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An Introduction
to HIV, HIV Infection, and AIDS
Course Number 056-968 (Revision of 913)
MEASURABLE OBJECTIVES:
Upon completion of this course, the reader will be able to:
- identify the cells in the body that can be infected by Human Immunodeficiency Virus (HIV)
- list the ways in which HIV is transmitted
- identify the precautions necessary to reduce occupational exposure and prevent infection
- describe the screening and confirmatory tests used for diagnosis of HIV infection
FREQUENTLY USED ABBREVIATIONS
AIDS - Acquired Immunodeficiency Syndrome
HIV - Human Immunodeficiency Virus
WBC - White blood cells
CD4 - Cell surface molecule found on certain WBC; primary cellular receptor
for HIV
TH - T helper cell (CD4-positive T cell)
IL-2 - Interleukin-2
CD8 T - CTL precursor (CD8-positive T cell)
CTL - Cytotoxic T lymphocyte
PCP - Pneumocystis pneumonia
KS - Kaposi's sarcoma
HAART - Highly-active anti-retroviral therapy; also known as combination therapy
or “anti-HIV cocktail”
CDC - The Centers for Disease Control and Prevention
HCW - Health care worker
PCR - Polymerase chain reaction
PEP - Post-exposure prophylaxis
ELISA - Enzyme-linked immunosorbent assay
WB - Western blot
NAT - Nucleic acid testing
INTRODUCTION
Since its recognition as an emerging clinical syndrome in the summer of 1981
(1), acquired Immunodeficiency Syndrome (AIDS) has impacted the delivery of
medical care at all levels. As the transmission pattern of AIDS emerged, followed
by the isolation of its etiologic agent, Human Immunodeficiency Virus (HIV),
assessment of HIV infection and prevention of occupational exposure became issues
of great importance to clinical laboratory scientists. In the more than two
decades since AIDS was first recognized, an extraordinary amount has been learned
about HIV and its effects on the body (2). This is due, at least in part, to
many major technical advances that have improved our understanding of and response
to HIV infection and AIDS. The purpose of this course is to introduce and/or
review several basic aspects of HIV, HIV infection, and AIDS in order to assist
clinical laboratory scientists in understanding and dealing with relevant issues
surrounding the HIV/AIDS epidemic.
In order to lay a foundation for understanding how and why HIV affects the immune
system, the course will first briefly review how the immune system responds
under normal conditions. Then an historical perspective on the HIV/AIDS epidemic
will provide an overview on the subject. It will be followed by a discussion
of the basic elements of HIV virology and transmission, with a special emphasis
on occupational exposure for clinical laboratory workers. The final section
of the course will describe the continuum of HIV infection and some of the laboratory
tests used to diagnose and follow HIV-infected individuals along the continuum.
NORMAL IMMUNE RESPONSES
The immune system is very complex, consisting of an array of cells, tissues,
and organs that collectively protect us from the bewildering assortment of pathogens
and other foreign materials to which we are constantly exposed. This remarkable
system has been the subject of another CAMLT distance learning course, where
the cellular interactions necessary for normal immune responses were reviewed
in some detail (3). In order to understand how and why HIV interferes with the
proper functioning of the immune system, it will be helpful to briefly review
what happens in a normal immune response.
The white blood cells (WBC) circulate in the blood and lymph fluid and migrate
through the tissues. They are the key to the ability of the immune system to
respond to foreign materials (known as antigens) that manage to get past the
skin and/or other physical barriers, and enter the body. Some WBC such as neutrophils,
monocytes, and macrophages, are non-specific scavenger cells that attempt to
remove any debris or organisms by engulfing or phagocytosing, then digesting
and eventually disposing of the unwanted material. They provide a rapid (but
generic) first line of defense inside the body against antigens of all types.
However, it is the antigen-specific lymphocytes upon which we depend for highly-focused
and reproducible responses against specific antigens, including infectious agents
(1).
There are two basic types of lymphocytes that are involved in antigen-specific
responses, i.e., immune responses that selectively recognize, eliminate, and
remember individual antigens. T and B lymphocytes (also known as T and B cells)
are capable of binding and responding to individual antigens in a highly specific
manner, and, ultimately, give rise to two different types of immune responses.
B cells bind soluble antigens in the circulation and secrete antibody in response
(humoral immunity), while T cells recognize cell-associated antigens and either
provide help to other cells (T helper or TH) or generate cytotoxic
T lymphocytes (CTL) capable of killing infected or defective cells (cell-mediated
immunity).
A single lymphocyte does not act in isolation when responding to
antigen. Rather, any one antigen-specific lymphocyte is dependent on interactions
with other cells in order to successfully mount a specific response (Figure
1). Regardless of whether a B cell or a CTL precursor (CD8 T) first encounters
antigen, neither of these lymphocytes can respond fully to that antigen without
the presence and assistance of a TH cell.
TH cells, while similar in appearance to CD8 T and B cells, can
be distinguished from the other lymphocytes by the presence of a cell surface
molecule known as CD4 (1). The CD4 molecule not only serves as a marker of the
helper cell population, but is physically involved in the recognition of antigen
by TH cells. Following successful recognition of antigen on the surface of an
antigen-presenting cell (shown as a macrophage in Figure 1),
a single TH cell will respond by secreting a cytokine known as interleukin-2
or IL-2. Cytokines, in general, are protein messenger molecules which send signals
between cells. IL-2 signals the TH cell which produced it to undergo proliferation,
or cell division, which gives rise to a number of progeny TH cells, all of which
are specific for the same antigen as the original parent cell. In addition,
IL-2 can diffuse to nearby B or CD8 T cells that have recognized antigen, and
deliver critical signals necessary for those cells to respond to the presence
of antigen. Therefore, the presence of TH cells with the ability to secrete
IL-2 in response to antigen is essential to initiate both humoral (B cell) and
cell-mediated (CTL) responses.
Following the initial secretion of IL-2 by TH cells in response
to antigen, TH cells secrete additional cytokines, which provide further help
to B and/or CD8 T cells that have bound antigen. This allows B cells to fully
develop into antibody-secreting plasma cells, and CD8 T cells to become cytotoxic
T lymphocytes (CTL) capable of killing (Figure 1). This
process of maturing and acquiring new function is known as differentiation.
In the case of B cells, TH cells provide help by establishing antigen-specific
cell-to-cell contact, delivering both cell-surface signals and cytokines. In
the case of CD8 T cells, no physical contact is necessary, and the TH provides
help solely through the secretion of IL-2 and other cytokines in the vicinity
of a CD8 T cell that has recognized antigen on the surface of a cell. As a result
of one or the other or both of these types of interactions, humoral and/or cellular
immunity is/are generated in response to an antigen, which hopefully eliminates
(or at least controls) the antigen and/or pathogen. In addition to dealing with
the antigen at the time of first exposure, antigen-specific immune responses
by TH, CTL, and B cells also give rise to immunologic memory, which allows the
immune system to mount a faster, much more effective response on subsequent
exposures to the same antigen(s). It is immunologic memory which provides immunity,
i.e., the protection from the same infectious disease after initial exposure
and recovery (1, 3).
