A. Test for HIV Antibody

• HIV Testing of Pregnant Women: HIV counseling and testing are recommended as the standard of care for all pregnant women.
• HIV-testing should be offered as early as possible during the prenatal period.
• If not tested during pregnancy, counseling and testing should be offered to women during the postnatal period.
• HIV Testing of Neonates: HIV antibody testing, accompanied by appropriate counseling of the mother, should also be the standard of care for neonates born to mothers who have not received HIV antibody testing during pregnancy or in whom antibody test results are not known to the pediatrician
• HIV Infection Status of Neonates: Infants at risk for HIV infection (mother or infant is HIV-antibody positive) must have a determination of their HIV infection status as soon as possible after birth.

 
1. HIV Antibody by EIA: Highly sensitive (>99%) assays for HIV-1/HIV-2 antibodies. The presence of HIV antibody in an infant born to a mother with HIV infection does not differentiate maternal from infant antibody. Maternal antibody may be detected in the infant until 12-15 months.
1. HIV-1-EIA: From 60-91% of HIV -2 infected persons will test repeatedly reactive by HIV-1 EIA. A repeatedly reactive test must be tested by the Western blot assay or by IFA to HIV-1 before reporting.
2. HIV-2-EIA: HIV-2 infection is rare in the U.S. except in travelers from West Africa or persons who have had sexual contact with West Africans infected HIV-2. A repeatedly reactive test must be confirmed by a supplemental test at the state laboratory.
3. HIV-1/HIV-2 (rDNA) EIA (Abbott Lab): This test has been available since February 1992 and test for both HIV types: 
• Repeatedly reactive test: Must do HIV-1 WB or IFA assay.
• Repeatedly reactive test with negative or indeterminate WB: Must do HIV-2 EIA, if repeatedly reactive do HIV-2 supplemental test
2. Supplemental HIV test: Any repeatedly reactive HIV-1, HIV-2 or HIV-1/HIV-2 EIA test must be tested by one or more of these supplemental test before reporting:
1. HIV-1 Western Blot Assay: This assay test for antibodies to specific HIV-1 proteins. This is a highly specific assay.
• Positive: A positive HIV-1 WB confirms the presence of antibodies to HIV. Although this does not always distinguish between antibodies to HIV-1 and HIV-2, further testing is not required for routine purposes. If the suspicion of HIV-2 infection (based on epidemiologic risk factors [ see appendix E]) is high, additional testing for HIV-2 is indicated.
• Negative: If the HIV-1 WB is negative, an EIA for HIV-2 only should be performed. If the HIV-2 EIA is repeatedly not reactive, the specimen should be considered negative for HIV antibodies.
• Indeterminate: If the HIV-1 WB is indeterminate, an EIA for HIV-2 only should be performed. If the HIV-2 EIA is repeatedly not reactive, the specimen should be considered indeterminate. Repeat testing is advised in 6 months to exclude the possibility of early HIV-1 infection.
2. Immunofluorescent Assay (IFA) for HIV-1 Antibody:
• A positive or negative HIV-1 IFA should be interpreted in the same manner as similar results from the WB test.
• An Indeterminate HIV-1 IFA should first be tested by HIV-1 WB and reported based on its results as above.
3. Supplement HIV-2 confirmatory test are not currently licensed, therefore those specimens with repeatedly reactivity to HIV-2 EIA must be sent to the state laboratory for further testing. The report will be positive, negative or indeterminate with similar interpretation as for the supplemental test for HIV-1.

• Approximately 50% of infected infants can be identified at or near birth.
• Greater than 95% of infected infants can be diagnosed by 3-6 months.
• At risk infants should have one or more of these tests performed as soon as possible after birth and these test should be repeated between 3-6 months of age.
• Seropositive infants who do not have a definitive virologic diagnosis of HIV infection should continue to be tested every 3 months by ELISA/WB Assays. After the first year, HIV antibody should be performed at 18 and 24 months of age.
• Seroreverter: A child of an HIV-infected mother who is repeatedly HIV-antibody-negative by 18 months of age and has never had a positive HIV culture/PCR/P24 antigen is considered as a seroreverter.

