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Dent Clin N Am 50 (2006) 635–657

HIV-Positive Patients: Dental

Management Considerations
Nicholas G. Mosca, DDSa,b,*,
Alicia Rose Hathorn, DMDc
Mississippi State Department of Health, 570 East Woodrow Wilson Drive,
Jackson, MS 39216, USA
Department of Pediatric and Public Health Dentistry, University of Mississippi School
of Dentistry, 2500 North State Street, Jackson, MS 39216, USA
Department of Restorative Sciences, University of Mississippi School of Dentistry,
2500 North State Street, Jackson, MS 39216, USA

A research team in France in 1983, led by Luc Montagnier, identified

HIV as the etiology of an immunological deficit in cell-mediated immunity
known as AIDS [1]. Since the first cases of AIDS, then known as gay-related
immunodeficiency syndrome (GRID) in 1981, the HIV epidemic has spread
beyond gay males, Haitians, and hemophiliacs, and affects an estimated 50
million people worldwide.
HIV is a blood-borne retrovirus infection transmitted primarily through
contact across genital mucosal surfaces, facilitated by breaks in the mucosal
barrier or local inflammation, such as genital ulcers or vaginitis. Retrovi-
ruses produce reverse transcriptase, which is a viral enzyme that allows
the virus to integrate its own DNA into the genome of an infected cell
and replicate itself using the infected cell’s ribosomes and protein synthesis
[2]. Dr. Robert Gallo and his research team at the National Institutes of
Health contributed to the discovery of HIV and were first to identify a hu-
man retrovirus in 1980, a T-cell lymphotropic virus (HTLV-1) that is asso-
ciated with human T-cell leukemia [3].
Two primary types of HIV can infect humans: HIV-1, the primary infec-
tion in most of the world; and HIV-2, an infection occurring primarily in
West Africa and having smaller molecular size and less pathogenicity than
HIV-1. In 1999, researchers at the University of Alabama at Birmingham
discovered that HIV-1 might have originated from an infection of subspecies

* Corresponding author. Mississippi State Department of Health, 570 East Woodrow

Wilson Drive, Jackson, MS 39216.
E-mail address: (N.G. Mosca).

0011-8532/06/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved.

of chimpanzees native to west equatorial Africa [4]. This simian virus may
have spread to humans through exposure to infected blood while hunting
chimpanzees, or through the consumption of infected chimpanzee ‘‘bush-
meat.’’ Each virus type has viral subtypes, known as clades, that have
been isolated in distinct geographical regions. Intracellular infection in hu-
man cells requires cell surface receptors and coreceptors, which exhibit ge-
netic polymorphisms that provide specificity and modulate the virus’s
ability to infect cells. In North America, clade B is the predominate viral
subtype. Researchers at Johns Hopkins showed that HIV disease may prog-
ress more rapidly with certain viral clades. For example, increased virulence
is associated with clade D in Africa [5].
HIV infects tissue-bound Langerhans or follicular dendritic cells, which
process virus as nonself antigen to activate circulating CD4þ T lympho-
cytes, also called helper T cells because they serve to coordinate HIV-specific
immune response. Cells with intracellular pathogens must express viral pro-
teins in association with specific receptors at the cell surface for infection to
be recognized by the cytotoxic immune cells or to stimulate antibody pro-
duction. Activated CD4þ T lymphocytes transport HIV to lymphoid or-
gans, such as the gut-associated lymphoid tissue, where virus replication is
accelerated through normal antigen amplification mechanisms. HIV-specific
CD8þ T lymphocytes differentiate to destroy activated CD4þ T lympho-
cytes infected with the virus, which in turn stimulates production of more
CD4þ T lymphocytes. In 1995, Shaw and colleagues [6] demonstrated
that viral loads are sustained by a delicate balance between T-cell–mediated
virus replication (production) and T-cell–mediated viral destruction (clear-
ance). Once this cycle of HIV infection is established, the immune system
cannot eliminate virus completely, causing a progressive T-lymphocyte de-
pletion, destruction of the architecture of the lymphoid organs, and inability
to mount a cell-mediated immune response to any infection. HIV-positive
individuals have increased susceptibility to opportunistic infections that
are challenging to treat and may lead to death.
HIV’s genome contains three structural and six regulatory genes that en-
code at least 15 viral proteins associated with its pathogenicity and viral rep-
lication. A cell envelope glycoprotein, GP160, is the principal viral antigen
and has a GP120 external segment and GP41 transmembrane segment
(Fig. 1). Viral proteins have become important targets for the development
of antiretroviral drug therapies. In the mid-1990s, researchers found that
some infected cells have beta-chemokine receptors, CCR5 and CXCR4,
that participate in binding and entry of HIV into host cells, and ligands
for these receptors could inhibit attachment [7]. HIV strains that use
CCR5 as coreceptors are called R5 viruses and those that use CXCR4 are
called X4 viruses. Clade-A HIV uses only CCR5 while clade D uses
CXCR4 and may be more virulent. R5 viruses cannot infect cells with
CXCR4 receptors and X4 viruses cannot infect cells with CCR5 receptors.
Studies of genetic polymorphisms led to the discovery that individuals

Fig. 1. Organization of the HIV-1 virion. (Courtesy of the Office of Communications and Pub-
lic Liaison, National Institute of Allergy and Infectious Diseases, National Institutes of Health,
Bethesda, MD.)

homozygous for a deletion of 32 base pairs in the CCR5 gene could not be
infected in vitro with R5 viruses [8]. These individuals comprise about 1% of
white populations and are extremely resistant to HIV, even with repeated
viral exposures.

