| Abstract|| |
Aims: The aim was to assess the prevalence of oral lesions in HIV-infected children undergoing highly active anti-retroviral therapy (HAART), and the association between the duration of HAART usage and oral lesions.
Subjects and Methods: Totally, 111 medical and dental records of HIV-infected children, aged from 2 to 16 years old were reviewed for medical data, presence of oral lesions, and caries prevalence. According to the type of medication, the children were grouped as follows: 51 were under HAART (G1), 46 were using anti-retroviral medication (G2), and 14 were using no medication (G3).
Results: The majority of the HIV children had AIDS (65.8%), of which 86.3% were in G1, 63% in G2, and 0% in G3. The mean length of therapy was 34.4 months, with no difference between groups (Kruskal-Wallis; P = 0.917). The prevalence of the oral lesions was 23.4%, namely, G1 was 27.5%, G2 was 21.7%, and G3 was 14.3% (P > 0.05). Gingivitis was the most common oral manifestation (15.3%) seen in the three groups, followed by gingival linear erythema and pseudomembranous candidiasis in G1 and G2. The mean values regarding deft and DMFT indexes were, respectively, 3.2 and 1.9 (G1), 2.8 and 1.6 (G2), and 3.8 and 3.0 (G3). For the patients without AIDS (n = 38), oral manifestations were seen in 29.4% of G2 compared to G1, with 0% (Chi-square; P > 0.05). In terms of therapy duration, 47.65% of the patients who had been under HAART for 18 months or less had oral manifestations, compared to 13.3% of those who had been treated for a longer time (Chi-square; P = 0.007).
Conclusions: Although the prevalence of oral lesions was similar between the groups, it was less in patients without AIDS and those under HAART. The duration of HAART usage had a significant influence on the prevalence of these lesions.
Keywords: Anti-retroviral therapy, child, highly active, Human immunodeficiency virus, oral manifestations
|How to cite this article:|
Oliscovicz NF, Pomarico L, de Ara˙jo Castro GB, Souza IR. Effect of highly active antiretroviral therapy use on oral manifestations in pediatric patients infected with HIV. Indian J Dent Res 2015;26:200-4
There are approximately 33.3 million people in the world infected with HIV, and approximately 2.5 million of them are children under 15 years old.  In Brazil, there are around 19,203 children aged 13 years old or less with AIDS.  Within this scenario, there are a great variety of drugs to fight this virus.
|How to cite this URL:|
Oliscovicz NF, Pomarico L, de Ara˙jo Castro GB, Souza IR. Effect of highly active antiretroviral therapy use on oral manifestations in pediatric patients infected with HIV. Indian J Dent Res [serial online] 2015 [cited 2020 Mar 31];26:200-4. Available from: http://www.ijdr.in/text.asp?2015/26/2/200/159169
The highly active anti-retroviral therapy (HAART) was introduced in 1995  and changed the infection into a chronic disease.  This triple therapy interferes with progression and suppression of the viral load in these patients, , and is characterized by the association of protease inhibitors and nucleosides reverse transcriptase or nonnucleoside reverse transcriptase inhibitors. Although, some patients on this therapy showed an improvement in their immune system, they also presented other infection-related diseases, thus characterizing a picture of an immune reconstitution syndrome. ,
Oral manifestations related to HIV are numerous and they usually occur precociously. ,, One such manifestation is candidiasis, which is often associated with the initial phase of the infection. , Many studies on oral lesions in HIV-infected patients were made before the introduction of HAART. ,,,,,,,,,, The influence of HAART caused significant differences in relation to these lesions. ,,, In fact, a decrease of 10-50% in the rate of HIV-related oral manifestations has been reported following the introduction of HAART. This suggests that this therapy plays an important role in controlling oral candidiasis. 
However, the reduction in the incidence of oral lesions with the use of HAART in industrialized countries is not significant, except for candidiasis. This is possibly due to the low prevalence of oral lesions in these countries. In contrast to other HIV oral manifestations, an increase in the prevalence of oral condylomas and salivary gland diseases in patients on HAART has been reported in the USA and UK. The re-emergence of HIV-related oral diseases may indicate treatment failure. In fact, a range of orofacial iatrogenic consequences of HAART therapy have been reported, and it is difficult to distinguish the actual oral manifestations related to HIV from those due to the adverse effects of HAART. 
