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Review

The Impact of HIV Infection and Aging on Periodontitis

by
Sophia DeVore
,
Dalia Seleem
* and
Miou Zhou
*
College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766, USA
*
Authors to whom correspondence should be addressed.
Oral 2025, 5(3), 64; https://doi.org/10.3390/oral5030064
Submission received: 1 August 2025 / Revised: 25 August 2025 / Accepted: 28 August 2025 / Published: 1 September 2025
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Abstract

Background: Periodontal disease is a common chronic inflammatory disease affecting the oral cavity involving the tissues supporting teeth. It is a significant oral health concern worldwide, particularly amongst individuals living with human immunodeficiency virus (HIV). Biological aging is associated with a natural decline in the immune system, which can also affect the severity of periodontitis and other potential risk factors. In people living with HIV (PLWH), the contribution of both the HIV infection and the aging process can lead to increased susceptibility to periodontal disease. Objectives: This paper aims to review the recent literature about the relationships between HIV infection and early aging and their impact on periodontitis, and to inform interested clinicians about the current literature on the intersection between and within these topics. Methods: This review explores the recent literature on the complex relationship between HIV, aging, and periodontitis. The PubMed, ScienceDirect, and Medline databases were used to find clinical research studies within the last 10 years to identify significant correlations between HIV, aging, and periodontitis. Results: These studies identify key pathogens, molecules, or cellular pathways that contribute to a more comprehensive understanding of the pathophysiologic processes that link HIV, aging, and periodontitis. This complex relationship is multifactorial, involving immune dysfunction, microbial dysbiosis, and inflammatory pathways that still need further research. Conclusions: Overall, this exploration through molecular and cellular mechanisms underlying the relationships between aging, HIV, and periodontitis can provide therapeutic implications for dental clinicians to prevent and treat their affected patients.

1. Introduction

Human immunodeficiency virus (HIV) is still considered a major public health concern worldwide due to the lack of research on mechanisms, effective therapy, and prevention for the aging HIV population specifically. People living with HIV (PLWH) who are 50 years of age or older are expected to account for 75% of the HIV population by 2030 in the United States [1]. The use of combination antiretroviral therapy (cART) is a major contributing factor to this increased life expectancy for the PLWH population [1]. This population is also more susceptible to systemic infections due to their state of reduced immunity [2]. For example, periodontitis and HIV have a linkage due partially to the affected host’s immune response and the overlap in many bacterial species found in both diseases [3]. Oral manifestations and periodontal disease also need further research in PLWH due to the complex molecular relationships and mechanisms that affect this population [4].
There is a bidirectional relationship between periodontitis and aging, with periodontitis identified as a risk factor for age-related disease and an increase in aging-related molecular markers in periodontitis patients [5,6]. Post-menopausal women are a key demographic to evaluate when considering how early aging and periodontitis are linked [7,8]. Multiple potential mechanisms linking osteoporosis to periodontitis have been suggested related to alveolar bone resorption and periodontal pathogens, but there is currently a lack of understanding of which mechanism is the main contributor [9,10]. The mechanisms between osteoporosis, aging, and periodontitis are reviewed, with an emphasis on molecular biomarkers for bone metabolism in relation to aging.
There is an increased importance of studying the combination of periodontitis, aging, and HIV infection because there is still a lack of consensus on which mechanisms and key pathogens are responsible for their associations with one another [11,12]. And importantly, the aging population of PLWH is increasing [13], and these populations may have higher risk of oral health problems, including periodontitis. This review summarizes studies within the past 10 years about the correlations between HIV, aging, and periodontitis. These studies identified key pathogens, molecules, or cellular pathways that contribute to a more comprehensive understanding of the pathophysiologic processes that link HIV, aging, and periodontitis.

