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An Update on HIV and Periodontal Disease*
Mark I. Ryder

With the advent of newer pharmacological ap- In the past 5 years, the face of HIV infection and the
proaches to the treatment of human immunodefi- AIDS global epidemic has changed significantly.
ciency virus (HIV) infection, the incidence and pro- Worldwide, approximately 36 million individuals have
gression of both atypical and conventional periodontal been infected with this form of lentivirus, resulting in
diseases are changing. The incidence of necrotizing 20 million deaths.1 While the death rate from HIV
periodontitis and gingival diseases of fungal origin among adults aged 25 to 44 years has markedly
appears to be on the decline as a result of these ther- declined in the United States,2 AIDS remains one of
apies that have led to increased life spans for HIV the 5 leading causes of death worldwide.1 Seventy-
patients. However, in cases where these therapies lose five percent of HIV-infected individuals reside in Sub-
their effectiveness and HIV patients relapse into an Saharan Africa, with higher rates also reported in
immunosuppressed state, these conditions may recur. Southeast Asia. Rates of new HIV infections are also
Recent evidence has shown that HIV patients with on the rise in Eastern Europe.1
more conventional periodontal diseases such as In recent years, the most encouraging news regard-
chronic periodontitis may have increased attachment ing management of the periodontal patient with HIV
loss and gingival recession when compared to their infection comes from new treatment approaches to
HIV-negative counterparts. This pattern of loss of peri- this disease on a systemic level. The goal of these
odontal support may be due in part to a diffuse inva- new approaches, or highly active antiretroviral thera-
sion of opportunistic bacterial infections, viruses, and pies (HAART), is to reduce the HIV virus to unde-
fungi into the gingival tissue, leading to a more ele- tectable levels in the bloodstream through the use of
vated and more diffuse destructive inflammatory a combination of reverse transcriptase inhibitors and
response in the periodontal soft and hard tissues. protease inhibitors.1,3,4 While the long-term effects of
While the accepted approaches to treating the spec- this type of combined antiviral therapy are still
trum of periodontal diseases in HIV patients remain unknown, and may have serious side effects,4 this
essentially unchanged over the past 15 years, the treatment approach may have widespread promise.
impact of newer systemic therapies on patient What is clear from these combination therapies such
immunocompetence may influence treatment deci- as HAART is that these pharmacological approaches
sions. J Periodontol 2002;73:1071-1078. have led to a dramatic decline in the mortality rate
from HIV infection in several industrialized countries.
KEY WORDS
In addition, in the future, there may be other effective
HIV; AIDS; periodontitis/therapy; herpesvirus; pharamacological strategies in the treatment of HIV by
inflammatory response; candidiasis. attacking other steps of the HIV infection process such
as attachment of the virus on target cells, invasion
into the cells, and integration into the target cell DNA.4
While the prospects for successful vaccine therapies
remain elusive at this time,5 these newer antiviral
approaches have led to increased life spans for HIV-
infected patients. For the dental practitioner, these new
developments in therapeutic approaches may alter the
incidence, severity, and management of oral manifes-
tations of HIV infection. In fact, recent reports have
shown a drop in total numbers of oral lesions such as
oral candidiasis, hairy leukoplakia, and necrotizing peri-
odontal diseases by approximately 30% in patients
using these combination therapies.6,7 In addition, the
incidence of necrotizing forms of periodontal disease
* Division of Periodontology, Department of Stomatology, University of
California-San Francisco, San Francisco, CA. also appears to be on the decline.7,8 Furthermore, the
development and refinement of treatments to prevent

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the occurrence and reduce the severity of some of the manifestations that may herald the HIV infection at
potentially fatal opportunistic infections in HIV through different stages of the disease, and referring patients
antimicrobials may indirectly reduce the incidence for viral and immunological testing. It is important to
and severity of several HIV-associated intraoral con- keep in mind that among patients with late-stage
ditions.9-11 However, the prospects of an older HIV immunosuppression from HIV, about 90% show one
population harboring the HIV virus in a chronic state or more HIV-associated oral manifestations.17,18 Thus,
may lead to an increase in the opportunity for trans- despite the recent advances in antiviral therapy and
mission of infection. This may, in turn, lead to an prevention, the dental practitioner will continue to
increase in selected oral and systemic conditions, par- treat both the unique oral and periodontal conditions,
ticularly among patients who do not have access to as well as conventional periodontal diseases in the
the most effective antiretroviral therapies. HIV-infected patient.
