J Oral Pathol Med (2015) 44: 296299

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

doi: 10.1111/jop.12243

wileyonlinelibrary.com/journal/jop

Oral mucosal lesions and immune status in HIV-infected

Indian children
Priya Subramaniam, Krishna Kumar
The Oxford Dental College and Hospital, Pedodontics and Preventive Dentistry Bangalore, India

OBJECTIVE: Pediatric HIV is growing at an alarming rate

in developing countries. Due to their compromised
immune status, children infected with HIV are prone to
a number of opportunistic infections. Oral manifestations
are the first signs of the disease in many of them. To
assess the oral mucosal status of Indian children with
HIV, based on their CD4 cell counts.
METHODOLOGY: Two hundred and twenty one HIV
infected children aged 618 years from various HIV
centers, were divided into three groups, based on their
CD4 cell counts; Group 1: 500, Group 2: 201499 and
Group 3: 200 cells. The children in each group were
further considered as prior to antiretroviral treatment
(ART) and on ART. Oral mucosal examination was
done based on presumptive criteria given by RamosGomez for diagnosis of oro-facial lesions commonly
associated with HIV infection in children. Data obtained
was subjected to statistical analysis.
RESULTS: Angular cheilitis and pseudomembranous candidiasis were the frequently seen oral lesions. Children
with CD4 cell count 500 had significantly fewer oral
lesions each.
CONCLUSION: A high percentage of HIV-infected children were affected with oral mucosal lesions. There was a
significant association between immune status and
frequency of oral lesions.
J Oral Pathol Med (2015) 44: 296299
Keywords: aphthous ulcerations; Candida; HIV infection; oral
mucosa

Introduction
There has been a worldwide increase in the prevalence of
children with HIV. Perinatal transmission has been found to

Correspondence: Priya Subramaniam, The Oxford Dental College and

Hospital, Pedodontics and Preventive Dentistry, Hosur Road, Bommanahalli, Bangalore, India. Tel: +91-80-30219733, Fax: +91-80-25734656,
E-mail: drpriyapedo@yahoo.com
Accepted for publication July 8, 2014

be the predominant mode of HIV acquisition (1). The global

estimate of children living with HIV infection in 2012 was
3.3 million (2). India is one of those countries where the
HIV epidemic is growing rapidly (3). The National AIDS
Control Organization estimated in 2008 that children in
India aged <14 years comprise 3.4% of the 2.31 million
living with HIV or AIDS (4). In most cases, it is due to
transmission from HIV seropositive mothers during pregnancy, delivery, or breast feeding.
It is estimated that in a decades time, more than
40 million children may be orphaned as a result of AIDS
(4). There is also an increasing rate of infection in these
children (4). Most children infected by HIV manifest the
initial symptoms of AIDS before their rst birthday, and
oral manifestations are the rst signs of the disease for
nearly half of them (5, 6).
Immune suppression resulting from HIV infection makes
these individuals more susceptible to the development of
opportunistic infections. The oral cavity is particularly
susceptible to infection as it harbors numerous microorganisms that thrive in conditions of immune suppression and
cause characteristic fungal, viral, bacterial, and neoplastic
lesions.
The World Health Organization in 2008 recommended
that all children <12 months of age receive antiretroviral
treatment (ART) irrespective of the clinical severity of
disease or the degree of immunosuppression. ART should
be initiated in HIV-infected children over 12 months of age
who attend clinics where CD4 monitoring is not possible
(7).
Most children with perinatally acquired HIV infection in
resource-rich countries are treated early with highly active
antiretroviral treatment (HAART). Such therapy consists of
a combination of three or more potent ARV drugs and has
been shown to dramatically modify the course of HIV
infection in children, reducing mortality and resulting in
high survival rates (8). Studies that examined the presence
of oral lesions in HIV- infected children have suggested a
decrease in their prevalence following introduction of ART
(9, 10).
Therefore, this study was undertaken to assess the oral
mucosal status of Indian children with HIV, based on their
CD4 cell counts and the changes occurring due to
introduction of antiretroviral therapy.

