Role of periodontitis in accelerated ageing in HIV-infected patients

Rationale: Combination antiretroviral therapy (cART) is a spectacular success
in the fight against HIV. However, the life expectancy of HIV-infected patients
using cART is still >10 years shorter than that of uninfected persons. This is
due to an increased risk of non-AIDS age-related co-morbidities, such as
cardiovascular disease, malignancies and liver disease. Persistent immune
activation, despite near-complete suppression of viral replication, is believed
to be responsible. Immune activation independently predicts mortality in
HIV-infected patients, but the mechanism behind HIV-related immune activation
is still unclear. Translocation of microbial products into the blood in
HIV-infected patients correlates with immune activation, suggesting an
important role for a disturbed balance between the microbiota and the immune
system. Current research has focused almost exclusively on the large intestine
as the site of this translocation. An important alternative source of microbial
translocation could be inflammation of the tooth-supporting tissues:
periodontitis. This condition is characterized by a distinct composition of the
oral microbiota, and is strongly associated with age-related diseases. Indeed,
markers of microbial translocation were found to be elevated in patients with
periodontitis. Periodontitis is frequently observed in HIV-infected patients,
but its role in HIV-related immune activation has not been studied. Notably,
oral health is an often neglected topic by both HIV-infected patients and their
doctors.

HYPOTHESIS
We hypothesize that chronic periodontitis contributes to systemic immune
activation in HIV-infected patients despite viral suppression by disturbing the
balance between oral microbiota and the immune system. Furthermore, we
hypothesize that HIV-infected patients with chronic periodontitis are
characterized by a hypercoagulable state. We presume that treatment of
periodontitis will reduce systemic immune activation and risk of co-morbidities
and thus could improve the life expectancy of HIV-infected patients.

1. Determine the relationship between periodontitis and HIV-related immune
activation and hypercoagulability.
2. Explore the role of oral microbiota as effect modificator of the
relationship between periodontitis and immune activation in HIV-infected
patients.

Phase 1: in a cross-sectional observational study we will determine the
prevalence of periodontitis in HIV-infected patients visiting the UMCG
outpatient clinic using the DPSI.

Phase 2: in a cross-sectional case-control study we will compare the
Periodontal Inflamed Surface Area (PISA), markers of immune activation,
hemostatic parameters and oral microbiota of 40 HIV-infected patients with
periodontitis (DPSI >2; cases) and 40 HIV-infected patients without
periodontitis (DPSI <=2; controls) selected from phase 1.

Other than standard care, subjects in Phase 1 will undergo a short screening of
periodontal disease. Patients in Phase 2 additionally will undergo venous blood
sampling, a brief questionnaire on dental hygiene and a more extensive
assessment of periodontal disease (PISA). As part of this assessment a
subgingival plaque sample will be obtained to identify the oral microbiota.