Correlation of clinical profile toward oral manifestations of HIV/AIDS patients

Introduction: Human Immunodeficiency Virus (HIV) exhibits the capability to weaken human immune system. The infected subject will later be more susceptible to suffer from opportunistic diseases when the CD4 cell count is lesser than 200 cell/μL. Oral Thrush, periodontal disease and xerostomia are common oral manifestations in AIDS patient which initially indicate the presence of HIV infection. No research has been conducted to discuss the association between oral manifestation HIV/AIDS toward socio-demographic and clinical profile of the HIV/AIDS patients. Therefore, this study was aimed to analyse the association between oral manifestation HIV/AIDS toward socio-demographic and clinical profile of the HIV/AIDS patients. Methods: This was an analysis study with cross sectional design performed in 2019. The data of clinical profil of HIV AIDS patient and oral manifestation were obtained from secondary data of medical record.The 55 samples were taken with total sampling technique. Results: Chi-square test showed there was a significant correlation between number of CD4 with candidiasis, oral thrush and periodontal disease. There was a significant correlation between duration of ARV therapy and candidiasis, oral thrush (p<0.05). Conclusion: There is a correlation between the number of CD4 cells and the duration of ARV treatment on candidiasis,oral thrush, periodontal disease and xerostomia.


INTRODUCTION
Human Immunodeficiency Virus (HIV) is a viral strain that instigate the weakening of body's immunity. Someone who is infected with HIV is usually prone to experience opportunistic diseases. 1 The infection will result in a group of manifestations known as Acquired Immunodeficiency Syndrome (AIDS) that can disrupt the human immune system. 2 Ministry of Health of the Republic of Indonesia in 2017 reported that there were 10376 HIV cases in Indonesia, while 673 other cases were disclosed as AIDS. The percentage of the disease based on age group were 17.6% in 20-24 year-olds group, 69.6% in  year-olds group, and 6.7% in >50 year-old group. Based on gender, the patients were dominated by men with a ratio of 2 : 1. The risk factors for most patients were due to samegender sexual intercourse (28%), heterosexual copulation (24%), injection needle use (2%) and others (9%). 3 Cluster of Differentiation (CD4) is an early indication for the progression of AIDS because CD4 number will decline faster than the clinical condition. CD4 count in HIV-infected patients are classified into four categories, that are the state of non-immunodeficiency (CD4 count of more than 500 cells / µL), the mild state of immunodeficiency (CD4 count of 350-499 cells / µL), the moderate state of immunodeficiency (CD4 count of 200-349 cells / µL), and the severe state of immunodeficiency (CD4 counts of less than 200 cells / µL). 4 When CD4 count is below 200 cells / µL, patient condition has entered the AIDS condition where opportunistic infections frequently occur. 5 There are opportunistic and neoplastic infections that may occur in HIV-infected patients, such as protozoan infections, fungal infections, bacterial infections, and viral infections. 6 Clinical manifestations that often appear in the oral cavity of HIV sufferers include oral candidiasis, periodontal disease, and disorders of salivary glands like xerostomia. 7 Dental practitioners have a high probability to detect HIV-infected patients who have yet been diagnosed when providing services in a dental practice, because they also hold a role in diagnosing and managing the disease. Some of oral diseases are present as the clinical manifestations of systemic diseases, like infectious diseases, inflammatory conditions, metabolic and endocrine disorders, hematological diseases and malignancies. Oral manifestations are very important to discern as it is often the first indication that a person is infected with HIV. 8,9 In South Kalimantan, there is still no data about the oral manifestation of HIV/AIDS. There are not any research that have discussed the interrelation between HIV/AIDS and oral manifestations before, especially in South Kalimantan. Therefore, this study aims to analyze the relationship between HIV/AIDS and oral manifestations in South Kalimantan.

METHODS
This study had been approved for ethical clearance that was issued by Faculty of Dentistry, University of Lambung Mangkurat No. 115 / KEPKG-FKGULM/ EC/I/2019. This research was an observational descriptive study with a cross-sectional design obtained from informed consent, history taking and clinical examination of oral cavity among HIV/ AIDS patients in Banjarmasin. The tools used were the oral diagnistic tools.
The population in this study was HIV/ AIDS patients treated at the VCT clinic of RSUD. Moh. Ansari Shaleh Banjarmasin and RSUD Ulin Banjarmasin in November 2018-March 2019. The 55 samples were taken with total sampling technique. The samples comprised of HIV/AIDS patients who were being treated at the VCT clinic and HIV/AIDS patients who were being hospitalized at RSUD Moh Ansari Shaleh Banjarmasin and RSUD Ulin Banjarmasin at the time of data collection. The patients were constantly assured to meet the inclusion and the exclusion criteria. The variables examined in this study were all of clinical manifestations in the oral cavity of HIV / AIDS patients based on CD4 count, age, gender, marital status and duration of ARV treatment. Oral thrush were diagnosed base on the clinical examination, periodontal disease were diagnosed base on the clinical examination by using probe, and xerostomia were diagnosed base on the anamnesis.
The operator visited the VCT clinic at RSUD Ulin and RSUD Moh. Ansari Shaleh Banjarmasin and informed the research subjects about the benefits and the procedures that will be carried out by the researcher. Patients then provided their consent as a sign of approval to be the subject of the study. Further, the operator performed anamnesis and the clinical examinations to collect the data.