Oral mucosa and immune status

P Subramaniam and K Kumar

Methodology
The study protocol was approved by the Ethical Committee
of our institution. Information was obtained regarding the
number of HIV-infected children from various centers in
Bangalore and Mysore, India. Prior to conducting the study,
the nature of the study was explained, and written permission was obtained from authorities of various HIV centers.
An undertaking was given to the authorities stating that the
identity of the children will not be disclosed. Written
informed consent was also taken from parents or caretakers
of the children. Only those who were willing to participate
and cooperative children were included.
A proforma was used to record childrens age/gender,
CD4 cell count, drug regimen, medical history, and both
extra-oral and intra-oral examination.
The study group consisted of 221 HIV-infected children
aged 618 years. They were divided into three groups,
based on their CD4 cell counts: Group 1: 500, Group 2:
201499, and Group 3: 200 cells. The children in each
group were further considered as prior to ART and on
ART.
Oral mucosal status was assessed by visual examination
of soft tissues using sterile disposable plastic mouth mirror
and CPI probe. Oral examination was performed by a single
examiner trained in the identication of HIV-related oral
lesions. The presumptive criteria given by Ramos-Gomez
(11) for diagnosis of orofacial lesions commonly associated
with HIV infection in children was followed to record each
oral lesion. Depapillation of tongue and oral pigmentation
were also recorded.
The data obtained were tabulated and subjected to
statistical analysis using Statistical Package of Social
Sciences (SPSS) 18.0 for windows. One-way ANOVA
was used to nd the signicance and correlation of study
parameters on categorical scale between the groups.

Results
Table 1 shows the distribution of the study group, according
to gender, CD4 cell count, and ART. In group 1, a higher
number of girls were observed. Angular cheilitis was seen in
3748% of children. The other frequently seen oral lesion
was pseudomembranous candidiasis. Aphthous ulcers were
seen to occur more in children with CD4 count <500. In
group 1, both types of candidial lesions were observed to be
signicantly more in children who were not on ART. In
group 2, this difference was signicant only for erythematous candidiasis. However, in children with CD4 cell count
200, pseudomembranous candidiasis was signicantly

higher in children on ART. Oral pigmentation was observed

in a higher number of children on ART, which was
signicant in group 1 and highly signicant in those with
CD4 cell count 200 (Table 2). In comparison with the
other two groups, children with CD4 cell count 500 had
fewer oral lesions each (P < 0.001) (Table 3).

297

Discussion
In developing countries, there is a negligence of children
diagnosed with HIV, especially with regard to their oral
health needs. Due to social ostracism, economic reason, and
reluctance exhibited by dental practitioners to treat these
children, they have very limited access to comprehensive
oral health care. Oral health is not considered a priority for
many of these children. Parents do not necessarily disclose
their childs HIV status on dental attendance. Reports on
oral mucosal status of HIV-infected children are mainly
from Thailand and Brazil (1214).
Oral mucosal lesions are one of the earliest clinical
indicators of HIV infection and progression in children and
are strongly associated with immune suppression (1517).
The prevalence of oral lesions in HIV-infected individuals is still high in developing countries, and Indian studies
are very few. Oral lesions in pediatric HIV infection are
varied and differ in clinical presentation from that of adults.
The fact that oral lesions can be readily detected by a trained
clinician in a standardized, objective fashion without any
complicated or expensive diagnostic technique has
increased their utility (18).
In our study, CD4 cell count values were taken from the
individual medical record of each child. Moreover, CD4 cell
counts are likely to vary on the day of examination.
Therefore, classication given by EC Clearinghouse modied by Ramos Gomez was used (11). The present
classication was based on orofacial lesions most commonly seen in pediatric HIV which are simple to follow and
easy to record. This classication was further modied to
include two commonly seen lesions, depapillation of tongue
and oral pigmentation in pediatric HIV.
In our study, children with low CD4 cell count were
affected with a higher number of oral lesions.
Oral candidiasis is the most commonly reported lesion in
HIV-infected children and may be the rst clinically visible
manifestation of the disease. According to Hube, the host
cellular immune deciency is a pre-disposing factor that
could switch the commensal fungi to a pathogenic form
(19).
Three clinical variants of oral candidiasis are recognized
currently as being associated with HIV infections are

Table 1 Distribution of study group according to CD4 cell count

CD4 cell count
Group 1 (500)
Antiretro viral treatment (ART)
Prior to ART (N = 112)
On ART (N = 109)

