HISTORY OF HIV & ITS DISCOVERY

The history of the human immunodeficiency virus (HIV) and acquired immunodeficiency
syndrome (AIDS) dates back to 1981, when homosexual men with symptoms of a disease
that now are considered typical of AIDS were first described in Los Angeles and New
York. The men had an unusual type of lung infection (pneumonia) called Pneumocystis
carinii (now known as Pneumocystis jiroveci) pneumonia (PCP) and rare skin tumors
called Kaposi's sarcomas. The patients were noted to have a severe reduction in a type of
cell in the blood (CD4 cells) that is an important part of the immune system. These cells,
often referred to as T cells, help the body fight infections. Shortly thereafter, this disease
was recognized throughout the United States, Western Europe, and Africa. In 1983,
researchers in the United States and France described the virus that causes AIDS, now
known as HIV, belonging to the group of viruses called retroviruses. While HIV infection
is required to develop AIDS, the actual definition of AIDS is the development of a low
CD4 cell count (<200 cells/mm3) or any one of a long list of complications of HIV
infection ranging from a variety of so-called "opportunistic infections," cancers,
neurologic symptoms, and wasting syndromes.

TEST FOR HIV

In 1985, a blood test became available that measures antibodies to HIV that are the
body's immune response to the HIV. The test used most commonly for diagnosing
infection with HIV is referred to as an ELISA. If the ELISA finds HIV antibodies, the
results must be confirmed, typically by a test called a Western blot. HIV antibody tests
remain the best method for diagnosing HIV infection. Recently, tests have become
available to look for these same antibodies in saliva, some providing results within one to
20 minutes of testing. Antibodies to HIV typically develop within several weeks of
infection. During this interval, patients have virus in their body but will test negative by
the standard antibody test, the so called "window period." In this setting, the diagnosis
can be made if a test is used that actually detects the presence of virus in the blood rather
than the antibodies, such as tests for HIV RNA or p24 antigen. Recently, a new test has
been approved that measures both HIV antibodies and p24 antigen, shrinking the duration
of the window period from infection to diagnosis. There also are many testing centers
around the country that are routinely screening blood samples that are HIV-antibody
negative for HIV RNA.

Although the tests for detecting HIV infection continue to improve, they still require that
people volunteer for testing. It is estimated that approximately 20% of those infected with
HIV in the United States are unaware of their infection because they have never been
tested. In order to decrease the number that are unaware of their HIV infection status, in
2006, the Centers for Disease Control and Prevention recommended that all people
between the ages of 13 and 64 years be provided HIV testing whenever they encounter
the health-care system for any reason. In addition, resources are available to facilitate
people finding local HIV testing centers.
TRANSMISSION OF HIV

HIV is present to variable degrees in the blood and genital secretions of virtually all
individuals infected with HIV, regardless of whether or not they have symptoms. The
spread of HIV can occur when these secretions come in contact with tissues such as those
lining the vagina, anal area, mouth, eyes (the mucus membranes), or with a break in the
skin, such as from a cut or puncture by a needle. The most common ways in which HIV
is spreading throughout the world include sexual contact, sharing needles, and by
transmission from infected mothers to their newborns during pregnancy, labor (the
delivery process), or breastfeeding. (See the section below on treatment during pregnancy
for a discussion on reducing the risk of transmission to the newborn.)

Sexual transmission of HIV has been described from men to men, men to women, women
to men, and women to women through vaginal, anal, and oral sex. The best way to avoid
sexual transmission is abstinence from sex until it is certain that both partners in a
monogamous relationship are not HIV-infected. Because the HIV antibody test can take
months to turn positive after infection occurs, both partners would need to test negative
for at least 12 and up to 24 weeks after their last potential exposure to HIV. If abstinence
is out of the question, the next best method is the use of latex barriers. This involves
placing a condom on the penis as soon as an erection is achieved in order to avoid
exposure to pre-ejaculatory and ejaculatory fluids that contain infectious HIV. For oral
sex, condoms should be used for fellatio (oral contact with the penis) and latex barriers
(dental dams) for cunnilingus (oral contact with the vaginal area). A dental dam is any
piece of latex that prevents vaginal secretions from coming in direct contact with the
mouth. Although such dams occasionally can be purchased, they are most often created
by cutting a square piece of latex from a condom.