AN HISTORICAL PERSPECTIVE ON HIV/AIDS
The discipline of virology (the study of viruses) deals with very
small infectious agents that are dependent on host cells to survive and reproduce.
Due to their extremely small size, viruses cannot be visualized using a light
microscope. Therefore, virologists must utilize electron microscopy to find
and examine viral particles. Since viruses reproduce only when inside an appropriate
host cell, they have been notoriously difficult to isolate and culture in the
laboratory. Not surprisingly, many advances in virology have come about only
when new or improved technology became available. This was very much the case
in December of 1980, when new culture techniques enabled the successful isolation
of Human T cell Leukemia Virus-1 (HTLV-1) (Table
I). This was a significant advance because HTLV-1 was the first human
retrovirus ever isolated. Retroviruses are a class of viruses with a unique
life cycle (as will be explained in a later section) that posed particular challenges
to virologists attempting to culture them. The isolation of a human retrovirus
was a notable accomplishment in itself. In retrospect, however, the success
with HTLV-I turned out to be extremely important and timely, as it laid the
foundation for attempts to identify the cause of a mysterious immunodeficiency
that was first recognized only months later.
In June of 1981, a cluster of cases of what was then known as Pneumocystis
carinii pneumonia (PCP), a rare infection usually seen only in immunocompromised
individuals, was reported in the Los Angeles area in relatively young homosexual
men with no previous history of immunodeficiency (1). This report was followed
immediately by others in the New York and San Francisco areas, where similar
clusters of PCP had been seen, along with cases of Kaposi’s sarcoma (KS),
a rare cancer usually seen only in men over sixty years of age. These cases
of PCP and KS were the first of what came to be known as Acquired Immunodeficiency
Syndrome or AIDS. It was soon recognized that this syndrome, characterized by
PCP, KS, and other unusual infections typically seen in association with immunodeficient
states, was spreading in much the same pattern as had been observed for Hepatitis
B—via homosexual and heterosexual contacts, through receipt of blood transfusions
or blood products (such as Factor VIII concentrate for hemophilia), and from
mother to infant. The similarity to Hepatitis B strongly suggested that a viral
agent was involved, leading to an intense search for an AIDS-related virus.
As an historical footnote, it should be mentioned that the organism responsible
for PCP was originally thought to be a protozoan capable of infecting multiple
mammalian species, but is now widely recognized to be a fungus that infects
only humans. As a result, a new name for the organism has been introduced, Pneumocystis
jiroveci, but the term PCP has been retained to mean “Pneumocystis
pneumonia” (see http://www.cdc.gov/ncidod/EID/vol8no9/02-0096.htm
).
The first isolate of a putative “AIDS virus” was recovered
not from a patient with AIDS, but from a patient with persistent lymphadenopathy,
a swelling of the lymph nodes that was considered a precursor to AIDS (part
of the so-called “AIDS-related complex” or ARC, a term which is
now considered obsolete, but was then used to describe a number of symptoms
that preceded AIDS). Named “lymphadenopathy-associated virus” or
LAV, the virus was isolated in late 1983 by a team led by Dr. Luc Montagnier
at the Pasteur Institute in France (Table
I). In early 1984, a team led by Dr. Robert Gallo at the National
Institutes of Health in the U.S. isolated a virus from a patient with AIDS that
was identical in appearance to LAV. Since it was Dr. Gallo’s laboratory
that had isolated HTLV-1 in 1980, and the new virus appeared to be a similar
retrovirus, the AIDS-associated virus isolated in Gallo’s laboratory was
named HTLV-III (HTLV-II had been isolated in the interim). At nearly the same
time, a team led by Dr. Jay Levy at University of California, San Francisco,
also isolated a virus from an AIDS patient, known as “AIDS-related virus”
or ARV. In an effort to standardize the nomenclature regarding the AIDS-associated
viruses, a consensus name, “human immunodeficiency virus” or HIV,
was agreed upon in 1986. The names of the original isolates, as well as hundreds
of other isolates of HIV, are still used to identify the individual and unique
strains of HIV. A related human retrovirus that causes a less severe immunodeficiency
was isolated and identified in 1986, leading to the designation of the original
virus as HIV-1, and the more recently described virus as HIV-2. For the remainder
of this course, HIV-1 will be referred to simply as HIV, unless otherwise noted.
Once the putative etiologic agent of AIDS had been isolated, the most pressing
need was to develop a means of screening for HIV infection to protect the blood
supply used for transfusions and blood products. It took slightly more than
a year to develop and implement an HIV-antibody test, using enzyme-linked immunosorbent
assay (ELISA) technology, for use in blood banks. HIV-1 antibody screening in
the United States began in March of 1985. HIV testing will be discussed in more
detail in a following section.
Since the isolation of HIV in 1983-84, much effort has been devoted to characterizing
the structure and life cycle of the virus, and understanding the changes in
the immune system brought about by infection with HIV. It has been said that
more is known by scientists about HIV than any other virus (2). While this may
be true, after the initial burst of new information regarding HIV, progress
in treating and evaluating this viral disease has been like many others—painfully
slow at times, and dependent on technical advances for clinical and/or scientific
breakthroughs.
With an understanding of the HIV retroviral life cycle, the mid 1980s saw the
clinical trial and approval of the first anti-retroviral drug for the treatment
of AIDS, AZT (also known as zidovudine or Retrovir™). While other similar
drugs would be approved over the next few years for use in place of AZT (ddI
[Videx™], 3TC [Epivir™]) or in combination with AZT (AZT+3TC or
AZT+ddI), it would be the mid 1990s before any antiviral treatment was offered
to HIV-infected pregnant women, and before any new types of highly effective
antiretroviral drugs became available to all HIV-infected persons. In the interim,
there were technical advances in testing with new generations of HIV-1 antibody
ELISA tests, and the introduction into blood banks of a combination HIV-1/HIV-2
ELISA and an HIV antigen test.
Pediatric HIV infection due to blood transfusion was virtually eliminated in
the U.S. in 1985 with the introduction of antibody screening of donated units,
leaving the transmission of HIV from mother to infant during pregnancy and/or
birth as the source of pediatric AIDS cases. In 1994, the first major breakthrough
in the prevention of pediatric HIV infection and AIDS came as treatment of HIV-infected
pregnant women with AZT was shown to be both safe and effective in reducing
transmission of HIV during pregnancy and delivery (2).
1995 marked the beginning of widespread use of an entirely new class of antiretroviral
drugs known as protease inhibitors (2). The rapid evaluation of these powerful
new drugs was possible only because of a technical development that paralleled
the pharmacological advances. This was the development of quantitative determinations
of HIV viral RNA (the genetic material of the virus) in serum or plasma specimens.