High-risk behaviors and HIV testing

HIV is transmitted by infection of genital mucosa, through inoculation
during an injection of drugs or during a transfusion, and, rarely, by infection
of oral mucosa. Transmission may also occur from an infected mother to
child in utero, during delivery (peripartum), or by breastfeeding. The risk
for transmission is closely linked to the plasma viral load of the transmitting
HIV-positive individual. Polymerase chain reaction (PCR) test can detect
HIV viral genes and is used to determine plasma viral load. The amount
of viral replication is measured as viral copies per milliliter of blood, and ex-
pressed as logs of the number of infected CD4þ T cells. Mellors and col-
leagues [9] demonstrated this direct relation between the viral load, or set
point, which is the amount of virus produced at production and destruction
equilibrium, and the rate of CD4þ T-cell decline.
Regardless of socioeconomic and cultural factors, the transmission of
HIV occurs primarily due to risky behavior. Box 1 provides a list of risky
activities and clinical symptoms for those unknowingly infected with HIV.
Individuals with viral load of O50,000 copies per milliliter have a more
than 50-fold increased risk of transmitting virus per risk behavior, while
those with viral load of !1000 copies have lower risk [10].
PCR is expensive and very labor-intensive to use as a screening test. Since
1984, standard serologic HIV testing uses enzyme-linked immunosorbant as-
say (ELISA) to detect antibodies to HIV and should be performed when
high-risk behaviors or symptoms of acute infection are evident. Primary

Box 1. Indications for HIV-antibody testing

Behaviors or history associated with high risk:
 Having unprotected vaginal, anal, or oral sex with men who
have sex with men, multiple partners, or anonymous partners
 Having recent or prior sexually transmitted disease, hepatitis,
or tuberculosis infections
 Exchanging sex for drugs or money
 Having male or female sexual partners who are at risk
 Injecting drugs or steroids, or sharing injection equipment with
 Having history of receiving blood products or clotting factor
between 1978 and 1985
 Having unprotected sex with anyone who exhibits risky
behaviors listed above
Clinical conditions associated with high risk:
 Sexually transmitted diseases
 Thrush (ie, chronic or recurrent oral and/or vulvovaginal
 Generalized lymphadenopathy
 Recurrent herpes simplex or herpes zoster
 Chronic diarrhea or wasting
 Anemia, leukopenia, or thrombocytopenia
 Opportunistic infections

antibody production to HIV after initial infection may take 2 to 4 weeks,

creating a period when ELISA will not be able to identify infection. If the
initial ELISA is negative, the test should be repeated in 3 months. If positive,
confirmatory testing using Western blot techniques is performed on all pos-
itive screening tests to assure reliability of results. Western blot detects anti-
bodies to HIV-1 proteins with a low frequency of error (!0.00004% false
positives). If a Western blot result is indeterminate or uncertain, nucleic
acid testing for viral RNA or proviral DNA can be performed. An HIV viral
core p24 antigen test is used to detect HIV in donated blood supplies, but the
viral core antigen may become undetectable about 40 days after seroconver-
sion, making the test less favorable to detect HIV when diagnosing humans
[11]. HIV longitudinal studies have also demonstrated that persons exposed
to HIV during risky behavior may undergo latent seroconversion, with no
detectable antibody production after initial exposure [12].
Tests have also been developed for urine and oral saliva using enzyme im-
mune assay (EIA) testing that detects IgG antibody, whose principal site of
action is serum. OraSure (OraSure Technologies, Bethlehem, Pennsylvania)

is an oral fluid test approved by the US Food and Drug Administration

(FDA) and Calypte (Calypte Biomedical, Alameda, California) is a urine
EIA test that can be used with needle-phobic individuals who shun blood
tests. Several rapid HIV tests, which provide results in about 20 minutes,
have also been approved by the FDA for use in the United States. These tests
include OraQuick Rapid HIV-1 and Advance HIV- Antibody Tests (Ora-
Sure Technologies), Reveal G2 HIV-Antibody Tests (MedMira, Halifax,
Canada), Multispot (Bio-Rad Laboratories, Hercules, California), and
Uni-Gold Recombigen (Trinity Biotech, Bray, Ireland). As with enzyme im-
mune assay testing, rapid test results must be confirmed by Western blot test.

HIV/AIDS epidemiology
The World Health Organization estimates that over 50 million people
have been infected with HIV worldwide, with more than 25 million infec-
tions reported in Africa. Southeast Asia, Latin America, and Eastern Eu-
rope account for about 10 million cases, and an estimated 1.2 million
people have HIV infection in North America. Western and Central Europe
combined have fewer than 750,000 reported cases of HIV infection. An es-
timated 40,000 cases of HIV infection occur in the United States each year.
In the United States, 33 states using confidential, name-based reporting,
provide HIV/AIDS prevalence data to the Centers for Disease Control, and
all 50 states report AIDS. In the past 2 decades, the number of reported
AIDS cases has fallen due primarily to improvements in antiretroviral treat-
ment regimens, and increased use of medical care through regional, state,
and local programs funded by the federal Ryan White Comprehensive
AIDS Resources Emergency Act. Trends demonstrate a decrease in AIDS
among white males who have sex with males, but an increase in AIDS
among non-Hispanic blacks. From 2001 through 2004 in the United States,
157,252 cases of HIV infection were reported to the Centers for Disease
Control. Non-Hispanic black males had the largest percentage of HIV infec-
tions in every transmission category, and, among females, non-Hispanic
blacks had the most cases (69%) [13]. Non-Hispanic blacks account for
up to 12% of the United States population, yet they accounted for half of
all AIDS cases diagnosed in 2004. In 2004, the rate of AIDS diagnoses
for non-Hispanic black women was 23 times the rate for white women;
the rate of AIDS diagnoses for non-Hispanic black men was 8 times the
rate for white men.

