HIV
Introduction And Etiology
- Definition: Pediatric HIV infection is a chronic viral infection caused by the Human Immunodeficiency Virus (HIV).
- It is characterized by progressive destruction of the immune system, specifically CD4+ T lymphocytes, leading to susceptibility to opportunistic infections and malignancies.
- Virology: Belongs to the family Retroviridae and genus Lentivirus.
- Types: HIV-1 is the predominant cause of the global pediatric epidemic, whereas HIV-2 is less pathogenic, less transmissible vertically, and confined primarily to West Africa.
- Structure: It is an RNA virus containing the enzyme reverse transcriptase.
- The viral envelope contains glycoproteins gp120 (binding site for CD4) and gp41 (fusion), while the core contains p24 antigen.
- Global Burden: An estimated 1.8 to 2.78 million children worldwide live with HIV, with the vast majority in sub-Saharan Africa, and India being a significant contributor.
Transmission And Pathogenesis
Routes Of Transmission
- Vertical Transmission (Mother-to-Child Transmission - MTCT): Accounts for >90% of pediatric HIV infections.
- Intrauterine (20-30%): Occurs transplacentally, mostly in late gestation. This is suggested by positive PCR within 48 hours of birth.
- Intrapartum (70-80%): Occurs during labor and delivery via mucosal exposure to infected blood, secretions, or micro-transfusions.
- Breastfeeding (Postpartum): Accounts for 15-20% of transmission risk in untreated populations. The risk increases with mixed feeding and duration of breastfeeding.
- Other Routes: Sexual transmission is the primary mode in adolescents. Parenteral transmission via infected blood products or contaminated needles is rare due to screening. Premastication of food by an infected caregiver has rare reports of transmission.
Risk Factors For Vertical Transmission
| Category | Specific Risk Factors |
|---|---|
| Viral | High maternal viral load (most critical factor), viral genotype and phenotype |
| Maternal | Advanced disease (low CD4 count), primary infection during pregnancy or breastfeeding, lack of antiretroviral therapy (ART), sexually transmitted infections |
| Obstetric | Vaginal delivery (if viral load >1000 copies/mL), prolonged rupture of membranes (>4 hours), chorioamnionitis, preterm delivery, invasive procedures |
| Infant | Prematurity, breastfeeding, oral thrush, mixed feeding |
Pathogenesis
- Viral Entry: HIV gp120 binds to the CD4 receptor on T-lymphocytes, monocytes, and macrophages. Co-receptors (CXCR4 or CCR5) are required for fusion and entry.
- Replication: Viral RNA is reverse-transcribed into DNA, integrated into the host genome as a provirus, and transcribed to produce new virions.
- Infant Immune System: Infants have an immature immune system with higher absolute CD4 counts than adults.
- Perinatally infected infants experience very high viral loads (often >1 million copies/mL) that persist for the first 2 years.
- This unchecked replication leads to rapid CD4 depletion and early onset of symptoms.
- Immunodeficiency: Progressive loss of CD4+ T cells leads to defects in both cellular and humoral immunity.
- B-cell Dysregulation: Polyclonal hypergammaglobulinemia is common due to unregulated B-cell activation, yet functional specific antibody responses are impaired.
- Central Nervous System (CNS): HIV enters the CNS early via monocytes and macrophages, causing direct neuronal damage, inflammation, and encephalopathy.
Clinical Manifestations And Disease Progression
Patterns Of Disease Progression
- Rapid Progressors (15-25%): Associated with intrauterine infection. They present with AIDS, encephalopathy, and failure to thrive in the first few months, resulting in high mortality without treatment.
- Slow Progressors (60-80%): Median survival of 6 years or more without treatment. Often infected intrapartum, presenting with intermediate symptoms like Lymphoid Interstitial Pneumonitis (LIP) or recurrent infections.
- Long-Term Non-Progressors (<5%): Remain asymptomatic with normal CD4 counts and low viral loads for >8 years without therapy.
