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Therefore the amount of virus in the blood is high early and late in the course of HIV infection. The number of CD4 cells in the blood slowly falls as the HIV infection progresses and the body is no longer able to replace the killed CD4 cells. The infection progresses much more rapidly in children than in adults, especially in those children infected during pregnancy, delivery or soon after birth. The increase in HIV and decrease in CD4 cells result in the children becoming progressively more ill.
HIV infects CD4 cells and slowly damages the immune system.
Figure 2-1: The changes in viral load, CD4 count and clinical features of HIV infection in adults
No. They do not become ill at the time of HIV infection. However, they may develop acute seroconversion illness soon after infection. Acute seroconversion illness is relatively common in adolescents and adults but rarely diagnosed in infants and children.
Infection with HIV may cause acute seroconversion illness.
At the time that HIV antibodies appear in the blood (seroconversion) about 50% of infected people develop a flu-like illness which lasts a few days or weeks. This illness occurs two to four weeks after infection with HIV and is called acute seroconversion illness.
During acute seroconversion illness (acute retroviral syndrome or acute HIV disease) the amount of virus in the blood is very high but the amount of antibody still very low. Therefore, the screening tests for HIV (which depend on the presence of HIV antibodies) may still be negative at the time of acute seroconversion illness, i.e. may still be the ‘window period’ (the period of time from infection to when the HIV tests become positive).
Acute seroconversion illness is often the first clinical sign of HIV infection in adults and older children.
During acute seroconversion illness the CD4 count may be temporarily depressed.
The common clinical features of acute seroconversion illness are:
The above symptoms and signs are similar to those found in glandular fever (infectious mononucleosis). Many people with acute seroconversion illness think they have severe ’flu. During infancy lymphadenopathy, rash and failure to thrive are common signs of acute seroconversion illness.
Patients with acute seroconversion illness are managed symptomatically with antipyretics (e.g. paracetamol) for fever. There is no role for antiretroviral treatment.
During the first few weeks of HIV infection, especially if the person develops seroconversion illness, large amounts of virus are present in the blood and other body fluids. As a result, the person is very infectious to others. It is therefore of particular importance in adults to abstain from sexual intercourse during this time. Unfortunately most are not aware that they have been recently infected with HIV.
Following the primary HIV infection (and acute seroconversion illness) there is a latent phase before chronic HIV illness develops.
HIV infection and seroconversion are followed by a latent period when the child looks and feels well. During this phase it is not obvious that the child has HIV infection. There may be no clinical signs at all or only persistent, painless, generalised lymphadenopathy during the latent phase.
During the latent phase the viral load is low and the CD4 count is normal or only mildly depressed.
Children in the latent phase of HIV infection appear well.
In adults this silent, asymptomatic period usually lasts five to 10 years. However, in children it is much shorter. Owing to their immature immune system, HIV infection progresses much faster from the latent phase to the symptomatic phase.
No. In some children the progression to symptomatic infection is much faster (‘fast progressors’) than in other children (‘slow progressors’). As a result their latent phase is shorter in ‘fast progressors’. The most important factor indicating how fast the HIV infection will progress is the timing of the infection:
The earlier the HIV infection, the shorter the asymptomatic latent phase.
When patients who have been clinically well during the latent (asymptomatic) phase of HIV infection become ill, they are said to have symptomatic HIV infection (HIV disease). The symptoms and signs of symptomatic chronic HIV infection only present when the damaged immune system is no longer able to protect the person from serious infections.
Chronic HIV infection can present with a very wide range of clinical symptoms and signs. These are usually due to secondary viral, bacterial, fungal or parasitic infections.
Common ways that HIV infection can present include:
The WHO clinical criteria divide HIV infection into four stages: an asymptomatic, latent stage (stage 1) followed by three symptomatic stages (stages 2, 3 and 4). As the HIV infection progresses and the illness becomes more severe, the clinical stage progresses from 2 to 4.
HIV infection can be divided into four clinical stages.
Knowing the clinical stage is a valuable way of predicting what the prognosis will be, especially if the child is not given antiretroviral treatment. Therefore the clinical stage can be used to estimate how long the child is likely to survive without treatment.
The clinical stage helps to predict the likely course of the illness.
The World Health Organisation defines advanced HIV disease as stage 3 or 4 HIV infection. AIDS (acquired human immunodeficiency syndrome) refers to stage 4 disease. Infants with AIDS are at high risk of dying within weeks or months unless correctly treated. With antiretroviral treatment AIDS is a manageable chronic condition.
AIDS is the most advanced form of HIV infection.
These children are clinically well. However, they may have persistent, generalised lymphadenopathy on clinical examination.
These children are moderately symptomatic and may present with any of the following clinical features:
Stage 2 presents with many common mild childhood infections.
