The Impact of Oral Health in HIV Patients on Antiretroviral Therapy

Study Overview
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Brief Summary
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This is a prospective cohort study designed to investigate the range of metabolic abnormalities observed in patients living with HIV on antiretroviral therapy. This study will also explore the concurrent role of poor oral health in supporting and driving chronic immune activation and inflammation in HIV infection.

Detailed Description
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This is a prospective cohort study designed to investigate the range of metabolic abnormalities observed in patients living with HIV (PLWH) on antiretroviral therapy (ART). This study will also explore the concurrent role of poor oral health in supporting and driving chronic immune activation and inflammation in HIV infection. Following enrollment in study, patients will be followed up every 6 months for approximately 2.5 years (30 months). During this period, comprehensive medical records will be obtained, and study data will be updated every 6 months; questionnaires will be handed to patients periodically to assess quality of life and effects of xerostomia on QoL; social history will be assessed using TAPS; oral health will be evaluated every 6 months and blood, saliva, and oral swabs collected every 6 months. DXA scan and panoramic radiographs will also be taken at baseline and 24 months. At the end of the study, caries rate, periodontal health, bone loss, QoL, salivary quantity and composition, presence or absence of white/red lesions, as well as inflammatory cytokines and immune activation markers will be assessed.

Official Title
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The Impact of Oral Health on Metabolism and Persistent Inflammation in HIV Patients on Antiretroviral Therapy

Conditions
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HIV, Periodontal Diseases, Caries, Non-communicable Disease, Xerostomia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Has been diagnosed with HIV (as documented by a prior laboratory report of positive HIV-1/2 antibody and/or detectable HIV RNA, available for review by the study team) Has received antiretroviral therapy for at least 12 months Able and willing to provide informed consent prior to initiation of study procedures Willing and able to comply with all study procedures, and likely to be available for the duration of the study Exclusion Criteria: Has been diagnosed with the following xerostomia-related autoimmune conditions: Sjorgen's and sarcoidosis Has never received radiation therapy to the head or neck (including radioactive iodine therapy) Was taking anti-osteoporotic agents (biphosphonates, denosumab) prior to HIV diagnosis. Women who are pregnant at the time of enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV Subjects with Non-Communicable Diseases<br>Patients living with HIV on Antiretroviral Therapy drugs for at least one year with no diagnosis of non-communicable diseases (diabetes, insulin resistance, hyperlipidemia/dyslipidemia, vascular disease, and/or osteoporosis). | |
| HIV Subjects without Non-Communicable Diseases<br>Patients living with HIV on Antiretroviral Therapy drugs for at least one year with a diagnosis of one or more systemic non-communicable diseases (diabetes, insulin resistance, hyperlipidemia/dyslipidemia, vascular disease, and/or osteoporosis). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dental Caries as assessed by DMFS Score | Decayed, missing and filled surfaces (DMFS) score to assess dental caries. Minimum value is 0 and maximum value is 128 for 28 teeth. Higher scores mean higher levels of dental decay. | Baseline | 
| Dental Caries as assessed by DMFS Score | Decayed, missing and filled surfaces (DMFS) score to assess dental caries. Minimum value is 0 and maximum value is 128 for 28 teeth. Higher scores mean higher levels of dental decay. | 6 months after baseline visit | 
| Dental Caries as assessed by DMFS Score | Decayed, missing and filled surfaces (DMFS) score to assess dental caries. Minimum value is 0 and maximum value is 128 for 28 teeth. Higher scores mean higher levels of dental decay. | 12 months after baseline visit | 
| Dental Caries as assessed by DMFS Score | Decayed, missing and filled surfaces (DMFS) score to assess dental caries. Minimum value is 0 and maximum value is 128 for 28 teeth. Higher scores mean higher levels of dental decay. | 18 months after baseline visit | 
| Dental Caries as assessed by DMFS Score | Decayed, missing and filled surfaces (DMFS) score to assess dental caries. Minimum value is 0 and maximum value is 128 for 28 teeth. Higher scores mean higher levels of dental decay. | 24 months after baseline visit | 
| Dental Caries as assessed by DMFS Score | Decayed, missing and filled surfaces (DMFS) score to assess dental caries. Minimum value is 0 and maximum value is 128 for 28 teeth. Higher scores mean higher levels of dental decay. | 30 months after baseline visit | 
| Periodontal disease | Incidence of periodontal disease | Baseline | 
| Periodontal disease | Incidence of periodontal disease | 12 months after baseline visit | 
| Periodontal disease | Incidence of periodontal disease | 24 months after baseline visit | 
| Periodontal disease | Incidence of periodontal disease | 30 months after baseline visit | 
