Safety of Recombinant HIV Vaccines in HIV Infected Young Adults on Stable Therapy

A Phase I, Open-Label Study to Evaluate the Safety and Tolerability of Recombinant HIV-1 Vaccines in HIV-1 Infected Young Adults With Control of HIV-1 Replication and on Stable Highly Active Antiretroviral Therapy (HAART)

The purpose of this study is to determine the safety of two recombinant HIV vaccines in HIV infected young adults on stable anti-HIV therapy.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: rMVA-HIV (env/gag [TBC-M358] + tat/rev/nef-RT [TBC-M335)]); Biological: rFPV-HIV (env/gag [TBC-F357] + tat/rev/nef-RT [TBC-F349])

Detailed Description

By helping to control viral replication, HAART has dramatically improved the prognosis for HIV infected individuals. However, because of extensive side effects, some of which may be acute and life-threatening, many patients find it difficult to tolerate a HAART regimen. HAART-associated long-term morbidity or mortality contribute to this difficulty. Administering an HIV therapeutic vaccine might allow HIV infected individuals to delay or interrupt treatment, avoiding the side effects associated with antiretroviral exposure. This study will evaluate the safety of two injections of two recombinant therapeutic vaccines in HIV infected young adults who are currently on stable HAART.

This study will last 72 weeks. All participants will receive two rMVA vaccines (env/gag and tat/rev/nef-RT) at study entry and at Week 4 and two rFPV vaccines (env/gag and tat/rev/nef-RT) at Weeks 8 and 24. Safety will be assessed immediately after each immunization and at 1 hour and 48 hours postimmunization. There will be 16 study visits over 72 weeks. A physical exam, blood collection, and administration of an adherence module will occur at most visits. An electrocardiogram (ECG) will occur at study entry and Weeks 2 and 10. Urine collection will occur at study entry and Weeks 4, 8, and 24.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico
    • Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Usc La Nichd Crs
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles NICHD CRS
  • Colorado
    • Aurora, Colorado, United States, 80218-1088
      • Univ. of Colorado Denver NICHD CRS
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Chicago Children's CRS
  • Maryland
    • Baltimore, Maryland, United States
      • Univ. of Maryland Baltimore NICHD CRS
  • New York
    • New York, New York, United States
      • Columbia IMPAACT CRS
  • North Carolina
    • Durham, North Carolina, United States
      • DUMC Ped. CRS
  • Tennessee
    • Memphis, Tennessee, United States, 38105-2794
      • St. Jude/UTHSC CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 24 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-1 infected
• CD4 count of 350 cells/mm3 or greater
• If hepatitis B or C infected, infection must be chronic and stable
• Normal electrocardiogram (ECG)
• On stable HAART consisting of at least 3 different antiretrovirals from 2 different classes AND with a viral load of less than 100 copies/ml for at least 6 months prior to study entry
• Willing to use acceptable forms of contraception. Females enrolled in the study must use contraception for at least 21 days prior to first vaccination until the last study visit. Males enrolled in the study must use a condom from the first vaccination until one month after the last vaccination.
• Willing to follow all study requirements
• Available for follow-up for the duration of the study

Exclusion Criteria:

• History of allergic reaction to eggs or egg products
• Known hypersensitivity to vaccine components
• Chemotherapy for active cancer in the 12 months prior to study entry
• Prior vaccination with any HIV-1 vaccine
• Prior vaccination against smallpox
• Prior vaccinia immunization
• Any immunization within 1 month of study screening
• History of or known active heart disease including myocardial infarction, angina pectoris, congestive heart failure, cardiomyopathy, pericarditis, stroke or transient ischemic attack, chest pain or shortness of breath with activity such as walking upstairs, mitral valve prolapse, or other heart conditions under a doctor's care
• Immunomodulatory agents, gamma globulin, or investigational agents within 6 months of study entry
• Systemic steroids, including nonprescription street steroids, within 6 months of study entry
• Documented or suspected serious bacterial infection, metabolic illness, cancer, or immediate life-threatening condition
• Any clinically significant diseases other than HIV infection or clinically significant findings during study screening that, in the investigator's opinion, may interfere with the study
• Current alcohol or drug abuse that, in the investigator's opinion, may interfere with the study
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; All participants in this study will receive two injections of the rMVA-HIV vaccine and the rFPV-HIV vaccine	Biological: rMVA-HIV (env/gag [TBC-M358] + tat/rev/nef-RT [TBC-M335)]); Recombinant experimental therapeutic vaccine using the modified vaccinia Ankara vector given at study entry and Week 4; Biological: rFPV-HIV (env/gag [TBC-F357] + tat/rev/nef-RT [TBC-F349]); Recombinant experimental therapeutic vaccine using fowlpox vector given at Weeks 8 and 24

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Development of any adverse events of Grade 3 or higher	Throughout study
Development of adverse events of Grade 3 or higher attributed to the study vaccines	Throughout study
Viral breakthrough to greater than 1,000 copies/ml	During the first 24 weeks of study

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Study Chair: Coleen K. Cunningham, MD, Pediatric Infectious Diseases, Duke University

Publications and helpful links

General Publications

• Caputo A, Gavioli R, Ensoli B. Recent advances in the development of HIV-1 Tat-based vaccines. Curr HIV Res. 2004 Oct;2(4):357-76. doi: 10.2174/1570162043350986.
• Cosma A, Nagaraj R, Buhler S, Hinkula J, Busch DH, Sutter G, Goebel FD, Erfle V. Therapeutic vaccination with MVA-HIV-1 nef elicits Nef-specific T-helper cell responses in chronically HIV-1 infected individuals. Vaccine. 2003 Dec 8;22(1):21-9. doi: 10.1016/s0264-410x(03)00538-3.
• Kent SJ, Zhao A, Best SJ, Chandler JD, Boyle DB, Ramshaw IA. Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus. J Virol. 1998 Dec;72(12):10180-8. doi: 10.1128/JVI.72.12.10180-10188.1998.
• Mwau M, Cebere I, Sutton J, Chikoti P, Winstone N, Wee EG, Beattie T, Chen YH, Dorrell L, McShane H, Schmidt C, Brooks M, Patel S, Roberts J, Conlon C, Rowland-Jones SL, Bwayo JJ, McMichael AJ, Hanke T. A human immunodeficiency virus 1 (HIV-1) clade A vaccine in clinical trials: stimulation of HIV-specific T-cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans. J Gen Virol. 2004 Apr;85(Pt 4):911-919. doi: 10.1099/vir.0.19701-0.
• Pancharoen C, Ananworanich J, Thisyakorn U. Immunization for persons infected with human immunodeficiency virus. Curr HIV Res. 2004 Oct;2(4):293-9. doi: 10.2174/1570162043351084.
• Shiu C, Cunningham CK, Greenough T, Muresan P, Sanchez-Merino V, Carey V, Jackson JB, Ziemniak C, Fox L, Belzer M, Ray SC, Luzuriaga K, Persaud D; Pediatric AIDS Clinical Trials Group P1059 Team. Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral therapy. J Virol. 2009 Oct;83(19):9731-42. doi: 10.1128/JVI.00570-09. Epub 2009 Jul 15.

Study record dates

Study Major Dates

• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: April 5, 2005
• First Submitted That Met QC Criteria: April 5, 2005
• First Posted (Estimate): April 6, 2005

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Treatment Experienced; HIV Therapeutic Vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: P1059; 10051 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); PACTG P1059