Periodontology 2000, Vol.
60, 2012, 78–97
Printed in Singapore. All rights reserved
Periodontal disease in HIV ⁄ AIDS
M A R K I. R Y D E R , W I P A W E E N I T T A Y A N A N T A , M A E V E C O O G A N ,
D E B O R A H G R E E N S P A N & J O H N S. G R E E N S P A N
Since the early 1990Õs, the face of HIV infection and
the AIDS global epidemic have changed significantly.
Although the death rate from AIDS among 25- to 44-
year-old adults has shown a marked decline in the
USA and in other developed countries, largely be-
cause of newer antiretroviral therapies and improved
access to these therapies, AIDS remains one of the
leading causes of premature death, particularly in the
developing world. The total number of new cases of
HIV infection worldwide has remained relatively
constant from 2006 to 2011 with approximately half
of all HIV-infected individuals receiving some form of
antiretroviral therapy (97). Therefore, despite the re-
cent advances in antiretroviral therapy and preven-
tion of HIV infection, dental and other healthcare
practitioners will be required to continue to treat oral
and periodontal conditions unique to HIV ⁄ AIDS as
well as conventional periodontal diseases in the HIV-
infected patient.
In order to present the full scope of the epidemi-
ological and clinical issues involved in HIV-associ-
ated oral and periodontal diseases and conditions of
infection in the developing world, we discuss the
current clinical and epidemiological trends of HIV
infection in general, and the oral and periodontal
manifestations of HIV infection in both the devel-
oping and developed worlds, in both adults and
children. This is followed by a brief update on recent
insights into the microbiology and pathogenesis of
periodontal diseases in HIV-infected patients, and
their implications for diagnosis and treatment in the
antiretroviral therapy era in developing and devel-
oped countries. The current standard accepted ther-
apies for the treatment of both the uncommon peri-
odontal lesions seen with greater frequency in HIV
infection, and the more common periodontal dis-
eases in both developing and developed countries are
then discussed. The concluding section of this paper
will discuss the broad implications of the current
state of knowledge of HIV infection and oral ⁄ perio-
dontal diseases in the developing world, and provide
78
 2012 John Wiley & Sons A/S
PERIODONTOLOGY 2000
recommendations for future epidemiological, basic
science and clinical investigations.
Trends of HIV infection and AIDS
in the developing and the
developed worlds
HIV infection and AIDS continue to have catastrophic
global medical and social effects, especially in regions
where the prevalence is relatively high, such as in
sub-Saharan Africa, Central and South-East Asia,
eastern Europe and South America. More than 60
million people have been infected with HIV world-
wide. More than 30 million have died, and 34 million
are currently living with HIV infection (168).
However, the growth rate of the pandemic appears
to have plateaued since the first case of AIDS was
reported by the US Centers for Disease Control and
Prevention in year 1981 (20, 97). In 2009, an esti-
mated 2.6 million people became newly infected with
HIV, which is nearly one-fifth (19%) fewer than the
3.1 million new cases in 1999. In sub-Saharan Africa,
the estimated 1.8 million people who became in-
fected in 2009 is lower than the estimated 2.2 million
new cases in 2001 (168).
However, some other parts of the world do not fit
this overall declining trend. For example, Central
Asia, defined by the World Health Organization as the
Republics of Kazakhstan, Kyrgyzstan, Uzbekistan,
Tajikistan and Turkmenistan, is experiencing one of
the fastest growing HIV epidemics in the world (177).
Following the collapse of the Soviet Union, there has
been a rise in sex work and injection drug use, both
risk factors associated with the HIV infection. High
rates of HIV transmission in this region continue to
occur among injecting drug users and their sexual
partners (160).
A combination of factors, including the impact of
HIV-prevention efforts and the scientific progress in
HIV ⁄ AIDS research, especially in the development of

antiretroviral therapy, has proven to be a life-saving
approach to many millions of HIV-infected individ-
uals worldwide (39). The availability of antiretroviral
therapy has resulted in dramatic reductions in
HIV ⁄ AIDS-related mortality and morbidity (167).
Consequently, more people infected with HIV are
able to have better health and lead productive lives.
Currently, approximately 30 anti-HIV agents are
licensed and evidence-based guidelines have been
developed for their optimal use.
More than 4 million people in low- and middle-
income countries, as well as approximately 1 million
people in the developed world, are receiving antiret-
roviral therapy. However, there are far more who
need, but are not receiving, these medications. With
improvements in antiretroviral therapy approaches,
the estimated life expectancy of certain HIV-infected
patients now approaches that of uninfected individ-
uals (157). Of interest, antiretroviral therapy has also
proven efficacious in HIV prevention, reducing the
risk of mother-to-child transmission and serving as
postexposure prophylaxis for individuals exposed to
HIV (2, 25, 55). Unfortunately, poverty, stigma, dis-
crimination, inadequate healthcare systems and
other social problems remain powerful barriers to
treatment and prevention programs. In addition,
many countries with HIV epidemics among hetero-
sexuals in the general population lack effective pre-
ventive interventions, such as programs of male cir-
cumcision, programs to prevent mother-to-child
transmission, and educational and cultural efforts to
discourage engagement in multiple concurrent sex-
ual partnerships (43).
HIV infection continues to erode health, economic
and social progress, particularly in developing coun-
tries. AIDS continues to reduce life expectancy by
years. As a result, the average life expectancy of a
person born between 1995 and 2000 in some African
countries, where the HIV prevalence is more than
20%, is now 49–13 years shorter than in the absence
of AIDS. In some other African countries that lack
access to antiretroviral programs, such as Swaziland,
Zambia and Zimbabwe, the average life expectancy is
predicted to drop below 35 years. In addition, HIV
infection is deepening the poverty of those infected.
HIV ⁄ AIDS-affected households are more likely to
suffer severe poverty than nonaffected households
because the infection reduces the income and pro-
ductivity of family members who are ill; it also creates
extraordinary care needs and increases household
medical expenses and other costs, which absorb a
significant proportion of the household monthly in-
come (130).
Periodontal disease in HIV ⁄ AIDS
The HIV ⁄ AIDS epidemic is also a significant
obstacle to the universal access of children to edu-
cation. In many African countries the epidemic is
expected to contribute substantially to the future
shortage of primary school teachers. The quality of
education has been affected as skilled teachers fall ill
and die. Children from AIDS-affected families are
often withdrawn from school in order to look after
the home and to find employment, to compensate for
the loss of income incurred through a parentÕs illness
and the expenses encountered as a result of caring for
ill relatives (130).
The HIV epidemic has negative effects on the
health sector, particularly in developing countries.
Many health services and facilities are struggling to
cope with the growing impact of HIV ⁄ AIDS. Severe
shortages of human and financial resources are
prominent, especially in the worst-affected countries
of Africa and Asia. In sub-Saharan Africa, people with
HIV-related illnesses occupy more than 50% of hos-
pital beds (167). Demand for health services is also
increasing because more healthcare personnel are
dying or are unable to work as a result of AIDS.
Therefore, more healthcare personnel will need to be
trained and new categories of healthcare workers,
including primary health workers, assistants and
health counselors should be established.
HIV-associated oral lesions in
developing and developed
countries in the pre- and
postantiretroviral therapy era
While the current trends of HIV infection in both
developing and developed countries remain in con-
tinuous flux, dental and other healthcare providers
need to remain cognizant of the oral lesions and
conditions that are associated with HIV infection. Of
particular importance is that these oral lesions may
represent the first clinical signs of HIV infection (62).
Furthermore, changing patterns of the incidence and
prevalence of oral lesions may serve as surrogate
markers for the efficacy of antiretroviral therapy. The
oral lesions of HIV infection are opportunistic and
their presence is somewhat correlated with viral load
and CD4 cell counts. Several authors have suggested
that these lesions could be used as markers of the
efficacy of antiretroviral therapy treatment, especially
in the developing world (101, 174). In this section, the
past and current patterns of these oral lesions will be
discussed in relation to both developing countries
79
Ryder et al.
and developed countries, with special emphasis on
lesions associated with the periodontium.
Oral candidiasis
In the pre-antiretroviral therapy era, the various
forms of oral candidiasis were the most common
HIV-related oral lesion seen in developed and
developing countries (Fig. 1a–c). Among adults in the
developed world, the prevalence of oral candidiasis
has been reported to range from 5% to 92% (129). In
the developing world, the reported prevalence of oral
candidiasis is 15% in Africa (155), 70% in India (9,
141) and 66% in Thailand (117). However, these fig-
ures were much higher in individuals who had full-
blown AIDS (9, 155). Pseudomembranous candidiasis
was associated with severe immunosuppression in
studies where clinical parameters were available (66,
141, 155, 165). Among HIV-infected women in Kigali,
Rwanda, oral candidiasis, although fairly rare, was
highly predictive of death (88). Another study on
children not receiving antiretroviral therapy found
that prior Candida infection was an important inde-
pendent predictor of high mortality (174).
There has been a marked change in the prevalence
of oral candidiasis since the introduction of antiret-
roviral therapy (42, 67). The largest cohort, followed
over 12 years, showed a 50% decrease in oral can-
didiasis (137). The relative risk was halved in subjects
on highly active antiretroviral therapy (HAART)
compared with untreated women in San Francisco,
and the rate of recurrence was reduced indepen-
dently of both the CD4 count and the HIV-RNA viral
load (61). Protease inhibitor therapy also decreased
both the frequency and the recurrence of oral can-
didiasis in HIV-infected individuals (32, 127). How-
ever, the effect of HAART on reducing the incidence
of other oral lesions does not appear to be as signif-
icant.
A B
1
2
Fig. 1. Oral candidiasis in an HIV-positive patient. (a) Note
the areas of whitish filamentous plaque-like lesions (1) and
areas of surface ulceration (2). (b) Erythematous candidi-
asis of the tongue (arrows). (c) Toluidine Blue stain of at-
80
Oral hairy leukoplakia
In the pre-HAART era, oral hairy leukoplakia (Fig. 2)
was the second most common oral lesion associated
with HIV infection, with a reported prevalence in the
USA and Europe of 7–30% and a lower rate among
women (129). In the developing world the prevalence
of hairy leukoplakia was lower, ranging from 0% in
Tanzania (155) to 20% in South Africa (10). In Thailand
the reported percentage of patients with hairy leuko-
plakia was 7–26% (116, 117). More recent studies re-
ported a prevalence of hairy leukoplakia in children of
6.9% in Tanzania (64) and 18.3% in Brazil (31).
Following the introduction of antiretroviral ther-
apy, a significant decrease of hairy leukoplakia was
found in populations from Germany and Mexico that
had previously reported a high prevalence of hairy
leukoplakia (137, 156). This was not the case for
women enrolled in the WomenÕs Interagency HIV
study in the USA (61).
KaposiÕs sarcoma
In the pre-antiretroviral therapy era, the percentage
of patients with KaposiÕs sarcoma (Fig. 3) varied
according to the region of the world and the cohort
examined. In the USA and Europe, the prevalence of
KaposiÕs sarcoma varied from 2% to 7% but reached
38% in a selected group of 84 patients with AIDS who
were referred to the National Institute for Dental
Research. In a similar group from San Francisco, the
prevalence was 32%. A high proportion of both of
these groups consisted of men who have sex with
men (128). Reports on KaposiÕs sarcoma in the
developing world were also variable. In two African
studies in Zimbabwe, the reported prevalence of
KaposiÕs sarcoma varied from 78% (77) to 19% in a
later report (22). In the 1990s there were no reports of
this lesion in South Africa (11), or in Thailand and
C
tached gingiva with candida invasion. Note the extension
of filamentous processes of the candida into the deeper
layers of the epithelium (arrows).

Fig. 2. Oral hairy leukoplakia in an HIV-positive patient.
Note the pronounced hyperkeratosis on the left lateral
border of the tongue.
Fig. 3. KaposiÕs sarcoma affecting the mucosa and at-
tached gingiva region of the right maxillary lateral and
central incisor.
India (77); however, in later studies from Africa and
Brazil there was a reported prevalence of 0.2–7%
among HIV-infected children (122, 182). The distri-
bution of these lesions is probably related to the
endemic presence of human herpesvirus-8 in sus-
ceptible populations (140).
