Antiretroviral Drugs (ARVs) – The discovery of antiretroviral therapy (ART) transformed HIV infection from a fatal disease into a manageable chronic condition. Antiretroviral drugs (ARVs) suppress the replication of the Human Immunodeficiency Virus (HIV)—a virus that attacks the immune system, particularly CD4+ T cells, leading to Acquired Immunodeficiency Syndrome (AIDS).
This comprehensive guide explains how antiretroviral medications work, the different classes (with focus on NRTIs), their mechanisms, side effects, drug interactions, and key nursing considerations.
What Are Antiretroviral Drugs?
Antiretrovirals (ARVs) are medications that prevent HIV from multiplying in the body. By reducing viral load, these drugs:
- Preserve immune function.
- Delay disease progression.
- Reduce the risk of HIV transmission to others.
The goal of ART is viral suppression—maintaining HIV levels so low that they become undetectable in the blood.
Classes of Antiretroviral Drugs
There are six main classes of antiretroviral drugs, each targeting a different stage of the HIV life cycle.
| Class | Example Drugs | Mechanism of Action |
|---|---|---|
| 1. NRTIs (Nucleoside/Nucleotide Reverse Transcriptase Inhibitors) | Zidovudine, Lamivudine, Abacavir, Tenofovir | Block viral DNA synthesis by mimicking nucleotides |
| 2. NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors) | Efavirenz, Nevirapine, Delavirdine | Directly inhibit reverse transcriptase enzyme |
| 3. PIs (Protease Inhibitors) | Ritonavir, Lopinavir, Indinavir | Block viral protease, preventing protein cleavage |
| 4. INSTIs (Integrase Strand Transfer Inhibitors) | Raltegravir, Dolutegravir | Block integration of viral DNA into host genome |
| 5. Fusion Inhibitors | Enfuvirtide | Prevent viral fusion with host cell membrane |
| 6. Entry (CCR5) Inhibitors | Maraviroc | Block viral entry by targeting the CCR5 receptor |
Combination therapy using drugs from different classes is known as Highly Active Antiretroviral Therapy (HAART).
NRTIs: The Foundation of HIV Therapy
Among all classes, NRTIs (Nucleoside Reverse Transcriptase Inhibitors) are considered the backbone of ART.
These include:
- Zidovudine (AZT)
- Didanosine (ddI)
- Stavudine (d4T)
- Lamivudine (3TC)
- Abacavir (ABC)
- Tenofovir (TDF)
Zidovudine (AZT): The Prototype NRTI
Class
Pharmacologic (P): Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Therapeutic (T): AntiretroviralRoutes of Administration
- PO (Oral)
- IV (Intravenous)
Uses
- Treatment of HIV infection in adults and children.
- Prevention of mother-to-child transmission of HIV during pregnancy, labor, and postpartum.
- Post-Exposure Prophylaxis (PEP) after accidental HIV exposure.
Mechanism of Action (MOA)
Zidovudine acts by inhibiting the reverse transcriptase enzyme, which converts viral RNA into DNA.
- It mimics natural nucleosides and is incorporated into the viral DNA chain.
- Once incorporated, it terminates chain elongation, halting viral replication.
Thus, Zidovudine effectively reduces viral multiplication and helps maintain immune function.
Adverse Effects – “FLINGS” Mnemonic
To remember the side effects of Zidovudine, use FLINGS:
| Letter | Effect | Description |
|---|---|---|
| F | Fatty Liver (Hepatomegaly) | Enlargement of the liver due to fat accumulation |
| L | Lactic Acidosis | Accumulation of lactic acid leading to metabolic imbalance |
| I | Insomnia | Difficulty sleeping |
| N | Nausea | Common gastrointestinal symptom |
| G | GI Discomfort | Diarrhea, abdominal cramps |
| S | Suppressed Bone Marrow | Anemia, leukopenia, and fatigue |
Black Box Warning
Zidovudine carries a black box warning for:
- Severe bone marrow suppression (leading to anemia or neutropenia).
- Myopathy with prolonged use.
Drug Interactions
| Interacting Drug | Effect |
|---|---|
| Probenecid, Valproic Acid, Methadone | ⬆️ Zidovudine levels (increased toxicity risk) |
| Clarithromycin, Phenytoin, Orlistat | ⬇️ Zidovudine levels (reduced effectiveness) |
Avoid combining with other bone marrow-suppressing agents unless absolutely necessary.
Contraindications
Zidovudine should not be used in patients with:
- Bone marrow suppression
- Hepatomegaly or hepatitis
- History of lactic acidosis
Other Common NRTIs
| Drug | Notable Effects | Important Notes |
|---|---|---|
| Didanosine (ddI) | Pancreatitis, neuropathy | Take on empty stomach |
| Stavudine (d4T) | Peripheral neuropathy, lipoatrophy | Avoid with zidovudine |
| Lamivudine (3TC) | Well-tolerated | Used for both HIV & Hepatitis B |
| Abacavir (ABC) | Hypersensitivity reaction | Test for HLA-B*5701 before use |
| Tenofovir (TDF) | Renal toxicity, bone loss | Use cautiously in renal disease |
Mechanism of Combination Therapy (HAART)
HIV mutates rapidly, leading to drug resistance if treated with a single medication. Therefore, combination therapy is essential.
Standard HAART Regimen
2 NRTIs + 1 drug from another class (usually an NNRTI, PI, or INSTI).Example:
Tenofovir + Lamivudine + Dolutegravir (TLD regimen – WHO-recommended).
This combination:
- Maximizes viral suppression.
- Reduces resistance.
- Improves immune recovery.
Monitoring and Nursing Considerations
1. Monitor CBC: Check for anemia or neutropenia due to bone marrow suppression.Prevention and Patient Counseling
Use protection: Always practice safe sex.Summary Table
| Aspect | Zidovudine (AZT) | Lamivudine (3TC) | Abacavir (ABC) |
|---|---|---|---|
| Drug Class | NRTI | NRTI | NRTI |
| Main Use | HIV therapy, PEP, pregnancy | HIV & Hepatitis B | HIV (HLA-B*5701 testing needed) |
| Mechanism | Inhibits reverse transcriptase | Inhibits viral DNA synthesis | Similar to AZT |
| Major Side Effect | Bone marrow suppression | Mild GI upset | Hypersensitivity reaction |
| Black Box Warning | Myopathy, anemia | None | Severe allergic reaction |
Antiretroviral therapy represents a medical breakthrough in controlling HIV infection. Drugs like Zidovudine (AZT) revolutionized HIV management by preventing viral replication and transmission.
Understanding their mechanism of action, adverse effects, drug interactions, and combination principles is essential for all healthcare and nursing students.
Effective HIV treatment relies on strict adherence, regular monitoring, and patient education to ensure safety, improve quality of life, and prevent the spread of infection.
FAQs About Antiretrovirals
Q1. What is the main function of antiretroviral drugs?
They suppress HIV replication and help maintain immune system function.
Q2. Why are NRTIs used in combination therapy?
To prevent drug resistance and achieve better viral suppression.
Q3. What is the black box warning for Zidovudine?
Severe bone marrow suppression and muscle myopathy.
Q4. Can pregnant women take antiretrovirals?
Yes, especially Zidovudine—it prevents transmission of HIV to the baby.
Q5. What is HAART?
HAART stands for Highly Active Antiretroviral Therapy, combining at least three drugs from different classes to effectively control HIV.
