Author : Frederick (Rick) Hecht, MD, is Professor of Medicine at the University of California, San Francisco, in the Division of HIV/AIDS at San Francisco General and the UCSF Osher Center for Integrative Medicine.
2009-02-18
2009-02-18
AIDS
Acquired Immunodeficiency Syndrome
Acquired
Immunodeficiency Syndrome (AIDS) is a state in which the immune system
no longer functions normally due to damage by the Human Immunodeficiency
Virus (HIV). The key ways HIV is transmitted are through sexual
contact and use of contaminated needles (for example those used for
injecting drugs). It is not transmitted through casual contact such as
sharing eating utensils or touching someone with HIV. Since it was
described in 1981, more that 25 million people are believed to have died
of AIDS; 33 million people were believed to be living with HIV in 2007
[1]
There are now a variety of effective antiretroviral drugs
that can halt HIV replication and prevent damage to the immune system by
HIV. These drugs have been a major advance in preventing the
development of AIDS in persons with HIV. Despite the development of
effective treatments and worldwide efforts to make treatment available,
many people who need treatment do not have access to anti-HIV drugs.
1. The cause of AIDS
1.1. HIV
In 1981, a new immunodeficiency syndrome that had appeared in homosexual men was first described and given the name AIDS. The
patterns of the disease spread (or epidemiology) appeared to be
infectious, and were similar to viral infections such as hepatitis B. These clues set off an intensive search for the potential cause of AIDS. In 1985, three different groups described a virus that they had identified as the likely cause of AIDS. Each group identified what appeared to be the same virus, one that was eventually named Human Immunodeficiency Virus (HIV).
Figure: Mature
HIV viruses budding from a cell as seen through
electron microscopy (from Public Health Image Library)
Although these
and other findings have convinced almost all experts and activists that
HIV causes AIDS, there were early critics of this concept, a few of
which have persisted to recent years. Perhaps most vocal among scientists was Peter Duesberg [2]. Some
of his key criticisms involved issues such as the failure to show free
virus in the blood in most persons, and the finding of up to 5% of
persons with AIDS who did not appear to have HIV antibodies. In
both cases, these issues appear to have resulted from shortcomings of
testing approaches. Newer methods of detecting virus in the blood have
found HIV in high quantities in nearly all persons with AIDS, and more
sensitive HIV antibody tests are positive in virtually all persons with
AIDS. Duesberg’s claims that HIV may not be the cause of AIDS have been carefully refuted [3]. The
dramatic success of treatments that stop HIV replication in reversing
AIDS and preventing death provide extremely strong evidence for both for
the cause of AIDS and the value of HIV treatment. Perhaps the biggest
consequence of doubts that HIV causes AIDS, however, has been in the
political arena rather than the scientific arena. In South Africa for example, the voicing of doubts
by key government leaders that HIV causes AIDS has been blamed for slow
responses to the country’s severe AIDS epidemic, including delayed
availability of treatment [4].
1.2. Loss of CD4+ T-cells
The hallmark of AIDS is the loss of CD4+ T-lymphocytes. These cells are a key part of the immune system and orchestrate responses by other parts of the immune system. The
loss of CD4+ T-lymphocytes leads to immunodeficiency (lack of certain
immune responses), which leaves the affected person vulnerable to
infections and certain cancers. Many of these infections
are ones that cause few, if any, problems in persons with healthy immune
systems; these infections are known as opportunistic infections as they
take advantage of the weakened immune system. Measurement
of CD4+ T-cell counts is the key laboratory test that is used to
determine how advanced the infection is (often referred to as staging). CD4+
counts are a widely available test in the developed world; efforts to
make them more available are now an important issue in improving the
availability of treatment in the developed world.
HIV (in green and red) binding to a CD4+ T-lymphocyte (from Frontier AIDS)
2. Staging and diagnosis
Shortly
after becoming infected by HIV, many people develop a brief period of
symptoms that resembles many other viral infections. These symptoms typically begin one to four weeks after infection and last from a few days to a few weeks. Common symptoms include fever, rash, severe fatigue, muscle and joint aches, and a sore throat. The only way to distinguish them with certainty from other viral illnesses is to perform testing. This
period of symptoms occurs before immune responses are well organized
against HIV, and the symptoms typically resolve as the levels of virus
begin to drop as immune responses develop further. This initial stage of
HIV infection is called primary or acute HIV infection.