In the postantiretroviral therapy era, there have
been conflicting reports about changes in the prev-
alence of oral KaposiÕs sarcoma. A German study re-
ported a significant decrease in the prevalence of
KaposisÕs sarcoma, from 9% to 1%, after initiation of
HAART (156), whereas studies from the USA (127)
and Mexico (137) found no significant change.
Salivary gland disease
In the pre-antiretroviral therapy era, salivary gland
disease, involving enlargement of the major salivary
glands and often accompanied by dry mouth, was
reported to be high in northern Africa and Thailand
(117). More recently, there was a reported prevalence
Periodontal disease in HIV ⁄ AIDS
of salivary gland disease of 47% among 192 adults (73
with AIDS and 119 HIV-positive patients not on an-
tiretroviral therapy) in Tanzania, 30 in Nigeria and 24
in Brazil. Salivary gland enlargement has been linked
with human leukocyte antigen gene products and
untreated advanced stage of AIDS in Africans (95).
Chronic malnutrition may play a role in salivary
gland disease because it reduces saliva flow and
promotes dental caries, as observed in Indian chil-
dren (76). Xerostomia may be influenced by the
concurrent use of traditional medicines (176).
Over the past 15 years in the antiretroviral therapy
era, there have been reports of a declining trend in
the prevalence of HIV-related salivary gland disease
in the USA and Europe (60, 114, 127). This trend was
not supported by studies in Mexico (137), where HIV-
infected women were at a significantly higher risk of
xerostomia and salivary gland hypofunction than
noninfected women. HAART was a significant risk
factor for these conditions (111).
Oral warts and antiretroviral therapy
In contrast to the declining trends of oral candidiasis,
oral hairy leukoplakia, KaposiÕs sarcoma and possibly
salivary gland disease following the introduction of
antiretroviral therapy, there has been an increased
prevalence of oral warts in the USA and the UK
(Fig. 4a,b) (60, 63, 81, 127, 185). Similar detection rates
of oral warts were documented in Mexican subjects on
antiretroviral therapy compared with those not on
therapy (137). This was also found in a prospective
multicenter study, which showed no change in inci-
dence with HAART therapy (61). The development of
human papillomavirus-related oral mucosal lesions in
HIV-infected individuals may be related to a decreased
HIV load (81) and ⁄ or a decreased CD4+ cell count (81,
82). The mechanism by which a reduction in HIV load
may lead to an increased risk of oral warts remains
unclear, but may represent a form of immune-recon-
stitution syndrome (81, 136).
Studies have shown that many oral lesions are
opportunistic and directly related to the immune
system and hence to the CD4 cell count. Several au-
thors have suggested that these lesions could be used
as markers of the efficacy of HAART treatment,
especially in the developing world (101, 174).
HIV and periodontal diseases
Periodontal lesions associated with HIV include lin-
ear gingival erythema (Fig. 5a,b) and necrotizing
81
Ryder et al.
A B
2
Fig. 4. (a) Extensive oral warts from possible herpetic infec-
tion in an HIV-positive patient, affecting both the hard palate
(1) and the gingival margin of the palate (2). (b) Human
papillomavirus infection in the gingival margin of an HIV-
A B
Fig. 5. Mild (a) (arrows) and more severe (b) forms of
linear gingival erythema in HIV-positive patients. While
the clinical appearance is somewhat similar to the clinical
inflammatory manifestation of plaque-induced gingival
Fig. 6. Necrotizing ulcerative gingivitis in an HIV-positive
patient. The clinical characteristics are identical to previ-
ous descriptions of acute necrotizing gingivitis in HIV-
negative patients with rapid necrosis of the soft tissue,
especially in the interproximal area.
periodontal diseases, which are subclassified as
necrotizing ulcerative gingivitis (Fig. 6), necrotizing
ulcerative periodontitis (Fig. 7) and necrotizing sto-
matitis (Fig. 8a,b), but appear to be different stages of
the same disease (36). There are reports of necrotiz-
ing ulcerative gingivitis that have progressed to nec-
82
infected patient. Note the multiple vesicular lesions in the
attached and free gingiva around the mandibular right ca-
nine. Such viral infections may also contribute to the necrotic
lesions of the gingival tissue seen in late-stage HIV infection.
disease, these lesions usually do not respond to conven-
tional treatment of plaque debridement and plaque
control. These lesions often resolve with topical and ⁄ or
systemic antifungal treatment.
Fig. 7. Necrotizing ulcerative periodontitis in an HIV-po-
sitive patient. In addition to the clinical features of soft
tissue necrosis, as seen in necrotizing ulcerative gingivitis,
there is also necrosis of the alveolar crest (arrows).
rotizing stomatitis (126, 146, 178). Studies have
shown that these diseases are strongly associated
with HIV infection and have implications not only for
oral health but also for systemic health (127, 166, 172,
173).
With the declines in the frequency of these less
common forms of destructive periodontal disease
in HIV-infected patients in both developed and

A B
Fig. 8. Further extension of acute necrotizing periodon-
titis into the supporting bone (arrows) in two severely
immune-compromised HIV patients. These necrotizing
stomatitis conditions require immediate treatment,
developing countries, and with the increased life-
span of these patients, the dental practitioner will
still be required to diagnose and treat the more
common forms of periodontal disease in these pa-
tients. Before the widespread use of antiretroviral
therapy, there were conflicting reports as to the
relationship of HIV infection with attachment loss
and bone loss. Several of these studies reported
that in patients with a pre-existing chronic peri-
odontal disease, periodontal attachment loss was
greater in HIV-infected patients (13, 23, 90, 147,
184), which correlated with declining CD4 counts.
Of particular importance to the delivery of antiret-
roviral therapies in the developing world was that
this relationship was apparent particularly in pop-
ulations that were not receiving antiretroviral ther-
apy or antimicrobial therapy (113). In studies that
Fig. 9. Chronic periodontitis in an HIV-positive patient.
This patient reported no previous history of necrotizing
periodontitis or gingivitis. This clinical presentation is
typical of chronic periodontitis in HIV patients, as there is
considerable gingival recession (indicated by arrows) with
loss of attachment. It is possible that necrotizing period-
ontitis and conventional periodontal diseases develop
through similar pathways in HIV patients.
Periodontal disease in HIV ⁄ AIDS
which includes removal of the necrotic bone and other
necrotic tissue, and antimicrobial therapy. After soft tis-
sue healing, there will be pronounced residual defects in
these areas.
added the parameter of gingival recession to clini-
cal studies of HIV and periodontal disease there
was a reported relationship of increased gingival
recession (96) (Fig. 9). While a similar pattern of
increased gingival recession was observed with
HIV-infected patients in other studies, there was no
observed increase in underlying alveolar bone lose
with advancing HIV status (3). The increased gin-
gival recession in HIV-infected patients with
chronic periodontitis may share pathological char-
acteristics with the more overt necrotic periodontal
lesions seen in these patients in that there may be
destructive patterns of common periodontal dis-
eases in HIV-infected patients that not only include
the bone and attachment apparatus, but also the
oral gingival epithelium (120, 121). These pat-
terns of increased attachment loss and recession in
HIV may be partly caused by atypical fungal,
bacterial and viral infections of the periodontium
and ⁄ or changes in the destructive inflammatory
response.
Furthermore, in the developing world, the fre-
quency of less common necrotizing forms of peri-
odontitis may be much higher than in developed
countries, regardless of HIV status. This may a par-
ticular issue in South Africa where recent studies
have shown that the clinical signs of necrotizing
periodontitis and necrotizing gingivitis, and other
severe forms of periodontitis, are much higher than
reported in developed countries (175), are similar in
HIV-seropositive and HIV-seronegative patients, and
are not related to the CD4+ T-cell count, to neutrophil
counts, to gender or to age (132, 180).
In some studies that have compared the preva-
lence of HIV-associated oral lesions in the pre- and
postantiretroviral therapy era, there is a reported
reduction in oral candidiasis and hairy leukoplakia,
and a shift in the prevalence of periodontal
83
Ryder et al.
diseases in HIV-infected adults (83). However, other
studies have found no differences in periodontal
parameters in patients using antiretroviral therapy
and in non-HIV-infected adults. For example, in a
large cross-sectional and longitudinal study con-
ducted from 1995 to 2002 in a female cohort, no
significant differences were found in baseline mean
clinical attachment levels and probing depths, or
on progression of attachment loss and pocket
depths, between HIV-positive and HIV-negative
women (8).
In the antiretroviral therapy era, no clear correla-
tion has been shown between viral load and CD4
counts (i.e. measures of HIV infection) and peri-
odontal attachment loss or pocket depth. Some
studies have reported that with the exception of the
presence of linear gingival erythema in some HIV-
infected patients, there were no major differences in
other periodontal parameters between HIV-infected
and non-HIV-infected patients (17) or in tooth-loss
patterns (37). Another study demonstrated a lower
degree of gingival inflammation in severely immune-
compromised HIV-positive patients with CD4 cell
counts of <200 cells ⁄ mm3, while in patients with
CD4 cell counts of >500 cells ⁄ mm3 there was no
association between CD4 cell count and periodontal
indices (171). However, a 10-fold increase in viral
load was associated with a marginal increase in tooth
loss (8). In another study on an HIV-infected cohort
of adults, the level and extent of periodontal disease
were high, even though most patients were being
treated with HAART. Those with CD4+ T-cell counts
of <200 cells ⁄ mm3 were at greater risk for peri-
odontal disease (173). These authors recommended
that earlier initiation of antiretroviral therapy may
decrease exposure to immunosuppression and re-
duce periodontal disease morbidity. In addition,
observations from HIV-infected cohorts in individual
countries have demonstrated that the overall levels of
oral care and disease are poorer when compared to
levels in other developed countries. For example, the
dental health status of HIV-infected Portuguese pa-
tients was reported to be unsatisfactory and related to
clinical, socioeconomic and behavioral variables
(152). From the findings of these recent studies it is
apparent that continuity of preventive and active
dental care remains important for HIV-infected
patients, either with or without antiretroviral
therapy ⁄ HAART, in both developing and developed
countries.
Much of the focus on periodontal disease in
HIV-positive patients in both the pre- and post-
antiretroviral therapy eras has shifted towards stud-
84
ies on children (182), with most studies investigating
the prepubertal form of these diseases. In the pre-
antiretroviral therapy era, one study reported that
92% of the children investigated in the USA had ei-
ther gingivitis or periodontitis and plaque indices
ranging from 55% to 94% (71). In a 2001 study in
Romania, Vaseliu et al. (170) reported that 49% of
children had gingivitis. The corresponding values
were lower in Brazil, ranging from 13.5% to 17.5%
(92, 153), whereas in Thailand the values were as low
as 2.2% (80, 143). In 2010, Duggal et al. (35) reported
a low incidence of linear gingival erythema in South
Africa. Ranganathan et al. (139) reported no cases of
linear gingival erythema in Indian patients, even
though the patients were not on antiretroviral ther-
apy. In contrast, in a study in India on HIV-infected
children not on antiretroviral therapy ⁄ HAART, the
prevalence of HIV-associated oral lesions was still
relatively high, with reports of the incidence of gin-
givitis being 10.8% (139). In 2010, Duggal et al. (35)
found that periodontal lesions, particularly linear
gingival erythema, were directly associated with viral
load and immune status, regardless of the use of
antiretroviral therapy. Despite these observations,
data from a large multicenter prospective cohort
study of 2767 children in the USA and Puerto Rico
show that these opportunistic infections are
uncommon and have a lower prevalence rate in
children on HAART compared with studies under-
taken during the pre-HAART era (49).