The spread of HIV by exposure to infected blood usually results from sharing needles, as
in those used for illicit drugs. HIV also can be spread by sharing needles for anabolic
steroids to increase muscle, tattooing, and body piercing. To prevent the spread of HIV,
as well as other diseases including hepatitis, needles should never be shared. At the
beginning of the HIV epidemic, many individuals acquired HIV infection from blood
transfusions or blood products, such as those used for hemophiliacs. Currently, however,
because blood is tested for both antibodies to HIV and the actual virus before transfusion,
the risk of acquiring HIV from a blood transfusion in the United States is extremely small
and is considered insignificant.

There is little evidence that HIV can be transferred by casual exposure, as might occur in
a household setting. For example, unless there are open sores or blood in the mouth,
kissing is generally considered not to be a risk factor for transmitting HIV. This is
because saliva, in contrast to genital secretions, has been shown to contain very little
HIV. Still, theoretical risks are associated with the sharing of toothbrushes and shaving
razors because they can cause bleeding, and blood can contain large amounts of HIV.
Consequently, these items should not be shared with infected people. Similarly, without
sexual exposure or direct contact with blood, there is little if any risk of HIV contagion in
the workplace or classroom.
The risk of HIV transmission occurring after any potential exposure to bodily fluids is
poorly defined. The highest risk sexual activity, however, is thought to be receptive anal
intercourse without a condom. In this case, the risk of infection may be as high as 3%-5%
for each exposure. The risk is probably less for receptive vaginal intercourse without a
condom and even less for oral sex without a latex barrier. Despite the fact that no single
sexual exposure carries a high risk of contagion, HIV infection can occur after even one
sexual event. Thus, people must always be diligent in protecting themselves from
potential infection.

During all stages of infection, literally billions of HIV particles (copies) are produced
every day and circulate in the blood. This production of virus is associated with a decline
(at an inconsistent rate) in the number of CD4 cells in the blood over the ensuing years.
Although the precise mechanism by which HIV infection results in CD4 cell decline is
not known; it probably results from a direct effect of the virus on the cell as well as the
body's attempt to clear these infected cells from the system. In addition to virus in the
blood, there is also virus throughout the body, especially in the lymph nodes, brain, and
genital secretions.

SYMPTOMS OF HIV

The time from HIV infection to the development of AIDS varies. Rarely, some
individuals develop complications of HIV that define AIDS within one year, while others
remain completely asymptomatic after as many as 20 years from the time of infection.
However, in the absence of antiretroviral therapy the time for progression from initial
infection to AIDS is approximately eight to10 years. The reason why people experience
clinical progression of HIV at different rates remains an area of active research.

Within weeks of infection, many people will develop the varied symptoms of primary or
acute infection which typically has been described as a "mononucleosis" or "influenza"
like illness but can range from minimal fever, aches, and pains to very severe symptoms.
The most common symptoms of primary HIV infection are

• fever
• aching muscles and joints
• sore throat
• and swollen glands (lymph nodes) in the neck

PREVENTION OF HIV

Early advances in preventing HIV transmission resulted from educational programs

describing how transmission occurs and providing barrier protection for those exposed to
genital secretions and new needles or bleach to those exposed to blood by sharing
needles. Despite these efforts, new infection in both the developed and developing worlds
has continued at high rates.
Historically, the greatest success in preventing viral transmission has resulted from the
development of preventative vaccines. Unfortunately, decades of research to develop an
HIV vaccine has led to little hope for success. In 2007, a major setback in this area
occurred when the STEP study investigating a promising vaccine candidate was
prematurely stopped due to the lack of evidence that it produced any protection from HIV
infection. In contrast, a glimmer of hope did emerge with the report in 2009 of the results
of the RV 144 Thai HIV vaccine trial which demonstrated borderline effectiveness in the
more than 16,000 recipients. While this vaccine demonstrated only limited evidence of
protection, research is under way to further explore what can be learned for future
vaccine development from this modest success.