Systemic Manifestations
| System | Key Clinical Features |
|---|---|
| General | Failure to thrive, generalized lymphadenopathy, hepatosplenomegaly, persistent fever, chronic diarrhea, parotitis |
| Respiratory | Pneumocystis jirovecii Pneumonia (PJP) (peaks at 3-6 months), Lymphoid Interstitial Pneumonitis (LIP), Tuberculosis (TB) |
| Neurologic | HIV Encephalopathy (progressive corticospinal tract signs, loss of milestones, acquired microcephaly), seizures, meningitis |
| Gastrointestinal | Chronic diarrhea, oral/esophageal candidiasis, malabsorption, HIV enteropathy |
| Dermatologic | Severe seborrheic dermatitis, recalcitrant fungal infections, molluscum contagiosum, scabies, herpes zoster |
| Other | Dilated cardiomyopathy, left ventricular dysfunction, HIV-associated nephropathy (nephrotic syndrome), cytopenias |
Classification And Staging
WHO Clinical Staging
| Stage | Clinical Criteria |
|---|---|
| Stage 1 | Asymptomatic, persistent generalized lymphadenopathy (PGL) |
| Stage 2 | Mild symptoms (hepatosplenomegaly, papular pruritic eruptions, fungal nail infections, angular cheilitis, extensive molluscum, herpes zoster, recurrent URI) |
| Stage 3 | Advanced symptoms (moderate malnutrition, persistent diarrhea/fever, oral candidiasis >2 months, oral hairy leukoplakia, pulmonary TB, LIP, severe bacterial pneumonia) |
| Stage 4 | Severe symptoms (severe wasting, PJP, recurrent severe bacterial infections, chronic HSV, esophageal candidiasis, extrapulmonary TB, Kaposi sarcoma, HIV encephalopathy, CNS toxoplasmosis) |
Immunologic Classification (CDC)
| Suppression Level | CD4 Percentage | Infant (<1 year) Absolute CD4 Count |
|---|---|---|
| No Suppression | >25% | >1500 |
| Moderate Suppression | 15-24% | 750-1499 |
| Severe Suppression (AIDS) | <15% | <750 |
Diagnosis
Infants <18 Months
- Antibody tests (ELISA) are not diagnostic due to transplacental transfer of maternal IgG.
- Test of Choice: HIV DNA PCR (proviral DNA) or HIV RNA PCR (viral load).
- Testing Schedule: Within 48 hours for high-risk infants, and routine testing at 6 weeks for all exposed infants.
- Confirmation: A positive PCR must be confirmed with a second sample.
- Exclusion of Infection: Requires two negative PCRs (one at ≥1 month and one at ≥4 months). Breastfed infants require repeat testing 6 weeks to 6 months after cessation of breastfeeding.
Children >18 Months
- Diagnosis relies on HIV Antibody tests (ELISA/Rapid tests).
- Confirmation requires a Western Blot or a second/third distinct ELISA/Rapid test.
Management
Antiretroviral Therapy (ART)
- Initiation: A Treat All Policy is adopted. ART should be initiated in all HIV-infected children regardless of clinical stage or CD4 count.
Recommended Regimens (WHO/NACO)
| Age/Weight Group | Preferred Regimen |
|---|---|
| Neonates (<4 weeks) | Zidovudine (AZT) + Lamivudine (3TC) + Nevirapine (NVP) (or Raltegravir) |
| Children <20 kg (<6 years) | Abacavir (ABC) + 3TC + Lopinavir/ritonavir (LPV/r) (or Dolutegravir if age/weight appropriate) |
| Children 20-30 kg (6-10 years) | ABC + 3TC + Dolutegravir (DTG) |
| Children >30 kg (>10 years) | Tenofovir (TDF) + 3TC + DTG (TLD regimen) |
Monitoring
- Virologic: Check viral load at 6 months, then every 6-12 months. The goal is <50 copies/mL (undetectable).
- Immunologic: Monitor CD4 count every 6 months.
- Clinical: Monitor growth, development, and signs of opportunistic infections or drug toxicity.
Supportive Care And Immunization
- Nutrition: Aggressive management of malnutrition and vitamin supplementation is required.