HIV and the microbiology and host
response in periodontitis:
implications for developing
countries
When considering the role of bacteria, fungi and
viruses in the pathogenesis of periodontal diseases in
the HIV-positive patient, in both developed and
developing countries, one needs to consider that
conditions such as linear gingival erythema and
necrotizing gingivitis and periodontitis, and ⁄ or
conventional periodontal diseases such as chronic
periodontitis, may present in the oral cavity as either
unique disease states or as a combination of these
lesions. The microbiological profile of each of these
lesions may present both with species normally
associated with periodontal diseases as well as with
unique opportunistic flora that may produce more
destructive and ⁄ or necrotic lesions. Earlier studies
on the microbiological profiles between linear gingi-

val erythema and necrotizing ulcerative periodontitis
were similar, with the implication that there is a
continuum between these lesions (102, 105, 106, 138,
186, 187). In addition, these studies demonstrated
that the microbial patterns were similar to those
observed in chronic periodontitis lesions in both
HIV-positive and HIV-negative patients.
In both developing and developed countries, the
availability of less expensive antiretroviral therapies,
either as single agents or in combinations of agents
(HAART), have had a variety of effects on the
microflora of periodontal diseases, with implications
for both diagnosis and treatment. In this current
antiretroviral therapy era, similar observations have
been made on the nature of the subgingival flora in
HIV-positive subjects with chronic periodontitis, with
several species such as Enterococcus faecalis and
Fusobacterium nucleatum present in higher numbers
with lower CD4 counts (50, 124). In addition, certain
combinations of suspected periodontal pathogens
are more prevalent in the HIV-positive patient (125).
More recent microbial studies in the antiretroviral
therapy era mirror the previous findings for the pre-
antiretroviral therapy era, in that there are essentially
few to no differences in the periodontal microflora of
patients with common forms of periodontitis, such as
chronic periodontitis, when comparing HIV-positive
and HIV-negative patients. In particular, the patterns
for the most suspected periodontal pathogens appear
similar between HIV-positive and HIV-negative pa-
tients with chronic forms of periodontitis (1). As these
combinations of putative pathogens may increase
susceptibility for periodontal breakdown in the HIV-
positive patient, there is a need to continue to de-
velop and apply low-cost and effective antimicrobial
therapies to HIV patients in the developing world.
One very important consideration for the preven-
tion and treatment of periodontal diseases and con-
ditions in HIV patients in the developing world is the
widely reported presence of opportunistic microor-
ganisms in general, and yeasts and viruses in particular,
that may have a major impact on the progression of
these periodontal lesions. For example, the preva-
lence and variety of treponemes (spirochetes) may
play a critical role in the pathogenesis of both chronic
periodontal diseases and necrotizing periodontal
diseases in the HIV-positive patient (24, 151). In the
current antiretroviral therapy era there continue to be
reports of atypical ⁄ opportunistic microbial species
isolated from the periodontal pockets of HIV patients
(94). Recent reports have demonstrated that in HIV-
positive patients, opportunistic pathogens such as
Helicobacter pylori, E. faecalis (37, 161) and Pseudo-
Periodontal disease in HIV ⁄ AIDS
monas aeruginosa (37, 161) are present at a higher
frequency in the subgingival biofilm.
In addition, yeasts (such as candida species) and
herpes-like viruses have also been observed in high
numbers in the plaque biofilm of HIV-positive pa-
tients (21, 24, 48, 59, 69, 90, 121). These yeasts and
viruses have been implicated in the progression of
necrotic lesions into the supporting alveolar bone.
More recently, considerable attention has been given
to the high prevalence of candida species in several
forms of periodontal disease in the HIV-positive pa-
tient and their role in the pathogenesis of destructive
and necrotic lesions. Although candida species are
detectable in almost all HIV subjects, invasion of
candida into the soft tissues is closely associated with
periodontal diseases (48, 121, 134). This invasion
occurs not only within the gingival crevice, but also
beneath the oral epithelium (Fig. 1c). These candida
infections may trigger the destructive arm of the local
host response (47, 48, 150), which may result in the
tissue necrosis seen in the necrotizing ulcerative
periodontitis lesion and ⁄ or facilitate further loss of
attachment and alveolar bone in chronic or aggres-
sive periodontal diseases. This destructive arm could
include the release of potentially destructive enzymes
into periodontal tissue from adjacent ÔprimedÕ neu-
trophils attempting to neutralize this candida inva-
sion (150). In addition to a ÔprimedÕ neutrophil
response, priming of other inflammatory responses
to HIV may play a role in the pathogenesis of peri-
odontal disease (166). These include excessive pro-
duction of interferon-gamma (4, 38), prostaglandins
(6), matrix metalloproteinase-9, tissue inhibitor of
metalloproteinase-1 and other metalloproteinases (7,
100), interleukin-1beta and interleukin-6 (57), trans-
forming growth factor-beta (5) and interleukin-2 and
interleukin-18 (38). As in HIV-uninfected patients,
several of these inflammatory cytokines are found at
higher concentrations in deeper vs. shallower peri-
odontal pockets (12, 58, 85, 86). This elevated
inflammatory cytokine response in HIV-infected pa-
tients may occur partly in response to the HIV
infection per se and ⁄ or partly in response to
opportunistic infections such as candida. This
primed inflammatory response may, in turn, play a
role in the pathogenesis of chronic periodontitis in
HIV-infected subjects (4). These patterns of tissue
destruction in the HIV-infected patient would occur
both within the gingival crevice and within the oral
gingival epithelium.
Xerostomia, associated either with HIV infection
per se or with concomitant HAART therapy, may also
contribute to an increased incidence of periodontal
85
Ryder et al.
diseases and dental caries (19, 115). In a study from
Thailand, the salivary flow rate of HIV-infected sub-
jects was found to be affected by HIV infection (118)
in that the rate was significantly decreased with ad-
vanced disease stage. Various factors, including
medication use, were associated with hyposalivation
and xerostomia among the subjects. The subjects on
long-term HAART were found to have a greater risk of
having oral lesions than those on short-term HAART.
A direct or indirect role for viruses in the progres-
sion of necrotic periodontal lesions in the HIV-posi-
tive patient has also received considerable attention
over the past 30 years. Early studies on cases of ne-
crotic gingival and periodontal lesions reported the
presence of cytomegalovirus (46), herpes zoster virus
(103) and papillomavirus (91). Such viruses may play
a role in the pathogenesis of destructive periodontal
lesions in the HIV-positive patient. In addition,
viruses in the herpesvirus family, including cyto-
megalovirus, Epstein–Barr virus, herpes simplex virus
and other human herpesviruses, may also play a role
in the initiation and progression of these destruc-
tive ⁄ necrotic lesions (33, 54, 84, 86, 159). HIV-posi-
tive patients harbor greater numbers of these viruses
in periodontal pockets than their HIV-negative
counterparts (26, 93). While the role of these herpe-
sviruses as a primary etiology or a contributory factor
has yet to be determined, the presence of elevated
levels of these viruses in periodontal tissues may lead
to the overgrowth of periodontal pathogens and to
the emergence of opportunistic infections through
suppression of the protective functions of the host
response and increased secretion of potentially
destructive inflammatory mediators (159).
Diffuse invasion of viruses, fungi and other
opportunistic organisms into the gingival tissue and
underlying periodontal support may also help, in
part, to explain the patterns of periodontal destruc-
tion in HIV infection. This diffuse invasion may be
facilitated by a reduction in key components of the
immune system though direct mechanisms such as
the effect of HIV infection on reducing CD4 counts or
through other, more indirect, mechanisms. Specifi-
cally, a diffuse microbial invasion could lead to a
diffuse destructive inflammatory infiltrate through-
out the gingiva and marginal breakdown of the soft
and hard tissues. This concept of a unique diffuse
gingival inflammatory infiltrate is supported by sev-
eral studies (107, 109, 110). This is in contrast to the
pattern of chronic periodontal diseases in non-HIV-
infected individuals, where inflammatory cells are
localized primarily in connective tissue regions
adjacent to the junctional epithelium. This greater
86
susceptibility for periodontal breakdown and devel-
opment of necrotic lesions in HIV-infected individ-
uals may also be caused partly by the reduced
numbers of host defense dendritic cells (e.g.
LangerhanÕs cells) on the oral epithelial side (110) and
reduced antibody reactivities to periodontal patho-
gens and other infections (7, 12, 58, 85, 99, 100, 108,
163).
These observations are particularly important in
the antiretroviral therapy era, as it appears that the
incidence and levels of bacteria, yeasts and viruses
are declining in both typical chronic periodontal
lesions and in atypical ⁄ necrotic periodontal lesions.
However, the use of these antiretroviral regimens,
while having some beneficial effects, may also have
some adverse effects, both directly and indirectly, on
periodontal diseases. In the current antiretroviral
therapy era, a high prevalence of oral infections
caused by bacteria, viruses and fungi has been de-
scribed in HIV-infected patients, and these infec-
tions include periodontal disease. As oral epithelial
cells, gingival crevicular fluid and saliva have been
shown to be a reservoir for HIV, finding low-cost
and easy-to-use treatments for oral chronic peri-
odontal diseases may be a critical issue in managing
HIV infections in both developed and developing
countries.
From a periodontal disease perspective this is a
particularly important issue because several recent
in vitro studies have implied that such chronic oral
inflammatory diseases and microbial diseases, such
as periodontal diseases, may facilitate HIV infection
of a host (74). For example, the common periodontal
pathogen P. gingivalis may facilitate transinfection of
HIV-1 from oral keratinocytes to dendritic cells and
other antigen-presenting cells (44). Oral infections
such as periodontitis may therefore increase the risk
for oral infection and dissemination of HIV. Evidence
for this potential pathway is further supported by in
vitro studies on cultured fibroblasts and epithelial
cells, which have demonstrated that the cell super-
natant contains inflammatory mediators (such as
interleukin-6, interleukin-8 and granulocyte–macro-
phage colony-stimulating factor) that are elevated in
periodontal diseases as a result of enhanced pro-
moter activation for HIV in HIV-infected monocytes,
macrophages, dendritic cells and T-cells. Another
finding with implications for the clinician in both
developing and developed countries is that several
common periodontal pathogens, including F. nucle-
atum, P. gingivalis and several other gram-negative
species associated with chronic periodontal diseases,
significantly enhance promoter activity for the HIV in

infected monocytes ⁄ macrophages (52, 53, 72, 73,
75). In addition, when the gingival epithelial barrier is
damaged or when there are inflammatory changes in
the underlying periodontal tissues, bacterial translo-
cation can occur, causing bacteremia. Therefore, it is
conceivable that a bacteremia of oral and periodontal
bacteria could trigger a similar re-activation of the
HIV at sites distant from the oral cavity.
While the effects of periodontopathic bacteria may
induce re-activation of the HIV, thereby adversely
affecting the potential benefits of antiretroviral ther-
apy, the effects of antiretroviral therapy per se may
have either adverse or beneficial effects on the mic-
robiota of the oral cavity. For example, in a study on
women receiving antiretroviral therapy, there was an
increased risk of recovering Fusobacterium, spe-
cies, enteric gram-negative rods, Peptostreptococcus
micros, Campylobacter species, Eubacterium species
and Tannerella forsythia (112). These authors spec-
ulated that HAART may result in a shift of the eco-
logical balance to a more pathogenic microbiota. By
contrast, in a study of HIV-infected children under-
going antiretroviral therapy, HIV-infected children
(almost all of whom were on antiretroviral therapy)
had a lower bacterial count of several salivary-spe-
cific bacteria compared with HIV-uninfected controls
(158).
When considering the treatment of periodontal
diseases in patients in the developing world, an
important question for the provider would be
whether inflamed periodontal tissues per se are
more susceptible to HIV infection. In periodontal
disease there is an increase in HIV primary recep-
tors (gp120) and co-receptors (such as CCR5) in
gingival cells but, counterbalancing this effect, a
concomitant tenfold increase in antiviral alpha de-
fensin-1 (29). Alpha defensin-1 is a protein of the
innate immune system, produced by neutrophils
and natural killer cells that have antiviral activity.
Therefore, to date it is unclear as to which of these
two opposing effects may play a bigger role. Two
other protective mechanisms against HIV invasion
of the oral cavity should also be considered: human
beta-defensins produced by oral epithelial cells,
which may play a protective role (29, 79); and the
oral mucosa, which normally expresses low levels of
CCR5 and may thus account for the low binding
affinity of the HIV to the oral epithelium (29).
Therefore, low expression of HIV-1 co-receptors in
healthy patients and high expression of alpha-
defensin in patients with chronic periodontitis may
provide protection from oral HIV-1 infection.
