CHAPTER

18 
AIDS, HIV Infection, and
Related Conditions

On June 5, 1981, when the Centers for Disease Control

Incidence and Prevalence
(CDC) reported five cases of Pneumocystis carinii (now
jiroveci) pneumonia in young homosexual men in Los An estimated 2.7 million people across the globe are
Angeles, few suspected that it heralded a pandemic of newly infected with HIV annually. At the end of 2009,
acquired immunodeficiency syndrome (AIDS). In 1983, there were an estimated 33.4 million persons globally
a retrovirus (later named the human immunodeficiency and an estimated 1.1 million persons in the United States
virus [HIV]) was isolated from a patient with AIDS. who were infected and living with HIV infection/AIDS.1
Since that first report, more than 70 million persons Worldwide, these rates represent a 3-fold higher preva-
have been infected with HIV, and more than 30 million lence since 1990, but a decline since the peak prevalence
have died of AIDS.1 The total number of deaths has that occurred in 1999. In the United States, approxi-
exceeded those caused by the Black Death of 14th-century mately 24% are undiagnosed and unaware of their infec-
Europe and the influenza pandemic of 1918 and 1919. tion, 42% are HIV-positive but not yet progressed to
About 95% of HIV-infected persons live in low- to AIDS, and 34% have AIDS.7
middle-income regions, countries, and in sub-Saharan The CDC estimated that approximately 56,300
Africa. More than 40% of new infections (excluding persons were newly infected with HIV in 2006 and
those in infants) occur in young people 15 to 24 years 42,000 were newly infected in 2009.7,8 A majority of
of age.2,3 those infected are between the ages of 20 and 45, male,
AIDS is an infectious disease that is transmitted pre- and disproportionately black. Recent estimates for cases
dominantly through intimate sexual contact and by par- of HIV infection diagnosed in the United States by age,
enteral means. In view of the nature of this bloodborne race, and transmission category are shown in Table 18-1.9
pathogen, HIV infection and AIDS have important The overall prevalence (among persons older than 13
implications for dental practitioners. Although HIV has years of age) is 70.8 for black men who have sex with
rarely been transmitted from patients to health care men (MSM) and 14.6 for white MSM per 100,000,10 and
workers, this may occur, and the patient with HIV infec- the number of cases of HIV infection due to heterosexual
tion or AIDS may be medically compromised and may transmission remains greater than 15,000 per year.11
need special dental management considerations. On the The estimated number of AIDS diagnoses in the United
basis of current statistics, the average dental practice is States for 2009 was approximately 34,000. Adult and
predicted to encounter at least two patients infected with adolescent AIDS accounted for about 99% of the cases,
HIV per year. 75% of which occurred in males and 25% in females.
The cumulative estimated number of AIDS diagnoses
through 2009 in the United States was 1.1 million.7,11
DEFINITION Since the introduction of protease inhibitors in 1996
The definition of AIDS provided by the CDC has been and the advent of highly active antiretroviral therapy
revised several times over the years, and in 2008 it was (HAART), the epidemic of AIDS in the United States has
revised to be laboratory-confirmed evidence of HIV slowed and stabilized. Still, the CDC reports approxi-
infection in a person who has stage 3 HIV infection (i.e., mately 2250 new cases per month. As of the end of 2006,
a CD4+ lymphocyte count less than 200 cells/µL).4 This 565,927 deaths have been reported in the United States
definition also includes HIV-infected persons whose due to AIDS, and 14,627 deaths occurred in 2006 alone.
CD4+ count may be above 200 but have an AIDS- Most deaths occur in adults, with few deaths reported
defining condition, as shown in Box 18-1. Of note, in children younger than age 13 in 2006.12 In the United
because of the provision of antiretroviral drug regimens, States, AIDS is the leading cause of death in men 25 to
not all patients progress to AIDS or develop life- 44 years of age. Worldwide, there are 2 million deaths
threatening opportunistic infections.5,6 per year, and more than 30 million persons have died of
284
 CHAPTER 18  AIDS, HIV Infection, and Related Conditions 285

(starting in 1985) of donor blood for HIV antibodies and

B O X 1 8 - 1 AIDS-Defining Conditions
the heating of factor VIII replacement preparations. Also,
•
an increase in the ratio of infected women to men occurred
Bacterial infections, multiple or recurrent*
•
a decade ago; this ratio has remained stable in about 25%
Candidiasis of bronchi, trachea, or lungs
of women but is particularly higher in the 30- to 40-year
• Candidiasis of esophagus† age group of black women.11
• Cervical cancer, invasive§ At present there is no effective vaccine to prevent HIV
• Coccidioidomycosis, disseminated or extrapulmonary infection, although large research efforts have and con-
• Cryptococcosis, extrapulmonary tinue to be made in this arena. Also, a nonpandemic
• Cryptosporidiosis, chronic intestinal (longer than 1 month in
relating strain of HIV, known as HIV-2, occurs less com-
duration)
•
monly throughout the world. Most cases of HIV-2 infec-
Cytomegalovirus disease (other than liver, spleen, or nodes),
onset at age >1 month tion have occurred in West Africa, with a limited number
• Cytomegalovirus retinitis (with loss of vision)† of cases occurring in Canada and the United States. Most
• Encephalopathy, HIV-related persons infected with HIV-2 are long-term nonprogres-
• Herpes simplex: chronic ulcers (>1 month’s duration) or bron- sors because viral loads generally are low, and the immu-
chitis, pneumonitis, or esophagitis (onset at age >1 month) nosuppression is not as severe.14,15
• Histoplasmosis, disseminated or extrapulmonary
• Isosporiasis, chronic intestinal (>1 month’s duration)
• Kaposi sarcoma† Etiology
• Lymphoid interstitial pneumonia or pulmonary lymphoid hyper- AIDS is caused by HIV, a nontransforming retrovirus of
plasia complex*†
•
the lentivirus family. There are two HIV subtypes, HIV-1
Lymphoma, Burkitt (or equivalent term)
•
and HIV-2, and many strains of each. HIV-1 was first
Lymphoma, immunoblastic (or equivalent term)
• Lymphoma, primary, of brain identified in 1983 by Francoise Barre-Sinoussi in the lab
• Mycobacterium avium complex or Mycobacterium kansasii of Luc Montaignier of the Pasteur Institute. They first
infection, disseminated or extrapulmonary† called it lymphadenopathy-associated virus. Within a
• Mycobacterium tuberculosis infection of any site, pulmonary,†§ year of this discovery, a team led by Robert Gallo from
disseminated,† or extrapulmonary† the National Institutes of Health isolated a retrovirus
• Mycobacterium infection, other species or unidentified species, identified as the human T lymphotropic virus III (HTLV-
disseminated† or extrapulmonary† III) and labeled it as the etiologic agent for AIDS. In
• Pneumocystis jiroveci pneumonia† 1984, Jay Levy’s team in San Francisco also isolated a
• Pneumonia, recurrent†§ retrovirus, AIDS-related virus (ARV), and designated it
• Progressive multifocal leukoencephalopathy
as the causative agent for AIDS. All three viruses were
• Salmonella septicemia, recurrent
similar retroviruses, but minor differences were observed
• Toxoplasmosis of brain, onset at age >1 month†
• Wasting syndrome attributed to HIV in their amino acid sequences. Variation in disease pat-
terns are attributed to the slight sequence differences
*Only among children younger than 13 years of age. (Data from Centers for among HIV strains, which also makes difficult the pro-
Disease Control and Prevention [CDC]: 1994 revised classification system duction of a vaccine. The three groups essentially were
for human immunodeficiency virus infection in children less than 13 years
describing the same retrovirus, which can change its
of age, MMWR Recomm Rep 43:1, 1994; Centers for Disease Control and
Prevention [CDC]: 2008 revised surveillance case definitions for HIV infec- antigenicity. Until 1986, most workers in the field
tion among adults, adolescents, and children aged <18 months and for HIV referred to the virus as HTLV-III and considered it to be
infection and AIDS among children aged 18 months to <13 years—United the causative agent for AIDS. In 1986, the World Health
States, MMWR Recomm Rep 57:9, 2008.) Organization (WHO) recommended that the AIDS virus
†
Condition that might be diagnosed presumptively.
§ be called the human immunodeficiency virus16-18 (Figure
Only among adults and adolescents 13 years of age and older. (Data from
Centers for Disease Control and Prevention [CDC]: 1993 Revised classifica- 18-1). Subsequent analysis of frozen tissue and serum
tion system for HIV infection and expanded surveillance case definition for samples from select patients who died of uncertain causes
AIDS among adolescents and adults, MMWR Recomm Rep 41: 1, 1993.) in the 1950s and 1960s demonstrated that HIV had
AIDS, Acquired immunodeficiency syndrome. infected these patients, indicating its presence in humans
for more than 60 years.19
AIDS.13 AIDS is the world’s leading cause of death in HIV is an enveloped RNA retrovirus about 100 nM
women and men aged 15 to 59 years.2,13 in diameter. Glycoproteins (gp41 and gp120) stud the
Several trends in the epidemiology of AIDS have surface of the envelope and serve to bind to human cells
emerged over the decades. In the United States, peak (Figure 18-2). Internal to the envelope is a protein capsid
incidence was in 1993 and peak incidence of death was (p24) that surrounds essential viral enzymes (protease,
50,877 in 1995. The past 2 decades witnessed a decline integrase, reverse transcriptase) and an RNA inner core.
in the number of cases of AIDS associated with blood and It infects most human cells. However, the cells most com-
blood products in transfusion and hemophiliac patient monly infected are those with CD4+ receptors, including
groups, specifically attributable to improved testing T helper lymphocytes (CD4+ cells) and macrophages.
286 CHAPTER 18  AIDS, HIV Infection, and Related Conditions

