Randomized, Open-label Phase II Trial to Assess the Safety and Immunogenicity of MVA-BN Smallpox Vaccine in Immunocompromised Subjects With HIV Infection

Inclusion Criteria

• Male and female subjects aged between 18-45 years, vaccinia-naïve.
• HIV-1 infection documented by ELISA and confirmed by Western blot at any time prior to study entry. HIV-1 deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), HIV-1 culture, HIV-1 antigen, plasma HIV-1 ribonucleic acid (RNA), or a second antibody test other than ELISA is acceptable as an alternative test at any time prior to study entry.
• On stable antiretroviral therapy (ART) i.e. Combination ART for at least 6 months. Subject must be on the same ART regimen for at least 12 weeks with no change prior to enrollment in this clinical trial.
• Screening HIV-1 RNA 60 ml/min as estimated by the Cockcroft-Gault equation.
• For men: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dl x 72) = CrCl (ml/min)
• For women: multiply the result by 0.85 = CrCl (ml/min).Adequate hepatic function defined as: Total bilirubin ≤ 2 x upper limit normal (ULN) in the absence of other evidence of significant liver disease
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 2.5 x ULN.
• Troponin I < 2 x ULN at entry in the clinical trial.
• Electrocardiogram (ECG) without clinically significant findings (e.g. any kind of atrioventricular or intraventricular conditions or blocks such as complete left or right bundle branch block, AV node block, QTc or PR prolongation, premature atrial contractions or other atrial arrhythmia, sustained ventricular arrhythmia, two premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia).

Exclusion Criteria

• Pregnant or breast-feeding women.
• Typical vaccinia scar.
• Known or suspected history of smallpox vaccination.
• History of vaccination with any poxvirus-based vaccine.
• Uncontrolled serious infection, i.e. not responding to antimicrobial therapy.
• History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject or would limit the subject's ability to complete the trial including uncontrolled diabetes as according to the 'Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events' Version 1.0, December 2004, Clarification August 2009.
• History of or active autoimmune disease, persons with vitiligo or thyroid disease taking thyroid replacement are not excluded.
• Known or suspected impairment of immunologic function except those defined in the inclusion criteria, including, but not limited to clinically significant liver disease, diabetes mellitus type I and moderate to severe kidney impairment.
• History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure. Subjects with history of skin cancer must not be vaccinated at the previous tumor site.
• History or clinical manifestation of clinically significant and severe hematological, pulmonary, central nervous, cardiovascular or gastrointestinal disorders (except HIV infection, chronic or active Hepatitis-B-Virus or Hepatitis-C-Virus infection).
• Clinically significant psychiatric disorder not adequately controlled by medical treatment.
• History of coronary heart disease, myocardial infarction, angina pectoris, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor.
• Known history of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before age 50 years.
• Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool (http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof). NOTE: This criterion applies only to subjects 20 years of