Periodontal disease in HIV ⁄ AIDS
Treatment of HIV-associated oral
and periodontal lesions in
developing and developed
countries
Treatment strategies in both developing and devel-
oped countries should include both general antiviral
approaches to the HIV and antimicrobial approaches
to suspected fungal, viral and bacterial etiologies of
the specific periodontal and oral diseases and con-
ditions that are associated with HIV infection, as well
as for conventional periodontal diseases. In both
developing and developed countries, the control and
elimination of candida infection may be a critical
approach in the prevention of overt clinical oral
candidiasis and in reducing the incidence and slow-
ing the progression of both common and atypical
necrotizing periodontal diseases in HIV-infected
individuals.
For treating oral candidiasis, a number of treat-
ment options are available and include both topical
and systemic antifungal drugs. The main classes of
antifungal agents used for the treatment of oral
candidiasis are polyenes (e.g. nystatin and ampho-
tericin), imidazoles (e.g. clotrimazole) and triazoles
(such as fluconazole). Even though topical agents
may be effective, they are very often unpalatable and
their use can be inconvenient. A low-dose miconaz-
ole mucoadhesive tablet (10 mg) has been shown to
be as effective as ketoconazole treatment (169). In a
recent study (14) it was reported that a 50-mg
miconazole mucoadhesive buccal tablet was well
tolerated and similar in efficacy to miconazole oral
gel in the treatment of oral candidiasis in patients
with head and neck cancer who were undergoing
radiation therapy. Some other studies have focused
on new delivery modes of antifungal drugs, the use of
natural remedies and the resurgence of older treat-
ments. Slow-release tablets are new methods used in
the treatment of oral candidiasis with the purpose of
sustained local oral drug delivery. To improve pa-
tientsÕ compliance, once-daily application of the
medications should be recommended. It should be
noted that medications used to treat conditions such
as candida infection associated with HIV may have
unfavorable interactions with other medications used
to treat HIV per se and other associated opportunistic
infections. For instance, fluconazole, ketoconazole,
itraconazole, metronidazole, ciprofloxacin, midazo-
lam and triazolam can interact with some antiretro-
viral medications such as zidovudine, nevirapine and
87
Ryder et al.
ritonavir (51). It should also be noted that antiretro-
viral therapy approaches that employ protease
inhibitors may have indirect benefit as antifungal
agents by inhibiting the aspartyl proteases secreted
by candida as part of their invasion into the oral soft
tissues. Thus, the antiproteases used in antiretroviral
therapy may have an indirect, beneficial effect on the
incidence and progression of candida invasion and
may help to reduce the potential role of candida in
necrotizing periodontal diseases (16).
In developing countries where there may be lim-
ited availability of these specific antifungal agents
there is a need to develop and to evaluate less
expensive and easy to access antifungal alternatives.
The use of inexpensive topical therapies such as oil of
melaleuca (tea tree oil), chlorhexidine, povidone-
iodine and gentian violet has been proposed for
managing oral candidiasis in resource-poor coun-
tries. Previous studies have revealed that gentian
violet is a promising and inexpensive antifungal
agent (28, 119, 164). The safety and efficacy of lemon
juice and lemon grass (Cymbopogon citratus) in the
treatment of oral candidiasis in HIV ⁄ AIDS patients
have been investigated and compared with gentian
violet aqueous solution (0.5%) used in the control
group. Lemon juice was found to yield better results
than gentian violet in the treatment of oral candidi-
asis (P < 0.02) (181).
A second atypical periodontal lesion associated
with HIV infection that may have serious conse-
quences on the periodontium is KaposiÕs sarcoma
caused by human herpesvirus-8. In the developing
world, KaposiÕs sarcoma is a common malignant
lesion seen in patients with HIV ⁄ AIDS. The gingiva
and hard palate are usually affected by the lesion
(Fig. 3). A wide range of treatments for KaposiÕs sar-
coma is available. Effective antiretroviral therapy,
especially with the use of protease-inhibitor-con-
taining regimens has been shown to be associated
with a reduction in the incidence of AIDS-related
KaposiÕs sarcoma, a regression in the size and num-
ber of existing lesions and histological regression of
existing KaposiÕs sarcoma lesions (18, 30).
Several antiviral agents, including ganciclovir, fo-
scarnet and cidofovir, have been shown to inhibit the
replication of human herpesvirus-8 in vitro. Appro-
priate treatment can be selected based on the clinical
context of KaposiÕs sarcoma, including HIV status,
and the extent and site of disease. Patients with
limited local disease may undergo intralesional che-
motherapy, cryotherapy, laser therapy, photody-
namic therapy and (infrequently) excisional surgery.
In contrast, radiation therapy can be applied for
88
KaposiÕs sarcoma that is not extensive enough to
warrant systemic therapy but is too extensive to be
treated with intralesional chemotherapy. Systemic
treatments have traditionally involved cytotoxic
chemotherapy using liposomal anthracyclines and
the taxane paclitaxel. These treatments should be
given to patients with rapidly progressing, extensive
cutaneous and ⁄ or visceral KaposiÕs sarcoma. Recent
clinical trials have focussed on other nontraditional
therapies, including thalidomide, rapamycin, bev-
acizumab, sunitinib and sorafenib (30, 162).
When considering periodontal treatment per se for
the HIV-infected patient in both developed and
developing countries, the practitioner must consider
approaches for treating both the relatively less com-
mon atypical periodontal lesions associated with
periodontal disease, such as necrotizing gingivitis,
necrotizing periodontitis and linear gingival ery-
thema, as well as the more common periodontal
conditions, such as plaque-induced gingival disease
and chronic periodontitis. For the treatment of the
more atypical necrotic lesions, the therapeutic prin-
ciples developed in the mid-1980s by Winkler and
others still remain the standard of care in both
developed and developing countries (56, 70, 98, 104,
131, 133, 142, 148, 149, 179, 183). Owing to the high
morbidity of these atypical periodontal conditions, it
would be difficult from both ethical and procedural
standpoints to conduct randomized control clinical
trials to test the efficacy of these approaches. There-
fore, a rigorous evidence-based approach to evaluate
these therapies may not be possible. Reports of the
management of these more atypical periodontal le-
sions generally involve case reports or a series of case
studies (Fig. 10a,b). The basic treatment principles
for these necrotic conditions can be readily applied to
both developing and developed countries with minor
modifications. These principles include some form of
gross scaling to remove visible plaque, soft debris and
necrotic tissue when present. Irrigation with povi-
dine-iodine, a relatively inexpensive antimicrobial
that should be readily available in developing coun-
tries, is often recommended during this debridement
procedure for its anesthetic and antiseptic effects
(56). Following this initial debridement, a more fre-
quent recall ⁄ follow-up interval has been recom-
mended for the HIV-positive patient as these patients
may be more prone to periodontal breakdown
(Fig. 9) (133). In necrotizing forms of periodontal
disease, this therapeutic approach should be given as
soon as possible because bone and soft tissue
necrosis may extend into the palate and adjacent
tissues, leading to a life-threatening condition such

A B
Fig. 10. Treatment of a necrotizing ulcerative periodontitis
lesion in an HIV-infected patient. (a) A necrotic lesion
extending to the alveolar crest is evident between the two
central incisors (arrow). (b) Three weeks after treatment
Fig. 11. Teeth of an HIV-infected patient with a history of
episodes of necrotizing ulcerative gingivitis and peri-
odontitis, now in maintenance therapy. Note the general
reverse architecture that requires special plaque control
by the patient to maintain the enlarged and irregular
interproximal areas, and the stain from long-term use of
chlorhexidine rinse.
as necrotizing stomatitis (144) (Fig. 8a,b). Patients
who have previously had necrotizing gingivitis, peri-
odontitis or stomatitis will usually have permanent
areas of gingival recession, large irregular embrasure
spaces and reverse gingival architecture (Fig. 11).
Plaque control is essential in these areas and may
require special brushes, toothpicks or specially
shaped cleaners to access these larger residual de-
fects.
Where antibiotics are more readily available in
developing countries, it should be noted that clinical
centers who treat relatively large cohorts of HIV-in-
fected patients recommend the use of certain anti-
biotics, such as metronidazole, as valuable adjuncts
to treatment (131). However, antibiotics should be
used with caution because of the risk of overgrowth
of candida species (144). Narrow-spectrum antibiot-
ics, such as metronidazole, may leave a greater pro-
portion of gram-positive flora intact and thus prevent
candida overgrowth. However, more recently, the use
Periodontal disease in HIV ⁄ AIDS
with debridement of necrotic tissue, systemic antibiotics
and antimicrobial rinses, the necrotic features of the lesion
have resolved leaving the altered architecture in this
interproximal area.
of a broad-spectrum antibiotic, such as tetracycline
or metronidazole, as an aid in periodontal treatment
has also been a factor for the development of su-
perinfections by resistant bacteria and Candida spe-
cies (154). Thus, the introduction of new drugs, such
as the next generation of azoles, is essential before
the onset of emergent species in periodontal disease.
In the dental literature there are several case re-
ports, employing these management principles,
which demonstrate a reduction in the acute symp-
toms of these conditions However, if there is no
resolution of these lesions with this therapeutic ap-
proach, the practitioner should consider other oral
lesions associated with HIV infection that may have a
similar clinical picture. These include lymphomas,
neoplastic growths and severe herpetic or aphthous
ulcerations of the gingiva (46, 65, 123). Where a
neoplasm is suspected, a biopsy of the area should be
performed to confirm the diagnosis.
With the development of new strategies for con-
trolling the HIV, such as antiretroviral therapy ⁄ HA-
ART, there may be a significant delay in the devel-
opment of overt AIDS in a larger proportion of the
infected population. As previously discussed, this has
led, in turn, to a downward trend in the occurrence of
some of these atypical and necrotic periodontal
conditions in the HIV-infected patient in both
developed and developing countries. However the
dental practitioner is still faced with the problem of
treating HIV patients with more common periodontal
conditions such as gingival inflammation associated
with plaque alone or modified by other factors. This
issue is of particular importance when considering
possible associations of more conventional peri-
odontal diseases in HIV-infected patients with sys-
temic diseases and conditions (172, 173). Therefore,
in developing countries the reduction of inflamma-
tion and plaque biofilm in conventional periodontal
diseases may have broad general public health ben-
89
Ryder et al.
efits. The question facing dental practitioners is how
the HIV infection in general, and specifically the
immune status, may affect conventional therapeutic
approaches to these diseases. In studies on the re-
sponse to periodontal treatment, as measured by
conventional parameters of attachment loss and
pocket depths, similar results were found for both
HIV-positive and HIV-negative patients (68, 78). As
with non-HIV-infected patients, oral hygiene com-
pliance is a key factor for successful treatment (68).
As discussed previously in the management of
necrotizing periodontal diseases, the vast majority of
HIV-infected periodontal patients with necrotic and ⁄
or conventional conditions will require some form of
debridement to remove local irritants and reduce
inflammation. Recent studies have demonstrated the
effectiveness of this approach in HIV-infected pa-
tients with periodontal diseases regardless of the
original CD4 counts or HIV staging (87). This
debridement approach may be the only feasible ap-
proach for the treatment of plaque-associated peri-
odontal diseases in developing countries. A concern
of the practitioner treating the HIV patient, particu-
larly in the developing world, may be the effects of
developing a systemic bacteremia and subsequent
systemic infections and, as discussed in the previous
section, possible activation of the HIV in distant
systemic sites. To date, the one study that investi-
gated this potential problem found a higher per-
centage of transient bacteremias in HIV-infected
patients immediately after scaling (89), which re-
turned to baseline levels after 30 min. Therefore,
from this limited evidence, it appears that it is safe to
perform scaling and debridement in HIV-infected
patients.
