Residency · Residency · Pediatrics

Pediatric HIV and Perinatal Infections

Overview

Prevention of mother-to-child transmission (PMTCT) has dramatically reduced pediatric HIV in high-income countries. Without intervention, the mother-to-child transmission (MTCT) rate is 15-45%; with comprehensive PMTCT, it falls to less than 1-2%. Diagnosis in infants requires HIV DNA or RNA PCR rather than antibody testing, because maternal antibodies cross the placenta and persist for up to 18 months. Current antiretroviral therapy (ART) regimens allow near-normal life expectancy when initiated early. Globally, pediatric HIV remains a major problem in sub-Saharan Africa, with approximately 1.7 million children living with HIV.

Prevention of Mother-to-Child Transmission (PMTCT)

Transmission Routes

In utero transplacental transmission accounts for 25-40% of MTCT. Intrapartum exposure to blood and secretions during delivery accounts for 60-75%. Postpartum breastfeeding adds approximately 15-20% additional risk without intervention.

PMTCT Strategy (US Guidelines)

The strategy involves five key steps. First, universal prenatal HIV screening uses opt-out testing at the first prenatal visit and the third trimester, with rapid testing at labor if status is unknown. Second, maternal ART is prescribed for all pregnant women with HIV regardless of CD4 count or viral load, with the goal of achieving an undetectable viral load (below 50 copies/mL) by delivery. Dolutegravir-based ART is the preferred regimen.

Third, intrapartum management depends on viral load: vaginal delivery is acceptable when the viral load is below 1,000 copies/mL near delivery, while a viral load of 1,000 or greater (or unknown) warrants scheduled cesarean section at 38 weeks and IV zidovudine (ZDV) infusion during labor.

Fourth, infant prophylaxis is stratified by risk. Low-risk infants (maternal viral load below 50 at delivery with ART throughout pregnancy) receive ZDV for 4 weeks. High-risk infants (maternal viral load 50 or greater, no or late ART, or acute HIV in pregnancy) receive presumptive HIV therapy with ZDV plus lamivudine plus nevirapine for 6 weeks.

Fifth, breastfeeding is avoided in high-income countries where safe alternatives are available. In resource-limited settings, breastfeeding with maternal ART is recommended because the benefits of breast milk outweigh the transmission risk when the mother is on suppressive ART.

<image>PMTCT cascade showing stepwise interventions: prenatal HIV screening, maternal ART to achieve viral suppression, intrapartum management (delivery mode and IV ZDV based on viral load), infant antiretroviral prophylaxis (low-risk vs. high-risk regimens), and infant feeding recommendations, with transmission risk reduction at each step</image>

Infant Diagnosis

Why Antibody Tests Don't Work in Infants

Maternal IgG anti-HIV antibodies cross the placenta and persist in the infant for up to 18 months. A positive HIV antibody test in an infant under 18 months may reflect maternal antibodies and not infant infection. Antibody testing becomes reliable only after 18-24 months of age.

HIV DNA/RNA PCR (Virologic Testing)

HIV DNA PCR or HIV RNA PCR (viral load) detects the virus directly. The US guidelines recommend testing at 14-21 days of life, 1-2 months of life, and 4-6 months of life. Definitive diagnosis requires 2 positive HIV PCR tests on separate specimens. Definitive exclusion requires 2 negative HIV PCR tests, at least one at 1 month or older and one at 4 months or older, in the absence of breastfeeding. Confirmatory serology with HIV antibody testing at 18-24 months documents seroreversion (loss of maternal antibodies). If any PCR is positive, it should be immediately repeated and ART initiated while awaiting confirmation.

Diagnostic Challenges

Very early testing (before 48 hours) has lower sensitivity (approximately 40% for HIV DNA PCR). Sensitivity increases with age, reaching about 95% by 2 weeks and over 99% by 4-6 months. Non-B subtypes (common outside North America) may require assays that cover relevant subtypes.

Clinical Manifestations of Pediatric HIV

Without ART (Natural History)

Rapid progressors (approximately 20%) develop AIDS within the first year, presenting with Pneumocystis pneumonia, encephalopathy, and wasting, with death by age 2-3 without treatment. Typical progressors (about 60%) develop symptoms by age 3-5. Slow progressors (about 20%) remain relatively well for 5-8 or more years.

CDC Pediatric HIV Classification

The classification is based on immune status (CD4 count and percentage by age) and clinical categories. Category A is mildly symptomatic (lymphadenopathy, hepatosplenomegaly, dermatitis). Category B is moderately symptomatic (lymphoid interstitial pneumonitis, thrombocytopenia, recurrent bacterial infections, candidiasis). Category C is severely symptomatic (AIDS-defining conditions): PCP, CMV disease, MAC, wasting syndrome, encephalopathy, recurrent serious bacterial infections, and malignancy (lymphoma).

Common Opportunistic Infections

Pneumocystis jirovecii pneumonia (PCP) peaks at 3-6 months and can be the presenting illness. Prophylaxis with TMP-SMX is started at 4-6 weeks and continued until HIV is excluded or the CD4 count is adequate. CMV causes retinitis, colitis, and pneumonitis. MAC (Mycobacterium avium complex) causes disseminated disease when CD4 is severely depleted. Candidiasis manifests as oral thrush and esophageal candidiasis. Tuberculosis has high co-infection rates in endemic areas.

Antiretroviral Therapy (ART)

Principles

All children with HIV should be treated regardless of CD4 count or symptoms, per both WHO and US guidelines. ART should be started as soon as possible after diagnosis, ideally within 2 weeks of confirmed diagnosis in infants. Early ART preserves immune function, reduces morbidity and mortality, and limits the viral reservoir.