As described in more detail later in this course, these measurements permit
the calculation of the concentration of virus present in an individual’s
blood, rather than just detecting the presence of antibody to the virus. In
the two most commonly used tests, the quantitation is performed by either polymerase-chain
reaction (PCR) or branched-DNA (bDNA) techniques, and is expressed as viral
copies or viral equivalents per milliliter of plasma. These measurements, known
as plasma HIV RNA viral load, or more simply as HIV viral load, could quickly
indicate if an antiviral drug was succeeding or failing in controlling the level
of HIV found in the blood. This was a tremendous advance over having to wait
months or years for clinical endpoints (such as an AIDS diagnosis or death)
indicating treatment success or failure. Viral load testing demonstrated that
the new protease inhibitor drugs were most likely to succeed when given in combination
with AZT and/or other existing drugs, and so helped to usher in the era of the
“anti-HIV cocktail” or “highly-active anti-retroviral therapy”
(HAART).
As can be seen in the HIV/AIDS Chronology (Table
I), there were significant decreases in the U.S. in the number of
new AIDS cases, and dramatic declines in deaths from HIV/AIDS in 1996 and 1997,
following the introduction of HAART in 1995. This led to a mistaken (and premature)
assumption among many persons in the U.S. that, because of new antiviral therapies,
the rate of AIDS cases and deaths would continue to decline, and therefore,
the AIDS epidemic no longer presented a threat to public health. In reality,
according to the statistics reported by the Centers for Disease Control and
Prevention (CDC), the federal agency responsible for tracking HIV infection
and AIDS (among a host of other infectious diseases), the estimated numbers
of both new AIDS cases and AIDS deaths per year leveled off in 1999, and were
relatively stable from 1999-2001 (4). However, according to the 2002 and 2003
HIV/AIDS Surveillance Reports from the CDC, the number of new AIDS
cases has increased in each of these years compared to the previous year, the
first such increases since the introduction of HAART in 1995 (4). Not surprisingly,
the CDC reports that the number of persons estimated to be living with an AIDS
diagnosis continues to dramatically increase every year, with more than 400,000
persons living with AIDS as of the end of 2003. Additional details on the topics
of anti-HIV therapy and statistical trends of the HIV/AIDS epidemic are beyond
the scope of this introductory course, but are presented in a second course
on HIV/AIDS (5). It is clear, however, that the history of the HIV/AIDS epidemic
is still unfolding.
HIV VIROLOGY
All viruses, including HIV, cause symptoms and/or disease because they act as
parasites that infect and then affect particular cells of a host organism. The
symptoms and diseases associated with a particular virus are dictated by the
type of cell which can be infected by that virus. In turn, the ability of a
virus to bind to and gain entry into a particular cell type is a function of
the structure of the virus. Therefore, in order to understand how HIV gains
entry into its host cells, we need to examine its structure.
Like all viruses, HIV is a very simple organism, consisting of
genetic material (two identical strands of RNA) contained within a protein shell
or coat, which is also known as the viral envelope (Figure
2) (1, 2). Protruding through the viral coat are proteins which are
glycosylated (i.e., have sugars attached), and so are called glycoproteins (gp).
Viral proteins are identified by their size, so the two glycoproteins on the
surface of HIV, which have molecular weights of 41 and 120 kilodaltons (Kd),
are known as “gp41” and “gp120”. Within its viral core,
HIV carries three viral enzymes that are essential for its lifecycle: reverse
transcriptase, integrase, and protease.
HIV is capable of binding to and infecting any human cell that has the CD4 molecule
on its cell surface (1, 2). This is accomplished by a direct interaction between
a gp120 molecule on the exterior of an HIV viral particle, and the CD4 molecule
on the surface of a cell. CD4, therefore, acts as the primary receptor molecule
that allows HIV to bind to the surface of a potential host cell. This means
that the critical TH cell population, which is necessary for all antigen-specific
immune responses, is a major target for infection by HIV. In addition, CD4 is
expressed at low levels on monocytes and macrophages, a type of antigen-presenting
cell known as a dendritic cell, and macrophage-like cells in the brain known
as glial cells, allowing all of these cell types to also serve as hosts (and,
perhaps more importantly, as long-lived reservoirs) for HIV.
The viral lifecycle of HIV is discussed in detail in another course
(5), but it is necessary to briefly review it here to provide a basic understanding
of the biology of the virus. Once HIV has attached to a cell via CD4, additional
co-receptor molecules on the surface of potential host cells interact with CD4
and HIV to permit the virus to enter the cell (1). Inside the cell, HIV initiates
a unique viral life cycle that is found only in viruses that are members of
the retrovirus family (1, 2). As the name implies, retroviruses are virus that
are “retro” or work in reverse. This distinction refers to the method
by which these viruses make copies of their genetic material (Figure
3). In all cells, the genetic material is DNA, which undergoes transcription
into RNA, which is then translated into protein. Regardless of the cell type,
this process goes only in this direction: DNA to RNA to protein. In retroviruses,
the genetic material is RNA, and the first step of transcription goes in reverse
of the normal cellular process, making DNA copies from viral RNA. This process,
known as reverse transcription, requires an enzyme, reverse transcriptase, which
is only made by retroviruses. As shown in Figure 2, HIV
carries two molecules of reverse transcriptase with it into the cell, so that
it is ready to make a DNA copy of the viral RNA.
The DNA copy of HIV, called a provirus, is transported to the nucleus of the
host cell, where it uses the viral enzyme integrase to randomly integrate itself
into the DNA that makes up the chromosomes of the cell. The proviral DNA will
remain inactive or latent among the genes of the infected cell until the cell
begins to respond to antigen and/or cytokines, which results in the production
of new virus particles. These new viruses bud from the surface of the infected
cell and circulate through the body, spreading the infection to other CD4-expressing
cells. It is the amount of HIV RNA present in the viral particles circulating
in the blood that is measured in determinations of HIV viral load.
TRANSMISSION OF HIV
Fortunately for us all, HIV is a very fragile virus that dies rapidly
outside the body. It is extremely susceptible to drying, and is easily killed
by disinfectants (such as 10% bleach solutions, betadine, or rubbing alcohol).
As a result, HIV is not transmitted by casual contact, but rather, only by one
of three modes of transmission: blood (or infectious body fluid)-to-blood contact,
sexual contact, and mother-to-infant during or immediately following pregnancy
(6).
HIV is present in the blood of an infected individual both as free-floating
viral particles and within infected CD4-positive T cells and monocytes/macrophages.
Although infection is possible due to free viral particles, the most efficient
means of transmission of HIV is probably via infected WBC (1). A single HIV
particle, with a diameter of approximately 100 nanometers (or 0.1 micron), would
require only a submicroscopic hole in a protective barrier in order to pass
through. In contrast, an infected lymphocyte with a diameter of 10 microns would
require an opening one hundred times larger than a viral particle. However,
even an opening of this size would still be far below the size detectable by
the naked eye. Therefore, any contact with blood from another person carries
a risk of HIV infection, whether through the skin due to needle sharing or needlestick,
or due to exposure of unprotected skin or a mucous membrane that appears perfectly
intact. This includes not only the obvious shared needle use found among injecting
drug users or accidental needle injury among health care workers (HCWs), but
any type of shared needle use (tattooing, ear piercing, home vitamin injections),
as well as any kind of occupational or accidental exposure to blood or other
body fluids containing significant amounts of virus and/or blood. Once through
the skin or membranes, HIV-infected WBC can gain access to the bloodstream,
where new viruses can be produced and a new infection established.
