Oral Diseases (2016) 22 (Suppl. 1), 149–157 doi:10.1111/odi.
12417
ORIGINAL ARTICLE
The global burden of oral diseases in pediatric HIV-
infected populations: a workshop report
E Arrive1,2, D Meless3, G Anaya-Saavedra4, M Gallottini5, LM Pinzon6,7, V Ramirez-Amador4
1
UFR d’Odontologie, University of Bordeaux, Bordeaux, France; 2Equipe VIH et Sant
e Globale, INSERM U897, Bordeaux, France;
3
UFR d’Odontostomatologie, F
elix Houphou€et Boigny University of Abidjan, Abidjan, C^ ote d’Ivoire; 4Department of Health Care,
Universidad Aut
onoma Metropolitana-Xochimilco, M
exico City, Mexico; 5Department of Stomatology, School of Dentistry, University
of Sao Paulo, Sao Paulo, Brazil; 6School of Dentistry, University of California, San Francisco, CA; 7School of Dentistry, University of
Utah, Salt Lake City, UT, USA
OBJECTIVES: To achieve a comprehensive understand-
ing about the global burden of oral diseases in HIV-
infected children and to identify research needs.
MATERIALS AND METHODS: A literature search was
conducted in PubMed (2009–2014) to address five ques-
tions: (i) prevalence of oral diseases in HIV-infected
compared with uninfected children, (ii) impact of oral
diseases on quality of life, (iii) effect of antiretroviral
exposure in utero on craniofacial and dental develop-
ment, (iv) important co-infections and antiretroviral
complications, and (v) value of atraumatic restorative
treatment.
RESULTS: Studies showed a high prevalence of dental
caries in HIV-infected children but the relationship
between HIV infection and dental caries remains
unclear. Also quality of life needs further investigation
supported by better study designs and improvement of
the instruments used. Up-to-date evidence suggested
long-term harms associated with in utero antiretroviral
exposure were minor but would require long-term
follow-up through National Registries. The reviews also
revealed the wide spectrum of metabolic disease due to
antiretroviral therapy and co-infections such as tubercu-
losis. Finally, atraumatic restorative technique appears
to be a simple and safe technique to treat dental caries
but outcomes need further evaluation.
CONCLUSIONS: The impact of antiretroviral therapy in
HIV-infected children has raised novel challenging ques-
tions in the field of oral health warranting future research.
Oral Diseases (2016) 22, 149–157
Keywords: HIV; children; antiretrovirals; oral lesions; dental
caries; oral-health-related quality-of-life
Correspondence: Velia Ramirez-Amador, Camino Sta. Teresa 277-9. Col.
Parques del Pedregal, Mexico D.F. 14010, Mexico. Tel: 5255 5606 1781,
Fax: 5255 5483 7206, E-mail: veliaram1@gmail.com
Received 23 June 2015; revised 22 July 2015; accepted 2 November
2015
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
All rights reserved
www.wiley.com
Introduction
Antiretroviral (ARV) coverage among pregnant women
living with HIV is reported to have reached 44% of those
afflicted across the world in 2013 and ARV drugs have
reduced the risk of mother-to-child transmission (MTCT)
to less than 1% in industrialized countries (Chou et al,
2012; Mandelbrot et al, 2014). Nonetheless, there were
still about 240 000 new pediatric infections acquired in
2013 especially in resource-limited countries, most of
them occurring in sub-Saharan Africa (UNAIDS 2014).
In 2013 just 24% [22–26%] of all children living with
HIV were receiving ARV with children being one-third less
likely to receive ARV compared to adults (UNAIDS 2014).
In addition, large collaborative studies on pediatric cohorts
have shown that the median age at initiation of ARV treat-
ment was still high i.e. 5 years old, even though most of
these children were infected through MTCT (Leroy et al,
2013). Nevertheless, mortality and severe morbidity in this
population have greatly decreased (Leroy et al, 2013).
Accordingly, the epidemiology of opportunistic
infections and chronic diseases including oral mucosal and
dental lesions has changed in frequency and nature
(Ramos-Gomez and Folayan, 2013; Gaitan-Cepeda et al,
2015). Improved coverage of ARV in resource-limited set-
tings has transformed the face of HIV from a fatal to a
chronic disease raising the need to use more comprehen-
sive health outcomes than mortality or severe morbidity,
such as quality of life. However, ARV may have deleteri-
ous effects in infants exposed in utero, such as alteration
of laboratory markers of mitochondrial dysfunction
(Mor
en et al, 2013), hematological abnormalities, and
echocardiographic markers of impaired myocardial growth
(Cristea et al, 2011). Children taking ARVs can suffer
from the same drug side effects as adults, especially seri-
ous metabolic complications, such as lipodystrophy (LD),
dyslipidemia, insulin resistance, and lactic acidosis (Bar-
low-Mosha et al, 2013). Regarding co-infections in the
pediatric population, the prevalence of hepatitis B (HBV),
hepatitis C (HCV), and tuberculosis (TB) and their impact
 Oral diseases in HIV-infected children
E Arrive et al
150
on HIV-infected children have been poorly characterized
and differ markedly in prevalence by geographic area
(Zhou et al, 2010; Venturini et al, 2014). Oral health is a
public health challenge in resource-limited countries, par-
ticularly for HIV-infected children. Cost-effective interven-
tions to prevent and control oral diseases are needed and
atraumatic restorative treatment could be one of these
(Frencken, 2014).
Therefore, this article reports on a workshop about the
global burden of oral diseases in pediatric HIV-infected
populations. The objectives of this workshop were to
achieve a comprehensive understanding of these issues
and to identify research needs in the field (Tappuni and
Shiboski, 2016).