2. Methods

A literature review was conducted using the PubMed, ScienceDirect, and Medline databases, as shown in Figure 1. The search period covered publications from January 2015 to July 2025. The initial search was conducted on 10 September 2024 and the final search was conducted on 1 July 2025. Relevant key words and Boolean phrases included ‘Periodontitis’ AND ‘Aging’ OR ‘Biological aging’, Periodontitis’ AND ‘HIV’, ‘Aging’ OR ‘Biological aging’ AND ‘HIV’, ‘Periodontitis AND ‘Aging OR ‘Biological Aging’ AND ‘HIV’, ‘Periodontitis’ AND ‘Osteoporosis’, ‘HIV’ AND ‘Osteoporosis’. For the field of periodontitis, search keywords included: “Periodontitis”, “periodontal disease”, “gum disease”, “dental disease”, “oral microbiome”, “oral microbiota”, “periodontal diseases”, “saliva”, “oral-systemic diseases”, and “periodontal medicine”. For the field of aging, the search keywords included: “aging”, “biological aging”, “osteoporosis”, “oxidative stress’, “biomarkers”, “immunity”, “immune system”, “bone health”, “post-menopausal”, and “frailty”. For the field of HIV, the search keywords included: “HIV”, “HAART”, “HIV-1”, “HIV-1 latency”, “PLWH”, “HIV-1 infection”, “CD4 lymphocyte count”, “highly active antiretroviral therapy”, and “viral load”.
Eligibility involved reviewing titles and abstracts to identify studies evaluating the impact of HIV and/or aging on periodontitis. For articles meeting the inclusion criteria, a thorough full-text review was conducted. Data collection was conducted independently by one reviewer and reviewed and discussed again with two additional reviewers. Inclusion Criteria: Clinical research studies within the last 10 years (2015–2025), published in English, were allowed to identify significant correlations between HIV, aging, and periodontitis. This included peer-reviewed research articles involving human or animal subjects in vivo or in vitro. The studies could be randomized or non-randomized clinical studies, cohort studies, case–control studies, or cross-sectional studies. Free full-text articles were preferred and utilized from each database search. Exclusion Criteria: Articles unrelated to the associations or connections between periodontitis, HIV, and aging were excluded. Other studies excluded were narrative reviews, non-peer-reviewed literature, published in a language other than English. Additionally, studies published before 2015 or after the final search on 1 July 2025, were excluded. The paper selection details, including the number of records identified per database, inclusion/exclusion criteria, and the process for duplicate removal, are summarized in a PRISMA-style flow diagram in Figure 1 [14]. In addition, the GRADE grading system was reviewed [15] for periodontitis, HIV, and aging studies with detailed experimental design, confidence intervals, and p values, and our results indicated 4 studies to be low-certainty, 7 studies to be moderate-certainty, and 2 studies to be high-certainty.
Data Analysis: The data analysis for this literature review was conducted through a comprehensive review of the selected literature.
  • Categorization: The selected studies were categorized into four main topics: periodontitis and aging, periodontitis and HIV, aging and HIV, and periodontitis, aging, and HIV. This classification allowed for a structured analysis through key associations amongst the three main topics;
  • Thematic analysis: Amongst each of the four main topics, themes such as host immune dysfunction, microbial dysbiosis, inflammatory pathways, osteoporosis, and HAART/ART therapy stood out as key points;
  • Clinical relevance: The clinical relevance of the literature reviewed from various studies was also evaluated for future clinicians to be aware of when treating these patients affected by periodontitis, HIV, and/or aging;
  • Quality assessment: The quality of evidence presented in each study was assessed, considering factors such as study design, sample size, and methodology.

3. Periodontitis, Aging, and Osteoporosis

3.1. Periodontitis and Aging

It is estimated that 60% of adults over 65 years old have periodontitis and 4 out of 10 adults have periodontitis [16]. An alteration in bacterial biofilm results in a host systemic inflammatory response known as periodontal disease [17,18]. The clinical signs of periodontal disease can be measured through bleeding on probing (BOP), pocket depths (PDs), clinical attachment loss (CAL), and radiographic bone loss (RBL) [17]. In the advanced stage, there is an irreversible destruction of the periodontium and alveolar bone labeled periodontitis [1,11]. Periodontitis is also the leading cause of tooth loss in adults [17,19]. Genetic factors contribute up to 50% of the risk factors for periodontitis [20].
Biological aging involves multifactorial physiological changes that vary among individuals. It does not always correspond to chronological age [21,22]. Aging is considered one of the key variables for bone metabolism and can increase the activity of bone resorption and thus bone fragility [23,24]. Aging affects osteoprogenitors, which aid in injury sites for tissue recovery and are important for surgical dental procedures, such as extractions and implants [23,25].
There is a close link between periodontitis and aging. Periodontitis can enhance biological aging in middle-aged and older adults. Biological aging is a risk factor for periodontitis, and patients with periodontitis are biologically older than their chronological age [26]. Telomere length is one type of cellular biomarker for aging. In one study, telomere length was seen to be significantly shortened in periodontal patients. Overall, the study concluded that increased periodontitis severity was associated with accelerated biological aging, but there was a lack of a causal link [22].
Other diseases have been considered as confounding variables when looking at the association between periodontitis and biological aging. For example, periodontitis is a systemic disease that can also affect other organs in the body, most notably linked to cardiovascular disease (CVD). The systemic inflammation caused by periodontitis and influenced by biological aging can both affect the cardiovascular system. CVD incidence is a leading cause of death worldwide and has been linked to periodontitis severity [27,28,29]. Both periodontitis and CVD are associated with biological aging, resulting in physiological changes affecting the host and bacterial environment (Figure 2). Periodontitis is associated with a higher risk of CVD, and has been found to play a causal role in strokes and myocardial infarctions, increasing the risk of periodontitis in return [30].