A second major concern of the practitioner is
whether the immune status of the HIV-infected pa-
tient could alter the decision to perform periodontal
surgical procedures. To date, no studies have been
performed to compare the healing response after
periodontal surgery between HIV-infected and non-
HIV-infected individuals. Some of the more complex
periodontal surgical procedures performed in devel-
oped countries may not be commonly performed in
developing countries. However, in developing coun-
tries, surgical extraction of teeth with more severe
periodontal involvement may be a more common
approach. With regard to the risks of tooth extraction
in HIV-infected patients, several studies have com-
pared healing responses between HIV-infected and
non-HIV-infected patients (34, 45, 135, 145): the
majority of these studies showed slight, but not sig-
nificant, increases in postoperative adverse events in
90
HIV-infected patients (15, 40, 41, 129). However, the
dental practitioner should bear in mind that the
immune status in general and the CD4 count in
particular may alter surgical decisions. For example,
low CD4 counts may affect the healing response to
periodontal treatment. In addition, some HIV-in-
fected subjects may exhibit a markedly depressed
platelet count during the course of their HIV infec-
tion (41), which may have an adverse effect on the
bleeding and clotting time during and after peri-
odontal surgical procedures. Therefore, in both
developing and developed countries, if tooth extrac-
tion is indicated the dental practitioner should ob-
tain, if at all possible, the necessary information
regarding the HIV-infected patientÕs most current
immune and hematological status prior to consider-
ing elective surgical procedures. In addition, patients
with platelet counts of <60,000 cells ⁄ mm3 and ⁄ or
neutrophil counts of <500 cells ⁄ mm3 may require
prophylactic antibiotic treatment before periodontal
procedures (27).
Conclusions and future directions
HIV ⁄ AIDS is a globally devastating problem. Con-
trolling and ending this pandemic requires a multi-
faceted global effort involving expanded testing,
treatment, striving for a cure in at least a proportion
of infected individuals and comprehensive preven-
tion programs. No single nation or organization can
accomplish this. A truly global commitment and ef-
fort are essential. It is believed that based on solid
scientific data and universal access to effective HIV
prevention, treatment, care and support, there is an
unprecedented opportunity to control and ultimately
end the AIDS pandemic (39).
In the postantiretroviral therapy era there have
been changes in the patterns of the incidence and
prevalence of both the more atypical periodontal
conditions, such as linear gingival erythema, necro-
tizing gingivitis and periodontitis, as well as more
conventional periodontal diseases, such as chronic
periodontitis (166). However, as discussed in this
review, the use of these antiviral approaches may
have both beneficial and detrimental effects on
oral ⁄ periodontal health and disease. In addition,
chronic local and systemic dissemination of the
microbiota and inflammatory products of common
periodontal diseases, found in greater prevalence in
developing countries, may have adverse effects both
on the progression of HIV infection and in the
effectiveness of the antiretroviral therapies. These

findings suggest that there is a need for more exten-
sive collaborative multicenter longitudinal studies to
monitor the progression of periodontal disease and
HIV infection with appropriate multidisciplinary
therapies. Parameters to be investigated should in-
clude probing depth, recession, the percentage of
radiographic bone loss, the prevalence and number
of periodontal pathogens, atypical microorganisms
and viruses in periodontal pockets, as well as viru-
lence factors and the host response (166).
In both the developing world and the developed
world perhaps the most critical issues with HIV and
oral conditions in general, and periodontal condi-
tions in particular, are the development of inexpen-
sive and easy-to-use diagnostic ⁄ screening and
treatment approaches for both adults and children.
These broad-based approaches should be readily
accessible and acceptable to both dental and non-
dental health providers and their patient populations.
Where it is both clinically feasible and ethically
acceptable, the safety and efficacy of topical and
systemic treatments of oral lesions associated with
HIV infection should be studied further using well-
designed randomized clinical trials. There is also a
need to develop newer drugs for the treatment of
resistant microorganisms. Finally, standardized out-
come measures should be developed for future clin-
ical trials to allow comparison of studies using dif-
ferent populations.
References
1. Aas JA, Barbuto SM, Alpagot T, Olsen I, Dewhirst FE, Pa-
ster BJ. Subgingival plaque microbiota in HIV positive
patients. J Clin Periodontol 2007: 34: 189–195.
2. Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler
AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana
KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N,
Mlotshwa M, Morris L, Taylor D. Effectiveness and safety
of tenofovir gel, an antiretroviral microbicide, for the
prevention of HIV infection in women. Science 2010: 329:
1168–1174.
3. Aichelmann-Reidy ME, Wrigley DL, Gunsolley JC. HIV
infection and bone loss due to periodontal disease. J Pe-
riodontol 2010: 81: 877–884.
4. Alpagot T, Font K, Lee A. Longitudinal evaluation of GCF
IFN-gamma levels and periodontal status in HIV+ pa-
tients. J Clin Periodontol 2003: 30: 944–948.
5. Alpagot T, Konopka K, Bhattacharyya M, Gebremedhin S,
Duzgunes N. The association between gingival crevicular
fluid TGF-beta1 levels and periodontal status in HIV-1(+)
patients. J Periodontol 2008: 79: 123–130.
6. Alpagot T, Remien J, Bhattacharyya M, Konopka K, Lun-
dergan W, Duzgunes N. Longitudinal evaluation of pros-
Periodontal disease in HIV ⁄ AIDS
taglandin E2 (PGE2) and periodontal status in HIV+
patients. Arch Oral Biol 2007: 52: 1102–1108.
7. Alpagot T, Suzara V, Bhattacharyya M. The associations
between gingival crevice fluid matrix metalloproteinase-9,
tissue inhibitor of metalloproteinase-1 and periodontitis
in human immunodeficiency virus-positive patients.
J Periodontal Res 2006: 41: 491–497.
8. Alves M, Mulligan R, Passaro D, Gawell S, Navazesh M,
Phelan J, Greenspan D, Greenspan JS. Longitudinal eval-
uation of loss of attachment in HIV-infected women
compared to HIV-uninfected women. J Periodontol 2006:
77: 773–779.
9. Anil S, Challacombe SJ. Oral lesions of HIV and AIDS in
Asia: an overview. Oral Dis 1997: 3(Suppl 1): S36–40.
10. Arendorf TM, Bredekamp B, Cloete CA, Sauer G. Oral
manifestations of HIV infection in 600 South African pa-
tients. J Oral Pathol Med 1998: 27: 176–179.
11. Arendorf TM, Bredekamp B, Cloete C, Wood R, OÕKeefe E.
Intergroup comparisons of oral lesions in HIV-positive
South Africans. Oral Dis 1997: 3(Suppl 1): S54–57.
12. Baqui AA, Meiller TF, Jabra-Rizk MA, Zhang M, Kelley JI,
Falkler WA Jr. Enhanced interleukin 1 beta, interleukin 6
and tumor necrosis factor alpha in gingival crevicular fluid
from periodontal pockets of patients infected with human
immunodeficiency virus 1. Oral Microbiol Immunol 2000:
15: 67–73.
13. Barr C, Lopez MR, Rua-Dobles A. Periodontal changes by
HIV serostatus in a cohort of homosexual and bisexual
men. J Clin Periodontol 1992: 19: 794–801.
14. Bensadoun RJ, Daoud J, El Gueddari B, Bastit L, Gourmet
R, Rosikon A, Allavena C, Ceruse P, Calais G, Attali P.
Comparison of the efficacy and safety of miconazole 50-
mg mucoadhesive buccal tablets with miconazole 500-
mg gel in the treatment of oropharyngeal candidiasis: a
prospective, randomized, single-blind, multicenter,
comparative, phase III trial in patients treated with
radiotherapy for head and neck cancer. Cancer 2008:
112: 204–211.
15. Bonito AJ, Patton LL, Shugars DA, Lohr KN, Nelson JP,
Bader JP, Jackman AW. Management of dental patients
who are HIV positive. Evid Rep Technol Assess (Summ)
2001: 37: 1–6.
16. Borg-von Zepelin M, Meyer I, Thomssen R, Wurzner R,
Sanglard D, Telenti A, Monod M. HIV-Protease inhibitors
reduce cell adherence of Candida albicans strains by
inhibition of yeast secreted aspartic proteases. J Invest
Dermatol 1999: 113: 747–751.
17. Brito A, Escalona LA, Correnti M, Perrone M, Bravo IM,
Tovar V. Periodontal conditions and distribution of
Prevotella intermedia, Porphyromonas gingivalis and
Aggregatibacter actinomycetemcomitans in HIV-infected
patients undergoing anti-retroviral therapy and in an HIV-
seronegative group of the Venezuelan population. Acta
Odontol Latinoam 2008: 21: 89–96.
18. Casper C, Wald A. The use of antiviral drugs in the pre-
vention and treatment of Kaposi sarcoma, multicentric
Castleman disease and primary effusion lymphoma. Curr
Top Microbiol Immunol 2007: 312: 289–307.
19. Cavasin Filho JC, Giovani EM. Xerostomy, dental caries
and periodontal disease in HIV+ patients. Braz J Infect Dis
2009: 13: 13–17.
91
Ryder et al.
20. CDC (Centers for Disease Control). KaposiÕs sarcoma and
Pneumocystis pneumonia among homosexual men: New
York City and California. MMWR Morb Mortal Wkly Rep
1981: 30: 305–308.
21. Chattin BR, Ishihara K, Okuda K, Hirai Y, Ishikawa T.
Specific microbial colonizations in the periodontal sites of
HIV-infected subjects. Microbiol Immunol 1999: 43: 847–
852.
22. Chidzonga MM. HIV ⁄ AIDS orofacial lesions in 156 Zim-
babwean patients at referral oral and maxillofacial surgical
clinics. Oral Dis 2003: 9: 317–322.
23. Choromanska M, Waszkiel D. Periodontal status and
treatment needs in HIV-infected patients. Adv Med Sci
2006: 51(Suppl 1): 110–113.
24. Cobb CM, Ferguson BL, Keselyak NT, Holt LA, MacNeill
SR, Rapley JW. A TEM ⁄ SEM study of the microbial plaque
overlying the necrotic gingival papillae of HIV-seroposi-
tive, necrotizing ulcerative periodontitis. J Periodontal Res
2003: 38: 147–155.
25. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseini-
pour MC, Kumarasamy N, Hakim JG, Kumwenda J,
Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S,
Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Es-
hleman SH, Piwowar-Manning E, Wang L, Makhema J,
Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D,
Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE,
Nielsen-Saines K, Celentano D, Essex M, Fleming TR.
Prevention of HIV-1 infection with early antiretroviral
therapy. N Engl J Med 2011: 365: 493–505.
26. Contreras A, Mardirossian A, Slots J. Herpesviruses in HIV-
periodontitis. J Clin Periodontol 2001: 28: 96–102.
27. Coogan M, Greenspan J, Challacombe S. Oral lesions in
infection with human immunodeficiency virus. Bull World
Health Organ 2005: 83: 1–16.
28. Cullough MJWA, Hodgson TA, Jorge JA. Susceptibility of
oral yeast isolated from patients in Blantyre, Malawi to
fluconazole and gentian violet [abstract 644]. In: Thirty-
ninth Annual Meeting of the Infectious Diseases Society of
America. San Francisco, CA: 2001.
29. Cutler CW, Jotwani R. Oral mucosal expression of HIV-1
receptors, co-receptors, and alpha-defensins: tableau of
resistance or susceptibility to HIV infection? Adv Dent Res
2006: 19: 49–51.
30. Di Lorenzo G, Konstantinopoulos PA, Pantanowitz L, Di
Trolio R, De Placido S, Dezube BJ. Management of
AIDS-related KaposiÕs sarcoma. Lancet Oncol 2007: 8: 167–
176.
31. Dias EP, Israel MS, Silva Junior A, Maciel VA, Gagliardi JP,
Oliveira RH. Prevalence of oral hairy leukoplakia in 120
pediatric patients infected with HIV-1. Braz Oral Res 2006:
20: 103–107.
32. Dios PD, Ocampo A, Miralles C, Limeres J, Tomas I.
Changing prevalence of human immunodeficiency virus-
associated oral lesions. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 2000: 90: 403–404.
33. Dodd CL, Winkler JR, Heinic GS, Daniels TE, Yee K,
Greenspan D. Cytomegalovirus infection presenting as
acute periodontal infection in a patient infected with the
human immunodeficiency virus. J Clin Periodontol 1993:
20: 282–285.
34. Dodson TB. HIV status and the risk of post-extraction
complications. J Dent Res 1997: 76: 1644–1652.