A literature search was conducted in PubMed between
2009 and October 2014 to answer each of the five follow-
ing questions.
Questions
Question 1: What is the prevalence of oral diseases (mucosal, dental,
and periodontal) in HIV-infected compared with
uninfected children in resource-limited countries?
Question 2: Is quality of life affected by oral disease burden in
HIV-infected children in resource-limited countries?
Question 3: What is the effect of antiretroviral therapy exposure
in utero on cranio-facial and dental development in
children?
Question 4: Which are the most important co-infections and
complications due to antiretroviral therapy in HIV-
positive children?
Question 5: Is atraumatic restorative technique a feasible solution for
caries control and prevention in HIV-infected children in
resource-limited countries?
Question 1: What is the prevalence of oral diseases
(mucosal, dental, and periodontal) in HIV-infected
compared with uninfected children in resource-limited
countries?
Compared to the previous review (Yengopal et al, 2011),
further studies providing data on the prevalence of oral
mucosal, dental, and periodontal lesions in HIV-infected
children in resource-limited countries have been published
(Table 1).
Most of the studies were cross-sectional, descriptive, and
included patients with diagnosed HIV infection (Yengopal
et al, 2011). The frequency of oral mucosal diseases asso-
ciated with HIV infection such as oral candidiasis and oral
hairy leukoplakia did not change. Oral candidiasis was still
the most frequent oral HIV-related lesion (HIV-OL)
(Rwenyonyi et al, 2011; Adebola et al, 2012; Kumar et al,
2013; Renju et al, 2013; Meless et al, 2014). As it was ini-
tially described, children with lower CD4 counts presented
more often with HIV-OLs (Meless et al, 2014; Subrama-
niam and Kumar, 2014a). However, since 2008, when a
Brazilian study showed that oral lesions had moderate sen-
sitivity, high specificity, and positive predictive value to
predict immune failure (Miziara and Weber, 2008), the evi-
dence of the accuracy of HIV-OL to predict HIV disease
progression or immunological failure in HIV-infected chil-
dren has not been reported. Also, there is a lack of studies
comparing oral status between HIV-infected children and
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uninfected children. The relationship between HIV infec-
tion and dental caries is still controversial. Many studies
report high caries prevalence in HIV-infected children
(Masiga and M’Imunya, 2013; Nabbanja et al, 2013;
Meless et al, 2014), mainly for primary dentition (Oliveira
et al, 2015). Others described low caries prevalence
(Sahana et al, 2013). Ponnam et al (2012) observed a high
frequency of dental caries in HIV-infected children (33%)
but without any difference compared with uninfected chil-
dren (28%) when matched by age and socioeconomic sta-
tus. However, no specific data on the severity of the dental
disease was presented. Considering different levels of car-
ies diagnosis (cavitated or non-cavitated lesions), a recent
meta-analysis showed that although studies demonstrated
high decayed, missing, and filled teeth (DMFT) scores, a
significant association between caries experience and HIV
infection was not established (Oliveira et al, 2015). Beena
(2011) described a greater dental caries experience in HIV-
infected children with advanced decreases in the absolute
lymphocyte CD4 count despite ARV therapy. Although the
impact of HIV infection on dental caries is unclear all
authors agreed that HIV-infected children could develop
dental caries due to prolonged and frequent use of pediatric
medications with high cariogenic potential (Subramaniam
and Kumar, 2014b).
Question 2: Is quality of life affected by oral disease
burden in HIV-infected children in resource-limited
countries?
Health-related quality of life is a multidimensional concept
that captures people’s perceptions about factors that are
important in their everyday lives (Slade, 2002). Oral dis-
eases are commonly described to have an impact on quality
of life because they may cause pain and impair nutrition,
speech and appearance (Coogan et al, 2005). In the last
Workshop in 2009, it was noticed that no studies had inves-
tigated the impact of oral lesions associated with HIV infec-
tion on oral-health-related quality of life (OHRQoL) in
children (Yengopal et al, 2011). Since then, five studies
exploring this issue (Table 2) have been published. Four
studies were conducted in Brazil (Buczynski et al, 2011;
Massarente et al, 2011; Raymundo de Andrade et al, 2011;
Rovaris et al, 2014) and one in Kenya (Masiga and M’Imu-
nya, 2013), all having cross-sectional designs. A high
prevalence of dental caries (51–80%) with variable severity
was found in the four studies which included a dental
assessment. In order to measure OHRQoL, six different
questionnaires were used. High viral load, receiving ARV
treatment and having AIDS conditions were medical factors
that were found associated with lower OHRQoL. Oral vari-
ables such as dental treatment needs, report of toothache,
sensitive teeth, bleeding and swollen gums, number of teeth
with overt cavities, having filled teeth, high DMFT and
dmft were also found to be associated with lower OHR-
QoL. However, these findings were inconsistent across
studies, there was no standardization of methods, and none
had taken account of potential confounders, except for one
where analyses were adjusted on age only. There are sev-
eral validated questionnaires (Gilchrist et al, 2014) but fur-
ther work is needed to improve them and to test them in
different cultures, especially in sub-Saharan Africa.
 Table 1 Prevalence of oral lesions among HIV-infected children

