Antiretroviral therapies are highly effective at preventing the progression of HIV illness and AIDS related morbidity and mortality. Approximately 80% of treatment recipients do well with adequate adherence and optimal virologic suppression. In this application, we propose to plan a clinical trial that would be directed at identifying and intervening with individuals who are at risk for the failure of antiretroviral treatment before failure occurs. The eventual trial would utilize a novel measure o drug exposure, ARV levels in hair, to trigger an in-depth assessment of adherence, and then intervene to increase adherence using the ARV levels as a tool. The assessment and intervention would be provided centrally via telephone and electronic means, and thus not burden highly stressed clinical providers. Additionally persons who have low drug levels despite reporting high adherence would undergo miniPK testing to determine if biologic factors are at play. A nested substudy would compare the ARV levels in hair to those in blood. Because both the trigger and the intervention are novel, the eventual trial would include 3 randomized groups: a hair level triggered group, a viremia triggered group and a usual care group. The requested R-34 funding would support selection of study sites (including exploration of existing trials networks), development of criteria for intervention triggers, adaptation of existing adherence and pharmacologic assessments, selection of a contract research organization, development of study materials. Web video conferencing would be used to obtain input from a scientific advisory committee. Provided these resources, we would then apply for funding to support an investigator-initiated RCT within one year.
This application requests funding for planning of an unusual clinical trial. The trial would compare methods for detecting risk of failure among patients who are starting a new antiretroviral regimen and then compare a state of the art intervention to improve treatment effects with usual care. The experimental method involves measuring how much medication is actually in the body by testing samples of about 10 scalp hairs. Once the planning process is complete, we will submit a grant application to conduct the trial. If it is fond effective, the hair sample approach could provide a means to include drug levels in routine HIV care with the goal of improving treatment outcomes.