3.2. Periodontitis and Osteoporosis

One of the main demographics affected by periodontitis and increased age is post-menopausal women. Menopause results in decreased hormone estrogen production in the ovaries [32], and this decreased estrogen contributes to women being affected by periodontitis at an earlier age than males [7,34]. Sex hormones play an important role in immunity and bone metabolism [23]. This hormonal change is also associated with periodontitis prevalence in post-menopausal women [7].
An imbalance between bone formation and resorption can lead to osteoporosis, resulting in age-related bone deterioration, fragility, and fractures [9]. Both osteoporosis and periodontitis contribute to bone loss, and osteoporosis in particular can worsen alveolar bone susceptibility to inflammation [32,35]. Bone mineral density (BMD) loss can lead to more resorption of alveolar bone [7], and low BMD and postmenopausal status are significantly associated with alveolar crestal height in women [32,36,37]. The interleukin (IL-1, IL-6, IL-8, and IL-10), tumor necrosis factor (TNF), and macrophage levels all increase the acceleration of the bone remodeling cycle [33]. These pro-inflammatory cytokines can then induce molecular changes in periodontal tissue and affect bone remodeling leading to eventual bone loss [31].
Osteoporosis does not initiate periodontitis directly, but BMD loss due to osteoporosis and increased susceptibility to alveolar bone resorption in periodontal sites are key risk factors for periodontitis. In addition to BMD loss, potential mechanisms for osteoporosis contributing to periodontitis have been proposed, including systemic factors and their interactions with bone remodeling, increased alveolar bone resorption due to periodontal pathogens, increased cytokine gene expression for osteoporosis and periodontitis in relation to aging, lifestyle factors such as cigarette smoking, and decreased calcium intake that act as risk factors for osteoporosis related periodontitis [9,10,38].
In one single-blinded cross-sectional study, BMD was found to be an important risk indicator for periodontitis in postmenopausal women [32,39], although BMD did not significantly affect the number of teeth lost due to periodontitis. In a separate double-blind case–control study, 100 women were split into osteoporotic and non-osteoporotic groups and the correlation between BMD and periodontal status was evaluated using dual-energy X-ray absorptiometry (DXA). The results showed that the osteoporotic group had significantly higher probing pocket depth (PPD), clinical attachment loss (CAL), and alveolar bone loss (ABL) when compared with the non-osteoporotic group. The study highlighted the important role of dentists in diagnosing osteoporosis early due to dental radiography equipment availability to assess the skeletal health of their patients. Periodontists can also monitor and maintain periodontal health in relation to osteoporosis along with educating and creating diagnostic and therapeutic approaches for their patients [9,40].
Another cross-sectional study looked at 94 post-menopausal women aged between 45 and 65 years old with periodontitis. The participants were scanned with DXA to assess BMD along with a periodontal examination. Although the study found no association between BMD and oral hygiene index (OHI), plaque index (PI), or body mass index (BMI), there was a statistical correlation between severity of periodontitis and osteoporosis for post-menopausal women. This study also emphasized the dentist’s role in the diagnosis and treatment of osteoporosis and periodontitis in post-menopausal women [7]. It is important for dentists to recognize the connection between osteoporosis and periodontitis which are more prevalent in middle-aged and older women. Both conditions involve bone resorption and deterioration of bone that typically progresses without noticeable symptoms until the advanced stages.
Antiresorptive agents, including hormone therapy, bisphosphonates, and vitamin supplements, are used to treat estrogen deficiency and could contribute to reducing alveolar bone destruction [33,41]. In a cross-sectional study that looked at osteoporosis treatment in the form of estrogen for postmenopausal women with periodontitis, individuals with osteoporosis but without periodontitis had reported seeing a dentist within the past two years compared with the individuals with periodontitis who did not regularly go to the dentist. Overall, the study showed a negative association between osteoporosis treatment in individuals with post-menopausal status along with severe periodontitis status for their periodontal health [33]. Another study with animal models identified methylsulfonylmethane (MSM) as a potential anti-inflammatory agent to increase osteoblast function for bone formation in the mandible. The study examined the effect of MSM in 36-week-old female mice in vivo by injecting MSM for 13 weeks. An increase in bone formation markers and a reduction in bone resorption markers along with increased trabecular bone density in mandibles were found in MSM-injected mice [31], suggesting that MSM could be a potential treatment to enhance alveolar bone regeneration in periodontal diseases with bone loss.

4. Periodontitis and HIV

4.1. HIV Infection and ART Therapy

Decreased immunity and increased susceptibility to other diseases are the main outcomes of HIV infection [2]. HIV is still considered a public health crisis, with 37.7 million people currently living with HIV based on the World Health Organization (WHO) world health statistics report in 2022. The introduction of antiretroviral therapy (ART) allows patients to live longer despite their chronic infection, and it has also been shown to decrease the frequency of periodontal diseases [12]. ART is an effective treatment for HIV suppression and restoration of CD4+ T cells [42]. A positive HIV status is considered a risk factor for periodontitis due to the patient’s comprised immunodeficiency from decreased CD4+ lymphocytes [43].
The introduction of highly active antiretroviral treatment (HAART) or ART has greatly increased the life expectancy of patients with HIV [43]. The increase in life expectancy for these patients exacerbates other comorbidities with age, such as cardiovascular disease, diabetes, osteoporosis, and periodontitis [44]. One study suggested that participants who started ART below or at 30 days of HIV infection had long-term benefits in terms of their reservoir clearance [45]. Reservoir clearance is the process of eliminating the CD4+ T cell supply in the body that contains HIV genetic material. This reservoir is usually established at the initial weeks of infection and is maintained at low levels with ART, although the reservoir cannot be prevented using ART [45]. HAART can be linked to the reduction in HIV infection-related oral manifestations [46]. A list of brief findings of the impact of HAART/ART treatment on HIV-related periodontal outcomes is included in Table 1.

