BURKETS HALAMAN 481

Human Immunodeficiency Virus (HI V)

After almost three decades, the scourge of HIV infection
continues to devastate the global landscape. The first indication
of a new human epidemic surfaced in 1981 with the
publication of reports of the rare opportunistic infection
Pneumocyctis carinii pneumonia and an aggressive form of
Kaposis sarcoma affecting clusters of young homosexual
men in California and New York.71,72 In September 1982,
the CDC formally introduced the term acquired immune
deficiency syndrome (AIDS) in describing the 593 cases
reported to the CDC through September 15, 1982.73 Working
independently, researchers in both France and the United
States announced the discovery of a virus they believed caused
AIDS.74,75 Whereas the French team referred to the virus as
lymphadenopathy-associated virus (LAV) and the US team
referred to the virus as human T-cell lymphotropic virus type
3 (HTLV-III), it became apparent that they were one and the
same. In May 1986, the unifying name of human immunodeficiency
virus (HIV) was adopted by the International
Committee on Taxonomy of Viruses.76 Current medical
therapies to manage HIV disease are both expensive and
compliance intense, rendering them unavailable to vast
segments of the world population. This section briefly
reviews our current understanding of the epidemiology,
pathogenesis, and management of HIV.
Epidemiology
There exist two recognized types of HIV: HIV-1 and HIV-2.77
Both have the same modes of transmission, and both may
cause immunosuppression and AIDS. However, compared
with HIV-1, HIV-2 rarely occurs outside Africa and tends
to follow a more indolent clinical course. HIV-1 is further
classified into three groups: M, N, and O. Twenty-seven forms
of the HIV-1 group M are recognized, and M forms collectively
account for 95% of human infections.78 Most scientists
believe that each type of HIV is a descendant of a specific
simian immunodeficiency virus (SIV). SIVs are primate
lentiviruses that infect at least 36 nonhuman primate species
in sub-Saharan Africa.79 Contact with nonhuman primates,
such as occurs during hunting and butchering, has been
shown to allow for species cross-contamination and is
believed to have sparked the HIV pandemic.80 Researchers
have established that the immediate precursor to HIV-1
is SIVcpz, whose natural host is the chimpanzee of the
subspecies Pan troglodytes troglodytes.81 Similarly, the immediate
precursor to HIV-2 is SIVsm, whose natural host is the
sooty mangabey.82
The prime modes of transmission for HIV are (1) unprotected
penetrative sex between men, (2) unprotected heterosexual
intercourse, (3) injection drug use, (4) unsanitary
injections and blood transfusions, and (5) mother to child
spread during pregnancy, delivery, or breast-feeding.
The initial case definition for AIDS was published by
the CDC in 1982 and subsequently updated and revised in
1985, 1987, and 1993 (Table 7).73,8385 During the 1980s,
when the temporal relationship between HIV exposure and
progression to AIDS was predictable, the tracking of AIDS
as a surrogate marker for HIV infection was adequate.
However, with advances in medical therapy significantly
delaying the progression to AIDS, the statistical coupling of
HIV infection and AIDS has become tenuous. Efforts to more
accurately determine the actual burden of HIV infection have
been undertaken.86,87 The results must be interpreted with
caution since there are no enforceable testing requirements
or protocols and not all agencies who do have data choose
to report.
During 2005, nearly 5 million people worldwide became
infected with HIV and the cumulative number of people
living with HIV disease exceeded 40 million.88 The estimated
number of people worldwide succumbing to HIV disease
in 2005 was greater than 3 million, and the cumulative death
toll of the epidemic exceeded 25 million.
In the United States, an estimated 1,039,000 to 1,185,000
persons were living with HIV/AIDS at the end of 2003.89 The
most recent surveillance information on HIV/AIDS in the
United States is available at the CDC Web site: <http://www.
cdc.gov/hiv/topics/surveillance/resources/reports/>.
Through 2005, the cumulative number of reported AIDS
cases in the United States and its territories reached 956,019. 90
Of the 41,983 new cases of AIDS reported in 2005, males
accounted for 74% and females accounted for 26%. The
cumulative death toll due to AIDS through 2005 is estimated
to be 550,394. African Americans, who account for 12%
of the US population, accounted for 49% of the HIV/AIDS
cases diagnosed in 2005. Although the national annual rate
of reported AIDS cases was 14 per 100,000, the rate varied
significantly according to geographic location. For the US
Pacific island of American Samoa, the reported rate was zero
per 100,000, whereas for the District of Columbia, the rate
was 128.4 per 100,000. Advances in the medical management
of AIDS have slowed disease progression and led to a dramatic
decrease in AIDS deaths and an increase in the number
of persons living with AIDS.
The United Nations and the World Health Organization
publish annual reports on the global epidemiology of
HIV disease. This information can be accessed at <http://
www.unaids.org/en/HIV_data/ and http://www.who.int/
healthinfo/statistics/en/>.
Diagnosis
The diagnosis of HIV infection is obtained by appropriate
laboratory testing.91 In the standard HIV-antibody test

