What is the diagnosis for an HIV‑exposed infant born to a mother living with HIV?

Diagnosis of HIV-Exposed Infant

An infant born to a mother living with HIV receives the diagnosis of "HIV-exposed infant" or "perinatally HIV-exposed infant" until infection status is definitively determined through virologic testing—not "HIV-infected" unless confirmed by two positive PCR tests. 1

Understanding the Diagnostic Challenge

The critical issue is that maternal HIV antibodies cross the placenta and persist in the infant's circulation until approximately 18 months of age, making standard antibody tests (ELISA, Western blot) unreliable for diagnosing true infection during this period. 1, 2 A positive HIV antibody test in an infant younger than 18 months indicates only exposure, not infection. 1

Immediate Classification and Management

Initial Diagnosis

• The infant is classified as "HIV-exposed" from birth until infection status is determined. 3, 1
• This classification triggers a specific management protocol regardless of whether the infant ultimately proves to be infected. 3

Urgent Interventions Required Within Hours of Birth

All HIV-exposed infants require three immediate interventions:

• Antiretroviral prophylaxis must begin within 12 hours of birth (preferably zidovudine), even before any diagnostic testing is performed. 1, 4
• Baseline complete blood count and differential should be obtained before starting antiretroviral prophylaxis. 3
• Rapid HIV antibody testing should be performed on the mother (or infant) if maternal status is unknown, to enable prophylaxis initiation within the 12-hour window. 1

Definitive Diagnostic Testing Schedule

Gold Standard: HIV DNA PCR

HIV DNA PCR is the preferred diagnostic method because it directly detects viral nucleic acid and is unaffected by maternal antibodies. 1, 2

Recommended testing timeline:

Timing	Test	Detection Rate	Purpose
Before 48 hours	HIV DNA PCR	38% of infected infants	Early detection of in-utero transmission [1]
14 days	HIV DNA PCR	93% of infected infants	Optimal early detection window [1]
1–2 months	HIV DNA PCR	—	Standard confirmation [3,1]
3–6 months	HIV DNA PCR	—	Final confirmation after prophylaxis completion [3,1]

Confirming Infection vs. Excluding Infection

Two positive virologic tests on separate specimens confirm HIV infection. 1, 2 Any initial positive result must be immediately repeated on a second specimen. 1

Presumptive exclusion of infection requires two negative virologic tests (one at ≥2 weeks and one at ≥4 months) in a non-breastfeeding infant with no clinical signs of HIV disease. 2

Definitive exclusion of infection is based on two negative virologic tests (one at ≥1 month and one at ≥4 months) or negative HIV antibody testing after 18 months of age. 2

Critical Testing Pitfalls to Avoid

• Never use umbilical cord blood for HIV testing due to possible maternal blood contamination. 1
• Do not rely on p24 antigen testing alone in infants <1 month because of high false-positive rates and lower sensitivity. 1
• HIV RNA assays may offer greater sensitivity but have limited validation data in newborns and are not first-line. 1
• Infants with negative tests during the first 6 weeks should have repeat testing after completing antiretroviral prophylaxis, as the effect of combination antiretroviral therapy on test sensitivity is unknown. 3

Prophylaxis Requirements for All HIV-Exposed Infants

PCP Prophylaxis

All infants born to HIV-infected women must begin Pneumocystis jirovecii pneumonia (PCP) prophylaxis at 4–6 weeks of age, regardless of CD4+ count. 3, 1 This is because:

• Most PCP cases in HIV-infected children occur in the first year of life. 3
• PCP risk increases dramatically at 2 months of age, when infection cannot yet be excluded. 3
• PCP carries high mortality in this population. 3

Continue PCP prophylaxis until HIV infection is definitively excluded. 1 If the infant is identified as HIV-exposed after 6 weeks of age, start prophylaxis immediately upon identification. 3

Monitoring During Prophylaxis

• Measure hemoglobin at minimum after completing the 6-week antiretroviral regimen, as anemia is the primary complication of neonatal zidovudine prophylaxis. 3
• Repeat hemoglobin measurement at 12 weeks, by which time any antiretroviral-related hematologic toxicity should resolve. 3
• Infants exposed to maternal combination antiretroviral therapy require more intensive monitoring of hematologic and serum chemistry measurements during the first few weeks of life due to limited toxicity data. 3

Feeding Guidance

Advise against breastfeeding when safe, nutritionally adequate alternatives are available, because breast milk can transmit HIV. 1 For breastfeeding infants, the diagnostic testing timeline starts from complete cessation of breastfeeding rather than birth. 2

Specialist Involvement

All HIV-exposed infants should be evaluated by or managed in consultation with a pediatric HIV specialist to ensure accurate interpretation of diagnostic results, timely initiation of therapy if infected, and appropriate prophylaxis management. 1

Summary of the Diagnostic Journey

The infant's diagnosis evolves through three possible pathways:

1. "HIV-exposed infant" → Two positive PCR tests → "HIV-infected infant" → Immediate antiretroviral therapy 1
2. "HIV-exposed infant" → Serial negative PCR tests → "Presumptively HIV-uninfected" → Discontinue prophylaxis 2
3. "HIV-exposed infant" → Negative tests through 18 months → "Definitively HIV-uninfected" → Discharge from HIV care 2

The key distinction is that "HIV-exposed" is the initial diagnosis for ALL infants born to mothers living with HIV, and this exposure status—not infection status—drives the immediate management protocol of prophylaxis and serial testing. 3, 1