A Prospective Cohort Study of Periodontal Disease Measures and Cardiovascular Disease Markers in HIV-Infected Adults

Abstract

The determinants of HIV-associated cardiovascular disease (CVD) are not well understood. Periodontal disease (PD) has been linked to CVD but this connection has not been examined in HIV infection. We followed a cohort of HIV-infected adults to ascertain whether PD was associated with carotid artery intima media thickness (IMT) and brachial artery flow-mediated dilation (FMD). We performed a longitudinal observational study of HIVinfected adults on HAART for < 2 years with no known heart disease. PD was characterized clinically and microbiologically. Cardiovascular disease was assessed by IMT/FMD. Linear mixed models assessed crosssectional and longitudinal associations between PD and FMD/IMT. Forty three HIV + adults completed a median of 24 (6-44) months on the study. Defining delta to be the change in a variable between baseline and a follow-up time, longitudinally, on average and after adjusting for change in time, CVD-specific and HIV-specific potential confounding covariates, a 1-log 10 increase in delta Porphyromonas gingivalis was associated with a 0.013 mm increase in delta IMT (95% CI: 0.0006-0.0262; p = 0.04). After adjusting for the same potential confounding covariates, a 10% increase in delta gingival recession was associated with a 2.3% increase in delta FMD (95% CI: 0.4-4.2; p = 0.03). In a cohort of HIV-infected adults, an increase in subgingival Porphyromonas gingivalis, a known periodontal pathogen, was significantly associated with longitudinal increases in IMT, while increased gingival recession, which herein may represent PD resolution, was significantly associated with longitudinal improvement in FMD. In the context of HIV infection, PD may contribute to CVD risk. Intervention studies treating PD may help clarify this association.

Effect of Nadir CD4+ T Cell Count on Clinical Measures of Periodontal Disease in HIV+ Adults before and during Immune Reconstitution on HAART

“…There are several methodological limitations in earlier studies proposing a low level of PD in HIV+ adult cohorts, as detailed in our 2009 report[5]. In our 2011 longitudinal report of 43 HIV+ patients on HAART, we found that PD improved significantly during immune reconstitution on HAART[8]. We subsequently hypothesized that longitudinal improvement in CD4+ T-cell count and/or decreased level of HIV RNA would be associated with longitudinal improvement in clinical measures of PD.…”

“…This was a prospective observational study of adult subjects recruited from three outpatient HIV medical clinics in Cleveland, Ohio as previously described[5,8]. IRB approval was obtained from University Hospitals Case Medical Center (UHCMC).…”

“…Inclusion criteria were: medication-compliant adult subjects, age 18 or older, who were taking highly active antiretroviral therapy (HAART) for < 2 years at baseline. HAART was defined previously[8] as a treatment regimen that included at least three different antiretroviral drugs from at least two different classes. All subjects were seen for evaluation and PD measurement at baseline and at one or more visits thereafter, typically at 8, 16 and 24 months.…”

“…CD4+ T cell count was measured by flow cytometry and HIV RNA by polymerase chain reaction (PCR) as previously described[5,8] Data on CD4+ T-cell count and HIV RNA was merged with periodontal measures using a window on immunological variables defined by less than 4 months before or 1 week after each study visit.…”

“…We subsequently hypothesized that longitudinal improvement in CD4+ T-cell count and/or decreased level of HIV RNA would be associated with longitudinal improvement in clinical measures of PD. To address this hypothesis, we extended the analysis of our earlier report[8] by modeling the effect of nadir CD4+ T cell count and the longitudinal change in CD4+ T cell count and level of HIV RNA on clinical measures of PD. We found that nadir CD4+ T cell count influences periodontal disease in HIV-infected adults both before and after HAART initiation, and that this influence varies prior to and after HAART initiation.…”