After primary HIV infection, there is a period of infection in which most people experience no symptoms from the infection.
Normal CD4+ T-cells counts are above 500 cells/µl. Most people experience no symptoms of HIV infection until the CD4+ T-cell count falls below 350 cells/µl (Table 1). Between
200 and 350 cells/µl, infected persons may begin to experience mild
symptoms that may not be easily recognized as related to HIV if the
infection is undiagnosed. These symptoms include mild
fatigue, and increased risk of developing shingles (herpes zoster),
thrush (yeast infection of the mouth), bacterial pneumonia, and
tuberculosis. Occasionally, Kaposi’s sarcoma (a type of cancer) may occur while CD4+ T-cell counts are still above 200 cells/µl.
Once
the CD4+ T-cell count falls below 200 cells/µl, serious opportunistic
infections and cancers begin to occur, especially once the CD4+ T-cell
count is below 100 cells/µl. Without any treatment, the
median time from infection to these AIDS defining illnesses is about 10
years, though many people progress more or less rapidly. These serious opportunistic infections are discussed further in the section on Conditions and Complications.
CD4+
T-cell counts are a component of the disease staging classification
from the United States Centers for Disease Control and Prevention (CDC)
[5]. The diseases noted in Table 1 with round bullets
represent those that are considered AIDS defining clinical conditions in
the CDC criteria. In addition, current CDC criteria
define someone with a CD4+ T-cell count below 200 cells/µl as having
AIDS even if one of these complications has not yet developed. The
World Health Organization (WHO) has provided an alternative system for
classifying HIV disease for use in resource limited settings in which
CD4+ T-cell counts are not available [6].
Table 1: Common HIV-related complications and AIDS defining conditions by stage of immunosuppression
| CD4+ T-cell count range | Typical Conditions |
| > 500 cells/µl | Normal range, no symptoms except during primary infection (first few months) |
| 350 to 500 cells/µl | Usually no symptoms. May have a slight increased risk of tuberculosis and long periods of time in this range may modestly elevate the risk of cancer and heart disease |
| 200 to 350 cells/µl | Increased risk of:
Ø Shingles (herpes zoster)
Ø Bacterial pneumonia
Ø Oral candidiasis (yeast infection of the mouth) and vaginal candidiasis
Ø Fatigue
Ø Oral hairy leukoplakia
· Tuberculosis *
· Kaposi's sarcoma
· Mycobacterium tuberculosis *
|
| 100 to 200 cells/µl |
· Cervical cancer, invasive *
· Lymphoma, Burkitt's or immunoblastic
· Pneumocystis carinii pneumonia (PCP)
· Toxoplasmosis of brain
· Coccidioidomycosis outside the lungs
· Cryptococcosis outside the lungs
· Histoplasmosis outside the lungs
· Pneumonia, recurrent
|
| < 100 cells/µl |
· Esophageal or bronchial candidiasis (yeast infection)
· Cryptosporidiosis greater than 1 month's duration
· Cytomegalovirus infection of retina, esophagus or intestines
· Herpes simplex: chronic ulcer lasting more than 1 month or esophagitis
· Lymphoma originating in the brain
· Mycobacterium avium complex (MAC)
· Progressive multifocal leukoencephalopathy (PML)
|
Conditions are listed by the CD4+ T-cell count range in which they commonly first occur. The risk of most conditions increases as the CD4+ T-cell count drops. Round
bulleted conditions indicate AIDS defining clinical conditions using
the 1993 CDC definitions
[http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm]. *
= a condition in which the CD4+ T-cell count must be < 200 cells/µl
and the HIV antibody test must be positive to meet criteria for a
clinical AIDS defining condition.
HIV antibody tests can detect whether someone has antibodies directed to the HIV virus. They are now central to diagnosis of HIV infection, and allow diagnosis before AIDS related complications have developed. Antibody tests typically take a month or more to become positive after infection has occurred. After
this time, they detect nearly everyone with HIV infection, and have a
very low rate of false positive tests (results are positive in someone
who does not have HIV).
