What are protease inhibitors? |

Definition

Protease inhibitors (PIs) are a class of drugs that treat or prevent infection
by viruses. They belong to a larger therapeutic category, antiretroviral drugs, and are used primarily to treat
human
immunodeficiency virus (HIV)
infection and hepatitis C.

Pharmacology

Viruses that are blocked by protease inhibitors are prevented from maturing,
infecting, or replicating. Protease inhibitors act on viruses at a very late stage
of replication, stopping a cell’s ability to incorporate proteins into viral
particles.

Risk Factors

Protease inhibitors have dramatically improved the life expectancy of persons
with HIV and hepatitis C, but PIs have a tendency to interact with other drugs,
causing undesirable side effects. There is also a risk of drug-resistant mutated
viruses. Persons who take PIs may experience kidney
stones, nausea, diarrhea, and abnormal sensations around the
mouth. Most of these side effects are not serious and tend to resolve rapidly.

Persons with acquired immunodeficiency syndrome (AIDS) who are taking PIs risk liver dysfunction, including
hepatitis
B and hepatitis C infections. Excess bleeding and blood clots
are rare side effects. Persons taking PIs also report side effects such as high
blood sugar, abdominal obesity, high triglycerides, fatty tissue disorders,
insulin resistance, sexual dysfunction, and pancreatitis.

Treatment and Therapy

To reduce the risks of PI side effects and drug
resistance, clinicians often implement combinations of drugs.
For example, clemizole increases the effectiveness of PIs, enabling them to be
used in smaller doses. Physicians have also had some success in treating persons
with drug combinations that do not involve PIs. However, the research-based
recommendation on this practice is to be cautious about removing a person from PI
therapy if he or she has already done well on it. Preliminary studies are underway
to see whether PIs might be used to treat cancer.

Impact

Pharmaceutical researchers developed the first protease inhibitors between 1989
and 1994. Additional drugs are under investigation, and a series of new PIs have
been brought to market for treatment. PIs are the largest class of drugs in the
fight against HIV infection. In terms of virology and
immunology and clinical and survival issues, PIs offer
patients a quality of life that was previously unattainable.

Bibliography

Carr, Andrew, et al. “A Syndrome of Peripheral Lipodystrophy, Hyperlipidemia, and Insulin Resistance in Patients Receiving HIV Protease Inhibitors.” AIDS 12 (1998): F51-F58.

Centers for Disease Control and Prevention. “Hepatitis C.” Available at http://www.cdc.gov/hepatitis/hcv.

John, Mina, et al. “Hepatitis C Virus-Associated Hepatitis Following Treatment of HIV-Infected Patients with HIV Protease Inhibitors: An Immune Restoration Disease?” AIDS 12 (1998): 2289-2293.

Kilby, J. Michael. “Switching HIV Therapies: Competing Host and Viral Factors.” The Lancet 375 (2010): 352.

Moatti, Jean-Paul, et al., eds. AIDS in Europe: New Challenges for the Social Sciences. New York: Routledge, 2000.

Villani, Paola, et al. “Antiretrovirals: Simlutaneous Determination of Five Protease Inhibitors and Three Nonnucleoside Transcriptase Inhibitors in Human Plasma.” Therapeutic Drug Monitoring 23 (2001): 380-388.

Wit, Ferdinand W. N. M., Joep M. A. Lange, and Paul A. Volberding. “New Drug Development: The Need for New Antiretroviral Agents.” In Global HIV/AIDS Medicine, edited by Paul A. Volberding et al. Philadelphia: Saunders/Elsevier, 2008.