Sponsored by the National Institute of Dental and Craniofacial Research, National Institutes of Health
Project Period: Completed
Gum disease has been reported to contribute to heart disease and adults with HIV infection have a higher risk for developing both heart disease and gum disease. We suspect that the effects of gum disease on the immune system promote heart disease. By observing HIV-infected adults before and after an intensive treatment of gum disease, we will see whether immune-related factors within blood improve as a result of treatment and whether this also improves the health of blood vessels. By performing this study, we may discover whether treating gum disease can lower an HIV-infected person's risks for heart disease and we may be able to learn specific details about how the immune system contributes to the risk for heart disease.
Cardiovascular disease (CVD) is a leading cause of death in HIV-infected adults, with both chronic HIV and sustained use of antiretroviral therapy (ART) contributing to heart disease. Identifying the specific mechanisms and any modifiable risk factors for CVD in this vulnerable population is a public health priority. We hypothesize that HIV-infected patients who are treated for periodontal disease (PD) will show significant improvement in endothelial function and key systemic biomarkers of immunity as compared to their own baseline values. We propose a pre-post observational study of immune, inflammatory, coagulation and vascular consequences following the treatment of severe PD in HIV-infected adults. Severe PD will be defined by A) >30% of teeth with ≥1 site with periodontal probing depth (PPD) ≥5mm in addition to clinical attachment level (CAL) ≥3.0 mm at these sites and B) bleeding on probing (BOP) at >30% of all sites. Subjects entering the study will receive clinically-indicated intensive periodontal therapy (IPT) consisting of: A) full-mouth scaling and root planing (SC/RP) with subgingival chlorhexidine gluconate (CHX) irrigation at baseline, 1 and 2 months, B) placement of minicycline microspheres in all sites with PPD ≥4.0 mm after each of three SC/RP visits, C) "hands-on" coaching of targeted oral hygiene improvements, and D) home use of CHX. Successful PD treatment will be defined a-priori as BOP occurring at ≤10% of sites, no PPD ≥5.0 mm and ≤15% of sites with PPD=4.0 mm. Our primary objective is to test whether IPT in immunologically stable HIV-infected adults significantly improves brachial artery flow mediated dilation (FMD) at six months as compared to each individual's baseline FMD value. Our secondary objective is to determine whether systemic biomarkers of inflammation (interleukin 6 and soluble E-selectin), microbial translocation (neutrophils and soluble CD14), coagulation (D-dimers and tissue factor expression on monocytes) and immune activation (%CD38+ HLA-DR+ on CD8+ T-cells) at two months predict improvement in FMD at six months. The primary endpoint is the percent change from baseline in FMD at six months. The secondary endpoint is to investigate the cross-sectional and longitudinal effects of the above biomarkers measured at baseline, 1, 2 and 6 months on FMD. A sample size of 35 patients is needed to detect a 15% change in FMD between baseline and 6 months after baseline with 80% power, based on a two-sided paired t-test and assuming 1) FMD has a lognormal distribution; 2) the coefficient of variation of FMD at each time point is 0.29; 3) the correlation between FMD at baseline and FMD at 6 months is 0.5; and 4) a significance level of 0.05. Assuming a 25% attrition rate, 44 patients will be needed to ensure that 35 patients complete the study. In addition to a lower socioeconomic HIV-infected cohort with poor dental care utilization and high levels of PD, our group has the requisite resources and infrastructure to successfully complete this innovative, highly translational observational study.
Lance Vernon, MPH, DMD – Department of Biological Sciences
Denise Babineau, PhD – Center for Clinical Investigation
Michael M. Lederman, MD – Department of Infectious Diseases and HIV Medicine
Grace McComsey, MD – Department of Pediatrics
Benigno Rodriguez, MD - Department of Infectious Diseases and HIV Medicine
Zahhra Toossi, MD – Department of Infectious Diseases and HIV Medicine
Aaron Weinberg, DMD, PhD – Department of Biological Sciences
Vernon LT, Babineau DC, Demko CA, Lederman MM, Wang X, Toossi Z, Weinberg A, Rodriguez B. A Prospective Cohort Study of Periodontal Disease Measures and Cardiovascular Disease Markers in HIV-Infected Adults. AIDS Research and Human Retroviruses