An obvious question that arises in light of the transmission of
HIV via blood is the safety of blood transfusions and blood products. As shown
in Table I, the blood supply
in the U.S. has been tested for the presence of HIV-1 antibodies since 1985,
and for HIV-1 and HIV-2 antibodies since 1992 (7). In 1996, a test for the HIV
core antigen p24 (Figure 2) was added to U.S. blood bank
screening. Although p24 is undetectable most of the time in an HIV-infected
person, the p24 antigen test is valuable in blood bank screening because it
is often detectable during the first few weeks of acute HIV infection, before
the development of antibodies to HIV. According to the American Red Cross, the
addition of the p24 antigen test reduced the “window period” (when
a donor might be HIV-infected, but would not be detected by antibody testing
alone), from 22 days to 16 days (7). Just as blood levels of p24 HIV antigen
typically spike during acute HIV infection, HIV viral loads are known to peak
in the first weeks following infection, prior to the development of HIV-specific
antibodies. Therefore, new technologies utilizing the same type of nucleic acid
testing (NAT) methods as those employed for HIV viral load testing (e.g., PCR),
were introduced by the Red Cross as an investigational protocol in 1999 in every
donor unit collected nationwide. Based on data from the Red Cross and other
blood centers, the FDA licensed the use of NAT screening for HIV-1 and hepatitis
C virus in 2002, and this technology is now in use for every non-autologous
blood donation in the U.S. According to the Red Cross, studies suggest that
the addition of the HIV NAT has the potential to further reduce the window period
by another 5 days (7). Approximately one HIV-infected donor in four million
total donors, or one or two donors per year, who would test negative by other
screening tests would be detected by HIV NAT. HIV NAT is performed on pooled
samples from 16 donors at a time, thus allowing a more efficient means of screening
for such a low-probability positive sample. This testing scheme, combined with
other improvements to minimize human and/or recordkeeping errors, has resulted
in an estimated risk of HIV per transfusion as 1 in 2.1 million (7). This is
a nearly ten-fold reduction in risk relative to 1987, when the risk of HIV infection
per transfusion was estimated to be 1 in 250,000. In comparison, the current
risks of Hepatitis B and Hepatitis C infection per transfusion are estimated
to be 1 in 200,000 and 1 in 1.9 million, respectively. In this context, it is
important to emphasize that, contrary to a common misconception, there is no
risk associated with donating blood for transfusion purposes, as all
equipment utilized is sterile and disposed of properly after a single use.
Clinical laboratory scientists are at risk for occupational exposure
to HIV, primarily through exposure to blood. It is appropriate, therefore,
in the context of a discussion on HIV transmission, to review what is known
about occupational transmission of HIV among HCWs, and what steps can be taken
to reduce risk of exposure to and infection by HIV.
If and when occupational exposure does occur with blood
from a person known to be HIV-infected, it usually does not result in infection.
The estimated risk of infection due to known HIV-infected blood is
estimated to be 1 in 200 to 1 in 500 for percutaneous exposures such as needlesticks,
and approximately 1 in 1000 for mucous membrane exposures (8). In the more typical
case, where the HIV infection status of the patient involved is not known, one
would expect that the risk of infection would be much lower, depending on the
prevalence of HIV infection in the patient population served. It is important
to note that occupational HIV infection has been documented to have occurred
following a single needlestick exposure. However, a lack of infection has also
been documented following multiple needlesticks in a single individual.
According to the CDC, there have been rare cases of occupationally
acquired HIV infection of HCWs. In this context, healthcare personnel are defined
as “those persons, including students and trainees, who have worked in
a healthcare, clinical, or HIV laboratory setting at any time since 1978”
(9). Through 2002, there had been more than 24,000 persons with AIDS who had
a history of healthcare employment. However, there are only 57 documented occupationally
acquired HIV infections, and another 139 possible occupationally acquired
infections. The CDC has not reported any additional documented occupationally
acquired cases among HCWs since 2002. While any such infections are regrettable,
keep in mind that 57 occupationally acquired HIV infections represent a very
tiny proportion of the tens of thousands of healthcare professionals that are
potentially exposed across the country. Not surprisingly, the vast majority
of infections were attributed to exposure to HIV-infected blood (48/57); the
remaining exposures involved other fluids or concentrated laboratory virus preparations.
Percutaneous exposure (puncture through the skin, as in a needlestick injury)
was the most common route of infection (48/57), and the most infections occurred
among nurses (42%), followed by clinical laboratory personnel (28%). For more
details on occupationally acquired HIV infections among HCWs, see reference
9.
As is true for all blood borne pathogens that may be encountered
by a clinical laboratory scientist, the best protection against occupational
exposure to HIV is universal blood precautions, i.e., the handling of anything
containing blood and/or body fluids as potentially infectious, regardless of
the source patient (6). In the 1980s, AIDS was first entering our consciousness
in the clinical lab, but hepatitis was already well-established as a health
threat. There are many of us who may recall that, at that time in the clinical
laboratory and throughout the hospital, handling of used needles and syringes,
and routine wearing of latex gloves might have been described as local rather
than universal! However, with increasing awareness of HIV and Hepatitis B and
C, many phlebotomy and laboratory procedures, equipment, and protocols have
been modified over the years to emphasize increased safety and reduced occupational
transmission of blood borne agents. In addition to the changes associated with
universal blood precautions, such as mandatory use of gloves and proper handling
and disposal of samples, occupational transmission can be reduced by well-designed
and well-maintained work areas that reduce clutter and minimize the chance of
accidental spills and/or exposures.
Many arguments have been made for testing all patient samples for
the presence of HIV antibodies as a means of protecting HCWs. However, truly
universal laboratory precautions are the best protection against occupational
exposure to HIV for clinical laboratory scientists, not universal testing of
patients. As mentioned above regarding testing of blood donated for transfusion
purposes, there is a window period early in HIV infection during which HIV antibody
testing would not detect an HIV-infected person. Any mass screening of patients
would likely miss such HIV-infected persons, leading to a false sense of security
that all “negative” patients were not infectious and a potentially
dangerous relaxation of infection precautions.
In its most recent recommendations on the management of HCW exposures
to HIV, the CDC stated “Although preventing blood exposures is the primary
means of preventing occupationally acquired HIV infection, appropriate postexposure
management is an important element of workplace safety.” (8) All institutions
that deal with human blood and/or body fluid samples should have an established
and well-publicized protocol that is to be followed in the case of a HCW exposure
to known or suspected HIV-infected blood and/or fluids. It is important to emphasize
that HCWs need to be aware of and informed about such a protocol before
an accidental exposure, because the most thorough protocol in the world is of
no use to someone who is unaware of its existence. If there is resistance to
establishing and/or educating employees about such protocols, administrators
should consider the ramifications of dealing with and/or caring for an employee
infected with HIV on the job in the absence of such a protocol. The CDC recommendations
state that “health-care organizations should make available to their workers
a system that includes written protocols for prompt reporting, evaluation, counseling,
treatment, and follow-up of occupational exposures that may place HCWs at risk…employers
also are required to establish exposure-control plans, including postexposure
follow-up for their employees, and to comply with incident reporting requirements
mandated by the Occupational Safety and Health Administration.” (8)
Postexposure protocols should include, at the very minimum, instructions
to wash potentially-exposed wounds and skin sites with soap and water; mucous
membranes should be flushed with water (8). Although the CDC does not recommend
the use of antiseptics, it states that their use is not contraindicated. In
our laboratory, we recommend soaking the exposed area for ten minutes in betadine
or alcohol, which are stored in the immediate vicinity where samples are handled.