Amid this encouraging news on the treatment front, The following questions will be addressed in this
the epidemiological course of the HIV epidemic has review: 1) what are the current clinical and epidemi-
taken several turns which should be of concern to ological trends in the oral and periodontal manifes-
both the medical and dental practitioner. The initial tations of HIV infection?; 2) what new information do
wave of HIV infection in the United States and Europe we have regarding the microbiology and pathogene-
was confined to a few geographical areas and high- sis of periodontal diseases in HIV-infected patients?;
risk groups, particularly male homosexuals and intra- and 3) what are the current standard accepted ther-
venous drug users. However, the prevalence and inci- apies for the treatment of both the uncommon peri-
dence of HIV infection are increasing, albeit at a much odontal lesions seen with greater frequency in HIV
slower rate, in the heterosexual population in almost infection, and the more common periodontal diseases?
all areas of the Western hemisphere, Europe, Asia, METHODS
and Africa.1,12 This infection trend is not only a con-
In order to prepare this update on HIV and peri-
cern for those infected, but also for future newborns
odontal diseases, the author reviewed several recent
of HIV-infected mothers, where the transmission rate
books and articles on HIV in general and HIV and
can be 25% to 30%.12,13 For the dentist, this mater-
periodontal diseases in particular, which are cited in
nal transmission is of concern due to the higher sus-
the reference section. The author then conducted a
ceptibility of HIV-infected children to oral opportunistic
MEDLINE and PubMed search for the years 1995
infections and other HIV-associated oral manifesta-
through 2002 using “HIV” and “periodontitis” as
tions.14,15 In addition, although the rate of new infec- subject key words. The author also consulted with
tion in the homosexual population dropped dramat- several acknowledged experts in the field (Dr. Deb-
ically during the late 1980s in the United States, due orah Greenspan, Dr. Sol Silverman, Dr. Ira Lamster,
in part to better educational prevention programs, and Dr. Michael Glick) to survey current trends and
the incidence of new infection in this group has risen future directions in basic and clinical HIV research,
in the last few years among younger generations.16 and in clinical practice.
This rise in the infection rate may be due in part to
a false sense of security in this population that HIV PERIODONTAL DISEASES IN HIV-POSITIVE
infection can be controlled with these new drugs and, PATIENTS
therefore, safe sex practices are not needed. In this The use of new antiviral treatment approaches such
younger generation, up to 70% to 80% of these as HAART may result in a decreased incidence and
infected individuals are unaware that they are har- severity of some atypical forms of periodontal dis-
boring the HIV virus.1,12 Finally, while there appears ease such as necrotizing ulcerative periodontitis and
to be a decline in the incidence and prevalence of the linear gingival erythema associated with gingival
oral conditions such as candidiasis, mucosal ulcera- diseases of fungal origin,6-8,19 as well as other oral
tions, necrotizing periodontal diseases, etc. that may lesions more commonly found with HIV infection
be associated with the short-term success rates of (such as oral candidiasis, hairy leukoplakia, and
HAART approaches, these oral conditions may begin mucosal ulcerations).18,20 However, these conditions
to recur in patients in whom HAART therapies lose may still serve as predictors for the progression of the
their long-term effectiveness, leading to recurrence overall course of HIV infection. In particular, the occur-
of immunosuppression and elevated viral loads. rence of an ulcerative form of periodontal disease
Therefore, the dental practitioner will continue to such as necrotizing ulcerative gingivitis or necrotiz-
play a critical role in recognizing periodontal and oral ing ulcerative periodontitis may indicate a decrease in

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CD4 lymphocyte counts below 200, with an increased sites of attachment loss ≥6 mm was approximately
tendency to progress to full-blown AIDS.9,10,21 From twice that in the HIV-infected group compared to the
previous epidemiological studies, the reported range uninfected group.29 In addition, a recent study has
of the prevalence of necrotizing periodontitis was 0% added the parameter of gingival recession to clinical
to 6.3%.22 While the current and future incidence of studies of HIV and periodontal disease.30 These stud-
these diseases may be on the decline in the HIV pop- ies demonstrate a relationship between increased gin-
ulation,7,8 the dental practitioner will still need to be gival recession with advancing HIV status. This
able to identify and treat these lesions and to under- increased recession may be due in part to destructive
stand their importance in monitoring the overall health patterns of common periodontal diseases in HIV
of the HIV patient. In addition, more recent investi- patients that not only include the bone and attach-
gations have used not only CD4 counts and clinical ment apparatus, but also the oral gingival epithelium.
