Estimation of prevalence of periodontal disease and oral lesions and their relation to CD4 counts in HIV seropositive patients on antiretroviral therapy regimen reporting at District General Hospital, Raichur.

INTRODUCTION: Acquired Immuno Deficiency Syndrome (AIDS) is a condition in which the body becomes susceptible to a host of opportunistic infections. This syndrome is a culmination of infection with a lenti virus called Human Immunodeficiency Virus (HIV) particularly HIV 1. A cross section of the population including adults and children are affected by HIV infection with estimate of 36.1 million affected by the end of 2014. HIV infection affects the T lymphocytes especially cluster of differentiation 4 (CD4) count reducing it drastically jeopardizing the acquired immunity. The advent of Anti Retroviral Therapy (ART) has proved as a ray of hope, at least reducing the misery and suffering although not permanently. This study attempts to understand the prevalence of periodontal disease and other oral lesions, further examining their relationship with CD4 counts in the HIV seropositive patients on ART.
MATERIALS AND METHODS: A total of 72 HIV positive patients on ART reporting at ART centre at Raichur District hospital were screened in the study for periodontal status, oral manifestations. The latest CD4 count values were obtained from the hospital records.
RESULTS: The study showed a 36.11% of prevalence of periodontal disease; however no statistically significant association was seen with its relation to CD4 counts. Other oral manifestations were seen in 46% of patients with a high prevalence of Oral Candidiasis lesions and a positive association with CD 4 counts was seen.
CONCLUSION: Under the limitations of this study no significant association was seen between CD4 counts and prevalence of periodontal disease however candiasis showed a stronger association. As HIV infection gradually becomes a chronic disease the features and course of chronic periodontal disease and other oral manifestations in HIV infected patients require more careful and extensive investigation.

INTRODUCTION

Two and half million people worldwide were infected with HIV in the year 2011 in comparison to 3.2 million in 2001, according to the United Nations AIDS report. Although reduction of new cases was seen, HIV infection until remains a global health problem leading to profound demographic changes in severely affected countries.

Development of highly active antiretroviral therapy (HAART) especially after 1995 has significantly modified the course of HIV disease. Despite the fact that eradication of HIV infection cannot be achieved with the currently available antiretroviral therapy (ART) regimens attributed to the pool of latently infected CD4 T-cells established during the early stages of acute HIV infection, ART reduces plasma load of the virus to a considerable extent in turn leading to elevation of CD4 counts.[1] Introduction of ART has transformed HIV into a manageable chronic disease with longer survival time and improved quality of life. HIV infection is generally recognized as a risk factor for chronic periodontitis although epidemiological studies have failed to confirm a causal link.[2] American Academy of Periodontics (AAP) regards HIV infection as a risk determinant for periodontal disease.[3] Among the HIV-associated infections, oral lesions have been recognized as prominent feature since the beginning of the epidemic and continue to be important. Thus, the periodontal and oral manifestations can have important diagnostic and prognostic value. Oral and periodontal manifestations belong amongst the earliest clinical features predicting the progression of HIV to AIDS.[3] It may also be mentioned that in patients who are on ART, HIV-associated oral manifestations may suggest possible treatment failure.

Thus the purpose of this study was to:

To access the periodontal status of HIV positive patients on HAART regimen

To access the relation between CD4 counts and periodontal status in HIV positive individuals on HAART regimen

To access the various oral manifestations in HIV positive patients reporting to ART center Raichur

To access the relation between CD4 counts and oral manifestations in HIV positive patients on HAART regimen.

MATERIALS AND METHODS

Seventy-two HIV positive patients reporting to the ART Centre in Government District Hospital, Raichur were assessed for the oral and periodontal status. The sample size of 72 was determined using historical study data for PI. A confidence level (1-α) of 95 was obtained with a type I and II error of 0.05 and 0.10. For the sample size of 72, power (1-β) of over 80% was obtained.

Permission for the study was obtained from the District Health Officer. The selected patients were known HIV positive patients who were being administered anti-retroviral therapy at the ART center. Informed consent was obtained from the patients and pledged confidentiality about medical records. The patients were examined at the ART center by two examiners with necessary precautions for infection control. The screening was done using disposable mouth mirrors and probes. Williams periodontal probe was used in the study. Full mouth probing depths and clinical attachment levels were recorded to assess the periodontal status of the patients. Both current and former smokers were excluded from the study. The latest CD4 counts were obtained from records of patients in central laboratory of the district hospital.