92
35. Duggal MS, Abudiak H, Dunn C, Tong HJ, Munyombwe
T. Effect of CD4+ lymphocyte count, viral load, and
duration of taking anti-retroviral treatment on pres-
ence of oral lesions in a sample of South African chil-
dren with HIV+ ⁄ AIDS. Eur Arch Paediatr Dent 2010: 11:
242–246.
36. ECC. EC-Clearinghouse on Oral Problems related to HIV
infection and WHO collaborating center on Oral mani-
festations of the immunodeficiency virus Classification
and diagnosis criteria for oral lesion in HIV infection.
J Oral Pathol Med 1993: 22: 289–291.
37. Engeland CG, Jang P, Alves M, Marucha PT, Califano J.
HIV infection and tooth loss. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2008: 105: 321–326.
38. Falasca K, Vecchiet F, Ucciferri C, Vignale F, Conti P,
Pizzigallo A, Piattelli A, Vecchiet J. Periodontitis and
cytokine patterns in HIV positive patients. Eur J Med Res
2008: 13: 163–168.
39. Fauci AS. AIDS: let science inform policy. Science 2011:
333: 13.
40. Fauci A, Lane HC. Human Immunodeficiency Virus (HIV)
Disease: AIDS and Related Disorders. In: Fauci AS,
Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper
DL, Hauser SL, Longo DL. editors. HarrisonÕs Principles of
Internal Medicine, 14th edn. New York, NY: McGraw Hill,
1998: 1791–1856.
41. Fauci A, Lane HC. Human Immunodeficiency Virus Dis-
ease: AIDS and Related Disorders. In: Kasper DL, Braun-
wald E, Hauser SL, Longo DL, editor. HarrisonÕs Principles
of Internal Medicine, 16th edn. New York, NY: McGraw
Hill, 2005: 1076–1139
42. Flint S, Tappuni A. Markers of immunodeficiency and
Mechanisms of HAART Therapy on Oral Lesions. Adv Dent
Res 2006: 19: 146–151.
43. Folkers GK, Fauci AS. Controlling and ultimately ending
the HIV ⁄ AIDS pandemic: a feasible goal. JAMA 2010: 304:
350–351.
44. Giacaman RA, Asrani AC, Gebhard KH, Dietrich EA, Vachar-
aksa A, Ross KF, Herzberg MC. Porphyromonas gingivalis
induces CCR5-dependent transfer of infectious HIV-1 from
oral keratinocytes to permissive cells. Retrovirology 2008: 5:
29.
45. Glick M, Abel SN, Muzyka BC, DeLorenzo M. Dental
complications after treating patients with AIDS. J Am Dent
Assoc 1994: 125: 296–301.
46. Glick M, Cleveland DB, Salkin LM, Alfaro-Miranda M,
Fielding AF. Intraoral cytomegalovirus lesion and HIV-
associated periodontitis in a patient with acquired
immunodeficiency syndrome. Oral Surg Oral Med Oral
Pathol 1991: 72: 716–720.
47. Glick M, Muzyka BC, Lurie D, Salkin LM. Oral manifes-
tations associated with HIV-related disease as markers for
immune suppression and AIDS. Oral Surg Oral Med Oral
Pathol 1994: 77: 344–349.
48. Gomez RS, da Costa JE, Loyola AM, de Araujo NS, de
Araujo VC. Immunohistochemical study of linear gingival
erythema from HIV-positive patients. J Periodontal Res
1995: 30: 355–359.
49. Gona P, Van Dyke RB, Williams PL, Dankner WM, Cher-
noff MC, Nachman SA, Seage GR III. Incidence of oppor-
tunistic and other infections in HIV-infected children in
the HAART era. JAMA 2006: 296: 292–300.

50. Goncalves Lde S, Ferreira SM, Silva A Jr, Villoria GE,
Costinha LH, Souto R, Uzeda MD, Colombo AP. Associa-
tion of T CD4 lymphocyte levels and subgingival micro-
biota of chronic periodontitis in HIV-infected Brazilians
under HAART. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 2004: 97: 196–203.
51. Goncalves Lde S, Goncalves BM, de Andrade MA, Alves FR,
Junior AS. Drug interactions during periodontal therapy in
HIV-infected subjects. Mini Rev Med Chem 2010: 10: 766–
772.
52. Gonzalez OA, Ebersole JL, Huang CB. Supernatants from
oral epithelial cells and gingival fibroblasts modulate hu-
man immunodeficiency virus type 1 promoter activation
induced by periodontopathogens in monocytes ⁄ macro-
phages. Mol Oral Microbiol 2010: 25: 136–149.
53. Gonzalez OA, Li M, Ebersole JL, Huang CB. HIV-1 reacti-
vation induced by periodontal pathogens Fusobacterium
nucleatum and Porphyromonas gingivalis involves TLR2
and TLR9 activation in monocytes ⁄ macrophages. Clin
Vaccine Immunol 2010: 17: 1417–1427. Erratum in: Clin
Vaccine Immunol 2010: 17: 1825.
54. Grande SR, Imbronito AV, Okuda OS, Lotufo RF, Ma-
galhaes MH, Nunes FD. Herpes viruses in periodontal
compromised sites: comparison between HIV-positive
and -negative patients. J Clin Periodontol 2008: 35: 838–
845.
55. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY,
Vargas L, Goicochea P, Casapia M, Guanira-Carranza JV,
Ramirez-Cardich ME, Montoya-Herrera O, Fernandez T,
Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M,
Bekker LG, Mayer KH, Kallas EG, Amico KR, Mulligan K,
Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle
B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe
HS, Martinez AI, Burns DN, Glidden DV. Preexposure
chemoprophylaxis for HIV prevention in men who have
sex with men. N Engl J Med 2010: 363: 2587–2599.
56. Grassi MWC, Winkler JR, Murray PA. Management of HIV-
associated periodontal diseases. In: Robertson PB,
Greenspan JS, editors. Perspectives on Oral Manifestations
of AIDS, San Diego, Calif. Littleton, MA: PSG Publishing Co
Inc, 1988: 119–130.
57. Graves DT, Cochran D. The contribution of interleukin-1
and tumor necrosis factor to periodontal tissue destruc-
tion. J Periodontol 2003: 74: 391–401.
58. Grbic JT, Lamster IB, Mitchell-Lewis D. Inflammatory and
immune mediators in crevicular fluid from HIV-infected
injecting drug users. J Periodontol 1997: 68: 249–255.
59. Grbic JT, Mitchell-Lewis DA, Fine JB, Phelan JA, Bucklan
RS, Zambon JJ, Lamster IB. The relationship of candidiasis
to linear gingival erythema in HIV-infected homosexual
men and parenteral drug users. J Periodontol 1995: 66:
30–37.
60. Greenspan D, Canchola AJ, MacPhail LA, Cheikh B,
Greenspan JS. Effect of highly active antiretroviral therapy
on frequency of oral warts. Lancet 2001: 357: 1411–1412.
61. Greenspan D, Gange SJ, Phelan JA, Navazesh M, Alves ME,
MacPhail LA, Mulligan R, Greenspan JS. Incidence of oral
lesions in HIV-1-infected women: reduction with HAART.
J Dent Res 2004: 83: 145–150.
62. Greenspan JS, Greenspan D. The epidemiology of the oral
lesions of HIV infection in the developed world. Oral Dis
2002: 8(Suppl 2): 34–39.
Periodontal disease in HIV ⁄ AIDS
63. Greenwood I, Zakrzewska JM, Robinson PG. Changes in
the prevalence of HIV-associated mucosal disease at
a dedicated clinic over 7 years. Oral Dis 2002: 8: 90–
94.
64. Hamza OJ, Matee MI, Simon EN, Kikwilu E, Moshi MJ,
Mugusi F, Mikx FH, Verweij PE, van der Ven AJ. Oral
manifestations of HIV infection in children and adults
receiving highly active anti-retroviral therapy [HAART] in
Dar es Salaam, Tanzania. BMC Oral Health 2006: 6: 12.
65. Hernandez Vallejo G, Garcia MD, Lopez A, Mendieta C,
Moskow BS. Unusual periodontal findings in an AIDS
patient with BurkittÕs lymphoma. A case report. J Period-
ontol 1989: 60: 723–727.
66. Hodgson TA. HIV-associated oral lesions: prevalence in
Zambia. Oral Dis 1997: 3(Suppl 1): S46–50.
67. Hodgson TA, Greenspan D, Greenspan JS. Oral lesions of
HIV disease and HAART in industrialized countries. Adv
Dent Res 2006: 19: 57–62.
68. Hofer D, Hammerle CH, Grassi M, Lang NP. Long-term
results of supportive periodontal therapy (SPT) in HIV-
seropositive and HIV-seronegative patients. J Clin Peri-
odontol 2002: 29: 630–637.
69. Holmstrup P. Non-plaque-induced gingival lesions. Ann
Periodontol 1999: 4: 20–31.
70. Holmstrup P, Westergaard J. Periodontal diseases in HIV-
infected patients. J Clin Periodontol 1994: 21: 270–280.
71. Howell RB, Jandinski JJ, Palumbo P, Shey Z, Houpt MI.
Oral soft tissue manifestations and CD4 lymphocyte
counts in HIV-infected children. Pediatr Dent 1996: 18:
117–120.
72. Huang CB, Alimova YV, Ebersole JL. HIV-1 reactivation in
HIV-latently infected dendritic cells by oral microorgan-
isms and LPS. Cell Immunol 2011: 268: 105–111.
73. Huang CB, Alimova YV, Strange S, Ebersole JL. Polybac-
terial challenge enhances HIV reactivation in latently in-
fected macrophages and dendritic cells. Immunology
2011: 132: 401–409.
74. Huang CB, Emerson KA, Gonzalez OA, Ebersole JL. Oral
bacteria induce a differential activation of human immu-
nodeficiency virus-1 promoter in T cells, macrophages
and dendritic cells. Oral Microbiol Immunol 2009: 24: 401–
407.
75. Imai K, Ochiai K, Okamoto T. Reactivation of latent HIV-1
infection by the periodontopathic bacterium Porphyro-
monas gingivalis involves histone modification. J Immu-
nol 2009: 182: 3688–3695.
76. Johansson I, Saellstrom AK, Rajan BP, Parameswaran A.
Salivary flow and dental caries in Indian children suffering
from chronic malnutrition. Caries Res 1992: 26: 38–43.
77. Jonsson N, Zimmerman M, Chidzonga MM, Jonsson K.
Oral manifestations in 100 Zimbabwean HIV ⁄ AIDS pa-
tients referred to a specialist centre. Cent Afr J Med 1998:
44: 31–34.
78. Jordan RA, Gangler P, Johren HP. Clinical treatment out-
comes of periodontal therapy in HIV-seropositive patients
undergoing highly active antiretroviral therapy. Eur J Med
Res 2006: 11: 232–235.
79. Jotwani R, Muthukuru M, Cutler CW. Increase in HIV
receptors ⁄ co-receptors ⁄ alpha-defensins in inflamed hu-
man gingiva. J Dent Res 2004: 83: 371–377.
80. Khongkunthian P, Grote M, Isaratanan W, Piyaworawong
S, Reichart PA. Oral manifestations in 45 HIV-positive
93
Ryder et al.
children from Northern Thailand. J Oral Pathol Med 2001:
30: 549–552.
81. King MD, Reznik DA, OÕDaniels CM, Larsen NM, Oster-
holt D, Blumberg HM. Human papillomavirus-associated
oral warts among human immunodeficiency virus-sero-
positive patients in the era of highly active antiretroviral
therapy: an emerging infection. Clin Infect Dis 2002: 34:
641–648.
82. Kreimer AR, Alberg AJ, Daniel R, Gravitt PE, Viscidi R,
Garrett ES, Shah KV, Gillison ML. Oral human papillo-
mavirus infection in adults is associated with sexual
behavior and HIV serostatus. J Infect Dis 2004: 189: 686–
698.
83. Kroidl A, Schaeben A, Oette M, Wettstein M, Herfordt A,
Haussinger D. Prevalence of oral lesions and periodontal
diseases in HIV-infected patients on antiretroviral therapy.