RESULTS
Based on the results, there were 55 subjects of AIDS patients in RSUD Ulin Banjarmasin and RSUD Moh. Ansari Shaleh Banjarmasin. The socio- demographic characteristic of subjects (age, marital status, gender) and clinical profile (CD4 count and duration of ARV therapy) can be seen in Table 1. The data obtained were analyzed using non-parametric because the scale used in this descriptive research is an ordinal scale. Chi-square Based on Table 3, it can be observed that there is a relationship between periodontal disease and CD4 count with p=0.02 (p<0.05), and there is no significant relationship between age, gender, marital status and duration of treatment on the presence of periodontal disease (p> 0.05).
Based on Table 4 show that there is no significant relationship between xerostomia with CD4, age, gender, marital status and duration of ARV therapy because of the number of values p> 0.05.
Based on Table 4 show that there is no significant relationship between CD4, age, gender, marital status and duration of ARV therapy on xerostomia because p > 0.05.  Table 2 shows the correlation between oral thrush and CD4 count with p = 0.01 (p <0.05). The table also presents that there is a significant relationship between oral thrush and the duration of ARV treatment with p = 0.01 (p <0.05). No significant relationship was observed between age, gender, and marital status with the occurrence of oral thrush (p> 0.05).
AIDS observed in this study. Xerostomia can be caused by the side effect of the drug that used by the patients. This is contrasting with the result of Etis (2019) showed that T cells in the salivary gland are interconnected with the sympathetic and parasympathetic nerves which are responsible in stimulating the flow of saliva and inhibiting the production of saliva. These nerves are associated with many cells in the salivary gland such as ducts, epithelial cells and blood vessels. When the salivary gland is inflamed and enlarged caused by microorganisms, the function of the parasympathetic nerve will be disrupted and will cause the decrease in salivary flow. Decreased flow of saliva will induce an acidic state in oral environment. Low pH in mouth (4,5-6,5) will cause microorganisms to become pathogens, one of which is Candida albicans. 10,11 An insignificant relationship was also found between xerostomia and the use of antiretroviral drugs after 6 months. This is contrasting with the result of Verna N et al. 12 showed that long-term use of antiretroviral drugs will cause a decrease in the salivary flow rate, especially in HIV-positive patients. HIV/AIDS sufferers prescribed with a long-term antiretroviral therapy have a risk to experience salivary gland hypo-function which will change the composition of saliva and cause xerostomia. 12 The results of this study did not show a significant relationship between xerostomia and age in people with HIV/ AIDS. This is contrasting with the result of Phuu Han's research 2015 that revealed a high level of vulnerability at the age of two to three decade. 13 It was found that candidiasis did not have a significant relationship with age in patients with HIV/AIDS. Based on Frimpong 2 HIV prevalence was reported to be higher in the second decade (23%) and the third decade (34.2%). The highest prevalence was observed between 20-35 yearolds age group which was associated with the most contagious factors of HIV/AIDS, namely homosexual intercourse. 16 Candidiasis and marital status did not show any significant relationship with people with HIV/AIDS ad well. This research is supported by a study from Anglewicz and Reniers which described that HIV/AIDS sufferers are mostly married individual who change partners and remarried with a prevalence of 66.4%. 17 The results of this study indicate no significant relationship

