|Year : 2016 | Volume
| Issue : 2 | Page : 123-129
Evaluation of oral lesions in HIV seropositive individuals and its correlation with CD4 + T-lymphocytic count
Shibani Shetty1, Kiran Kumar Kattappagari2, Kaveri Hallikeri3, Rekha Krishnapilli4
1 Department of Oral Pathology and Microbiology, Mathrusri Ramabai Ambedkar Dental Collage, Bangalore, India
2 Department of Oral Pathology and Microbiology, SIBAR Institute of Dental Sciences, Guntur, Andhra Pradesh, India
3 Department of Oral Pathology and Microbiology, Sri Dharmasthala Manjunatheshwara College of Dental Sciences, Dharwad, Karnataka, India
4 Department of Oral Pathology and Microbiology, Annoor Dental Collage, Muvattupuzha, Kerala, India
|Date of Web Publication||5-Jul-2016|
Kiran Kumar Kattappagari
Department of Oral Pathology and Microbiology, SIBAR Institute of Dental Sciences, Guntur, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background and Objectives: Human immunodeficiency virus (HIV) infection is characterized by a gradual reduction in the counts of cluster of differentiation (CD)4 + T-lymphocytes that in turn leads to opportunistic infections and specific neoplastic processes. The introduction of antiretroviral therapy (ART)/highly active ART (HAART) has led to a decrease in the morbidity and mortality associated with HIV infection. The aim of this study is to evaluate the prevalence of HIV-related oral lesions and to correlate these lesions with laboratory parameter such as CD4 + T-lymphocyte count before and after the administration of ART.
Materials and Methods: In the present study, a total of 120 patients were evaluated, out of which 79 patients who presented with oral lesions were further assessed for oral lesions and respective CD4 + T-lymphocyte counts. The oral examination was carried out using presumptive criteria by European Community (EC) Clearinghouse and CD4 + T- lymphocyte counts was assessed by flow cytometry. Same group of patients were followed up for next 6 months to determine the changes in the CD4 + T-lymphocyte counts and oral lesions.
Results: HIV-related oral lesions were found to be more prevalent in the age group of 31-40 years, with a relatively high frequency of occurrence in male patients. The CD4 + T-lymphocyte count was significantly increased after the administration of ART when compared to that before the administration of ART in all the patients. However, the lesions did not subside completely even after the increase in of CD4 + T-lymphocyte counts.
Interpretation and Conclusion: The difference in the prevalence of oral manifestations may be the result of variations in data of the study population such as race, socioeconomic status, sex, drug therapy, genetics, oral habits, and degree of immune suppression and variation in diagnostic criteria.
Keywords: Antiretroviral therapy (ART)/highly active ART (HAART), CD4 + T-lymphocyte counts, human immunodeficiency virus (HIV)-related oral lesions
|How to cite this article:|
Shetty S, Kattappagari KK, Hallikeri K, Krishnapilli R. Evaluation of oral lesions in HIV seropositive individuals and its correlation with CD4 + T-lymphocytic count. J NTR Univ Health Sci 2016;5:123-9
|How to cite this URL:|
Shetty S, Kattappagari KK, Hallikeri K, Krishnapilli R. Evaluation of oral lesions in HIV seropositive individuals and its correlation with CD4 + T-lymphocytic count. J NTR Univ Health Sci [serial online] 2016 [cited 2020 Apr 9];5:123-9. Available from: http://www.jdrntruhs.org/text.asp?2016/5/2/123/185445
| Introduction|| |
Human immunodeficiency virus (HIV) is a retrovirus affecting more than 45 million people worldwide. It represents an enormous and multifaceted challenge at an individual level and also in the public health domain, which leads to a gradual decrease of immune system with subsequent development of aquired immuno deficiency syndrome (AIDS).  HIV-related oral lesions are frequent and often an early finding in patients with HIV infection. They affect the quality of life of the patients and are useful markers of disease progression and immunosuppression and their importance has been demonstrated in various studies.  Oral manifestations are the first features of HIV/AIDS or they may be the indication in determination of general health; some of oral manifestations are considered as poor prognosis.  The oral lesions found in patients with HIV infection can be of fungal, viral, and bacterial origin. 
Oral manifestations of HIV individuals include candidiasis; oral hairy leukoplakia (OHL); xerostomia; and periodontal diseases such as linear gingival erythema and necrotizing ulcerative periodontitis (NUP), Kaposi's sarcoma, human papilloma virus associated warts, and ulcerative conditions (herpes simplex virus lesions, recurrent aphthous ulcers, and neutropenic ulcers).  The cluster of differentiation (CD)4 + T-lymphocyte count and viral load are the most important laboratory parameter to evaluate the evaluation of the diseases.  The laboratory test is generally accepted as the best indicator of the immediate state of immunological competence of the patients with HIV infection  and it is an important determinate of the diseases stage and prognosis in sero positive individuals. 