4.2. Impact of HIV on Periodontitis

Although the prognosis of HIV has improved, this has introduced the need to treat age-related diseases such as periodontitis in an aging population. This specific population is also more susceptible to comorbidities and other complications that could increase the severity of periodontal disease [12]. Oral health problems are common in patients with HIV, with more than 50% of HIV patients experiencing oral manifestations [49,50]. These manifestations are also considered the main signs of the infection, making the dentist’s role in identifying and managing HIV patients critical [2].
The oral manifestations and periodontal disease in PLWH are a significant concern influenced by altered immunity and microbial dysbiosis relating to genetic diversity in specific bacterial species [4]. There are 24 distinct oral lesions currently found, but only oral candidiasis, oral hairy leukoplakia, HSV-1 related lesions, and Kaposi’s sarcoma are the most prevalent and observed consistently in PLWH [3]. Approximately 60–90% of individuals living with HIV/AIDs experience at least one oral lesion during their disease despite ART availability [47]. HIV-related oral lesions, such as human papillomavirus (HPV), are present in about one-third to one-half of all PLWH [49,51]. Oral candidiasis is another oral manifestation that presents in different clinical forms in PLWH [4]. Proper salivary flow is vital for mastication and key nutrient absorption. Xerostomia and decreased salivary flow are also common in aging patients, especially patients with HIV [49].
The oral manifestations in PLWH are a result of the complex relationship amongst the altered oral microbial community and are still not fully understood [4]. When the health-related quality of life (HRQoL) survey was used to assess women with HIV, it was found that unmet dental needs had a strong positive association with poor oral health-related quality of life measures [49]. HIV-related pathogens that can contribute to periodontitis should be evaluated for the risk of periodontitis development in PLWH [20]. Along with oral manifestations, the virological profiles of PLWH including CD4/CD8 T-cell counts are important to the progression of periodontal disease [43].
One observational study found that male patients with HIV but not on ART had a significantly higher risk of periodontitis [43]. A total of 205 patients were involved in this retrospective cross-sectional study, including 74 HIV+ and 131 HIV− patients. A direct relationship between HIV-1 infection and BOP was observed, supporting the importance for dentists to monitor gingival bleeding of the gums for prevention and management of HIV patients on HAART. This would include frequent checkups in the form of a periodontal exam, continued oral hygiene education, nutritional counseling, and dental treatments such as scaling and root planing (SRPs) or periodontal surgery as needed. Another study found that periodontitis was affected by increased age, poor oral hygiene, and carotid thickness (cIMT), and cIMT values were greater in HIV patients with periodontitis compared with equivalent controls [52].
Periodontal health results from the interaction between bacteria and the host’s unique response along with genetic factors, which contributes up to 50% of the risk factors for periodontitis [20,53]. The human leukocyte antigen (HLA), also known as the human specific major histocompatibility complex (MHC), is a molecule found in humans used for immune response by presenting T cells with antigen peptides. The HLA binding capacity to periodontal pathogens differs in humans, contributing to the unique host response [20]. A specific HLA in HIV patients is HLA-B57.1, associated with virus replication restriction and which has also been shown to be an independent resistance indicator of generalized periodontitis. One study assessed the association between HLA-B57.1 and chronic periodontitis in patients with HIV, with 45 subjects on ART and 55 subjects who had never taken antiretroviral drugs before. The study found HLA-B57.1 to be an independent risk factor for generalized periodontitis in patients with HIV infection [20]. These findings infer that if HLA-B57.1 is present, then the immune system can suspend a more successful immune response against viral infections compared with patients without HLA-B57.1 (Figure 3).

5. HIV and Aging

Molecular and cellular aging results in a functional decline of the immune system, which then increases susceptibility to infections in older adults [54,55]. ART has increased the life expectancy for HIV patients and PLWH who have continued access to ART have a similar life span to that of the HIV-negative population [56,57]. However, these longer lifespans come with consistently higher rates of chronic diseases and functional impairments [58]. Although the rates of liver disease, cardiovascular, and unrelated infectious diseases have not been affected by cART access, HIV infection accelerates aging [59]. A different study focusing on comorbidities in geriatric patients with HIV found that multiple morbidities and polypharmacy are related to increased HIV infection length [60]. The most common comorbidities in HIV patients include diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary diseases (COPD) [61].
Important changes in the immune system include inflammation, which is considered a hallmark of aging [55,62]. The progression of HIV contributes to accelerated aging through inflammation due to proinflammatory cytokines and oxidative stress resulting in cellular damage. Another hallmark of aging is frailty, which is generally found in the geriatric population, and especially in the HIV-infected aging population possibly related to chronic inflammation [55]. HIV infection and aging affect immunity differently in myeloid and lymphoid cells, yet both individually and collectively contribute to immunosenescence, or the decline in immune function. CD14+, IL-6, and D-dimer play a role in systemic inflammation and can result in accelerated aging [63,64]. The mechanism of immune aging in HIV-1 infection challenges the immune system to regulate homeostasis for cell turnover in CD4+ T cells [65]. The biological aging mechanisms of HIV patients include immune dysregulation, immune cell senescence, and chronic inflammation [59].
In comparison with non-infected individuals, PLWH are proposed to have accelerated aging [66]. Aging involves DNA damage and an accumulation of cells undergoing senescence due to inefficiency in the host immune response [67]. This can then result in abnormal inflammation and a less effective host immune response. Faster aging in PLWH compared with non-infected persons results in a negative effect on health span for PLWH. One cross sectional study including 150 PLWH ≥ 40 years old documented BMI, IL-6, TNF-α, C-X-C motif chemokine 10 (CXCL10), and sex hormones to identify inflammation and hormones in relation to age and physical function. The study found that, in PLWH, age was positively associated with TNF-α receptor and CXCL10 [68].
Genetic instability plays a role in the individual host response of PLWH and is a major trigger of aging [69]. One of the potential aging markers is telomere length. Telomere shortening is an important aging marker due to its contribution to genomic instability in relation to the PLWH population. In comparison with uninfected individuals, PLWH have significantly shorter telomeres, which can continue to shorten by 13% after 3 months in response to HIV infection [70]. A study reported that this shortened length process for PLWH equals one decade of aging and affects viral load and CD4 T-cell counts [71]. ART such as tenofovir is a potent inhibitor of telomerase and it can be involved in telomere shortening and accelerated aging in PLWH [72].

