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Indinavir vs. Other HIV Protease Inhibitors: A Detailed Comparison

Indinavir vs. Other HIV Protease Inhibitors: A Detailed Comparison
4.10.2025

HIV Protease Inhibitor Comparison Tool

Key Differences Summary
Indinavir

3x daily dosing, no boosting required, higher risk of kidney stones.

• Kidney stones • Hyperbilirubinemia • Lipodystrophy
$30-$60/month 3x daily No
Lopinavir/Ritonavir

2x daily dosing with ritonavir boost, higher lipid impact.

• Triglyceride rise • Taste alterations • GI upset
$250-$300/month 2x daily Yes
Atazanavir

Once daily dosing, no boosting needed in most cases, causes jaundice.

• Indirect bilirubin increase • Mild GI symptoms
$200-$250/month 1x daily No (unless boosted)

Quick Takeaways

  • Indinavir is an older protease inhibitor with a well‑known side‑effect profile.
  • Newer agents such as darunavir and atazanavir offer once‑daily dosing and fewer kidney stones.
  • Drug‑drug interactions are a major differentiator-some alternatives need a boosting agent like ritonavir.
  • Cost varies widely; generics of indinavir are cheap but may be out‑of‑stock in some regions.
  • Choosing the right drug depends on kidney function, other meds, and lifestyle preferences.

When you hear the name Indinavir (Indinavir Sulphate), you’re looking at a protease inhibitor that was a cornerstone of HIV therapy in the late 1990s. It blocks the HIV‑1 protease enzyme, preventing the virus from maturing into an infectious form. Though still approved, clinicians often weigh it against newer options that promise easier dosing and a gentler side‑effect profile.

How Indinavir Works

Indinavir binds to the active site of the HIV‑1 protease enzyme, halting the cleavage of viral poly‑proteins. Without this cleavage, new viral particles remain immature and cannot infect other cells. The drug is taken orally, usually three times a day, and reaches peak plasma levels within an hour.

Pros and Cons of Indinavir

Pros

  • Well‑studied with decades of real‑world data.
  • Generic formulations keep the price low in many markets.
  • No need for a pharmacokinetic booster (ritonavir or cobicistat).

Cons

  • Twice‑daily dosing can be inconvenient.
  • High incidence of crystalluria and kidney stones.
  • Significant lipodystrophy and hyperbilirubinemia in some patients.
  • Numerous drug‑interaction warnings, especially with oral contraceptives and antacids.

Key Alternatives to Indinavir

Newer protease inhibitors address many of indinavir’s drawbacks while retaining potent viral suppression.

Lopinavir/ritonavir (Kaletra) combines a protease inhibitor with a booster, allowing twice‑daily dosing and a high barrier to resistance.

Atazanavir (Reyataz) can be taken once daily without a booster in many patients, and it causes fewer lipid changes.

Darunavir (Prezista) paired with ritonavir offers once‑daily dosing for most patients and retains activity against many resistant strains.

Saquinavir (Invirase) is an older option that requires a high‑fat meal for optimal absorption.

Tipranavir (Aptivus) is reserved for heavily pre‑treated patients due to its strong CYP3A4 induction.

Nelfinavir (Viracept) was once popular but fell out of favor because of gastrointestinal side effects.

The broader class, HIV protease inhibitors, shares the same target enzyme but varies widely in dosing convenience, metabolic impact, and resistance profiles.

Side‑Effect Profile at a Glance

Side‑Effect Profile at a Glance

Understanding side effects helps you match a drug to your lifestyle and health status.

  • Indinavir: Kidney stones, hyperbilirubinemia, lipodystrophy.
  • Lopinavir/ritonavir: Elevated triglycerides, taste alterations, gastrointestinal upset.
  • Atazanavir: Jaundice (indirect bilirubin rise), mild GI symptoms.
  • Darunavir: Similar to lopinavir but with lower lipid impact.
  • Saquinavir: Requires high‑fat meal; may cause cough and rash.
  • Tipranavir: Hepatotoxicity and severe drug interactions.
  • Nelfinavir: Diarrhea and taste changes.