Preferred Regimens (Pediatric, US Guidelines)

For neonates under 4 weeks, the regimen is ZDV plus lamivudine plus nevirapine or raltegravir. For infants and children from 4 weeks to under 6 years, a dolutegravir-based regimen (dolutegravir plus 2 NRTIs) is used when weight-appropriate formulations are available. For children 6 years and older and adolescents, dolutegravir plus tenofovir alafenamide (TAF) plus emtricitabine (or lamivudine) is preferred. Backbone NRTIs include abacavir plus lamivudine (with HLA-B*5701 testing first due to hypersensitivity risk) or ZDV plus lamivudine as an alternative.

Monitoring

HIV viral load should be undetectable (below 50 copies/mL) within 6 months of starting ART and checked every 3-4 months. CD4 count and percentage are monitored every 3-6 months, with CD4 percentage being more reliable than absolute count in young children. Adherence is the most critical determinant of success and must be addressed at every visit. Resistance testing (genotype) is performed before starting ART and at virologic failure. Comprehensive care includes monitoring growth, development, school performance, and metabolic parameters (lipids, glucose) for ART-associated effects.

Adherence Challenges in Pediatrics

Challenges include the palatability of liquid formulations, pill burden and frequency, disclosure to the child and family or school, adolescent adherence (the highest risk group for virologic failure), and the transition from pediatric to adult care, which represents a critical vulnerability period.

<image>Pediatric HIV diagnosis timeline showing virologic testing schedule (HIV PCR at 14-21 days, 1-2 months, and 4-6 months), criteria for definitive diagnosis (2 positive PCR tests) and exclusion (2 negative PCR tests at >= 1 month and >= 4 months), confirmatory antibody testing at 18-24 months, and the recommended timing for initiating ART upon confirmed diagnosis</image>

PCP Prophylaxis

TMP-SMX prophylaxis should be started at 4-6 weeks of age for all HIV-exposed infants and continued until HIV is excluded. The dose is TMP 75 mg/m2/dose twice daily, given 3 days per week (or daily). Prophylaxis is continued in HIV-infected children based on age-specific CD4 thresholds. Alternatives for TMP-SMX-intolerant patients include dapsone and atovaquone. PCP in infancy has approximately 50% mortality without prophylaxis, making prophylaxis life-saving.

Immunizations

HIV-infected children should receive all routine vaccines with modifications. Live vaccines (MMR, varicella) can be given if CD4 is 15% or greater but should be avoided in severely immunocompromised patients. BCG is contraindicated in HIV-infected children due to the risk of disseminated BCG disease. Annual inactivated influenza vaccine, pneumococcal vaccines (PCV13 plus PPSV23), and COVID-19 vaccine per standard recommendations should all be given. Responses to vaccines may be diminished, and titers should be checked when possible.

Curative Approaches and Long-Acting ART

Broadly Neutralizing Antibodies (bNAbs)

Monoclonal antibodies targeting conserved HIV envelope epitopes have potential roles in prevention, treatment simplification, and functional cure. Clinical trials are ongoing in pediatric populations.

Long-Acting ART

Cabotegravir plus rilpivirine (Cabenuva) is an injectable regimen given every 2 months, approved for adults with pediatric trials underway. It could dramatically improve adherence in adolescents. Lenacapavir, a long-acting capsid inhibitor given every 6 months, has promising adult data.

Gene Therapy and Cure Research

Approaches include CCR5 modification through gene editing, "shock and kill" strategies, and immune-based approaches. The "Mississippi baby" and other early-treated infants demonstrated that early ART can limit the viral reservoir but does not reliably achieve cure. Research continues to define what constitutes a "functional cure" in children treated from birth.

Clinical Pearls

All pregnant women should be screened for HIV through universal opt-out screening at the first prenatal visit, as this prevents pediatric HIV. HIV antibody tests are unreliable in children under 18 months; HIV DNA or RNA PCR must always be used for infant diagnosis. PCP prophylaxis with TMP-SMX starting at 4-6 weeks is life-saving, and clinicians should not wait for HIV diagnostic results before starting prophylaxis in exposed infants. Adherence is the single most important factor in ART success and should be addressed at every visit with age-appropriate strategies. Adolescents transitioning to adult HIV care are at the highest risk for disengagement and virologic failure, making structured transition programs essential. An undetectable viral load on ART means the person effectively cannot transmit HIV sexually (U=U: Undetectable = Untransmittable), which applies to pregnant women as well.

Key Controversy: Long-Acting ART and Cure Strategies in Pediatric HIV

Long-acting injectable ART (cabotegravir-rilpivirine) has transformed adult HIV care but is not yet approved for children. Pediatric formulations and dosing studies are ongoing and could revolutionize adherence in adolescents. Broadly neutralizing antibodies (VRC01, 3BNC117) are being studied for PMTCT and as treatment in children. Cure research has shown that very early ART in neonates can limit the viral reservoir, but achieving sustained remission off ART remains elusive. Ethical considerations include the risk-benefit analysis of cure research in children and challenges related to informed consent and assent. Global equity remains a pressing concern: while high-income countries approach zero pediatric HIV, approximately 150,000 new pediatric infections occur annually in sub-Saharan Africa, where treatment access is the immediate priority.

References

• Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. NIH. Updated 2023.
• Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs During Pregnancy. NIH. Updated 2023.
• Luzuriaga K, et al. Early Combination Antiretroviral Therapy Limits HIV-1 Persistence in Children. Sci Transl Med. 2015;7(319):319ra206.
• World Health Organization. Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring. WHO. 2021.
• Persaud D, et al. Absence of Detectable HIV-1 Viremia After Treatment Cessation in an Infant (Mississippi Baby). N Engl J Med. 2013;369(19):1828-1835.

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