TA B L E 1 8 - 1 Select Patient Characteristics in HIV Infection and AIDS*

Estimated No. of Cases

AIDS:
Cumulative
Patient Characteristic HIV Infection AIDS Data
Age (Years)
Under 13 166 13 9448
13-19 2057 542 8535
20-29 12,188 5571 172,559
30-39 10,252 8936 448,724
40-49 10,384 11,155 319,617
50-59 5327 6174 111,352
60 and older 1636 1056 38,376
Race or Ethnicity
American Indian/Alaska Native 189 155 3700
Asian 470 429 8324
Black 21,652 16,741 466,351
Hispanic/Latino 7347 6719 190,263
Native Hawaiian/other Pacific Islander 34 50 839
White 11,803 9467 426,102
Multiple races 516 686 12,726
Transmission Category
Male-to-male sexual contact 23,846 17,005 529,908
Injection drug use 3932 4942 273,444
Male-to-male sexual contact and 1131 1580 77,213
injection drug use
Heterosexual contact 12,860 10,393 198,820
Perinatal 131 12 8640
Other* 111 313 20,583
*U.S. 2009 data, including cases of hemophilia, blood transfusion, and risk not reported or not identified (adults, adolescents, and infants).
Data from Centers for Disease Control and Prevention: HIV/AIDS statistics and surveillance/basic statistics (article online), http://www.cdc.gov/hiv/topics/
surveillance/basic.htm?source=govdelivery#international; accessed on March 5, 2010.

Accordingly, these cells are most deeply involved in

p17 matrix
p24 capsid HIV infection. Additional coreceptors that allow HIV
Lipid
to infect human cells include CCR5, CXCR4 (fusin),
bilayer and CCR2.20
HIV-1 infection is divided into stages: entry, reverse
Protease transcription of RNA to DNA, export of the viral DNA
from the cytoplasm to the nucleus and integration into
Integrase the host chromosome, transcription, translation and
cleavage of the polyproteins produced, assembly of
RNA virions, and budding of virions. The process is largely
gp41 regulated by the proteins tat, rev, and nef, which are
gp120 necessary for viral replication. Virulence has been
Reverse mapped to the carboxyl-terminal half of the gp120,
transcriptase which has been referred to as the V3 loop.20 (For addi-
tional information see Chapter 182 in Fauci AS, et al.,
100 nm (editors): Harrison’s Principles of Internal Medicine,
FIGURE 18-1  The structure of human immunodeficiency virus, ed 17, New York, 2008, McGraw Medical.)
showing the p24 capsid protein surrounding two strands of viral
RNA. (From Copstead LC, Banasik JL: Pathophysiology, ed 4,
St. Louis, 2010, Saunders.) Pathophysiology and Complications
Transmission of HIV is by exchange of infected bodily
fluids from sexual contact and through blood and
blood products. The most common method of sexual
 CHAPTER 18  AIDS, HIV Infection, and Related Conditions 287

HIV
virion

Viral
assembly
and budding

HIV Cell HIV

virion Injects viral RNA RNA
Protease
cleaves
Fuses with cell Reverse Provirus protein
transcriptase integrated
transforms into host Viral
into DNA cell’s DNA proteins

Cell
Migrates nucleus
Messenger
to nucleus Activates RNA
cell

FIGURE 18-2  Life Cycle of the Human Immunodeficiency Virus. (From Copstead LC, Banasik JL: Pathophysiology, ed 4, St. Louis, 2010,
Saunders.)

transmission in the United States is anal intercourse in Once HIV has gained access to the bloodstream, the
MSM, in whom the risk of HIV infection is 40 times virus selectively seeks out T lymphocytes (specifically T4
higher than in other men and in women.21 Heterosexual or T helper lymphocytes) (see Figure 18-2). The virus
transmission (male to female or female to male) is the binds to the CD4+ lymphocyte cell surface specifically
second most common form of transmission in the United through the highly glycosylated outer surface envelope
States but accounts for 80% of the world’s HIV infec- (gp120) proteins. Upon infection, reverse transcriptase
tions. Heterosexual transmission of HIV can occur catalyzes the synthesis of a haploid, double-stranded
through sexual contact of carriers who are heterosexual DNA provirus, which becomes incorporated into the
injection drug users, bisexual men, or blood recipients chromosomal DNA of the host cell. Thus integrated, the
of either gender. Transmission from injection drug use is provirus genetic material may remain latent in an unex-
the third largest group to be affected in the United pressed form until events occur that activate it, at which
States.22 time DNA transcription rapidly occurs and new virions
The virus is found in blood, seminal fluid, vaginal are produced. The virus is lymphotropic; hence, the cells
secretions, tears, breast milk, cerebrospinal fluid, amni- it selects for replication are soon destroyed. Once the
otic fluid, and urine. Blood, semen, breast milk, and virus takes hold, it causes a reduction in the total number
vaginal secretions are the main fluids that have been of T helper cells, and a marked shift in the ratio of CD4+
shown to be associated with transmission of the virus. to CD8+ lymphocytes occurs. The normal ratio of T
Vertical transmission to infants born of infected helper to T suppressor lymphocytes is about 2 : 1 (60%
mothers can occur at birth or transplacentally. HIV has T helper, 30% T suppressor). In AIDS, the T4/T8 ratio
been found in saliva, and transmission by transfer of is reversed. This marked reduction in T helper lympho-
saliva possibly contaminated with blood has been cytes, to a great degree, explains the lack of an effective
reported from providing premasticated food from HIV- immune response seen in patients with AIDS and con-
infected parents to infants.23 Casual contact has not been tributes to the increase in malignant disease that has been
demonstrated as a means of transmission. Inflammation found to be associated with AIDS, including Kaposi
and breaks in the skin or mucosa (e.g., presence of other sarcoma, lymphoma, carcinoma of the cervix, and car-
sexually transmitted diseases) and high concentrations of cinoma of the rectum.20
HIV in bodily fluids increase the risk of transmission.24-26 Table 18-2 presents the clinical stages of HIV infec-
Oral sex is an inefficient but documented mode of trans- tion through frank AIDS. More than 50% of persons
mission.27 The risk of transmission from a blood transfu- exposed to the virus develop an acute and brief viremia
sion is estimated to be less than 1 in 1 million because (seroconversion sickness) within 2 to 6 weeks of HIV
of current screening measures. Occupational exposure exposure and then develop antibodies (anti-gag, anti-
also is a source of transmission and health care provider gp120, anti-p24) between weeks 6 and 12. A few
to patient transmission has occurred (see later under may take 6 months or longer to achieve seroconversion.
“Dental Management”). A concomitant, transient fall in CD4+ cells occurs
288 CHAPTER 18  AIDS, HIV Infection, and Related Conditions