These children are more ill than children with stage 2 HIV infection. They have advanced signs and may present with any of the following:
Stage 3 presents with common severe infections.
These children are severely symptomatic and are seriously ill with any of the following:
Stage 4 presents with uncommon severe infections.
Other non-specific skin rashes are also common in children with HIV infection.
Skin rashes are common in children with HIV infection.
This is very common in children with HIV infection and presents with a persistent severe itch and scattered pigmented papules, especially on the trunk and limbs (‘itchy bump disease’). It responds to topical steroids.
By testing for the presence of antibodies to HIV (antibody tests) or the presence of HIV itself (viral tests). In adults the diagnosis of HIV infection is usually based on finding antibodies to HIV in the blood or other body fluids (e.g. saliva). However, in young children it is necessary to show that the virus (HIV) itself is present.
Screening for HIV infection should be done in all sick children in countries where AIDS is common, including South Africa.
Wherever possible, the HIV status of all children should be established.
Only in older children (18 month of age or more) if the mother is HIV positive. Mothers who are infected with HIV produce antibodies to HIV and these antibodies pass across the placenta to their fetus. Therefore, if the mother has antibodies to HIV, her newborn infant will also have HIV antibodies whether the infant is infected with HIV or not. These maternal antibodies slowly disappear from the infant’s blood during the months after birth but may remain up to the age of 18 months. As a result, positive antibody screening tests for HIV antibody (ELISA test and rapid test) cannot be used to diagnose HIV infection in children before the age of 18 months. However, if the antibody test is negative, the child has not been exposed to HIV.
Antibody testing for diagnosing HIV infection is only reliable in children of 18 months or older.
Many HIV-exposed but uninfected children will already have a negative HIV antibody screening test by nine months of age when the child attends clinic for the first measles immunisation. Most, but not all, uninfected children will have a negative antibody screening test by 12 months. All uninfected children will get an HIV-negative result by 18 months.
An antibody screening HIV test is also useful if the mother’s HIV status is unknown or cannot be obtained, e.g. for orphans or abandoned children. If the infant’s antibody test is negative the mothers test must also be negative and therefore the infant has not been exposed to HIV.
Where PCR testing is not available, clinical features and antibody screening should be used to make a probable diagnosis on HIV infection until testing at 18 months.
The PCR test is used to diagnose HIV infection in children younger than 18 months.
This is the time after infection with HIV when the blood tests may still be negative. For both the antibody tests and the viral tests the window period may last up to six weeks.
During the six-week window period the tests for HIV infection may be negative, even if the child is infected with HIV.
In addition to the clinical staging of HIV infection, patients should also be staged immunologically. This is based on the number of CD4 cells (helper or CD4+ T cells) in the blood. As HIV destroys more and more CD4 cells the body’s immune system becomes weaker and weaker. The number of CD4 cells in the blood is therefore a direct measure of the degree of damage to the immune system and the risk of HIV-associated infections.
The number of CD4 cells indicates whether the immune system has been damaged.
This is the number of CD4 cells in one µl of serum (i.e. a 1000th of a ml). In normal healthy adults who are HIV negative, the CD4 count is above 500 cells/µl (usually about 1000 cells/µl). In children the normal range is higher, especially in younger children who have an immature immune system. As the CD4 count varies according to the child’s age, it is preferable to use the CD4 percentage rather than the absolute CD4 count in younger children (under the age of five years). The CD4 percentage is the per cent of lymphocytes in the blood that are CD4 cells.
In normal healthy children, more than 25% of the lymphocytes in their blood should be CD4 cells. This indicates that there is no immunosuppression (no damage to the immune system). If the immune system of children with HIV infection is suppressed, their percentage of CD4 cells will be less than 25%.
Normal children have a CD4 percentage of 25 or more.
A CD4 percentage below 15% indicates severe immunosuppression.
The lower the CD4 percentage, the greater the risk of severe illness and death.
Yes. It is best if both systems of staging are used together, especially when deciding whether a child needs to be started on antiretroviral treatment. While the immunological staging indicates the degree of immunosuppression, the clinical staging indicates the effect of the immunosuppression. Both are important.
Yes. It is very important that informed consent is always obtained before any form of HIV testing is done. This means that counselling must be provided before obtaining consent.
Consent must be obtained before testing a child for HIV.
When children need to be tested, consent is usually obtained from a responsible adult, such as the parent or guardian (caretaker). Adolescents of 12 years or more can give their own consent, although it is always preferable to get consent from a parent or legal guardian as well. Children who give consent must receive pretest counselling which they can understand. If a child is not able to give consent, the person providing consent must receive appropriate counselling.