RESULTS

Of the 72 HIV positive patients screened, 26 (36.11%) presented with chronic moderate to severe periodontitis and 46 (63.88%) were periodontally healthy [Table 1]. The classification followed was according to the AAP classification 1999.

Table 1

Health and disease, age and PDs

The mean probing depths seen in periodontally healthy individuals was 2.78 mm with a standard deviation of 0.46 and in Periodontitis patients the mean probing depths was 6.07 mm with a standard deviation of 1.02 mm.

The mean age in periodontally healthy individuals was estimated at 34 years with a standard deviation of 11.11 years whereas in chronic periodontitis group the estimated mean age was 36 years with a standard deviation of 11.10 years.

Of the 72 patients, fourteen patients showed CD4 counts below 200, 32 showed CD4 counts in the range of 200–500 and 26 patients had a CD4 counts over 500 [Table 2]. Among patients with CD4 counts below 200, eight had severe periodontal disease amounting to the prevalence of 57.1%. Among patients with CD4 counts between 200 and 500, 12 had periodontal disease amounting to prevalence rate of 37.5%. In patients with CD4 counts above 500, six had periodontal disease with a prevalence rate of 23.07%.

Table 2

CD4 counts

Intra group comparison using ANNOVA showed no statistical significance between CD4 counts and periodontal disease with a P = 0.099.

When CD4 counts of 500 were considered as a cut off for estimation of relation to periodontal disease the results showed that in chronic periodontitis group 77% of patients were recorded to have CD4 counts <500 whereas periodontally healthy patients showed 56.5%. The number of chronic periodontitis patients with CD4 counts >500 was 23.1% whereas the percentage of patients in Periodontally healthy was 43.5% [Table 3].

Table 3

CD4 counts

The intergroup comparison with t-test showed no statistical significance with a P = 0.083.

The range of CD4 counts in periodontally healthy was 160–1800 with a median of 410 and in chronic periodontitis the range was from 164, and the median was 263.

Of the screened population, 32 patients (44%) showed oral manifestations and 40 patients (66%) had no noticeable oral manifestations [Chart 1].

Chart 1

Distribution of oral manifestations

Of the 40 patients presenting with oral manifestations, 26 (81.5%) showed oral candidiasis lesions [Figure 1].

Figure 1

Oral Candidiasis lesions (original)

The next most common oral lesion recorded was angular cheilitis [Figure 2].

Figure 2

Angular cheilitis lesion (original)

Many cases of nonhealing ulcers were noted in this study, [Figure 3] and one case of linear gingival erythema (LGE) [Figure 4] was recorded in this study:

Figure 3

Non healing ulcer (original)

Figure 4

Linear gingival erythema (original)

Of the 26 patients with candidiasis, 14 patients (53.8%) had a CD4 counts below 200, whereas 9 patients (34.6%) had a CD4 counts of between 200 and 500 [Chart 2].

Chart 2

Percentage distribution of CD4 counts in candidiasis patients

Although a higher number of patients with CD4 count below 200 showed candidiasis lesions no statistical significance using ANOVA was seen among the three groups. When CD4 counts and candidiasis lesions were analyzed with the cut off as 500, statistically significant association was observed using t-test.

DISCUSSION

HIV infection in adults is linked to the expression of various types of periodontal lesions that include specific forms of gingival and necrotizing periodontal disease as well as possible exacerbations of preexisting periodontal disease.[1] Seven cardinal oral lesions which have been identified internationally as follows: Oral candidiasis, oral hairy leukoplakia, Kaposi's sarcoma, LGE, necrotizing ulcerative periodontitis (NUG) and non-Hodgkin lymphoma.[23]