3. Conditions and complications
The
immune deficits that occur with HIV infection result in a wide range of
complications that can affect every part of the body. Most
of these complications result from infections that take advantage of a
weakened immune system, but some involve cancers and auto-immune
problems; some problems also appear to represent direct effects of HIV. Detailed guidelines from expert panels for treatment and prevention of opportunistic infections can be found at http://www.aidsinfo.nih.gov/Guidelines
3.1. Malignancies (cancer)
Kaposi’s sarcoma causes purplish tumor areas on the skin, lining of the gastrointestinal tract (including the mouth), and lung. The tumors have proliferations of small blood vessels. Before AIDS, Kaposi’s sarcoma was a rare cancer found mainly in parts of Africa and around the Mediterranean. It is the most common cancer in AIDS. In
AIDS, this cancer usually results from the effects of two different
infections: HIV reduces immune responses, while a second virus, human
herpes virus 8 predisposes to the development of Kaposi’s sarcoma. Kaposi’s sarcoma in persons with AIDS can often be treated by antiretroviral treatment of HIV alone. If this is not effective, it usually responds well to chemotherapy if immune function can be restored by HIV treatment.
3.2. Pulmonary (lung)
Pneumocystis pneumonia (PCP) is the most common serious opportunistic infection in AIDS in much of the developed world. It occurred in 70-80% of persons with AIDS before HIV treatments and prevention for PCP was developed [7]. It is caused by Pneumocystis jiroveci,
an organism that can often be found in very small numbers in healthy
persons, but appears to cause no problems in persons with healthy immune
systems. PCP usually has a gradual onset, often over one to two weeks. Patients
usually experience shortness of breath, which occurs first during
activities that demand extra oxygen such as climbing stairs, but
progresses to shortness of breath at rest. The cough most commonly results in clear or whitish phlegm, or is a dry cough. Fever is common. If not treated promptly, PCP is fatal. Even
with optimal treatment, this is a life threatening infection with a
fatality rate of 5% or more in experienced treatment centers. Several treatments are effective for PCP. The most effective is high dose trimethoprim-sulfamethoxazole (Bactrim or Septra). Because
of the frequency and severity of PCP in AIDS, prophylaxis (treatment to
prevent the disease) is recommended for persons with AIDS who have a
CD4+ T-cell count below 200 cells µl using a low daily dose of
trimethoprim-sulfamethoxazole.
Tuberculosis often appears similar to tuberculosis in persons without HIV. Typical
symptoms include gradual onset over days to weeks of cough, fever,
night sweats, weight loss, and general feelings of illness and fatigue. Tuberculosis in HIV usually responds well to treatment with the same drugs used in persons without HIV. A
very serious emerging problem, however, is that the combination of AIDS
and pre-existing problems with drug resistant tuberculosis have led to
epidemics of drug resistant tuberculosis in different parts of the
world, including southern Africa and eastern Europe. A
recently detected epidemic of tuberculosis in South Africa with
tuberculosis that is resistant to all commonly used first and second
line treatment currently poses a major potential global health threat if
it is not contained; this threat underlines the importance of global
efforts to treat and prevent both AIDS and tuberculosis. The risk of tuberculosis is dramatically increased in HIV infection. The increased risk results from two factors. First, persons with HIV who are exposed to tuberculosis have an increased risk of becoming infected. Secondly,
most active tuberculosis does not occur following exposure, but from
reactivation of tiny areas of infection that persist for years after an
initial exposure that causes few, if any symptoms. In
persons with healthy immune systems, the lifetime risk of reactivation
of disease once the initial infection is contained is less than 10%. In persons with AIDS, the risk of reactivation of tuberculosis infection is about 10% per year. Because
of this risk, there is a strong recommendation that persons with HIV
and a positive skin test for tuberculosis exposure (PPD test) get
prophylactic treatment to prevent active disease.
Bacterial pneumonia occurs much more frequently in patients with HIV. The causes are similar to those in persons without HIV. Pneumococcal pneumonia is the most common cause, and Haemophilus influenzae pneumonia is also frequent. Bacterial pneumonia in AIDS responds to the same antibiotic treatments given to persons without HIV. Vaccination
to pneumococcus is recommended to prevent this type of pneumonia,
though responses to vaccinations are reduced in persons with HIV and
decreased CD4+ T-cell counts. Influenza vaccination (a flu
shot) is also recommended for persons with HIV as bacterial pneumonia
is a common complication of influenza.
A variety of other complications can
affect the lungs in AIDS. Fungal infections of the lung that are
associated with AIDS include cryptococcus, histoplasmosis, and
aspergillious. Cancers that can affect the lung that are more common in AIDS include Kaposi’s sarcoma and lymphoma.
