Safety and immunogenicity of a candidate therapeutic vaccine, p24 virus-like particle, combined with zidovudine, in asymptomatic subjects. Community HIV Research Network Investigators

AIDS. 1998 Jan 22;12(2):175-82. doi: 10.1097/00002030-199802000-00007.

Abstract

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 microg) in intramuscular alum monthly; group C, placebo capsules plus p24-VLP (500 microg) 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / adverse effects
  • AIDS Vaccines / therapeutic use*
  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Combined Modality Therapy
  • Disease Progression
  • Female
  • HIV Antibodies / blood
  • HIV Core Protein p24 / adverse effects
  • HIV Core Protein p24 / therapeutic use*
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / therapy*
  • HIV Infections / virology
  • HIV-1* / drug effects
  • HIV-1* / immunology
  • HIV-1* / physiology
  • Humans
  • Hypersensitivity, Delayed
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Treatment Outcome
  • Vaccination
  • Viral Load
  • Zidovudine / adverse effects
  • Zidovudine / therapeutic use*

Substances

  • AIDS Vaccines
  • Anti-HIV Agents
  • HIV Antibodies
  • HIV Core Protein p24
  • p24-VLP vaccine
  • Zidovudine