With the antiretroviral therapy (ART) implementation for the treatment of HIV/AIDS some investigations have emphasized the decrease in the oral lesions occurrence in AIDA seropositive individuals. 
Hence, we have undertaken this study to determine the prevalence of oral lesions in a group of HIV-positive individuals and its correlation with CD 4 + T-lymphocyte count before and after the administration of ART.
| Materials and methods|| |
The study was conducted in an ART center at the Karnataka Institute of Medical Sciences (KIMS). Ethical approval was obtained from the Institutional Ethical Review Board and KIMS. All the individuals who attended the ART center were included for this study. Blood sample was collected from the brachial artery with a sterile 5-mL plastic syringe and was centrifuged at 1,000 rpm for 10 min. After centrifugation, the collected serum sample of all individuals is sent for HIV-positivity by rapid assay test (Tri Dot Kit). The individuals who already underwent ART were not included in the study. The selected individuals were explained about the study and verbal and written consents were obtained from them. For all the individuals, detailed clinical case history and oral examination were done subsequently. The oral examination was done at a clinic with bright light. All the oral manifestations were recorded in detail. The oral manifestations are included according to the European Community (EC) Clearinghouse classification [Table 1].
Collection of sample
Blood samples were collected from all these patients on the day of the oral examination. A volume of 2 mL of sterile, disposable syringe collected the blood from antecubital vein. The collected blood was then transferred into a sterile K3EDTA vacationer blood collection tube and was tested for CD4 + T-lymphocyte count immediately. BD Tri test TM CD4 phycoerythrin (PE) that is a tricolor direct immunofluorescence reagent is used with a suitably equipped flow cytometry to identify and determine the CD4 + T-lymphocyte cell count. The obtained sample was analyzed on the flow cytometry (BD FACS caliber), and the dot plot was visually inspected. The lymphocyte population appears as bright compact cluster. The obtained results were reported as percentage (%) of positive cells per lymphocytic population or as the number of positive cell per microliter (μL) of blood.
During the analysis of the absolute number (cells/μL) of positive cells in the sample counted using MULTISET TM software. Once the cell count was completed we calculated absolute number using the formula: Absolute number = Number of true cellular events/number of dead events XTru count bead concentration. The examined individuals were administrated ART and subsequently followed up after a 6-month therapy. A similar protocol was followed for these patients in clinical examinations as well as for the measurement of CD4 + T-lymphocytic count. The data were entered in an Excel sheet and were subjected to statistical analysis using Statistical Package for the Social Sciences (SPSS) (SPSS-Inc., Chicago, IL) package version 20.0 using Karl Pearson's correlation coefficient, Student's t-test, and Wilcoxon matched signed rank test.
| Results|| |
The present study enrolled 79 HIV-positive individuals. Among 79 individuals, 44 (55.6%) were males and 35 (44.5%) were females. The age range was 14-63 years. The maximum individuals are in the age group of 31-40 years. The mean age was 31.40 ± 10.1 for males, whereas that for the females was 31.40 ± 6.69 years. Mean age was stastically significant. Maximum oral lesions are seen in the fourth decade of life (48.10%) followed by third decade (29.11%). Oral lesions such as candidiasis is seen in all the age groups; however, angular cheilitis was absent in the older age groups. In total, 12 individuals have leukoplakia and 7 individuals belong to younger age group (21-30 years), followed by third and fourth decade of life. Herpes zoster and OHL were observed in only one case in the third and fourth decade of life [Table 2]. Oral candidiasis (50%) and angular cheilitis (27.2%) are seen in males, whereas oral candidiasis (48.5%) and angular cheilitis (20.0%) were seen in females. Leukoplakia were noted more in males (16.0%) compared to females (14.2%) [Table 3]. Other oral lesions such as pigmentation, periodontitis, herpes zoster, oral ulcers, and OHL are very minimal in both the genders.
|Table 2: prevalence of specific oral lesions in HIV patients with age group (pre-art)|
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|Table 3: prevalence of specific Oro-facial lesions in HIV patients by gender (pre-art)|
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Comparison of mean CD4 + T-lymphocyte count in males was 231.19 ± 15.4 whereas in females it was 182.7 ± 163. Stastically not significant difference when comparison of mean CD4 + count between the genders [Table 4]. The comparison of different lesions in respect to their CD4 + lymphocyte count statistical was not significant [Table 5]. Prevalence of specific oral lesions after the administration of ART in HIV-positive individuals by gender the specific lesions number was reduced in 33 individuals [Table 6]. Comparison of males and females with respect to CD4 lymphocytic count in both pre- and post-ART period, this finding was statistically significant [Table 7].