3.3. Neurologic (brain, spinal cord, nerves)
Several infections of the brain are common complications of AIDS. Toxoplasmosis is
a tiny parasite that usually causes asymptomatic infection in persons
without HIV, or can cause a mild illness with enlarged lymph nodes,
fever, and mild fatigue. In AIDS, toxoplasmosis can infect
the brain, causing a variety of symptoms that depend on the part of the
brain that is affected, such as weakness in specific parts of the body. Headache and seizures are common. On
imaging of the brain with CT or MRI scanning, specific areas of
abnormal brain tissue can be seen that enhance around the margins of
infected areas when imaging contrast agents are given (“ring enhancing
lesions”); usually more than one location is affected. Toxoplasmosis usually responds well to treatment with a combination of pyrimethamine plus sulfadiazine plus leucovorin. Toxoplasmosis is another example of reactivation of an old infection that was contained by the immune system. Cats are the natural host of toxoplasmosis in which toxoplasmosis can reproduce and spores are passed in the feces. Farm animals commonly become infected by ingesting spores spread from the feces of infected cats. Once
these spores are ingested, they spread throughout the body and can form
tiny spores in muscle tissue. The most common cause of toxoplasmosis
infection is eating raw or under-cooked meat from infected cows or pigs. The frequency of toxoplasmosis infection varies according to culinary customs. In
France and Germany, where steak tartare is popular, over 50% of persons
have been infected with toxoplasmosis and it is a very common
complication of AIDS; in most of the US about 15% of people have been
infected. Toxoplasmosis infection can also occur by
ingesting spores from cat litter. To prevent toxoplasmosis exposure, it
is recommended that people with HIV avoid eating raw or undercooked meat
or changing cat litter. TMP-SMX, which is given to prevent PCP, also
helps to prevent toxoplasmosis.
Cryptococcal meningitis is
a another common infection in persons with CD4+ T-cell counts below 200
cells/µl, occurring in 5-8% of people with AIDS before HIV treatment
was developed [7]. The typical symptoms are severe
headache and fever, sometimes accompanied by confusion and other “mental
status changes.” Cryptococcus is a yeast that is found commonly in the
environment, and rarely causes significant illness in persons with an
intact immune system. In persons with AIDS, however, cryptococcal infections begin in the lung and can then enter the blood stream. The
fluid around the brain appears to provide a good culture media for
cryptococcus when it is poorly defended by the immune system. Cryptococcal meningitis is another infection that is fatal in AIDS if not treated promptly. Even with treatment, it can often still be fatal. Treatment is usually started with amphotericin B, sometimes with flucytosine added, for the first two weeks. This
treatment must be given intravenously, and has significant side
effects, including causing chills and fevers while it is given, and
causing kidney problems. If patients are stable after the
first two weeks, treatment can be switched to fluconazole, which can be
given by mouth. After successful treatment, a lower dose of fluconazole
is given to prevent relapse unless the immune system can be at least
partially restored by HIV treatment.
HIV dementia is thought to be a direct effect of HIV on the brain. It is common in persons with advanced AIDS. It
causes a gradual loss of short-term memory over a period of months to a
couple of years, and can lead to confusion and personality changes. It
is rare in persons on HIV medications, even when these are not
completely effective in preventing damage to the immune system.
Progressive multifocal leukoencephalopathy (PML) usually
has a gradual onset over weeks to months, In addition to causing
dementia, patients develop other neurologic problems such as difficultly
walking, paralysis, and seizures. It is caused by the JC
polyoma virus. Most people become infected with this virus during
childhood, but have no symptoms from the infection. In
AIDS, it causes a gradual loss of the myelin (demyelination), a
protective sheath around some nerves that is also affected in diseases
such as multiple sclerosis. Brain tissue with myelinated
nerves is white, while other brain tissues are grey, resulting in the
description of PML as a “brain disease of the white matter.” PML is a feared disease among HIV physicians because there is no direct treatment. The
course, while variable, usually relentlessly robs patients of
functioning before progressing to death over a period of months.
Currently, the only hope for treatment of PML is to use effective HIV
treatment to restore the CD4+ T-cell count. This approach is only occasionally effective. Patients often do not live long enough to allow the immune system to recover. In
addition, when the immune system does begin to recover, the attack of
the re-awakened immune system on the brain infection can cause new and
sometimes fatal problems, part of a picture known as “immune
reconstitution syndrome.”