Mucosal resistance to HIV

Much progress has been made in understanding protective anti–HIV-1
immune responses in mucosal tissues, such as that in the oral cavity. The
first line of defense against mucosal HIV infections begins with virus neu-
tralizing immunoglobulin or antibodies. In the oral cavity, secretory IgA

produced by subepithelial plasma cells is trancytosed by epithelia cells. IgG

is transferred from blood by passive diffusion through the gingival sulcus.
CD8þ cytotoxic T lymphocytes present in the lamina propria (intraepithe-
lial region) may limit or prevent localized virus production in epithelial
Langerhans cells and subepithelial dendritic cells. Factors that limit the ef-
ficient immune system elimination of HIV include immune exhaustion, lack
of adequate CD4þ T-lymphocyte function, protected viral reservoirs, po-
tential infection of CD8þ cytotoxic cells, and defects in antigen-presenting
cells [14].

HIV treatment therapies

Initial infection of HIV in adults causes an acute viral syndrome within
4 to 11 days of infection, probably due to rapid viral replication in lymphoid
tissues. Clinical symptoms may occur 2 to 6 weeks after viral inoculation,
and the most common signs and symptoms are fever, rash, headache,
lymphadenopathy, and pharyngitis. A healthy, uninfected person usually
has 800 to 1200 CD4þ T cells per mm3 of blood. Transient immunosupres-
sion associated with acute infection may lead to a decrease in CD4þ T lym-
phocytes; interstitial inflammatory infiltrates in the skin, causing a skin rash
on the upper torso; and ulcerations in the oral cavity and pharynx. Oppor-
tunistic infections, such as candidiasis, may also occur in the oropharynx.
Co-infections may be transmitted with HIV, including hepatitis, syphilis,
and Kaposi’s-sarcoma–associated human herpes virus 8. A small percentage
of people will have no acute symptoms during initial infection.
Early therapy using antiretroviral drugs can be initiated in acute infection
to lower the viral load and boost the initial immune response, but this has
not been effective in eradicating virus completely. The decision to begin
early treatment should include consideration of the long-term effects of
drug-related toxicities, and include genotypic testing to identify antiviral-
drug–resistant strains of HIV. Genotypic and phenotypic drug resistance
testing permits the optimal use of available antiretroviral drug therapies.
Clinical drug failure occurs when control over viral replication is lost.
Immune seroconversion with antiviral antibody production may take up
to 3 months after the acute infection. Life expectancy with HIV infection re-
mains unpredictable. A small group of HIV-positive people are known as
long-term nonprogressors because they show no signs of immune deficiency
after O16 years of infection. For the infected majority, HIV is considered
a chronic disease because drug therapies have suppressed viral production
but fail to completely eradicate viral replication. Between 2% and 4% of
new infections in the United States are with multidrug-resistant HIV.
In 2005, there were 21 anti-retroviral pharmaceuticals in use, not includ-
ing multidrug-combination preparations. The spectrum of drug discovery
for HIV centers on an appreciation of vulnerable targets in the replication
of the virus. Antiretroviral drug therapies decrease viral set points, leading

to an increase of CD4þ T lymphocytes, improving immune function and re-

ducing vulnerability to opportunistic infections. Symptomatic HIV-positive
patients should be treated with antiretroviral medications regardless of their
CD4þ T-cell count or viral load. Asymptomatic patients with CD4þ T cells
!200/mL should also begin treatment. It is generally recommended that
asymptomatic patients with CD4þ T cells O350/mL and viral loads
!100,000 copies/mL defer therapy due to patient readiness, probability
of adherence, and drug side effects and interactions. However, those with vi-
ral loads O100,000 copies/mL should consider initiation of antiretroviral
therapies. A cure for HIV infection would require an antiretroviral therapy
that penetrates all cells where virus is replicating, strict adherence by pa-
tients to the drug regimen until all infected cells are destroyed, and minimal
morbidity from drug toxicity and complications. Current therapies might
achieve and sustain viral loads at values at least 0.5 log10 copies per mm be-
low baseline [15].
The first effective drug against HIV was azidovudine (AZT), a nucleoside
reverse transcriptase inhibitor (NRTI), licensed in 1987. AZT was also asso-
ciated with increased melanin hyperpigmentation of the tongue and oral
mucosa. Other NRTIs are listed in Table 1. The subsequent phase of drug
therapy focused on specific points in the virus replication cycle. Protease in-
hibitors were licensed in 1995. Combination therapies have proved promis-
ing, and are known as highly active antiretroviral therapies (HAART). In
2003, the FDA approved the use of enfuvirtide, which blocks the fusion
of the viral envelope to the cell membrane. Therapeutic strategies have cen-
tered on the association of a given viral set point in asymptomatic untreated
individuals and their prognosis for disease progression.