|Table 4: comparison of mean cd4+ counts of study subjects according to the gender|
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|Table 5: comparison of orofacial lesions with respect to their cd4 + counts|
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|Table 6: prevalence of specific orofacial lesions in HIV patients according to gender (post-art)|
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|Table 7: comparison of male and female with respect to cd4+ t-lymphocyte counts in pre and post art (n = 33)|
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The correlation between age of HIV-positive individuals with pre- and post-ART values by Karl Pearson's correlation coefficient showed post-ART CD4 + T lymphocytic count to be statistically significant (P ≤ 0.05) [Table 8]. The comparison between pre- and post-ART CD4 + T-lymphocytic count with gender by Wilcoxon rank test showed statically significant values (P ≤ 0.05) [Table 9]. The comparison of different lesions in pre and post to grades by Kruskal-Wallis test showed statistically significant values [Table 10].
|Table 8: correlation between age, pre art and post art values by Karl Pearson's correlation coefficient|
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|Table 9: comparison of pre and post art periods with respect to cd4+ t-lymphocyte counts by Wilcoxon matched signed rank test|
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|Table 10: comparison of different lesions with respect to grades by Kruskal-Wallis test (post art)|
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| Discussion|| |
Acquired immune deficiency syndrome (AIDS) is a chronic progressing disease characterized by immunodeficiency that is the result of HIV attacking the host CD4 + T-lymphocytes. It is generally thought that immunodeficiency is the main cause of susceptibility to various opportunistic infections in HIV infected and AIDS patients.  The recognition of some oral manifestation of HIV disease is considered to be of greater significance as they may represent some of the first signs of the disease and have been shown to be highly predictive of the severe immune suppression and diseases progression.  The oral lesions are often characteristic and in majority of cases can be diagnosed by their clinical features alone.  A review of literature shows that the reports of oral lesions from developing countries are few when compared with those from the developed countries. 
The presence of oral lesions in HIV infected persons as well as the presence of a wide range of other opportunistic infections is generally accepted as the result of the sever immune suppression caused primarily by destruction of T-helper cells after infected by HIV 1 virus. It has been showed that the low circulating CD 4 + cell count is associated with the progression of HIV infection to AIDS and is used as a marker for the staging of the disease.  In our study, majority of the individual's age ranged from 10-65 years and more than 50% of the individuals are male, our results coincide with those of the studies by Nittayanata et al. ,, and Challacombe 1997, Ranganathan et al. 2000, Nittyanata et al. 2001. In our finding regarding age, youngest individual noted in our study was 14 years and the oldest individual was 63 years, mean age and standard deviation of male and females in our study were 35.88 ± 10 years and 31.4 ± 6.69 years, respectively, similar to results observed by Sharma et al. in 2006.  In our study only 65.83% of the patients had oral lesions, whereas several studies have been reported that oral lesions range from 15% to 90% , Ramirex Amaror et al. reported higher prevalence of 75%, whereas Aguirre Urizer observed the oral lesions in all the cases except in two patients (99.5%) in a Spanish population.  Among Indian population studies, the highest prevalence was reported to be 79.2%.  The differences between the frequency of oral lesions in the present study and the frequency described in other reports may reflect in part that those included for this study were diagnosed for HIV sero positive rather than oral manifestations.  Majority of the oral lesions were found in the age group of 31-40 years, which was followed by 21-30 years, our finding is consistent with that of Chidzonga's (2003)  study. In our study, the males were affected more (55.69%) when compared with the females (44.30%). This finding is in accordance with the findings of Khongkunthian et al. (2001) and Nittyanata et al. (2001)  in North Thailand and Thailand population, respectively.
