Protease Inhibitor Selector
This tool helps you determine the most appropriate HIV protease inhibitor based on your medical conditions and treatment priorities. Answer the questions below to get a personalized recommendation.
Key Takeaways
- Indinavir is effective but can cause kidney stones and metabolic changes.
- Modern alternatives such as darunavir, atazanavir, and lopinavir/ritonavir often have simpler dosing and fewer renal issues.
- When choosing a protease inhibitor, consider viral suppression rates, resistance profile, pill burden, drug interactions, and cost.
- Patients with existing kidney disease usually avoid Indinavir and favor agents with a better renal safety record.
- Discuss with your clinician to match the drug’s side‑effect profile to your lifestyle and comorbidities.
What Is Indinavir?
Indinavir is a protease inhibitor marketed as Indinavir Sulphate. Approved in the mid‑1990s, it blocks the HIV‑1 protease enzyme, preventing viral particles from maturing.
Typical dosing for treatment‑naïve adults is 800mg three times daily on an empty stomach, and it must be taken with plenty of water to reduce crystalluria. Its half‑life is short (about 1.5hours), which is why the regimen feels burdensome compared with once‑daily options.
Clinical trials showed a 72% reduction in viral load after 48weeks, but real‑world data flagged kidney stone formation in up to 4% of patients and lipid spikes in many users.
How to Evaluate an HIV Protease Inhibitor
Before jumping into the list of alternatives, it helps to know the criteria most clinicians and patients use:
- Efficacy: Percentage of patients achieving U=U status (HIV‑RNA <50copies/mL) after 24weeks.
- Resistance barrier: How many mutations the virus needs to escape the drug.
- Side‑effect profile: Renal toxicity, lipid changes, gastrointestinal upset, and CNS effects.
- Dosing convenience: Once‑daily vs. multiple doses, food requirements.
- Drug‑drug interactions: Especially with statins, anti‑epileptics, and hormonal contraceptives.
- Cost & access: Generic availability, insurance coverage, and patient‑assistance programs.
Keep this checklist handy while you read through the alternatives.
Leading Alternatives to Indinavir
Below are the most widely used protease inhibitors that have largely supplanted Indinavir in current guidelines.
1. Darunavir (Boosted with Ritonavir)
Darunavir is a high‑potency protease inhibitor introduced in 2006. When paired with a low dose of ritonavir (often 100mg), its half‑life extends to about 15hours, allowing once‑daily dosing.
- Efficacy: >90% suppression in treatment‑naïve patients.
- Resistance barrier: Very high; works against many PI‑resistant strains.
- Side‑effects: Generally mild - occasional nausea, rare rash. No significant renal toxicity.
- Interactions: Strong CYP3A4 inhibitor; caution with certain anti‑arrhythmics and sedatives.
- Cost: Generic versions available; moderately priced.
2. Atazanavir (Boosted with Ritonavir or Cobicistat)
Atazanavir debuted in 2003 and is known for its once‑daily regimen and relatively mild lipid profile. It can be boosted with ritonavir or cobicistat.
- Efficacy: Around 85-90% viral suppression.
- Resistance barrier: Moderate; better when boosted.
- Side‑effects: Hyperbilirubinemia (yellow eyes) in ~10% of users, but usually harmless. Low impact on cholesterol.
- Interactions: Sensitive to antacids; must be taken with food.
- Cost: Generic options have lowered price dramatically.
3. Lopinavir/Ritonavir (Kaletra)
Lopinavir/ritonavir is a fixed‑dose combination often called Kaletra. It requires twice‑daily dosing and a higher pill burden.
- Efficacy: 78-85% suppression, slightly lower than newer agents.
- Resistance barrier: Moderate; resistance can develop quickly if adherence falters.
- Side‑effects: Diarrhea, nausea, and noticeable lipid elevations.
- Interactions: Strong CYP3A4 inhibition; many meds need dose adjustment.
- Cost: Widely available as a generic; price is low but tolerability issues are common.
4. Saquinavir (Boosted)
Saquinavir was the first protease inhibitor on the market. The boosted formulation (with ritonavir) improves its bioavailability.
- Efficacy: 70-80% when adherence is excellent.
- Resistance barrier: Lower compared with darunavir.
- Side‑effects: Gastrointestinal upset, rash, and metabolic changes.
- Interactions: Similar to other boosted PIs.
- Cost: Generic version inexpensive, but side‑effect profile limits use.
5. Fosamprenavir (Boosted)
Fosamprenavir is a pro‑drug of amprenavir. When boosted, it offers once‑daily dosing for many patients.
- Efficacy: 80-85% viral suppression.
- Resistance barrier: Moderate; works well in non‑resistant strains.