Group 2 (201499)

Group 3 (200)

Males
n (%)

Females
n (%)

Males
n (%)

Females
n (%)

Males
n (%)

Females
n (%)

25 (11.3)
22 (10)

42 (19)
38 (17.2)

15 (6.8)
12 (5.4)

9 (4.1)
10 (4.5)

12 (5.4)
13 (5.9)

9 (4.1)
14 (6.3)

J Oral Pathol Med

Oral mucosa and immune status

P Subramaniam and K Kumar

298

Table 2 Number of children presenting with each oral lesion in the three groups
CD4 cell count
500 (Group 1)
N = 127
Prior to ART
n (%)

Oral lesions
Angular cheilitis
Pseudomembranous candidiasis
Erythematous candidiasis
Apthous ulcer
Depapillation
Oral pigmentation
Linear gingival erythema
Oral hairy leukoplakia

54
36
7
10
6
0
2
0

On ART
n (%)

(42.5)
(28.3)
(5.5)
(7.9)
(4.7)

50
21
2
4
2
4
0
0

(1.6)

P-value

(39.4)
(16.5)
(1.6)
(3.2)
(1.6)
(3.2)

200 (Group 3)
N = 48

201499 (Group 2)
N = 46

0.124
0.001*
0.001*
0.001*
0.553
0.001*
0.380
0.332

Prior to ART
n (%)
22
24
11
16
13
3
7
0

(47.8)
(52.2)
(23.9)
(34.8)
(28.3)
(6.5)
(15.2)

On ART
n (%)
18
19
6
13
9
8
2
0

(39.1)
(41.3)
(13)
(28.3)
(19.6)
(17.4)
(4.3)

P-value
0.231
0.374
0.002*
0.276
0.361
0.001*
0.543
0.367

Prior to ART
n (%)
18
17
10
12
7
4
6
2

(37.5)
(35.4)
(20.8)
(25)
(14.6)
(8.3)
(12.5)
(4.2)

On ART
n (%)
19
24
14
12
8
15
3
0

(39.6)
(50)
(29.2)
(25)
(16.7)
(31.3)
(6.3)

P-value
0.227
0.001*
0.347
0.253
0.287
0.000**
0.489
0.573

ART, antiretroviral treatment.

*P 0.05 is signicant, **P < 0.001 is highly signicant.
Table 3 Association of immune status with number of oral lesions
Number of oral lesions (n)
CD4 cell count

P-value

500
201499
200

38
5
1

43
17
15

22
12
5

14
8
8

6
3
6

4
1
6

0
0
7

0.001*

*P 0.05 is signicant.

pseudomembranous, erythematous, and angular cheilitis.

The pseudomembranous form occurs most frequently in
patients with advanced immune suppression or fully developed AIDS. The erythematous form appears in the early
phases of HIV infection and is difcult to diagnose; these
lesions may go unnoticed (20).
The presence or absence of candidiasis in HIV-infected
children may be directly related to the use of antiretroviral
agents and the time of AIDS diagnosis. HAART decreases
the prevalence of oral lesions, particularly oral candidiasis in
HIV-infected children. Two mechanisms have been proposed to explain this nding: (i) a reduction in the infection
as a result of the immune reconstitution resulting from the
increase in numbers of CD4 cells and (ii) a potential direct
antiyeast effect. The protease inhibitors present in HAART
can also inhibit candidal secreted aspartly proteinases
(SAPs), interfering with the growth and pathogenicity of
Candida spp. (21).
Development of oral candidiasis has been shown to be
signicantly associated with a low CD4 cell count (22,
23). In our study also, a higher percentage of children
with CD4 cell count <500 were more affected with
candidial infection. Most of the candidial lesions were
seen as creamy-white pseudomembranous plaques.
Among those with CD4 cell counts 200, a signicantly
lower number of children on ART were found to have
candidial lesions. However, the contrary was observed in
children with CD4 cell count 200. Reasons could be due
to the severe immune suppression present in this group
even earlier to initiation of ART or due to lack of
compliance to therapy.
J Oral Pathol Med