TA B L E 1 8 - 2 Features of HIV Infection and Disease Progression

Status Signs/Symptoms Laboratory Findings Comments

Recent infection No signs or symptoms HIV nucleic acid: positive p24 Patient is unaware of his or
antigen; positive DNA PCR her HIV infection.
assay; ELISA and Western Can transmit the infection
blot may or may not be by blood or sexual
positive. activity.
Stage 1 Symptoms occur within about 1-3 weeks after HIV antibody–negative at start The severity of the acute
Acute seroconversion infection in about 70% of infected patients: of syndrome. syndrome varies among
syndrome Fever, weakness, diarrhea, nausea, vomiting, Seroconversion occurs near end infected persons.
myalgia, headache of the syndrome. The period for
Weight loss CD4+ and CD8+ lymphocytes seroconversion of 30%
Pharyngitis reduced in numbers, but of patients without
Skin rashes (roseola-like or urticarial) >500 cells/µL acute symptoms varies
Lymphadenopathy After acute symptoms, they tend and can be 1-6 months
Symptoms clear in about 1 to 2 wk to return toward normal or longer.
levels.
ELISA and Western blot are
positive.
Stage 2 Median time from initial infection to onset of ELISA and Western blot are Viral replication is ongoing
Latent period clinical symptoms: 8-10 years positive. and progressive.
(asymptomatic stage) About 50-70% of patients develop persistent A slow but usually steady A steady decline in CD4+
generalized lymphadenopathy (PGL). increase in viral load. cell counts occurs,
Usually, a steady decline in   except in the less
CD4+ cell count; CD4+/CD8+ than 1% who are
ratio begins to approach 1. nonprogressors (also
have low viral load).
Stage 2 Without treatment, lasts for 1 to 3 years. Any ELISA and Western blot are The spectrum of disease
(Early symptomatic stage) of the following: positive. changes as CD4+ cell
PGL HIV antigen, RNA, and DNA tests count declines.
Fungal infections are positive.
Vaginal yeast and trichomonal infections Signs and symptoms increase as
Oral hairy leukoplakia CD4+ cell count declines and
Herpes zoster approaches 200/µL; often
Herpes simplex between 200 and 300/µL.
HIV retinopathy Viral load continues to increase.
Constitutional symptoms: Platelet count may decrease in
fever, night sweats, fatigue diarrhea, weight about 10% of patients.
loss, weakness
Stage 3 Opportunistic infection(s): High viral load. CD4+ cell count Death usually occurs
(AIDS) Pneumocystis jiroveci pneumonia below 200/ µL. because of wasting,
Cryptococcosis CD4+ cell count below 50/µL at opportunistic infection,
Tuberculosis high risk for lymphoma and or malignancies.
Toxoplasmosis death. The use of combination
Histoplasmosis Platelet count may be low. antiretroviral agents
Others Neutrophil count may be low. has slowed the death
Malignancies: ELISA and Western blot are rate, but long-term
Kaposi sarcoma positive. outlook must depend on
Burkitt’s lymphoma HIV antigen, RNA, and DNA tests vaccines for prevention
Non-Hodgkin’s lymphoma are positive. and treatment because
Primary CNS lymphoma the virus promotes
Invasive cervical cancer, carcinoma of rectum resistance to these
Slim (wasting) disease agents.
AIDS, Acquired immunodeficiency syndrome; CNS, Central nervous system; ELISA, Enzyme-linked immunosorbent assay; HIV, Human immunodeficiency virus;
PCR, Polymerase chain reaction.
 CHAPTER 18  AIDS, HIV Infection, and Related Conditions 289

FIGURE 18-3  The natural history of human immunodeficiency virus infection. (From Brookmeyer R, Gail MH: AIDS epidemiology: a quan-
titative approach, New York, 1994, Oxford University Press.)

(lymphopenia, along with high titers of plasma HIV), but including Pneumocystis pneumonia, toxoplasmosis, cryp-
patients do not develop evidence of immunosuppression. tococcosis, influenza, histoplasmosis, tuberculosis, cyto-
Various flulike symptoms occur during this acute infec- megalovirus (CMV) infection, mucocutaneous diseases
tion, which usually lasts about 2 to 4 weeks. Only an such as candidiasis, and neoplasms previously discussed.
estimated 20% of affected persons seek medical atten- Neurologic disease is common and includes secondary
tion. During primary infection, HIV disseminates opportunistic infections as well as primary HIV infection
throughout the lymphoid tissue, incubates and repli- of macrophages, neurons, and microglial cells in the CNS
cates. These events allow HIV to establish a chronic that leads to rapidly progressive dementia.
infection and reservoirs of latently infected cells. Evidence suggests that persons most susceptible to
As time progresses, a steady-state viremia develops, developing AIDS are those with repeated exposure to the
and several thousand copies of HIV are present in the virus who also have an immune system that has been
blood (Figure 18-3). This clinical latency period is char- challenged by repeated exposure to various antigens
acterized by evolution of the virus within its host to (semen, hepatitis B, or blood products).20 The median
generate closely related, yet distinct mutant viruses that time from primary infection to the development of AIDS
serve to evade the surveying immune response and cir- in untreated patients is about 10 years. About 30% of
culating antibodies. Although the infection is clinically patients with AIDS can be expected to live approxi-
latent, there is a progressive decline in immune function mately 2 to 3 years, with most others living 10 years or
evident as progressive depletion of CD4+ lymphocytes longer. Long-term survival with HIV infection (beyond
with ultimate pancytopenia, impaired lymphocyte pro- 15 years) occurs and is associated with less virulent HIV
liferation, and cytokine responses to mitogens and anti- strains, lower-level viremia, HAART, and robust immune
gens; impaired cytotoxic lymphocyte function and responses.28
natural killer cell activity; anergy to skin testing; and
diminished antibody responses to new antigens.20
CLINICAL PRESENTATION
In untreated persons and in persons in whom therapy
is ineffective, the CD4+ count continues to decline
Signs and Symptoms
while HIV proliferates. As the CD4+ count drops and
approaches 200 cells/µL, persons can exhibit weight loss, During the first 2 to 6 weeks after initial infection with
diarrhea, and night sweats (see Figure 18-3). When the HIV, more than 50% of patients develop an acute flulike
CD4+ count drops to below 200 cells/µL, the person has syndrome marked by viremia that may last 10 to 14
AIDS and is susceptible to opportunistic infections, days. Others may not manifest this symptom complex.
290 CHAPTER 18  AIDS, HIV Infection, and Related Conditions

BO X 1 8 - 2 CDC Staging of HIV Infection in Laboratory Findings

Adults and Adolescents
Most patients exposed to the virus, with or without clini-
Stage 1: Laboratory confirmation of HIV infection, no AIDS-defining cal evidence of disease, show antibodies to the virus by
conditions and CD4+ T lymphocyte count of ≥500 cells/µL or the 6th month of infection. Patients with advanced HIV
CD4+ T lymphocyte percentage of total lymphocytes of ≥29. infection or AIDS have an altered ratio of CD4+/CD8+
Stage 2: Laboratory confirmation of HIV infection, no AIDS-defining lymphocytes, a decrease in total number of lymphocytes,
condition, and laboratory confirmation of HIV infection and CD4+ thrombocytopenia, anemia, a slight alteration in the
T lymphocyte count of 200-499 cells/µL or CD4+ T lymphocyte humoral antibody system, and a decreased ability to
percentage of total lymphocytes of 14-28. show delayed allergic reactions to skin testing (cutaneous
Stage 3 (AIDS): Laboratory confirmation of HIV infection and CD4+ anergy).20 CD4+ and CD8+ cell counts should be per-
T lymphocyte count is <200 cells/µL or CD4+ T lymphocyte formed at the time of HIV diagnosis and then every 3 to
percentage of total lymphocytes is <14 or documentation of
4 months.2
an AIDS-defining condition (see Box 18-1). Documentation of an
The enzyme-linked immunosorbent assay (ELISA) is
AIDS-defining condition supersedes a CD4+ T lymphocyte count
of ≥200 cells/µL and a CD4+ T lymphocyte percentage of total the screening test for identification of antibodies to HIV.
lymphocytes of ≥14. It is 90% sensitive but has a high rate of false-positive
results. Current practice is to screen first with ELISA. If
CDC, Centers for Disease Control and Prevention; HIV, Human immunodefi- the results are positive, a second ELISA is performed. All
ciency virus; AIDS, Acquired immunodeficiency syndrome. positive results are then confirmed with Western blot
analysis. This combination of tests is accurate more than
99% of the time. Positive ELISA and Western blot test
results indicate only that the individual has been exposed
to the AIDS virus. If results of the Western blot are inde-
Symptomatic persons often develop lymphadenopathy, terminate, HIV infection is rarely, if ever, present. These
fever, pharyngitis and a skin rash but generally do not tests, however, do not indicate the status of the HIV
display circulation antibodies until the 6th week to 6th infection or whether AIDS is present. However, patients
month. The severity of the initial acute infection with with positive results on the ELISA and Western blot test
HIV (i.e., level of viremia) is predictive of the course the are considered potentially infectious. ELISA testing for
infection will follow. In one study, 78% of persons with HIV in saliva is an alternative approach that is 98%
a long-lasting acute illness developed AIDS within 3 sensitive in detecting antibodies to HIV.30 More recently,
years; by contrast, only 10% of those patients with no Abbott has developed a combination assay, the ARCHI-
acute illness at seroconversion developed AIDS within 3 TECT HIV Ag/Ab Combo assay (Abbott Laboratories,
years.29 Abbott Park, Illinois), that can simultaneously detect the
The CDC defines three stages of HIV infection.4 Box combined presence of HIV antigens (the p24 antigen
18-2 illustrates the definitions for each stage. Briefly, produced by HIV) and antibodies to HIV. This recently
stage 1 generally begins immediately after HIV exposure FDA approved test is expected to be important for diag-
and may last for years. Affected persons are HIV nosing HIV infection in the acute phase of the disease
antibody–positive but are asymptomatic and show no when antibodies are not yet present and for ongoing
other laboratory abnormalities. Stage 2 is characterized monitoring of patients.31
by progressive immunosuppression and symptomatic Nucleic acid amplification using polymerase chain
disease. Patients who demonstrate various laboratory reaction (PCR)-based assays of the viral RNA is per-
changes (i.e., lymphopenia: T helper/T suppressor ratio formed to determine the viral load in the blood (i.e.,
usually less than 1) in addition to HIV antibody positiv- degree of viremia) and monitor response to therapy.
ity also may show clinical signs or symptoms, such as Detection ranges are from 40 copies/mL to more than
enlarged lymph nodes, night sweats, weight loss, 750,000 copies/mL. The greatest viral load is found
oral candidiasis, fever, malaise, and diarrhea. Persons during the first 3 months after initial infection and during
in stage 3 have AIDS and can demonstrate a variety late stages of the disease. Direct detection of HIV by PCR
of immunesuppression-related diseases. Opportunistic assay is superior to testing for HIV antigen in serum, but
infections predominate as the CD4+ T count approxi- more expensive.32 Antiviral resistance testing is recom-
mates 200 cells/µL; then malignancies, wasting syn- mended when treatment is failing.33
drome, and a progressive form of dementia can develop.
Patients may become confused and disoriented or may
experience short-term memory deficits. Others develop
MEDICAL MANAGEMENT
severe depression or paranoia and show suicidal tenden-
cies. Figure 18-3 depicts the natural history of HIV, and Medical management of the HIV-infected patient has
Table 18-2 lists the diseases associated with the progres- four main treatment goals: (1) to reduce HIV-associated
sion of HIV infection through frank AIDS. morbidity and prolong the duration and quality
 CHAPTER 18  AIDS, HIV Infection, and Related Conditions 291

