Indinavir, commonly marketed under the brand name Crixivan, is a powerful antiviral medication used in the management of HIV/AIDS (Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome). It belongs to the class of antiretroviral drugs known as HIV protease inhibitors, which play a crucial role in combination antiretroviral therapy (cART or HAART). Developed to interrupt the replication cycle of HIV, Ininavir has significantly contributed to improving the quality of life for people living with HIV.
Indenavir is a synthetic hydroxy aminopentane amide agent that appears as a white to off-white crystalline powder. It is not naturally occurring but is manufactured chemically to target viral replication. The molecular weight of Indinavir is 613.7 gm/mol, and it has a melting point between 167⁰C to 168⁰C.
Chemical structure of Indinavir:-
- The molecular formula of indinavir is [C36H47N5O4].
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| Structure of Indinavir |
- The IUPAC name of indinavir is,
(2S)-1-[(2S,4R)-4-benzyl-2-hydroxy-5-{{(1S,2R)-2-hydroxy-2,3-dihydro-1-inden-1-yl}amino}-5-oxopentyl]-N-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide.
Mechanism of action: How Indinavir Works
Indinavir is a potent HIV-1 protease inhibitor, which plays a vital role in preventing the maturation of infectious viral particles. The HIV protease enzyme is an as partly the protease essential for cleaving polyprotein precursors, especially the gag and gag-pol polyproteins-into smaller, functional viral proteins required for assembling mature virions.
During the HIV replication cycle, after the virus enters a host CD4+ T-Cell and reverse transcription occurs, long polypeptide chains are produced that need to be cleaved into structural proteins (such as capsid, matrix, and nucleocapsid proteins) and enzymes (reverse transcriptase, integrase, and protease) to form infectious virus particles. Indinavir binds reversibly to the active site of the HIV-1 protease enzyme, thereby blocking its catalytic activity.
This inhibition halts the cleavage of viral polyproteins, resulting in the formation of immature, non-infectious and defective virus particles. These defective particles cannot go on to infect new cells, thus reducing the overall viral load in the patients blood stream.
Indinavir is selective for HIV-1 protease and does not significantly inhibit human protease, making it effective and specific in its action. However, as it does not eliminate the virus from the body, it was always used in combination with antiretroviral therapy (cART) to prevent the emergence of drug resistance and to maximise therapeutic outcomes.
Moreover, ritonavir, another protease inhibitor, is often co-administered with indinavir to boost its plasma concentration by inhibiting cytochrome P450 3A4 metabolism, allowing for sustained therapeutic levels.
In summary, indinavir disrupts a critical step in the HIV life cycle, helping to control infections and prolong the health of individuals living with HIV/AIDS.
Dosage and Administration Guidelines:-
Indinavir is typically prescribed at 800 mg every 12 hours, combined with ritonavir (100-200 mg) to boost effectiveness. It should be taken on an empty stomach or with a light, low-fat meal to maximise absorption. Adequate hydration, at least 1.5 litres of water daily, is essential to prevent kidney stones, a known side effect. Strict dose adherence is crucial to maintain viral suppression and avoid HIV drug resistance. Dosing may be adjusted in patients with liver issues. Always follow your healthcare provider's instructions when using Indinavir as part of your HIV/AIDS treatment plan.
Clinical uses of Indinavir:-
Indinavir is not a cure for HIV or AIDS, but when used in combination with other anti-retroviral drugs, it significantly reduces viral load and improves immune system health. Its main uses include:
- Treatment of HIV infections in adults and adolescents
- Slowing disease progression and reducing the likelihood of opportunistic infections
- Preventing viral transmission when the viral load is suppressed
Potential Side Effects of Indinavir:-
Like most anti-retroviral medications, indinavir may lead to side effects, particularly if not taken correctly or if overdosed. Some of the common and serious side effects include:
- Hemolytic anemia
- Nausea and vomiting
- Diarrhea and abdominal discomfort
- Kidney stone (nephrolithiasis)
- Fatigue and weakness
- Lipodystrophy (abnormal fat redistribution)
- Hyperglycemia and insulin resistance
Conclusion:-
While newer HIV protease inhibitors have largely overtaken indinavir in popularity due to improved tolerability and dosing convenience, Indinavir will play a revolutionary role in the early treatment of HIV. It remains a part of the therapeutic arsenal in select cases and provides critical insights into viral replication inhibition. Whether you are a healthcare professional, patient, or researcher, understanding Indinavir's mechanism, uses, and impact can offer valuable knowledge in the fight against HIV/AIDS.
Frequently Asked Questions (FAQs):-
1. Is Indinavir still used in HIV treatment?
Indinavir has largely been replaced by newer protease inhibitors with better side effect profiles, but it may still be used in some resource-limited settings or treatment-experienced patients.
2. Can Indinavir cure HIV/ AIDS?
No. Indinavir helps manage HIV infection and reduce viral load, but does not cure HIV/AIDS.
3. What should I avoid while taking indinavir?
Avoid fatty meals, alcohol, and medications that interact with CYP3A4 enzymes. Drink plenty of fluids to prevent kidney stones.
4. Is Indinavir safe during pregnancy?
Use during pregnancy should be discussed with a healthcare provider, as safer alternatives may be available.
5. What happens if I miss a dose?
Take the missed dose as soon as you remember. If it's almost time for the next dose, skip the missed one. Never double up doses.
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