title: Failure time analysis of HIV vaccine effects on viral load and antiretroviral therapy initiation.
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.
authors.affiliation: Department of Biostatistics, University of Washington and Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. pgilbert@scharp.org
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Sun
mesh_terms: D016915:AIDS Vaccines / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001699:Biometry; D016001:Confidence Intervals; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D013997:Time Factors; D014766:Viremia / Q000517:prevention & control
chemical_list: D016915:AIDS Vaccines; D019380:Anti-HIV Agents