Indinavir vs Alternatives: 2025 Comparison of HIV Protease Inhibitors
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| Characteristic | Indinavir | Atazanavir | Darunavir | Lopinavir/Ritonavir | Saquinavir |
|---|---|---|---|---|---|
| Approval Year | 1997 | 2003 | 2006 | 2000 | 1995 |
| Dosing Frequency | Twice daily | Once daily | Once daily | Twice daily | Twice daily |
| Food Requirement | Empty stomach | Low-fat meal | With or without food | With or without food | High-fat meal |
| Typical Cost (USD/month) | $1,200 | $900 | $1,100 | $800 | $950 |
| Notable Side Effects | Kidney stones, hyperbilirubinemia | Jaundice, mild GI upset | Diarrhea, rash | Hypertriglyceridemia, GI intolerance | Metabolic changes, taste alteration |
Important Considerations
When selecting a protease inhibitor, consider factors such as:
- Renal Function: Indinavir carries a significant risk of kidney stones; newer agents are safer for patients with CKD.
- Dosing Convenience: Once-daily regimens reduce pill burden and improve adherence.
- Drug Interactions: Some drugs may interact with antacids or affect lipid metabolism.
- Resistance Profile: Darunavir remains active against many resistant strains.
Quick Summary
- Indinavir is an older HIV protease inhibitor with twice‑daily dosing but notable kidney stone risk.
- Modern alternatives like atazanavir, darunavir and lopinavir/ritonavir offer once‑daily dosing and fewer renal side effects.
- When choosing, consider resistance profile, drug‑food interactions, pill burden and cost.
- For patients with chronic kidney disease, newer agents are generally safer.
- All options require combination with other antiretrovirals to achieve full viral suppression.
What is Indinavir?
When treating HIV, Indinavir is a protease inhibitor that blocks the HIV‑1 protease enzyme, preventing the virus from maturing into infectious particles. Marketed under the brand name Crixivan, it received FDA approval in 1997.
Key attributes:
- Typical dose: 800mg taken twice daily, preferably on an empty stomach.
- Drug class: Protease inhibitor (PI).
- Common side effects: Crystalluria, hyperbilirubinemia, lipodystrophy, and mild nausea.
- Major safety concern: Indinavir can precipitate in the urinary tract, leading to kidney stones in up to 10% of patients.
- Cost (2025 US average): Approximately $1,200 per month for generic formulation.
Indinavir’s efficacy is well documented, achieving viral load suppression comparable to newer PIs when paired with a robust backbone regimen. However, its dosing frequency and renal risks have pushed clinicians toward alternatives for most patients today.
Modern Protease Inhibitor Alternatives
The HIV treatment landscape now includes several next‑generation protease inhibitors that improve convenience and safety. Below are the most widely used alternatives.
Atazanavir, often combined with ritonavir (boosted atazanavir), was approved in 2003. It can be taken once daily with a low‑fat meal.
Darunavir entered the market in 2006. When boosted with ritonavir or cobicistat, it allows once‑daily dosing and retains activity against many PI‑resistant strains.
Lopinavir/ritonavir (Kaletra) is a fixed‑dose combination approved in 2000. It is taken twice daily but has a well‑known tolerability profile.
Saquinavir, another early PI, is now mostly used in its boosted form (Saquinavir/ritonavir) and requires administration with a high‑fat meal to improve absorption.
Side‑by‑Side Comparison
| Drug | Brand (if any) | FDA approval | Dosing frequency | Food requirements | Typical cost (US$/month) | Notable side effects |
|---|---|---|---|---|---|---|
| Indinavir | Crixivan | 1997 | Twice daily | Empty stomach (1h before or 2h after meals) | ~$1,200 (generic) | Kidney stones, hyperbilirubinemia |
| Atazanavir (boosted) | Reyataz | 2003 | Once daily | Low‑fat meal | ~$900 (generic) | Jaundice, mild GI upset |
| Darunavir (boosted) | Prezista | 2006 | Once daily | Can be taken with or without food | ~$1,100 (generic) | Diarrhea, rash |
| Lopinavir/ritonavir | Kaletra | 2000 | Twice daily | With or without food | ~$800 (generic) | Hypertriglyceridemia, GI intolerance |
| Saquinavir (boosted) | Invirase | 1995 (boosted 2003) | Twice daily | High‑fat meal | ~$950 (generic) | Metabolic changes, taste alteration |
Pros and Cons by Drug
Indinavir
Pros: Proven efficacy, lower cost for brand‑name generic, minimal CYP3A4 interactions.
