A 42-year-old man living with HIV presents with intermittent flank pain and difficulty passing urine. His antiretroviral regimen includes two nucleoside analogue agents and one protease-inhibitor–based drug. Imaging reveals radiopaque stones within the ureter. Which medication in his treatment plan is most strongly linked to crystal formation and urinary tract stone disease?
A. Abacavir
B. Saquinavir
C. Indinavir
D. Efavirenz
E. Dolutegravir
Detailed ExplanationÂ
Some HIV medications—especially older protease inhibitors—can form crystals in the urine because they do not dissolve well. When enough crystals accumulate, they clump together to form stones (nephrolithiasis). This can cause flank pain, blood in urine, or obstruction.
Why Indinavir?
- Indinavir is a protease inhibitor (PI).
- It has poor solubility in urine, so it can precipitate and form crystals.
- About 10–20% of patients may develop stones if they do not maintain good hydration.
- Prevention: drink ≥1.5–2 L/day to reduce crystal concentration.
Why the others are not correct:
- Abacavir (NRTI) → hypersensitivity reaction (HLA-B*5701 associated), not stones.
- Saquinavir (PI) → GI upset, metabolic syndrome, not nephrolithiasis.
- Efavirenz (NNRTI) → vivid dreams, mood changes, rash, not stones.
- Dolutegravir (Integrase inhibitor) → insomnia, weight gain, occasional ↑creatinine, not renal stones.
✔ Correct answer: Indinavir
Cheat Sheet: Antiretroviral Drugs & Key Toxicities
| Drug Class | Examples | Key Adverse Effects |
|---|---|---|
| NRTIs | Zidovudine, Abacavir, Didanosine, Lamivudine, Tenofovir | Mitochondrial toxicity, lactic acidosis; Zidovudine → anemia; Didanosine → pancreatitis, neuropathy; Tenofovir → renal injury, ↓bone density |
| NNRTIs | Efavirenz, Nevirapine | Rash, SJS; CNS effects (efavirenz); hepatotoxicity |
| Protease Inhibitors | Indinavir, Ritonavir, Saquinavir | Metabolic syndrome: diabetes, hyperlipidemia, lipodystrophy; P450 inhibition; Indinavir → renal stones |
| Integrase Inhibitors | Dolutegravir, Raltegravir | Generally well tolerated; mild CK rise; insomnia |
| Entry/Fusion Inhibitors | Maraviroc, Enfuvirtide | Maraviroc → CCR5 testing required; enfuvirtide → injection site reactions |
| General ART Principle | Start ART at diagnosis; standard regimen = 2 NRTIs + 1 INSTI/PI/NNRTI |
Flashcards (20)
- Q: Which HIV drug most classically causes kidney stones?
A: Indinavir. - Q: Why does indinavir cause nephrolithiasis?
A: Poor solubility in urine → crystal precipitation. - Q: How to prevent indinavir stone formation?
A: Maintain ≥1.5–2 L/day hydration. - Q: Class of indinavir?
A: Protease inhibitor. - Q: Main toxicity of didanosine?
A: Pancreatitis. - Q: Main toxicity of tenofovir?
A: Renal tubular injury + reduced bone density. - Q: Zidovudine major adverse effect?
A: Bone marrow suppression (anemia). - Q: Abacavir toxicity?
A: Hypersensitivity reaction (HLA-B*5701). - Q: Efavirenz notable side effects?
A: Vivid dreams, neuropsychiatric symptoms. - Q: Nevirapine major toxicity?
A: Severe rash, hepatotoxicity. - Q: Protease inhibitors metabolic effects?
A: Lipodystrophy, insulin resistance, hyperlipidemia. - Q: Ritonavir is mainly used for?
A: Boosting levels of other PIs (CYP inhibition). - Q: Entry inhibitor requiring CCR5 testing?
A: Maraviroc. - Q: Fusion inhibitor?
A: Enfuvirtide. - Q: Integrase inhibitors example?
A: Dolutegravir. - Q: When should ART be started?
A: As soon as HIV diagnosis is made. - Q: Standard ART regimen contains how many drugs?
A: Three (2 NRTI + 1 other class). - Q: NRTIs share what general toxicity?
A: Mitochondrial toxicity → lactic acidosis. - Q: Which drug produces asymptomatic hyperbilirubinemia?
A: Indinavir. - Q: Which ARV class commonly interacts with CYP450?
A: Protease inhibitors and NNRTIs.
MCQsÂ
1. A patient on ART develops flank pain and sterile crystalluria. Which drug is most likely responsible?
A. Efavirenz
B. Tenofovir
C. Indinavir
D. Lamivudine
E. Dolutegravir
Answer: C
2. A 35-year-old man on a protease inhibitor develops hyperlipidemia and insulin resistance. Which PI is known for renal stones?
A. Atazanavir
B. Ritonavir
C. Saquinavir
D. Indinavir
E. Darunavir
Answer: D
3. Which adverse effect is a hallmark of NRTI mitochondrial toxicity?
A. Renal stones
B. Lactic acidosis
C. SJS
D. Jaundice
E. Diarrhea
Answer: B
4. Which ARV requires HLA-B*5701 testing prior to use?
A. Abacavir
B. Zidovudine
C. Nevirapine
D. Efavirenz
E. Dolutegravir
Answer: A
5. A patient starts efavirenz. What should they be warned about?
A. Kidney stones
B. Severe anemia
C. Vivid dreams and mood changes
D. Pancreatitis
E. Injection-site nodules
Answer: C
SummaryÂ
Indinavir is the antiretroviral drug most strongly linked to nephrolithiasis because it crystallizes easily in urine due to poor solubility, making hydration essential for prevention. Protease inhibitors in general can cause metabolic complications such as dyslipidemia, insulin resistance, and lipodystrophy, but indinavir is unique for its renal stone risk and occasional hyperbilirubinemia. Other ARVs have distinct toxicities: zidovudine causes bone marrow suppression, abacavir may trigger a hypersensitivity reaction in HLA-B*5701–positive individuals, didanosine can cause pancreatitis and neuropathy, and tenofovir is associated with renal tubular injury and reduced bone density. NNRTIs such as efavirenz can produce neuropsychiatric symptoms and vivid dreams, while nevirapine is known for severe rashes and hepatotoxicity. Integrase inhibitors like dolutegravir are generally well tolerated. Modern HIV management recommends initiating ART at diagnosis, typically using a combination of two NRTIs plus one drug from another class. Understanding hallmark toxicities is essential for safe prescribing and early recognition of complications. Nephrolithiasis from indinavir remains a classic examination question because of its strong and specific association among antiretroviral agents.