Antiseptics will be of little use if stored in a remote cabinet not readily
accessible and/or not known to employees and/or if HCWs are unaware of their
possible use.
It is the recommendation of the CDC that any HCW with a significant exposure
to blood or other potentially infectious materials be evaluated to determine
the need for HIV post-exposure prophylaxis (PEP) (8). This refers to anti-viral
drug therapy that is designed to prevent HIV infection following a possible
exposure. PEP usually consists of a combination of two or three drugs that may
include protease inhibitors (the newest class of anti-HIV drugs). PEP is not
necessarily the same combination and/or dose of drugs that would be used to
treat an established infection (as in HAART), but rather, uses drugs chosen
specifically to prevent infection following exposure. In order to be most effective
at preventing HIV infection, PEP should be started as soon as possible after
the exposure (ideally, within the first hour or hours). Therefore, it is essential
that a procedure for seeking and receiving PEP be clearly established, so that
it can be administered in a timely fashion.
The variables that dictate whether or not PEP is offered include
the type of body fluid involved in the exposure, and the severity and route
of exposure (percutaneous, mucocutaneous, cutaneous). Reference 8 contains a
detailed algorithm for determining the need for PEP after an occupational exposure,
which includes evaluating the HIV disease stage, viral load, and/or previous
drug treatment of the source person if known. It is important to emphasize
that if no information regarding HIV status is available in the medical record
of the source person at the time of exposure and/or is not willingly provided
by the source person, all applicable laws regarding HIV testing and confidentiality
must be respected (8). If the HIV status of the source person is unknown, use
of PEP should be decided “after considering the type of exposure and the
clinical and/or epidemiologic likelihood of HIV infection in the source.”
(8). If an exposure is deemed to pose a risk of transmission of HIV, the particular
drugs and dosing schedule to be used for PEP should be determined in each case
either by a clinician with expertise in HIV PEP protocols or following consultation
with an expert in prescribing PEP. Exposed HCWs who choose to take PEP should
be advised of the importance of completing the recommended 4-week regimen, and
be provided with appropriate information regarding potential side effects, possible
drug interactions, etc.
All postexposure protocols should provide a mechanism for a baseline
blood sample to be obtained from the potentially exposed HCW around the time
of exposure, in order to document HIV antibody status at that time (8). This
is for the protection of both the HCW and the institution, and should respect
all applicable laws regarding informed consent by the HCW and confidentiality
of HIV antibody testing. In addition, pregnancy testing should be offered to
all women whose pregnancy status is unknown. If the baseline HIV antibody test
is negative, potentially exposed HCWs should receive follow-up counseling, postexposure
testing, and medical evaluation regardless of whether they receive PEP. The
CDC recommends that “HIV-antibody testing should be performed for at least
6 months postexposure (e.g., at 6 weeks, 12 weeks, and 6 months)” to check
for evidence of seroconversion, i.e., a change from HIV-negative to HIV-positive,
indicating recent HIV infection (8). The exact schedule of postexposure antibody
testing should be established within each institution in consultation with the
appropriate occupational health and/or infectious disease officials.
Blood is not the only body fluid that is capable of HIV transmission
(6). Like blood, semen and vaginal secretions from HIV-infected individuals
can contain sufficient levels of free virus particles and/or HIV-infected WBC
to transmit the virus successfully during sexual contact. By its very nature,
sexual activity involves delicate mucous membranes that are subjected to physical
stresses that can easily cause microscopic breaks and tears in the membranes.
Therefore, any kind of sexual activity that results in exposure to semen or
vaginal fluid, regardless of the anatomic location of such an activity, carries
a risk of HIV infection. Once HIV carried in semen or vaginal fluid passes through
skin or membranes, it gains access to the bloodstream, where a new infection
can be established. It is not surprising that the presence of other sexually-transmitted
diseases, especially those that cause genital lesions such as gonorrhea or syphilis,
greatly increase both the risk of transmission of and infection by HIV as a
result of a single sexual encounter. Such STDs increase the number of WBC present
in the semen and vaginal fluid, increasing both the possible source of and possible
target for HIV infection, and open lesions provide easy access to the bloodstream.
While blood, semen, and vaginal secretions are clearly capable
of transmitting HIV, most other commonly-encountered body fluids are not considered
to pose a risk of HIV transmission (6). HIV can be found in the urine, saliva,
and tears of HIV-infected persons, but it is found in very low concentrations.
In the absence of contaminating blood, there have been no documented transmissions
of HIV attributed to these body fluids (6). In contrast, breastmilk has been
implicated in maternal-fetal HIV transmission, which is discussed below. It
is important to remember that, like blood, some other less commonly-encountered
fluids (such as cerebrospinal, pleural, peritoneal, and amniotic fluids) are
considered to pose an occupational risk of HIV transmission (8). In addition,
body fluids that do not transmit HIV may still be capable of transmitting other
more hardy viruses such as Hepatitis A, B, or C, so universal precautions are
still recommended for all body fluids.
Blood/body fluid or sexual contact as a means of HIV transmission
are very similar—in either case, HIV gains access to the blood where it
can establish new infections in new WBC. Transmission from an HIV-infected woman
to her infant before, during, or immediately following birth is also similar,
in that HIV is gaining access to the baby’s bloodstream. Unfortunately,
maternal-fetal or perinatal transmission is more complex because there are multiple
ways in which it can occur.
The observed rate of transmission of HIV from an infected mother
to her infant ranges in various studies from 13-40% (6). HIV infection can occur
in utero, i.e., across the placenta, as some infants are clearly infected
and often symptomatic at birth. Transmission also occurs as a result of exposure
to the mother’s blood during the birth process, where even in the simplest
vaginal delivery, there is ample opportunity for creation of microscopic breaks
and tears in an infant’s skin during his or her transit of the birth canal.
Delivery by cesarean section does little to decrease the risk of transmission,
as there is still ample exposure of the infant to the mother’s blood.
When infected during delivery, infants have no evidence of HIV at birth, but
show evidence of infection in the weeks that follow. And finally, infants who
were not infected before or during birth can become infected after birth via
breastfeeding, as breastmilk from an infected woman contains viral particles
and HIV-infected WBC. This mode of maternal-fetal transmission is particularly
prominent in developing countries, where the risk of an infant dying if not
breastfed may be greater than the risk of transmitting HIV via breastmilk (6).
As mentioned previously and shown in Table
I, antiviral therapy of HIV-infected pregnant women was successfully
introduced in the U.S. in 1994. Treatment with AZT of HIV-infected mothers during
pregnancy and/or delivery, and of infants during the first six weeks of life
(with no breastfeeding) reduced the rate of transmission from 26% to 8%; more
recent studies in developing countries using shorter AZT treatments in mothers
only, some of whom breastfed their infants, reduced the rate of transmission
by one-third to one-half (see http://www/unaids.org).
