A 32-year-old man with newly diagnosed HIV-1 infection is being counselled about antiretroviral therapy (ART). Regarding adverse effects and drug interactions of commonly used antiretrovirals, all of the following are true EXCEPT:

Question

Accepted Answer

A. Abacavir (NRTI) carries a significant risk of severe hypersensitivity reaction that is NOT associated with HLA-B*5701 genotype and occurs unpredictably in all patients. ## Adverse Effects and Drug Interactions in Antiretroviral Therapy

### Correct Statements

**High-Yield:** Efavirenz is notorious for CNS side effects — dizziness, insomnia, vivid dreams, and impaired concentration occur in 40–50% of patients. These effects are typically **transient and resolve within 2–4 weeks** as tolerance develops, though some patients require dose adjustment or switch to an alternative NNRTI.

**Key Point:** Tenofovir (a nucleotide NRTI) has two major toxicities:
  - **Nephrotoxicity:** dose-dependent renal dysfunction, especially in patients with baseline renal impairment or concurrent nephrotoxic drugs
  - **Bone mineral density loss:** increased risk of osteoporosis and fractures, particularly in older patients
  - Baseline and periodic monitoring of eGFR and bone density (DEXA) is mandatory.

**Key Point:** Ritonavir is a potent **CYP3A4 inhibitor**. At low doses (100–200 mg), it is used as a "pharmacokinetic booster" to increase and prolong serum levels of other protease inhibitors (e.g., lopinavir, darunavir), allowing for lower doses and less frequent dosing.

### The Incorrect Statement

**Warning:** Abacavir hypersensitivity reaction IS strongly associated with **HLA-B*5701 genotype**. This is a critical pharmacogenetic association:

| Feature | Detail |
| --- | --- |
| **HLA-B*5701 prevalence** | ~5–8% in European ancestry, ~1–2% in African ancestry |
| **Sensitivity of HLA-B*5701 for HSR** | ~100% (nearly all HSR cases carry the allele) |
| **Specificity** | ~95% (most carriers do not develop HSR) |
| **Recommendation** | **Mandatory HLA-B*5701 screening before abacavir initiation** |
| **Timing of HSR** | Typically within 6 weeks of initiation; rare after 6 weeks |

**Clinical Pearl:** The abacavir hypersensitivity reaction (HSR) presents with fever, rash, GI symptoms (nausea, vomiting, diarrhea), and respiratory symptoms. It is **NOT unpredictable** — it is highly predictable by HLA-B*5701 genotype. Rechallenge after HSR can cause severe, potentially fatal reaction.

**Mnemonic:** **ABC = Always Be Checking** (HLA-B*5701 before abacavir).

Answer

B. Tenofovir (NRTI) can cause nephrotoxicity and bone mineral density loss, necessitating baseline and periodic renal function and bone density monitoring

Answer

C. Ritonavir is used as a pharmacokinetic booster in PI-based regimens because it inhibits CYP3A4 and increases serum levels of other protease inhibitors

Answer

D. Efavirenz (NNRTI) commonly causes CNS side effects including dizziness and vivid dreams, which typically resolve within 2–4 weeks of initiation

A 32-year-old man with newly diagnosed HIV-1 infection is being counselled about antiretroviral therapy (ART). Regarding adverse effects and drug interactions of commonly used antiretrovirals, all of the following are true EXCEPT:

Explanation

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