6. Interactions Between Periodontitis, Early Aging, and HIV Infection

The oral microbiome undergoes significant changes due to age-related modifications and HIV infection. This then contributes to a progressive decline in host defenses within oral tissues [73]. The interaction between aging, HIV infection, and the oral microbiome is still not well understood, particularly the oral microbiome in the aging subsection of PLWH [74]. Several studies reviewed here explore how HIV infection and aging influence the oral microbiome along with periodontal health, highlighting the affected microbial changes and the resulting clinical outcomes.
There is a connection between the oral and gut microbiome diversity, including bacterial and fungal communities within the immune system of patients with HIV. One study cohort included HIV-infected patients with a high prevalence of periodontal disease and mostly included post-menopausal women. With the use of specific ART regimens, there were different alterations in gut and oral bacteria. The study found that both bacterial and fungal oral microbiome communities are associated with chronic systemic immune activation in patients with HIV+ status [42].
A different study found that PLWH exhibited a higher prevalence of certain microorganisms compared with HIV-negative patients. In the study by Toljić et al., male participants were grouped by age (<35 years and >50 years) and HIV status (HIV-positive and HIV-negative) [73]. Oral manifestations of HIV infection were more frequent in older HIV-infected individuals, who had significantly worse periodontal health, including higher clinical attachment loss and greater probing depths, compared with the younger control group. Similarly, Lewy et al. used 16S rDNA sequencing of saliva samples to examine pathogenic bacteria associated with HIV infection in women of young and aging groups [74]. The study compared HIV-infected women aged >50 and <35 years with HIV-negative, age-matched women. The results showed a marked increase in Prevotella melaninogenica (a type of Bacteroidetes) and Rothia mucilaginosa (an Actinobacteria), indicating a dysbiosis in the oral microbiome of HIV-infected women, especially in older age groups.
Further research on HIV, menopause, and periodontal health was conducted by analyzing cytokine levels and clinical periodontal measurements in 135 post-menopausal women (76 HIV-positive, 59 HIV-negative) [75]. The study assessed various biomarkers in gingival crevicular fluid (e.g., IFN-γ, TNF-α, and IL-1β) and clinical indicators such as BOP, probing depth, and alveolar bone measurements. While BOP and clinical attachment loss did not show a significant difference between the HIV-positive and the HIV-negative groups, HIV-positive women had elevated levels of RANKL, fewer teeth present, and poorer bone quality, suggesting that post-menopause women with HIV have accelerated skeletal bone loss. The result also indicated compromised periodontal status for HIV positive post-menopausal women.
A Brazilian cross-sectional study of 200 participants (100 HIV-positive and 100 HIV-negative individuals) provided another linkage between HIV and periodontitis. The study found that individuals older than 43 years with HIV were at increased risk of periodontitis, with those on non-nucleoside reverse-transcriptase inhibitors (NNRTIs)-based antiretroviral therapy twice as likely to develop moderate to severe periodontitis [11]. NNRTIs have been associated with oxidative stress and reactive oxygen species (ROS) production, which then can accelerate the aging process and increase the cycle of inflammation and oxidative damage that exacerbates periodontal disease [76]. Age and HIV status were the primary risk factors for severe periodontitis in this cohort, with PLWH being five times more likely to develop moderate to severe periodontitis compared with controls [11].
In a larger cross-sectional study of 797 participants (258 HIV-positive and 539 HIV-negative controls) from the Netherlands, severe periodontitis was found to be more prevalent in HIV-infected patients [77]. The study also identified age and male sex as additional risk factors for severe periodontitis, with a higher risk of severe periodontitis in older male HIV patients. HIV-positive individuals treated with cART were included in the study, and regression analyses confirmed that HIV status significantly increased the risk of periodontitis. The risk continued to increase with age until around 55 years. Smoking was also identified as a significant risk factor for periodontitis in both the general and HIV-infected populations. Interestingly, 44% of participants did not disclose their HIV status to their dentist, though disclosure was not associated with periodontal disease severity, as measured by the Dutch Periodontal Screening Index (DPSI).
Overall, these studies allude to the complex interplay between aging, HIV infection, and periodontal health. HIV-infected individuals, particularly older adults, have an elevated risk of moderate to severe periodontitis. The aging process, HIV-related immune dysfunction, and the inflammatory and microbial shifts associated with HIV can also contribute to the progressive decline in oral health observed in this population. The risk factors and the physiological outcomes shared by or independently associated with periodontitis, aging, and HIV infection are summarized in Figure 4.

