Protease inhibitors
Protease inhibitors (PIs) are a class of antiretroviral drugs primarily used to treat infections caused by human immunodeficiency virus (HIV) and hepatitis C. They work by blocking the maturation and replication of viruses at a late stage of their life cycle, preventing cells from integrating essential proteins into viral particles. The introduction of PIs has significantly improved the life expectancy of individuals with HIV and hepatitis C. However, they can interact with other medications, leading to potential side effects such as kidney stones, nausea, and gastrointestinal issues, along with more serious risks like liver dysfunction and drug-resistant viral mutations. To mitigate these risks, clinicians may use combinations of drugs, enhancing the effectiveness of PIs while minimizing doses. Since their development in the late 1980s to early 1990s, PIs have become the largest class of drugs in the fight against HIV, providing patients with a previously unattainable quality of life. Ongoing research is even exploring the potential use of PIs in cancer treatment.
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.