syndromes to follow the progression of HIV infection These patterns of increased attachment loss and reces-
(viz: the U.S. Centers for Disease Control and Pre- sion in HIV may be due in part to atypical fungal, bac-
vention classification system) but also now include the terial, and viral infections of the periodontium and/or
actual HIV viral load in the bloodstream as both an elevation of the destructive arm of the host re-
HIV disease classification method and as a thera- sponse.31,32 While it is possible that side effects of
peutic endpoint.7,23 In the future, epidemiological antiretroviral therapies may contribute to these destruc-
studies on HIV infection and manifestations in the tive periodontal patterns, this area needs to be explored
oral cavity that use systemic and/or local (e.g., in the future. In the next section, we will discuss some
crevicular fluid24) viral load as a benchmark may of these new insights into the microbiology of and host
shed new insights on the relationship between viral response to periodontal diseases in HIV patients.
load and oral manifestations of HIV. These new
approaches may also help the dental practitioner THE MICROBIOLOGY AND PATHOGENESIS OF
make treatment decisions for their HIV patients. In PERIODONTAL DISEASES IN HIV-POSITIVE
addition, the dental practitioner will need to continue PATIENTS
to address the different patterns of oral lesions in HIV- In the past several years, perhaps the most interest-
infected individuals from different risk groups. Specif- ing new insights into the microbial etiology and con-
ically, epidemiological studies have shown a higher tribution to the incidence and progression of peri-
incidence of candida in HIV-infected intravenous drug odontal diseases in HIV-infected patients are the role
users when compared to HIV-infected homosexual of opportunistic infections such as Candida and
men.7,25 In addition, there are different epidemiolog- viruses. Recent studies on the microbial flora of peri-
ical patterns of other oral conditions, with or without odontal lesions in HIV patients with periodontal dis-
antiretroviral therapy, between these 2 risk groups.25 ease have confirmed the general observations from
However, the underlying causes for these differences previous studies that the prevalence of the more com-
between risk groups are unknown at this time. mon periodontopathic bacterial species from peri-
With the apparent recent declines in the incidence odontal lesions is similar between HIV-positive and
of some less common forms of destructive periodontal HIV-negative patients,33-43 with some studies report-
disease in HIV patients, and the increased life span ing higher levels of these periodontopathic bacteria in
of these patients, the dental practitioner will still need HIV-positive patients41,42 and other studies finding lower
to address more common forms of periodontal dis- levels in HIV-positive patients.40 However, from recent
ease in these patients. In the past, there were con- studies, there appears to be an emerging pattern of
flicting reports as to the relationship of HIV infection elevated levels of opportunistic bacterial, fungal, and
to attachment loss and bone loss. Some studies have viral species associated with tissue necrosis within the
shown that in patients with a preexisting chronic peri- periodontal tissues of HIV-positive patients.32,33,44,45
odontal disease, the degree of attachment loss is One of these opportunistic infectious agents is the
greater in HIV patients,11,26-28 particularly as CD4 candida fungi, particularly Candida albicans. The pres-
counts decline. In addition, the degree of attachment ence of Candida albicans is strongly associated with
loss appears to be greater in patients with elevated the presence of a broad gingival marginal band of ery-
serum and crevicular fluid viral loads.24 This rela- thema previously described as “linear gingival ery-
tionship has been noted particularly in patient pop- thema”22,46,47 and now classified as a gingival dis-
ulations who are not receiving antiretroviral or antimi- ease of fungal origin.19 However, Candida species may
crobial therapy, where the number of subjects with not only play a role in this clinical sign of linear gin-

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gival erythema, but also in the progression of other Diffuse invasion from viruses, fungi, and other
