Determining Responses to Two Different Vaccines in HIV and HCV Infected Individuals

Phase 1

Completed

• Conditions: HIV Infections; Hepatitis C
• Interventions: Biological: Twinrix; Biological: Decavac

• Registration Number: NCT00393276
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

Infection with either HIV or hepatitis C virus (HCV) affects immune system responses. The purpose of this study is to investigate the immune responses to two different vaccine formulations in HIV-infected, HCV-infected, and HCV/HIV- coinfected individuals.

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.

Study Timeline

• Study First Submitted: 2006-10-25
• Study First Submitted QC: 2006-10-25
• Study First Posted: 2006-10-27
• Study Start: 2007-08
• Primary Completion: 2009-07
• Study Completion: 2009-07
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-28
• Last Update Posted: 2021-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
B	Decavac	HIV-infected and ARV naive, with a CD4 cell count of 300 cells/mm3 or greater, with no prior or current opportunistic infection, and with no indication for HIV therapy. These participants will be HCV-uninfected.
A	Twinrix	HCV-infected defined as a positive result using polymerase chain reaction (PCR) without previous HCV-based therapy and without the presence of Child's B or C cirrhosis. These participants will be HIV-uninfected.
A	Decavac	HCV-infected defined as a positive result using polymerase chain reaction (PCR) without previous HCV-based therapy and without the presence of Child's B or C cirrhosis. These participants will be HIV-uninfected.
C	Decavac	HCV/HIV-coinfected as defined above in Arms A and B.
B	Twinrix	HIV-infected and ARV naive, with a CD4 cell count of 300 cells/mm3 or greater, with no prior or current opportunistic infection, and with no indication for HIV therapy. These participants will be HCV-uninfected.
C	Twinrix	HCV/HIV-coinfected as defined above in Arms A and B.

Primary Outcome Measures

Name	Time	Method
B-cell humoral responses	At Week 8
T-cell responses as reflected by hepatitis B and tetanus antibody titers	At Week 8
Dendritic cell, B-cell, and T-cell functional markers	At Study Entry

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (12)

UCSD Antiviral Research Center CRS; 🇺🇸 San Diego, California, United States

University of Colorado Hospital CRS; 🇺🇸 Aurora, Colorado, United States

Duke Univ. Med. Ctr. Adult CRS; 🇺🇸 Durham, North Carolina, United States

MetroHealth CRS; 🇺🇸 Cleveland, Ohio, United States

The Ohio State University Medical Center; 🇺🇸 Columbus, Ohio, United States

Massachusetts General Hospital Clinical Research Site (MGH CRS) CRS; 🇺🇸 Boston, Massachusetts, United States

IHV Baltimore Treatment CRS; 🇺🇸 Baltimore, Maryland, United States

Ucsf Aids Crs; 🇺🇸 San Francisco, California, United States

Case CRS; 🇺🇸 Cleveland, Ohio, United States

Columbia P&S CRS; 🇺🇸 New York, New York, United States

Trinity Health and Wellness Center CRS; 🇺🇸 Dallas, Texas, United States

Puerto Rico AIDS Clinical Trials Unit CRS; 🇵🇷 San Juan, Puerto Rico