Download HIV/AIDS: A Global Epidemic

HIV/AIDS: A Global Epidemic
Holly Hannam
Rachel Mackie
Sara Smith
Rick Williams
Biology 240- T. Kibota
July 21, 2005
CAUSATIVE AGENT
Acquired Immunodeficiency Syndrome (AIDS) is caused by the Human
Immunodeficiency Virus (HIV) microbe. Due to the fact that the causative microbe is a
virus, it follows that host cell is necessary for replication. By definition, a virus is a
pathogen consisting of a nucleic acid inside a protein shell or coat, known as a capsid,
without organelles or ribosomes. Because viruses lack organelles and ribosomes, they do
not have the machinery to self-replicate and therefore must employ the replication
machinery of a host cell.
Specifically, HIV is a retrovirus. A retrovirus is a type of virus that requires the enzyme
reverse transcriptase to transcribe its genetic material, RNA, into DNA. HIV is an
enveloped virus outside of the capsid is a lipid bilayer membrane. The envelope, or lipid
bilayer membrane, is very important because it is the attachment place for the
glycoproteins. It is via the glycoproteins (specifically glycoprotein 41 which is
embedded in the lipid bilayer membrane, and glycoprotein 120, which is attached to
glycoprotein 41; collectively these two glycoproteins are called glycoprotein 160) that
HIV attaches to the CD4 receptor. It can invade CD4 T lymphocyte cells (known
commonly as helper-T cells), macrophages, monocytes, and microglial cells (dendritic
cells of the central nervous system; considered to be the CNS counterpart to
macrophages). The major difference among the invasion of these various cells is that
only the helper-T cells are ultimately destroyed; the other types of cells act as reservoirs
for HIV. HIV is considered to be a retrovirade and therefore is approximately 120 nm in
size.
We now know that there are in fact two types of the HIV virus: HIV-1 and HIV-2. HIV1 is found worldwide. HIV-2 was discovered in 1986 and is mainly found in Western
Africa. Studies have been limited on the natural history of HIV-2, but differences
between the two types have been noted: lower perinatal transmission with HIV-2, lower
mortality rate with HIV-2 (about two-thirds that of HIV-1), and variances in the genetic
sequences of the viruses have been detected. Both HIV-1 and HIV-2 have the same
modes of transmission and are associated with the same opportunistic infections and
AIDS. Those infected with HIV-2 seem to develop AIDS more slowly and are less
infectious in the early period of infection, thus HIV-2 is considered less pathogenic than
HIV-1.
HIV-1 exists in many sub-types, with various geographic distribution, therefore subtype
analysis has been used to investigate the introduction and spread of the HIV infection into
many countries.
HISTORY
According to the CDC, the Centers for Disease Control and Prevention, HIV has existed
in the United States since the mid to late 1970s, indicated by studies of previously stored
blood samples. Between the years of 1979 and 1981, doctors in Los Angeles, San
Francisco, and New York reported that gay men were dying of rare cancers (especially
Kaposi’s sarcoma) and pneumonias (specifically Pneumocystis carinii pneumonia, or
PCP). The fact that these men were dying from these particular illnesses was very
unusual because these conditions were not found in people with healthy immune systems.
In 1982, public health officials developed the term acquired immunodeficiency syndrome
(AIDS) to describe the prevalence of opportunistic infections like Kaposi’s sarcoma and
PCP in people who, by all other accounts, had been perfectly healthy. During the
following year, 1983, scientists at the CDC and the NIH, the National Institutes of
Health, along with scientists from the Pasteur Institute in France discovered the virus that
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causes AIDS. The scientists originally named the virus HTLV-III/LAV (for human t-cell
lymphotropic virus-type III/lymphadenopathy-associated virus), but the name was later
changed to HIV (human immunodeficiency virus).
During the late 1970s and early 1980s, only gay men in the United States were affected
by HIV/AIDS. However, in different parts of the world, such as Germany and France,
both men and women of all social classes and sexual orientations were affected by
HIV/AIDS. Because the AIDS epidemic initially developed among the gay community
in the United States, it was considered to be a “gay disease.” At this point, researchers
were still trying to figure out what was causing AIDS and exactly how it was being
transmitted. Because it was affecting the gay community, AIDS was discussed at great
length in the gay press but was not given much coverage in the straight press. In an
example of the extreme marginalization of this disease during the early years of the
epidemic, President Ronald Reagan did not utter the term “AIDS” until 1985, when more
than 5000 Americans had died of AIDS. This all began to change, however, once other
groups began to be diagnosed with AIDS as well. Other groups that began to be affected
included hemophiliacs, recipients of blood transfusions, and infants. This forced the
public, as well as the scientific community, to realize that AIDS could not just be
considered a “gay disease.”