Peripheral neuropathy, a set of problems with the nerves outside of the brain and spinal cord, is a fairly common problem in AIDS. Symptoms
can vary, but typically include a pain syndrome that is often described
as a burning sensation, loss of reflexes, and muscle weakness.
Peripheral neuropathy is thought to be caused directly by HIV, as well
as by cytomegalovirus infection in AIDS patients with very suppressed
immune systems. The treatment is effective HIV therapy. Peripheral neuropathy, however, can also be caused by some HIV medications. The
key step to treat HIV neuropathy caused by HIV medicines is to stop the
medications suspected of causing the neuropathy, if this is possible,
and change to other medication. In patients in which peripheral
neuropathy develops while on treatment that is not fully effective in
stopping HIV replication, it can sometimes be difficult to discern
whether the problem is caused by HIV treatment or by incomplete
treatment of HIV infection. In this situation, the goal,
if possible, is to stop medications that might be causing the neuropathy
while changing to medications that may be more effective in controlling
drug resistant HIV- which can be a challenge.
3.4. Gastrointestinal (stomach, intestines)
HIV can affect the gastrointestinal tract from its beginning in the mouth to its end at the anus. Several infections can affect the mouth, throat, and esophagus. The most common is candida. This is the same yeast that causes vaginal yeast infections in woman. In the mouth, candida causes thrush. Thrush
occurs in people without HIV (especially babies), and is one of the
early diseases that can signal immune deficits in HIV. It is characterized by white plaques on the sides of the mouth and throat that do not scrape off easily and feel irritated. Topical
treatments such as sucking on a lozenge with clotrimazole (troches) or
swishing a nystatin solution around the mouth usually work, but have to
be given multiple times per day for one or more weeks. Fluconazole pills are highly effective and preferred by most patients as they can be given once daily.
Candida esophagitis occurs when candida extends into the esophagus. This
rarely occurs until CD4 + T-cell counts are at least close to 100
cells/µl, significantly lower than when thrush begins to occur. The primary symptom is usually pain on swallowing (dysphagia). The
diagnosis is usually made based on a typical set of symptoms in someone
with a low CD4+ T-cell count; candidiasis in the mouth provides
supporting evidence. The most common treatment is fluconazole, taken as a daily pill; other drugs such as itraconazole are alternatives. If
symptoms do not at least mostly resolve after a week of treatment, it
should prompt diagnostic testing using endoscopy (a fiber optic tube) to
look at the esophagus. The most common alternatives causes of dysphagia
in AIDS are herpes simplex or cytomegalovirus (CMV) infections of the esophagus, both members of the herpes virus family. Herpes is usually treated by acyclovir or other related anti-viral drugs, while CMV is usually treated with ganciclovir.
Diarrheal illness is common in AIDS. While
patients with HIV may develop diarrhea from all the causes that afflict
persons without HIV, certain causes are particularly important in AIDS.
Cryptosporidiosis is a fairly common cause of diarrhea in persons without HIV, especially in children. It can be transmitted by contaminated drinking water or food. In
an infamous outbreak in 1993 the water supply for the city of Milwaukee
became contaminated with cryptosporidiosis, resulting in massive
outbreak that led to the deaths of dozens of AIDS patients. Cryptosporidiosis usually causes a mild diarrhea that lasts a few days to a week. In AIDS it causes a relentless diarrhea that can gradually kill a patient through dehydration and malnutrition. Over
90 medications have been tested for cryptosporidiosis; none seem
clearly effective though a few may have modest effects in slowing
disease. The key to treatment of cryptosporidiosis is
anti-HIV treatment that successfully raises the CD4+ T cell count above
100 cells/µl.
Isosporiasis is another parasitic infection that is related to cryptosporidiosis and causes a similar diarrhea picture in AIDS. Unlike cryptosporidiosis, it is more readily treatable. TMP-SMX is the drug of choice, and is often effective in eliminating isospora.
CMV in the intestines can cause diarrhea. Diagnosis relies on a biopsy of affected areas of the intestines using endoscopy. CMV in the intestines can be treated with ganciclovir. Other less common causes of diarrhea in AIDS include microsporidiosis and Kaposi’s sarcoma.