Introduction of ART, mainly HAART in 1995 has changed the epidemiology of opportunistic infections in HIV-infected patients. The prevalence of periodontal disease in HIV-infected individuals remains a controversial issue.[4] Data from relevant studies vary widely due-to several variable factors such as stage of AIDS and type of ART regimen. Other important factors like age, immune system competence, smoking habits, and oral hygiene levels are not always taken into consideration in many studies. The prevalence of periodontal disease in the present study was 36.11%. The prevalence rate is in accordance with a study conducted by Ranganathan et al. in India, which gave a prevalence rate of 33%.[5] Another study by Kroidl et al. Germany also recorded a prevalence rate of 30%.[6] However, the results of the study differed with that of Brady et al. and Alpagot et al. that recorded a higher prevalence rate of 52% and 73% respectively.[78]

In the 26 patients with periodontal disease, it was observed that 57.1% that is, eight patients had a CD 4 count of <200, 12 patients fell into the 200–500 CD4 count range and six patients fell into >500. A P = 0.099 was obtained using ANOVA showing no statistical significant relation between CD4 counts and periodontal disease. The above-mentioned findings are in accordance with the findings by Schuman et al. who reported no association between periodontal disease and HIV serostatus or CD4 lymphocyte count.[910]

However, a study by Margiotta et al. reported that periodontal disease prevalence significantly increased with CD 4 counts below 200 cell mm3[910] contradicting the findings of our study. Although no statistical significance (P = 0.099) could be attributed to an association between periodontal disease and CD4 counts in the present study, it can be observed that a higher percent of Periodontitits patients fell into the range of CD4 counts <200. In the present study, it was observed that 76.9% of patients with periodontal disease showed CD 4 counts of < 500, nevertheless no statistical significance using t-test (P = 0.083) was also observed when CD4 count of <500 was considered.

If parameters such as gingival index, loss of attachment had been considered, more information could be drawn on the subtle association between CD4 counts and periodontal disease. The other parameter that could have been considered is oral hygiene status, which would have evaluated the periodontal tissue reaction to different plaque and calculus scores in relation to CD4 counts.

After the introduction of HAART considerable decline in the trends of hospital admissions were reported world wide however an opportunistic infection continues to be the commonest discharge diagnosis.[1112] In the present study, around 46% of the individuals showed oral manifestations, this is in agreement with the study by Patton et al. 2002 and Schmidt-Westhausen et al. 2002, who stated that a significant decrease in the overall prevalence of oral manifestations from 45 to 85% to about 32–46% occurred after the introduction of HAART.[13] However, in a study by Aquino-Garcia much lower prevalence rate of 32% was seen in patients on HAART.[14] In another study by Ferreira et al. 2007 in Brazil significantly lower rates of oral manifestations were recorded.[15]

About 81.5% of patients having oral manifestations presented with oral candidiasis, 53.8% of patients with oral candidiasis had CD 4 counts <200 and all the patients had CD4 counts <500. This finding is in agreement with previous studies by Lamster et al. 1997 who noted that low CD4 counts can be considered a risk factor for the development of oral lesions especially oral candidiasis.[16] The other most common lesions seen were non healing oral ulcers, angular cheilitis [Figures 1 and 4]. One case of LGE was also recorded.

HIV prevalence in the low-risk general population in Raichur District is moderate at 0.51% (2009), and the trend has been constant for over 6 years. The north Karnataka region figures in the most neglected areas with respect to health care sector in the country. Multi-center study involving a wider demographic area and a much larger sample size would definitely give a better perspective of the association between CD4 counts periodontal disease and oral manifestations.

As HAART prolongs the life expectancy of HIV-infected individuals significantly, periodontal health should also be considered as an important factor contributing to the improvement of the quality of life. This is especially relevant in the rural Indian context where much data doesn’t exist regarding the changing scenarios post introduction of HAART.

Conflicting data exist regarding the association between CD4 counts in HIV positive patients and periodontal disease, with reports of severe destruction of periodontal tissues in some studies to some recording no difference between HIV positive and healthy individuals, some studies have even suggested HIV-positive patients with extreme immunosuppression experienced less periodontal destruction when compared to HIV-positive patients with mild immunosuppression. For periodontal disease to be regarded as a serious complication of HIV, more extensive investigations are required; however, oral manifestation especially candidiasis may have important diagnostic and prognostic value and belong to the earliest clinical features of the infection and could predict progression of HIV to AIDS.