Authors (year), HAART AOL OC PC EC AC OHL RHL (HSV) KS RA LGE OW SGD CARIES DMFT NUG/NUP
Country N (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) mean
SD (%)

Nabbanja et al, 2013; 368 67.4 77.4 60.8 50.5 10.3 4.3 0.5 3.3 1.6 25.5 T: 63.4 T: 11.8 NUG: 4.1
Uganda P: 47.3 P: 2.7 NUP: 0.3
Masiga and 220 T: 50.0 T: 1.75
M’Imunya, 2013; P: 30.9 P: 1.08
Kenya
Kumar et al, 2013; 326 100 61.6 20.9 16.6 2.8 5.5 NUG: 8.3
India NUP: 7.7
Meless et al, 2014; 420 100 8.3 4.8 2.4 1.9 1.4 1.2 1.0 16.4 0.5 T: 76.9 T: 4.0
3.9 NUG/NUP: 1.7
Cote d’ivoire, Mali, P: 65.8 P: 2.2
2.5
Senegal
Renju et al, 2013; 100 47.0 63.8a 29.8a 2.1a 14.9a 4.3a 6.4a 6.4a 21.3a 17.0a
India 49.1b 35.8b 3.8b 18.9b 5.7b 1.9b 1.9b 5.7b 15.1b
Rwenyonyi et al, 237 49.8 67.8a 19.5a 13.6a 2.5a 3.4a 0.8a 0.0a 0.8a 0.0a 2.5a T: 41.5
2011; Uganda 78.2b 37.0b 18.5b 6.7b 10.1b 1.7b 0.8b 0.0b 1.7b 8.4b P: 13.6
Gait
an-Cepeda et al, 87 100 26.4 21.8 2.3 4.6 1.1
E Arrive et al

2010; Mexico
Adebola et al, 2012; 105 61.9 62.0 79.1 26.7 8.6 43.8 1.9 14.3 2.9 3.8
Nigeria
Ribeiro et al, 2013, 77 100 50.6 7.6 7.6 19.2 15.3 15.3 11.5 T: 7.0
5.9
Brazil P: 3.4
2.4

AOL, any oral lesions; OC, oral candidiasis; PC, pseudomembranous candidiasis; EC, erythematous candidiasis; AC, angular cheilitis; OHL, oral hairy leukoplakia; RHL, recurrent herpetic lesions; KS,
kaposi0 s sarcoma; RA, recurrent aphthous; LGE, linear gingival erythema; OW, oral warts; SGD, salivary gland diseases; DMFT, decayed, missing, filled teeth; P, permanent dentition; T, temporary denti-
Oral diseases in HIV-infected children

tion, NUG, necrotizing ulcerative gingivitis; NUP, necrotizing ulcerative periodontitis; SD, Standard Deviation.
a
On antiretroviral treatment.
b
Not on antiretroviral treatment.

