The Voluntary Discontinuation of Amprenavir
Amprenavir was one of the early protease inhibitors (PIs) used for HIV treatment, working by blocking the HIV protease enzyme to prevent viral replication. However, it had drawbacks such as a high pill burden and challenging side effects. Its manufacturer, GlaxoSmithKline, developed a more advanced version, fosamprenavir (Lexiva). GlaxoSmithKline announced the discontinuation of Agenerase (Amprenavir) oral solution and 50 mg capsules in the U.S. by the end of October 2007, with adult 150 mg capsules withdrawn earlier. This was a commercial decision based on declining demand and the availability of fosamprenavir, not due to safety or efficacy issues. Patients on amprenavir were advised to switch to other antiretroviral medications, with Lexiva being the closest alternative.
The Evolution from Amprenavir to Fosamprenavir
Fosamprenavir was an improvement over amprenavir, formulated as a prodrug that converted to amprenavir in the body. This offered better solubility and bioavailability, leading to more consistent drug levels. It also reduced the daily pill burden and was generally better tolerated. Despite these advantages, fosamprenavir was also discontinued in the U.S. as of January 1, 2024, by ViiV Healthcare due to ongoing advancements in HIV care.
Comparison of Older vs. Modern HIV Treatments
The progression from amprenavir to modern antiretroviral therapy (ART) showcases significant improvements in effectiveness, tolerability, and convenience. Below is a comparison:
| Feature | Older Regimens (e.g., Amprenavir) | Modern Regimens (e.g., Biktarvy, Dovato) |
|---|---|---|
| Availability | Discontinued | Widely available, current standard of care |
| Pill Burden | High (required multiple pills throughout the day) | Low (often a single tablet once daily) |
| Dosage Frequency | Complex, requiring multiple administrations daily | Simplified (typically once daily), improving adherence |
| Tolerability | Significant gastrointestinal side effects, skin rash | Generally well-tolerated with fewer side effects |
| Effectiveness | Effective at the time, but less potent than newer drugs | Highly potent, achieves rapid viral suppression |
| Drug-Drug Interactions | Significant potential for interactions via CYP3A4 inhibition | Potential interactions exist, but often more manageable |
| Long-Acting Options | Not available | Long-acting injectables now available (e.g., Cabenuva) |
The Landscape of Modern Antiretroviral Alternatives
The discontinuation of amprenavir and fosamprenavir reflects positive advancements in HIV treatment. The current standard of care, highly effective antiretroviral therapy (HAART), typically combines drugs from different classes. Modern regimens prioritize convenience and efficacy, incorporating drug classes such as:
- Integrase Strand Transfer Inhibitors (INSTIs): Like dolutegravir and bictegravir, these block the integrase enzyme essential for HIV.
- Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs): Including emtricitabine and tenofovir, these form a core part of many regimens.
- Protease Inhibitors (PIs): Modern PIs such as darunavir are still used, often boosted with other medications.
- Capsid Inhibitors: A newer class like lenacapavir disrupts the HIV capsid at multiple stages.
Single-tablet regimens (STRs), such as Biktarvy, combine multiple drugs into one daily pill to simplify treatment and improve adherence. Long-acting injectable options like Cabenuva also offer alternatives to daily oral medication.
Conclusion
In summary, amprenavir is no longer available, having been discontinued along with its successor, fosamprenavir, in favor of contemporary antiretroviral drugs. This change was a positive development, driven by the creation of more effective, convenient, and better-tolerated HIV treatments. The move from older, more complex regimens to modern therapies, including single-tablet and long-acting injectable options, has significantly improved the lives and prognoses of individuals with HIV. Patients who previously used amprenavir or are seeking HIV treatment should consult a healthcare provider to explore the current range of advanced treatment choices.
For additional information on current HIV treatment guidelines, resources are available from the National Institute of Allergy and Infectious Diseases (NIAID)(https://www.niaid.nih.gov/diseases-conditions/antiretroviral-drug-development).
