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

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          Abstract

          Background

          The contribution of HIV-infection to periodontal disease (PD) is poorly understood.  We proposed that immunological markers would be associated with improved clinical measures of PD.

          Methods

          We performed a longitudinal cohort study of HIV-infected adults who had started highly active antiretroviral therapy (HAART) <2 years. PD was characterized clinically as the percent of teeth with ≥1 site with periodontal probing depth (PPD) ≥5.0mm, recession (REC) >0mm, clinical attachment level (CAL) ≥4.0mm, and bleeding on probing (BOP) at ≥4 sites/tooth and microbiologically as specific periodontopathogen concentration. Linear mixed-effects models were used to assess the associations between immune function and PD.

          Results

          Forty (40) subjects with median 2.7 months on HAART and median nadir CD4+ T-cell count of 212 cells/μl completed a median 3 visits. Over 24 months, CD4+ T-cell count increased by a mean 173 cells/µl (p<0.001) and HIV RNA decreased by 0.5 log 10 copies/ml (p<0.001); concurrently, PPD, CAL and BOP decreased by a mean 11.7%, 12.1%, and 14.7% respectively (all p<0.001). Lower nadir CD4+ T-cell count was associated with worse baseline REC (-6.72%; p=0.04) and CAL (9.06%; p<0.001). Further, lower nadir CD4+ T-cell count was associated with a greater relative longitudinal improvement in PPD in subjects with higher baseline levels of Porphyromonas gingivalis (p=0.027), and BOP in subjects with higher baseline levels of Porphyromonas gingivalis or Treponema denticola (p=0.001 and p=0.006 respectively). Longitudinal changes from baseline in CD4+ T-cell count and level of HIV RNA were not independently associated with longitudinal changes in any clinical markers of PD.

          Conclusion

          Degree of immunosuppression was associated with baseline gingival recession. After HAART initiation, measures of active PD improved most in those with lower nadir CD4+ T-cell counts and higher baseline levels of specific periodontopathogens. Nadir CD4+ T-cell count differentially influences periodontal disease both before and after HAART in HIV-infected adults.

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          Most cited references32

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          Case definitions for use in population-based surveillance of periodontitis.

          Many definitions of periodontitis have been used in the literature for population-based studies, but there is no accepted standard. In early epidemiologic studies, the two major periodontal diseases, gingivitis and periodontitis, were combined and considered to be a continuum. National United States surveys were conducted in 1960 to 1962, 1971 to 1974, 1981, 1985 to 1986, 1988 to 1994, and 1999 to 2000. The case definitions and protocols used in the six national surveys reflect a continuing evolution and improvement over time. Generally, the clinical diagnosis of periodontitis is based on measures of probing depth (PD), clinical attachment level (CAL), the radiographic pattern and extent of alveolar bone loss, gingival inflammation measured as bleeding on probing, or a combination of these measures. Several other patient characteristics are considered, and several factors, such as age, can affect measurements of PD and CAL. Accuracy and reproducibility of measurements of PD and CAL are important because case definitions for periodontitis are based largely on either or both measurements, and relatively small changes in these values can result in large changes in disease prevalence. The classification currently accepted by the American Academy of Periodontology (AAP) was devised by the 1999 International Workshop for a Classification of Periodontal Diseases and Conditions. However, in 2003 the Centers for Disease Control and Prevention and the AAP appointed a working group to develop further standardized clinical case definitions for population-based studies of periodontitis. This classification defines severe periodontitis and moderate periodontitis in terms of PD and CAL to enhance case definitions and further demonstrates the importance of thresholds of PD and CAL and the number of affected sites when determining prevalence.
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            Estimation of HIV incidence in the United States.

