What is the most appropriate treatment plan for a patient with HIV (Human Immunodeficiency Virus) and HCV (Hepatitis C Virus) genotype 1a, taking darunavir (Prezista), ritonavir (Norvir), and emtricitabine/tenofovir alafenamide (Descovy), with normal CD4 (Cluster of Differentiation 4) count and undetectable HIV RNA (Ribonucleic Acid)?

Recommended Treatment Plan

For this HIV/HCV genotype 1a coinfected patient without cirrhosis who is treatment-naïve, glecaprevir/pibrentasvir 300/120mg daily for 8 weeks (Option A) is the most appropriate treatment.

Rationale for Glecaprevir/Pibrentasvir

The 2020 EASL guidelines explicitly recommend glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with genotypes 1a without cirrhosis, achieving high SVR rates with excellent tolerability 1. This represents the most current guideline-based recommendation for this specific patient population.

Supporting Evidence for 8-Week Duration

• Treatment-naïve patients infected with HCV genotype 1a without cirrhosis should receive glecaprevir/pibrentasvir for 8 weeks 1
• Clinical trials demonstrate 99% SVR12 rates in genotype 1a patients with compensated cirrhosis treated with this regimen 2
• Real-world data from 246 non-cirrhotic DAA-naïve patients with genotype 1 or 2 showed 89% SVR12 in intention-to-treat analysis with the 8-week regimen 3
• The EXPEDITION-1 trial showed 99% SVR12 in patients with compensated cirrhosis, supporting efficacy even in more advanced disease 4

HIV Coinfection Considerations

HIV coinfection does not alter the treatment recommendation, as the same HCV regimens are used regardless of HIV status 2. However, drug-drug interactions must be carefully evaluated:

• The patient's current antiretroviral regimen (darunavir/ritonavir/emtricitabine/tenofovir alafenamide) requires interaction assessment 2
• Glecaprevir/pibrentasvir has demonstrated safety and efficacy in HIV-coinfected populations 5
• No dose adjustments of glecaprevir/pibrentasvir are needed for HIV coinfection 2

Why Other Options Are Less Appropriate

Option B: Ledipasvir/Sofosbuvir

While ledipasvir/sofosbuvir is effective, it requires 12 weeks of treatment compared to 8 weeks with glecaprevir/pibrentasvir in this non-cirrhotic, treatment-naïve patient 1. The 2015 EASL guidelines recommended 12 weeks for patients without cirrhosis 1, but newer pangenotypic regimens offer shorter duration with equivalent efficacy.

Option C: Sofosbuvir/Velpatasvir

Sofosbuvir/velpatasvir requires 12 weeks of treatment 1. While highly effective (98% SVR12 in genotype 1a patients) 1, the 8-week glecaprevir/pibrentasvir regimen offers equivalent efficacy with shorter treatment duration 1.

Option D: Elbasvir/Grazoprevir

Elbasvir/grazoprevir has significant limitations in genotype 1a infection due to NS5A resistance-associated polymorphisms (RASs) 1, 6:

• Patients with genotype 1a and baseline NS5A polymorphisms require 16 weeks plus ribavirin 6
• Testing for NS5A RASs is recommended before initiating this regimen 6
• This patient's high viral load (7 million IU/mL) and lack of RAS testing make this option less favorable 1
• The FDA label specifically requires RAS testing for genotype 1a patients 6

Treatment Monitoring

Pre-Treatment Requirements

• Hepatitis B testing (HBsAg and anti-HBc) must be completed before initiating therapy 6
• Baseline hepatic laboratory testing is required 6

On-Treatment Monitoring

• Hepatic laboratory testing should be performed at treatment week 8 6
• Assessment for adverse events, particularly fatigue and headache (most common with glecaprevir/pibrentasvir) 4
• No specific HCV RNA monitoring is required during the 8-week treatment course 1

Post-Treatment Assessment

• SVR12 assessment (HCV RNA <15 IU/mL at 12 weeks post-treatment) confirms cure 2
• Continued monitoring for hepatocellular carcinoma is not required in this non-cirrhotic patient after achieving SVR 2

Common Pitfalls to Avoid

Drug-drug interactions are the primary concern in this HIV-coinfected patient 2:

• Ritonavir (part of the patient's HIV regimen) may interact with glecaprevir/pibrentasvir, though this combination is generally manageable 5
• Strong CYP3A inducers are contraindicated with glecaprevir/pibrentasvir 6
• Careful review of all concomitant medications is essential before initiating therapy 6

Do not extend treatment duration unnecessarily: The 8-week regimen is sufficient for this treatment-naïve, non-cirrhotic patient 1. Extending to 12 weeks does not improve outcomes and increases treatment burden 1.

Avoid elbasvir/grazoprevir without RAS testing in genotype 1a: This regimen requires baseline NS5A RAS testing, and patients with RASs need 16 weeks plus ribavirin 6, making it a less practical choice.