Model Answer
0 min readIntroduction
Hepatitis C virus (HCV) infection is a major global health concern, affecting an estimated 71 million people worldwide. Historically, treatment involved interferon-based regimens with limited efficacy and significant side effects. However, the advent of direct-acting antiviral agents (DAAs) has revolutionized HCV therapy, offering cure rates exceeding 95% with improved tolerability. These DAAs target specific viral proteins essential for HCV replication, disrupting the viral life cycle. This answer will detail the various classes of DAAs currently used in the treatment of Hepatitis C infection.
Direct-Acting Antiviral Agents for Hepatitis C Infection
DAAs are categorized based on their target within the HCV lifecycle. The primary targets are the NS3/4A protease, the NS5A protein, and the NS5B RNA-dependent RNA polymerase.
1. NS3/4A Protease Inhibitors
These agents block the NS3/4A serine protease, an enzyme crucial for cleaving the HCV polyprotein into functional viral proteins. They are typically administered with ritonavir (a pharmacokinetic enhancer) to boost their levels in the blood.
- Telaprevir: First-generation protease inhibitor, less commonly used now due to higher side effect profile and lower efficacy compared to newer agents.
- Boceprevir: Similar to telaprevir, also less frequently used.
- Grazoprevir: A second-generation protease inhibitor, often combined with elbasvir.
2. NS5A Inhibitors
NS5A is a multifunctional protein involved in viral RNA replication, assembly, and secretion. NS5A inhibitors disrupt these processes, effectively halting viral propagation. These are generally well-tolerated.
- Ledipasvir: Typically combined with sofosbuvir for pan-genotypic treatment.
- Velpatasvir: Highly potent and pan-genotypic, often combined with sofosbuvir.
- Elbasvir: Combined with grazoprevir, effective against genotypes 1 and 6.
- Pibrentasvir: Combined with glecaprevir, offering pan-genotypic coverage.
3. NS5B Polymerase Inhibitors
The NS5B polymerase is responsible for replicating the HCV RNA genome. These inhibitors can be nucleoside/nucleotide analogs or non-nucleoside inhibitors.
- Sofosbuvir: A nucleotide analog inhibitor, highly effective and well-tolerated. It is a cornerstone of many HCV treatment regimens.
- Dasabuvir: A non-nucleoside inhibitor, used in combination with other DAAs, particularly for genotype 1.
- Beclabuvir: Another non-nucleoside inhibitor, currently under investigation.
4. Combination Regimens
DAAs are rarely used as monotherapy. Effective treatment typically involves combinations of two or more DAAs to maximize efficacy and minimize the development of resistance.
| Regimen | Target Proteins | Genotypes Covered |
|---|---|---|
| Sofosbuvir/Ledipasvir | NS5B, NS5A | 1, 4, 5, 6 |
| Sofosbuvir/Velpatasvir | NS5B, NS5A | All (Pan-genotypic) |
| Grazoprevir/Elbasvir | NS3/4A, NS5A | 1, 6 |
| Glecaprevir/Pibrentasvir | NS3/4A, NS5A | All (Pan-genotypic) |
Common Side Effects: DAAs are generally well-tolerated. Common side effects include fatigue, headache, nausea, and rash. Serious side effects are rare.
Conclusion
The development of DAAs has dramatically improved the treatment landscape for Hepatitis C, offering high cure rates and improved quality of life for patients. The availability of pan-genotypic regimens like sofosbuvir/velpatasvir and glecaprevir/pibrentasvir simplifies treatment decisions. Ongoing research focuses on developing even more potent and convenient DAAs, as well as strategies to improve access to treatment globally, particularly in resource-limited settings. Continued surveillance for resistance is also crucial to maintain the long-term effectiveness of these therapies.
Answer Length
This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.