7. Conclusions

In conclusion, this review highlights the complex interplay between HIV, aging, and periodontitis, and reveals significant correlations between these conditions (please see Table 2 for the main findings and the p value/effect size of these studies), with evidence pointing to immune dysfunction, microbial dysbiosis, and inflammation as key contributors to the increased susceptibility to periodontitis in HIV-infected aging populations [44,78,79]. Although ART has improved the lifespan and quality of life of PLWH, it has also introduced new challenges in managing oral health, particularly periodontitis and oral lesions [50,60,78]. These findings stress the importance of preventative oral care and early intervention by dental clinicians to mitigate the impact of periodontitis on the aging PLWH.
This review is limited in its findings due to the variety of study designs, different methods and clinical parameters, and specific study populations assessed in the studies reviewed. There are few randomized control trials targeting the interactions between periodontitis, aging, and HIV. This makes it difficult for researchers to agree on specific associations or causations among these three. Many studies did not mention how genetic factors, which contribute up to 50% of the risk factors for periodontitis [20], and other confounding factors such as non-HIV medications and smoking could account for periodontitis, aging, and HIV. The lack of standardization in these studies diminishes the strength of the data despite the variety of evidence presented in this review.
There is a need for further research into the molecular and cellular mechanisms that connect HIV, aging, and periodontitis [23,42,73,80]. Future studies on periodontitis and aging can prioritize longitudinal designs with larger sample sizes to better elucidate the relationship between periodontitis, osteoporosis, and aging. Research is also needed on the prevention and treatment of osteoporosis, particularly its potential to mitigate periodontitis and tooth loss. Comprehensive periodontal assessments using clinical measurements are essential for investigating the biological mechanisms underlying age and periodontal health. The combined use of anti-inflammatory agents such as MSM and stem cells for alveolar bone regeneration in cases of periodontal bone loss also warrants further exploration across diverse populations [31]. Additionally, interventions targeting both inflammation and the oral microbiome may be critical for reducing chronic immune dysregulation, especially in older individuals living with HIV. Clinically, these findings emphasize the importance of comprehensive periodontal care in aging individuals living with HIV, with closer monitoring for early signs of periodontal breakdown. Collaboration between dental and medical providers should be prioritized to manage systemic inflammation, polypharmacy, and comorbidities in this vulnerable population.

Author Contributions

Conceptualization, S.D., D.S. and M.Z.; methodology, S.D., D.S. and M.Z.; writing—original draft preparation, S.D. and M.Z.; writing—review and editing, S.D., D.S. and M.Z.; supervision, D.S. and M.Z. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Acknowledgments

We thank Hubert Chan and the ADEA ADCFP for their support in this work.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

ABLAlveolar Bone Loss
AIDSAcquired Immunodeficiency Syndrome
ARTAntiretroviral Therapy
BMIBody Mass Index
BOPBleeding on Probing
BMDBone Mineral Density
CALClinical Attachment Loss
cART Combined Antiretroviral Therapy
CD4+ Cluster of Differentiation 4 (Helper T-Cell Protein)
COPD Chronic Obstructive Pulmonary Diseases
CiMTCarotid Intima-Media Thickness
CVDCardiovascular Disease
DPSIDutch Periodontal Screening Index
DXADual-energy X-ray Absorptiometry
HAARTHighly Active Antiretroviral Treatment
HIVHuman Immunodeficiency Virus
HLAHuman Leukocyte Antigen
HPVHuman Papillomavirus
HRQoLHealth-Related Quality of Life
MHCMajor Histocompatibility Complex
MSMMethylsulfonylmethane
NNRTINon-Nucleoside Reverse-Transcriptase Inhibitors
OHIOral Hygiene Index
PDsPocket Depths
PIPlaque Index
PLWH People Living With HIV
PPDProbing Pocket Depth
RANKLReceptor Activator of Nuclear Factor-κB Ligand
RBLRadiographic Bone Loss
ROSReactive Oxygen Species
rDNARibosomal Deoxyribonucleic Acid
SRPScaling and Root Planing
TNFTumor Necrosis Factor
WHOWorld Health Organization