Dental treatment
Oral health and medical care providers should collaborate in the manage-
ment of patients with HIV disease. The immunological deficit in cell-medi-
ated immunity leads to oral conditions that provide a ‘‘window’’ to the onset
of acute HIV infection. By examining oral conditions, care providers can
measure adherence and effectiveness of antiretroviral treatment regimens,
and detect changes in quality of life. The most effective professional rela-
tionships in HIV patient care are personal, caring, and ‘‘relationship-
centered.’’ To enhance patient-care relationships, the health care profes-
sional may find that the best opportunities to confer with patients are at
any of the three milestones along the course of a person’s experience with
HIV infection. These milestones are the initial diagnosis, the onset of clinical
symptoms, and the initiation of antiretroviral treatment regimens. A de-
tailed health history should be taken using a nonjudgmental approach.
This must include specific nonjudgmental questioning about sexual activity
and illicit drug use. Box 1 details health history findings that indicate the
need for voluntary HIV testing.
Table 1
Antiretroviral drug therapies for HIV infection


Generic name abbreviation Food restrictions Common adverse reactions
Nucleoside reverse transcriptase inhibitors or nucleoside analogues
Zidovudine AZT, ZDV No food restrictions Anemia, neutropenia, headaches, nausea, melanin
Didanosine ddI Empty stomach Diarrhea, pancreatitis, peripheral neuropathy
Stavudine d4T No food restrictions Peripheral neuropathy
Lamivudine 3TC No food restrictions Headache, nausea
Abacavir ABC No food restrictions Hypersensitivity reaction (fever, malaise, rash),
nausea, vomiting, diarrhea
Emtricitabine FTC No food restrictions Headache, nausea, diarrhea
Tenofovir TFV, TDF, PMPA No food restrictions Nausea, vomiting, flatulence, diarrhea
Combination nucleoside reverse transcriptase inhibitors or nucleoside analogues
Zidovudine and lamivudine AZT þ 3TC No food restrictions Same as AZT, 3TC above
Lamivudine and abacavir 3TC þ ABC No food restrictions Same as 3TC, ABC above
Tenofovir and emtricitabine TDF þ FTC No food restrictions Same as TDF, FTC above
Non-nucleoside reverse transcriptase inhibitors
Nevirapine NVP No food restrictions Rash
Delavirdine DLV No food restrictions Rash, impaired liver function
Efavirenz EFV Empty stomach Central nervous system effects (dizziness, somnolence,
insomnia, confusion)
Protease inhibitors
Hard-gel capsule saquinavir SQV With meals Diarrhea, nausea, abdominal pain
Indinavir IDV Empty stomach, light snack Nausea, increased bilirubin, kidney stones
Ritonovir RTV With meals Nausea, vomiting, diarrhea; inhibits liver enzymes
(increases drug interactions)
Nelfinavir NFV With meals Diarrhea, nausea, vomiting
Amprenavira APV No high-fat meals Nausea, diarrhea, rash, perioral and oral parathesias
Lopinavir/ritono LPV With meals Diarrhea, nausea, increased cholesterol, increased triglycerides
Atazanavir ATV With meals Hyperbilirubinemia, nausea
Fosamprenavir f-APV No food restrictions Same as amprenavir
Tipranavir TPV With meals Diarrhea, nausea, vomiting, fatigue, headache
Fusion inhibitors
Enfuvirtide T-20 None (administered subcutaneous) Injection reaction, insomnia, myalgia, pneumonia

Used with pediatric HIV infection.


Many HIV-positive patients who receive medical care do not receive den-
tal care primarily because of the burden of medical costs and a lack of dental
insurance requiring additional out-of-pocket expense. A study of 635 HIV-
positive patients at the University of Alabama School of Medicine showed
that medical expenditures for HAART were relatively constant at approxi-
mately $10,500 per patient per year no matter the CD4þ cell count [16]. The
HIV Cost and Services Use Study provides a national perspective on self-
reported measures for HIV-infected persons. The study used nationally rep-
resentative sample of 2466 HIV-positive subjects and a weighted design to
control for nonresponse, making the sample representative of a broader
population of 219,700 [17,18]. Total out-of-pocket health expenditures for
this population were $20.5 million. Those working full-time or part-time
spent $207 on dental treatment compared with $108 spent by those not
working. Cost of care was highest for people with CD4 counts !50 cells/mL
($172) compared with higher CD4 counts. Thirty-four percent (72,700) felt
their overall oral health was ‘‘fair to poor,’’ and 18% (22,000) had not re-
vealed their HIV status to their dental provider.
Xerostomia or dry mouth may occur in up to 40% of HIV-positive pa-
tients in association with side effects from antiretroviral and antidepressant
medications, tobacco use, and proliferation of CD8þ T lymphocytes in sal-
ivary gland tissue. Xerostomia may significantly increase the risk for dental
caries and acute gingivitis in HIV-positive patients. Patients should receive
counseling about these risks and instructions to use artificial saliva products
as needed.

HIV-associated opportunistic conditions

Oral conditions associated with HIV infection may identify a person who
is unknowingly infected with HIV; is used in staging, classification, and pre-
diction of progression to AIDS; and may be used as clinical entry or end-
point indicators in HIV drug therapy.
Most HIV-associated oral conditions are caused by opportunistic infec-
tions, which occur progressively due to immune system deficiency. While
the use of HAARTs has reduced the frequency of almost all opportunistic
conditions, dental care workers should be vigilant to identify signs and
symptoms associated with nonoral opportunistic infections, which may ap-
pear as first signs of viral therapy failure or noncompliance with medica-
tions. Treatment recommendations for oral conditions are found in Table 2.
The following are HIV-associated opportunistic conditions:

Bartonella is a gram-negative bacterial infection that causes cat scratch
disease and an oral condition called bacillary angiomatosis, which may
clinically resemble Kaposi’s sarcoma lesions in mucosa. Regional