setpoint, the more rapid the progression to AIDS.106 However,

the overall variability regarding the rate of natural disease
progression is high. An estimated 10% of patients develop
AIDS within 2 to 3 years of exposure to HIV, whereas 10
to 17% of HIV-infected patients may not develop AIDS
even 10 years after exposure.111 The manner in which HIV
successfully persists and ultimately overwhelms the hosts
immune system likely results from a multitude of factors,
such as host genetic predisposition, viral pathogenicity,
high viral mutation rates, perturbations of antigen processing
and presentation, immunologic sanctuary, and proviral
latency.104
Medica l Ma nagement
Tremendous strides in terms of medical management have
largely turned this once almost universally fatal infection into
a manageable chronic illness. A review of current therapeutic
recommendations may be found at the AIDSinfo Web site:
<http://AIDSinfo.nih.gov>. The initial patient workup of the
HIV-infected patient should identify the state of current
infection (acute or chronic) and the presence of comorbidities.
It consists of a complete medical history, physical examination,
and laboratory evaluation. Essential laboratory tests
include HIV antibody testing, CD4+ count, and plasma HIV
RNA (viral load). Medical therapy is essentially two pronged,
targeting the opportunistic infections associated with immunosuppression
and the HIV itself. This chapter limits its
discussion to the antiretroviral arm of therapy. The decision
to initiate antiretroviral therapy is primarily based on the
baseline CD4+ count and viral load. In general, antiviral
therapy is recommended for any patient with a history of
an AIDS-defining illness, regardless of CD4+ counts, or any
asymptomatic patient with a CD4+ count < 200 cells/mm3.112
The efficacy of antiretroviral therapy is determined by
frequent monitoring of both the CD4+ count and the viral
load.
Available antiretroviral drugs target structural and functional
differences between viral and human proteins. Four
classes exist: (1) fusion inhibitors, (2) nucleoside reverse
transcriptase inhibitors (NRTIs), (3) non-nucleoside reverse
transcriptase inhibitors (NNRTIs), and (4) protease inhibitors
(PIs).112,113 The fusion inhibitor enfuvirtide (T20) is
an anti-HIV peptide structurally similar to HIV gp41 and
competitively inhibits viral entry into host cells. NRTIs mimic
deoxyribonucleoside triphosphate, the natural substrate for
reverse transcriptase. As they become incorporated into the
growing DNA chain, they terminate elongation and decrease
or prevent HIV replication in infected cells. NRTIs include
abacavir (ABC), didanosine (ddI), emtricitabine (FTC),
lamivudine (3TC), stavudine (d4T), tenofovir disoproxil
fumarate (TDF), zalcitabine (ddC), and zidovudine (AZT,
ZDV). NNRTIs bind near the catalytic site of reverse transcriptase
and inhibit a crucial step in the transcription of
the RNA genome into a double-stranded retroviral DNA.
NNRTIs include delavirdine (DLV), efavirenz (EFV), and
nevirapine (NVP). PIs block the cleavage of viral proteins
during assembly and maturation, a process essential for
the newly formed virus to become infectious. PIs include
amprenavir (APV), atazanavir (ATV), fosamprenavir
(f-APV), indinavir, lopinavir+ritonavir (LPV/r), nelfinavir
(NFV), ritonavir (RTV), saquinavir (SQV, SQV-sge), and
tipranavir (TPV).
The treatment of HIV infection requires combination
therapy known as highly active antiretroviral therapy
(HAART). Antiretroviral regimens currently recommended
for the treatment of naive patients may be NNRTI based
(1 NNRTI+2 NRTIs), PI based (1 or 2 PIs+2 NRTIs), or
triple NRTI based (3 NRTIs).112 The treatment of patients
with acute HIV infection, HIV-infected adolescents, injection
drug users, HIV-infected women of reproductive age and
pregnant women, and patients with coinfections (HBV, HCV,
and tuberculosis) requires special antiretroviral regimens.
Although HAART can dampen viremia, delay disease progression,
and thus prolong and improve the quality of life for
the HIV-infected patient, it is not curative and not a panacea
to address the worldwide HIV burden. Furthermore, HAART
drugs are expensive, rendering them unavailable for much of
the infected population; they often incur significant toxicity
and serious adverse drug interactions; their use is frequently
compliance intense; and the emergence of drug resistance
remains a serious concern. Potentially serious or lifethreatening
adverse reactions associated with antiretroviral
therapy are usually drug specific and include bleeding
episodes, bone marrow suppression, hepatoxicity, hepatic
necrosis, hypersensitivity reactions, lactic acidosis, nephrolithiasis,
nephrotoxicity, pancreatitis, and Stevens-Johnson
syndrome/toxic epidermal necrolysis.114,115
Although HAART usually results in improved CD4+
counts and decreased viral load, a subset of patients experience
a paradoxical condition termed immune reconstitution
inflammatory syndrome (IRIS).116,117 In these patients,
HAART-induced immune recovery results in a spectrum of
presentations ranging from clinical worsening of established
opportunistic infection and the appearance of new opportunistic
infections to autoimmune disorders. Most cases of IRIS
manifest themselves within the first few months of HAART,
and those at highest risk are patients with low baseline CD4 +
counts and/or an underlying opportunistic infection when
HAART is initiated.
There are no oral lesions that are specific to HIVinfected
patients. However, numerous oral lesions have been
documented to occur in association with the HIV-induced
immunosuppression.118,119 The most recently published
formal listing categorized oral lesions as either (1) strongly
associated with, (2) less commonly associated with, or
(3) simply seen with HIV infection.120 The most strongly
associated lesions in adult patients are candidiasis (erythematous,
pseudomembranous), hairy leukoplakia, Kaposis
sarcoma, non-Hodgkins lymphoma, and periodontal
disease (linear gingival erythema, necrotizing ulcerative
gingivitis, necrotizing ulcerative periodontitis). For pediatric
patients, the most strongly associated lesions are candidiasis