DISCUSSION
There was no significant relationship between xerostomia and CD4 counts in people with HIV/ between Oral thrush and gender in people with HIV/AIDS. Men have twice the risk of getting HIV/ AIDS compared to women. Based on Yuliandra 18 this gender differences is associated with the frequency of changing sexual partners where the largest proportion were discovered in men. 18 The results of this study also indicate that there is a significant relationship between oral cavity manifestations namely candidiasis with CD4 counts <200 cells / µL. This is contrasting with the result of Pakfetrat A (2015) this prompted by the immunocompromized conditions which generally present in HIV / AIDS patients and the high incident rates of opportunistic infections found in the oral cavity. 19 The most common oral manifestations of opportunistic infections in people with HIV / AIDS are candidiasis. It may also relate to low levels of serum vitamin B12 and folate were shown in HIV patients, indicating the need for early nutritional intervention to ensure optimal nutritional status and prevention of oral lesions in HIV patients. 20 The analysis between the duration of ARV treatment and candidiasis resulted in a significant relationship. Based on Tesimen 21 ARV therapy will reduce the number of viruses or viral load and increase CD4 cell counts in the body to improve the dysregulation of body's immune system. 21 When consuming ARVs, the production of proteinase in HIV will be hindered, which also generate the inhibition of Candidal growth in vitro and in vivo. Consumption of anti-retrovirals may increase the number of CD4 cell. An increase in CD4 cell counts were reported with an increase in the amount of sIgA. SIgA is a specific humoral response to Candida which is responsible in inhibiting candidal colonization and attachment to the oral epithelium. 22 In this study, there is a significant relationship between periodontal disease showed bone reduction was seen with x-rays and there was a probe examination pocket over 3mm and age in people with HIV/AIDS. HIV/AIDS sufferers who experienced periodontal disease in this research were found in the age of 20-35 years old. Previous study, pathognomonic periodontal manifestation such as Necrotizing Ulcerative Gingivitis (NUG) and Necrotizing Ulcerative Periodontitis (NUP) was found in Indonesian PLWHA which are associated with low CD4+ level reflecting the immune suppression level, and it can be used to predict HIV/AIDS stage of progression. Toljic (2018) reported that the number of gingivitis and periodontitis cases was significant in patients aged over 50 years, whereas the number of linear gingival erythema cases were mostly observed in patients aged <35 years. 23 Periodontal disease and marital status shows no significant relationship in people with HIV/AIDS. This is related to the transmission route of HIV/AIDS, namely sexual activity outside marriage with the same or opposite sex. 24 No significant relationship is found between gender and periodontal disease. Valentine's research showed that men suffer more from periodontal disease than women in 26-35 yearolds age group. 25 Treatment of ARVs also has no significant relationship with periodontal disease which is ratified by Fricke's research where no significant relationship was distinguished. Patients who took ARVs for longer period had better periodontal health than those who did not. Patients who took part in the monitoring programs will be benefited and become healthier in general than those who did not follow the therapy program. 19 Periodontal disease begins with the presence of bacterial colonization on tooth surface and gingival sulcus which will affect the gingiva and the supporting bone of the tooth. The disease is initiated with an inflammatory process that involves natural and adaptive immune system. Phagocyte cells, such as PMN, monocytes, neutrophils and magrophages, are the components of natural immune systems, while the adaptive immune system are consisted of T cells and B cells that requires time to recognize antigens before retaliate. In periodontal conditions, T cells are more dominant in secreting CD4 cells compared to CD8 cells. CD4 T cells function to maintain homeostasis in the presence of biofilm plaques when periodontal diseases occurred. Macrophage cells act as APC (antigen presenting cell) which possesses MHC class II molecules that will be presented towards the surface of T cells to bind CD4 cells. CD4 cells in the presence of periodontal disease will secrete cytokines and activate B cells to produce antibodies. The cytokines that play roles during periodontal diseases are IL-1, IL-6, TNF-α, and IFN-ϒ. If cytokines are produced inappropriately, the destruction of periodontal tissue will occur. 26 This study reveals that there is a significant relationship between periodontal disease and the number of CD4 cells. The result is supported by Valentine 24 It was caused by T cells and macrophages dysfunction in the body when CD4 cell counts in HIV/AIDS patients is less than 200 cells/µL. CD4 cells play an important role in immune reactions because they function to produce various types of cytokines, chemokines and hematopoietic growth factors (granulocytes and macrophages). Therefore, losing this "master cell" has a detrimental effect on other components of the immune system. 7 This result is supported by Matafsi 26 who proved that there is a reduction in cytokine secretion among HIV/AIDS sufferers with CD4 cell count less than 200 cells/µL which may interfere in the production of IL-1, IL-6, TNF-α, and INF-ϒ. This gives rise to more severe signs and symptoms of HIV/AIDS-associated periodontal disease with lower responsiveness in periodontal therapy. [22][23][24]27 CONCLUSION It can be concluded that there is a relationship between HIV/AIDS and the oral manifestations such as xerostomia, oral thrush and periodontal disease with CD4 count, age, marital status, gender, and ARV therapy duration in HIV/AIDS patients in Banjarmasin, South Kalimantan.