Eur J Med Res 2005: 10: 448–453.
84. Lamster IGJ, Grbic J, Fine J, Bucklan R, Mitchall-Lewis D,
Phelan J, Zambon J. A critical review of periodontal dis-
eases as a manifestation of HIV infection. In: Greenspan
JS, Greeenspan D, editors. Oral Manifestations of HIV
Infection. Chicago, IL: Quintessence Publishing Company,
1995: 247–256.
85. Lamster IB, Grbic JT, Bucklan RS, Mitchell-Lewis D, Rey-
nolds HS, Zambon JJ. Epidemiology and diagnosis of HIV-
associated periodontal diseases. Oral Dis 1997: 3(Suppl 1):
S141–148.
86. Lamster IB, Grbic JT, Mitchell-Lewis DA, Begg MD, Mitchell
A. New concepts regarding the pathogenesis of periodontal
disease in HIV infection. Ann Periodontol 1998: 3: 62–75.
87. Lemos SS, Oliveira FA, Vencio EF. Periodontal disease and
oral hygiene benefits in HIV seropositive and AIDS pa-
tients. Med Oral Patol Oral Cir Bucal 2010: 15: e417–421.
88. Lindan CP, Allen S, Serufilira A, Lifson AR, Van de Perre P,
Chen-Rundle A, Batungwanayo J, Nsengumuremyi F,
Bogaerts J, Hulley S. Predictors of mortality among HIV-
infected women in Kigali, Rwanda. Ann Intern Med 1992:
116: 320–328.
89. Lucartorto FM, Franker CK, Maza J. Postscaling bactere-
mia in HIV-associated gingivitis and periodontitis. Oral
Surg Oral Med Oral Pathol 1992: 73: 550–554.
90. Lucht E, Heimdahl A, Nord CE. Periodontal disease in HIV-
infected patients in relation to lymphocyte subsets and
specific micro-organisms. J Clin Periodontol 1991: 18: 252–
256.
91. Madinier I, Monteil RA. Human papillomaviruses in oral
epithelial lesions. Comparative study between histopa-
thology and immunohistochemistry in routine diagnosis.
J Biol Buccale 1987: 15: 105–110.
92. Magalhaes MG, Bueno DF, Serra E, Goncalves R. Oral
manifestations of HIV positive children. J Clin Pediatr
Dent 2001: 25: 103–106.
93. Mardirossian A, Contreras A, Navazesh M, Nowzari H,
Slots J. Herpesviruses 6, 7 and 8 in HIV- and non-HIV-
associated periodontitis. J Periodontal Res 2000: 35: 278–
284.
94. Mataftsi M, Skoura L, Sakellari D. HIV infection and
periodontal diseases: an overview of the post-HAART era.
Oral Dis 2011: 17: 13–25.
95. McArthur CP, Africa CW, Castellani WJ, Luangjamekorn
NJ, McLaughlin M, Subtil-DeOliveira A, Cobb C, Howard
P, Gustafson S, Palmer D, Miranda RN. Salivary gland
94
disease in HIV ⁄ AIDS and primary SjogrenÕs syndrome:
analysis of collagen I distribution and histopathology in
American and African patients. J Oral Pathol Med 2003: 32:
544–551.
96. McKaig RG, Thomas JC, Patton LL, Strauss RP, Slade GD,
Beck JD. Prevalence of HIV-associated periodontitis and
chronic periodontitis in a southeastern US study group.
J Public Health Dent 1998: 58: 294–300.
97. McNeil D. New cases of AIDS hit plateau. New York Times
November 21, 2011.
98. Mealey BL. Periodontal implications: medically compro-
mised patients. Ann Periodontol 1996: 1: 256–321.
99. Mellanen L, Ingman T, Lahdevirta J, Lauhio A, Ainamo A,
Konttinen YT, Sukura A, Salo T, Sorsa T. Matrix metallo-
proteinases-1, -3 and -8 and myeloperoxidase in saliva of
patients with human immunodeficiency virus infection.
Oral Dis 1996: 2: 263–271.
100. Mellanen L, Salo T, Ingman T, Konttinen YT, Lahdevirta J,
Sorsa T. 72-kDa and 92-kDa gelatinases in saliva of pa-
tients with human immunodeficiency virus infection. Acta
Odontol Scand 1998: 56: 135–142.
101. Miziara ID, Weber R. Oral candidosis and oral hairy leu-
koplakia as predictors of HAART failure in Brazilian HIV-
infected patients. Oral Dis 2006: 12: 402–407.
102. Moore LV, Moore WE, Riley C, Brooks CN, Burmeister JA,
Smibert RM. Periodontal microflora of HIV positive sub-
jects with gingivitis or adult periodontitis. J Periodontol
1993: 64: 48–56.
103. Moskow BS, Hernandez G. Aggressive periodontal
destruction and herpes zoster in a suspected AIDS patient.
J Parodontol 1991: 10: 359–369.
104. Murray PA. Periodontal diseases in patients infected by
human immunodeficiency virus. Periodontol 2000 1994: 6:
50–67.
105. Murray PA, Grassi M, Winkler JR. The microbiology of
HIV-associated periodontal lesions. J Clin Periodontol
1989: 16: 636–642.
106. Murray PA, Winkler JR, Peros WJ, French CK, Lippke JA.
DNA probe detection of periodontal pathogens in HIV-
associated periodontal lesions. Oral Microbiol Immunol
1991: 6: 34–40.
107. Myint M, Odden K, Schreurs O, Halstensen TS, Schenck K.
The gingival plasma cell infiltrate in HIV-positive patients
with periodontitis is disorganized. J Clin Periodontol 1999:
26: 358–365.
108. Myint MM, Steinsvoll S, Odden K, Dobloug J, Schenck K.
Salivary IgA responses to bacteria in dental plaque as re-
lated to periodontal and HIV infection status. Eur J Oral
Sci 1997: 105: 562–570.
109. Myint M, Steinsvoll S, Yuan ZN, Johne B, Helgeland K,
Schenck K. Highly increased numbers of leukocytes in
inflamed gingiva from patients with HIV infection. AIDS
2002: 16: 235–243.
110. Myint M, Yuan ZN, Schenck K. Reduced numbers of
Langerhans cells and increased HLA-DR expression in
keratinocytes in the oral gingival epithelium of HIV-in-
fected patients with periodontitis. J Clin Periodontol 2000:
27: 513–519.
111. Navazesh M, Mulligan R, Barron Y, Redford M, Greenspan
D, Alves M, Phelan J. A 4-year longitudinal evaluation of
xerostomia and salivary gland hypofunction in the
WomenÕs Interagency HIV Study participants. Oral

Surg Oral Med Oral Pathol Oral Radiol Endod 2003: 95:
693–698.
112. Navazesh MMR, Pogoda J, Greenspan D, Alves M, Phelan
J, Greenspan J, Slots J. The effect of HAART on salivary
microbiota in the WomenÕs Interagency HIV Study
(WIHS). Oral Surg Oral Med Oral Pathol Oral Radiol En-
dod 2005: 100: 701–708.
113. Ndiaye CF, Critchlow CW, Leggott PJ, Kiviat NB, Ndoye I,
Robertson PB, Georgas KN. Periodontal status of HIV-1
and HIV-2 seropositive and HIV seronegative female
commercial sex workers in Senegal. J Periodontol 1997: 68:
827–831.
114. Nicolatou-Galitis O, Velegraki A, Paikos S, Economopou-
lou P, Stefaniotis T, Papanikolaou IS, Kordossis T. Effect of
PI-HAART on the prevalence of oral lesions in HIV-1 in-
fected patients. A Greek study. Oral Dis 2004: 10: 145–150.
115. Nittayananta W, Chanowanna N, Jealae S, Nauntofte B,
Stoltze K. Hyposalivation, xerostomia and oral health
status of HIV-infected subjects in Thailand before HAART
era. J Oral Pathol Med 2010: 39: 28–34.
116. Nittayananta W, Chanowanna N, Sripatanakul S, Winn T.
Risk factors associated with oral lesions in HIV-infected
heterosexual people and intravenous drug users in Thai-
land. J Oral Pathol Med 2001: 30: 224–230.
117. Nittayananta W, Chungpanich S. Oral lesions in a group of
Thai people with AIDS. Oral Dis 1997: 3(Suppl 1): S41–45.
118. Nittayananta W, Talungchit S, Jaruratanasirikul S, Sil-
papojakul K, Chayakul P, Nilmanat A, Pruphetkaew N.
Effects of long-term use of HAART on oral health status of
HIV-infected subjects. J Oral Pathol Med 2010: 39: 397–406.
119. Nyst MJ, Perriens JH, Kimputu L, Lumbila M, Nelson AM,
Piot P. Gentian violet, ketoconazole and nystatin in oro-
pharyngeal and esophageal candidiasis in Zairian AIDS
patients. Ann Soc Belg Med Trop 1992: 72: 45–52.
120. Odden K, Schenck K, Hurlen B. High numbers of T cells in
gingiva from patients with human immunodeficiency
virus (HIV) infection. J Oral Pathol Med 1995: 24: 413–419.
121. Odden K, Schenck K, Koppang H, Hurlen B. Candidal
infection of the gingiva in HIV-infected persons. J Oral
Pathol Med 1994: 23: 178–183.
122. Olaniyi TO, Sunday P. Oral manifestations of HIV infection
in 36 Nigerian children. J Clin Pediatr Dent 2005: 30: 89–
92.
123. Palmer GD, Morgan PR, Challacombe SJ. T-cell lymphoma
associated with periodontal disease and HIV infection. A
case report. J Clin Periodontol 1993: 20: 378–380.
124. Paster BJ, Russell MK, Alpagot T, Lee AM, Boches SK,
Galvin JL, Dewhirst FE. Bacterial diversity in necrotizing
ulcerative periodontitis in HIV-positive subjects. Ann Pe-
riodontol 2002: 7: 8–16.
125. Patel M, Coogan M, Galpin JS. Periodontal pathogens in
subgingival plaque of HIV-positive subjects with chronic
periodontitis. Oral Microbiol Immunol 2003: 18: 199–201.
126. Patton LL, McKaig R. Rapid progression of bone loss in
HIV-associated necrotizing ulcerative stomatitis. J Peri-
odontol 1998: 69: 710–716.
127. Patton LL, McKaig R, Strauss R, Rogers D, Eron JJ Jr.
Changing prevalence of oral manifestations of human
immuno-deficiency virus in the era of protease inhibitor
therapy. Oral Surg Oral Med Oral Pathol Oral Radiol En-
dod 2000: 89: 299–304.
Periodontal disease in HIV ⁄ AIDS
128. Patton LL, Phelan JA, Ramos-Gomez FJ, Nittayananta W,
Shiboski CH, Mbuguye TL. Prevalence and classification of
HIV-associated oral lesions. Oral Dis 2002: 8(Suppl 2): 98–
109.
129. Patton LL, Shugars DA, Bonito AJ. A systematic review of
complication risks for HIV-positive patients undergoing
invasive dental procedures. J Am Dent Assoc 2002: 133:
195–203.
130. Petersen PE. Policy for prevention of oral manifestations
in HIV ⁄ AIDS: the approach of the WHO Global Oral
Health Program. Adv Dent Res 2006: 19: 17–20.
131. Phelan J. Dental lesions: diagnosis and treatment. Oral Dis
1997: 3: S235–237.
132. Phiri R, Feller L, Blignaut E. The severity, extent and
recurrence of necrotizing periodontal disease in relation
to HIV status and CD4+ T cell count. J Int Acad Periodontol
2010: 12: 98–103.
133. Pistorius A, Willershausen B. Cases of HIV-associated
characteristic periodontal diseases. Eur J Med Res 1999: 4:
121–125.
134. Portela MB, Souza IP, Abreu CM, Bertolini M, Holandino
C, Alviano CS, Santos AL, Soares RM. Effect of serine-type
protease of Candida spp. isolated from linear gingival
erythema of HIV-positive children: critical factors in the
colonization. J Oral Pathol Med 2010: 39: 753–760.