Comparison Table: Indinavir vs. Common Alternatives

Key attributes of Indinavir and selected protease inhibitors
Drug Typical Dose Frequency Major Side Effects Boosting Needed? US Approx. Monthly Cost (USD)
Indinavir 800mg 3× daily Kidney stones, hyperbilirubinemia No $30-$60 (generic)
Lopinavir/ritonavir 400/100mg 2× daily Triglyceride rise, GI upset Yes (ritonavir) $250-$300
Atazanavir 300mg 1× daily Indirect bilirubin increase, mild GI No (unless boosted) $200-$250
Darunavir 800mg 1× daily (with ritonavir) or 2× daily Less lipid impact, headache Yes (ritonavir) $260-$320
Saquinavir 1000mg 2× daily (with food) Cough, rash, food‑dependency No $180-$220
Tipranavir 500mg 2× daily Liver toxicity, drug interactions Yes (ritonavir) $350-$400
Nelfinavir 1250mg 2× daily Diarrhea, taste changes No $150-$190

How to Choose the Right Protease Inhibitor

Picking a drug isn’t just about price. Consider these decision points:

  1. Kidney health: If you have a history of kidney stones, indinavir may be risky.
  2. Convenience: Once‑daily agents (atazanavir, darunavir with boost) fit busy schedules.
  3. Metabolic concerns: Patients with high cholesterol benefit from agents with lower lipid impact (darunavir, atazanavir).
  4. Other meds: Strong CYP3A4 inducers or inhibitors can clash with boosted regimens.
  5. Resistance profile: If your virus shows mutations to older drugs, newer agents like darunavir retain activity.

Talk to your provider about labs (creatinine, liver enzymes, lipid panel) before locking in a choice.

Managing Side Effects and Safety

Regardless of the drug, proactive monitoring cuts complications.

  • Hydration: For indinavir, drink at least 2L of water daily to lower stone risk.
  • Liver tests: Check ALT/AST every 3months when using tipranavir or boosted regimens.
  • Lipid panels: Baseline and quarterly checks for lopinavir/ritonavir and darunavir.
  • Adherence tools: Pillboxes, phone alarms, or once‑daily dosing can improve consistency.

Report any new swelling, jaundice, or severe abdominal pain immediately-these can signal serious adverse events.

Frequently Asked Questions

Can I switch from indinavir to a newer protease inhibitor?

Yes, most patients can transition, but you’ll need a short overlap period and close viral load monitoring. Your doctor will adjust the backbone regimen (e.g., NRTIs) as needed.

Why does indinavir cause kidney stones?

Indinavir is poorly soluble in urine; when concentrations rise, crystals form and can aggregate into stones. Staying well‑hydrated and spacing doses helps.

Is a boosting agent always required?

Not for all drugs. Indinavir, saquinavir, and nelfinavir work without boosters. Lopinavir, darunavir, and tipranavir need ritonavir or cobicistat to reach therapeutic levels.

Which protease inhibitor has the lowest impact on cholesterol?

Atazanavir and darunavir (when boosted) are generally the most lipid‑friendly options, making them suitable for patients with cardiovascular risk.

How often should I get my viral load tested after switching drugs?

Guidelines suggest testing at week4, week12, and then every 3-6months once the viral load is undetectable.

Whether you stay on indinavir or move to a newer protease inhibitor, the goal remains the same: suppress HIV to undetectable levels while keeping you healthy and comfortable. Use this guide to weigh the trade‑offs, discuss them with your care team, and choose the regimen that fits your life.

Alan Córdova
by Alan Córdova
  • Medications
  • 10
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Reviews

