Failure time analysis of HIV vaccine effects on viral load and antiretroviral therapy initiation

Biostatistics. 2005 Jul;6(3):374-94. doi: 10.1093/biostatistics/kxi014. Epub 2005 Apr 14.

Abstract

The world's first efficacy trial of a preventive HIV vaccine was completed in 2003. Study participants who became HIV infected were followed for 2 years and monitored for HIV viral load and initiation of antiretroviral therapy (ART). In order to determine if vaccination may have altered HIV progression in persons who acquired HIV, a pre-specified objective was to compare the time until a composite endpoint between the vaccine and placebo arms, where the composite endpoint is the first event of ART initiation or viral failure (HIV viral load exceeds a threshold x(vl) copies/ml). Specifically, with vaccine efficacy, VE(tau, x(vl)), defined as one minus the ratio (vaccine/placebo) of the cumulative probability of the composite endpoint (with failure threshold x(vl)) occurring by tau months, the aim was to estimate the four parameters {VE(tau, x(vl)): x(vl) is an element of {1500, 10,000, 20,000, 55,000} copies/ml} with simultaneous 95% confidence bands. A Gaussian multipliers simulation method is devised for constructing confidence bands for VE(tau, x(vl)) with x(vl) spanning multiple discrete values or a continuous range. The new method is evaluated in simulations and is applied to the vaccine trial data set.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Vaccines / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Biometry
  • Confidence Intervals
  • HIV Infections / drug therapy
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • Humans
  • Models, Biological
  • Models, Statistical
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Time Factors
  • Viremia / prevention & control

Substances

  • AIDS Vaccines
  • Anti-HIV Agents