Abandoned or orphaned children have the same legal rights as other children. Adoptive or foster parents are legal guardians and can give consent. If there is no available guardian, the provincial minister for social services should be approached for consent. This is often needed when abandoned children who are ill are admitted to hospital.
Confidentiality is important and children of 12 years or more can be tested and keep the result of their HIV test from their parents if they so wish. Consent for the clinic or hospital staff to disclose the result of the HIV test to the parents must first be obtained from these children. Therefore, older children should be tested without their parents knowledge or permission if this is their wish.
As a diagnosis of HIV infection in a child has important implications for the parents and whole family, the parents should be counselled before they give consent for the child to be tested. In most children a positive diagnosis in the child implies HIV infection in the mother and often the father. The parents need to understand what HIV infection is, how a child becomes infected with HIV and the clinical presentation and course of HIV infection.
A 15-year-old adolescent presents with a fever, sore throat, headache and general feeling of tiredness. On examination she has pharyngitis and a measles-like rash. When questioned she gives a history of recent sexual relations with an older man.
Acute seroconversion illness. This presents in some people two to four weeks after infection with HIV. The symptoms and signs usually disappear after a few weeks. Acute seroconversion illness is uncommon in young children.
Usually an HIV screening test (rapid test) is done. However, the test may still be negative even though the person is infected with HIV because they are still in the window period.
This is the time between infection and the first appearance of symptoms and signs due to chronic HIV infection (i.e. symptomatic HIV infection).
It is shorter than in adults where the latent period is usually a number of years. In children who are infected around the time of birth, the latent period is usually weeks or months (‘fast progressors’). It is longer in children who are infected via breast milk (‘slow progressors’).
Persistent, painless, generalised lymphadenopathy.
Yes. At the age of 15 years she can give consent for the test. However, it is always preferable to also obtain the parents’ consent.
A two-year-old child is brought to a clinic by a woman who was HIV positive when screened during her pregnancy. The infant was never breastfed. She reports that the child has had an itchy skin rash for the past few days. On examination he also has an enlarged liver and spleen, as well as a chronic otitis media.
Yes. The hepatosplenomegaly, skin rash and chronic otitis media all suggest symptomatic HIV infection, especially if the mother is HIV positive. A positive rapid test would confirm the HIV infection.
Pruritic papular eruption or ‘itchy bump disease’. It responds to topical steroids.
The child has some features of stage 2 infection (a typical rash, hepatosplenomegaly and chronic upper respiratory tract infection).
Enlarged painless parotid glands, other skin rashes such as warts and molluscum, fungal nail infections, mouth ulcers and inflamed gums, other upper respiratory tract infections and Herpes zoster.
Consent must always be obtained first before testing anyone for HIV infection.
A six-month-old child with known HIV infection presents at the outpatients department of the local hospital. His mother says that he has lost weight recently, has a sore mouth and a chronic cough. On examination the child has oral candidiasis (thrush).
Stage 3, as he has oral candidiasis. He is probably malnourished as well.
Pulmonary tuberculosis. However, he should be fully investigated as there are many other causes of chronic cough and lung infection in children with HIV infection.
Severe recurrent bacterial pneumonia, symptomatic lymphoid interstitial pneumonitis and chronic lung disease.
No. This is a feature of stage 4 HIV infection.
No. The CD4 percentage is used to immunologically stage the illness. Both the clinical and the immunological staging are important as they are used to decide when to start antiretroviral treatment.
Yes. Advanced HIV disease in children is defined as stage 3 or 4 HIV infection.
A woman with asymptomatic HIV infection delivers a preterm infant who is clinically healthy. The infant is not breastfed. She wants to know whether her infant is also infected with HIV. The mother has a normal CD4 count.
No. In an HIV-exposed infant, these tests can only be used to diagnose HIV infection after 18 months. The rapid test will be positive even if the infant is not infected with HIV.
Once this infant is six weeks old, the PCR test for HIV or the ultra-sensitive p24 antigen can be used. A negative test at six weeks or more would indicate that the infant has not been infected with HIV while a positive test would indicate HIV infection. The PCR test should be done before 6 weeks if the infant has any clinical signs of HIV infection. If negative it should still be repeated at 6 weeks after birth. All breastfed infants should in addition be retested with the PCR test six weeks after the last feed of breast milk, and at any stage during breast feeding period if clinical features of HIV infection develop.
This is a test to determine whether the immune system has been damaged. The CD4 percentage rather than the CD4 count is used in children.
More than 25%. A CD4 percentage of 15 to 24% indicates moderate immune suppression while a CD4 percentage below 15% indicates severe immunosuppression.
It helps to predict how fast the HIV infection will progress. Children with a low CD4 percentage will reach stage 3 or 4 sooner than children with a higher CD4 percentage.