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Table 2 Characteristics of the studies about oral-health-related quality of life in HIV-infected children

Dmft/DMFT Statistical Associated

Authors Country OHRQoLQ Sample Age (years) ARV (%) HIV parameters (%) Oral lesions (%) Caries (%) mean
SD analysis factors

Rovaris et al, Brazil ECOHIS 29/36 children Mean: 10 82.8 CD4 < 500: 18 Herpes simplex: 50 75.9 Dmft: 3.7
4.0 Univariate Age ≥12, dental
2014; CPQ8-10 from 4 public s.d.
4.4 VL ≥10 000: 17.2 Gingival changes: dt: 2.63
2.92 Fisher treatment needs
CPQ11-14 reference HIV 20.7 DMFT: 2.8
3.4
OHIP centers Linear gingival DT: 2.04
2.74
erythema: 100
Massarente Brazil CPQ11-14 88 AIDS 10–15 NI Low CD4 count for NI NI NI Poisson regression VL≥ 10 000
et al, 2011; children age: 41 analysis adjusted brushing teeth <2 per
VL ≥10 000: 28 on age day
Raymundo de Brazil Child-OIDP 59 patients of 2 10–12 69.5 High viral load: 33.9 88.1: 79.6 Cavitary lesions: Univariate: Mann- ARV treatment
Andrade public AIDS: 25.4 Lymphadenopathy 4.1
4.3 Whitney test Report of
E Arrive et al
Oral diseases in HIV-infected children

et al, 2011; reference HIV 22.4: toothache,

centers hypertrophy of sensitive tooth,
parotids bleeding gum,
swollen gum,
number of teeth
with cavitary
lesions
Buczynski Brazil ECOHIS 31 Mean: 4.52 17.2 VL >10 000: 48.1 NI 51.6 Cavity lesions: Univariate: VL ≥10 000, AIDS,
et al, 2011; s.d.
1.22 Severe immune- 2.42
3.24 Student’s test and having filled tooth
suppression: 51.9 Spearman’s
AIDS: 51.9 correlation
Masiga and Kenya WHO simplified 220 patients of 3–15 NI NI NI 65 Dmft: 1.75 Univariate: High DMFT and
M’Imunya, oral health a national Mean: dt: 1.63 Student test dmft
2013 questionnaire hospital 8.36
3.48 DMFT: 1.08
for children DT: 1.04