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Figure 1. PRISMA flow diagram illustrating the study selection process.
Figure 1. PRISMA flow diagram illustrating the study selection process.
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Figure 2. Mechanisms associated with osteoporosis, aging, and periodontitis. In this diagram, the pathophysiological mechanisms of osteoporosis, biological aging, and periodontitis are listed [22,27,31]. One of the key pathways starts with menopause and osteoporosis, which contributes to biological aging and increased expression of pro-inflammatory cytokines [32,33]. Enhanced systemic inflammation is observed in periodontitis, as well as alveolar bone loss and resorption through bone remodeling. The figure was created with BioRender.com.
Figure 2. Mechanisms associated with osteoporosis, aging, and periodontitis. In this diagram, the pathophysiological mechanisms of osteoporosis, biological aging, and periodontitis are listed [22,27,31]. One of the key pathways starts with menopause and osteoporosis, which contributes to biological aging and increased expression of pro-inflammatory cytokines [32,33]. Enhanced systemic inflammation is observed in periodontitis, as well as alveolar bone loss and resorption through bone remodeling. The figure was created with BioRender.com.
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Figure 3. HLA-B57.1 is an independent resistance indicator of generalized periodontitis in patients with HIV. In the top row, the MHC gene for HLA-B57.1 is present. This results in a normal host response with the outcomes of healthy periodontium and minimal HIV replication. The bottom row represents a negative of HLA-B57.1 polymorphism. This results in a compromised host immune response with the outcomes of periodontitis and increased HIV replication.
Figure 3. HLA-B57.1 is an independent resistance indicator of generalized periodontitis in patients with HIV. In the top row, the MHC gene for HLA-B57.1 is present. This results in a normal host response with the outcomes of healthy periodontium and minimal HIV replication. The bottom row represents a negative of HLA-B57.1 polymorphism. This results in a compromised host immune response with the outcomes of periodontitis and increased HIV replication.
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Figure 4. Intersection of periodontitis, aging, and HIV infection. Risk factors independently associated with periodontitis, aging, and HIV infection, and the physiological outcomes or shared risk factors by all three are listed in this pie graph.
Figure 4. Intersection of periodontitis, aging, and HIV infection. Risk factors independently associated with periodontitis, aging, and HIV infection, and the physiological outcomes or shared risk factors by all three are listed in this pie graph.
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Table 1. Impact of HAART/ART treatment on HIV-related periodontal outcomes.
Table 1. Impact of HAART/ART treatment on HIV-related periodontal outcomes.
Subjects and MethodsHAART/ART Effect on Periodontal Health Authors and Published Year
Subgingival plaque samples from 24 HIV+ patients were assessed using PCR and amplicon sequencing.HAART reduced the prevalence of HIV-related oral lesions.Ponce et al., 2025 [4]
OHRQoL of 110 PLWH were assessed using OHIP-14. There was a significant association between oral mucosal lesions and OHRQoL. 60–90% of PLWH had at least one oral lesion despite ART availability.Sufiawati et al., 2024 [47]
Five databases were searched to identify longitudinal and cross-sectional studies on prevalence of NG, NP and periodontitis among HIV patients with or without HAART treatment.NG prevalence was significantly reduced in patients with HAART therapy. HAART was linked to the reduction in HIV infection related oral manifestations.Ntolou et al., 2023 [46]
A total of 200 (100 HIV+, 100 HIV−) subjects were examined. Each subject had a clinical periodontal examination, questionnaire on personal data and oral hygiene, and medical records reviewed.No observed effect of ART on periodontitis. The use of NNRTIs was also associated with moderate and severe periodontitis.Pereira et al., 2023 [11]
165 (44 ART-naïve and 121 ART-experienced) patients had their periodontal status assessed and a standard-questionnaire were given. ART-naïve patients had a higher risk of periodontitis. This is indicative of the protective impact ART has on this population. Fokam et al., 2020 [43]
554 children and adolescents infected with HIV on ART were included in this cross-sectional study to study the gingival recession and localized aggressive periodontitis.Gingival recession and aggressive periodontitis occurred more in patients that had a significantly shorter duration of ART treatment and suboptimal HIV control. Blignaut et al., 2019 [48]
Abbreviations: ART: antiretroviral therapy, HAART: highly active antiretroviral therapy, NG: necrotizing gingivitis, NNRTIs: nonnucleoside reverse transcriptase inhibitors, NP: necrotizing periodontitis, OHIP-14: oral health impact profile-14 questionnaire, OHRQOL: oral health related quality of life, PCR: polymerase chain reaction, PLWH: people living with HIV.
Table 2. Summary of studies about HIV, aging, and periodontitis.
Table 2. Summary of studies about HIV, aging, and periodontitis.
Subjects and MethodsMain Findingp-Value and/or Confidence IntervalsAuthors and Year
Analyzing subgingival plaque samples from 24 HIV+ patients7 species were detected, highlighting the complex oral microbial interactions in PLWH. Intraclass correlation coefficient of 0.86 for probing depth and 0.80 for clinical attachment lossPonce et al., 2025 [4]
Cross-sectional study with 9558 participants from the National Health and Nutrition Examination Survey (2009–2014)Periodontitis was associated with increased biological aging; Subgroup analysis found stronger associations in males for BioAgeAccele and current smokers for PehonAgeAccel. Periodontitis and biological aging association, with 0.57-year (95% CI: 0.28–0.86, p < 0.001) increases in BioAgeAccel and 0.41-year (95% CI: 0.04–0.78, p = 0.034) increases in PhenoAgeAccel.Song et al., 2024 [22]