periodontal diseases in HIV-positive patients.38,41 Can- opportunistic organisms into the gingival tissue may
dida invasion into the periodontal soft tissues is asso- help explain in part the patterns of periodontal
ciated with the severity of a variety of periodontal dis- destruction in HIV infection. This diffuse invasion
eases in HIV patients.32,48 Recent studies have reported could lead to the marginal breakdown of the gingi-
unique species of Candida within the periodontal val tissues both from the epithelial attachment and
pocket that were not isolated from other areas of the from the external oral epithelium. Specifically, a dif-
oral cavity.47 In addition, other species of Candida have fuse microbial invasion could lead to a diffuse
been recovered from periodontal lesions in HIV-infected destructive inflammatory infiltrate throughout the gin-
patients.49 These observations point to a unique niche giva and marginal breakdown of the soft and hard
that Candida may occupy within the periodontal flora tissues. This concept of a unique diffuse gingival
both within the pocket and in the periodontal soft tis- inflammatory infiltrate is supported by several recent
sues. This unique niche for Candida within the peri- studies.57,58 Using a variety of immunostaining meth-
odontium of HIV patients may lead to a suppression of ods, HIV-infected subjects demonstrated a more dif-
the protective arm of the host response and stimula- fuse infiltrate of plasma cells of various IgG and IgA
tion of the destructive arm of the host response, which subclasses from the pocket epithelium to the oral
in turn may contribute to tissue necrosis and recession, epithelium (as opposed to a concentration of these
and loss of clinical attachment and alveolar bone. cells toward the pocket epithelium in HIV-negative
Viruses may also play a similar role in the patho- subjects with periodontal disease).57 A similar diffuse
genesis of periodontal diseases in HIV patients. For distribution was seen in antigen-presenting epithelial
example, the HIV virus itself may play a local role cells, mast cells, macrophages, and neutrophils
in the destruction of periodontal tissues by sup- toward the oral epithelium.58,59 Such a diffuse dis-
pressing T-helper cells and/or by acting as a “super- tribution may be in response to microbial invasion
antigen” which may provoke an unregulated and of the gingiva from the oral epithelial side.58,59 The
destructive host response.50 However, other viruses, reduced numbers of host defense dendritic cells
particularly those in the herpesvirus family including (Langerhans’ cells) on the oral epithelial side58 and
cytomegaloviruses, Epstein-Barr viruses, herpes sim- reduced antibody reactivities to periodontal
plex virus, and human herpesviruses, may also play pathogens and other infections60,61 may result in
a role in the pathogenesis of periodontal disease in greater susceptibility of the periodontal tissues to
HIV-infected patients.51-55 In HIV-negative patients, opportunistic infections. This unique pattern of
higher numbers of a variety of herpesviruses have inflammatory infiltrate could then contribute to the
been recovered from deeper periodontal pockets increased breakdown of periodontal support through
when compared to the relatively shallower pockets elevation of a non-specific antibody response47 that
in gingivitis.53,54 HIV-positive patients harbor greater would nevertheless lead to tissue breakdown, and/or
numbers of these viruses in periodontal pockets than to an increase in destructive inflammatory cytokines
their HIV-negative counterparts.55,56 While the role of such as IL-1β, IL-6, TNF-α, and in destructive
these herpesviruses as a primary etiology or a con- enzymes such as the metalloproteinases (e.g., col-
tributory factor has yet to be determined, the pres- lagenase and gelatinase). In fact, studies have
ence of elevated levels of these viruses in the peri- demonstrated elevated levels of both destructive
odontal tissues may lead to overgrowth of periodontal cytokines22,23,47,62 and metalloproteinases38,63 in the
pathogens and opportunistic infections through sup- crevicular and/or salivary fluid of HIV-positive
pression of the protective arm of the host response, patients. Furthermore, these cytokine levels are
and to increased secretion of potentially destructive related to the HIV viral load,23 and thus the pro-
inflammatory mediators such as interleukin-1 (IL-1) gression of HIV.
