6Diagnosis of HIV infection in infants and children

6.1.1. Infants (<12 months of age)

Available research confirms that, for infants acquiring HIV before or around delivery, disease progression occurs rapidly in the first few months of life and often leads to death. Over 80% of HIV-infected infants who are well at 6 weeks progress to become eligible to start ART before 6 months of age. Early determination of HIV exposure and definitive diagnosis is thus critical. Therefore,

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All infants and children should have their HIV exposure status established at their first contact with the health system, ideally before 6 weeks of age. To facilitate this, all Maternal, Neonatal and Child service delivery points in health facilities should offer HIV serological testing to mothers and their infants and children. In most cases the HIV status is established by:

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asking about maternal HIV testing in pregnancy, labour or postpartum period

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checking the child's and/or mother's health card,

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offering a rapid antibody test to all infants and or mothers whose HIV status is unknown, especially where the national HIV prevalence is >1% .

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Viral testing (e.g. PCR) should be conducted at 4-6 weeks of age for infants known to be HIV-exposed, or at the earliest possible opportunity for those seen after 4-6 weeks of age.

Urgent HIV antibody testing should be carried out for any infant or child presenting with signs, symptoms, or medical conditions that indicate HIV.

Infants with detectable HIV antibodies should go on for a viral test.

6.1.2. Children over 12 months of age

18 months of age and older: HIV antibody tests can provide definitive diagnosis in children ≥18 months of age, with known or unknown exposure to HIV.

HIV antibody testing should be carried out for children of this age group who present with signs, symptoms or medical conditions that indicate HIV (see section 2.1.3).

12-18 months of age: Viral testing for diagnostic purposes is recommended since HIV antibody tests may not accurately reflect infection of the child as a result of the possible persistence of maternal HIV antibodies. However this group of children should be offered antibody test, and only those who are positive subjected to viral test. Those who are negative on antibody test and have not breastfed for more than six weeks are not infected.

6.2.1. Signs or conditions that may indicate possible HIV infection

HIV's clinical expression in children is highly variable. Many HIV-infected children develop severe HIV-related signs and symptoms in the first year of life. Other HIV-infected children remain asymptomatic or mildly symptomatic for more than a year and may survive for several years.

Suspect HIV if any of the following symptoms, signs, and/or clinical events are present, as they are not common in children without HIV:

Signs that may indicate possible HIV infection

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Recurrent infection: three or more severe episodes of a bacterial infection (such as pneumonia, meningitis, sepsis, cellulitis) in the past 12 months.

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Oral thrush: erythema and white-beige pseudomembranous plaques on the palate, gums and buccal mucosa. After the neonatal period the presence of oral thrush is highly suggestive of HIV infection when it is: occurring when there has been no antibiotic treatment, lasting over 30 days despite treatment, recurring, extending beyond the tongue, or presenting as oesophageal candidiasis.

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Chronic parotitis: unilateral or bilateral parotid swelling for ≥14 days, with or without associated pain or fever.

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Generalized lymphadenopathy: enlarged lymph nodes in two or more extra-inguinal regions without any apparent underlying cause.

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Hepatomegaly with no apparent cause: in the absence of concurrent viral infections such as cytomegalovirus (CMV).

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Persistent and/or recurrent fever: fever (≥38°C) lasting ≥7 days, or occurring more than once over a period of 7 days.

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Neurological dysfunction:_progressive neurological impairment, microcephaly, delay in achieving developmental milestones, hypertonia, or mental confusion.

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Herpes zoster (shingles): painful rash with blisters confined to one dermatome on one side.

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HIV dermatitis: erythematous purpular rash. Typical skin rashes include extensive fungal infections of the skin, nails and scalp, and extensive molluscum contagiosum.

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Chronic suppurative lung disease.

Signs or conditions very specific to HIV-infected children

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Strongly suspect HIV-infection if the following conditions, which are very specific to HIV, are present: pneumocystis pneumonia (PCP), oesophageal candidiasis, lymphoid interstitial pneumonia (LIP), or Kaposi's sarcoma, and in girls, acquired recto-vaginal fistula.