| Oral mucosal lesions coinfection as assessed by the presence or absence of candidiasis, red/white lesions, ulcers and warts intraorally | Prescence or absence of warts, red or white lesions and candidia | Baseline | 
| Oral mucosal lesions coinfection as assessed by the presence or absence of candidiasis, red/white lesions, ulcers and warts intraorally | Prescence or absence of warts, red or white lesions and candidia | 6 months after baseline visit | 
| Oral mucosal lesions coinfection as assessed by the presence or absence of candidiasis, red/white lesions, ulcers and warts intraorally | Prescence or absence of warts, red or white lesions and candidia | 12 months after baseline visit | 
| Oral mucosal lesions coinfection as assessed by the presence or absence of candidiasis, red/white lesions, ulcers and warts intraorally | Prescence or absence of warts, red or white lesions and candidia | 18 months after baseline visit | 
| Oral mucosal lesions coinfection as assessed by the presence or absence of candidiasis, red/white lesions, ulcers and warts intraorally | Prescence or absence of warts, red or white lesions and candidia | 24 months after baseline visit | 
| Oral mucosal lesions coinfection as assessed by the presence or absence of candidiasis, red/white lesions, ulcers and warts intraorally | Prescence or absence of warts, red or white lesions and candidia | 30 months after baseline visit | 
| Osteopenia as assessed by DXA scan findings | Incidence of osteopenia | Baseline | 
| Osteopenia as assessed by DXA scan findings | Incidence of osteopenia | 24 months after baseline visit | 
| Quality of life as assessed by the Xerostomia Quality of Life Scale (XeQoLS) | The XeQoLS consists of 15 questions. The first 14 questions assess how dryness in the mouth impacts the individual's life, with answer options of not at all, a little, somewhat, quite a bit, and very much. The final question asks if you were to spend the rest of your life with your dry mouth/throat dryness just the way it is now, how would you feel about this? and includes options ranging from delighted to terrible. All 15 questions can be translated to a score of 0-4, with a score of 4 indicating the most dry mouth-related problems and 0 indicating no dry mouth-related problems. | Baseline | 
| Quality of life as assessed by the Xerostomia Quality of Life Scale (XeQoLS) | The XeQoLS consists of 15 questions. The first 14 questions assess how dryness in the mouth impacts the individual's life, with answer options of not at all, a little, somewhat, quite a bit, and very much. The final question asks if you were to spend the rest of your life with your dry mouth/throat dryness just the way it is now, how would you feel about this? and includes options ranging from delighted to terrible. All 15 questions can be translated to a score of 0-4, with a score of 4 indicating the most dry mouth-related problems and 0 indicating no dry mouth-related problems. | 12 months after baseline visit | 
| Quality of life as assessed by the Xerostomia Quality of Life Scale (XeQoLS) | The XeQoLS consists of 15 questions. The first 14 questions assess how dryness in the mouth impacts the individual's life, with answer options of not at all, a little, somewhat, quite a bit, and very much. The final question asks if you were to spend the rest of your life with your dry mouth/throat dryness just the way it is now, how would you feel about this? and includes options ranging from delighted to terrible. All 15 questions can be translated to a score of 0-4, with a score of 4 indicating the most dry mouth-related problems and 0 indicating no dry mouth-related problems. | 24 months after baseline visit | 
| Quality of life as assessed by the Xerostomia Quality of Life Scale (XeQoLS) | The XeQoLS consists of 15 questions. The first 14 questions assess how dryness in the mouth impacts the individual's life, with answer options of not at all, a little, somewhat, quite a bit, and very much. The final question asks if you were to spend the rest of your life with your dry mouth/throat dryness just the way it is now, how would you feel about this? and includes options ranging from delighted to terrible. All 15 questions can be translated to a score of 0-4, with a score of 4 indicating the most dry mouth-related problems and 0 indicating no dry mouth-related problems. | 30 months after baseline visit | 
| Quality of life as assessed by the Oral Health Related Quality of Life (OHRQoL) | Oral health related quality of life will be assessed using the questionnaire developed for the National Health and Nutrition Examination Survey (NHANES). This questionnaire assesses the topic areas of last visit to dentist or lack of dental care; direct conversation with dental professional about your dental health; dental health perception; oral cancer exam; use of dental floss or dental rinse product; and periodontal disease self-report. Each topic area uses a separate scoring system and may be assessed individually. | Baseline | 
| Quality of life as assessed by the Oral Health Related Quality of Life (OHRQoL) | Oral health related quality of life will be assessed using the questionnaire developed for the National Health and Nutrition Examination Survey (NHANES). This questionnaire assesses the topic areas of last visit to dentist or lack of dental care; direct conversation with dental professional about your dental health; dental health perception; oral cancer exam; use of dental floss or dental rinse product; and periodontal disease self-report. Each topic area uses a separate scoring system and may be assessed individually. | 12 months after baseline visit | 