of survival, (2) to restore and preserve immunologic combinations known as ART or HAART and should be
function, (3) to maximally and durably suppress plasma given long-term.
HIV viral load, and (4) to prevent HIV transmission.33 The drug regimen that is initiated should be individu-
The physician managing these patients should be an alized to be potent enough to suppress the viral load to
expert in infectious disease and in the use of antiretrovi- below the level of assay detection for a prolonged period,
ral drugs. Antiretroviral therapy (ART) should be used while reducing the virus mutation rates that can lead to
in a manner that will achieve viral suppression and drug resistance. Currently, preferred regimens for the
immune reconstitution while at the same time preventing ART-naive patient consist of either efavirenz + tenofovir
emergence of resistance and limiting drug toxicity. Long- + emtricitabine or ritonavir-boosted atazanavir/darunavir
term goals are to delay disease progression, prolong life, plus tenofovir/emtricitabine, or raltegravir + tenofovir +
and improve quality of life. Treatment often is organized emtricitabine. Several alternative drug regimens also
into three major areas: (1) ART, (2) prophylaxis for appear in recent Department of Health and Human Ser-
opportunistic infections, and (3) treatment of HIV- vices guidelines; however, no regimen has proved supe-
related complications. Monitoring response to therapy is rior to efavirenz-based regimens with respect to virologic
a long-term requirement, as more than 70% of HIV responses.33 Patients who respond to therapy generally
infected persons survive beyond 10 years from the time show an increase in CD4+ count in the range of 50 to
of diagnosis in the United States, especially if treatment 150 cells/µL per year and viral loads of less than 75
is not delayed.12,34 copies/mL.33 Virologic suppression is defined as less than
48 copies/mL, and virologic failure is defined as a con-
firmed viral load of greater than 200 copies/mL in the
ART and HAART presence of ART.33
Over the past decade, much progress has been made in Patients who are on ART medications must be closely
the treatment of AIDS because of ART and HAART. monitored for drug effectiveness (which often wanes over
Both ART and HAART involve use of combinations of time), development of antiviral resistance, drug toxicity,
antiretroviral drugs; however strictly speaking, HAART and drug interactions. Some important toxicities include
is defined as the use of at least three active antiretroviral hyperlactemia, mitochondrial dysfunction, peripheral
medications. Today the terms ART and HAART are neuropathy, hepatotoxicity, and lipodystrophy. Compli-
essentially equivalent. ance also is a major challenge for patients in view of
The benefits of ART are now well known. ART recognized drug toxicities, costs, and inconvenience.35 To
increases survival, reduces systemic complications, and this end, several drugs are now formulated as combina-
improves the quality of life in patients infected with tion agents to simplify and improve treatment of the
HIV.2 The major goal of ART is to inhibit HIV replica- disease. Atripla, Epzicom, and Trizivir are combinations
tion completely such that the viral load is below the of three antiretrovirals, and Combivir, Epzicom, Trizivir,
detection limit of the assay at 4 to 6 months. However, and Truvada are combinations of two nucleoside–
there are no conclusive studies that show when therapy nucleotide reverse transcriptase inhibitors. Only a decade
should be initiated. Experts recommend starting treat- ago, when cocktails of AIDS drugs began to be used,
ment in all patients with symptoms ascribed to HIV patients sometimes had to take two dozen or more pills a
infection, all pregnant mothers infected with HIV, and day. Currently, immune modulators also are being tested
all HIV-infected infants. ART currently is recommended in conjunction with ART.
when the CD4+ count is less than 350 cells/µL and in In about 25% of patients, particularly those with a
those with plasma HIV RNA levels greater than 55,000 very low CD4+ T cell count, weeks after initiation of
copies/mL.33 Treatment is generally initiated for asymp- ART, an exacerbation of preexisting opportunistic infec-
tomatic patients who have a rapid drop in CD4+ T cell tions occurs.36 This condition, known as immune recon-
count or high viral loads. Asymptomatic patients with stitution inflammatory syndrome (IRIS), probably results
stable CD4+ T cell counts and low viral loads are gener- from elicitation of an inflammatory response in associa-
ally followed without treatment. ART is strongly recom- tion with the antiviral drugs, leading to focal lymphad-
mended for patients with CD4+ T cell counts lower than enitis and reactivation of a viral disease (e.g., shingles)
200/µL and for those with AIDS.20,33 or granulomatous infection.20
Antiretroviral drugs are used to restore immune Chemoprophylaxis.  Chemoprophylaxis regimens are
dysfunction by inhibiting viral replication. More than recommended when CD4+ lymphocyte counts drop to
20 antiretroviral drugs are currently available for the specific levels to prevent initial episode of a disease or to
management of HIV infection/AIDS (Table 18-3). suppress a developing opportunistic infection. These
The antiretroviral agents available are classified into regimens exist for the prevention of Pneumocystis pneu-
five categories: protease inhibitors (PIs), nucleoside monia, tuberculosis, toxoplasmosis, and other opportu-
reverse transcriptase inhibitors (NRTIs), non-nucleoside nistic diseases. Also, select vaccines are recommended for
reverse transcriptase inhibitors (NNRTIs), nucleotides, the HIV-infected adult before the CD4+ T cell count
and entry inhibitors. These agents usually are used in drops to below 200/µL. Standard resources such as the
292 CHAPTER 18  AIDS, HIV Infection, and Related Conditions

TA B L E 1 8 - 3  Antiretroviral Drugs Used to Treat HIV Infection

Drug Toxicity Interactions Comments

Protease Inhibitors (PIs)
Amprenavir Nausea, vomiting Amiodarone PIs act at the end of the virus
Atazanavir Nausea, vomiting, liver, tingling Midazolam, triazolam replication cycle, blocking
arms/legs the catalytic center of the
Darunavir Nausea, diarrhea, lipodystrophy Midazolam, triazolam, quinidine protease enzyme, resulting
Fosamprenavir Nausea, vomiting Midazolam, triazolam in viral particles that are
Indinavir Diarrhea Quinidine ineffective and immature.
Lopinavir* Abdominal discomfort Rifampin
Nelfinavir Paresthesias Ergotamine
Ritonavir* Fatigue St. John’s wort
Saquinavir Anemia, leukopenia Midazolam
Thrombocytopenia Triazolam
Altered taste
Hypercholesterolemia
Hypertriglyceridemia
Xerostomia
Tipranavir Nausea, vomiting, diarrhea, liver Midazolam, triazolam, quinidine
damage
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Abacavir** Headache Avoid mixing zidovudine and Drug adverse effects often
Emtricitabine Insomnia stavudine, ribavirin, or are dose-related and can
Didanosine Fatigue doxorubicin. be minimized with lower
Lamivudine** Anemia, neutropenia Ganciclovir and interferon-α must doses. Use of zalcitabine
Stavudine Nausea be avoided. is restricted because of
Zalcitabine Diarrhea the small therapeutic
Zidovudine** Neuropathy window. Stavudine is the
Pancreatitis most frequently used drug
Myopathy in the group.
Xerostomia
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Delavirdine Dizziness, insomnia, dyslipidemia Midazolam The most important
Efavirenz Confusion, agitation Triazolam negative adverse effects
Etravirine Rash, nausea Clarithromycin are neuropsychiatric
Nevirapine Hallucinations Clarithromycin (rash, <drug events, skin reactions,
Depression, mania concentration) GI alterations, and liver
Skin rashes Sertraline (<drug concentration) alterations.
Nausea, vomiting
Diarrhea Warfarin (>drug effect)
Stevens-Johnson syndrome Ketoconazole (<drug concentration)
Xerostomia, taste alteration
Nucleotides
Adefovir Dizziness NSAIDs, acyclovir, and ganciclovir Adefovir is not used often
Tenofovir Nausea, diarrhea affect the metabolism of because of GI and renal
Weakness tenofovir. toxicity. Tenofovir is used
Depression, anxiety Vancomycin, NSAIDs, and in patients on multiple-
Skin rash—allergy cyclosporine increase risk for drug therapy who are
Neuropathy kidney disease. not responding. Tenofovir
Liver, kidney failure usually is well tolerated.
Lactic acidosis (rapid breathing,
drowsiness, muscle aches)
 CHAPTER 18  AIDS, HIV Infection, and Related Conditions 293

