HIV Protease Inhibitor: What They Are, How They Work, and Which Ones Matter

When you hear HIV protease inhibitor, a class of antiviral drugs that block a key enzyme HIV needs to multiply. Also known as PIs, these drugs are one of the backbone treatments in combination antiretroviral therapy (cART). Without them, HIV can’t make new infectious copies of itself. Think of it like stopping a factory from assembling broken parts—once the protease enzyme is blocked, the virus falls apart before it can spread.

These drugs don’t work alone. They’re always paired with other antiretrovirals like zidovudine, a nucleoside reverse transcriptase inhibitor that stops HIV from copying its genetic material or tenofovir, another key drug that interferes with viral replication. This combo approach keeps the virus suppressed and reduces the chance of drug resistance. Studies show that patients on full regimens including protease inhibitors live longer, stay healthier, and are far less likely to pass the virus to others.

Common HIV protease inhibitors include darunavir, lopinavir, atazanavir, and ritonavir. Each has its own profile—some need to be taken with food, others cause fewer stomach issues, and some are used as boosters to make other drugs work better. Ritonavir, for example, is rarely used just to fight HIV. Instead, it’s often used in low doses to slow down how fast the body breaks down other protease inhibitors, letting them stay active longer. This trick, called pharmacokinetic boosting, is why you’ll see drugs like darunavir/ritonavir sold as a single pill.

Side effects vary. Some people report nausea, diarrhea, or changes in fat distribution. Others notice higher cholesterol or blood sugar levels. But compared to older HIV drugs, today’s protease inhibitors are much easier to tolerate. Many are taken once a day, with fewer pills and less strict timing. That makes sticking to treatment simpler, which is critical—missing doses can lead to resistance.

These drugs aren’t just for people newly diagnosed. They’re also used in treatment-experienced patients who’ve tried other regimens, and even in emergency situations like post-exposure prophylaxis after potential HIV exposure. They’re part of the reason HIV is no longer the death sentence it once was.

What you’ll find below are real, practical guides on how these drugs fit into daily life—what works, what doesn’t, and how patients and doctors make choices. From how zidovudine reduces illness and death to how newer treatments stack up against older ones, the posts here cut through the noise. No fluff. No theory without application. Just clear, usable info for anyone managing or learning about HIV treatment today.