Therapeutic vaccination with p24-VLP and zidovudine augments HIV-specific cytotoxic T lymphocyte activity in asymptomatic HIV-infected individuals.
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.
Department of Clinical Immunology, ICPMR, Westmead Hospital, Wentworthville, NSW, Australia. elizab@westmead.wh.usyd.edu.au
E M
EM
Benson
J
J
Clarkson
M
M
Law
P
P
Marshall
A D
AD
Kelleher
D E
DE
Smith
G
G
Patou
G J
GJ
Stewart
D A
DA
Cooper
R A
RA
French
D016915:AIDS Vaccines / Q000627:therapeutic use*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000628:therapy* / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D015331:Cohort Studies; D005260:Female; D006678:HIV / Q000302:isolation & purification; D016655:HIV Core Protein p24 / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use*
D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D012367:RNA, Viral; C065031:p24-VLP vaccine; D015215:Zidovudine