TA B L E 1 8 - 3  Antiretroviral Drugs Used to Treat HIV Infection—cont’d

Drug Toxicity Interactions Comments

Entry Inhibitors
Enfuvirtide Bacterial pneumonia No significant drug interactions Inhibits fusion of HIV-1 and
Rash, fever CD4+ T cells.
Nausea, vomiting Only one fusion inhibitor
Glomerulonephritis has been approved
Guillain-Barré syndrome (enfuvirtide), and it has to
Taste disturbance be injected.
Hyperglycemia Three other entry inhibitors
Myalgia are available.
Xerostomia
Anorexia
Maraviroc Liver None
Immune-Based Therapies§
Chloroquinine, Stomach upset, muscle weakness, Gold salts These drugs reduce cellular
hydroxychloroquine retinopathy activation thus reducing
Interleukin-2 Fever, chills, nausea, vomiting Pain medications, steroids HIV replication and boost
Interleukin-7 Transient elevations of liver None yet reported. the immune response.
function tests Several others are in
testing.
Agents are grouped by drug class.
*Available in combination as Kaletra.
**Available in combination as Combivir, Epzicom, Trizivir, and Truvada.
ART, Antiretroviral therapy; GI, Gastrointestinal; HIV, Human immunodeficiency virus; NSAIDs, Nonsteroidal antiinflammatory drugs; VL, Viral load.
§
Although not ART drugs, immune-based therapies also are being used in the management of HIV infection.
ART is associated with many drug interactions, only a few are listed. For more detailed recommendations, see guidelines at http://aidsinfo.nih.gov/guidelines.

National Institutes of Health AIDS information Web site conditions should be referred for HIV testing, and
(http://www.aids.info.nih.gov) are available for more medical evaluation. The dentist can undertake diagnostic
information on this topic. laboratory screening using saliva (Oraquick Advance;
Hope exists for improving outcomes with HIV infec- OraSure Technologies, Inc., Bethlehem, Pennsylvania),39
tion. Vaccine development is ongoing,37 and stem cell or serum testing can be done with a referral to a medical
transplantation with CCR5-deficient cells has led to facility. Discussions with the patient should emphasize
reduction of the HIV viral reservoir in one patient and importance of testing and should ascertain risk factors
may prove effective in eradicating HIV in the clinical including sexual habits, intravenous drug use, and so
setting.38 forth. Patients with high-risk factors should be strongly
encouraged to seek diagnostic testing.
Patients at high risk for AIDS and those in whom
DENTAL MANAGEMENT AIDS or HIV has been diagnosed should be treated in a
Health history, head and neck examination, intraoral manner identical to that for any other patient—that is,
soft tissue examination, and complete periodontal and with standard precautions. Several guidelines have
dental examinations should be performed on all new emerged regarding the rights of dentists and patients
patients. History and clinical findings may indicate that with AIDS, including the following:
the patient has HIV infection/AIDS. Of note, however,
patients who know they are seropositive and those at • Dental treatment may not be withheld if the patient
high risk for these conditions may not answer questions refuses to undergo testing for HIV exposure. The
honestly, on account of the stigma or concern for privacy. dentist may then assume that the patient is a potential
Accordingly, the patient history should be obtained carrier of HIV and should treat the person using
whenever possible with this understanding, verbal com- standard precautions, just as for any other patient.
munication in a quiet, private location, and the sharing • A patient with AIDS who needs emergency dental

of knowledge and facts in an atmosphere of honesty and treatment may not be refused care simply because the
openness. dentist does not want to treat patients with AIDS.
Patients who, on the basis of history or clinical find- • No medical or scientific reason exists to justify why

ings, are found to be at high risk for AIDS or related patients with AIDS who seek routine dental care may
294 CHAPTER 18  AIDS, HIV Infection, and Related Conditions

be declined treatment by the dentist, regardless of the blood cell and differential counts, as well as a platelet
practitioner’s personal reason. However, if the dentist count, should be ordered before any surgical procedure
and the patient agree, the dentist may refer this is undertaken. Patients with severe thrombocytopenia
patient to another provider who is more willing or may require special measures (platelet replacement)
better suited (in keeping with the patient’s oral health before surgical procedures (including scaling and curet-
status) to provide treatment. tage) are performed. Medical consultation should
• A patient who has been under the care of a dentist precede any dental treatment for patients with these
and then develops AIDS or a related condition must abnormalities.
be treated by that dentist or receive a referral that is Patients may be medicated with drugs that are pro-
satisfactory for and agreed to by the patient. phylactic for Pneumocystis pneumonia, candidiasis,
• The CDC and the American Dental Association rec- herpes simplex virus (HSV) or CMV infection, or other
ommend that infected dentists inform the patient of opportunistic disease, and these medications must be
their HIV serostatus and should receive consent or carefully considered in dental treatment planning. Care
refrain from performing invasive procedures.40 in prescribing other medications must be exercised with
these, or any, medications after which the patient may
experience adverse drug effects, including allergic reac-
Treatment Planning Considerations
tions, toxic drug reactions, hepatotoxicity, immunosup-
A major consideration in dental treatment of the patient pression, anemia, serious drug interactions, and other
with HIV infection/AIDS involves determining the potential problems. Most often, consultation with the
current CD4+ lymphocyte count and level of immuno- patient’s physician is beneficial.42 For example, acetamin-
suppression of the patient. Another point of emphasis in ophen should be used with caution in patients treated
dental treatment planning is the level of viral load, which with zidovudine (Retrovir) because studies have sug-
may be related to susceptibility to opportunistic infec- gested that granulocytopenia and anemia, associated
tions and rate of progression of AIDS. The dentist should with zidovudine, may be intensified; also, aspirin should
be knowledgeable about the presence and status of not be given to patients with thrombocytopenia. Meperi-
opportunistic infections and the medications that the dine should be avoided in patients taking ritonavir,
patient may be taking for therapy or prophylaxis for because ritonavir increases the metabolism of meperidine
such conditions. Patients who have been exposed to the to normeperidine which is associated with adverse effects
AIDS virus and are HIV-seropositive but asymptomatic such as lethargy, agitation, and seizures. Propoxyphene
may receive all indicated dental treatment. Generally, levels may be increased by ritonavir which may poten-
this is true for patients with a CD4+ cell count of more tially lead to toxic effects such as drowsiness, slurred
than 350/µL. Patients who are symptomatic for the early speech, or incoordination. Antacids, phenytoin, cimeti-
stages of AIDS (i.e., CD4+ cell count lower than 200) dine, and rifampin should not be given to patients who
have increased susceptibility to opportunistic infection are being treated with ketoconazole, because of the pos-
and may be medicated with prophylactic drugs.33 sibility of altered absorption and metabolism. Also, mid-
The patient with AIDS can receive almost any dental azolam and triazolam should be avoided in patients
care needed and desired once the possibility of significant taking select protease inhibitors, because benzodiazepine
immunosuppression, neutropenia, or thrombocytopenia metabolism may be inhibited, leading to excessive seda-
has been ruled out. Complex treatment plans should not tion and/or respiratory depression.42
be undertaken before an honest and open discussion Medical consultation is necessary for symptomatic
about the long-term prognosis of the patient’s medical HIV-infected patients before surgical procedures are per-
condition has occurred. formed. Current platelet count and white blood cell
Dental treatment of the HIV-infected patient without count should be available. Patients with abnormal test
symptoms is no different from that provided for any results may require special management. All these matters
other patient in the practice.41 Standard precautions must be discussed in detail with the patient’s physician.
must be used for all patients. Any oral lesions found Any source of oral or dental infection should be elimi-
should be diagnosed, then managed by appropriate local nated in HIV-infected patients, who often require more
and systemic treatment or referred for diagnosis and frequent recall appointments for maintenance of peri-
treatment. Patients with lesions suggestive of HIV infec- odontal health. Daily use of chlorhexidine mouth rinse
tion must be evaluated for possible HIV. may be helpful.43
In planning invasive dental procedures, attention In patients with periodontal disease whose general
must be paid to the prevention of infection and exces- health status is not clear, periodontal scaling for several
sive bleeding in patients with severe immunosuppres- teeth can be provided to allow assessment of tissue
sion, neutropenia, and thrombocytopenia. This may response and bleeding. If no problems are noted, the rest
involve the use of prophylactic antibiotics in patients of the mouth can be treated.43 Adjunctive antibacterial
with CD4+ cell counts below 200/µL and/or severe neu- measures may be required if the patient’s CD4+ cell
tropenia (neutrophil count lower than 500/µL ).42 White count is below 200/µL or if tissues remain unresponsive
 CHAPTER 18  AIDS, HIV Infection, and Related Conditions 295