3.5. Other opportunistic infections
Mycobacterium avium complex (MAC) is common infection in AIDS. Mycobacterium
refers to a special family of slow growing bacteria, of which
tuberculosis is the most famous cause of human disease. Many mycobacteria are harmless to humans and commonly present in our environment. MAC is harmless to healthy persons, but can cause substantial problems in AIDS patients. It
typically spreads through the blood stream and causes a variety of
problems that can vary depending on which organs are affected. Most
characteristic is a picture of intermittent fevers and night sweats in
which there is no clear source that can be identified and the patient
appears less sick than would be expected in an illness causing fever. The diagnosis is usually made through special blood cultures (acid fast bacterial cultures). First line treatment consists of either clarithromycin or azithromycin, combined with ethambutol. Rifampin is added as a third drug by many physicians. Because
of how common MAC infection is in advanced disease, prophylaxis to
prevent infection has been recommended for patients with CD4 counts
below 100 cells µl. The most effective approach to preventing MAC, when
this is possible, is to treat HIV infection and raise the CD4+ t cell
count.
Histoplasmosis is
a fungus that is common in the environment in the Midwestern US
(especially the Ohio river valley area), and in parts of Central
America. In AIDS, it can infect the lungs and spread throughout the body. This usually results in a severe illness with fever, fatigue, and weight loss. A cough may be present. The diagnosis can be made by detecting antigen (parts of the organism) in blood or urine. Treatment is usually started with intravenous amphotericin B and then changed to itraconazole, which can be given by mouth.
3.6. Skin conditions
Staph aureus skin infections are very common in people without HIV and are often not thought of as an HIV related infection. In persons with HIV, they occur much more commonly, and may not respond as easily to treatment. Especially
common is staph folliculitis, infection of the hair follicles, which
results in multiple 1-2 mm acne like spots on the chest, arms, and legs. Staph aureus infections are treated with same antibiotics used for this common cause of skin infections in persons without HIV. While
antibiotics in the penicillin family such as dicloxicillin were the
mainstay of treatment for these infections until recently, the frequency
of methicillin resistant staph aureus (MRSA) has forced a change in
this strategy in many settings. Methicillin is a
penicillin class drug that treats staph aureus; resistance to this drug
is used as a term to describe staph that is resistant to the whole class
of penicillin related drugs. The frequency of MRSA has
forced a switch to other drugs such as trimethoprim-sulfamethoxazole
(brand names Bactrim or Septra) in many cases in which the sensitivity
of the bacteria causing the infection is not known. Unfortunately, these alternative drugs are often not quite as effective.
Seborriac dermatitis is also common without HIV, and even more common and severe in HIV. It is characterized by flaking skin and redness in patches on the face and scalp. Treatment is the same as in persons without HIV: topical steroid creams.
4. Transmission and prevention
HIV is not an easily transmitted virus. The virus is reasonably fragile and skin is an effective barrier. To
cause infection HIV has to pass through a break in skin, or through
mucous membranes (the lining of internal organs such as the vaginal
wall). It is not transmitted through casual contact such as sharing eating utensils or touching someone with HIV. The most common ways that HIV is transmitted are through sexual contact and through sharing needles or other equipment used to inject drugs. It can also be transmitted from mothers to infants. This
can occur while the fetus is still in the uterus, but the greater risk
is during childbirth. Cesarean section reduces the risk of transmission
to an infant during birth. Giving HIV drugs to the mother
before and during childbirth can reduce the risk of transmission to an
infant from about 25% to less than 2%. HIV can also be transmitted through breast feeding. This risk can be reduced two ways. Bottle feeding eliminates this risk. In the developing world, this is often not practical, and can increase the risk of other infections. Recent
data suggest that the risk of HIV transmission through breast feeding
is greatest when infants are fed solid food or even water or animal milk
before age six months. An alternative to formula feeding
in settings in which formula feeding is difficult or impossible is to
exclusively breast feed infants to six months.
Use of condoms by men has been shown to reduce the risk that men will transmit HIV to male or female sexual partners. Condoms also reduce the risk for men of acquiring HIV infection if they have sex with an infected partner. The success of male condoms has led to efforts to provide female condoms that can be used in the vagina (or in the anus). Though these appear to work, they are much less widely used than male condoms.