Oral candidiasis was the most common findings in this present study for about 49.36% of the patients. This frequency of occurrence is in concordance with that of the study done by Ramirez (1990) (51.0%) and Gillespie et al. (1993) (51%) , ; however, literature shows that the prevalence rate of candidacies ranged 0-94% by Ranganathan et al. study.  In contrast to our study, the higher prevalence of oral candidiasis (81%) has been noted in other Indian study done by Anil and Challacombe (1997).  Angular cheilitis was noted in 24.0% of cases, majority of which was bilateral in distribution. The findings of our study are consistent with that of the study done by Butt et al.  (2001) (28.0%) and Magalhaes et al. (2001) (29%).  OHL has been reported from all the countries with a frequency of 2-38%; however, the prevalence of OHL in the present study was found to be only 2.5%, all of which were present in the lateral border of the tongue. It is in concordance with the studies done in India, which shows a lower frequency of 2-7% ,, The cause for the variation in the frequency could be based on diagnostic criteria and difficulty in differentiation between candidal lesion and hairy leukoplakia all of which could lead to misdiagnosis as mentioned by Sharma et al. (2006).  The highest prevalence of oral pigmentation was noted in Indian population by Ranganathan et al. (2004) (26%).  Oral pigmentation was observed only 3.75% of the cases that were observed in this study; these results were in accordance with the findings of Ramirez-Amador et al. (1998)  in which only 5% of population observed oral pigmentation. In our study, periodontal-related lesions were seen in only 2.5% that is slightly higher than the prevalence rate as found by Riley et al. (2006).  However, gingivitis is usually attributed to either the poor nutrition status or poor oral hygiene practices of the individuals. Only one individual has Herpes zoster who belong to the age range of 31-40 years accounting for only 1.26% of the cases; however, one study by Hodgson (1997)  reported lowest rate as 4% prevalence in HIV-positive individuals. In our study, oral ulceration was found only in 1.26% which was in accordance with the studies done by Anteyi et al. (2003)  and Gillespie et al. (1993)  that showed only prevalence of 2%. Leukoplakia was noted in our study in only 15% of the cases, most of the lesions were seen in buccal mucosa. Ranganathan et al.'s (2000)  studies showed one case of leukoplakia when 300 HIV-positive individuals in south Indian population were evaluated. This study shown that prevalence of leukoplakia may be because of habits prevalent in the area in which the study was conducted.
Progressive clinical immunologic decline in HIV-infected individuals is usually correlated with the falling CD4 + T -lymphocytes count, and the absolute CD4 + count has been used to decide when to initiate ART for opportunistic infection prophylaxis. Changes in CD4 + T-lymphocyte count have also been used as part of therapeutic monitoring of patients with HIV (Balakrishnan et al., 2004).  In the present study, the changes in the CD4 + T-lymphocyte count has been used as a therapeutic modality to monitor the changes in the oral lesions. However, the correlation between the age and CD4 + T-lymphocyte count as well as the comparison of mean CD4 + T-lymphocytic count of study individuals by gender was statistically significant after first evaluation of patients for oral lesions and CD4 + T cell count. Same group of patients were administered ART and were followed up for next 6 months. At follow-up, only 33 out of 79 individuals could be re-evaluated for the status of oral lesions and CD4 + T cell count, and the remaining patients were lost to the follow-up.
Total 33 individuals that were followed up had increased mean CD4 + cell count that is indicative of increased good immunological response, and their mean CD4 + count increased more than 200 cells/mm 3 irrespective of their gender. Our findings are consistent with the study done by Schmidt-Westhansen et al., 2000.  On comparison of pre- and post-ART with CD4 + counts were highly significant at the 0.1% levels that was in contrast to the findings of Bravo et al. (2006).  Correlation between age in pre- and post-ART value were also found to be significant at the 5% level of significant (P ≤ 0.05) in the present study. There are a few studies showing period of HAART reported a decline in the prevalence of HIV-related oral lesions. ,,
A longitudinal study by Schmidt-Westhansen et al. (2000)  also confirmed the decline of oral opportunistic infections. The present study shows moderate alteration in the predominating lesions after the administration of therapy in second evaluation after a 6-month interval that is consistent with the study done by Eyeson et al. (2002).  HAART have been able to demonstrate the absence of oral lesions among the global patients receiving successful ART. An important observation is that fact that despite reaching quantitatively optimum CD4 + T-lymphocyte counts, patients can still manifest with oral lesions. This could be the result of a reconstitutive immune responses as proposed by Gaitan Cepeda et al. (2008)  The present study aims to show that most oral lesions associated with HIV infection increases in frequency as the CD4 + lymphocyte cell count decreases. Prevalence becomes particularly important when the count falls below 200 cells/mm 3 . However, there was a notable rise in the CD 4 + lymphocyte cell count after the administration of ART, with minimal-to-moderate reduction in the severity of these lesions.
| Conclusion|| |
The difference in the prevalence of oral manifestations may be the result of variations in study population such as race, socioeconomic status, sex, drug therapy, genetics, oral habits, degree of immune suppression, and variation in diagnostic criteria. These reasons may make comparisons difficult even with a single country.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]