to routine therapy. Root canal therapy has good success setting is minimized by adherence to standard infection
in patients with HIV infection, and no modifications are control procedures.49
required.44 Infection can be treated through local and
systemic measures.
Oral Complications and Manifestations
Oral lesions can be one of the early signs of HIV infection
Occupational Exposure to HIV and risk for progression to AIDS. For these reasons, the
The risk of HIV transmission from infected patients to clinician should be cognizant of the oral manifestations
health care workers is very low, reportedly about 3 of of HIV infection. Common oral manifestations include
every 1000 cases (0.3%) in which a needlestick or other candidiasis of the oral mucosa (Figures 18-4 to 18-7),
sharp instrument transmitted blood from a patient to a bluish purple or red lesion(s) that on biopsy are identified
health care worker.35 In comparison, the risk of infection as Kaposi sarcoma (Figures 18-8 to 18-11), and hairy
from a needlestick is 3% for hepatitis C and is 30% for leukoplakia of the lateral borders of the tongue (Figure
hepatitis B. 18-12). Other oral conditions that occur in association
After a needlestick, the rate of transmission of HIV with HIV infection are HSV, herpes zoster, recurrent aph-
can be reduced by postexposure prophylaxis (PEP).45 thous ulcerations, linear gingival erythema (Figure 18-13),
The CDC recommends PEP as soon as possible after necrotizing ulcerative periodontitis (Figure 18-14), and
exposure to HIV-infected blood.45 The number of PEP necrotizing stomatitis, oral warts (Figure 18-15), facial
drugs recommended is based on the severity of the
exposure as well as the HIV status of the source-
patient.46 A less severe exposure (solid needle or super-
ficial injury) from a source-patient who is asymptomatic
or has a low viral load (<1500 viral copies/mL) has a
two-drug PEP. Use of at least a three-drug PEP regimen
is recommended for more severe exposure (large-bore
hollow needle, deep puncture, visible blood on device or
needle used in patient’s artery or vein) or when the
patient is symptomatic, has AIDS, or a high viral load.
The recommended basic regimen for HIV PEP is tenofo-
vir plus emtricitabine or zidovudine plus lamivudine.
The expanded regimen includes a standard two-drug
regimen plus a protease inhibitor such as ritonavir-
boosted (/r) lopinavir, darunavir/r, atazanavir/r, or ralte-
gravir. PEP should be continued for 4 weeks, during
which time the exposed clinician should be provided FIGURE 18-4  White lesions on the palate in a patient with AIDS.
The lesions could be scraped off with a tongue blade. The underly-
expert consultation, and follow-up monitoring for ing mucosa was erythematous. Clinical and cytologic findings sup-
compliance, adverse events, and possible seroconver- ported the diagnosis of pseudomembranous candidiasis. (From
sion. Tests for seroconversion should be performed at 3, Silverman S Jr: Color atlas of oral manifestations of AIDS, ed 2,
6, and 12 months. To date, there have been six reports St. Louis, 1996, Mosby.)
of occupational HIV seroconversion despite combina-
tion PEP.45
If the exposed dental health care worker is pregnant,
risk of infection versus unknown yet possible risks of
PEP to the fetus, should be discussed.

Risk of Transmission From Health

Care Personnel
In 1990, an HIV-infected Florida dentist transmitted, in
some undetermined way, HIV infection to six of his
patients. All of these patients are now deceased.47 The
only other report of HIV transmission involving den-
tistry came from Bucaramanga, Colombia, in 1997,
where 14 cases of HIV infection occurred among hemo-
dialysis patients at a university hospital. Transmission of FIGURE 18-5  Note the white lesions on the oral mucosa. The
the virus appeared to occur through contaminated dental diagnosis of pseudomembranous candidiasis was established.
instruments.48 The risk of transmission in the dental (Courtesy Eric Haus, Chicago, Illinois.)
296 CHAPTER 18  AIDS, HIV Infection, and Related Conditions

FIGURE 18-6  Erythematous palatal lesion in a human immunode-

ficiency virus antibody–positive patient. Smears taken from the
lesion showed hyphae and spores consistent with Candida. The
lesion healed after a 2-week course of antifungal medications. A
diagnosis of erythematous candidiasis was made on the basis of
clinical laboratory findings. (Courtesy Eric Haus, Chicago, Illinois.)

FIGURE 18-8  Multiple erythematous lesions on the face of a

patient with AIDS. With the use of biopsy, lesions were established
as Kaposi sarcoma. (Courtesy Sol Silverman, San Francisco,
California.)

FIGURE 18-7  Angular cheilitis in a patient with AIDS. The lesion

responded to antifungal medication. (Courtesy Eric Haus, Chicago,
Illinois.)

palsy, trigeminal neuropathy, salivary gland enlargement,

xerostomia, and melanotic pigmentation.50,51 Candi­
diasis, hairy leukoplakia, specific forms of periodontal
disease (i.e., linear gingival erythema and necrotizing
ulcerative periodontitis), Kaposi sarcoma, and non-
Hodgkin’s lymphoma are reported to be strongly associ- FIGURE 18-9  Multiple large, flat, erythematous lesions involving
ated with HIV infection. Features and management of the the palatal mucosa. Biopsy revealed the lesions to be Kaposi
oral manifestations of HIV infection are discussed in sarcoma, and the patient was eventually given a diagnosis of AIDS.
Tables 18-4 and 18-5. In addition, clinicians should be (Courtesy Sol Silverman, San Francisco, California.)
aware that oral lesions can be a feature of the stage of the
disease or a sign of treatment failure or disease progres-
sion52,53 (Table 18-6).
Worldwide, candidiasis is the most common oral
manifestation of HIV infection. Oral candidiasis diag-
nosed in HIV-infected patients with persistent general-
ized lymphadenopathy may be of predictive value for the
 CHAPTER 18  AIDS, HIV Infection, and Related Conditions 297

FIGURE 18-10  Palatal lesion in a patient with AIDS. Biopsy

revealed Kaposi sarcoma. (Courtesy Sol Silverman, San Francisco, FIGURE 18-13  Band of linear gingival erythema involving the free
California.) gingival margin of a human immunodeficiency virus–infected
patient. (From Neville B, et al: Oral and maxillofacial pathology, ed
3,St. Louis, 2009, Saunders.)

subsequent development of AIDS. The appearance of

pseudomembranous candidiasis in HIV-infected persons
has been shown to be a strong indicator for progression
of infection to AIDS. The erythematous form of candi-
diasis also indicates progression toward AIDS.54 The
percentage of patients with HIV/AIDS who also have
candidiasis has been reported by several investigators
and is summarized in Table 18-7. This information might
be helpful to dental clinicians in evaluating patients for
the initial diagnosis of HIV/AIDS or in determining stage
of infection and level of immunosuppression. However,
the oral manifestations of candidiasis that occurred more
FIGURE 18-11  Kaposi sarcoma of the gingiva. (From Silverman S recently may be masked by earlier use of prophylactic
Jr: Color atlas of oral manifestations of AIDS, ed 2, St. Louis, 1996, antifungal agents.54
Mosby.) Kaposi sarcoma is a malignant tumor of endothelial
cells caused by human herpesvirus type 8 (HHV-8).
MSM who are HIV-infected are more commonly affected.
In these patients, Kaposi’s sarcoma most often is dis-
seminated throughout the body and runs a fulminant
clinical course. Before 1996, the survival rate was 35%
at 2 years. However, survival rates have improved to
81% since the introduction of protease inhibitors into
the ART regimen.55
Hairy leukoplakia is an asymptomatic, corrugated
white lesion of the lateral borders of the tongue due to
reactivation and replication of Epstein-Barr virus (EBV).
This lesion can appear in any patient who is immunosup-
pressed, irregardless of HIV status. The diagnosis can be
made on cell scrapings or from a biopsy. Histologic fea-
tures include koilocytosis and hyperkeratotic, hairlike
surface projections from the lesion. Treatment is with
antiviral agents.
Lymphadenopathy at cervical and submandibular
FIGURE 18-12  Diffuse white lesion involving the tongue. Biopsy
supported the diagnosis of hairy leukoplakia. (From Silverman S Jr: locations often is an early finding in patients infected
Color atlas of oral manifestations of AIDS, ed 2, St. Louis, 1996, with HIV. This condition is persistent and may be found
Mosby.) in the absence of any current infection or medications
298 CHAPTER 18  AIDS, HIV Infection, and Related Conditions

FIGURE 18-14  Necrotizing ulcerative periodontitis in a human

immunodeficiency virus–infected patient. The diagnosis was estab-
lished after the patient was referred for medical evaluation. (Cour- FIGURE 18-15  Multiple areas of condylomata acuminata on the
tesy Sol Silverman, San Francisco, California.) gingivae of a human immunodeficiency virus–positive patient.
(From Silverman S Jr: Color atlas of oral manifestations of AIDS,
ed 2, St. Louis, 1996, Mosby.)

