PROJECT ABSTRACT Serious non-AIDS events (SNAE), including emphysema, diabetes, osteoporosis, cardiovascular disease, and cognitive impairment, have emerged as important contributors to HIV-related morbidity and mortality. SNAE are likely driven by systemic inflammation, which remains heightened in people with HIV (PWH), compared to HIV-negative persons, despite virologic suppression. Specifically, elevated circulating markers of systemic inflammation [high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6)] and evidence of monocyte activation [sCD14, sCD163, CD14+CD16+ intermediate monocytes] are associated with greater risks of SNAE. Insomnia is a known risk factor for poor health outcomes in the general population, perhaps via its link with greater systemic inflammation. Fortunately, insomnia is modifiable, and the clear first-line treatment has been identified. The 2016 American College of Physicians guideline concluded that the preferred treatment for chronic insomnia in adults is not pharmacologic therapy but rather CBT for insomnia (CBT-I), given the strong evidence that it is safe, effective, and broadly applicable with durable benefits. A feasible and effective internet CBT-I tool called Sleep Healthy Using The Internet (SHUTi) was developed and validated by this application’s consultant, Dr. Lee Ritterband. In multiple RCTs, SHUTi has proven effective for treating insomnia in the general population. To our knowledge, internet CBT-I in PWH has not previously been studied. Thus, our proposal represents an innovative application of an established intervention technology in a new patient population. The central objective of this application is to evaluate SHUTI’s ability to reduce systemic inflammation, and, in particular, monocyte activation in PWH. We will meet this objective by addressing the following Specific Aim: To evaluate the effects of cognitive-behavioral therapy for insomnia (CBT-I) on measures of systemic inflammation in virologically-suppressed, HIV-positive adults with insomnia disorder. We will conduct a single-site, phase II RCT comparing SHUTi to an Active Comparator group receiving sleep hygiene education program in 50 virologically-suppressed PWH with insomnia disorder to reduce biomarkers of inflammation and monocyte activation. A positive phase II trial would provide the proof-of-concept data and effect size estimates needed to justify and properly design a multisite, phase III RCT to establish the long-term effects of SHUTi (a practical and readily scalable intervention) on HIV-related inflammation and prevention of SNAE.

NARRATIVE This proposal will fill a critical gap in our knowledge by assessing the relationships between insomnia and inflammation in HIV. The results from this initial trial will determine if an internet cognitive behavioral therapy for insomnia can reduce blood measures of inflammation and thus will help shape a new pathologic model from which we can formulate new clinical screening and therapeutic strategies to reduce the heightened risk of serious non-AIDS events in the aging HIV-positive population.