(erythematous, pseudomembranous, angular cheilitis),

herpes simplex infection, linear gingival erythema, parotid
enlargement, and recurrent aphthous stomatitis (minor,
major, herpetiform). The risk of developing these lesions is
inversely related to the CD4+ counts. Thus, these lesions often
serve as good clinical markers signaling a loss in therapeutic
efficacy of HAART.121,122
Oral Health Considerations
Dental practitioners should anticipate that HIV-infected
patients will seek care either for their routine dental concerns
or oral conditions associated with their underlying
disease.123,124 Prior to initiating therapy, the clinician should
ascertain the patients immune status, presence of comorbidities,
current medication profile, and prognosis. In this regard,
it may be necessary to obtain permission from the patient to
liaise with his or her physician in order to adequately determine
the patients medical status. The most pertinent criteria
related to the provision of oral health care are the CD4+
count, HIV viral load, neutrophil count, platelet count, and
the medications the patient is taking.
As with other medically complex patients, significant
concerns for the HIV-infected patient are impaired hemostasis,
susceptibility to dentally induced infection, adverse
drug effects/interactions, and the patients ability to tolerate
the stresses associated with the delivery of dental care. In
general, HIV-infected patients presenting in the outpatient
dental setting are sufficiently healthy to tolerate the full spectrum
of modern dental services.125127 The goals of therapy
should be to optimize oral hygiene and function, establish a
recall schedule, monitor for and manage HIV-associated oral
lesions, and monitor for and manage drug-induced oral side
effects, such as xerostomia.
There are no evidence-based studies demonstrating either
a need or justification for the routine use of antimicrobial
prophylaxis to reduce the occurrence of a bacteremia
arising from routine dental procedures in the HIV-infected
patient.127 An indication where antimicrobial prophylaxis is
empirically recommended is neutropenia (ie, neutrophil
counts <500/mm3). Patients with low platelet counts (ie,
<50,000 cells/mm3) are at risk for increased bleeding and
should be managed accordingly. The medication profile
for the HIV-infected patient is typically complex, reinforcing
the obligation of the dental practitioner to routinely monitor
for adverse drug effects/interactions. Common side effects
that may require modification of routine dental protocols
include hepatotoxicity, hyperglycemia, and an increased
susceptibility for coronary artery disease. HAART appears to
modulate, but not eradicate, the risk of oral lesions in the
HIV-infected patient.128,129 It is postulated that an increased
occurrence of some oral conditions, such as oral warts,
salivary gland enlargement, and dry mouth, may represent
the oral consequences of IRIS.130 Management protocols for
a specific oral lesion or condition are discussed elsewhere in
the text.
The transmission of HIV infection from patients to health
care personnel (HCP) may occur after percutaneous (cut
with a sharp instrument or needle stick) and, infrequently,
mucocutaneous exposure to blood and other body fluids
containing blood. A retrospective case-control study found
that the risk of infection among HCP following percutaneous
exposure to HIV-infected blood was more likely (1) in the
presence of visible blood on the instrument before injury; (2)
if the injury involved a needle, which was placed directly into
the patients vein or artery; (3) if the injury caused by the contaminated
instrument or needle was deep; or (4) if the source
patient has an increased viral load, that is, was terminally
ill.131 Prospective studies of HCP estimate that the average
risk for HIV infection after percutaneous and mucous
membrane (eyes, nose, mouth) exposure to HIV-infected
blood is approximately 0.3 and 0.09%, respectively.132,133 The
transmission of HIV infection after nonintact skin exposure
is estimated to be less than the risk following mucous
membrane exposure.134 Similarly, the risk of transmission
after exposure to fluids or tissues other than HIV-infected
blood is probably considerably lower than the risk following
exposure to blood.132 As of 2002, occupational exposure to
HIV was confirmed in 57 HCP, and of these, none were oral
HCP.135 Clearly, when adequate infection control precautions
are observed, the risk of HIV transmission in the oral
health care setting is extremely low.