In light of the limited ability of counseling and testing to curb the spread of the HIV
pandemic, many researchers have moved toward other biologic strategies for preventing
HIV that do not rely solely on people changing their behavior. It is in this area where
there has been some success. During the last 10 years, there were several large studies
showing that male circumcision along with behavioral counseling reduced the risk of
heterosexual men acquiring HIV infection. This provides a novel prevention strategy for
at-risk, HIV-uninfected heterosexual men. Since the summer of 2010, there have been
several other promising advances in the field of HIV prevention. This included the
CAPRISA 004 study which showed that vaginal administration before and after
intercourse of a gel containing the antiretroviral agent tenofovir reduced the risk of
transmission of both HIV and herpes simplex virus to heterosexual women. Other studies
are under way to confirm the results of this study as well as to determine whether the
results are any different if the agent is administered daily rather than simply around the
time of intercourse. Finally, in the fall of 2010 the iPrEx study reported the results of the
first large study testing the effectiveness of pre-exposure prophylaxis, so called "PrEP."
In this study, HIV-uninfected men who had sex with men who took tenofovir
DF/emtricitabine (TDF/FTC, Truvada) once daily along with a comprehensive program
to promote safe sex practices and early treatment of sexually transmitted diseases,
experienced a markedly reduced risk of acquiring HIV compared with those receiving
similar prevention practice without TDF/FTC. There are several other studies under way
testing the safety and effectiveness of PrEP in other at-risk groups such as heterosexuals
and intravenous drug users. These data are very new, and the use of antiretrovirals for
PrEP is not yet approved or considered the standard of care. A great deal of discussion
will ensue over the coming months between government agencies, academia, industry,
and the community to determine how PrEP should move forward.

A final prevention strategy of last resort is the use of antiretrovirals as post-exposure

prophylaxis, so called "PEP" to prevent infection after a potential exposure to HIV-
containing blood or genital secretions. Animal studies and some human experience
suggest that PEP may be effective in preventing HIV transmission and it is based upon
these limited data that current recommendations have been developed for health-care
workers and people in the community exposed to potentially infectious material. Current
guidelines suggest that those experiencing a needle stick or are sexually exposed to
genital secretions of an HIV-infected person should take antiretrovirals for four weeks.
Those individuals considering this type of preventative treatment, however, must be
aware that post-exposure treatment cannot be relied upon to prevent HIV infection.
Moreover, such treatment is not always available at the time it is most needed and is
probably best restricted to unusual and unexpected exposures, such as a broken condom
during intercourse. If PEP is to be initiated, it should occur within hours of exposure and
certainly within the first several days.

SUMMARY OF HIV

The human immunodeficiency virus (HIV) is a type of virus called a retrovirus, which
infects humans when it comes in contact with tissues such as those that line the vagina,
anal area, mouth, or eyes, or through a break in the skin. HIV infection is generally a
slowly progressive disease in which the virus is present throughout the body at all stages
of the disease.

Three stages of HIV infection have been described. The initial stage of infection (primary
infection), which occurs within weeks of acquiring the virus, and often is characterized
by a flu- or mono-like illness that generally resolves within weeks. The stage of chronic
asymptomatic infection (meaning a long duration of infection without symptoms) lasts an
average of eight to 10 years. The stage of symptomatic infection, in which the body's
immune (or defense) system has been suppressed and complications have developed, is
called the acquired immunodeficiency syndrome (AIDS). The symptoms are caused by
the complications of AIDS, which include one or more unusual infections or cancers,
severe loss of weight, and intellectual deterioration (called dementia).

When HIV grows (that is, by reproducing itself), it acquires the ability to change (mutate)
its own structure. This mutation enables the virus to become resistant to previously
effective drug therapy. The goals of drug therapy are to prevent damage to the immune
system by the HIV virus and to halt or delay the progress of the infection to symptomatic
disease. Therapy for HIV includes combinations of drugs that decrease the growth of the
virus to such an extent that the treatment prevents or markedly delays the development of
viral resistance to the drugs. The best combination of drugs for HIV has not yet been
defined, but one of the most important factors is that the combination be well tolerated so
that it can be followed consistently without missing doses.
AIDS, ITS HISTORY & CAUSES

AIDS stands for "acquired immunodeficiency syndrome." AIDS is a disease that weakens
the immune system to the point where an affected person is vulnerable to a wide range of
infections and cancers that result in death if not treated. Careful investigation has helped
scientists determine where AIDS came from. Studies have shown that the human
immunodeficiency virus first arose in Africa. It spread from primates to people decades
ago, possibly when humans came into contact with infected blood during a chimpanzee
hunt. By testing stored blood samples, scientists have found evidence of human infection
as long ago as 1959. Once introduced into humans, HIV was spread through sexual
intercourse from person to person. As infected people moved around, the virus spread
from Africa to other areas of the world. In 1981, U.S. physicians noticed that a large
number of young men were dying of unusual infections and cancers. Initially, U.S.
victims were predominately homosexual men, probably because the virus inadvertently
entered this population first in this country and because the virus is transmitted easily
during anal intercourse. However, it is important to note that the virus also is efficiently
transmitted through heterosexual activity and contact with infected blood or secretions. In
Africa, which remains the center of the AIDS pandemic, most cases are heterosexually
transmitted.

