Indinavir vs Other HIV Protease Inhibitors: Detailed Comparison of Benefits, Side Effects, and Cost

Quick Takeaways

• Indinavir (Indinavir Sulphate) is a first‑generation HIV protease inhibitor approved in 1997.
• Newer protease inhibitors like darunavir and atazanavir offer higher potency and fewer kidney‑related side effects.
• Cost varies widely - generic indinavir is cheap, but newer agents may be covered by public plans in Canada.
• Choosing an alternative depends on viral resistance profile, kidney function, and pill burden.
• All protease inhibitors require strict adherence; missing doses can lead to resistance.

When you hear the name Indinavir, you’re probably thinking of the classic HIV drug that helped turn a deadly diagnosis into a manageable condition. But the HIV treatment landscape has moved on, and clinicians now have a toolbox of newer protease inhibitors (PIs). This article breaks down indinavir side by side with the most common alternatives, so you can see where each one shines and where it falls short.

Indinavir is a protease inhibitor that blocks the HIV‑1 protease enzyme, preventing the virus from maturing and infecting new cells. Marketed as Crixivan, it was FDA‑approved in 1997 and is typically taken as 800 mg three times daily. Its main advantage is low cost, especially in generic form, but it’s notorious for kidney stones and lipodystrophy.

Below, we compare indinavir with five widely used alternatives: Ritonavir, Saquinavir, Lopinavir/ritonavir (often called Kaletra), Atazanavir, and Darunavir. Each has a unique profile that matters for efficacy, safety, and cost.

How Protease Inhibitors Work

All the drugs in this comparison belong to the same class: they target the HIV‑1 protease enzyme, which cuts long viral polyproteins into functional pieces. By binding to the protease active site, they stop the virus from producing mature, infectious particles. Because the mechanism is shared, cross‑resistance can occur, but newer agents are designed to retain activity against strains that have become resistant to older drugs like indinavir.

Key Comparison Factors

We’ll look at five practical dimensions that patients and prescribers weigh when picking a PI:

1. Efficacy and resistance barrier - how well the drug suppresses viral load and how hard it is for HIV to become resistant.
2. Side‑effect profile - especially kidney issues, lipid changes, and gastrointestinal tolerance.
3. Dosing convenience - pill burden, food requirements, and dosing frequency.
4. Drug‑drug interactions - importance of CYP3A4 metabolism and impact on other medicines.
5. Cost and insurance coverage - generic availability, provincial formularies, and out‑of‑pocket expenses.

Head‑to‑Head Comparison Table

Deep Dive Into Each Alternative

Ritonavir - The Booster

Originally launched as a standalone PI, ritonavir is now prized for its ability to inhibit CYP3A4, raising blood levels of co‑administered drugs. At 100 mg twice daily, it’s rarely used alone because its antiviral potency is modest. The biggest drawback is its distinct, metallic taste and frequent lipid abnormalities. If you already need a booster for darunavir or atazanavir, ritonavir remains a cost‑effective option.

Saquinavir - The Food‑Dependent Pill

Saquinavir’s absorption jumps dramatically when taken with a high‑fat meal. The standard dose is 1000 mg twice daily, which translates to two large tablets each time. This requirement makes it less convenient for patients with erratic eating habits. Its side‑effect profile leans toward gastrointestinal distress and, in rare cases, QT interval prolongation. Because a generic version hasn’t hit the Canadian market yet, price can be a barrier.

Lopinavir/ritonavir (Kaletra) - Fixed‑Dose Duo

Lopinavir/ritonavir combines two PIs in a single tablet, simplifying prescribing but not dosing. It’s taken twice daily with meals to improve tolerability. The combination is powerful against wild‑type HIV but can trigger significant triglyceride rises, especially in patients with metabolic syndrome. While still brand‑only in Canada, its fixed‑dose nature reduces pill count compared with taking the drugs separately.

Atazanavir - The Low‑Lipid Choice

Atazanavir’s claim to fame is its relatively mild impact on cholesterol and triglycerides. Taken once daily with a meal, it’s a favorite for patients concerned about cardiovascular risk. Hyperbilirubinemia occurs in up to 20 % of users, manifesting as a mild yellowing of the skin-usually harmless but occasionally prompting a switch. Since a generic version entered the market in 2024, cost has become comparable to older drugs.

Darunavir - The Resistance‑Proof Veteran

Darunavir is the go‑to PI when resistance is a concern. Boosted with ritonavir, it maintains high drug levels even against multi‑mutated viruses. The 800 mg twice‑daily regimen can be demanding, but a once‑daily formulation (800 mg + ritonavir) is now approved for patients without baseline resistance. Side effects include rash and mild liver enzyme elevations. Generic darunavir has been available in Canada since 2023, making it a financially viable option for treatment‑experienced individuals.

When to Stick With Indinavir

Even with newer options, indinavir still makes sense in specific scenarios:

• Budget constraints: Generic indinavir costs as little as CAD 30‑40 per month, far less than most branded PIs.
• No kidney issues: Patients with normal renal function and no history of nephrolithiasis can tolerate it well.
• Established viral suppression: If a patient is already virologically suppressed on indinavir with no side‑effects, switching may introduce unnecessary risk.
• Formulary coverage: Some provincial drug plans still list indinavir as a preferred first‑line option.

However, clinicians should monitor urine for crystals and counsel patients to stay well‑hydrated, especially in hot climates.

Choosing the Right Alternative - A Decision Tree

1. Does the patient have impaired kidney function?
   If yes, avoid indinavir and consider atazanavir or darunavir.
2. Is cardiovascular risk a concern?
   If yes, atazanavir (low lipid impact) or darunavir (requires lipid monitoring) are better than ritonavir‑boosted regimens.
3. Is pill burden a barrier?
   If yes, once‑daily atazanavir or a single‑tablet regimen like lopinavir/ritonavir works well.
4. Is the virus resistant to older PIs?
   If yes, darunavir (high resistance barrier) is the safest bet.
5. Is cost the primary driver?
   If yes, generic indinavir or generic ritonavir are the cheapest options.

Use this flow to align clinical needs with patient preferences.

Practical Tips for Switching From Indinavir

• Check baseline labs: serum creatinine, lipid panel, and liver enzymes.
• Review current drug‑drug interactions-especially CYP3A4 substrates like statins.
• Provide a clear dosing schedule; many newer PIs are once daily with food.
• Educate about possible transient side effects (e.g., bilirubin rise with atazanavir).
• Schedule a follow‑up viral load test 4‑6 weeks after the switch.

Frequently Asked Questions

Bottom Line

Indinavir remains a viable, low‑cost option for patients without kidney concerns and who are already stable on the regimen. For most new starts, however, clinicians favor newer PIs-especially atazanavir for its lipid profile or darunavir for resistance‑prone cases. Weigh efficacy, side effects, dosing convenience, interactions, and price to land on the best fit for each individual.