Where it is available, combination antiviral drug therapy similar to HAART is
currently being used to treat HIV-infected pregnant women in hopes of further
reducing maternal-fetal HIV transmission.
THE CONTINUUM OF HIV INFECTION
Any discussion of HIV infection and AIDS needs to emphasize that
HIV infection is a continuum, of which the serious medical condition known as
AIDS is only a small part (Figure 4).
In the first few weeks following HIV infection, a newly-infected person may
experience an acute illness with flu-like or mononucleosis-like symptoms such
as fever, muscle aches, and headaches (2). In most cases, no serious illness
occurs, and within another few weeks, an HIV-infected individual is usually
completely asymptomatic. This asymptomatic phase of the HIV continuum can last
for years, during which the infected person will look and feel well, with no
outward sign of HIV infection. In an adult who has not been treated with anti-viral
therapy, the average time between HIV infection and the development of the clinical
diagnosis of AIDS is eight to ten years (Figure
4). Keep in mind that this is an average, as some HIV-infected persons
have developed AIDS in the first one or two years after infection while others
continue to be asymptomatic nearly twenty years after infection (2). In contrast,
in the absence of effective anti-viral treatment such as HAART, the time between
a diagnosis of AIDS and death from AIDS-related causes is typically only two
to three years. Therefore, in most cases, the vast majority of time a person
spends on the HIV continuum is during the asymptomatic phase, when an individual
could be completely unaware of his or her infection. It is extremely important
to understand that, although an HIV-infected individual may be asymptomatic
for many years (and may or may not know that he/she is infected), HIV-infected
persons are infectious as soon as they become infected. In other words, as soon
as HIV has successfully established an infection in a person, that person is
capable of transmitting the virus to other persons via blood, sexual, or maternal-fetal
contact, and that such contacts could continue for many years before they themselves
become noticeably ill due to their HIV infection.
Regardless of the presence or absence of symptoms, the only routinely available
way to determine if a person is infected with HIV is by performing an HIV antibody
test. Contrary to what is frequently reported in the popular press, this is
not an “AIDS test”, but rather, a test for HIV-specific antibodies
which indicate infection with HIV. As with any infection, when HIV successfully
infects an individual, the immune system of that individual makes antibodies
that will recognize and bind to HIV. These antibodies are intended to neutralize
the virus, limit disease, and assist in clearance of the virus from the body.
However, because the antibodies are specific to HIV, tests can be designed to
detect the HIV-specific antibodies, making them an invaluable tool for diagnosis
of HIV infection. Screening HIV antibody tests are usually performed by an enzyme-linked
immunosorbent assay (ELISA, or sometimes called EIA). Depending on the test,
it can utilize blood serum or plasma, urine, or oral fluids collected with special
devices. If a sample is “reactive”, i.e., gives a positive result
on the ELISA, suggesting the presence of HIV-specific antibodies, it is tested
a second time by ELISA. If “repeatedly-reactive” (positive on both
ELISA tests), the presence of HIV-specific antibodies in the sample is confirmed
or ruled out by Western blot (WB) analysis (1, 6). The WB assay is a highly
specific but labor-intensive means of detecting specific antibodies. If a sample
is reactive on WB with two or more HIV antigens, it is confirmed as truly HIV-antibody
positive. If a sample is not reactive on WB, or reactive with only one of the
HIV antigens, it is considered to be one of the rare false-positive ELISA results
due to non-specific cross-reactions—such a sample would be reported as
HIV-antibody negative. Alternatively, a positive ELISA result can be confirmed
by an immunofluorescence assay (IFA). The combination of a repeatedly-reactive
ELISA test and a confirmatory WB is considered to be greater than 99% accurate
(6). It should be noted that ELISA testing for HIV antibody cannot be used in
newborn infants, as the test will pick up maternal antibodies that have crossed
the placenta into the baby’s circulation. Therefore, the criteria for
diagnosing neonatal HIV infection rely on other types of testing (such as NAT),
as well as clinical signs and symptoms.
The average time in an adult between HIV infection and the development
of detectable HIV antibodies is estimated by the CDC to be 25 days (6); in the
vast majority of HIV-infected persons, an HIV antibody test will be positive
four to eight weeks after infection (Figure 4). In its recommendations
for exposed HCW, the CDC suggests that antibody testing be performed up to six
months post-exposure (8). Whether used in the weeks/months after a known or
suspected exposure or many years after high-risk behavior, HIV antibody testing
can be an extremely powerful tool in determining whether or not a person is
HIV-infected, especially during the asymptomatic period. However, keep in mind
that a single negative antibody test does not guarantee that a person
is not infected (6). As mentioned previously, there is the “window”
period during which a person could be HIV-infected, but not yet have enough
antibodies to be detected by ELISA testing.
Not all sample collection and testing for HIV antibodies is performed
in the clinical laboratory. Home sample collection kits have been available
since 1996 that allow persons to collect a finger-stick sample of blood which
is then mailed anonymously to a laboratory for HIV antibody testing by ELISA
(6). Four rapid tests for detection of HIV-1 and/or HIV-2 antibodies that produce
results in 5 to 20 minutes are licensed for use in the United States (6, 10)
(Table II). These rapid tests vary somewhat on the technology
used, but all are based on same concept as the standard ELISA, i.e., the detection
of antibodies in blood or oral fluid that are specifically reactive with HIV.
Rapid HIV antibody tests vary in their CLIA status, with either waived or moderate
complexity depending on the sample type and the test device used. Rapid HIV
tests are particularly valuable in emergency room and community clinic settings,
where individuals needing HIV testing can be provided results and counseling
in a single visit. Like the traditional ELISA, it is recommended that a sample
that is reactive on a rapid test be retested immediately using the rapid test,
and all repeatedly-reactive samples must be confirmed by a WB or IFA (6, 10).
The HIV antibody tests (ELISA, rapid tests, and confirmatory WB
or IFA) are the only tests approved for diagnosis of HIV infection
in adults, and so is the only testing which should be used for that purpose.
However, there are a variety of clinical laboratory and/or reference laboratory
tests available for evaluating an individual’s immunologic and virologic
status throughout the continuum of HIV infection. One very important measurement
is the determination of lymphocyte subsets by flow cytometry (3), especially
to determine percentage and absolute number of CD4-positive TH cells.
One established normal range for TH cells is 32-60% of total lymphocytes
and 544-1663 TH cells/mm3 of blood. However, in HIV infection, it
is a loss of TH helper cells that leads to the immunodeficiency known
as AIDS (1, 2). Therefore, monitoring of TH cell numbers can help
to determine how far along the HIV continuum an individual may be and/or how
quickly he or she is moving along the continuum.