1. HIV Culture: Not readily available, large volume of blood required and may require several weeks growth for detection.
2. HIV-P24 Antigen Assay: 
• Standard Assay: The P24 Antigen in the serum of infants is bound to maternal HIV antibody. This test is insensitive for the detection of HIV infection in infants. Less than 20% have detectable P24 antigen 1-6 months of age. It only detects free antigen.
• ICD-HIV-P24 Assay: If acid hydrolysis is used to disrupt antigen-antibody complexes in serum, the sensitivity of P24 antigen detection can be increased, and this assay may be a tool for early diagnosis. 100% are positive by 1-3 months of age.
3. HIV-DNA-PCR: A highly sensitive and specific test for early detection of HIV infection in infants. All infected infants detected by 6 months of age.
4. HIV-IgA Antibody Test: Maternal IgA antibodies do not cross the placenta, therefore the detection of HIV specific antibodies in the infant serum indicates the presence of HIV infection. This assay is insensitive for the detection of infection in the first 3 months. (17% at one month, 67% at 3 months), but a very sensitive assay in infants 6 months. (94% detected at 6 months, 100% detected 9 months). This assay is not yet commercially available.

C. Immunologic Test:

1. Lymphocyte subsets: CD4, CD8 and CD4/CD8 ratio - Should be performed on all infants born to HIV-infected mothers at 1, 3, and 6 months of age, then every 3-months until HIV status of the child in known. - Should be monitored every 3-6 months in children proven to be HIV-infected.
2. Quantitative immunoglobulin: IgG, IgM, IgA
3. Skin Test: Candida, Mumps, Tuberculin Skin Test (PPD)

D. Diagnosis of HIV infection in Children:

1. Diagnosis: HIV Infected
1. A child less than18 months of age who is known to be HIV seropositive or born to an HIV-infected mother and:
1. Has positive results on two separate determinations (excluding cord blood) from one or more of the following HIV detection tests: 
• HIV culture
• HIV - DNA-PCR
• HIV-P24 Antigen or
2. Meets criteria for AIDS diagnosis based on the 1987 AIDS surveillance definition.
2. A child 18 months of age born to an HIV-infected mother or any child infected by blood, blood products, or other known modes of transmission (e.g. sexual contact) who:
1. Is HIV-antibody positive by repeatedly reactive EIA and confirmatory test (e.g. WB or IFA) OR
2. Meets any of the criteria in 1 above.
2. Diagnosis: Perinatally Exposed
1. A child who does not meet the criteria above who:
1. Is HIV seronegative by EIA confirmatory test (e.g., WB or IFA) and is <18 months of age at the time of test; or
2. Has unknown antibody status, but was born to a mother known to be infected with HIV.
3. Diagnosis: Seroreverter (SR)

A child who is born to an HIV-infected mother and who:
1. Has been documented as HIV-antibody negative (i.e, two or more negative EIA test performed at 6-18 months of age or one negative EIA test after 18 months of age); and
2. Has had no other laboratory evidence of infection (has not had two positive viral detection test, if performed); and
3. Has not had an AIDS-defining condition.
4. Criteria for HIV Infection for Persons >13 years:
• Repeat reactive screening test for HIV antibody (e.g. Enzyme Immunoassay) with specific antibody identified by the use of supplemental test (e.g. Western Blot, immunofluorescence assay)
• Direct identification of virus in host tissues by virus isolation.
• HIV antigen detection
• A positive result on any other highly specific licensed test for HIV

1. Pediatric HIV Classification
 

TABLE 1. Pediatric human immunodeficiency virus (HIV) classification*

	Clinical categories
Immunologic Categories	N: No signs/symptoms	A: Mild signs /symptoms	B: **Moderate signs /symptoms	C: **Severe signs/symptoms
1: No evidence of suppression	N1	A1	B1	C1
2: Evidence of moderate suppression	N2	A2	B2	C2
3: Severe suppression	N3	A3	B3	C3

* Children whose HIV infection status is not confirmed are classified by using the above grid with a letter E (for perinatally exposed) placed before the appropriate classification code (e.g., EN2)
** Both Category C and lymphoid interstitial pneumonitis in Category B are reportable to state and local health departments as acquired immunodeficiency syndrome.

Category A: Mildly Symptomatic Children with two or more of the conditions listed below but none of the conditions listed in Categories B and C.

