Mechanism of Action

Highly Active Antiretroviral Therapy (HAART) combines at least three drugs from at least two classes to suppress HIV replication to undetectable levels. Each class blocks a different step of the viral life cycle — reverse transcription (NRTIs, NNRTIs), integration (integrase inhibitors), and protease-mediated maturation (protease inhibitors) — so the rapidly mutating virus cannot develop simultaneous resistance to all agents. HAART suppresses but does not cure: it lets the immune system recover (rising CD4) while viral load falls. Therapy is lifelong and started at diagnosis regardless of CD4.

Common Medications

tenofovirPrototype

NRTI backbone; TDF nephrotoxic/lowers bone density, TAF safer

emtricitabine

NRTI; common backbone partner

zidovudine

NRTI; bone-marrow suppression

lamivudine

NRTI

efavirenz

NNRTI; CNS effects, dose at bedtime

nevirapine

NNRTI; hepatotoxicity risk first 18 weeks

atazanavir

protease inhibitor; benign indirect hyperbilirubinemia

lopinavir/ritonavir

protease inhibitor; ritonavir is a boost

dolutegravir

integrase inhibitor; raises creatinine w/o true kidney damage

raltegravir

integrase inhibitor; can elevate creatine kinase

Indications

HIV infection

treat all clients at diagnosis regardless of CD4 count

maintain undetectable viral load

goal <200 copies/mL, ideally undetectable, within 3–6 months

immune reconstitution

rising CD4 count toward goal >500 cells/mm³

Side Effects

bone marrow suppression

zidovudine — anemia, neutropenia; monitor CBC

vivid dreams

efavirenz CNS effect; dose at bedtime

dizziness

efavirenz (NNRTI) CNS effect

hyperglycemia

protease inhibitor metabolic syndrome

hyperlipidemia

protease inhibitor; monitor fasting lipid panel

lipodystrophy Hallmark

protease inhibitor hallmark — buffalo hump, truncal obesity, facial wasting

indirect hyperbilirubinemia

atazanavir; benign jaundice — teach it is expected, NOT hepatotoxicity

GI distress

protease inhibitors

Contraindications & Interactions

Contraindications

monotherapy

never a single agent — promotes irreversible resistance; ≥3 drugs/≥2 classes always

stopping therapy when undetectable

virus persists in latent reservoirs; rebound + resistance — therapy is lifelong

Interactions

concurrent nephrotoxic drugs

compound tenofovir renal risk

other QT-prolonging or CYP-interacting drugs

ritonavir-boosted PIs are potent CYP inhibitors — check interactions

Administration & Monitoring

monitor CD4 count

immune status marker; goal >500 cells/mm³

monitor viral load

treatment-effectiveness marker; goal undetectable within 3–6 months

monitor serum creatinine and BUN

tenofovir nephrotoxicity surveillance

monitor serum phosphorus

tenofovir proximal tubular toxicity

monitor CBC

zidovudine bone-marrow suppression

monitor LFTs

nevirapine hepatotoxicity, especially first 18 weeks

monitor fasting glucose and lipids

protease inhibitor metabolic effects

assess adherence each visit

must exceed 95% to maintain suppression

Patient Teaching

take every dose, never skip

>95% adherence required; one missed dose can breed resistance

therapy is for life

undetectable means suppressed, not cured; you remain HIV-positive

take efavirenz at bedtime

minimizes dizziness and vivid dreams

report yellowing of skin or eyes

possible hepatotoxicity — but atazanavir jaundice is expected and benign

report unexplained rapid breathing or fatigue

possible NRTI lactic acidosis

report muscle pain

raltegravir creatine-kinase elevation

undetectable = untransmittable

U=U; sustained suppression prevents sexual transmission

do not stop even when feeling well

Report Nowescalate immediately

lactic acidosis Hallmark

NRTI mitochondrial toxicity; unexplained tachypnea, fatigue, rising lactate — can be fatal

tenofovir nephrotoxicityrising creatinine

TDF proximal tubular toxicity; proteinuria, glycosuria with normal glucose, GFR decline — switch TDF→TAF

nevirapine hepatotoxicity

highest risk first 18 weeks; rising LFTs, jaundice — distinguish from benign atazanavir jaundice

immune reconstitution inflammatory syndrome

IRIS 2–12 wks after start; paradoxical worsening of opportunistic infection (e.g. TB) — continue ART, treat infection

Clinical Pearl

Three drugs, two classes, one goal: undetectable. Match the class to its organ — NRTIs hit mitochondria (marrow, kidneys), NNRTIs the brain and liver, PIs metabolism (glucose, lipids, fat). If adherence drops below 95%, resistance wins and you lose drug options permanently.