Table 2
Treatment recommendations for oral conditions associated with HIV
Oral conditions Treatment options
Angular cheilitis Ketoconazole 2% cream
Dispense 30 g; apply to area 4/d for 2 wk.
Erythematous candidiasis Clotrimazole troches 10 mg
Dispense 70. Dissolve in mouth 5/d for 2 wk.
Nystatin oral suspension 500,000 U
Swish 1 teaspoon in mouth for 5 min,
4/d for 2 wk.
Pseudomembranous candidiasis Fluconazole 100 mg
Dispense 15 tabs, 2 tabs on first day,
then 1 tab/d for rest of period.
Diflucan 200 mg
Dispense 5 tabs, take 1 tab/d.
Oral hairy leukoplakia Acyclovir 4 g/d
For temporary relief. Treatment
usually not required.
Oral warts Cryotherapy or surgical excision
Imiquimod 5% cream
For lesion on lips. Dispense 3 g, apply
1/d at bedtime, 3d per wk.
Apthous ulcerations Orabase cream
Place with a cotton swab over ulcer 3/d.
Ulcerations from Herpes simplex virus Acyclovir 400 mg
Dispense 30 tabs, 1 tab 3/d for 10 d.
Linear gingival erythema 0.12% chlorhexidine rinse
With oral hygiene instruction and dental cleaning.
Necrotizing ulcerative periodontitis Augmentin 875 mg
Dispense 14 tabs, 1 tab 2/d for 7 d.
Rigorous debridement along with 0.12%
chlorhexidine rinse.
Kaposi’s sarcoma Incisional biopsy
With follow-up with patient’s primary physician.
Possible radiation or chemotherapy as treatments.

lymphadenopathy, fever, malaise, vomiting, and headache may accompany

Bartonella infections. Tissue biopsy, preferably a 5-mm punch biopsy, and
Warthin–Starry silver stain or in situ immunohistochemical staining, is
used to confirm the diagnosis. Treatment of choice is oral erythromycin
500 mg every 6 hours for at least 3 months. An alternative therapy is doxy-
cycline 100 mg every 12 hours if patient compliance is problematic.

Candidiasis (mucocutaneous)
Oropharyngeal candida (OPC), as with esophageal and vulvovaginal can-
didiasis, is caused by yeast, chiefly Candida albicans, and less frequently
by Candida glabata, Candida tropicalis, and Candida kruseii. Fungi are nor-
mal inhabitants of the gastrointestinal tract and colonization of oral mucosa
is common. Diagnosis is made by clinical appearance, and the

pseudomembranous variant, also known as thrush (Fig. 2), is the most com-
mon presentation, especially in HIV-positive children. The pseudomembra-
nous variant appears as a cottage-cheese–like or curd-like exophytic
material on the epithelial tissue on all locations in the oral cavity, and it
can be easily wiped off. Histological examination is generally not necessary,
but specimen samples can be used to confirm diagnosis. Typically, scraping
with a blade or cytology brush collects material, which can be gently
smeared on a glass slide and viewed microscopically after placing one or
two drops of 10% potassium hydroxide solution. Fungal organisms have
characteristic pseudohyphae and budding characteristic of reproduction.
The erythematous or atrophic variant appears as flat or macular with red
color, and is sometimes accompanied by pain (Fig. 3). It may occur simul-
taneously with or independent of the pseudomembranous variant. Angular
cheilitis is a fungal infection of the labial commissures that characteristically
appears as erythema or depigmentation with tissue fissures or ‘‘cracking’’
(Fig. 4).
Mild episodes can be treated with topical antifungal medications, while
moderate-to-severe conditions will typically require systemic therapy. Nys-
tatin is a topical azole antifungal drug with minimal side effects, but sweet-
ening agents in its suspension may be cariogenic. Clotrimazole is another
azole that is available as a spray, solution, and troche for oral usage. It
has few side effects but is poorly absorbed in the gastrointestinal tract and
must dissolve slowly in the mouth to be effective. Clotrimazole may be
less cariogenic than nystatin. Fluconazole was the first triazole drug avail-
able as tablet or suspension, and it demonstrates good gastrointestinal ab-
sorption with minimal dependence on gastric acidity or food intake.
Itraconazole, available as a capsule or oral suspension, is a triazole drug
that demonstrates better absorption after food intake. Voriconazole has
the most significant drug interactions with some antiretroviral drugs and
should be considered for use if resistance to fluconazole occurs [19]. The
most commonly reported side effects for the triazole drug class are head-
ache, dyspepsia, diarrhea, nausea, vomiting, hepatitis, and skin rash.

Fig. 2. Pseudomembranous candidiasis (thrush).


Fig. 3. Erythematous candidiasis (hard palate).

Ketoconazole is rarely used as an oral formulation due to its dependence on

gastric acidity, but it can be used as a topical agent in the treatment of an-
gular cheilitis.

Condyloma acuminatum
Condyloma acuminatum is an asymptomatic mucocutaneous infection of
the skin or mucosa of the oral cavity or anogenital region caused by human
papilloma virus (HPV), which can be transmitted sexually (Fig. 5). More
than 100 HPV types have been identified. HPV is a DNA virus type and
is epitheliotropic, which means it contains epithelia growth factor and
may induce distinct squamous cell proliferations. Some high-risk HPV geno-
types have been associated with premalignant and malignant lesions, and
HPV types 6 and 11 are most commonly associated with condylomata.

Fig. 4. Angular cheilitis.


Fig. 5. Human papilloma virus.