NI, no information; VL, viral load; OHRQoLQ, oral-health-related quality-of-life questionnaire; WHO, World Health Organization; dmft, decayed missing or filled teeth in primary dentition; DMFT,
decayed missing or filled teeth in permanent dentition; ARV, antiretroviral; ECOHIS, Early Childhood Oral Health Impact Scale; CPQ, Child Perception Questionnaire; OHIP, oral health impact profile;
OIDP, oral impact on daily performance; SD, Standard Deviation.
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153
Table 3 Comparison between outcomes at first- and second/third-trime- Unfortunately, an important limitation of the studies is
ster ARV exposure in different studies that dental alterations (eruption age, structure, and mineral-
ization) have not been recorded as potential outcomes
First-Trimester Second- or Third-Trimester
Exposure Exposure (Fern
andez Ibieta et al, 2009). Moreover, the reports have
n (%) n (%) been focused in perinatally HIV-infected children not includ-
ing HIV-exposed but uninfected children, an important
European Collaborative Study Data (1984–2007) (Patel et al, 2005) group that deserves to be followed in order to identify poten-
Live births 880 1765 tial abnormalities in both primary and secondary dentition.
Congenital defects 18 (2.0) 21 (1.2)
Eye, ear, face, neck 0 (0) 1 (0.1) The decrease in bone mineral density is one of the most
Cleft lip and/or palate 0 (0) 2 (0.1) studied adverse effects of prenatal ARV use (Mora et al,
Pediatric AIDS Clinical Trial (1997–2000) (Watts et al, 2011) 2004; Amorosa and Tebas, 2006); however, only one
Live Births 636 778 recent study on pregnant rats and their offspring
Congenital defects 30 (1.7) 30 (3.8)
Eye, ear, face, neck 2 (0.3) 2 (0.2)
(Maciejewska et al, 2015) has demonstrated a decrease in
Cleft lip and/or palate 0 (0) 2 (0.2) calcium ion concentration in bone and teeth, as well as
National Study United Kingdom and Ireland (1990–2013) (Towsend disorders of trace elements, following indinavir adminis-
et al, 2009) tration. Also, a delay in the development of organic dental
Live births 5191 8917 matrix in teeth of newborn rats of mothers exposed to in
Congenital defects 170 (3.3) 265 (3.0)
Eye, ear, face, neck 3 (0.1) 11 (0.1) utero to zidovudine was demonstrated.
Cleft lip and/or palate 2 (0.1) 10 (0.1) An interesting 5-year study (2004–2009) of the risk of
APR prospective reports (through January 2014) (Antiretroviral cleft lip/palate (CLP) based on the United States Food and
Pregnancy Registry Steering Committee, 2014) Drug Administration (FDA) Adverse Events Reporting
Live births 7383 8765
Congenital defects 212 (2.9) 246 (2.8)
System (Cartsos et al, 2012), showed a high reporting
Eye, ear, face, neck 26 (0.4) 31 (0.3) odds ratio (ROR) for efavirenz (196), lamivudine (60.2),
Cleft lip and/or palate 10 (0.1) 15 (0.2) abacavir/zidovudine (59.3), and nelfinavir (50.5), as drugs
APR retrospective reports (through January 2014) (Antiretroviral associated with the presence of CLP. In this respect, it is
Pregnancy Registry Steering Committee, 2014) essential to consider the multifactorial nature of facial
Live births 310 1567
Congenital defects 14 (4.5) 23 (1.5) clefts, as well as the lack of consideration of important
Eye, ear, face, neck 0 (0) 1 (0.1) confounder variables such as age, diet, and genetic predis-
Cleft lip and/or palate 0 (0) 1 (0.1) position in the FDA Adverse Reporting System study.
In conclusion, studies related to the incidence of birth
ARV, antiretrovirals; APR, antiretroviral pregnancy registry. defects should include and record congenital dental abnor-
malities. Furthermore, children of mothers exposed to ARVs
Question 3: What is the effect of antiretroviral therapy during pregnancy should be monitored for several years in
exposure in utero on cranio-facial and dental development order to determine the real impact of prenatal administration
in children? of ARV drugs on dental and craniofacial development.
Drug-associated birth abnormalities depend directly on the
time of administration, therefore, considering that ARV Question 4: Which are the most important co-infections
use in HIV-positive pregnant women starts from the first and complications due to antiretroviral therapy in HIV-
trimester of pregnancy when organogenesis occurs, birth positive children?
defects might appear with significant frequency (Cristea The advent of highly active ARVs dramatically improved
et al, 2011). Nevertheless, as displayed in Table 3, the lit- the prognosis for HIV-infected children; however, nucle-
erature search performed showed a low incidence of con- oside reverse transcriptase inhibitors are associated with
genital defects following ARV administration at any lipodystrophy (LD) and lactic acidosis. Protease inhibitors
trimester of pregnancy. Congenital defects were slightly have been linked with dyslipidemias (increased cholesterol
higher in children born from mothers who started ARVs and triglycerides) and are associated or not with abnormal-
in the first trimester (1.7–4.5%) (Watts et al, 2011; APR, ities of body-fat distribution (lipohypertrophy and lipoatro-
2014) compared to those who were exposed only in the phy). These complications may increase the risk of
second/third trimester (1.2–3.8%) (Patel et al, 2005; Watts cardiovascular diseases in adulthood, since children
et al, 2011). Moreover, the results of a 10-year Italian require lifelong therapy with multiple drug regimens. Fur-
study showed that ARV drug first-trimester exposure did thermore, lipohypertrophy and lipoatrophy may affect self-
not increase the risk of congenital abnormalities (Floridia image, leading to depression and ultimately disturbing
et al, 2013). One of the best tools currently available to adherence to treatment (Wedekind and Pugatch, 2001).
register child outcomes of ARVs during pregnancy is the The prevalence of LD ranges from 1 to 57% among
Antiretroviral Pregnancy Registry (APR) (APR, 2014), a HIV-infected children on ARV treatment regimens and
prospective exposure-registration cohort study. Consistent from 2 to 84% among HIV-infected adults, depending on
with previous studies (Patel et al, 2005; Towsend et al, studied population, ARV regimens, and differences in
2009; Watts et al, 2011), the APR interim report (APR, methods used to determine LD. Fat redistribution and
2014) showed that the prevalence of defects among off- hyperlipidemia was found to be significantly associated
spring of women with exposure to ARVs during the first with sexual maturity and it was uncommon in children
trimester (2.8 per 100 live births) was comparable to those younger than 5 years (Amaya et al, 2002; Mu~noz-Hern
an-
exposed during the second and/or third trimester. dez and Pav
ıa-Ruz, 2009).