Among the oral mucosal lesions present in children and

adolescents, oral ulceration has been least reported, ranging
from 0.9% to 39.2% (24). All these observations were based
on different approaches including clinical examination, selfreported history, and other tests. Pharmacologic agents are
among the most common causes of recurrent aphthous
lesions (25). However, our nding was that more children
with CD4 cell count <500 had ulcerations, regardless of
antiretroviral therapy.
Oral pigmentation is seen frequently in children with HIV
as a result of release of a melanocyte-stimulating hormone
caused by dysregulation of cytokines, and it is also induced
by antiretroviral therapy (26, 27). The latter was evident in
the present study, where a signicantly higher number of
children on ART had oral pigmentation.
Linear gingival erythema which is the most common
form of HIV-associated periodontal disease in HIV-infected
children (28) was seen in those with severe immune
suppression. Candida species have been related as an
etiological factor of linear gingival erythema. Although
oral hairy leukoplakia has been reported to vary from 0% to
22.5% in HIV-positive pediatric population (6, 2931), only
two children with CD4 cell count 200 and who were not on
ART presented with the lesion.
A limitation of this study was that it did not include a
longitudinal follow up of the patients. This was due to
foreseen reasons such as inability and lack of interest
exhibited by parents or caregivers to bring their young
children for repeated examinations, their nancial limitations, and also due to the possible demise of some of these
children.
It is essential for pediatric dentists to be aware of the oral
manifestations of HIV. This would help in early recognition
of the disease and implementation of preventive oral
measures, in these immune-suppressed children.

Conclusions
1 A high percentage of HIV-infected children were
affected with oral mucosal lesions.
2 There was a signicant association between immune
status and frequency of oral lesions.

Oral mucosa and immune status

P Subramaniam and K Kumar

3 The effect of ART on oral mucosal health cannot be

ignored. Although lesser number of children on ART
presented with oral lesions, oral pigmentation was
more prevalent in these children.

References
1. Madhivanan P, Mothi SN, Kumarasamy N, et al. Clinical
manifestations of HIV infected children. Indian J Pediatr
2003; 70: 61520.
2. http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/201309_epi_core_en.pdf
(accessed on 5 June 2014).
3. Bodhade AS, Ganvir SM, Hazarey VK. Oral manifestations of
HIV infection and their correlation with CD4 count. J Oral Sci
2011; 53: 20311.
4. Naidoo S, Chikte U. Oro-facial manifestations in pediatric
HIV: a comparative study of institutionalized and hospital
outpatients. Oral Dis 2004; 10: 138.
5. Centers for Disease Control Prevention. Revised classication
system for human immunodeciency virus infection in children less than 13 years of age. MMWR Recomm Rep 1994; 43:
110.
6. Magalh~aes MG, Bueno DF, Serra E, Goncalves R. Oral
manifestations of HIV positive children. J Clin Pediatr Dent
2001; 25: 1036.
7. Penazzato M, Prendergast A, Tierney J, Cotton M, Gibb D.
Effectiveness of antiretroviral therapy in HIV-infected children
under 2 years of age. Cochrane Database Syst Rev 2012; 7:
CD004772.
8. McConnell MS, Byers RH, Frederick T, et al. Trends in
antiretroviral therapy use and survival rates for a large cohort
of HIV-infected children and adolescents in the United
States, 19892001. J Acquir Immune Dec Syndr 2005; 38:
48894.
9. Schmidt-Westhausen AM, Priepke F, Bergmann F, Reichart
PA. Decline in the rate of oral opportunistic infections
following introduction of highly active antiretroviral therapy.
J Oral Pathol Med 2000; 29: 33641.
10. Inthachark K, Pongsiriwet S, Akarathum M, Sriburee P,
Iamaroon A. Oral lesions and dental caries status in vertically
HIV-infected children: an epidemiological survey at the
Sanpathong Hospital, Chiang Mai. Chiang Mai Dental J
2009; 30: 102.
11. Ramos-Gomez FJ, Flaitz C, Catapano P, Murray P, Milnes AR,
Dorenbaum A. Classication, diagnostic criteria, and treatment
recommendations for orofacial manifestations in HIV- infected
pediatric patients. J Clin Pediatr Dent 1999; 23: 856.
12. Pongsiriwet S, Iamaroon A, Kanjanavanit S, Pattanaporn K,
Krisanaprakornkit S. Oral lesions and dental caries status in
perinatally HIV-infected children in Northern Thailand. Int J
Paediatr Dent 2003; 13: 1805.
13. Portela MB, Souza IP, Costa EM, Hagler AN, Soares RM,
Santos AL. Differential recovery of Candida species from
subgingival sites in human immunodeciency virus-positive
and healthy children from Rio de Janeiro, Brazil. J Clin
Microbiol 2004; 42: 59257.
14. Khongkunthian P, Grote M, Isaratanan W, Piyaworawong S,
Reichart PA. Oral manifestations in 45 HIV-positive children
from Northern Thailand. J Oral Pathol Med 2001; 30: 54952.