Clinical presentation differs from pedunculated exophytic cauliflower-like

papules to smooth, flat-topped papules known as focal epithelial hyperpla-
sia. Infections typically have multiple papillomas and appear most com-
monly on the labial and buccal mucosa, tongue, and gingival. Tissue
biopsy is necessary to confirm diagnosis. While there is no therapy to erad-
icate the infection, treatments include removal of papules using cryosurgery,
electrosurgery, or scalpel incision. However, the likelihood of recurrent in-
fection requiring re-treatment is high. Surgeons should use face shields
with laser or electrosurgery to minimize exposure to aerosolized HPV. Top-
ical podophylin or topical 5-fluorouracil have also been used to treat lesions.

Cryptococcus neoformans is a fungal infection that most commonly man-
ifests as a meningoencephalitis. Symptoms include headache, nausea, irrita-
bility, and diminished cognitive function, and physical findings include
cranial nerve palsies, hyperreflexia, and papilledema. Rarely, intraoral ulcer-
ations may occur in mucosal tissues with dissemination of cryptococcosis
[20]. Treatment of crytococcal meningoencephalitis requires multiple drug
therapies using amphotericin B, flucytosine, and fluconazole.

Cryptosporidium is a spore-forming protozoa infection that causes severe
watery diarrhea and epigastric pain. The most common site of infection is
the small intestine, and infection may be transmitted person-to-person or
by drinking contaminated water. Precautions to prevent disease include
proper hand washing and disinfectant cleaning or disposal of contaminated
materials. Treatment includes replacement of lost fluid volume and the use
of the antibiotic combination of trimethoprim and sulfamethoxazole or

Hairy leukoplakia
Hairy leukoplakia is caused by infection of epithelia cells with Epstein–
Barr virus, and presents clinically as white, ragged, and corrugated or irreg-
ular lesions involving the later and dorso-lateral tongue. Lesions may be
unilateral or bilateral. Diagnosis can be confirmed by tissue biopsy. Histio-
logically, hairy leukoplakia exhibits hyperparakeratosis, often with hair-like
projections, epithelia hyperplasia, vacuolated epithelial cells (koilocyte-like),
and little or no inflammatory infiltrate in the underlying connective tissue
(Fig. 6). Hairy leukoplakia generally does not require treatment unless cos-
metically objectionable. Treatment options include the use of zidovidine,
podophyllin, and interferon. Regardless of treatment, lesions may spontane-
ously resolve and recur.

Histoplasma capsulatum is a fungus comprised of hyphae with characteris-
tic macroconidia or sexual spores. Histoplasma is found in soil and transmis-
sion is exogenous, but person-to-person transmission does not occur. Defense
against infection requires a healthy-cell–mediated response to stimulate mac-
rophages that engulf fungus and halt progression of disease. Histoplasmosis
may infect lungs, bone, and the central nervous system, and clinical findings
include fever, weight loss, skin or mucosal lesions, and respiratory symptoms,
such as cough and shortness of breath. Dissemination of histoplasmosis to the
oral mucosa may occur primarily on the gingival, tongue, palate, and buccal
mucosa. Gingival lesions will appear as diffuse granulomatous inflammation
with progressive alveolar bone erosion and loosening of teeth. Management of
histoplasmosis includes obtaining blood cultures for fungal sepsis and treat-
ment with liposomal amphotericin B or itraconazole.

Kaposi’s sarcoma
Kaposi’s sarcoma is the most prevalent AIDS-associated intraoral malig-
nancy. Kaposi’s sarcoma occurs more commonly in homosexual and

Fig. 6. Oral hairy leukoplakia.


bisexual males and is rarely seen in HIV-positive women and children. Ka-
posi’s sarcoma is an angioproliferative disease which may develop from hu-
man herpesvirus 8 (HHV-8) infection of mesenchymal progenitor cells.
Defined as a hyperplastic reactive inflammatory disease, Kaposi’s sarcoma
is characterized by mucosal lesions that begin as macular patches with red
or bluish-purple color, which may become darker and exophytic with ulcer-
ations as lesions advance (Figs. 7 and 8). Kaposi’s sarcoma may resemble
bacillary epithelial angiomatosis. Male homosexuals have the highest risk
of contracting Kaposi’s sarcoma. The hard palate is the most common
oral site, followed by the maxillary gingival. Small intraoral lesions may
be treated using intralesional injections of vinblastine sulfate or sclerosing
solution sodium tetradecyl sulfate. Local anesthesia should be infiltrated be-
fore injections to minimize pain associated with intralesional chemotherapy.

Linear gingival erythema

Linear gingival erythema describes a deep red appearance of the marginal
gingiva with increased risk for bleeding in some HIV-positive patients
(Fig. 9). Linear gingival erythema is most common on the facial gingiva
of the anterior teeth. It can also present on attached gingival as macular
red patches. Etiology of this condition remains unknown but candida infec-
tion may have a role. Treatment consists of improving self-hygiene habits,
professional gingival debridement, and twice-daily use of 5 mL 0.12% chlo-
rhexidine gluconate mouth rinse for 14 days.

Lymphoma is malignant neoplasm of lymphoid cells. The risk for AIDS-
related lymphomas increases with a CD4þ T-cell counts of !100 cells/mL.
Lymphomas are primarily non-Hodgkin’s, B-cell (humoral) malignancies,

Fig. 7. Kaposi’s sarcoma (palate).


Fig. 8. Kaposi’s sarcoma (palate).

possibly caused by a viral co-infection, such as Epstein–Barr virus, and

B-cell gene mutations. Symptoms include fever, night sweats, weight loss,
and anorexia. Lesions may occur in the oral cavity, and diagnosis is estab-
lished by tissue biopsy. Treatment options include systemic chemotherapy
and radiation therapy of lymphoid tumors.

