Perinatal HIV

Approach to HIV

Introduction

The management of infants born to HIV-seropositive mothers involves a dual approach: minimizing the risk of vertical transmission (prevention) and early identification and treatment of those who acquire the infection. Vertical transmission is the primary route of HIV infection in children.

Transmission and Risk Factors

Transmission can occur during pregnancy (intrauterine), labor and delivery (intrapartum), or through breastfeeding (postpartum). Without intervention, transmission rates range from 15% to 45%.

Modes of Transmission

• Intrauterine (20–30%): Occurs transplacentally, mostly in late gestation. Suggested by positive PCR within 48 hours of birth.
• Intrapartum (70–80%): Occurs through mucosal exposure to infected blood and secretions during delivery or micro-transfusions during labor. Suggested by negative PCR at birth but positive at 1–2 weeks.
• Postpartum: Transmission through breast milk accounts for a significant proportion of infections in resource-limited settings.

Risk Factors for Vertical Transmission

• Viral Factors: High maternal viral load (most important factor), advanced clinical disease, low CD4 count.
• Obstetric Factors: Vaginal delivery (if viral load is high), prolonged rupture of membranes (>4 hours), chorioamnionitis, preterm delivery.
• Infant/Postnatal Factors: Breastfeeding, mixed feeding (breast milk + other liquids/solids), oral thrush in the infant.

Diagnosis of HIV in Infants

Standard antibody tests (ELISA) are not diagnostic in infants <18 months due to the persistence of passively transferred maternal IgG antibodies. Diagnosis relies on virologic assays.

Virologic Testing (DNA or RNA PCR)

• Method: HIV DNA PCR (detects proviral DNA) or HIV RNA PCR (detects viral load) are the gold standards.
• Testing Schedule:
  • Birth: Recommended for high-risk infants to detect intrauterine infection.
  • 4–6 Weeks: Routine testing for all exposed infants.
  • 4–6 Months: Repeat testing to detect intrapartum or early breastfeeding transmission.
  • Post-weaning: For breastfed infants, testing is required 6 weeks to 6 months after cessation of breastfeeding.
• Definitive Infection: Confirmed by two positive virologic tests on separate samples.
• Exclusion of Infection:
  • Two negative virologic tests: one at ≥1 month and one at ≥4 months of age.
  • Negative antibody test at >18 months.

Management of the HIV-Exposed Infant

The immediate goal is to prevent the establishment of infection using antiretroviral (ARV) prophylaxis and to prevent opportunistic infections like Pneumocystis jirovecii pneumonia (PCP).

1. Antiretroviral Prophylaxis (prevention of MTCT)

Prophylaxis strategies depend on the infant's risk categorization.

• Low-Risk Infants: Born to mothers on ART with suppressed viral load (<1,000 copies/mL) near delivery.
  • Regimen: Daily Nevirapine (NVP) or twice-daily Zidovudine (AZT).
  • Duration: Typically 6 weeks (some guidelines allow 4 weeks if mother suppressed >4 weeks before delivery).
• High-Risk Infants: Born to mothers with unsuppressed viral load, no antenatal ART, or primary infection during pregnancy/breastfeeding.
  • Regimen: Combination prophylaxis is recommended to act as presumptive treatment.
    • Option A: AZT + NVP (dual prophylaxis) for 6–12 weeks.
    • Option B: AZT + Lamivudine (3TC) + NVP (triple prophylaxis) for 6 weeks.
  • Duration: At least 6 weeks, often extended to 12 weeks for breastfed infants.

2. Cotrimoxazole Prophylaxis

• Rationale: To prevent PCP, which has high mortality in HIV-infected infants, peaking at 3–6 months of age.
• Indication: All HIV-exposed infants starting at 4–6 weeks of age.
• Dose: Trimethoprim/Sulfamethoxazole (TMP-SMX) 150/750 mg/m² or approx 5 mg/kg TMP daily or 3 days/week.
• Duration: Continue until HIV infection is definitively excluded (typically 18 months or after cessation of breastfeeding with negative testing).

3. Infant Feeding

• Resource-Rich Settings: Formula feeding is recommended to eliminate the risk of postnatal transmission.
• Resource-Limited Settings:
  • Exclusive Breastfeeding (EBF): Recommended for the first 6 months if formula is not Affordable, Feasible, Acceptable, Sustainable, and Safe (AFASS).
  • Conditions: The mother must be on effective ART. Mixed feeding should be strictly avoided as it increases transmission risk.
  • Weaning: Should be gradual over 1 month around 12 months of age (or up to 24 months per WHO), ensuring adequate complementary foods.

4. Immunization

• Standard Vaccines: Administer according to the national schedule.
• Live Vaccines:
  • BCG: WHO recommends BCG at birth for asymptomatic HIV-exposed infants in endemic areas. It should not be given to symptomatic HIV-infected infants due to risk of disseminated BCG disease.
  • OPV: Generally contraindicated in known HIV-infected children (IPV preferred), but often given in endemic areas to exposed infants.
  • MMR & Varicella: Contraindicated in severe immunosuppression (CD4 <15%), but recommended for asymptomatic or mildly symptomatic children.

Clinical Manifestations of HIV Infection in Infants

If transmission occurs, the disease course in infants is often more aggressive than in adults due to an immature immune system.

Patterns of Progression

• Rapid Progressors (15–25%): Associated with intrauterine infection. Present with AIDS-defining illnesses, encephalopathy, and failure to thrive in the first few months. High mortality without treatment.
• Slow Progressors (60–80%): Median survival of 6 years or more without treatment. Often infected intrapartum.

Common Clinical Findings

• General: Failure to thrive, lymphadenopathy, hepatosplenomegaly, chronic parotitis.
• Infections:
  • Bacterial: Recurrent pneumonia, sepsis, otitis media.
  • Fungal: Persistent oral candidiasis (thrush) beyond 6 weeks of age, esophageal candidiasis.
  • Viral: CMV retinitis or pneumonitis, persistent HSV, Varicella.
  • Opportunistic: Pneumocystis jirovecii pneumonia (PCP) is the most common AIDS-defining illness in infants. Lymphoid Interstitial Pneumonitis (LIP) is a chronic lung disease specific to pediatric HIV.
• Neurologic: HIV encephalopathy (loss of milestones, acquired microcephaly, motor deficits).

Treatment of HIV-Infected Infants

• Initiation: Universal ART is recommended for all HIV-infected infants <1 year of age immediately upon diagnosis, regardless of CD4 count or clinical stage, to reduce mortality.
• Regimens:
  • First-line: Two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) + one Integrase Strand Transfer Inhibitor (INSTI) or Protease Inhibitor (PI) or Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI).
  • Preferred: Zidovudine (AZT) or Abacavir (ABC) + Lamivudine (3TC) + Lopinavir/Ritonavir (LPV/r) or Dolutegravir (DTG) (where approved for age/weight). Nevirapine-based regimens are less preferred for infants with prior NVP exposure due to resistance.
• Monitoring: Regular assessment of growth, neurodevelopment, viral load, and CD4 counts is essential to monitor response and adherence.