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

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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)

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])


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 24 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>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)])<br>* Recombinant experimental therapeutic vaccine using the modified vaccinia Ankara vector given at study entry and Week 4<br>Biological: rFPV-HIV (env/gag [TBC-F357] + tat/rev/nef-RT [TBC-F349])<br>* Recombinant experimental therapeutic vaccine using fowlpox vector given at Weeks 8 and 24<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Treatment Experienced, HIV Therapeutic Vaccine