Signs common in HIV-infected children, but also common in sick non-HIV-infected children

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Chronic otitis media: ear discharge lasting more ≥14 days.

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Persistent diarrhoea: diarrhoea lasting ≥14 days.

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Moderate or severe malnutrition: weight loss or a gradual but steady deterioration in weight gain from expected growth, as indicated on the child's growth card. Suspect HIV particularly in breastfed infants <6 months old who fail to thrive.

6.2.2. WHO Paediatric Clinical Staging for HIV

In a child with diagnosed or highly suspected HIV infection, the clinical staging system helps to assess the degree of damage to the immune system, and to plan treatment and care options. The stages determine the likely prognosis of HIV and are a guide when to start, stop, or switch ARV therapy.

The clinical stages identify a progression sequence from least to most severe (number 1 through 4)—the higher clinical stage, the poorer the prognosis. For classification purposes, once a stage 3 clinical condition has occurred, the child's prognosis will likely remain in stage 3 and will not improve to stage 2, even once the original condition is resolved, or a new stage 2 clinical condition appears. Antiretroviral treatment with good adherence dramatically improves prognosis.

The clinical staging events can also be used to identify the response to ARV treatment if there is no easy or affordable access to viral load or CD4 testing.

Table

WHO Paediatric HIV Clinical Staging.

6.2.3. Antibody test (ELISA or Rapid Test)

This is the most common test available for diagnosing HIV infection in health facilities within resource-limited settings.

Rapid test is available in most health facility outpatient clinics. Its benefits include: it is easy to carry out, it does not require a laboratory set up, most health workers (including nurses) can be trained to carry out the test, and the results can be given to the patient within 30 minutes, so all patients tested should go home aware of their HIV status. There is a need to make sure that the diagnostic kits for rapid test are made constantly available to all health facility service delivery points—including maternal and child health clinics, all outpatient clinics, and inpatient wards.

ELISA test requires laboratory equipment, a regular supply of reagents, and laboratory-trained health personnel to determine the test result.

Both rapid test and ELISA test are useful for diagnosing HIV infection in children aged 18 months and above. These tests should be performed according to the standard diagnostic HIV serological testing algorithm used in adults. All infants and children, especially in countries with HIV prevalence > 1%, should be offered an HIV test at first contact with a health facility.

Maternal antibodies may persist until 18 months of age, so antibody tests are not reliable for diagnosing children less than 18 months of age. However, it is used in this age group for screening if a child has been exposed to HIV.

It is strongly recommended that HIV serological assays used for the purpose of clinical diagnostic testing have a minimum sensitivity of 99% and specificity of 98% under quality-assured, standardized, and validated laboratory conditions.

6.2.4. Virological Test (WHO 2010 recommendation)

This is the most reliable method for diagnosing HIV infection in infants and children less than 18 months of age. However it is expensive, and requires a sophisticated laboratory set up with trained staff to carry out the test. While such laboratories are situated in central hospitals away from most of the population, the use of the Dried Blood Spots (DBS) system should enable all health facilities in a country to access virological testing services.

It is strongly recommended that all HIV-exposed infants, and all infants with unknown or uncertain HIV status, should have an HIV virological test performed at 4–6 weeks of age or at the earliest opportunity thereafter. For infants and children with a positive result, a confirmatory test should be done. In infants and children undergoing virological testing, the following assays can be used,

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HIV DNA on whole blood specimen or DBS

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HIV RNA on plasma or DBS,

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Up24 Ag on plasma or DBS.

These assays should have a sensitivity of at least 95%—and ideally greater than 98%—and specificity of 98% or more under quality-assured, standardized and validated laboratory conditions.

All infants with an initial positive virological test result should be started on ART without delay and, at the same time, a second specimen be collected to confirm the initial positive virological test result. Do not delay ART. Immediate initiation of ART saves lives and it should not be delayed while waiting for the results of the confirmatory test. A positive virological test result should reach the mother/infant pair within A MAXIMUM OF FOUR weeks (of the result being established) to ensure early onset of treatment.