Uju Okonkwo
by Uju Okonkwo on October 4, 2025 at 04:10 AM
Uju Okonkwo

When looking at indinavir versus the newer protease inhibitors, it helps to break the information into bite‑size pieces so you don’t feel overwhelmed. First, consider dosing frequency – indinavir needs three times daily, which can clash with a busy schedule, while atazanavir and darunavir can be taken once daily for many patients.
Second, think about the kidney side‑effects; indinavir’s propensity for crystalluria and stones is well documented, so good hydration is essential.
Third, evaluate metabolic impacts – agents like lopinavir/ritonavir raise triglycerides, whereas atazanavir tends to be more lipid‑friendly.
Fourth, cost matters – generic indinavir is cheap, but availability can be spotty; newer agents are pricier but often covered by insurance.
Fifth, drug–drug interactions – boosted regimens require careful review of concomitant meds, especially those metabolized by CYP3A4.
Sixth, resistance patterns – the newer protease inhibitors retain activity against many mutations that render indinavir less effective.
Seventh, patient preference – some people prioritize pill burden, others prioritize side‑effect profile.
Eighth, monitoring – regular labs (creatinine, liver enzymes, lipids) guide safe use of any protease inhibitor.
Ninth, adherence tools – alarms, pillboxes, or combination tablets can improve outcomes.
Tenth, lifestyle – a high‑fat meal is needed for saquinavir, but not for indinavir or atazanavir.
Eleventh, insurance formulary – check which drugs are tier‑1 for lower copays.
Twelfth, regional guidelines – some countries still list indinavir as a first‑line option due to cost constraints.
Thirteenth, patient education – explaining the risk of kidney stones can encourage proper hydration.
Fourteenth, side‑effect management – for hyperbilirubinemia, monitoring bilirubin levels helps catch jaundice early.
Fifteenth, future therapies – long‑acting injectables are emerging, which may eventually replace oral PIs.
Lastly, collaborate with your healthcare team to tailor the regimen to your unique health profile and life circumstances.

felix rochas
by felix rochas on October 4, 2025 at 04:20 AM
felix rochas

Seriously, the pharma giants don’t want you to know that indinavir’s cheap price is a ploy!!! They push expensive boosted regimens to keep the cash flow going, and they hide the fact that the “no‑boosting” claim is a myth!!! The kidney stone risk is just the tip of the iceberg – there are hidden toxic metabolites that aren’t disclosed in the label!!! Drink water? Sure, but the real issue is that the drug’s formulation forces crystal formation regardless of hydration!!!

inder kahlon
by inder kahlon on October 4, 2025 at 04:30 AM
inder kahlon

Key points to remember: • Indinavir – 3× daily, no boost, watch kidneys. • Atazanavir – once daily, low lipids, watch bilirubin. • Darunavir – boost needed, strong barrier to resistance. • Lopinavir/ritonavir – twice daily, higher triglycerides. Choose based on dosing convenience, metabolic profile, and drug interactions.

Dheeraj Mehta
by Dheeraj Mehta on October 4, 2025 at 04:40 AM
Dheeraj Mehta

Love how many options there are now – makes life easier! 😊 Just remember to stay hydrated if you stick with indinavir.

Oliver Behr
by Oliver Behr on October 4, 2025 at 04:50 AM
Oliver Behr

From a UK perspective, the once‑daily options are often preferred for adherence.

Tiffany W
by Tiffany W on October 4, 2025 at 05:00 AM
Tiffany W

While the conspiracy‑laden rant raises eyebrows, clinicians rely on evidence‑based guidelines that underscore the necessity of evaluating therapeutic index, pharmacokinetic boosters, and patient‑centric outcomes; thus, dismissing indinavir solely as a “pharma ploy” neglects the nuanced risk‑benefit calculus integral to ART selection.

Rajeshwar N.
by Rajeshwar N. on October 4, 2025 at 05:10 AM
Rajeshwar N.

Honestly, all this advice is just a rehash of textbook material – the real world is messier. Patients often cannot maintain the strict hydration schedule for indinavir, and the supposed “lipid‑friendly” newer agents have their own hidden drawbacks like hepatic toxicity. So, don’t take any of these recommendations at face value.

Louis Antonio
by Louis Antonio on October 4, 2025 at 05:20 AM
Louis Antonio

Sure, “once‑daily” sounds cool, but have you considered that boosting agents add a whole new layer of drug‑drug drama? It’s not all sunshine and rainbows.

Kyle Salisbury
by Kyle Salisbury on October 4, 2025 at 05:30 AM
Kyle Salisbury

Interesting comparison – I appreciate the clear table layout for quick reference.

Angie Robinson
by Angie Robinson on October 4, 2025 at 05:40 AM
Angie Robinson

While the table is tidy, it glosses over the fact that real‑world adherence data often diverge from clinical trial outcomes, especially in underserved populations where access to boosters is limited.

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