Predictors of Time to Viremia With an Analytic Treatment Interruption

The HIV field has made a dramatic shift to an emphasis on finding a cure for HIV. However, there is no agreed upon test of cure, or even what the definition of a cure might be. The investigator believes the most reliable test of cure will be an analytic treatment interruption (ATI) with time to viremia as a standard measure of the impact of an intervention on the degree to which the reservoir has been depleted. This is rational as modeling studies utilizing ATI data point to reservoir size as an important predictor of time to viremia(1) and other studies have shown that levels of HIV DNA(2) and cell associated HIV RNA(3) prior to starting antiretroviral therapy (ART) are associated with time-to-rebound. However, these studies used a limited sampling strategy to determine when viremia rebounded and it is likely that greater sensitivity in measures of time-to rebound will be needed to accurately assess the impact of an intervention. The investigators have tested an ATI strategy where plasma HIV is sampled three times each week and ART is resumed once the virus becomes detectable. In this small, pilot study, the investigators sampled lymph nodes, GALT, plasma, and PBMC before, during, and after the ATI and found the time-to-rebound was 14 days (range 5 to 30 days) and that total years of ART exposure was associated with the time-to-rebound (4). The investigators propose a similar study that includes more intensive blood and lymphoid tissue sampling to identify factors that predict time to-rebound to provide a necessary foundation for future studies that utilize a treatment interruption as a test of efficacy for curative interventions.