| Quality of life as assessed by the Oral Health Related Quality of Life (OHRQoL) | Oral health related quality of life will be assessed using the questionnaire developed for the National Health and Nutrition Examination Survey (NHANES). This questionnaire assesses the topic areas of last visit to dentist or lack of dental care; direct conversation with dental professional about your dental health; dental health perception; oral cancer exam; use of dental floss or dental rinse product; and periodontal disease self-report. Each topic area uses a separate scoring system and may be assessed individually. | 24 months after baseline visit | 
| Quality of life as assessed by the Oral Health Related Quality of Life (OHRQoL) | Oral health related quality of life will be assessed using the questionnaire developed for the National Health and Nutrition Examination Survey (NHANES). This questionnaire assesses the topic areas of last visit to dentist or lack of dental care; direct conversation with dental professional about your dental health; dental health perception; oral cancer exam; use of dental floss or dental rinse product; and periodontal disease self-report. Each topic area uses a separate scoring system and may be assessed individually. | 30 months after baseline visit | 
| Quality of life as assessed by the Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) Tool | The TAPS tool screens for substance use (including tobacco, alcohol, prescription medication, and other drugs) and includes a brief assessment of abuse risk for those who screen positive. Individuals who screen positive for use of any of the substances are then scored as 0 (no use in the past 3 months), 1 (problem use), and 2+ (high risk for substance use disorder). | Baseline | 
| Quality of life as assessed by the Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) Tool | The TAPS tool screens for substance use (including tobacco, alcohol, prescription medication, and other drugs) and includes a brief assessment of abuse risk for those who screen positive. Individuals who screen positive for use of any of the substances are then scored as 0 (no use in the past 3 months), 1 (problem use), and 2+ (high risk for substance use disorder). | 12 months after baseline visit | 
| Quality of life as assessed by the Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) Tool | The TAPS tool screens for substance use (including tobacco, alcohol, prescription medication, and other drugs) and includes a brief assessment of abuse risk for those who screen positive. Individuals who screen positive for use of any of the substances are then scored as 0 (no use in the past 3 months), 1 (problem use), and 2+ (high risk for substance use disorder). | 24 months after baseline visit | 
| Quality of life as assessed by the Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) Tool | The TAPS tool screens for substance use (including tobacco, alcohol, prescription medication, and other drugs) and includes a brief assessment of abuse risk for those who screen positive. Individuals who screen positive for use of any of the substances are then scored as 0 (no use in the past 3 months), 1 (problem use), and 2+ (high risk for substance use disorder). | 30 months after baseline visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Xerostomia as assessed by stimulated saliva secretion rate | Prevalence of xerostomia | Baseline | 
| Xerostomia as assessed by stimulated saliva secretion rate | Prevalence of xerostomia | 6 months after baseline visit | 
| Xerostomia as assessed by stimulated saliva secretion rate | Prevalence of xerostomia | 12 months after baseline visit | 
| Xerostomia as assessed by stimulated saliva secretion rate | Prevalence of xerostomia | 18 months after baseline visit | 
| Xerostomia as assessed by stimulated saliva secretion rate | Prevalence of xerostomia | 24 months after baseline visit | 
| Xerostomia as assessed by stimulated saliva secretion rate | Prevalence of xerostomia | 30 months after baseline visit | 
| Saliva proteins | levels of amylase expression will be assessed | Baseline | 
| Saliva proteins | levels of amylase expression will be assessed | 6 months after baseline visit | 
| Saliva proteins | levels of amylase expression will be assessed | 12 months after baseline visit | 
| Saliva proteins | levels of amylase expression will be assessed | 18 months after baseline visit | 
| Saliva proteins | levels of amylase expression will be assessed | 24 months after baseline visit | 
| Saliva proteins | levels of amylase expression will be assessed | 30 months after baseline visit | 
| Saliva proteins | levels of IgA expression will be assessed | baseline visit | 
| Saliva proteins | levels of IgA expression will be assessed | 6 months after baseline visit | 
| Saliva proteins | levels of IgA expression will be assessed | 12 months after baseline visit | 
| Saliva proteins | levels of IgA expression will be assessed | 18 months after baseline visit | 
| Saliva proteins | levels of IgA expression will be assessed | 24 months after baseline visit | 
| Saliva proteins | levels of IgA expression will be assessed | 30 months after baseline visit | 
| Correlative measures | Salivary cytokines: levels of IL-6, IL-7, IL-10, TNF-α, neopterin, β-2-microglobulin (β2M) and monocyte chemotactic protein-1 will be assessed | Baseline through 30 months |