment.
This is not uncommon in children with TB. In children with HIV infection and TB, the Mantoux skin test may also be negative. Even the chest X-ray may appear normal. Therefore, the diagnosis of TB can be difficult in children with HIV infection.
Yes. It is one of the commonest HIV-associated infections. Children with pulmonary TB are classified as stage 3 while extra-pulmonary TB is classified as stage 4.
A persistent cough for more than 2 weeks in a child who is generally unwell. Poor appetite, weight loss and fever are common.
When HIV-infected children, who have no signs of TB, are exposed to an adult with TB in their home. It is also given to children under five years who are clinically well but have a positive Mantoux skin test. It is important to exclude TB before starting prophylaxis.
A 7 year old boy has been on antiretroviral treatment for two months. He develops a cough and a chest X-ray suggests pulmonary TB. A grandfather at home has recently been diagnosed with TB. The medical officer is not sure whether she should stop antiretroviral treatment and start TB treatment.
It is important not to stop antiretroviral treatment. Anti-TB treatment should be started. The child must be carefully monitored for signs of adverse effects (side effects) such as hepatitis. It would be best if this child was under the care of a doctor experienced in managing patients with HIV and TB co-infection.
Rifampicin, INH, pyrazinamide and ethambutol are given for two months followed by rifampicin and INH only for a further four months. This treatment course is longer than that used in children without HIV infection. If the chest X-ray at six months does not show adequate clearing the maintenance treatment should be continued for an additional three months.
Rifampicin is the usual cause of adverse drug interactions when HIV and TB are treated at the same time. Rifampicin lowers the blood level of many drugs, especially nevirapine and lopinavir/ritonavir. Therefore, nevirapine is usually swapped for efavirenz and extra ritonavir is added to the lopinavir/ritonavir treatment. Not making these changes may lead to drug resistance and failure of antiretroviral treatment.
Side effects are more common and severe when both treatment regimens are used together. Nausea, rash, hepatitis and peripheral neuropathy may be caused by both anti-TB treatment and antiretroviral treatment. It is important to monitor children for these side effects.
Yes. It increases the chance of poor adherence and making mistakes with taking the medication correctly.
TB is an important cause of meningitis in children with HIV infection.