Principles Of Therapy
- Antiretroviral therapy transforms pediatric HIV from a rapidly fatal disease into a manageable chronic condition.
- Primary goals include maximal plasma viral load suppression, immune function restoration, morbidity reduction, and normal growth.
- Combination therapy strictly utilizes at least three drugs from at least two different classes to prevent viral resistance.
- A universal treat-all policy mandates therapy initiation in all infected children regardless of clinical stage or CD4 count.
- Early initiation significantly reduces mortality, particularly in infants younger than one year.
- Treatment success strictly requires adherence exceeding 90% to 95%.
Classes Of Antiretroviral Drugs
| Drug Class | Mechanism Of Action | Key Examples |
|---|---|---|
| Nucleoside Reverse Transcriptase Inhibitors | Act as chain terminators during viral DNA synthesis; serve as the dual backbone of first-line regimens. | Zidovudine, Lamivudine, Abacavir, Tenofovir. |
| Non-Nucleoside Reverse Transcriptase Inhibitors | Bind directly to reverse transcriptase enzyme; possess a low genetic barrier to resistance. | Nevirapine, Efavirenz. |
| Protease Inhibitors | Inhibit viral protease, preventing virion maturation; exhibit a high genetic barrier to resistance. | Lopinavir/ritonavir, Atazanavir/ritonavir. |
| Integrase Strand Transfer Inhibitors | Prevent integration of viral DNA into the host genome; possess a high barrier to resistance. | Dolutegravir, Raltegravir. |
Recommended First-Line Regimens
Regimen selection is strictly stratified by age and weight.
| Age And Weight Category | Preferred Regimen |
|---|---|
| Neonates (< 4 Weeks) | Zidovudine + Lamivudine + Nevirapine (Or Raltegravir). |
| Children < 6 Years And < 20 kg | Abacavir + Lamivudine + Lopinavir/ritonavir. |
| Children 6 To 10 Years And 20 To 30 kg | Abacavir + Lamivudine + Dolutegravir. |
| Adolescents > 10 Years And > 30 kg | Tenofovir + Lamivudine + Dolutegravir. |
Monitoring Protocol
- Clinical Monitoring: Assess growth, developmental milestones, adherence, and opportunistic infections at every visit.
- Viral Load: Targets undetectable levels (<50 copies/mL). Monitored at baseline, 6 months, 12 months, and annually.
- CD4 Count: Monitored at baseline and every 6 months to guide opportunistic infection prophylaxis.
Treatment Failure Definitions
- Virological Failure: Plasma viral load remains $\ge$ 1000 copies/mL after at least 6 months of compliant therapy.
- Immunological Failure: Persistent decline in CD4 count or percentage.
- Clinical Failure: New or recurrent WHO Stage 3 or 4 events or neuro-regression after 6 months of therapy.
Common Adverse Effects
| Drug | Key Adverse Effects |
|---|---|
| Zidovudine | Anemia, neutropenia, lactic acidosis. |
| Abacavir | Severe hypersensitivity reaction; requires HLA-B*5701 screening if possible. |
| Tenofovir | Renal toxicity, decreased bone mineral density. |
| Nevirapine | Hepatotoxicity, severe Stevens-Johnson syndrome rash. |
| Lopinavir/ritonavir | Metabolic syndrome, diarrhea, lipodystrophy. |
Special Clinical Situations
- Tuberculosis Co-Infection: Rifampicin potently induces CYP450 enzymes, reducing antiretroviral levels.
- Dolutegravir dosing must be doubled to twice daily during tuberculosis treatment.
- Lopinavir/ritonavir requires super-boosting by increasing the ritonavir ratio to 1:1.
- Immune Reconstitution Inflammatory Syndrome: Paradoxical worsening of pre-existing infections post-initiation requires continuing antiretroviral therapy and treating the underlying infection.