Mycobacterium tuberculosis
Approximately one third of AIDS-related deaths worldwide are due to
tuberculosis (TB), and in Africa one third of people infected with TB are in-
fected with HIV. This pattern is most likely due to increased reactivation of
latent TB infections as well as higher primary rates of TB. All patients with
TB should be tested for HIV. Pulmonary TB is the most common clinical
manifestation. However extrapulmonary disease affecting the liver, spleen,
or kidney may occur in HIV-positive patients with CD4þ T cells !100
cells/mm3 [21]. Tuberculin skin testing with purified protein derivative
(delayed-type hypersensitivity response) is used to identify latent TB.
Some patients may have a problem complying with the requirement to

Fig. 9. Linear gingival erythema.


return so that skin induration can be checked. Tests read after a delay of 72
hours or more and found to be negative should be repeated. Active TB in
HIV-positive patients increases HIV viral RNA levels, which decrease after
treatment of TB is initiated. Treatment includes 6 months of treatment with
isoniazid, rifampin, pyrazinamide, and ethambutol. Side effects of therapy
include liver function abnormalities, rash, and peripheral neuropathy.

Necrotizing periodontal diseases

Two periodontal conditions have been identified in association with se-
vere immunosuppression: necrotizing ulcerative gingivitis (NUG) and nec-
rotizing ulcerative periodontitis (NUP). Both conditions are characterized
by rapid tissue destruction, severe pain, and bleeding, and affect about
2% to 6% of HIV-positive patients. In comparison, conventional periodon-
titis may occur in up to 30% of HIV-positive patients. NUP can be differ-
entiated from NUG by rapid periodontal attachment loss secondary to
necrosis of alveolar bone. Molecular biologists at the Forsyth Institute dis-
covered NUP did not possess conventional periodontopathic bacteria such
as Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola,
and Actinobacillus actinomycetemcomitans [22]. Instead, 26 ‘‘novel’’ phylo-
types were commonly detected in HIV-positive patients with NUP,
including Bulleidia extructa, Dialister, Fusobacterium, Selenomonas, Pep-
tostreptococcus, and Veillonella. Other research suggests that necrotizing
periodontal conditions occur more frequently and progress more rapidly
due to herpesvirus infection of periodontal tissues [23].

Due to the efficacy of antiretroviral agents and use of prophylactic regi-
mens, pneumocystis carinii pneumonia (PCP) now occurs less frequently
than it did during the first decade of the AIDS epidemic. The occurrence
of PCP is more likely due to lack of medication compliance, poor access
to medical care, or lack of awareness of HIV infection, though drug resis-
tance is also possible. Clinical symptoms include fever, nonproductive
cough, and shortness of breath. Chest radiographs reveal characteristic
diffuse infiltrative pulmonary infiltrates, and diagnosis is confirmed by
bronchoalveolar lavage and induced sputum examination. Trimethoprim–
sulfamethoxazole remains the drug of choice in treatment, and prophylactic
use of one single-strength tablet per day is still considered the standard of
care for patients with CD4þ T-lymphocyte counts of !200/ml or who pres-
ent with oropharyngeal candidiasis or other AIDS-defining infection.

Toxoplasma gondii, a protozoal infection in the general population, rep-
licates intracellularly in the host tissues, yet produces no or few clinical

manifestations in immunocompetent individuals. In immunodeficient per-

sons, latent toxoplasma infection reactivates, most commonly in intracere-
bral, ocular, and pulmonary tissues. Symptoms include headache,
confusion, altered mental status, low-grade fever, arthralgias, myalgias, fa-
tigue, and sore throat accompanied by cervical or generalized lymphadenop-
athy. Primary prophylaxis with trimethoprim–sulfamethoxazole is used to
prevent AIDS-related toxoplasmosis in persons with CD4þ T-cell counts
!100 cells/mL.

Vesicular-ulcerative conditions
Aphthous ulceration
Aphthous ulceration is the most commonly reported type of ulcers in
HIV-positive patients and its etiology remains undetermined (Fig. 10). Ul-
cers appear clinically as painful, round-to-oval, yellow or white, and are sur-
rounded by a halo of erythema. HIV-positive patients usually experience
increased frequency and severity of typical minor aphthous ulcers. Aph-
thous ulcers are usually treated with topical or systemic corticosteroids.
Thalidomide is also used, but pregnant women must be excluded because
of thalidomide’s teratogenic effects.

Herpes simplex
Herpes simplex virus (HSV) is a double-stranded DNA capsule enclosed
in a lipid envelope that is characteristically able to induce latency with peri-
odic reactivation of infection. HSV-1 is associated primarily with orolabial
lesions and HSV-2 with genital lesions. HIV infection on oral mucosa pres-
ents as an erythematous pruritus that develops into painful vesicles and
ulcerates over a brief period, accompanied by painful regional lymphade-
nopathy. In contrast to the yellow or white pseudomembrane in aphthous
ulcerations, HSV ulcers typically have a red center surrounded by a yellow
or white border. Orolabial HSV infections may occur on all oral mucosa
and can be more prolonged and severe than with HIV-negative individuals.

Fig. 10. Major aphthous ulceration.


Diagnosis can be confirmed using cytopathologic examination of scrapings

of ulcerations (Tzanck smear) or by DNA detection using PCR. Primary
treatment includes oral acyclovir therapy, with the use of famiciclovir and
valacyclovir as alternative agents.