Therefore, the objective of the present work was to determine the prevalence of oral lesions in HIV-infected children who are on HAART, as well as the influence of treatment time on the lesions.
| Subjects and Methods|| |
The medical and dental records of all the patients who attended the pediatric AIDS Outpatient Clinic of a Public University Hospital in Rio de Janeiro, Brazil, were reviewed by means of retrospective analysis. Our sample consisted of 111 medical and dental records of HIV-infected children aged from 2 to 16 years old, selected by convenience, based on the frequency in which these patients attended the outpatient clinic during a 7-month period. All children had been definitively diagnosed with HIV infection according to criteria established by the Center of Disease Control and Prevention. 
The following data were collected from the children's medical records: Personal information, medical history (diagnosis of AIDS), type of anti-retroviral (ARV) therapy and results (the closest ones to the sample collection time) of laboratory tests (CD4 count and viral load). We considered AIDS when a patient has a CD4 count <15% and patients were considered to be using HAART when the ARV therapy involved the use of three or more drugs. According to the type of ARV drugs used, the sample was divided into three groups: HAART group (G1) with 51 patients, ARV (up to 2 ARV drugs) (G2) with 46 patients and G3 (no medication) with 14 patients. With regard to the length of time under medication, the children were regrouped into: Short period (taking ARV therapy for a period ranging from 1 to 18 months) and long period (taking the drugs for more than 18 months). However, when there was no clinical and/or laboratorial indication for treatment, according to criteria by the Brazilian Consensus of ARV Treatment for Children, no medications were used. 
Clinical oral data, including caries and oral lesions, were obtained from outpatient records regarding dental examinations performed by the dentist every 3 months during visits for tooth brushing with fluoride dentifrice and topical application of 1.23% acidulated phosphate fluoride gel. During the dental visits, both children and their caregivers were instructed about tooth brushing and oral hygiene. Furthermore, examinations for oral lesions  and determination of deft/DMFT indexes based on diagnostic criteria for caries in enamel and dentine were realized. , After such examinations, all the children received dental treatment according to their needs.
The collected data were entered and stored in a database created by the Epi Info TM 6.04. Kruskall-Wallis and Chi-square tests were performed to analyze the variables between and within groups, at a significance level of 5%.
| Results|| |
The sample consisted of 111 medical records of the children, all divided into three groups as follows: G1 (45.9%), G2 (41.4%), and G3 (12.6%). The mean age of the sample was 112.5 months and more than half were male (61.3%).
Overall, 65.8% of the children had AIDS, and most of them were in the G1 group (Qui-square, P < 0.05). The mean length of time on medication was 34.4 months, with no difference observed between groups G1 and G2 (Kruskal-Wallis, P > 0.05). [Table 1] lists data by groups.
|Table 1: General characteristics of the sample, whose children were divided into G1 (HAART), G2 (ARV), and G3 (no medication) |
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With regard to the prevalence of oral manifestations, 23.4% showed some type of oral lesion related to the infection. Gingivitis (15.3%) was the most common manifestation found in the three groups, followed by parotid hypertrophy. Linear gingival erythema also had a high prevalence (9.8%) in G1 [Table 2].
|Table 2: Prevalence of oral manifestations and deft/DMFT indexes distributed between the three groups (%) |
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When only considering patients without AIDS (n = 38), 29.4% of those who were using up to 2 ARV medications (G2) showed some type of lesion compared to 0% of those on HAART (G1) (Chi-square, P > 0.05). Furthermore, 47.65% of the children who had been taking HAART for a short time (<18 months) had lesions compared to 13.3% of the children who had being treated for a long period (Chi-square, P < 0.05). The deft/DMFT indexes data by groups is presented in [Table 2].