Since its introduction in the mid-1990s (Table
I), plasma HIV RNA viral load has joined TH cell number as an important
indicator of an HIV-infected individual’s status along the HIV continuum
(2). HIV viral load measurements determine the amount of extracellular viral
RNA present in the circulation and are usually expressed as viral copies or
viral equivalents per milliliter of plasma. Although the HIV viral load is undetectable
at the very beginning of an HIV infection, it peaks during the first weeks after
infection, and then falls to some lower level that is usually stable in the
absence of anti-viral treatment. This stable level or “set point”
will differ from person to person, i.e., from undetectable (<50 or 500 viral
copies/ml depending on the assay) to >100,000 copies/ml, but will vary only
slightly over time within a single individual (2). Studies thus far have suggested
that the lower an individual’s set point, the better the chance that he
or she will survive the next 5-10 years without developing AIDS (2). Therefore,
viral load measurements in the absence of or prior to treatment can help to
predict the length of time an individual may stay in the asymptomatic portion
of the HIV infection continuum. They are also extremely valuable in assessing
the efficacy of anti-viral drug therapy such as HAART, where the viral load
(hopefully) drops significantly and remains lower unless viral resistance to
the drug therapy develops. There are three different commercial assays for plasma
HIV RNA: Amplicor from Roche, which uses reverse-transcription polymerase chain
reaction (RT-PCR), branched DNA or bDNA from Chiron, and nucleic acid sequence
based amplification or NASBA from Organon Teknika. They differ in their sample
collection and handling requirements, so it is essential that clinical laboratory
personnel who are involved in such sample collection are well-informed and well-trained
regarding the particular requirements of the viral load assay utilized by their
institution (either in house or through a reference lab).
In the average adult without effective anti-retroviral treatment,
the asymptomatic phase of the HIV continuum lasts 8-10 years (Figure
4). Since there is no outward sign of viral activity during this time, this
is often referred to as a period of “clinical latency”. However,
in the blood, lymph nodes, and tissues of an HIV-infected person’s body,
the virus is anything but latent (1, 2). Even in an individual who has an undetectable
HIV viral load, HIV is busy infecting and affecting TH cells, monocytes, macrophages,
dendritic cells, and brain cells. Therefore, even though an individual is asymptomatic,
HIV is slowly damaging the immune system (and in many cases, the brain as well).
In particular, HIV infection results in the decline in the number of TH cells
over time, and the function of the remaining TH cells becomes abnormal (1, 2).
When the TH cells are unable to provide adequate help to B cells and CD8 T cells
(Figure 1) due to reduced number and/or function, the immune
system becomes unable to prevent disease caused by certain types of pathogens
and/or cancers. As of the latest major revision of the AIDS-defining criteria
for adults by the CDC in January of 1993, there are now 27 different conditions
that qualify for a diagnosis of AIDS in an HIV-infected person (4). It is the
occurrence of any one of these unusual “opportunistic” infections,
or cancers associated with immunodeficiency, or a dangerously low TH cell count
(less than 200 cells/µl on two successive occasions), that indicates that
an HIV-infected individual has moved into the final, symptomatic phase of HIV
disease known as AIDS (1, 2, 4). While it is still unclear as to exactly how
and why infection with HIV has such a dramatic impact on TH cells, there is
no dispute among mainstream scientists over the fact that HIV infection causes
AIDS (1, 2, 4).
There are many additional aspects of HIV infection and AIDS that
may be of interest to clinical laboratory scientists. The information covered
in this course is intended to provide a review and/or a foundation for understanding
HIV and AIDS at a very basic level. In another course (5), some of the issues
touched upon briefly here are examined in more detail, including the lifecycle
of HIV, how new drugs and/or vaccines are designed to combat the virus, and
statistics and trends of the HIV/AIDS epidemic in the U.S. and around the world.
REFERENCES
- Goldsby, Kindt, and Osborne. Kuby Immunology, 4th Ed. W.H. Freeman
and Company, New York. 2000.
- Special Report: New Victories against HIV. Scientific American
279(1):81-107. 1998.
- Breen E.C. An Overview of the Immune System, Part 2: The Generation and
Evaluation of Immune Responses (3.0 CEU). California Association for Medical
Laboratory Technology.
- Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report,
2002 14:1-40. 2003; HIV/AIDS Surveillance Report, 2003 15:1-46. 2004.
www.cdc.gov/hiv/stats/hasrlink.htm
- Breen E.C. HIV/AIDS Part II—Life and Times of the Human Immunodeficiency
Virus (3.0 CEU). California Association for Medical Laboratory Technology
(revised 2005).
- Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention.
Survival of HIV in the environment, HIV transmission, Evaluation of testing,
www.cdc.gov/nchstp/hiv_aids/hivinfo;
Facts about the human immunodeficiency virus and its transmission, www.cdc.gov/nchstp/hiv_aids/pubs/facts/transmis.pdf;
General and Laboratory Considerations: Rapid HIV Tests Currently Available
in the United States, www.cdc.gov/hiv/pubs/rt-lab.htm.
- The American Red Cross. www.redcross.org
and www.redcross.org/services/biomed/bloood/supply/nucleic.html
and www.bloodsafety.org
- Centers for Disease Control and Prevention. Updated U.S. Public Health
Service Guidelines for the Management of Occupational Exposures to HBV, HCV,
and HIV and Recommendations for Postexposure Prophylaxis. MMWR 50(RR-11).
2001. www.cdc.gov/mmwr/PDF/rr/rr5011.pdf
- Centers for Disease Control and Prevention, Division of Healthcare Quality
Promotion. Surveillance of Healthcare Personnel with HIV/AIDS. 2002. www.cdc.gov/ncidod/hip/BLOOD/hivpersonnel.htm
- Branson, B.M. Rapid HIV Testing: 2005 Update. www.cdc.gov/hiv/rapid_testing/materials.UCSA_Branson.pdf
Figure 1: The Generation of Humoral
and Cell-Mediated Immune Responses
interleukin-2 (IL-2), immunoglobulin (Ig), T helper cell (TH), B cell (B), CD8-positive T cell/CTL precursor (CD8 T), cytotoxic T lymphocyte (CTL)
Figure 2: A Schematic Representation of the Structure
of HIV
Adapted from reference 1. Abbreviations: glycoprotein (gp), protein (p), single-stranded
ribonucleic acid (ssRNA)
Figure 3: Reverse Transcription in Retroviruses
In contrast to all cells that start with DNA as genetic material and make RNA
copies through the process known as transcription, retroviruses have the unique
ability to perform reverse transcription, i.e., start with RNA and make DNA
copies.
Figure 4: The Continuum of HIV Infection
Adapted from: R.A. Weiss. How Does HIV Cause AIDS? Science 260: 1273.