For
drug users, a key effort has been to provide sterile needles for drug
injection by persons who are not ready to stop drug use. Although
these have been controversial because of concerns that they may
encourage drug use, there is now strong evidence that they reduce the
risk of HIV infection (and other infections) in drug users, and have
little if any effect on drug use. Needle exchange programs
may actually be effective in providing services that ultimately
encourage entry into drug treatment. More information on HIV
transmission can be found on the Centers for Disease Control and Prevention website
Efforts to prevent HIV
have focused on five areas: (1) behavioral interventions designed to
reduce risk behaviors for HIV transmission, (2) male circumcision,
because uncircumcised men tend to be at greater risk for infection (3)
treatment of other conditions that may increase risk of HIV transmission
such as sexually transmitted diseases, (4) microbicides that can be
placed in the vagina and protect women from becoming HIV infected
through sex, and (5) vaccines.
5. Epidemiology: The Pattern of Disease Spread
The United Nations program on HIV/AIDS (UNAIDS)
has estimated that in 2007 there were 33 million people living with HIV
worldwide, 15 million of whom were women, and 2.1 million of whom were
children. There were an estimated 2.5 million new infections in 2007, and 2.1 million deaths.
In the North America, the prevalence of HIV infection is estimated to be about 0.6% while in Western Europe it is 0.3%. Although
some HIV transmission in both regions is heterosexual, injection drug
users and men who have sex with men are the hardest hit populations.
6. Treatment
The key treatment for AIDS is antiretroviral therapy of HIV infection. There are currently five classes of drugs for HIV that target different stages of the HIV life cycle. Current
treatment recommendations in the US suggest starting treatment for most
patients when the CD4+ T cell count is less than 350, though in some
cases treatment may be suggested at lower or higher CD4+ T cell counts. Antiviral
therapy for HIV can now increase the CD4+ T cell count back to a normal
range in most patients, though this may take several years. In
some patients treatment is not fully effective due to drug resistance
or the challenge of taking medication every day, which not all patients
follow through with.
The use
of combination anti-retroviral treatment has dramatically changed the
course of HIV infection. A recent study found that the mortality rate of
persons with HIV in countries where HAART was available between 2004
and 2006 was only 6% as high as it was before 1996.
This type of data, combined with that of clinical trials of different
HIV treatments, has produced highly convincing evidence of the
effectiveness of current HIV treatment. The success of treatments that
are based on blocking HIV replication in preventing (and actually
reversing) AIDS has also provided powerful evidence supporting the role
of HIV in causing AIDS.
For years, treatment of HIV was available almost exclusively in the developed world. Starting
around 1991, Brazil began making HIV treatment broadly available, and
some middle income countries have followed this example. More recently there has been a concerted effort to disseminate HIV treatment to the developing world. This has led to broad availability of HIV treatment in many countries. In 2001 an estimated 240,000 persons in low and middle income countries were receiving HIV treatment according to UNAIDS. By 2006 this number had increased to about 2 million.
Resources
AIDS info: http://www.aidsinfo.nih.gov.
This is a website maintained by the US Department of Health and Human Services. This
is an excellent source for high quality, up to date information on a
variety of AIDS issues, in particular treatment guideline documents from
expert panels. It also provides information on clinical trials and both
patient and physician oriented information on HIV drugs.
HIV Insite: http://hivinsite.ucsf.edu/
This website provides information on HIV treatment, prevention and policy from the University of California, San Francisco. This is generally a source of high quality information on HIV. Much of the website is targeted toward health care professionals, but it has a specific patient/public section as well.
The Body: http://www.thebody.com/
This is a website with comprehensive information on HIV, oriented toward patients and the general public.
References
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3. O'Brien SJ, Goedert JJ. HIV causes AIDS: Koch's postulates fulfilled. Curr Opin Immunol 1996,8:613-618.
4. Watson J. Scientists, activists sue South Africa's AIDS 'denialists'. Nat Med 2006,12:6.
5. 1993
revised classification system for HIV infection and expanded
surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992,41:1-19.
6. Interim proposal for a WHO Staging System for HIV infection and Disease. Wkly Epidemiol Rec 1990,65:221-224.
7. Benson CA, Kaplan JE, Masur H, Pau A, Holmes KK. Treating
opportunistic infections among HIV-infected adults and adolescents:
recommendations from CDC, the National Institutes of Health, and the HIV
Medicine Association/Infectious Diseases Society of America. MMWR Recomm Rep 2004,53:1-112.