A double-blind randomized placebo-controlled trial to further investigate glecaprevir/pibrentasvir (GLE/PIB), a direct acting antiviral (DAA) that has been associated with posttraumatic stress disorder (PTSD) symptom improvement when prescribed for the treatment of chronic hepatitis C viral infection (HCV).

N=92 patients with posttraumatic stress disorder (PTSD) will be enrolled into a double-blind randomized placebo-controlled trial to further investigate glecaprevir/pibrentasvir (GLE/PIB), a direct acting antiviral (DAA) that has been associated with PTSD symptom improvement when prescribed for the treatment of chronic hepatitis C viral infection (HCV). The research is intended to test the efficacy of GLE/PIB for PTSD symptom improvement in the absence of HCV.

Primary Aims:

Aim 1: Determine the efficacy of GLE/PIB for PTSD symptom improvement. Aim 2: Determine the efficacy of GLE/PIB for functioning improvement among patients with PTSD.

Aim 3: Assess the safety and tolerability of GLE/PIB treatment for patients with PTSD in the absence of HCV.

Inclusion Criteria:

1. Age 19-70 years
2. Weight ≥ 45 kg
3. Diagnosed with PTSD as determined by the CAPS-5 within seven days of enrollment
4. Eligible for Veterans Affairs healthcare
5. If person with childbearing potential, use of acceptable method of birth control (i.e., effective contraceptives, abstinence) is required.
6. Able to read, understand, and sign the informed consent document.

Exclusion (unable to participate) Criteria:

1. Pregnant or lactating person
2. Moderate or severe hepatic impairment (Child-Pugh B or C)
3. History of prior hepatic decompensation
4. Current use of drugs listed as having significant drug interactions on prescribing label
5. Advanced liver disease
6. Current or prior hepatitis B infection
7. Prior clinical use of GLE/PIB or HCV NS5A inhibitor AND NS3/4A protease inhibitor
8. Current HCV infection
9. Current psychosis or mania
10. Significant suicidal ideation
11. Unstable medical conditions
12. Current severe alcohol or substance use disorder (excluding nicotine)
13. Evidence-based PTSD psychotherapy changes in the past two months
14. Evidence-based PTSD medication changes in the past two months