• Lymphadenopathy ( 0.5 cm at more than two sites; bilateral= one site)
• Hepatomegaly
• Splenomegaly
• Dermatitis
• Parotitis
• Recurrent or persistent upper respiratory infection, sinusitis, or otitis media

Children who have symptomatic conditions or other than those listed for Category A or C that are attributed to HIV infection. Examples of conditions in clinical Category B include but are not limited to:

• Anemia (<8 gm/dL), neutropenia (<1,000/mm3), or thrombocytopenia (<100,000/mm3) persisting 30 days
• Bacterial meningitis, pneumonia, or sepsis (single episode)
• Candidiasis, oropharyngeal (thrush), persisting (>2 months) in children >6 months of age
• Cardiomyopathy
• Cytomegalovirus infection, with onset before 1 month of age
• Diarrhea, recurrent or chronic
• Hepatitis
• Herpes simplex virus (HSV) stomatitis, recurrent (more than two episodes within 1 year)
• HSV bronchitis, pneumonitis, or esophagitis with onset before 1 month of age
• Herpes zoster (shingles) involving at least two distinct episodes or more than one dermatome
• Leiomyosarcoma
• Lymphoid interstitial pneumonia (LIP) or pulmonary lymphoid hyperplasia complex
• Nephropathy
• Nocardiosis
• Persistent fever (lasting >1 month)
• Toxoplasmosis, onset before 1 month of age
• Varicella, disseminated (complicated chickenpox)

• Serious bacterial infections, multiple or recurrent (i.e., any combination of at least two culture-confirmed infections within a 2-year period), of the following types: septicemia, pneumonia, meningitis, bone or joint infection, or abscess of an internal organ or body cavity (excluding otitis media, superficial skin or mucosal abscesses, and indwelling catheter-related infections).
• Candidiasis, esophageal or pulmonary (bronchi, trachea, lungs)
• Coccidioidomycosis, disseminated (at site other than or in addition to lungs or cervical or hilar lymph nodes)
• Cryptococcoses, extra pulmonary
• Cryptosporidiosis or isosporiasis with diarrhea persisting > 1 month
• Cytomegalovirus disease with onset of symptoms at age > 1 month (at site other than liver, spleen, or lymph nodes)
• Encephalopathy (at least one of the following progressive findings present for at least 2 months in the absence of a concurrent illness other than HIV infection that could explain the findings): a) failure to attain or loss of developmental milestones or loss of intellectual ability, verified by standard developmental scale or neuropsychological tests; b)impaired brain growth or acquired microcephaly demonstrated by head circumference measurements or brain atrophy demonstrated by computerized tomography or magnetic resonance imaging (serial imaging is required for children <2 years of age); c) acquired symmetric motor deficit manifested by two or more of the following: paresis, pathologic reflexes, ataxia, or gait disturbance
• Herpes simplex virus infection causing a mucocutaneous ulcer that persists for > 1 month; or bronchitis, pneumonitis, or esophagitis for any duration affecting a child > 1 month of age
• Histoplasmosis, disseminated (at a site other than or in addition to lungs or cervical or hilar lymph nodes)
• Kaposi's sarcoma
• Lymphoma, primary, in brain
• Lymphoma, small, noncleaved cell (Burkitt's), or immunoblastic or large cell lymphoma of B-cell or unknown immunologic phenotype
• Mycobacterium tuberculosis, disseminated or extra pulmonary
• Mycobacterium, other species or unidentified species, disseminated (at a site other than or in addition to lungs, skin, or cervical or hilar lymph nodes)
• Mycobacterium avium complex or Mycobacterium kansasii, disseminated (at a site other than or in addition to lungs, skin, or cervical or hilar lymph nodes)
• Pneumocystis carinii pneumonia
• Progressive multifocal leukoencephalopathy
• Salmonella (nontyphoid) septicemia, recurrent
• Toxoplasmosis of the brain with onset at > 1 month of age
• Wasting syndrome in the absence of a concurrent illness other than HIV infection that could explain the following findings:
• a) persistent weight loss >10% of baseline OR
• b) downward crossing of at least two of the following percentile lines on the weight-for-age chart (e.g., 95th, 75th, 50th, 25th, 5th) in a child 1 year of age  OR
• c) <5th percentile on weight-for-height chart on two consecutive measurements, 30 days apart
PLUS
• a) chronic diarrhea (i.e., at least two loose stools per day for 30 days) OR
• b) documented fever (for 30 days, intermittent or constant)

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