Antiretroviral Therapy
Key Points
- Antiretroviral therapy (ART) suppresses HIV replication by targeting multiple steps of the HIV life cycle using combination regimens.
- Adherence is critical — nonadherence leads to viral resistance and treatment failure.
- First-line regimens typically include 2 NRTIs + an integrase strand transfer inhibitor (INSTI).
- Goals of therapy: undetectable viral load and CD4 count ≥500 cells/mm³.
- ART does not cure HIV but prevents AIDS-defining illnesses and viral transmission.
Pathophysiology
HIV targets CD4 T lymphocytes (helper T cells). The virus binds to the CD4 receptor, enters the cell, and uses reverse transcriptase to convert viral RNA to DNA. Integrase incorporates viral DNA into host DNA, and protease cleaves viral proteins to produce mature viral particles.
As CD4 cells are progressively destroyed, the immune system becomes increasingly compromised. When the CD4 count drops below 200 cells/mL, the patient is diagnosed with AIDS and is at high risk for opportunistic infections (e.g., PCP, CMV, Kaposi’s sarcoma).
HIV Stages
| Stage | Characteristics |
|---|---|
| Acute HIV | High viral load; flu-like symptoms; highly infectious |
| Chronic HIV (Clinical Latency) | Asymptomatic; viral replication continues; transmissible |
| AIDS | CD4 <200 cells/mL; opportunistic infections; high viral load |
ART Drug Classes and Mechanisms
| Drug Class | Mechanism | Examples |
|---|---|---|
| NRTI (Nucleoside RT inhibitors) | Chain terminators — block DNA elongation by reverse transcriptase | Tenofovir, abacavir, zidovudine |
| NNRTI (Non-nucleoside RT inhibitors) | Directly bind to reverse transcriptase to alter its shape | Efavirenz, rilpivirine, etravirine |
| Protease inhibitors (PI) | Block protease enzyme → immature, non-infectious viral particles | Atazanavir, darunavir, ritonavir |
| Integrase inhibitors (INSTI) | Block viral DNA integration into host DNA | Dolutegravir, raltegravir, elvitegravir |
| Fusion inhibitors | Prevent HIV fusion with CD4 cell membrane | Enfuvirtide (SC injection; reserved for resistant HIV) |
| CCR5 antagonists | Block CCR5 coreceptor used by HIV to enter cells | Maraviroc |
| Pharmacokinetic boosters | Inhibit CYP3A4 to increase ART blood levels | Cobicistat, ritonavir |
Nursing Assessment
NCLEX Focus
Adherence monitoring is the highest-priority nursing intervention. A missed dose can allow viral replication and resistance. Assess for barriers to adherence at every visit.
- Monitor viral load — goal: undetectable (<20–50 copies/mL) with effective therapy.
- Monitor CD4 count — goal ≥500 cells/mm³; <200 = AIDS, high opportunistic infection risk.
- Assess hepatic function: multiple ART drugs cause hepatotoxicity.
- Assess for GI side effects: nausea, vomiting, diarrhea are common with many ART agents.
- Monitor lipid panel and blood glucose — protease inhibitors cause dyslipidemia and glucose intolerance.
- Assess for peripheral neuropathy (older NRTIs: zidovudine, didanosine).
- Screen for lactic acidosis symptoms (NRTI-associated): muscle cramps, abnormal heartbeat, abdominal pain.
- Screen for HLA-B*5701 before abacavir — positive result contraindicates use (anaphylaxis risk).
Nursing Interventions
- Emphasize lifelong adherence: missed doses → resistance → treatment failure.
- Instruct to take medications at consistent times with or without food (varies by agent).
- Monitor for immune reconstitution inflammatory syndrome (IRIS) — paradoxical worsening of symptoms when ART is started; occurs as immune system recovers and mounts an inflammatory response.
- Teach injection technique if patient is using enfuvirtide (SC injection).
- Educate on transmission prevention: condom use, clean needle programs, and treatment as prevention (undetectable viral load = essentially non-infectious).
- Monitor for drug-drug interactions — especially CYP3A4 interactions with ritonavir/cobicistat.
Abacavir Hypersensitivity
Screen for HLA-B5701 allele before starting abacavir. Presence of HLA-B5701 significantly increases risk of life-threatening hypersensitivity reaction. Do NOT restart abacavir after a hypersensitivity reaction.
Pharmacology
| Combination Product | Drugs | Notes |
|---|---|---|
| Bictegravir/TAF/emtricitabine (Biktarvy) | INSTI + 2 NRTIs | Common first-line once-daily; high resistance barrier |
| Dolutegravir/rilpivirine (Juluca) | INSTI + NNRTI | 2-drug regimen; once-daily; food required |
| Tenofovir/emtricitabine (Truvada) | 2 NRTIs | Core NRTI backbone; also used for PrEP |
Clinical Judgment Application
Clinical Scenario
A patient with HIV on antiretroviral therapy has a recent viral load of 2,500 copies/mL (was undetectable 3 months ago). The patient admits to often missing weekend doses.
- Recognize Cues: Detectable viral load in a patient with known adherence issues.
- Analyze Cues: Nonadherence is likely causing viral rebound and could lead to drug resistance.
- Prioritize Hypotheses: Viral resistance development is the highest priority concern.
- Generate Solutions: Assess barriers to adherence; explore simplifying regimen or reminder systems.
- Take Action: Provide non-judgmental adherence counseling; coordinate pharmacy and social work support.
- Evaluate Outcomes: Viral load returns to undetectable with consistent adherence.
Related Concepts
- hiv — Pathophysiology, stages, and nursing care for HIV/AIDS.
- immune-system — CD4 T cell role in adaptive immunity and HIV immunosuppression.
- active-and-passive-immunity — Immunosuppression as a risk factor for opportunistic infections.
- antibiotics — Prophylactic antibiotics for opportunistic infection prevention in AIDS.
- infection-control — Transmission-based precautions for opportunistic infections.
Self-Check
- What is the goal viral load for a patient on effective antiretroviral therapy?
- Why is combination therapy with multiple drug classes required rather than using one drug alone?
- Which genetic screening test must be performed before prescribing abacavir, and why?