Antiretroviral Therapy

A single missed dose of antiretrovirals doesn't just skip treatment — it hands HIV a blueprint for resistance. Understanding HAART principles explains why adherence is the entire ballgame.

Highly Active Antiretroviral Therapy (HAART) uses a combination of at least three drugs from at least two different classes to suppress HIV replication to undetectable levels (viral load <200 copies/mL). The rationale for combination therapy is resistance prevention: HIV mutates rapidly, and using a single agent allows resistant strains to emerge within days. Multiple drugs targeting different steps in the viral life cycle — reverse transcription, integration, protease-mediated maturation, viral entry — make it exponentially harder for the virus to develop simultaneous resistance mutations. HAART does not cure HIV; it suppresses viral replication so the immune system can recover, reflected by a rising CD4 count. Treatment is initiated at diagnosis regardless of CD4 count per current guidelines. The goal is an undetectable viral load within 3–6 months. Adherence must exceed 95% to maintain suppression — missing more than one dose per month of a once-daily regimen drops below this threshold. The nurse monitors two key labs: CD4 count (immune function, goal >500 cells/mm³) and viral load (treatment effectiveness, goal undetectable).

Key Distinctions

Don't confuse HAART principles (why combination therapy, adherence rationale, treatment goals) with individual drug class side effects — that's the sibling atom. Students often think HAART is started only when CD4 drops below a threshold; current guidelines recommend starting at diagnosis. Undetectable viral load does NOT mean cured — the patient remains HIV-positive and must continue therapy lifelong.

Clinical Pearl

Three drugs, two classes, one goal: undetectable. If adherence drops below 95%, resistance wins — and you lose drug options permanently.

Drug Classes & Side Effects

NRTIs (zidovudine, tenofovir, lamivudine) carry a class-wide risk of lactic acidosis from mitochondrial toxicity; watch for unexplained tachypnea, fatigue, and rising lactate. Zidovudine specifically causes bone marrow suppression — monitor CBC for anemia and neutropenia. Tenofovir is nephrotoxic and decreases bone density; track serum creatinine, BUN, and phosphorus. NNRTIs (efavirenz, nevirapine) cause vivid CNS effects (dizziness, vivid dreams, mood changes) — advise taking efavirenz at bedtime. Nevirapine carries a hepatotoxicity risk requiring LFT monitoring, especially in the first 18 weeks. Protease inhibitors (atazanavir, lopinavir/ritonavir) produce metabolic syndrome: hyperglycemia, hyperlipidemia, lipodystrophy (fat redistribution), and GI distress. Monitor fasting glucose and lipid panels. Atazanavir causes indirect hyperbilirubinemia with visible jaundice that is benign but alarming to patients — teach them it is expected. Integrase inhibitors (raltegravir, dolutegravir) are generally well tolerated; raltegravir can elevate creatine kinase — report unexplained muscle pain. Dolutegravir may raise serum creatinine by inhibiting tubular secretion, not from true kidney damage. Across all classes, teach adherence: missing doses promotes resistance, which is irreversible.

Key Distinctions

Don't confuse NRTI lactic acidosis (metabolic, rising lactate, tachypnea) with a simple GI complaint — it can be fatal. Students mix up tenofovir nephrotoxicity with amphotericin B nephrotoxicity; both damage kidneys but belong to entirely different drug classes. Lipodystrophy is a protease inhibitor hallmark, not an NRTI effect — the fat redistribution pattern (buffalo hump, truncal obesity, facial wasting) points to PIs specifically.

Clinical Pearl

Match the class to its organ target: NRTIs hit mitochondria (marrow, kidneys), NNRTIs hit the brain and liver, PIs hit metabolism (glucose, lipids, fat). Class → organ → lab.