An Ad5-Vectored HIV-1 Vaccine Elicits Cell-mediated Immunity but does not Affect Disease Progression in HIV-1-infected Male Subjects: Results From a Randomized Placebo-Controlled Trial (The Step Study)

• Published in: The Journal of infectious diseases Vol. 203; no. 6; pp. 765 - 772
• Main Authors: Fitzgerald, D. W., Janes, H., Robertson, M., Coombs, R., Frank, I., Gilbert, P., Loufty, M., Mehrotra, D., Duerr, A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.03.2011
• Subjects: Adenovirus; Adenoviruses, Human - genetics; Adenoviruses, Human - immunology; Adult; AIDS; AIDS Vaccines - immunology; Anti-Retroviral Agents - therapeutic use; Applied microbiology; Biological and medical sciences; Blotting, Western; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; Circumcision, Male; Disease-Free Survival; Double-Blind Method; Fundamental and applied biological sciences. Psychology; Genetic Vectors; HIV; HIV 1; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - prevention & control; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - physiology; HIV/AIDS; HLA antigens; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunity, Cellular; Infections; Infectious diseases; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Placebos; Proportional Hazards Models; RNA; RNA, Viral - blood; RNA, Viral - immunology; T lymphocytes; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral load; Viral Load - drug effects; Virology; Young Adult; Disease development; Immunopathology; HIV-1 virus; Retroviridae; AIDS; Cellular immunity; Vaccine; Immune deficiency; Lentivirus; Virus; Infection; Viral disease; Human immunodeficiency virus; Vector
• ISSN: 0022-1899; 1537-6613; 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiq114

Background. The Step study was a randomized trial to determine whether an adenovirus type 5 (Ad5) vector vaccine, which elicits T cell immunity, can lead to control of human immunodeficiency virus (HIV) replication in participants who became HIV-infected after vaccination. Methods. We evaluated the effect of the vaccine on trends in HIV viral load, CD4⁺ T cell counts, time to initiation of antiretroviral therapy (ART), and AIDS-free survival in 87 male participants who became infected with HIV during the Step study and who had a median of 24 months of post-infection follow-up. Results. There was no overall effect of vaccine on mean log 10 viral load (estimated difference between groups, -0.11; P = .47). In a subset of subjects with protective HLA types (B27, B57, B58), mean HIV-1 RNA level over time was lower among vaccine recipients. There was no significant difference in CD4⁺ T cell counts, time to ART initiation, or in AIDS-free survival between HIV-1-infected subjects who received vaccine versus those who received placebo. Conclusions. HIV RNA levels, CD4⁺ T cell counts, time to initiation of ART, and AIDS-free survival were similar in vaccine and placebo recipients. There may have been a favorable effect of vaccine on HIV-1 RNA levels in participants with HLA types associated with better control of HIV-1.