Therapeutic vaccination with p24-VLP and zidovudine augments HIV-specific cytotoxic T lymphocyte activity in asymptomatic HIV-infected individuals

• Published in: AIDS research and human retroviruses Vol. 15; no. 2; p. 105
• Main Authors: Benson, E M, Clarkson, J, Law, M, Marshall, P, Kelleher, A D, Smith, D E, Patou, G, Stewart, G J, Cooper, D A, French, R A
• Format: Journal Article
• Language: English
• Published: United States 20.01.1999
• Subjects: Acquired Immunodeficiency Syndrome - immunology; Acquired Immunodeficiency Syndrome - therapy; Acquired Immunodeficiency Syndrome - virology; Adult; AIDS Vaccines - therapeutic use; Anti-HIV Agents - therapeutic use; CD4-CD8 Ratio; Cohort Studies; Female; HIV - isolation & purification; HIV Core Protein p24 - therapeutic use; Humans; Male; Middle Aged; Polymerase Chain Reaction; RNA, Viral - blood; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; Viral Load; Zidovudine - therapeutic use
• ISSN: 0889-2229; 1931-8405
• DOI: 10.1089/088922299311538

This study evaluates the impact of therapeutic vaccination with p24-VLP and zidovudine on the induction or maintenance of HIV-specific cytotoxic lymphocyte activity in a cohort of asymptomatic patients with CD4 counts greater than 400 cells/microl. In a dummy, randomized, phase II clinical trial of the therapeutic vaccine, participants were randomized to one of three arms for 6 months: p24-VLP (500 microg) in alum monthly plus zidovudine 200 mg tds, alum adjuvant plus zidovudine, or p24-VLP plus placebo. Subjects were studied for a total of 52 weeks from baseline. Monitoring included viral load, CD4 and CD8 counts, markers of immune activation, delayed-type hypersensitivity (DTH) skin testing, and cytotoxic T lymphocyte (CTL) measurement. The nine subjects who received p24-VLP and zidovudine had an augmentation and/or broadening of their CTL response compared with baseline (p = 0.004). The eight subjects receiving p24-VLP and seven subjects receiving zidovudine did not have a statistically significant increase or broadening of CTL activity. The augmentation of the CTL response in the subjects who received p24-VLP and zidovudine was not associated with a decline in viral load or an increase in CD8 counts. This study suggests that HIV-specific CTL activity can be augmented in HIV-infected individuals receiving p24-VLP and zidovudine, supporting the hypothesis of therapeutic vaccination in the presence of antiretroviral therapy.