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154
The most common strategy to manage LD is switching mately 30% of HIV-infected children experience xerosto-
the suspected offending ARV agent, followed by met- mia associated with their medications (Kozinetz et al,
formin, thiazolidinediones, and testosterone but results 2000; Massarente et al, 2011). Xerostomia is a major con-
have been conflicting. Reconstructive surgery may be con- tributing factor to the high caries risk of HIV-infected
sidered for adolescents with disfiguring fat maldistribution patients (Ramos-Gomez et al, 1999).
and psychological problems (Piloya et al, 2012; Barlow- A possible solution for controlling and preventing den-
Mosha et al, 2013). tal caries in this population could be atraumatic restorative
For dyslipidemia and insulin resistance, the lifestyle treatment (ART). This technique was initially tested in
changes in diet and exercise are the first intervention; Tanzania in the mid-1980s. ART was presented to the
however, prescription of lipid-lowering drugs such as sta- World Health Organization in 1994 as a new approach to
tins may be considered for children (Barlow-Mosha et al, treat dental caries (Frencken et al, 1997). The technique
2013). Mild to moderate asymptomatic hyperlactatemia is consists of the excavation and removal of the softest por-
frequently reported with an estimated prevalence of 15– tions of carious lesions using hand instruments only and
30% in adults and 35–50% in children. Most of the chil-
dren with hyperlactatemia are asymptomatic and do not Table 4 Future research directions in pediatric HIV-infected populations
require a specific intervention (Noguera et al, 2003).
Co-infections with HBV, HCV, and tuberculosis (TB) Questions Future directions
are a major concern in HIV/AIDS patients. Hepatitis B
and C infection impacts negatively on disease progression What is the prevalence of More research is need to compare the
oral diseases (mucosal, burden of oral diseases between HIV-
in HIV-infected children, thereby the co-infected children dental, and periodontal) in infected and non-infected children
were more likely to have lower CD4 cell percentages and HIV-infected compared Further studies should evaluate the
higher HIV-1 RNA levels (Zhou et al, 2010). with uninfected children in predictive value of oral lesions for the
The prevalence of HBV in HIV-infected children in resource-limited countries? progression of HIV infection in
children
Thailand (3.3%) was comparable with studies in the Uni- The impact of HIV infection on the
ted States of America (USA) (2.6%) (Healy et al, 2013). prevalence and incidence of dental
In contrast, this is low compared to studies in China caries should be assessed
(4.9%), and in Nigeria (19.0%) (Healy et al, 2013). The Is quality of life affected by Further studies are needed with better
incidence of HIV-HCV co-infections among children was oral disease burden in HIV- methodological design and in sub-
infected children in Saharan Africa
low in USA, ranging from 1.5% to 3.1% (Toussi et al, resource-limited countries? OHRQoL could be used in addition to
2007), and 9.6% in China (Zhou et al, 2010). At present, clinical outcomes, in randomized
treating HIV disease and monitoring HCV and HBV control trials, to evaluate interventions
infection and hepatotoxicity induced by ARV seem to be OHRQoL could be used to optimize
adherence to the intervention
the more reasonable approach to such co-infections in Qualitative research is needed to
childhood (Resti et al, 2002). develop or improve OHRQoL
Estimated rates of TB among children with HIV vary questionnaires
widely depending on geographic area, type of ARV used, A cross-cultural adaptation of the
and on the difficulties of reaching a definitive diagnosis of questionnaires may be necessary
What is the effect of More research on maternal effects of
TB, being around 5.5% in the United Kingdom (UK), 3% antiretroviral therapy ARV use during pregnancy is needed;
in the USA, and 23% in South Africa (Venturini et al, exposure in utero on studies must include potential
2014). Pediatric TB and HIV have overlapping clinical cranio-facial and dental confounders for congenital craniofacial
manifestations, including fever, weight loss, and lym- development in children? abnormalities
Long-term studies on HIV-negative
phadenopathy, combined with persistent cough, which children exposed to ARV in utero
could lead to missed or late diagnosis (Venturini et al, should continue to identify unexpected
2014). HIV alters the pathogenesis of TB, increasing the or emerging long-term harms
risks of developing active TB in those with latent infec- It is recommended to incorporate dental
tion as well as in those newly exposed to TB (Venturini and/or minor craniofacial abnormalities
in National Registries
et al, 2014). Which are the most Future studies could be directed to
important co- infections and document the incidence, risk factors,
Question 5: Is atraumatic restorative technique a feasible complications due to and effectiveness of treatment
solution for caries control and prevention in HIV-infected antiretroviral therapy in strategies of spectrum of metabolic
HIV-positive children? disease in children and in adolescents
children in resource-limited countries? Future studies could be directed to
The caries burden in the deciduous dentition in HIV- access the incidence and better
infected children is substantially greater than that seen in therapeutic strategies for tuberculosis
the general USA pediatric population and an increase in and viral hepatitis among HIV-positive
caries burden was observed as the CD4+ T-lymphocyte children
Is atraumatic restorative Future research for caries prevention
percentage decreased (Hicks et al, 2000; Massarente et al, technique a feasible and treatment in pediatric population
2011). There are many contributing factors to the higher solution for caries control should focus on management of the
caries rate in HIV-infected children, including diets with and prevention in HIV- caries process over time for individual
high sugar content, poor oral hygiene, lack of fluoride, infected children in patients, with a minimally invasive,
resource-limited countries? tissue-preserving approach such as
medications that are sweetened with sugar and/or cause ART.
xerostomia, and a lack of access to dental care. Approxi-