Cons: Twice‑daily schedule, strict fasting requirement, high risk of renal calculi, requires adequate hydration.
Atazanavir (boosted)
Pros: Once‑daily dose, less impact on lipid profiles, tolerable in patients with cardiovascular risk.
Cons: Can cause indirect hyperbilirubinemia (jaundice), modest drug‑drug interaction with antacids.
Darunavir (boosted)
Pros: Strong activity against PI‑resistant HIV strains, flexible with food, once‑daily option available.
Cons: Requires boosting agent, potential for increased serum creatinine, higher pill burden when boosted.
Lopinavir/ritonavir
Pros: Widely studied, often used in pediatric formulations, robust barrier to resistance.
Cons: Twice‑daily dosing, notable impact on triglycerides and cholesterol, frequent GI side effects.
Saquinavir (boosted)
Pros: Useful when other PIs are contraindicated, effective in some salvage regimens.
Cons: Requires high‑fat meal for absorption, twice‑daily schedule, metabolic side effects.
How to Choose the Right Protease Inhibitor
Picking a PI isn’t a “one‑size‑fits‑all” decision. Here’s a quick decision framework:
- Renal function: If eGFR<60mL/min/1.73m², avoid Indinavir because of stone risk.
- Resistance profile: For patients with prior PI exposure, darunavir offers the broadest coverage.
- Pill burden & lifestyle: Once‑daily options (atazanavir, darunavir) improve adherence for busy schedules.
- Metabolic concerns: Atazanavir has the mildest impact on lipids; lopinavir/ritonavir can raise triglycerides substantially.
- Cost considerations: Generic Indinavir remains the cheapest, but insurance formularies may favor newer generics with better safety.
- Drug‑food interactions: Assess whether the patient can consistently take a high‑fat or low‑fat meal as required.
In practice, many clinicians start with a boosted atazanavir or darunavir regimen for treatment‑naïve patients, reserving Indinavir for specific cases where cost constraints outweigh its drawbacks.
Monitoring and Managing Side Effects
Regardless of the chosen PI, regular monitoring is key.
- Kidney function: Serum creatinine and urine analysis every 3‑6months for Indinavir users.
- Liver function: Bilirubin and transaminases quarterly when using atazanavir.
- Lipid panel: Fasting lipids at baseline and then annually, more frequently if on lopinavir/ritonavir.
- Adherence checks: Pharmacy refill data or patient self‑report to catch missed doses early.
If side effects emerge, clinicians can switch to an alternative PI without compromising the overall regimen, provided resistance testing supports the change.
Frequently Asked Questions
Is Indinavir still prescribed in 2025?
Yes, but primarily for patients who need a low‑cost option and have no significant renal issues. Many clinicians prefer newer PIs for their safety and convenience.
Can I take Indinavir with food?
Indinavir must be taken on an empty stomach-at least 1hour before or 2hours after a meal-to avoid reduced absorption and higher risk of crystal formation.
What is the main advantage of atazanavir over Indinavir?
Atazanavir offers once‑daily dosing, fewer renal side effects, and a lower impact on cholesterol, making it easier for long‑term adherence.
Do boosted protease inhibitors increase drug interactions?
Boosting agents (ritonavir or cobicistat) inhibit CYP3A4, so they can raise levels of many co‑administered drugs. A thorough medication review is essential when prescribing boosted regimens.
How often should viral load be checked after switching PIs?
Guidelines recommend measuring plasma HIV‑1 RNA at 4weeks post‑switch, then at 12weeks, and subsequently every 3-6months if the patient remains suppressed.
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Jay Ram
October 6, 2025 AT 16:21Yo folks, just skimmed through this massive comparison and thought I’d drop a quick take. Indinavir’s old‑school vibe is still solid in terms of raw potency, but the twice‑daily schedule and that dreaded kidney stone risk can be a real pain. The newer PIs like atazanavir and darunavir really shine with once‑daily dosing, making life easier for anyone juggling a busy schedule. Cost‑wise, Indinavir isn’t the cheapest anymore, especially when you factor in the generic competition. Overall, if you’ve got good renal function and don’t mind the fasting rule, it can still be a decent option. Otherwise, I’d say check out the newer agents for a smoother ride.