| Discussion|| |
Oral diseases can affect the quality of life of HIV-infected patients, and one of the objectives of their treatment is to improve such symptoms,  thus improving the patient's overall health. In the present study, gingivitis was the most commonly found lesion, followed by parotid hypertrophy and linear gingival erythema; this latter lesion had a high prevalence in G1. In another study, also involving children, the most commonly found lesions were parotid hypertrophy (19.6%), oral candidiasis (11.8%), and Kaposi sarcoma (3.9%).  In the study conducted by Miziara et al.,  however, oral candidiasis (11.5%) was the most prevalent lesion, followed by parotid hypertrophy and angular cheilitis. The presence and development of such oral lesions are usually used as a criterion for starting prophylaxis and drug therapy. Among the therapeutic approaches developed for these patients, one can highlight HAART. The indication for this therapy takes into account the clinical presence of lesions such as oral candidiasis and pilous leukoplakia,  since these opportunistic infections are directly related to the immunosuppression in HIV-infected individuals  and the infection progress. Therefore, HAART is used in more severely immunosuppressed patients. 
The frequency of many of these HIV-related lesions can be reduced with HAART therapy.  The prevalence of lesions such as oral candidiasis, oral pilous leukoplakia, Kaposi sarcoma, and HIV-related periodontal diseases have been reported to decrease with the use of HAART. ,,,,,,, On the other hand, salivary gland diseases, human papillomavirus (HPV), xerostomy, and recurrent oral ulcers have shown an increase in their prevalence. ,,,, However, there are also some reports indicating no change in the occurrence of these lesions in children on HAART. , The reasons for such different results are not fully understood. Some authors have associated these variations with differences in oral care habits, social and demographic factors, HIV-transmission mode, types of co-infections, disease stage, and immune reconstitution. ,, In the present work, a great difference in oral manifestations between HIV-infected patients and those on HAART or using ARV medications was found as no oral lesions were observed in the former, whereas the latter had 29.4%. Similar results were also reported by Miziara et al.,  who found percentages of 24.7% and 37.6%, respectively-a statistically significant difference. On the other hand, Hamza et al.  found no significant difference between children using HAART and those using no medication, although higher values were observed among the latter group.
Nevertheless, one should emphasize that oral lesions may develop again due to HAART failure and multi-drug resistance.  The results found in the literature on this issue are controversial. For instance the effect of HAART on reducing the incidence of oral lesions, including candidiasis, does not seem to be significant in industrialized countries, probably because of the low percentage of these oral manifestations in such nations.  Based on the positive results with HAART life expectancy of HIV-infected patients has increased. However, oral cancer seems to be a common clinical complication in these patients over time,  a finding also observed by Hamza et al.  and Olaniyi and Sunday,  who found the presence of oral warts and Kaposi sarcoma, respectively. In the present study, however, such lesions were not found.
Another factor to be taken into consideration is the length of time that the patient has been taking HAART. In the present work, among those children who had used HAART for up to 18 months, 47.65% had oral lesions compared to 13.3% of those who had used it for a longer time (Chi-square P = 0.007). Another study, however, reported no relationship between time of HAART use and decrease in oral manifestations, although the methodologies employed were different. In the latter case, the short time of HAART was considered to be between 24 and 28 weeks. 
However, despite the decrease in the presence of oral lesions following introduction of HAART, some factors must be considered. The first factor has to do with the long-term consequences of hyposalivation for patients on this therapy. The second factor is the increase in the prevalence of oral warts, which is directly related to HPV, as commented earlier. The third factor is the fact that the CD4 cell counts and oral manifestations no longer correlate over time. In view of this, surgeon-dentists should check the oral health of these patients carefully, mainly for any early signs of oral cancer- a fact which has been recently linked to infection, and pay attention to lesions commonly related to HIV.  This is relatively simple due to the fact that the oral cavity can be investigated easily with a clinical examination. Thus, oral lesions indicating important signs of infection progression can be diagnosed earlier, and a prompt intervention can then be carried out.
| Conclusion|| |
The prevalence of oral lesions was found to be similar between the groups, but less frequent in those patients without AIDS or who were on HAART. However, the length of time on HAART significantly influenced the prevalence of such lesions.
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Prof. Luciana Pomarico
Department of Pediatric Dentistry and Orthodontics, Universidade Federal do Rio de Janeiro, Rio de Janeiro
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]