Cytomegalovirus oral ulceration

Cytomegalovirus oral ulceration may occur in HIV-positive patients with
disseminated cytomegalovirus (CMV) disease, a DNA virus that causes la-
tency and reactivation of infection. Ulcers may occur anywhere in the oral
cavity and resemble major aphthous ulceration in size. However, instead of
an erythematous margin, CMV ulcers appear necrotic with a white halo.
Deep tissue biopsy with biopsy punch or scalpel is used to confirm diagnosis
and large intracellular inclusion bodies are characteristic of infection. Pa-
tients may develop CMV retinitis, esophagitis, colitis, pneumonitis, and neu-
rological disease. Treatment includes the use of drugs that treat human
herpesvirus infections, such as ganciclovir and foscarnet.
Neutropenic ulcerations are painful and appear intraorally when a pa-
tient’s absolute granulocyte counts drop below 800/mL and appear clinically
as very large, necrotic or fulminate ulcers. These ulcers may resemble squa-
mous cell carcinoma and diagnosis should include testing for absolute neu-
trophil count and differential. Lesions may become secondarily infected with
other opportunistic infections, and treatment requires the use of corticoste-
roid medications. Patients should be considered for treatment with granulo-
cyte-colony–stimulating factor.

Treatment planning considerations

Dentists should obtain a thorough health history and conduct a head-
and-neck examination checking for enlarged lymph nodes, and a comprehen-
sive intraoral soft tissue, periodontal and hard tissue examination at the
initial assessment. A baseline laboratory assessment of HIV-positive pa-
tients performed by medical physicians usually includes a complete blood
count and routine chemistries to assess liver and kidney function. While pa-
tients undergo medical treatment, dental check-ups should not be disrupted
or discontinued. Pseudomembranous candidiasis and oral hairy leukoplakia
are sensitive clinical markers of immunosupression. Dental providers should
be vigilant to monitor these markers at each assessment visit. With the ad-
vent of HAART, the prevalence of oral candidiasis, oral hairy leukoplakia,
and HIV-associated periodontal disease have decreased in adults. However,
there is evidence of an increase in the benign human papilloma-virus–
associated oral lesions, including papillomas, condylomas, and focal epithe-
lial hyperplasia, since HAART use. The prevalence of Kaposi’s sarcoma has
not changed.
Patients should receive counseling about modifiable risk factors, such as
cigarette smoking, which pose additional risks. Current smokers with low

CD4þ T-lymphocyte counts have greater risk than nonsmokers for develop-
ing candidiasis and hairy leukoplakia. Prior or current use of alcohol and
other drugs may increase complications, especially if hepatomegaly occurs
with viral co-infection or drug therapy. Patients should also receive safe-
sex counseling regarding oral sexual behaviors. For example, patients
should be told that Epstein–Barr virus may be transmitted by oral sex.
Dental treatment sequencing should be approached as a component of
medical care. Patients with low CD4þ T-lymphocyte counts (ie, !200
cell/mL) are predisposed to HIV-associated oral infections that require spe-
cific treatment. The dentist’s first priorities are to relieve pain and treat the
infection. Next, the dentist should implement prevention regimens to pre-
vent concomitant disease. The third task is to restore function so that pa-
tients can eat and maintain their nutrition. Enhanced preventive care
compromising bimonthly prophylaxis and chlorhexidine mouth rinses to
prevent gingivitis may improve the patient’s psychological health, but there
is no evidence that this will reduce the occurrence of AIDS-related opportu-
nistic infections. Lastly, the dentist must provide esthetic procedures to im-
prove self-esteem and enhance psychological health. It is both safe and
desirable to assure that regular comprehensive dental care is available to
HIV-positive patients. In the United States, Title I, II, III and IV of the fed-
eral Ryan White Comprehensive AIDS Resources Emergency Act supports
oral health services for HIV-positive persons. Additionally, Section F of the
act provides the Dental Reimbursement Program, which retrospectively
compensates unreimbursed dental schools, dental hygiene programs, and
postdoctoral dental training programs for providing dental care to people
with HIV.

Table 3
Web resources for dental care providers
Website Name Description HIV Dent Developed by Dr. David Resnick at
Grady Health Systems in Atlanta,
Georgia. Provides basic information
about clinical care and about
manifestations of HIV. International Provides treatment guidelines and
AIDS Society publishes Topics in HIV Medicine. New York State Provides treatment guidelines and
Department of best practices.
Health AIDS
Institute National HIV/AIDS Developed by the University of
Clinicians’ California at San Francisco.
Consultation Center Provides treatment guidelines and
best practices. Dental Alliance for Dental treatment site that contains
AIDS/HIV Care links to other information sites.

Dental treatment can be provided in outpatient settings without hospital-

ization. No modification of irreversible procedures or surgical dental treat-
ment is recommended unless patients have reduced platelet count to
!60,000 cells/mL, which may affect clotting time, or white–blood-cell neu-
trophil counts !500 cells /mL, which may require antibiotic prophylaxis.
A careful history will detect abnormal bleeding or signs of severe bleeding
disorder known as idiopathic thrombocytopenia pupura, which presents
with characteristic intraoral mucosal petechiae and ecchymoses. Routine an-
tibiotic use is contraindicated and may predispose patients to superinfection
and microorganism drug resistance. Consult with the patient’s physician re-
garding antibiotic prophylaxis use for prosthetic joints or heart valve condi-
tions. Antiretroviral therapies have been associated with new-onset glucose
intolerance and hyperlipidemia. Patients may have periodic screening with
fasting blood glucose and lipid determinations. Useful resources on the
Internet for dental care providers are listed on Table 3.

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