EPIDEMIOLOGY
According to the Global Summary of the AIDS Epidemic that was published in
December 2004, the total number of people living with HIV is approximately 39.4
million people worldwide. This is the highest number of people ever recorded to be
currently living with the human immunodeficiency virus. Of these 39.4 million people,
approximately 4.9 million were newly infected with HIV in 2004, 40,000 of these in the
United States. Nearly 60% of the 39.4 million infected are women and girls between the
ages of 15 and 24. An estimated 950,000 Americans are currently living with
HIV/AIDS, up from 900,000 in 2001. In 2003, there were an estimated 15 million AIDS
orphans around the world, expected to increase to 25 million by 2010. It should also be
noted that approximately 3.1 million people died of AIDS in 2004. Overall, since the
beginning of the epidemic, nearly 14 million people have died worldwide.
The AIDS epidemic does not discriminate. The HIV/AIDS epidemic is most prevalent in
Sub-Saharan Africa; their numbers account for approximately two-thirds of the overall
HIV/AIDS cases. However, HIV is greatly increasing in Eastern Europe, Central and
Eastern Asia, and the Caribbean as well. In the United States, HIV/AIDS is increasing
most quickly and disproportionately among minorities and women. HIV/AIDS is now
the leading cause of death among African-American women between the ages of 25-34.
The mode of transmission for HIV is as follows: sexual activity (both heterosexual and
homosexual), blood product transfusion, intravenous drug use that includes the sharing of
needles, accidental needle sticks (this affects mostly health care workers; this mode is
very rare, accounting for approximately 0.3% of infections), and mother-to-infant
transmission, both in utero (across the placenta) and during delivery, as well as via
breastfeeding.
As stated before, the CD4 T lymphocyte cells are the only cells destroyed by HIV.
However, because HIV is also capable of invading macrophages, monocytes, and
microglial cells (all of which also have CD4 receptors), these sites serve as reservoirs for
the virus. In other words, unlike the CD4 T-helper cells, these other cells are not
ultimately destroyed by the virus. Instead, the reservoirs may be activated by normal
immune processes, leading to the production of more virus. The infected monocytes and
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macrophages do seem to contribute to central nervous system damage (manifested in
about half of HIV cases, and including symptoms such as impaired short-term memory,
reduced concentration, tremor, fine motor clumsiness, social withdrawal, and irritability),
however, as they can travel into the brain and serve as a reservoir there. These symptoms
usually appear in patients with high viral loads.
PATHOLOGY
The course of HIV infection is considered to consist of three phases: an initial phase that
follows infection, a middle phase during which the person remains asymptomatic, and a
late phase, when AIDS occurs.
During the initial phase, once the person has become infected with HIV, the virus
undergoes massive replication due to the fact that at this time, there is an abundance of
CD4 T lymphocyte cells to infect (a healthy immune system has 800-1200/cubic milliliter
of blood) and no antibodies present in the body. At this time, approximately 50-90% of
those infected experience what is known as acute retroviral syndrome, an illness that is
most often mistaken for the flu. The signs and symptoms of acute retroviral syndrome
include fever, lymphadenopathy, pharyngitis, myalgia, diarrhea, nausea, and vomiting.
At this time, the viral load of HIV in the blood is very high. The body’s immune system
springs into action, which ultimately causes blood levels of HIV to decrease. This is the
beginning of the middle phase, which is known as clinical latency. During this phase, the
blood levels remain low and the person is asymptomatic. The middle phase of HIV
infection typically lasts 8-10 years. It should be noted, although blood levels of HIV
remain low during this time, the virus is actively replicating in the lymph tissue. Also,
the macrophages and monocytes that are infected with HIV travel throughout the body
and can therefore infect various organs. Even though the person remains relatively
symptom-free, the level of CD4 T lymphocyte cells continues to decline during this
middle phase.
AIDS, the late phase of HIV infection, is considered to occur when the CD4 T-cell count
drops below 200 per cubic milliliter of blood or an AIDS-defining illness is present.
These include Kaposi’s sarcoma, cytomegalovirus, or Pneumocystis carinii pneumonia
(PCP). Most commonly, these two indicators tend to occur hand-in-hand because once
the T-cell count drops below 200, the person becomes much more vulnerable to
opportunistic infections such as PCP and Kaposi’s sarcoma, which characterize AIDS.
Between 5-10% of infected persons have been identified as “long survivors” who do not
experience a significant decline in immune function. These individuals tend to have low
viral load counts, a stable CD4 lymphocyte count, and favorable antibody responses.
RESPONSE AND TREATMENT
As has been stated before, HIV attacks and ultimately destroys the CD4 T-cells.
