Indinavir

Indinavir (IDV; trade name Crixivan, manufactured by Merck) is a protease inhibitor used as a component of highly active antiretroviral therapy (HAART) to treat HIV infection and AIDS.

History
The Food and Drug Administration (FDA) approved indinavir March 13, 1996, making it the eighth approved antiretroviral. Indinavir was much more powerful than any prior antiretroviral drug; using it with dual NRTIs set the standard for treatment of HIV/AIDS and raised the bar on design and introduction of subsequent antiretroviral drugs. Protease inhibitors changed the very nature of the AIDS epidemic from one of a terminal illness to a somewhat manageable one.

Increasingly, it is being replaced by newer drugs that are more convenient to take and less likely to promote resistant virus, such as lopinavir or atazanavir.

Administration
Unfortunately, indinavir wears off quickly after dosing and therefore requires dosing very precisely every eight hours in order to thwart HIV from forming drug resistant mutations including resistances to other protease inhibitors. It has restrictions on what sorts of food may be eaten concurrently.

Side effects
Side effects include:
 * Kidney stones
 * Kidney failure
 * Metabolic abnormalities including hyperlipidemia (cholesterol or triglyceride elevations)
 * Alterations in body shape known as lipodystrophy

Endothelial cells produce nitric oxide (NO) which causes blood vessels to dilate, lowers blood pressure, allows oxygen to reach and nutrients to reach tissues, and allows carbon dioxide and metabolic waste to be removed. Nitric oxide is highly reactive and quickly reacts with molecular oxygen (O2) to form nitrogen dioxide (NO2).


 * 2NO + O2 → 2NO2

A further reaction between nitrogen dioxide (NO2) and water (H2O) can produce nitrate (NO3). The nitrate is then removed from the body in the urine. The kidney is filled with small blood vessels. In the absence of nitric oxide, these blood vessels may become constricted, and the kidney may become ischemic, leading to kidney disease.

Indinavir inhibits urinary nitrous oxide production and may inhibit nitric oxide production. Treatment with this drug is frequently associated with renal abnormalities, sterile leukocyturia, and reduced creatinine clearance.

Indinavir impairs endothelial function in healthy HIV-negative men and may accelerate atherosclerotic disease.