To reduce the cost of virological testing, a serological test should be done for HIV-exposed infants and children age 9 to 18 months. Only those with reactive serological assays should have a virological test to confirm HIV infection and determine who needs ART.

If access to viral tests is limited, it is recommended that the first viral testing should be conducted at 4-6 weeks following birth. However, a positive viral test at any age confirms HIV infection, and a repeat viral test on a separate specimen should be done to confirm the initial positive test. In children diagnosed with HIV infection on the basis of only one positive viral test, HIV antibody testing should preferably be performed once the child has reached 18 months of age in order to definitively confirm HIV infection.

Table 6.2.4

Summary of testing methods for infant and children.

6.3.1. Provider Initiated Testing and Counselling

Provider initiated testing and counselling (PITC) means that health care providers should recommend HIV testing and counselling to all children (and their family) presenting to a health facility, for whatever reason. The purpose of PITC is to make sure that the medical and other care interventions that would improve HIV-infected individuals' quality of life are provided in a timely manner. However,

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All HIV testing must be voluntary, confidential, and undertaken with the patient's and/or their family's consent.

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Informed consent from a child's parent or guardian is required, and every effort should be made to explain to the child what is happening and obtain her/his assent, according to their level of development.

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Patients have the right to decline the test. They should not be tested for HIV against their will, without their knowledge, without adequate information, or without receiving their test results.

6.4.1. Presumptive diagnosis of severe HIV disease in infants and children aged under 18 months where viral testing is not available

No single clinical diagnostic algorithm has proved to be consistently and highly sensitive or specific for diagnosing HIV infection, and in particular, they are less reliable in infants. However, there are situations where the use of a clinical algorithm may be required to initiate treatment of a seriously ill child.

Table

The child is confirmed as being HIV antibody-positive The infant is symptomatic with two or more of the following:

For infants and children less than 18 months of age, where access to viral testing is not available, but when they have symptoms suggestive of HIV infection and positive HIV antibody testing, a presumptive clinical diagnosis of severe HIV-infection may be necessary in order to permit the initiation of potentially life-saving ART. Criteria for diagnosis are shown in the table below. HIV serological test should be repeated at 18 months of age to confirm HIV infection. Note that WHO clinical staging of HIV disease can only be employed where HIV infection has been established.

6.4.2. Diagnosing HIV infection in breastfeeding infants

A breastfeeding infant is at risk of acquiring HIV infection throughout the breastfeeding period. Breastfeeding should not be stopped in order to perform diagnostic HIV viral testing. Positive test results should be considered to reflect HIV infection, with the usual confirmatory algorithms followed. However, interpreting negative results is difficult. A six-week window period after the complete cessation of breastfeeding is required before negative viral test results can be assumed to reliably indicate HIV infection status. For children over 12 months of age, the six week window is also required before HIV antibody testing.

6.4.3. Diagnosing HIV infection when mother or infant has received ARVs for PMTCT

HIV DNA assays are reliable for diagnosis when the mother or infant has been given ARV drugs for PMTCT. HIV-1 DNA remains detectable in the peripheral blood mononuclear cells and lymphoid tissue of HIV-infected children who have received ART and have undetectable viral replication as measured by HIV-RNA assays. DNA detection in the infant is not affected by maternal ART when the mother is breastfeeding.

It is not known whether maternal ART during breastfeeding affects HIV-RNA or Up24Ag detection in infants. Research indicates that all types of viral testing can be used from 6 weeks of age, even if the mother is breastfeeding and on ART--despite theoretical concerns about the sensitivity of HIV -RNA and Up24Ag assays in infants exposed to ARVs. Mothers should not discontinue the use of ART and should not discontinue breastfeeding for the purposes of testing for HIV.

Figure 3Testing sequence for initial and subsequent visits of HIV-exposed infant

^a The risk of HIV transmission remains as long as the breastfeeding continues

^b Usually HIV antibodies testing from 9-18 months of age

Figure 4Diagnostic HIV testing for sick infants where viral testing is available

Figure 5Diagnostic HIV testing for sick infants where viral testing is not available