Although the immune system mounts an attack after the initial infection, ultimately HIV
prevails as far as the T-cells are concerned. Given that the T lymphocyte cells are
necessary for our immune system to function properly, this is, in a sense, ultimately a
death sentence for a person infected with HIV. A cure does not exist at this time, though
treatments are now available that improve the odds.
Today’s standard treatment is known as HAART, an acronym for highly active
antiretroviral therapy. HAART consists of a drug regimen that includes three to four
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drugs used in combination; these combinations are known as drug “cocktails.” There are
currently three classes of antiretroviral drugs: reverse transcriptase inhibitors, protease
inhibitors, and HIV fusion inhibitors. A standard HAART regimen consists of two
reverse transcriptase inhibitors and a protease inhibitor. The HIV fusion inhibitor,
Enfuvirtide, is reserved for patients that have become resistant to other antiretroviral
drugs. The reasons for this resistance development are the speed with which the virus
replicates and its replication methods. For this reason, the drugs in the HAART regimen
are rotated out and different drugs from the same class are introduced into the
combination cocktail as the patient develops resistance. The use of HAART can make
HIV practically undetectable in the blood, and has prolonged the lives of many HIV and
AIDS patients. However, treatment is very expensive and must be used continuously.
Additionally, HAART is not a cure, merely a treatment.
In order to understand how these medications work, it is important to first understand
how HIV invades and infects a CD4 T-cell and how it then replicates. HIV is an
enveloped virus, meaning that it has a lipid bilayer membrane. The glycoproteins that are
embedded and attached to the lipid bilayer membrane attach to the CD4 receptor of a Tcell, macrophage, monocyte, or microglial cell. Once the HIV is attached to the CD4
receptor, the virus fuses (in a process similar to endocytosis) with the host cell and its
contents enter the cell. HIV reverse transcriptase converts the virus’s RNA into viral
DNA (known as a provirus), which then enters the host cell’s nucleus. The viral DNA is
then spliced into the cell’s DNA with the enzyme HIV integrase. mRNA copies are then
transcribed from the DNA and the mRNA moves to the cytoplasm, where it uses the
cell’s own ribosomes to translate viral proteins and enzymes. Due to the speed of the
replication (the virus carries a gene that actually encodes a protein that hastens
transcription) and the lack of a complementarity check in RNA molecules (which are
single-stranded), the mutation rate for the replicated viral genetic material is quite high.
After the virus has replicated in the T-cell, it buds off of the host cell, taking part of the
host cell’s membrane with it as its envelope (this process is similar to exocytosis). This
effectively kills the T-cell. When the virus is budding off, or immediately after it buds
off the host cell, the enzyme protease cleaves the polyproteins that have been made into
the smaller, functional parts that are necessary in order for HIV to be infectious. When
HIV enters and invades macrophages, monocytes, and microgilal cells, it remains within
the cell; the cell then serves as a reservoir for the virus.
The reverse transcriptase inhibitors work by interrupting the reverse transcriptase
process, therefore the RNA is not able to be converted into DNA and therefore the virus
cannot replicate. The protease inhibitors work in a similar fashion. They block the
enzyme protease that is essential for HIV to be infectious. The fusion inhibitors are the
newest class of antiretroviral drugs, and currently there is only one drug available,
Enfuvirtide. Enfuvirtide blocks the entry of HIV into the CD4 T-cell by binding to
glycoprotein 41. By binding to glycoproteins on the CD4 T-cell, Enfuvirtide effectively
blocks the human immunodeficiency virus, as this is where it needs to attach in order to
be able to fuse with the host cell. It is important to remember that these drugs can help to
decrease the serum levels of HIV, but as of yet there is not a cure for HIV/AIDS.
In order to prevent the spread of HIV/AIDS, we have to prevent the mode of transmission
from one person to another. This is very difficult, because in order to prevent the mode
of transmission, we have to address all of the modes of transmission, including sexual
activity, blood transfusion, IV drug use with the sharing of needles, and from mother to
infant. Obviously, one way to prevent the spread of HIV/AIDS is to practice safe sex.
Another way to prevent the spread of HIV/AIDS is to test donated blood. There are ways
that we can begin to address these issues, however, as we will examine in the next section
of this paper. A variety of social, political, and economic factors must be considered.
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SOCIAL, POLITICAL, AND ECONOMIC FACTORS
As mentioned in the History section of this paper, the AIDS epidemic in the United States
was initially thought to be a “gay disease.” This fact alone hindered research during the
early 1980s and therefore enabled the disease to be spread simply due to lack of
knowledge and public awareness. Once AIDS started to affect other groups, not just gay
men, more money was put into research and prevention programs. Although the United
States and the developed world have come a long way in terms of knowledge regarding
HIV/AIDS, there are many other places in the world where this is not the case.
