ART in HIV

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%.

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.

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.

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.

Virological Failure: Plasma viral load remains $\geq$ 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.

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.

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.