Extended evaluation of the virologic, immunologic, and clinical course of volunteers who acquired HIV-1 infection in a phase III vaccine trial of ALVAC-HIV and AIDSVAX B/E

J Infect Dis. 2013 Apr 15;207(8):1195-205. doi: 10.1093/infdis/jis478. Epub 2012 Jul 26.

Abstract

Background: The Thai Phase III Trial of ALVAC-HIV and AIDSVAX B/E showed an estimated vaccine efficacy (VE) of 31% to prevent acquisition of human immunodeficiency virus (HIV). Here we evaluated the effect of vaccination on disease progression after infection.

Methods: CD4(+) T-cell counts and HIV viral load (VL) were measured serially. The primary analysis evaluated vaccine efficacy (VEP) as the percent reduction (vaccine vs placebo) in cumulative probability of a primary composite endpoint of clinical and CD4(+) count components at prespecified time points after infection. Secondary analyses of biomarker-based endpoints were assessed using marginal mean and linear mixed models.

Results: There were 61 endpoints in the modified intent-to-treat cohort (mITT; n = 114). There was no evidence for efficacy at 30, 42, 54, and 60 months in the mITT and per protocol (n = 90) cohorts. Estimated VEP (mITT) was15.8% (-21.9, 41.8) at 60 months postinfection. There was weak evidence of lower VL and higher CD4(+) count at 60 and 66 months in the vaccine group. Lower mucosal VL was observed among vaccine recipients, primarily in semen (P = .04).

Conclusions: Vaccination did not affect the clinical course of HIV disease after infection. A potential vaccine effect on the genital mucosa warrants further study.

Trial registration: ClinicalTrials.gov NCT00337181.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology*
  • Adult
  • Antiretroviral Therapy, Highly Active / methods
  • CD4 Lymphocyte Count
  • Disease Progression
  • Female
  • Follow-Up Studies
  • HIV Infections / immunology
  • HIV Infections / pathology
  • HIV Infections / prevention & control
  • HIV Infections / virology*
  • HIV-1 / immunology*
  • HIV-1 / pathogenicity
  • Humans
  • Linear Models
  • Male
  • Prospective Studies
  • Risk-Taking
  • Semen / virology
  • Thailand
  • Time Factors
  • Vaccination
  • Vagina / virology
  • Viral Load
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*
  • Young Adult

Substances

  • AIDS Vaccines
  • AIDSVAX B-E
  • ALVAC vaccine
  • Viral Vaccines

Associated data

  • ClinicalTrials.gov/NCT00337181