AIDS is caused by the human immunodeficiency virus (HIV). The virus is spread
through contact with infected blood or secretions. At first (stage 1 HIV infection), there is
little evidence of harm. Over time, the virus attacks the immune system, focusing on
special cells called "CD4 cells" which are important in protecting the body from
infections and cancers, and the number of these cells starts to fall (stage 2). Eventually,
the CD4 cells fall to a critical level and/or the immune system is weakened so much that
it can no longer fight off certain types of infections and cancers. This advanced stage of
infection (stage 3) with HIV is called AIDS.

HIV is a very small virus that contains ribonucleic acid (RNA) as its genetic material.
(Animal cells, plant cells, bacteria, parasites, and some viruses use deoxyribonucleic acid
[DNA] as their primary genetic material rather than RNA.) When HIV infects animal
cells, it uses a special enzyme, reverse transcriptase, to turn (transcribe) its RNA into
DNA which, in turn, directs the formation of HIV RNA that can be used to form new
HIV. This is different from the way human cells reproduce (directly transcribing their
DNA into RNA), so HIV is classified as a "retrovirus." When HIV reproduces, it is prone
to making small genetic mistakes or mutations, resulting in viruses that vary slightly from
each other. This ability to create minor variations allows HIV to evade the body's
immunologic defenses, essentially leading to lifelong infection, and has made it difficult
to make an effective vaccine. The mutations also allow HIV to become resistant to
medications.
SYMPTOMS OF AIDS

AIDS is an advanced stage of HIV infection. Because the CD4 cells in the immune
system have been largely destroyed, people with AIDS develop symptoms and signs of
unusual infections or cancers. When a person with HIV infection gets one of these
infections or cancers, it is referred to as an "AIDS-defining condition." Examples of
AIDS-defining conditions are listed in Table 1. Significant, unexplained weight loss is
also an AIDS-defining condition. It is possible for people without AIDS to get some of
these conditions, especially the more common infections like tuberculosis.

People with AIDS may develop symptoms of pneumonia due to Pneumocystis jiroveci,
which is rarely seen in people with normal immune systems. They also are more likely to
get pneumonia due to common bacteria. Globally, tuberculosis is one of the most
common infections associated with AIDS. In addition, people with AIDS may develop
seizures, weakness, or mental changes due to toxoplasmosis, a parasite that infects the
brain. Neurological signs also may be due to meningitis caused by the fungus
Cryptococcus. Complaints of painful swallowing may be caused by a yeast infection of
the esophagus called candidiasis. Because these infections take advantage of the
weakened immune system, they are called opportunistic infections.

The weakening of the immune system in AIDS can lead to unusual cancers like Kaposi's
sarcoma. Kaposi's sarcoma develops as raised lesions on the skin which are red, brown,
or purple. Kaposi's sarcoma can spread to the mouth, intestine, or respiratory tract. AIDS
also may cause lymphoma (a type of cancer) of the brain or other types of lymphomas.

In people with AIDS, HIV itself may cause symptoms. Some people experience relentless
fatigue and weight loss, known as "wasting syndrome." Others may develop confusion or
sleepiness due to infection of the brain with HIV, known as HIV encephalopathy. Both
wasting syndrome and HIV encephalopathy are AIDS-defining illnesses.
SUMMARY OF AIDS

AIDS stands for "acquired immunodeficiency syndrome.” AIDS is an advanced stage of

infection with the human immunodeficiency virus (HIV). HIV is spread from person to
person through contact with infected secretions or infected blood. People with AIDS have
weakened immune systems that make them vulnerable to selected conditions and
infections.

For people infected with HIV, the risk of progression to AIDS increases with the number
of years the person has been infected. The risk of progression to AIDS is decreased by
using highly effective treatment regimens called HAART. In people with AIDS, HAART
therapy improves the immune system and substantially increases life expectancy. Many
patients who are treated with HAART have near-normal life expectancies.

HAART is a treatment that must be continued for life. It is not a cure. It is possible for
HIV to become resistant to some of the HAART medications. The best way to prevent
resistance is for the patient to take their HAART medications as directed. If the patient
wants to stop a drug because of side effects, he or she should call the physician
immediately. If a person is exposed to blood or potentially infectious fluids from a source
patient with HIV, the exposed person can take medications to reduce the risk of getting
HIV. Research is under way to try to find a vaccine and a cure for HIV.