Safety and immunogenicity of a candidate therapeutic vaccine, p24 virus-like particle, combined with zidovudine, in asymptomatic subjects

Objectives: To evaluate the impact of therapeutic immunization with p24 virus-like particle (VLP) and zidovudine (ZDV) on p24 antibody titre (primary endpoint), CD4+ cell counts, cellular responses to the immunogen and recall antigens, and viral load (secondary endpoints) in subjects with asymptomatic HIV infection and CD4+ counts greater than 400 x 10(6) cells/l. Design: A double dummy, double-blind randomized placebo-controlled Phase II trial of the therapeutic vaccine p24-VLP, with or without ZDV. Methods: ZDV-naive subjects were randomized to one of three groups for 6 months: group A, ZDV 200 mg three times daily plus intramuscular administration of alum adjuvant monthly; group B, ZDV 200 mg three times daily plus p24-VLP (500 mu g) in intramuscular alum monthly; group C, placebo capsules plus p24-VLP (500 mu g) in intramuscular alum monthly. Subjects were followed for a further 6 months. Results: Sixty-one patients received vaccinations. The mean CD4+ cell counts pretherapy for groups A, B, and C were 605 +/- 25, 668 +/- 43, and 583 +/- 30 x 10(6) cells/l, respectively. Treatment was well tolerated. At both 24 and 52 weeks there were no significant differences between the treatment groups in terms of antibody responses to p24, CD4+ or CD8+ cell counts, viral load, T-cell responses to p24, p17, recall antigen or mitogen, or markers of immune activation, despite induction of antibody and proliferative responses to the carrier protein of the vaccine. Conclusion: Vaccination with p24-VLP was well tolerated. p24-VLP either alone or in combination with ZDV did not significantly alter either antibody or proliferative responses to p24, or CD4+ cell number, immune activation or viral load over 12 months.