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 lymph ocyte activity in a cohort of asymptomatic patients with CD4 counts greater than 400 cells/mu l. In a dummy, randomized, phase II clinical trial of th e therapeutic vaccine, participants were randomized to one of three arms fo r 6 months: p24-VLP (500 mu g) in alum monthly plus zidovudine 200 mg tds, alum adjuvant plus zidovudine, or p24-VLP plus placebo. Subjects were studi ed for a total of 52 weeks from baseline. Monitoring included viral load, C D4 and CD8 counts, markers of immune activation, delayed-type hypersensitiv ity (DTH) skin testing, and cytotoxic T lymphocyte (CTL) measurement. The n ine subjects who received p24-VLP and zidovudine had an augmentation and/or broadening of their CTL response compared with baseline (p = 0.004). The e ight subjects receiving p24-VLP and seven subjects receiving zidovudine did not have a statistically significant increase or broadening of CTL activit y, The augmentation of the CTL response in the subjects who received p24-VL P and zidovudine was not associated with a decline in viral load or an incr ease 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 ant iretroviral therapy.