135. Porter SR, Scully C, Luker J. Complications of dental sur-
gery in persons with HIV disease. Oral Surg Oral Med Oral
Pathol 1993: 75: 165–167.
136. Race EM, Adelson-Mitty J, Kriegel GR, Barlam TF, Rei-
mann KA, Letvin NL, Japour AJ. Focal mycobacterial
lymphadenitis following initiation of protease-inhibitor
therapy in patients with advanced HIV-1 disease. Lancet
1998: 351: 252–255.
137. Ramirez-Amador V, Esquivel-Pedraza L, Sierra-Madero J,
Anaya-Saavedra G, Gonzalez-Ramirez I, Ponce-de-Leon S.
The changing clinical spectrum of human immunodefi-
ciency virus (HIV)-related oral lesions in 1,000 consecutive
patients: A 12-year study in a referral center in Mexico.
Medicine (Baltimore) 2003: 82: 39–50.
138. Rams TE, Andriolo M Jr, Feik D, Abel SN, McGivern TM,
Slots J. Microbiological study of HIV-related periodontitis.
J Periodontol 1991: 62: 74–81.
139. Ranganathan K, Geethalakshmi E, Krishna Mohan Rao U,
Vidya KM, Kumarasamy N, Solomon S. Orofacial and
systemic manifestations in 212 paediatric HIV patients
from Chennai, South India. Int J Paediatr Dent 2010: 20:
276–282.
140. Ranganathan K, Hemalatha R. Oral lesions in HIV infec-
tion in developing countries: an overview. Adv Dent Res
2006: 19: 63–68.
141. Ranganathan K, Reddy BV, Kumarasamy N, Solomon S,
Viswanathan R, Johnson NW. Oral lesions and conditions
associated with human immunodeficiency virus infec-
tion in 300 south Indian patients. Oral Dis 2000: 6: 152–
157.
142. Reddy J. Control of HIV ⁄ AIDS and AIDS-related condi-
tions in Africa with special reference to periodontal dis-
eases. J Int Acad Periodontol 2007: 9: 2–12.
143. Reichart PA, Khongkhunthian P, Bendick C. Oral mani-
festations in HIV-infected individuals from Thailand and
Cambodia. Med Microbiol Immunol 2003: 192: 157–160.
95
Ryder et al.
144. Robinson P. Treatment of HIV-associated periodontal
diseases. Oral Dis 1997: 3: S238–240.
145. Robinson PG, Cooper H, Hatt J. Healing after dental
extractions in men with HIV infection. Oral Surg Oral Med
Oral Pathol 1992: 74: 426–430.
146. Robinson PG, Sheiham A, Challacombe SJ, Wren MW,
Zakrzewska JM. Gingival ulceration in HIV infection. A
case series and case control study. J Clin Periodontol 1998:
25: 260–267.
147. Robinson PG, Sheiham A, Challacombe SJ, Zakrzewska JM.
Periodontal health and HIV infection. Oral Dis 1997:
3(Suppl 1): S149–152.
148. Ryder MI. Periodontal management of HIV-infected pa-
tients. Periodontol 2000 2000: 23: 85–93.
149. Ryder MI. An update on HIV and periodontal disease.
J Periodontol 2002: 73: 1071–1078.
150. Ryder MI, Winkler JR, Weinreb RN. Elevated phagocytosis,
oxidative burst, and F-actin formation in PMNs from
individuals with intraoral manifestations of HIV infection.
J Acquir Immune Defic Syndr 1988: 1: 346–353.
151. Salama C, Finch D, Bottone EJ. Fusospirochetosis causing
necrotic oral ulcers in patients with HIV infection. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 2004: 98:
321–323.
152. Santo AE, Tagliaferro EP, Ambrosano GM, Meneghim MC,
Pereira AC. Dental status of Portuguese HIV+ patients and
related variables: a multivariate analysis. Oral Dis 2010: 16:
176–184.
153. Santos LC, Castro GF, de Souza IP, Oliveira RH. Oral
manifestations related to immunosuppression degree in
HIV-positive children. Braz Dent J 2001: 12: 135–138.
154. Sardi JC, Almeida AM, Mendes Giannini MJ. New anti-
microbial therapies used against fungi present in subgin-
gival sites-A brief review. Arch Oral Biol 2011: 56: 951–959.
155. Schiodt M, Bakilana PB, Hiza JF, Shao JF, Bygbjerg IB,
Mbaga I, Vestergaard BF, Nielsen CM, Lauritzen E, Lerche
B, Kuijlen K. Oral candidiasis and hairy leukoplakia cor-
relate with HIV infection in Tanzania. Oral Surg Oral Med
Oral Pathol 1990: 69: 591–596.
156. Schmidt-Westhausen AM, Priepke F, Bergmann FJ, Rei-
chart PA. Decline in the rate of oral opportunistic infec-
tions following introduction of highly active antiretroviral
therapy. J Oral Pathol Med 2000: 29: 336–341.
157. van Sighem AI, Gras LA, Reiss P, Brinkman K, de Wolf F.
Life expectancy of recently diagnosed asymptomatic HIV-
infected patients approaches that of uninfected individu-
als. AIDS 2010: 24: 1527–1535.
158. Silva-Boghossian C, Castro GF, Teles RP, De Souza IP,
Colombo AP. Salivary microbiota of HIV-positive children
and its correlation with HIV status, oral diseases, and total
secretory IgA. Int J Paediatr Dent 2008: 18: 205–216.
159. Slots J, Contreras A. Herpesviruses: a unifying causative
factor in periodontitis? Oral Microbiol Immunol 2000: 15:
277–280.
160. Smolak A. Contextual factors influencing HIV risk
behaviour in Central Asia. Cult Health Sex 2010: 12: 515–
527.
161. de Souza Goncalves L, Souto R, Colombo AP. Detection of
Helicobacter pylori, Enterococcus faecalis, and Pseudomo-
nas aeruginosa in the subgingival biofilm of HIV-infected
subjects undergoing HAART with chronic periodontitis.
Eur J Clin Microbiol Infect Dis 2009: 28: 1335–1342.
96
162. Stallone G, Schena A, Infante B, Di Paolo S, Loverre A,
Maggio G, Ranieri E, Gesualdo L, Schena FP, Grandaliano
G. Sirolimus for KaposiÕs sarcoma in renal-transplant
recipients. N Engl J Med 2005: 352: 1317–1323.
163. Steinsvoll S, Myint M, Odden K, Berild D, Schenck K. Re-
duced serum IgG reactivities with bacteria from dental
plaque in HIV-infected persons with periodontitis. J Clin
Periodontol 1997: 24: 823–829.
164. Traboulsi RS, Mukherjee PK, Ghannoum MA. In vitro
activity of inexpensive topical alternatives against Candida
spp. isolated from the oral cavity of HIV-infected patients.
Int J Antimicrob Agents 2008: 31: 272–276.
165. Tukutuku K, Muyembe-Tamfum L, Kayembe K, Odio W,
Kandi K, Ntumba M. Oral manifestations of AIDS in a
heterosexual population in a Zaire hospital. J Oral Pathol
Med 1990: 19: 232–234.
166. Umadevi M, Adeyemi O, Patel M, Reichart PA, Robinson
PG. Periodontal diseases and other bacterial infections.
Adv Dent Res 2006: 19: 139–145.
167. UNAIDS ⁄ WHO. AIDS Epidemic Update. December 2004.
Geneva, Switzerland: UNAIDS ⁄ WHO, 2004.
168. UNAIDS ⁄ WHO. UNAIDS Report on the Global AIDS Epi-
demic. Geneva, Switzerland: UNAIDS ⁄ WHO, 2010.
169. Van Roey J, Haxaire M, Kamya M, Lwanga I, Katabira E.
Comparative efficacy of topical therapy with a slow-re-
lease mucoadhesive buccal tablet containing miconazole
nitrate versus systemic therapy with ketoconazole in HIV-
positive patients with oropharyngeal candidiasis. J Acquir
Immune Defic Syndr 2004: 35: 144–150.
170. Vaseliu N, Carter AB, Kline NE, Kozinetz C, Cron SG,
Matusa R, Kline MW. Longitudinal study of the prevalence
and prognostic implications of oral manifestations in
romanian children infected with human immunodefi-
ciency virus type 1. Pediatr Infect Dis J 2005: 24: 1067–
1071.
171. Vastardis SA, Yukna RA, Fidel PL Jr, Leigh JE, Mercante DE.
Periodontal disease in HIV-positive individuals: associa-
tion of periodontal indices with stages of HIV disease. J
Periodontol 2003: 74: 1336–1341.
172. Vernon LT, Babineau DC, Demko CA, Lederman MM,
Wang X, Toossi Z, Weinberg A, Rodriguez B. A prospective
cohort study of periodontal disease measures and car-
diovascular disease markers in HIV-infected adults. AIDS
Res Hum Retroviruses 2011: 27: 1157–1166.
173. Vernon LT, Demko CA, Whalen CC, Lederman MM, Toossi
Z, Wu M, Han YW, Weinberg A. Characterizing tradition-
ally defined periodontal disease in HIV+ adults. Commu-
nity Dent Oral Epidemiol 2009: 37: 427–437.
174. Walker AS, Mulenga V, Sinyinza F, Lishimpi K, Nunn A,
Chintu C, Gibb DM. Determinants of survival without
antiretroviral therapy after infancy in HIV-1-infected
Zambian children in the CHAP Trial. J Acquir Immune
Defic Syndr 2006: 42: 637–645.
175. Wandera MN, Engebretsen IM, Rwenyonyi CM, Tumwine J,
Astrom AN. Periodontal status, tooth loss and self-reported
periodontal problems effects on oral impacts on daily per-
formances, OIDP, in pregnant women in Uganda: a cross-
sectional study. Health Qual Life Outcomes 2009: 7: 89.
176. Wang Q, Liu H, Qiao N. Effects of traditional Chinese
medicine on salivary glands in the patients with head and
neck cancer during radiotherapy. Zhongguo Zhong Xi Yi
Jie He Za Zhi 1998: 18: 662–664.

177. WHO. AIDS Epidemic Update: Eastern and Central Asia.
Geneva: World Health Organization. 2006.
178. Williams CA, Winkler JR, Grassi M, Murray PA. HIV-asso-
ciated periodontitis complicated by necrotizing stomatitis.
Oral Surg Oral Med Oral Pathol 1990: 69: 351–355.
179. Winkler JR, Murray PA, Grassi M, Hammerle C. Diagnosis
and management of HIV-associated periodontal lesions.
J Am Dent Assoc 1989: 119(Suppl): 25S–34S.
180. Wood NH, Blignaut E, Lemmer J, Meyerov R, Feller L.
Necrotizing periodontal diseases in a semirural district of
South Africa. AIDS Res Treat 2011: 2011: 638584.
181. Wright SC, Maree JE, Sibanyoni M. Treatment of oral
thrush in HIV ⁄ AIDS patients with lemon juice and lemon
grass (Cymbopogon citratus) and gentian violet. Phyto-
medicine 2009: 16: 118–124.
182. Yengopal V, Bhayat A, Coogan M. Pediatric oral HIV re-
search in the developing world. Adv Dent Res 2011: 23: 61–
66.
Periodontal disease in HIV ⁄ AIDS
183. Yeung S, Serb P. HIV infection and the dentist. 2. The
diagnosis and management of gingivitis and periodontitis.
Aust Dent J 1994: 39: 73–76.
184. Yeung SC, Stewart GJ, Cooper DA, Sindhusake D. Pro-
gression of periodontal disease in HIV seropositive pa-
tients. J Periodontol 1993: 64: 651–657.
185. Zakrzewska JM, Atkin PA. Oral mucosal lesions in a UK
HIV ⁄ AIDS oral medicine clinic. a nine year, cross-sec-
tional, prospective study. Oral Health Prev Dent 2003: 1:
73–79.
186. Zambon JJ. Rapid diagnosis of periodontal infections:
findings in AIDS patients. Immunol Invest 1997: 26: 55–65.
187. Zambon JJ, Reynolds HS, Genco RJ. Studies of the sub-
gingival microflora in patients with acquired immunode-
ficiency syndrome. J Periodontol 1990: 61: 699–704.
97