Optimizing the efficiency of therapeutic HIV vaccine trials: A case for CTN 173

BackgroundThe introduction of highly active antiretroviral therapy (HAART) has enabled the dramatic reduction in viral replication and the partial restoration of host immune function, albeit at the expense of drug toxicity. Strategies to enhance HIV-specific immunity are required in order to limit ART exposure. Therapeutic vaccination is a promising new approach to enhance immunogenicity and anti-viral activity in people infected with HIV.PurposeEfficient clinical trial designs are required to optimize therapeutic HIV vaccination strategies. Herein, we describe unique design features and investigational procedures that were applied to a prime-boost therapeutic vaccine trial (CTN 173) to enhance HIV immunity.MethodsCTN 173 was a multicentre, randomized, 3-arm, double-blind placebo controlled trial to evaluate anti-viral activity of therapeutic vaccination with ALVAC ± Remune in chronically infected individuals on HAART. CTN 173 was developed with the specific aim to better characterize patient factors and immunologic parameters associated with vaccine response. This paper discusses the relevance of choice of primary endpoint and statistical approach used in this trial, in relation to vaccine response, patient safety and the identification of optimal target populations for future vaccine trials.ResultsTime to event surrogate endpoints of viral response and frequent immunologic monitoring allow for a better characterization of immunologic correlates of vaccine response.LimitationsThe clinical implications of delayed viral rebound associated with therapeutic vaccination with ALVAC + Remune are not yet known and will need to be evaluated on long-term follow-up.ConclusionsRandomized controlled trials such as CTN 173, with well-defined surrogate endpoints and frequent immunologic and virologic monitoring, are necessary to streamline the approach to effective vaccine discovery and to ensure patient safety.