beta and tumor necrosis factor-alpha (TNF-α).53 Ele-
vated levels of these viruses in the periodontal soft TREATMENT OF PERIODONTAL DISEASES IN
tissues may contribute to the increased incidence of THE HIV PATIENT
necrotizing forms of periodontal disease. This intrigu- When discussing the state of the art for treatment of
ing concept that herpes viral agents may play a role some of the atypical forms of periodontal disease in
in the necrotic and more rapidly destructive features the HIV-positive patient, the therapeutic principles
of periodontal diseases in HIV-positive patients mer- developed in the mid-1980s still remain the standard
its further investigation. of care.64-73 Due to the high morbidity of these peri-

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odontal conditions, it would not be ethically accept- However, if there is no resolution of these lesions with
able to conduct a controlled study to test the efficacy this therapeutic approach, the practitioner should con-
of these approaches. Therefore, these reports on the sider other oral lesions associated with HIV infection that
management of these more atypical periodontal may give a similar clinical picture. These include lym-
lesions generally involve a series of case studies. phomas, neoplastic growths, and severe herpetic or
These treatment principles involve gross scaling to aphthous ulcerations of the gingiva.75-77 In some cases,
remove visible plaque, soft debris, and necrotic tis- particularly where a neoplasm is suspected, a biopsy
sue when present. Povidone iodine irrigation is often of the area should be performed to confirm the diag-
recommended during this debridement procedure due nosis.
to its anesthetic and antiseptic effects.64 Following With the development of new strategies for control-
this initial debridement, frequent follow-up visits are ling the HIV virus such as HAART, we may see a sig-
recommended to thoroughly remove the remaining nificant delay in the development of overt AIDS in a
plaque, calculus, and other deposits, and to provide larger portion of the infected population. This may in
plaque control instruction to the patient. In one study turn lead to a downward trend in the occurrence of
of 89 HIV-infected patients with necrotizing periodontal some of these atypical periodontal conditions in the
disease, favorable results were achieved with debride- HIV-infected patient. Of particular interest to the den-
ment followed by local irrigation with a 0.2% chlorhex- tal practitioner are recent studies which indicate that
idine rinse and a 3-day course of systemic metroni- protease inhibitors in HAART may directly inhibit Can-
dazole.73 In these necrotizing forms of periodontal dida aspartic proteinases.78 However, the dental prac-
disease, this therapeutic approach should be applied titioner will still be faced with the problem of treating
as soon as possible since bone and soft tissue necro- HIV patients with more common periodontal condi-
sis may extend into the palate and adjacent tissues, tions such as chronic periodontitis, gingivitis associated
leading to a life-threatening NOMA condition. with plaque alone, gingivitis associated with plaque
Some clinical centers that treat relatively large modified by other factors, etc. The question facing den-
cohorts of HIV patients recommend the use of selected tal practitioners is how the HIV infection, in general,
antibiotics such as metronidazole as valuable adjuncts and specifically the immune status may affect con-
to treatment.73 However, antibiotics should be used ventional therapeutic approaches to these diseases.
with caution due to the risk of overgrowth of Candida To date, there have been only a few studies on peri-
species.73 Narrow-spectrum antibiotics such as metron- odontal treatment outcomes in HIV patients. Much of
idazole may leave the greater portion of Gram-positive what can be recommended at this time is based upon
flora intact in order to prevent Candida overgrowth. other dental and medical therapies.