TA B L E 1 8 - 4 Head, Neck, and Oral Lesions Commonly Associated with HIV Infection and AIDS

Oral Condition Comment Treatment

Persistent generalized An early sign of HIV infection, found in about Usually not treated directly, may need biopsy to
lymphadenopathy 70% of infected patients during the latent rule out lymphoma or other conditions.
stage of infection.
Must be present longer than 3 months and in
two or more extrainguinal locations.
Anterior and posterior cervical, submandibular,
occipital, and axillary nodes are most
frequently involved.
Oral candidiasis Most common intraoral manifestation of Nystatin often is ineffective. Topical clotrimazole
Pseudomembranous HIV infection. First found during the early is effective but has high rate of recurrence.
Erythematous symptomatic stage of infection. This indicates Systemic fluconazole and itraconazole are
Hyperplastic that AIDS will develop within 2 years in effective but have a number of drug interactions
Angular cheilitis untreated patients. and may result in drug-resistant candidiasis. If
About 90% of patients with AIDS will develop azoles fail, then intravenous amphotericin B can
oral candidiasis at some time during their be administered.
disease course.
HIV-associated periodontal
disease
Linear gingival erythema LGE does not respond to improved plaque control LGE usually responds to plaque removal, improved
(LGE) procedures. Condition is associated with oral hygiene, and chlorhexidine rinses. Persistent
candidiasis. cases usually respond to local measures plus
Necrotizing ulcerative NUG relates to ulceration and necrosis of one systemic antifungal medications. Therapy
gingivitis (NUG)16 or more interdental papillae with no loss of for NUG, NUP, and NS involves debridement
periodontal attachment. (removal of necrotic tissue and povidone-iodine
Necrotizing ulcerative NUP consists of gingival ulceration and necrosis irrigation), chlorhexidine rinses, metronidazole,
periodontitis (NUP) with attachment loss and does not respond to follow-up care, and long-term maintenance.
conventional periodontal therapy.
Necrotizing stomatitis (NS) May be seen as an extension of NUP or may
involve oral mucosa separate from the
gingiva.
 CHAPTER 18  AIDS, HIV Infection, and Related Conditions 299

TA B L E 1 8 - 4 Head, Neck, and Oral Lesions Commonly Associated with HIV Infection and AIDS—cont’d

Oral Condition Comment Treatment

Herpes simplex virus (HSV) Immunocompetent persons and HIV-infected Systemic acyclovir, valacyclovir, or famciclovir for at
infection patients experience about the same rate least 5 days can be effective. Higher doses may
of recurrent HSV infection (10-15%), but in be needed during severe immunosuppression.
HIV-infected patients, the lesions are more An elixir or syrup of diphenhydramine (Benadryl)
widespread, occur in an atypical pattern, and of 12.5 mg/5 mL can be used for pain control.
may persist for months.
Varicella-zoster virus (VZV) Recurrent VZV infection is common in HIV- Valacyclovir 1 g PO tid; famciclovir 500 mg
infection infected patients, but the course is more PO tid; acyclovir 800 mg PO 5 times per
severe. Intraoral lesions are often severe and day. Intravenous acyclovir may be needed
can lead to bone involvement with loss of for severe herpes zoster in patients with
teeth. immunosuppression.
Oral hairy leukoplakia (OHL) White lesion most often found on the lateral Treatment often is not needed. Acyclovir or
border of the tongue. OHL on rare occasions desiclovir can result in rapid resolution, but
has been found on the buccal mucosa, soft recurrence is likely. Retinoids or podophyllum
palate, and pharynx. Associated with Epstein- resin therapy can lead to temporary remission.
Barr virus infection. HIV therapy with ART can result in significant
In an untreated patient with HIV symptomatic regression.
infection, the finding of OHL indicates that
AIDS will develop in the near future.
Kaposi sarcoma (KS) Human herpes virus type 8 (HHV-8) involved in Often regresses with HAART. Treatment involves
KS development. About 50% of patients with irradiation, local and systemic chemotherapy.
KS have oral lesions, and the oral cavity is the Focal symptomatic lesions can be excised, or
initial site of involvement in 20% to 25% of injected with vinblastine or a sclerosing agent
cases. The most common sites are the hard (sodium tetradecyl sulfate). Other options
palate, gingival, and tongue. KS that occurs in for dealing with these types of lesions are
an HIV-infected patient is diagnostic of AIDS. cryotherapy, laser ablation, and electrosurgery,
but care must be taken to protect operating
personnel from aerosolization of viral particles
when the laser or electrosurgery unit is used.
AIDS, Acquired immunodeficiency syndrome; HIV, Human immunodeficiency virus.

TA B L E 1 8 - 5 Less Common Oral Conditions Associated with HIV Infection

Oral Condition Comment Treatment

Aphthous stomatitis About 66% of lesions are of the more Treatment of major lesions that persist involves potent
Minor uncommon forms—major and herpetiform. topical or intralesional corticosteroids. Systemic
Major With more severe reduction of CD4+ cell steroids generally are avoided, to prevent further
Herpetiform count, major lesions become more prevalent. immunosuppression. Thalidomide treatment has
Lesions that are chronic or atypical, or that yielded good response but should be used for only
do not respond to treatment, should be a short time, because the drug can enhance HIV
biopsied. replication. Granulocyte colony-stimulating factor has
produced significant improvement in a limited number
of patients.
Human papillomavirus (HPV) The usual HPV types are found in oral lesions, Treatment of choice is surgical removal of the lesion(s).
Verruca vulgaris (wart) but some uncommon variants such as HPV-7 Other treatment modalities include topical
Oral squamous papilloma and HPV-32 also are found. Lesions usually podophyllin, interferon, and cryosurgery. Laser ablation
are multiple and may be found on any oral and electrocoagulation have been used, but care must
mucosal site. be taken because the plume may contain infectious
HPV.
Continued
300 CHAPTER 18  AIDS, HIV Infection, and Related Conditions

TA B L E 1 8 - 5 Less Common Oral Conditions Associated with HIV Infection—cont’d

Oral Condition Comment Treatment

Histoplasmosis Histoplasmosis is the most common endemic The treatment of choice for disseminated histoplasmosis
respiratory fungal infection in the United is intravenous amphotericin B. Oral itraconazole also
States and usually is subclinical and self- has been found to be effective and has fewer adverse
limiting. Dissemination of infection occurs in effects, with better patient compliance.
about 5% of patients with AIDS who live in
areas in the United States where the fungus
is endemic.
Molluscum contagiosum Molluscum contagiosum is caused by a Curettage, cryosurgery, and cautery have been used
poxvirus. The lesions are small papules to treat these lesions, but they are painful and
with a central depressed crater. In recurrences are common. Resolution of multiple
immunocompetent persons, the lesions are lesions has been reported with HAART.
self-limiting and are found on the genitals
and trunk. In patients with AIDS, multiple
lesions (hundreds) are found that do not
regress (5% to 10% of patients with lesions
have lesions of the facial skin).
Thrombocytopenia Thrombocytopenia is found in about 10% of Platelet counts below 50,000/mm3 may result in
HIV-infected patients. It may occur during significant bleeding with minor surgical procedures.
any stage of the disease. Skin manifestations Platelet replacement may be indicated for these
are most common, but petechiae, patients.
ecchymosis, and spontaneous gingival
bleeding can occur in the oral cavity.
HIV-associated salivary gland Found in 5% of HIV-infected patients and can Risk is increased for cysts of the parotid and lymphoma.
disease occur any time during the infection. Bilateral Treatment involves antiretroviral therapy ± immune
swelling of the parotid is most common. modulators. Associated xerostomia can be managed
In some patients, CD8+ lymphocytes with sialogogues and saliva substitutes.
infiltrate the gland and are associated with
lymphadenopathy. Xerostomia may occur.
Patients are at increased risk for B cell
lymphoma.
Hyperpigmentation Melanin pigmentation has been reported to Usually, no treatment is indicated. Single lesions may
occur in HIV-infected patients. Several of have to be biopsied so that melanoma can be ruled
the medications (ketoconazole, clofazimine, out. Patients with Addison disease may require
and zidovudine) used to treat these corticosteroids.
patients may cause melanin pigmentation.
Addison-like pigmentation also may occur
because of destruction of the adrenal gland.
HIV infection itself may cause melanin
pigmentation.
Lymphoma Found in about 3% of patients with AIDS. Most Treatment usually involves a combination of
are found in extranodal locations. Most chemotherapy and radiation and is used for local
lesions are non-Hodgkin B cell lymphoma control of disease. Prognosis is very poor, with death
and are related to the EBV. The CNS is the occurring within months of the diagnosis. HAART has
most common site, but oral lesions occur reduced the prevalence of opportunistic infections and
in the palate and gingiva and in other Kaposi sarcoma in HIV-infected patients but has not
locations. affected the prevalence of lymphoma.
Oral squamous cell Can be found in the oral cavity, pharynx, and Treatment of oral squamous cell carcinoma is the same
carcinoma larynx in HIV-infected persons. The same risk as for non–HIV-infected patients: surgery, irradiation,
factors apply as for the general population, chemotherapy, or combination therapy.
but the cancer occurs at a younger age (it
appears that HIV infection accelerates onset
of carcinoma).
AIDS, Acquired immunodeficiency virus; CNS, Central nervous system; EBV, Epstein-Barr virus; HAART, Highly active antiretroviral therapy; HIV, Human
immunodeficiency virus.
 CHAPTER 18  AIDS, HIV Infection, and Related Conditions 301

