Determinants of periodontitis according to the immunological and virological profiles of HIV-infected patients in Yaoundé, Cameroon

The Human immunodeficiency Virus (HIV) remains a global health problem with over 36.7 million infected people in 2016 according to WHO [1]. Worth noting, sub-Saharan Africa carries about 70% of the global burden and the prevalence of HIV in Cameroon was 3.4% in 2018 [2]. HIV is a retrovirus, whose infection is characterized by a combination of clinical manifestations which are caused by the infection directly and killing of CD4+ lymphocytes, thus decreasing the natural defense mechanism leading and severe immunodeficiency.

The introduction of Highly Active Antiretroviral Treatment (HAART) has greatly increased the life expectancy of patients living with HIV. Yet HIV infection is still associated to different oral manifestations [3] such as oral hairy leukoplakia, oral candidiasis, Kaposi's sarcoma, non-Hodgkin lymphoma, as well as periodontal diseases such as linear gingival erythema, necrotizing ulcerative gingivitis, necrotizing ulcerative periodontitis and possible exacerbation of pre-existing periodontal conditions.

HIV is therefore a risk factor for periodontitis, as immunological changes in HIV infection may alter the patient’s ability to respond appropriately to infection, including those due to sub-gingival bacterial [4]. There are various types of cells found in the gingival fluid including Type 1 and Type 2 helper cells whose imbalance in cytokine production can induce bone resorption hence clinical attachment loss (CAL) [5]. Pro-inflammatory cytokine such as Interlukin-1 (IL-1) and alpha-tumor necrosis factor (TNf-α) stimulate the production of osteoprotegerin ligand by osteoblastic cells which later differentiate into precursor osteoclast and then osteoclast leading to bone resorption, hence periodontitis in patients [6]. To reduce the risk of opportunistic infections, including oral manifestations, international medical associations developed guidelines for starting antiretroviral treatment despite the CD4 cell counts in these patients known as the test and treat approach implemented in Cameroon since 2016 [7]. Importantly, patients with HIV may present distinct immunological/virological profiles and different oral manifestations [8]. The immunological parameter usually used for this evaluation is the CD4/CD8 T-lymphocyte counts in peripheral blood and plasma viral load, which appear to play an important role in the progression of periodontal disease and the course of HIV-infection [9].

Despite the high prevalence of HIV infection in Cameroon [2], little or no reports about the periodontal status of HIV-infected Cameroonians have been published. With the aim to identify high risk populations so as to set up better preventive measures, the present study tested the hypothesis that periodontal disease in persons living with HIV was significantly related to low CD4/CD8 ratio and an increase in plasma viral load.

The present study evaluated immunological and virological determinants of periodontitis in patients with HIV. 65% of the population were females, the male to female ratio is similar to the gender distribution reported in the general population of people living with HIV in Cameroon as well as in other studies, thus supporting the vulnerability of women to HIV and the possible representatives of our findings to the target population of adults living with HIV in Cameroon [10, 11]. The median CD4 in the ART-naïve (176 cells/mm³) was lower than in the ART-experienced (443 cells/mm³) patients but both appeared to be lower as compared to findings reported by Khammissa et al. [11] where the median CD4 in ART-naïve patients was higher than in the ART-experienced population. This is likely attributed to the late diagnosis of HIV in their study population. On the other hand, higher levels of viral load in the ART-naïve compared to the ART-experienced groups basically reflects the selective pressure of HAART among the ART-experienced patients.

The overall prevalence of periodontitis (39.4%) was similar to that in other studies carried out in HIV-infected patients (with prevalence 36.11% and 34% respectively) [12, 13]. Worth noting, the significantly higher rate of periodontitis among ART- naïve compared to ART-experienced patients (p = 0.03) supports the fact that naïve patients have a higher risk of presenting with periodontitis. This in turn highlights the protective role of ART in the current era of “test all” or “test and treat” in resource limited settings like Cameroon. However, ART regimen did not specifically alter the occurrence of periodontitis as previously supported by Fricke et al. [14]. Furthermore Fricke et al. reported an association between the duration of infection and periodontitis which was not considered in our present study.

Subsequently there was no significant association with low CD4 (CD4 < 200 cells/mm³) and the occurrence of periodontitis in both ART-naïve and ART-experienced populations. These results are in agreement with that of Umeizudike et al. [10], who did not find any statistical association as well (p = 0.623). It’s worth noting that ART-naïve population with CD4 cells less than 200 had three times higher risk of having periodontitis than the ART group. This is similar to the findings of Vernon et al. [15] in which those with CD4 cells less than 200 had two times higher risk of presenting with periodontitis than those with CD4 cells greater than 200 (p = 0.001). These concordant evidences therefore support that having CD4 cells less than 200 is a strong predictor of periodontitis in population living with HIV.

There was no significant associations with CD4 cells < 200/mm³ and other periodontal clinical parameters. This observation was concordant with a previous study reporting no significant association between CD4 cells < 200/mm³ and clinical periodontal parameters [16] A study carried out in India showed a statistically significant association between the immune status and periodontitis, thus calling for context specific investigations in delineating such disparities [13, 17].

Our study revealed men had a significantly higher risk of presenting with periodontitis than women (p = 0.0008), as supported by several previous findings in the same population on different countries [18, 19]. This could be explained by the fact that men have a less positive attitude towards their oral health than women, and men generally attend clinics lately as compared to women thus favoring advanced disease conditions in the frame of late diagnosis. Age was significantly associated with CAL, suggesting the potential role of age as a risk factor of periodontitis, similar to the findings of Umeizudike where those with age > 35 years where significantly associated with periodontitis [18].

Our study was limited by the small sample size of the ART-naïve population. Second there was lack of follow-up for these patients. Third, characterization of the oral microbiome in HIV-infected and HIV-uninfected subjects with their ART status was not done and could have been worth evaluating. Hence, studies covering these aspects should be carried out especially for the ART-naïve populations.

Overall, our evidence-based findings suggest the following algorithm for an improved management of oral health in HIV highly-burdened resource limited settings, Fig. 3.

In our study, ART-naïve HIV-infected patients especially those of male gender with severe immunodeficiency (CD4 cells < 200/mm³) had a significantly higher risk of periodontitis. Thus, priority intervention towards a better prevention of periodontitis among people living with HIV requires the need for clinicians to ensure systematic referral for periodontal screening (bucco-dental checkups) for every HIV-infected male or immunodeficiency patient.