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restoration with fluoride containing glass ionomers
(Molina et al, 2014). Previous studies in a high-risk popu-
lation showed that glass ionomer vs. amalgam restorations
plus daily application of fluoride in xerostomic patients
did not present recurrent caries but the patients treated
with amalgam without fluoride developed recurrent caries
(Haveman et al, 2003). There are some concerns about
the possibility of leaving untreated caries under the
restorations; however, there is the potential for remineral-
ization of the affected dentin due to the fluoride release by
the glass ionomer.
Conclusions
The literature search performed in this Workshop on pedi-
atric oral HIV highlighted key issues that continue to be
challenging and warrant future research (Table 4).
Regarding the prevalence of oral mucosal, dental, and
periodontal lesions in HIV-infected children in resource-
limited countries, the articles published in the last years
(2009–2014), have shown that oral candidiasis was still
the most frequent oral HIV-related lesion. The literature
search also demonstrated that the relationship between
HIV infection and dental caries is still controversial but
probably related to the prolonged and frequent use of
pediatric medications with high cariogenic potential.
Regarding the impact of oral lesions associated with
HIV infection on OHRQoL in children, the literature
review indicated that there were few studies conducted in
sub-Saharan Africa and most of them lacked standardiza-
tion and appropriate methodological design.
In relation to the craniofacial long-term harms associ-
ated with in utero ARV exposure, up-to-date evidence
suggested harms are minor; however, there are few data
on the consequences of ARV use in the dentition (eruption
age, structure, and mineralization alterations). The review
of the use of ARV by HIV/AIDS children and adolescents
revealed the wide spectrum of metabolic disease as well
as co-infections of HBV, HCV, and TB.
Finally, the discussion of ART showed it could be a
possible solution for controlling and preventing dental car-
ies in this population, because it is a safe technique based
on minimal intervention.
Suggestions for future research
The suggestions for future research generated by the
discussion are summarized in Table 4.
Author contributions
E. Arrive, D. Meless, G. Anaya Saavedra, M. Gallottini,
L .M. Pinzon and V. Ramirez-Amador contributed to the
design, drafting, and editing of the manuscript and tables.
All authors read and approved the final manuscript.
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