- Live Vaccines: BCG, OPV, MMR, and Varicella are generally contraindicated in severe immunosuppression (CD4 <15%).
- BCG should be given at birth to asymptomatic exposed infants but is contraindicated in symptomatic HIV-infected infants.
- MMR/Varicella are safe in children with CD4 >15%.
- Inactivated Vaccines: Safe and strongly recommended, including Pneumococcal, Hib, Influenza, Meningococcal, Hepatitis B, and HPV vaccines.
Prophylaxis For Opportunistic Infections
| Infection | Drug | Indication |
|---|---|---|
| Pneumocystis (PJP) | Cotrimoxazole | All exposed infants starting at 4-6 weeks until infection is excluded. All infected infants <1 year, and children >1 year if CD4 <15% or symptomatic. |
| Tuberculosis (TB) | Isoniazid Preventive Therapy | All HIV-infected children >12 months without active TB. |
| Mycobacterium Avium Complex (MAC) | Azithromycin or Clarithromycin | Children with severe immunosuppression (CD4 <50-75 cells/uL). |
Prevention Of HIV
Prevention Of Mother-To-Child Transmission (PMTCT)
- Vertical transmission without intervention ranges from 15% to 45%. Effective interventions reduce this to less than 2%.
Antenatal Interventions
- Universal Screening: All pregnant women should be tested early, with repeat testing in the third trimester for high-risk populations.
- Maternal ART: Adopt Treat All Policy. Lifelong combination ART should be initiated immediately regardless of CD4 count.
- Viral Suppression: Maintaining a maternal viral load <1,000 copies/mL near delivery is the most critical preventative factor.
- Recommended Regimen: Fixed-dose combination of Tenofovir (TDF) + Lamivudine (3TC) + Dolutegravir (DTG) once daily.
Intrapartum Interventions
- Mode of Delivery: Vaginal delivery is safe if the mother is on effective ART with suppressed viral load (<1,000 copies/mL).
- Elective Cesarean Section is recommended at 38 weeks for women with viral load >1,000 copies/mL or unknown viral load.
- Obstetric Management: Avoid artificial rupture of membranes, fetal scalp monitoring, instrumental delivery, and routine episiotomy.
Infant Antiretroviral Prophylaxis
| Infant Risk Category | Prophylactic Regimen | Duration |
|---|---|---|
| Low-Risk (Mother on ART, viral load <1000) | Daily Nevirapine (NVP) or twice-daily Zidovudine (AZT) | Typically 6 weeks |
| High-Risk (No maternal ART, unsuppressed viral load) | Option A: AZT + NVP. Option B (Presumptive Therapy): Zidovudine + Lamivudine + Nevirapine (or Raltegravir) | Minimum 6 weeks, extended up to 12 weeks or throughout breastfeeding |
Infant Feeding Practices
- Resource-Rich Settings: Replacement feeding (formula) is recommended to eliminate postnatal transmission.
- Resource-Limited Settings: Exclusive Breastfeeding (EBF) is recommended for the first 6 months as formula feeding lacks AFASS criteria (Affordable, Feasible, Acceptable, Sustainable, Safe).
- Maternal ART must continue to maintain viral suppression.
- Mixed feeding must be strictly avoided as it damages the gut lining and increases transmission risk.
- Weaning should be gradual over 2-4 weeks around 12 months.
Prevention Of Sexual Transmission In Adolescents
- Behavioral Interventions: Comprehensive sex education and consistent condom use.
- Biomedical Interventions: Pre-exposure Prophylaxis (PrEP) using daily oral Tenofovir + Emtricitabine is approved for high-risk adolescents weighing >35 kg. Male circumcision reduces acquisition risk by 50-60%. Treatment as Prevention (TasP) eliminates transmission risk when the partner has an undetectable viral load.
Post-Exposure Prophylaxis (PEP)
- Indication: Percutaneous injury, mucous membrane exposure, or sexual assault.
- Timing: Initiate within 24-72 hours of exposure.
- Regimen: A three-drug regimen for 28 days.
- Follow-up: HIV testing at baseline, 4-6 weeks, and 3 months post-exposure.