There are many factors that are intertwined that affect the spread of HIV/AIDS. For
example, one method of preventing the spread of HIV/AIDS is to practice safe sex. Even
this single aspect, however, has many complicating dimensions. Safe sex entails using
latex condoms treated with an approved spermicidal agent. Availability of such
protection is not universal, and even where available, there are those who refuse to use
them, or use them improperly. Another factor is the decision to engage in intercourse in
the first place. Depending on the culture of the society in question, for some women, this
may not be a matter of choice. A woman in such a position would likely find it difficult
or impossible to persuade her partner to use a condom.
Another seemingly easy target for transmission prevention is IV drug use. Clean needle
exchanges are a low-cost solution, and programs such as this have been in place in
Europe since the early years of the epidemic. These programs have reduced needle
transmission of not only HIV but also Hepatitis B. This straightforward solution has met
with great controversy in the United States; some object strongly to needle exchange
programs by arguing that they encourage drug use.
Another important factor to consider is the cost of therapy to treat HIV and the
opportunistic infections associated with AIDS. In developed countries, some people are
able to access treatment, but not all, due to the prohibitively high cost. In
underdeveloped nations, even when treatment is available, it is often beyond the reach of
most of the citizens due to the cost.
The extent of the AIDS epidemic is both far and deep. HIV/AIDS has had a devastating
effect on whole societies, most notably in Sub-Saharan Africa. Poverty and lack of
economic development often allow it a greater foothold (such as when individuals cannot
find work near home, and thus the population becomes more mobile in search of work,
giving rise to the opportunity for wider ranges of infection), and in return, poverty is
reinforced by the loss of individuals and resources to the epidemic. All of these factors
make HIV/AIDS an exceptionally complicated problem for the world as a whole.
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LITERATURE CITED
And the Band Played On. 1993. Home Box Office, Inc.
Auerbach, Judith. 2004. The Overlooked Victims of AIDS. The Washington Post.
October 14, page A31.
Barks-Ruggles, Erica. 2001. Meeting the Global Challenge of HIV/AIDS.
http://www.brookings.edu/comm/policybriefs/pb75.pdf
Centers for Disease Control and Prevention. A Glance at the HIV Epidemic.
http://www.cdc.gov/nchstp/od/news/At-a-Glance.pdf
Centers for Disease Control and Prevention. 1998. Human Immunodeficiency Virus
Type 2. http://www.cdc.gov/hiv/pubs/facts/hiv2.htm
Centers for Disease Control and Prevention. Milestones in the U.S. HIV Epidemic.
http://www.cdc.gov/nchstp/od/mmwr/TimeLine%20rev2.pdf
Centers for Disease Control and Prevention. 2003. Where did HIV come from?
http://www.cdc.gov/hiv/pubs/faq/faq3.htm
Cimons, Marlene. 1985. Health experts glad Reagan cited AIDS; pleased by attention,
disappointed he did not quell school fear. Los Angeles Times September 19,
1985.
Eberstadt, Nicholas. 2002. The Future of AIDS. Foreign Affairs. November/December.
Gladwin, M., M.D. and B. Trattler, M.D. 2004. Clinical Microbiology Made Ridiculously
Simple. 3rd ed. MedMaster, Inc., Miami, FL.
Internet Pathology Laboratory for Medical Education, Florida State University College of
Medicine. HIV Tutorial. http://wwwmedlib.med.utah.edu/WebPath/TUTORIAL/AIDS/HIV.html
Lehne, R.A. 2004. Pharmacology for Nursing Care. 5th ed. W.B. Saunders, St. Louis,
MO.
National Institutes of Health, Office of Communications and Public Liaison. 2005. HIV
Infection and AIDS: An Overview, NIAID Fact Sheet.
http://www.niaid.nih.gov/factsheets/hivinf.htm
National Institutes of Health, Office of Communications and Public Liaison. 2004. How
HIV causes AIDS, NIAID Fact Sheet.
http://www.niaid.nih.gov/factsheets/howhiv.htm
Preston-Whyte, Eleanor. 2004. Framing the South African Epidemic: A Sociological
Perspective. School of Developmental Studies, University of Kwazulu-Natal.
http://www.ukzn.ac.za/csds/PUBLICATIONS/CONF50/PrestonWhyte,%20Eleanor.pdf
Taber's Cyclopedic Medical Dictionary. 19th ed. 1997. F.A Davis Company,
Philadelphia, PA.
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UNAIDS. 2004. Global Summary of the AIDS Epidemic.
http://www.unaids.org/bangkok2004/GAR2004_html/ExecSummary_en/ExecSu
mm_00_en.htm
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