The non-response of the linear gingival erythema asso- The vast majority of HIV-infected periodontal
ciated with gingival diseases of fungal origin to con- patients will require some form of debridement to
ventional therapy may be due in part to a Candida inva- remove local irritants and reduce inflammation. A
sion of the gingival tissues. In order to prevent the concern of the practitioner treating the HIV patient
overgrowth of Candida, the generally accepted may be the effects of developing a systemic bac-
approach is to use a topical antifungal agent, such as teremia and subsequent systemic infections. To date,
clotrimazole troches or nystatin vaginal tablets, and the one study that has investigated this potential prob-
systemic fluconazole or itraconazole in cases of more lem found a greater percentage of transient bac-
severe immunosuppression. One recent study has teremias in HIV patients immediately after scaling.79
shown that some species of Candida, as well as strains However, these bacteremia levels returned to normal
within each of these species, may become resistant to within 30 minutes. Therefore, at least from this study,
fluconazole but not itraconazole.74 Therefore, itra- it appears that the scaling and debridement procedure
conazole may be used as an alternative to Candida is safe to perform on HIV-infected patients.
infections that do not respond to or become resistant A second major concern to the practitioner is
to fluconazole. In these cases, the use of an antifungal whether the HIV status of the patient could alter the
may be of benefit in reducing the inflammatory changes treatment plan for periodontal surgical procedures.
in this condition. To date, there have been no studies that compare the
In the dental literature, we continue to see clinical post-periodontal surgery healing response between
case reports, employing these management principles HIV-infected and non-HIV-infected individuals. One
which demonstrate the effectiveness of this approach surgical procedure that has been studied more exten-
in reducing the acute symptoms of these conditions. sively, and may have similar healing response con-

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cerns, is tooth extraction.80-83 Such studies on post- Zakrzewska JM. Periodontal health and HIV infection.
operative complications of tooth extraction include Oral Dis 1997;3(Suppl. 1):S149-S152.
observations on delayed hard and soft tissue heal- 12. Fauci AS, Lane HC. Human immunodeficiency virus
(HIV) disease: AIDS and related disorders. In: Fauci
ing. While the majority of these studies showed a AS, Braunwald E, Isselbacher KJ, et al., eds. Harri-
slight increase in these postoperative complications son’s Principles of Internal Medicine, 14th ed. New York:
in HIV-infected patients, these increases were not sig- McGraw Hill; 1998:1791-1856.
nificant. However, as in all dental procedures, the 13. Peckham C, Gibb D. Mother to child transmission of
general immune status and the CD4 count in partic- the human immunodeficiency virus. N Engl J Med
1995;333:298-302.
ular may alter surgical decisions. For example, if CD4 14. Del Toro A, Berkowitz R, Meyerowitz C, Frenkel LM.
counts are below 200, this may indeed affect the Oral findings in asymptomatic (P-1) and symptomatic
healing response to periodontal treatment. Of par- (P-2) HIV-infected children. Pediatr Dent 1996;18:114-
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that a percentage of HIV-infected subjects will exhibit 15. Howell RB, Jandinski JJ, Palumbo P, Shey Z, Houpt
MI. Oral soft tissue manifestations and CD4 lympho-
some degree of thrombocytopenia during the course cyte counts in HIV-infected children. Pediatr Dent
of their HIV infection.12 This depressed platelet count 1996;18:117-120.
may have an adverse effect on the bleeding and clot- 16. Centers for Disease Control. Update: Trends in AIDS
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17. Greene VA, Chu SY, Diaz T, Schable B. Oral health
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most current immune and hematological status prior infected adults. J Am Dent Assoc 1997;128:1417-1422.
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