1993.
|
| TABLE II: RAPID TESTS FOR HIV ANTIBODIES | |||||||||
| Test kit name | HIV Ab detection | Time to result | Manufacturer | Specimen type | CLIA category | ||||
| OraQuick Advance Rapid HIV-1/2 Antibody Test |
HIV-1 and HIV-2a |
20 min | Orasure Technologies, Inc. |
|
|
||||
| Reveal G2 HIV-1 Antibody Test | HIV-1 | 5 min | MedMira, Inc | Serum, plasma | Moderate complexity | ||||
| Uni-Gold Recombigen HIV Test | HIV-1 | 10 min | Trinity BioTech, plc |
|
|
||||
| Multispot HIV-1/HIV-2 Rapid Test |
HIV-1 or HIV-2b | 10 min | Bio-Rad Laboratories, Inc. | Serum or Plasma | Moderate complexity | ||||
(compiled from references 6 and 10)
Review Questions Course #: 056-968 - Select the one best answer for each question
- In order to mount antigen-specific humoral responses, B cells require:
a. interactions with monocytes
b. cell-to-cell contact with TH cells
c. intracellular infection of target cells
d. only secreted cytokines from T-H cells
- The CD4 molecule is found on:
a. TH cells
b. CTLs
c. B cells
d. skin cells
- IL-2 produced by TH cells:
a. signals the TH cell that produced it to differentiate into a stem cell
b. drives CD4 T cells to proliferate and become plasma cells
c. provides help for CD8 T cell differentiation into a CTL
d. acts only during cell-to-cell contact with a TH cell
- TH cells are critical for:
a. cell-mediated responses only
b. humoral responses only
c. both humoral and cell-mediated responses
d. non-specific phagocytic responses only
- The first human retrovirus successfully isolated in the laboratory was:
a. HTLV-II
b. HIV-1
c. HIV-2
d. HTLV-I
- The cases of Pneumocystis pneumonia and Kaposi’s sarcoma that were
the first of what came to be known as AIDS were reported in:
a. 1981
b. 1985
c. 1991
d. 1995
- Antibody testing for HIV-1 was introduced into U.S. blood banks in:
a. 1981
b. 1985
c. 1991
d. 1999
- Nucleic Acid Testing (NAT) is utilized in blood banks to:
a. detect antibodies specific for HIV-1 and HIV-2
b. screen for infection with more than five different blood-borne human viruses
c. replace the confirmatory Western blot assay
d. provide earlier detection of the presence of HIV compared to antibody testing alone
- In 1996 and 1997, there were declines in the number of new U.S. AIDS cases
reported each year, and dramatic declines in the number of AIDS-related deaths.
These declines are attributed to:
a. an increase in federal funding for sex education
b. the introduction of federal policies mandating access to medical care for persons with AIDS
c. the introduction of a new class of antiretroviral drugs known as protease inhibitors
d. changes by the CDC in the definition of AIDS
- In 2003, the number of new AIDS cases:
a. continued the decline seen since the mid-1990s
b. increased for the second year in a row
c. was greater than the number of persons estimated to be living with AIDS
d. was nearly zero, signaling the end of the AIDS epidemic
- HAART is an acronym for:
a. “highly-active anti-retroviral therapy”
b. “hepatitis A-associated recovery therapy”
c. “HIV-associated anti-reverse transcription”
d. “high amplification anti-retroviral testing”
- Cells that can be infected by HIV include:
a. TH cells, monocytes, and glial cells
b. B cells and T cells
c. CTLs
d. T cells, macrophages, and skin cells
- The unique genetic process that distinguishes retroviruses is called:
a. reverse translation
b. reverse transcription
c. post-translation modification
d. DNA transcription
- HIV is not transmitted by:
a. sexual contact
b. blood contact
c. casual contact
d. breastfeeding
- The most efficient means of transmission of HIV is probably via:
a. viral particles bound to the surface of uninfected WBC
b. free viral particles
c. food-borne viral particles
d. infected WBC
- The addition of HIV p24 antigen testing and NAT in blood bank screening
has reduced the period during which a donor might be HIV-infected but not
be detected by the screening tests:
a. from 6 months to 6 weeks
b. from 8-10 years to 6 months
c. from approximately 3 weeks to 11 days
d. to less than one week
- The estimated risk of HIV infection following a needlestick exposure to
blood from a known HIV-infected individual is:
a. 0.03 % (3 out of 10,000)
b. 3.0 % (3 out of 100)
c. 30% (3 out of 10)
d. 0.3% (3 out of 1,000)
- The vast majority of documented occupationally-acquired HIV infections
among HCW are the result of exposure to:
a. urine
b. cerebrospinal fluid
c. blood
d. concentrated virus preparations
- The best protection against occupational exposure to HIV for clinical
laboratory scientists is:
a. universal blood precautions
b. universal HIV-antibody testing of patients
c. screening of patients for HIV infection upon hospital admission
d. recapping of all used needles and/or syringes
- It is the recommendation of the CDC that any HCW with a significant exposure
to blood or other potentially infectious materials be evaluated:
a. for referral for possible HIV post-exposure prophylaxis at a later date
b. as soon as possible to determine the need for HIV post-exposure prophylaxis
c. during the next regular working hours of the occupational health service
d. for potential legal liability in the absence of post-exposure protocols
- Variables that dictate whether or not PEP is offered to an exposed HCW
include:
a. full or part-time employment status of worker
b. type of body fluid, severity, and route of exposure
c. HIV-antibody testing on source person without consent
d. presence or absence of insurance coverage for source person
- A baseline blood sample from a potentially-exposed HCW:
a. is not recommended
b. should be obtained and tested for HIV antibodies with his/her consent
c. should be obtained and tested for HIV antibodies over the objections of the HCW
d. should be obtained, but discarded without testing
- HIV cannot be transmitted from an HIV-infected mother to her infant:
a. by kissing
b. through breastfeeding
c. as a result of blood exposure during birth
d. across the placenta
- HIV infection:
a. is indistinguishable from AIDS
b. never causes an acute illness
c. cannot be diagnosed by any means for an average of 8-10 years
d. is a continuum, of which AIDS is only a small part
- A positive result on an HIV antibody ELISA:
a. is valid on a newborn infant
b. can be reported without any further testing
c. can be disregarded in the absence of HIV-related symptoms
d. must be confirmed as positive by WB or IFA
- Jane Doe had a one-time sexual contact with a known HIV-infected person
on January 1, 2005. Jane Doe then had an HIV antibody test performed on January
15, 2005, which gave a negative result. This result means:
a. Jane Doe cannot possibly be infected because she has no symptoms yet
b. Jane Doe is definitely not infected as a result of the January 1 exposure
c. Jane Doe may or may not be infected – it is too soon to rule out a January 1 infection
d. Jane Doe is infected, but will need 8-10 years before her infection can be diagnosed
- HIV viral load measurements determine:
a. the amount of HIV viral RNA present in the circulation
b. the number of HIV-infected cells in the body
c. the length of time a person has been infected
d. the amount of virus to which a person has been exposed
- Rapid HIV-antibody tests do not:
a. provide results in less than one hour
b. eliminate the need for confirmatory WB or IFA testing
c. provide results on oral fluid
d. utilize whole blood
- In an adult without effective anti-retroviral treatment, the average amount
of time between infection with HIV and development of a diagnosis of AIDS
is:
a. 6 weeks
b. 6 months
c. 8-10 years
d. 22 days
- HIV infection results in AIDS because:
a. HIV causes a decrease in the number and function of TH cells
b. HIV depletes the body of monocytes and macrophages
c. HIV infects and destroys all types of lymphocytes
d. HIV selectively infects only certain segments of the population