TA B L E 1 8 - 6  Specific Oral Lesions Related to Stage of HIV Infection: Percentage of Patients with Lesions

Seropositive,
But Data Not
Seronegative + Separated Into Asymptomatic
Lesion High Risk (%) Clinical Stages (%) + PGL (%) ARC (%) AIDS (%)
Hairy leukoplakia 0.3-3 19 8-21   9-44   4-23
Candidiasis 0.8-10 11-31 5-17 11-85 29-87
Kaposi’s sarcoma 0 0.3-3 1-2 0 35-38
Herpes simplex 0-0.5 0-1 0-5 11-29 0-9
Aphthous 0-2 0-1 2-8 11-14 2-7
Venereal warts 0-0.7 0-1 0-1 0 0-1
NUG 0-0.2 1-5 0-1 0 51
HIV periodontitis 0 0 0-2 0-21 19
AIDS, Acquired immunodeficiency syndrome; NUG, Necrotizing ulcerative gingivitis; ARC, AIDS-related complex; HIV, Human immunodeficiency virus; PGL,
Persistent generalized lymphadenopathy.
Data from Barone R, et al: Oral Surg 69:169-173, 1990; Barr C, et al; IADR 1443:289, 1990; Feigal DW, et al: IADR 65:190, 1989; Little JW, Melnick SL, Rhame
FS: Gen Dent 42:446-450, 1994; Melnick SL, et al: Oral Surg 68:37-43, 1989; Roberts MW, Brahim JS, Rinne NF: J Am Dent Assoc 116:863-866, 1988; Silverman
S Jr, et al: J Am Dent Assoc 112:187-192, 1986.

TA B L E 1 8 - 7 Summary of Statistics Related to Oral Candidiasis in HIV-Infected Persons*

Prevalence Frequencies
Published Weighted
Disease State Studies Range† Mean (%) Mean
Oral candidiasis 17 11-96 30.0 45.2
Erythematous 7 10-96 40.5 33.0
Pseudomembranous 6 6-69 22.2 25.6
Hyperplastic 6 2-20 3.8 3.8
Angular cheilitis 4 1-23 12.5 16.0
*Data from 17 published reports in the United States.
†
Weighted by overall number of patients with oral candidiasis in each study.
HIV, Human immunodeficiency virus.
From Samaranayake LP, Holmstrup P: Oral candidiasis and human immunodeficiency virus infection, J Oral Pathol Med 18:554-564, 1989.

known to cause lymph node enlargement. The nodes to establish a diagnosis. This may involve cell study,
tend to be larger than 1 cm in diameter, and multiple culture, and biopsy by the dentist or referral to an oral
sites of enlargement may be found. surgeon. If red or purple lesions are found that cannot
The overall general dental management of the patient be explained by history (e.g., trauma, burn, chemical,
with AIDS is summarized in Box 18-3. The dentist physical) or proved by clinical observation (healing
should perform head and neck and intraoral soft tissue within 7 to 10 days), biopsy is indicated. Persistent
examinations on all patients. White lesions in the lymphadenopathy must be investigated by referral for
mouth must be identified, and appropriate steps taken medical evaluation, diagnosis, and treatment.
302 CHAPTER 18  AIDS, HIV Infection, and Related Conditions

BO X 1 8 - 3 Dental Management
Considerations in the Patient with HIV Infection or AIDS

P C
Patient Evaluation/Risk Assessment (see Box 1-1) Chair position No issues.
• Evaluate and determine whether HIV infection exists. Cardiovascular Confirm cardiovascular status. Some ART drugs
• Obtain medical consultation if poorly controlled or undiagnosed can increase risk of cardiovascular disease.
problem, or if uncertain. D
Potential Issues/Factors of Concern Devices No issues.
A Drugs There are many drug interactions and drug
toxicities associated with ART. Clinicians are
Analgesics Aspirin and other NSAID use can worsen bleeding
advised to check drug reference resources
in a patient who has thrombocytopenia. Avoid
before prescribing medications to patients on
during thrombocytopenic episodes. Check drug
ART, to minimize drug interactions. Also, some
interactions before use.
ART drugs can cause mucosal eruptions (see
Antibiotics Prophylactic use not required unless severe
Table 18-3).
immune neutropenia (<500 cells/µL) is present.
E
Manage postoperative infections with usual
antibiotic use. Check for drug interactions Equipment No issues.
before use of antibiotics. Emergencies/ No issues.
Anesthesia No issues. urgencies
Anxiety No issues. F
Allergy No issues. Follow-up Routine and periodic follow-up evaluation is
B advised for patients in stage 1. Patients in
Bleeding Excessive bleeding may occur in the patient with stage 2 or 3 may require more frequent
untreated or poorly controlled disease as a follow-up or additional prophylactic agents and
result of thrombocytopenia, which fortunately may require hospital-like environment for care.
is not a common finding. Inspect for oral lesions to monitor for disease
Breathing Ensure that patient does not have a pulmonary progression or ART treatment failure.
infection. Delay treatment until pulmonary
infections are resolved.
Blood pressure No issues.

REFERENCES www.cdc.gov/hiv/topics/surveillance/basic.htm?source=
govdelivery; accessed on March 31, 2011.
1. Global HIV and AIDS estimates, end of 2009 (article online), 10. Hall HI, et al: Racial/ethnic and age disparities in HIV preva-
http://www.avert.org/worldstats.htm; accessed on March 31, lence and disease progression among men who have sex with
2011. men in the United States, Am J Public Health 97:1060-1066,
2. Piot P: Human immunodeficiency virus infection and acquired 2007.
immunodeficiency syndrome: a global overview. In Goldman 11. Lansky A, et al: Epidemiology of HIV in the United States,
L, Ausiello D, editors: Cecil textbook of medicine, ed 23, J Acquir Immune Defic Syndr 55(Suppl 2):S64-S68, 2010.
St. Louis, 2008, Saunders, pp 2553-2554. 12. Centers for Disease Control and Prevention: Deaths among
3. Merson MH: The HIV-AIDS pandemic at 25—the global persons with AIDS through December 2006. HIV/AIDS Sur-
response, N Engl J Med 354:2414-2417, 2006. veillance Supplemental Report, vol 14, no. 3 (publication
4. Schneider E, et al: Revised surveillance case definitions for online), http://www.cdc.gov/hiv/surveillance/resources/reports/
HIV infection among adults, adolescents, and children aged 2009supp_vol14no3/pdf/table6.pdf; accessed on March 31,
<18 months and for HIV infection and AIDS among children 2011.
aged 18 months to <13 years—United States, 2008, MMWR 13. AIDS epidemic update, Geneva, WHO/UNAIDS, 2009; avail-
Recomm Rep 57:1-12, 2008. able at http://www.unaids.org/en/media/unaids/contentassets/
5. The HIV/AIDS epidemic: the first 10 years, MMWR Morb dataimport/pub/report/2009/jc1700_epi_update_2009_
Mortal Wkly Rep 40:357, 1991. en.pdf; accessed on March 31, 2011.
6. World Health Organization (WHO): WHO case definitions of 14. Campbell-Yesufu OT, Gandhi RT: Update on human immu-
HIV for surveillance and revised clinical staging and immuno- nodeficiency virus (HIV)-2 infection, Clin Infect Dis 52:780-
logical classification of HIV-related disease in adults and 787, 2011.
children, Geneva, 2007, WHO Press, available at http:// 15. Update: HIV-2 infection among blood and plasma donors—
www.who.int/hiv/pub/guidelines/hivstaging/en/index.html; United States, June 1992-June 1995, MMWR Morb Mortal
accessed on March 31, 2011. Wkly Rep 44:603-606, 1995.
7. HIV prevalence estimates—United States, 2006, MMWR 16. Barre-Sinoussi F, et al: Isolation of a T-lymphotropic retrovirus
Morb Mortal Wkly Rep 57:1073-1076, 2008. from a patient at risk for acquired immune deficiency syn-
8. Hall HI, et al: Estimation of HIV incidence in the United drome (AIDS), Science 220:868-871, 1983.
States, JAMA 300:520-529, 2008. 17. Gallo RC, et al: Frequent detection and isolation of cytopathic
9. Centers for Disease Control and Prevention: HIV/AIDS statis- retroviruses (HTLV-III) from patients with AIDS and at risk
tics and surveillance. Basic statistics (article online), http:// for AIDS, Science 224:500-503, 1984.