            Incidence of human immunodeficiency virus (HIV) in the United States has not been directly measured. New assays that differentiate recent vs long-standing HIV infections allow improved estimation of HIV incidence. To estimate HIV incidence in the United States. Remnant diagnostic serum specimens from patients 13 years or older and newly diagnosed with HIV during 2006 in 22 states were tested with the BED HIV-1 capture enzyme immunoassay to classify infections as recent or long-standing. Information on HIV cases was reported to the Centers for Disease Control and Prevention through June 2007. Incidence of HIV in the 22 states during 2006 was estimated using a statistical approach with adjustment for testing frequency and extrapolated to the United States. Results were corroborated with back-calculation of HIV incidence for 1977-2006 based on HIV diagnoses from 40 states and AIDS incidence from 50 states and the District of Columbia. Estimated HIV incidence. An estimated 39,400 persons were diagnosed with HIV in 2006 in the 22 states. Of 6864 diagnostic specimens tested using the BED assay, 2133 (31%) were classified as recent infections. Based on extrapolations from these data, the estimated number of new infections for the United States in 2006 was 56,300 (95% confidence interval [CI], 48,200-64,500); the estimated incidence rate was 22.8 per 100,000 population (95% CI, 19.5-26.1). Forty-five percent of infections were among black individuals and 53% among men who have sex with men. The back-calculation (n = 1.230 million HIV/AIDS cases reported by the end of 2006) yielded an estimate of 55,400 (95% CI, 50,000-60,800) new infections per year for 2003-2006 and indicated that HIV incidence increased in the mid-1990s, then slightly declined after 1999 and has been stable thereafter. This study provides the first direct estimates of HIV incidence in the United States using laboratory technologies previously implemented only in clinic-based settings. New HIV infections in the United States remain concentrated among men who have sex with men and among black individuals.
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              Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis.

              HIV-seropositive patients are at higher risk for atherosclerosis than HIV-seronegative persons. This has been variably attributed to antiretroviral drug toxicity, immunodeficiency, and/or HIV-associated inflammation. To evaluate the contributions of these factors to HIV-associated atherosclerosis, we assessed carotid artery intima-media thickness in a diverse cohort of HIV-seronegative and seropositive adults, including a unique group of HIV-infected patients who were untreated, had undetectable viral loads, and had preserved CD4 T-cell counts (HIV controllers). Carotid intima-media thickness was measured in 494 participants, including 33 HIV controllers and 93 HIV-seronegative controls. HIV controllers had higher intima-media thickness than seronegative controls even after adjustment for traditional risk factors (P = 0.003). Intima-media thickness in controllers was similar to antiretroviral-untreated patients with detectable viremia. Across all participants, intima-media thickness was strongly associated with the presence of HIV disease rather than viral load or CD4 T-cell count. C-reactive protein was higher in HIV controllers than HIV-seronegative persons. Antiretroviral drug exposure was also associated with higher intima-media thickness. Increased atherosclerosis with HIV infection can occur in the absence of antiretroviral therapy, detectable viremia, or overt immunodeficiency. Chronic inflammation - which is higher in controllers than in HIV-uninfected persons - may account for early atherosclerosis in these patients.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                11 October 2013
                : 8
                : 10
                : e76986
                Affiliations
                [1 ]Department of Biological Sciences, Case Western Reserve University School of Dental Medicine, Cleveland, Ohio, United States of America
                [2 ]Department of Community Dentistry, Case Western Reserve University School of Dental Medicine, Cleveland, Ohio, United States of America
                [3 ]Center for Clinical Investigation, Case Western Reserve University, Cleveland, Ohio, United States of America
                [4 ]Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, Cleveland, Ohio, United States of America
                [5 ]Center for AIDS Research, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, Ohio, United States of America
                New York University, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LTV CAD DCB XW ZT AW BR. Performed the experiments: LTV ZT. Analyzed the data: LTV CAD DCB ZT XW AW BR. Contributed reagents/materials/analysis tools: ZT DCB XW. Wrote the manuscript: LTV CAD DCB XW ZT AW BR.

                Article
                PONE-D-13-31772
                10.1371/journal.pone.0076986
                3795634
                6df5fdb5-27d7-4a18-a4c6-cf4daefc0bf5
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 August 2013
                : 4 September 2013
                Funding
                Funding was from National Institute of Dental and Craniofacial Research, Grants K23 DE15746-01A1 and R21 DE21376-01, The Center for AIDS Research (CFAR), AI36219, the William T. Dahms, M.D. Clinical Research Unit (Dahms CRU) of the Clinical and Translational Science Center, UL1 RR024989, NIH, M01 RR000080, the CWRU Department of Biological Sciences, OPR892515, and the Case Western Reserve University/Cleveland Clinic CTSA Grant, UL1 RR024989 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health and NIH roadmap for Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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