Optimizing Vaccine Responsiveness in HIV-1 and HCV Infections by Identifying Determinants of Responsiveness: A Pilot Study

Brief Summary

Detailed Description

Individuals with HCV and HIV coinfection are especially hard to treat, and as a result, account for a high rate of deaths each year. Because HCV and HIV share transmission routes, HCV/HIV coinfection is common. Liver disease has emerged as a significant cause of death in individuals coinfected with HCV and HIV. Currently, the mechanisms by which HCV and HIV interact in HCV/HIV-coinfected individuals, including how these infections affect immune responses, are poorly understood. Research suggests that vaccination may prevent other comorbidities associated with HCV/HIV coinfection; however, responses to new vaccine antigens have been shown to be impaired in HCV or HIV-infected individuals. The purpose of this study is to identify the innate and adaptive immune defects present in HCV-infected, HIV-infected, and HCV/HIV-coinfected individuals. This study will evaluate whether these innate and adaptive immune defects predict responses to HBV neoantigen in the form of both a diphtheria/tetanus toxoid immunization (Decavac)and a hepatitis A-hepatitis B immunization (Twinrix). This study will last approximately 24 weeks. Participants will be stratified to one of three arms, based on their HCV and HIV status: * Arm A will enroll HCV-infected individuals who are HIV-uninfected * Arm B will enroll HIV-infected individuals who are HCV-uninfected * Arm C will enroll HCV/HIV-coinfected individuals Arms B and C will open for enrollment before Arm A. Opening of enrollment for Arm A will be determined by the accrual progress of Arms B and C as evaluated by the ACTG Scientific Agenda Steering committee. All participants will receive Decavac vaccination on Day 0, and a Twinrix vaccination on Days 0, 7, and 21. Study visits will occur around Days 0, 7, and 21, and at Weeks 6, 8, 12, and 24; all visits will include medical and medication history, blood collection, and a physical exam. Medication to treat HCV or HIV will not be provided by the study.

Primary Outcomes

Secondary Outcomes

• B-cell functional marker(At Week 6)
• T-cell responses to hepatitis A, hepatitis B, and tetanus antigens(At Weeks 3 and 8)
• Longitudinal serum antibody titers to hepatitis A, hepatitis B, and tetanus (B-cell responses)(At Study Entry and Weeks 1, 3, 6, 8, 12, and 24)
• CD4/CD8 and HCV genotype(At Study entry)
• Baseline antibody status for hepatitis B core antigen (anti-HBc)(At Study entry)