- Side‑effects: Nausea, increased bilirubin, and occasional skin reactions.
- Interactions: CYP3A4 substrate - similar precautions to other boosted PIs.
- Cost: Generic reduces price; still less popular than darunavir or atazanavir.
Head‑to‑Head Comparison
| Drug | Typical Dose | Viral Suppression (24wks) | Renal Safety | Lipid Impact | Pill Burden | Generic Availability |
|---|---|---|---|---|---|---|
| Indinavir | 800mg TID (empty stomach) | ≈72% | Risk of crystalluria & kidney stones | ↑ cholesterol & triglycerides | 3 tablets daily | Yes (off‑patent) |
| Darunavir/ritonavir | 800mg + 100mg QD (with food) | >90% | Very low renal risk | Modest ↑ lipids | 2 tablets daily | Yes |
| Atazanavir/ritonavir | 300mg QD (with food) | 85‑90% | Low renal impact | Minimal lipid rise; ↑ bilirubin | 1‑2 tablets daily | Yes |
| Lopinavir/ritonavir | 400mg/100mg BID | 78‑85% | Low renal risk | Significant ↑ LDL/ TG | 2‑4 tablets BID | Yes |
| Saquinavir/ritonavir | 1000mg BID | 70‑80% | Low renal risk | ↑ lipids | 2‑3 tablets BID | Yes |
| Fosamprenavir/ritonavir | 700mg QD | 80‑85% | Low renal risk | ↑ cholesterol (moderate) | 1 tablet QD | Yes |
Choosing the Right Protease Inhibitor for You
Use the following decision tree to narrow down the best fit:
- Do you have kidney disease or a history of stones? If yes, skip Indinavir and consider darunavir or atazanavir.
- Is once‑daily dosing a priority? Darunavir, atazanavir, and fosamprenavir all allow QD dosing; lopinavir/ritonavir and saquinavir require BID.
- Are you concerned about cholesterol? Atazanavir has the mildest lipid impact; lopinavir/ritonavir tends to raise LDL the most.
- Do you take medications metabolized by CYP3A4? All boosted PIs affect CYP3A4, but atazanavir’s interaction profile is slightly less complex.
- What does your insurance cover? Generic darunavir and atazanavir are often reimbursed; newer branded combos may need prior auth.
When in doubt, discuss these points with your HIV specialist. Blood work (renal panel, lipid profile, liver enzymes) before and after switching is a must.
Practical Tips & Common Pitfalls
- Stay hydrated with Indinavir. At least 1.5L of water per day reduces crystal formation.
- Take boosted PIs with food. Food improves absorption and lessens gastrointestinal upset.
- Monitor labs regularly. Check serum creatinine, fasting lipids, and bilirubin at baseline and every 3‑6months.
- Beware of grapefruit juice. It can dramatically increase PI levels, especially with atazanavir.
- Adherence matters. Missing doses of boosted regimens can cause rapid resistance.
Frequently Asked Questions
Can I switch from Indinavir to darunavir without a wash‑out period?
Yes. Because both drugs are protease inhibitors, you can transition on the same day after confirming that your viral load is suppressed and your renal function is stable. Your clinician will adjust the ritonavir boosting dose as needed.
Why does Indinavir cause kidney stones?
Indinavir is poorly soluble in urine. When concentration spikes, it can crystallize, forming stones. Adequate hydration dilutes the urine and lowers this risk.
Is atazanavir safe for patients with high bilirubin?
Atazanavir often raises indirect bilirubin, which appears as a harmless yellowing of the skin. If you already have liver disease or Gilbert’s syndrome, discuss alternative options with your doctor.
Which protease inhibitor is cheapest for a UK patient?
Generic darunavir and atazanavir are typically the most affordable in the NHS formulary. Prices vary by region, so check local prescription services.
Do all boosted PIs require the same amount of ritonavir?
No. Darunavir and atazanavir usually need 100mg of ritonavir once daily, while lopinavir/ritonavir already includes a fixed 100mg/400mg combo taken twice daily. Dosage depends on the PI and the patient’s metabolic profile.
Whether you stay on Indinavir or move to a newer protease inhibitor, the goal remains the same: keep the virus suppressed and your body healthy. Use the comparison table, weigh the side‑effect profile, and have an open conversation with your care team. The right choice today can make a big difference in your long‑term wellbeing.
Rafael Lopez
October 14, 2025 AT 13:56Indinavir certainly has its place, but when you weigh renal risk, dosing frequency, and lipid profile, newer agents such as darunavir or atazanavir often provide a smoother therapeutic experience, especially for patients who struggle with adherence, and the generic availability keeps costs manageable.