Safety and Immunogenicity of ChAdV63.HIVconsv and MVA.HIVconsv Candidate HIV-1 Vaccines in Recently HIV-1 Infected Individuals

It is a Phase I, multicenter primary/booster therapeutic vaccination study to evaluate the safety and immunogenicity of ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly according to a 0-8 weeks or a 0-24 weeks schedule to recently HIV-1 infected individuals with early viral suppression 6 months after initiation of Tenofovir/Emtricitabine plus Raltegravir.

24 patients who meet all eligibility criteria will be enrolled, first 10 individuals will be assigned in the 0-24 week prime/boost regimen (ARM A). The next 10 volunteers will be assigned in the 0-8 week prime/boost regimen (ARM B).Four additional volunteers will be included as 'back-up' and assigned 2 in ARM A and 2 in ARM B to cover a possible 10% of patients who drop-off during the follow-up. Purpose of staging of 2 study arms is just to shorten overall study duration (from screening of first volunteer to 6 months after last immunisation of last volunteer).

Lastly, 24 patients who also meet all eligibility criteria will be enrolled as controls, will also initiate promptly antiretroviral treatment with Tenofovir/Emtricitabine plus Raltegravir but will not receive the investigational vaccines. Control patients will consecutively be assigned to the 0-24w control arm (ARM C 'long control') or 0-8w control arm (ARM D 'short control') until 12 patients per arm are reached. The purpose of the control arms is to have a study population to compare the viral reservoir decay kinetics in the absence of vaccination.

Inclusion criteria

• Male or female, aged 18-60 years
• Confirmed HIV-1 seropositive documented in the past 6 months (by acute antiretroviral syndrome, p24 antigenemia and/or ELISA seroconversion)
• Willing and able to give written informed consent for participation in the study
• Willing and able to adhere to an effective HAART regimen for the duration of the study
• Cluster of differentiation 4 (CD4)+ T cell count > 350 cells/ml at screening and at the preceding clinic visit
• No new AIDS-defining diagnosis or progression of HIV-related disease.
• Haematological and biochemical laboratory parameters as follows: Haemoglobin > 10g/dl, Platelets > 100.000/dl, alanine aminotransferase (ALT) ≤ 2.5 x ULN, Creatinine ≤ 1.3 x upper limit of normal (ULN)
• Serology: negative for hepatitis B surface antigen OR HbsAg positive with Hepatitis B Virus (HBV)-DNA < 1000 copies/ml; negative for hepatitis C antibodies OR confirmed clearance of Hepatitis C Virus (HCV) infection (spontaneous or following treatment); negative syphilis serology or documented adequate treatment of syphilis if positive enzimeimmunoassay (EIA) Immonoglobulin G (IgG) or Treponema pallidum hemagglutination assay (TPHA)
• Available for follow up for duration of study (screening + 72 weeks) and willing to comply with the protocol requirements
• Women of child-bearing age must not be pregnant, not be planning a pregnancy or breast-feeding. Sexually active women must be willing to use an approved method of contraception from screening until 4 months after the second immunisation. Sexually active men in heterosexual relationships must be willing to use an approved method of contraception with their partners from screening until 4 months after the second immunisation.

Exclusion criteria

• Confirmed HIV-2 seropositive
• Positive pregnancy test
• Presence of Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTI) mutation in the screening genotype
• Participation in another clinical trial within 12 weeks of study entry
• History of autoimmune disease other than HIV-related auto-immune disease.
• History or clinical manifestations of any physical or psychiatric disorder which could impair the subject's ability to complete the study
• History of anaphylaxis or severe adverse reaction to vaccines
• Previous immunisation with any experimental immunogens
• Receipt of blood products within 6 months of study entry
• Treatment for cancer or lymphoproliferative disease within 1 year of study entry
• Receipt of vaccines other than Hepatitis B vaccine within 2 weeks of study entry or planned receipt within 2 weeks of vaccination
• Any other prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study
• Current or recent use (within last 3 months) of interferon or systemic corticosteroids or other immunosuppressive agents