135 self-reported postmenopausal women were recruited (including 59 HIV−, 76 HIV+ on cART) The mean age of participants was 57.04 ± 6.25 years. Postmenopausal women with HIV had deterioration of the alveolar trabecular bone microarchitecture.Women with HIV had higher RANKL expression in gingival crevicular fluid (p < 0.001), fewer teeth (p < 0.001), and lower trabecular number (p = 0.004) compared with women without HIV.Wadhwa et al., 2024 [75]
3269 participants from the National Health and Nutrition Examination Survey (2009–2014) were includedParticipants with periodontitis had increased biological aging, which was associated with increased CVD risk. Reverse MR analysis showed that DNAm Hannum age acceleration could increase the risk of periodontitis (95% CI 1.01–1.11 p  =  0.023); and there was a two-way causal relationship between CVD and biological aging (95% CI 0.87–0.99 p  =  0.017 and 95% CI 1.01–1.20 p  =  0.027).Zhang et al., 2024 [27]
52 (28 young, 24 aged) 129-Sv mice were used to extract their upper right incisorAge and gender significantly contributed to slower bone healing in craniofacial bones. Aged females (6.03  ±  1.03) had significantly reduced mineralized bone content in alveolar sockets compared with young females (12.25  ±  3.09 p < 0.05) and aged males (9.86  ±  2.10 p < 0.05).Biguetti et al., 2023 [23]
200 (100 HIV+, 100 HIV−) subjects were examined, 81 (40.3%) had periodontitisPLWH and those older than 43 were more likely to develop moderate and severe periodontitis, suggesting an association between HIV, advanced age, and periodontitis.Individuals who were over 43 years old (OR  =  1.557; CI  =  0.882−2.747) and were HIV+ (OR  =  3.064; CI  =  1.698–5.529) were more likely to develop periodontitis.Pereira et al., 2023 [11]
351 WLWH and 52 WRH participants had pocket depths and clinical periodontal attachment loss assessmentsThere was no association between BMI and periodontitis among women with or without HIV infectionaOR of mild, moderate, and severe periodontitis in obese women were: 1.14 (95% CI: 0.51–2.52), 1.02 (95% CI: 0.46–2.29), and 0.24 (95% CI: 0.06–1.07), respectively.Janorkar et al., 2022 [17]
205 patients (74 HIV+ and 131 HIV−) were tested for PPD, CAL, BOP, and VSB.HIV patients on HAART had direct association of HIV-1 infection with BOP, suggesting that monitoring gingival bleeding would be beneficial in the periodontitis prevention in HIV-1 patients on HAART.HIV-1 infection (OR = 5.53, p < 0.0001, 95% CI: 2.45–13.64) and age (compared to young (18–35 years old), 35–50 years old: OR = 5.73, p < 0.0001, 95% CI: 2.49–13.20, >50 years old: OR = 6.29, p = 0.002, 95% CI: 1.94–20.42) had significant association with BOP outcome.Gonçalves et al., 2022 [44]
Periodontal status was assessed in 65 patients (44 ART-naïve and 121 ART-experienced) by measuring CAL, PPD, plaques index.ART-naïve patients had a higher risk, indicating the protective role of ART; severely immune-compromised patients and men were vulnerable to periodontitis.Periodontitis risk of the (a) ART-naïve population versus the ART-experienced population was doubled (OR 2.06, p = 0.03), (b) ART-naïve, CD4 < 200 cells versus those with higher CD4-values was threefold higher (OR 3.21, p = 0.06).Fokam et al., 2020 [43]
82 HIV+ adults with <200 CD4 T-cells/μL were examined at 0 and 3 months after ART; 32 patients were reassessed after 5 years.5 years after ART, periodontitis was higher with greater age and poor oral hygiene, while smoking, oral candidiasis, or low CD4 T-cell counts showed no effect.Periodontitis was potentiated by older age (p = 0.03) and poor oral hygiene (p = 0.05).Wulandari et al., 2020 [52]
Prevalence and severity of periodontitis were assessed in 258 HIV+ patients and 539 controlsSevere periodontitis (DPSI 4) was higher in HIV+ patients than in controls. Periodontitis prevalence and severity were increased in HIV+ patients compared with controls, particularly in older males.HIV-infection (95% CI: 1.13–2.34, p = 0.008), increasing age (95% CI: 1.16–1.35, p < 0.001), and male sex (95% CI: 1.18–2.3, p = 0.003) were significant risk factors of severe periodontitis with logistic regression analysis.Groenewegen et al., 2019 [77]
94 postmenopausal women in the range of 45–65 years oldPeriodontitis severity and osteoporosis among postmenopausal women were correlated.There was a significant correlation between periodontitis and osteoporosis (x2 = 9.76, p = 0.045).Mashalkar et al., 2018 [7]
60 HIV+ male, including 30 younger (≤35 years) and 30 older (≥50 years) patientsAll periodontal parameters were higher in older HIV+ patients. HIV-associated gingivitis and periodontitis were more frequent in patients over 50 years.HIV-associated gingivitis (p = 0.007) and HIV-associated periodontitis (p = 0.010) were higher in older than younger HIV+ patients. Toljić et al., 2018 [73]
Abbreviations: aOR: adjusted odds ratio, BioAgeAccel: biological age acceleration, BMI: body mass index, BOP: bleeding on probing (BOP), CAL: clinical attachment loss (CAL), CI: confidence interval, DPSI: Dutch periodontal screening index, MR: Mendelian randomization, OR: odds ratio, PhenoAgeAccel: phenotypic age acceleration, PLWH: people live with HIV, PPD: Periodontal probing depth, RANKL: receptor activator of NF-κB ligand, VSB: visible supragingival biofilm (VSB), WLWH: women living with HIV, WRH: women at risk of HIV.
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DeVore, S.; Seleem, D.; Zhou, M. The Impact of HIV Infection and Aging on Periodontitis. Oral 2025, 5, 64. https://doi.org/10.3390/oral5030064

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DeVore S, Seleem D, Zhou M. The Impact of HIV Infection and Aging on Periodontitis. Oral. 2025; 5(3):64. https://doi.org/10.3390/oral5030064

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DeVore, Sophia, Dalia Seleem, and Miou Zhou. 2025. "The Impact of HIV Infection and Aging on Periodontitis" Oral 5, no. 3: 64. https://doi.org/10.3390/oral5030064

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DeVore, S., Seleem, D., & Zhou, M. (2025). The Impact of HIV Infection and Aging on Periodontitis. Oral, 5(3), 64. https://doi.org/10.3390/oral5030064

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