15. Kozinetz CA, Carter AB, Simon C. Oral manifestations of

pediatric vertical HIV infection. AIDS Patient Care STDS
2000; 14: 8994.
16. Ramos-Gomez F. Dental considerations for the pediatric
AIDS/HIV patient. Oral Dis 2002; 8: 4954.
17. Moniaci D, Greco D, Flecchia G, Raiteri R, Sinicco A.
Epidemiology, clinical features and prognostic value of HIV-1
related oral lesions. J Oral Pathol Med 1990; 19: 47781.
18. Hilton JF. Staging the natural history of HIV disease. In:
Greenspan JS, Greenspan D, eds. Oral manifestations of HIV
infection. Carol Stream: Quintessence, 1995; 428.
19. Hube B. Extracellular proteinases of human pathogenic fungi.
Contrib Microbiol 2000; 5: 12637.
20. Leggott PJ. Oral manifestations of HIV infection in children.
Oral Surg Oral Med Oral Pathol 1992; 73: 18792.
21. Korting HC, Schaller M, Eder G, Hamm G, Bohmer U, Hube
B. Effects of the human immunodeciency virus (HIV)
proteinase inhibitors saquinavir and indinavir on in vitro
activities of secreted aspartly proteinases of Candida albicans
isolates from HIV-infected patients. Antimicrob Agents Chemother 1999; 43: 203842.
22. Barasch A, Safford MM, Catalanotto FA, Fine DH, Katz RV.
Oral soft tissue manifestations in HIV-positive vs. HIVnegative children from an inner city population: a two-year
observational study. Pediatr Dent 2000; 22: 21520.
23. Kerdpon D, Pongsiriwet S, Pangsomboon K, et al. Oral
manifestations of HIV infection in relation to clinical and CD4
immunological status in northern and southern Thai patients.
Oral Dis 2004; 10: 13844.
24. Furlanetto DL, Crighton A, Topping GV. Differences in
methodologies of measuring the prevalence of oral mucosal
lesions in children and adolescents. Int J Paediatr Dent 2006;
16: 319.
25. Exp
osito-Delgado AJ, Vallejo-Bola~
nos E, Martos-Cobo EG.
Oral manifestations of HIV infection in infants: a review
article. Med Oral Patol Oral Cir Bucal 2004; 9: 41020.
26. Ranganathan K, Umadevi M, Saraswathi TR, Kumarasamy N,
Solomon S, Johnson N. Oral lesions and conditions associated
with human immunodeciency virus infection in 1000 South
Indian patients. Ann Acad Med Singapore 2004; 33: 3742.
27. Umadevi KMR, Ranganathan K, Pavithra S, et al. Oral lesions
among persons with HIV disease with and without highly
active antiretroviral therapy in southern India. J Oral Pathol
Med 2007; 36: 13641.
28. Ramos-Gomez FJ, Hilton JF, Canchola AJ, Greenspan D,
Greenspan JS, Maldonado YA. Risk factors for HIV-related
orofacial manifestations in children. J Pediatr Dent 1996; 18:
1216.
29. Valdez IH, Pizzo PA, Atkinson JC. Oral health of pediatric
AIDS patients: a hospital-based study. J Dent Child 1994; 61:
1148.
30. Ketchem L, Berkowitz RJ, McIlveen L, Forrester D, Rakusan
T. Oral ndings in HIV-seropositive children. Pediatr Dent
1990; 12: 1436.
31. del Toro A, Berkowitz R, Meyerowitz C, Frenkel LM. Oral
ndings in asymptomatic (P-1) and symptomatic (P-2) HIV
infected children. Pediatr Dent 1996; 18: 1146.

299

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