Steven Merrill
January 31, 2011
WCH

Acquired Immune Deficiency Syndrome

Causative Agent

Acquired immune deficiency syndrome (AIDS) is a condition which causes the slowly advancing failure of a patient’s immune system.  While there are other forms of immune deficiencies both congenital and acquired, AIDS is the most common acquired form and the nearly inevitable result of infection with the human immunodeficiency virus (HIV).  HIV uses reverse transcriptase (def) and integrase (def) enzymes to convert viral RNA into DNA and insert it into the genome of the host cell.  Because this process is the reverse of normal cellular transcription –where DNA is converted to RNA –HIV is known as a retrovirus.  HIV is a member of the family Retroviridae and the genus Lentivirus.  The virus is relatively average in size, approximately 120 nanometers (def) in diameter, and roughly circular.  The outermost layer is a viral envelope comprising a phospholipid bilayer (def) taken from the host cell membrane as freshly made virus particles bud off.  Integrated into the viral envelope are host cell membrane proteins and important HIV virulence factors (def) gp120 and gp41.  Beneath this, a spherical protein matrix (def) of the viral protein p17 gives the HIV particles structure.  Inside the matrix (def) there is a final layer known as the capsid (def) which contains enzymes and two copies of the single-stranded RNA genome.

Epidemiology
              

The CDC estimates 56,000 people a year became infected with HIV in the United States alone.  Almost all of them will eventually develop AIDS.  In 2007, over 14,000 Americans died from the disease.  Worldwide roughly 2.7 million people contract HIV each year.  As determined by the World Health Organization, HIV infection and AIDS is now a pandemic.  In 2008, there were 33.4 million people living with HIV and 2 million people died from AIDS.  Since its discovery in 1981 some 29 million people have been killed by the disease.  It is truly a global illness with new epidemics in Eastern Europe and South-East Asia.  However, Sub-Saharan Africa is by far the hardest hit with some 5% of the population infected with HIV.  In some regions the prevalence is as high as %25 or more.
              

HIV in the U.S. was originally identified in homosexual males and intravenous drug users and it continues to infect these groups in disproportionately large numbers.  However, the virus itself has no preference and infection is by no means limited to these groups.  In Sub-Saharan Africa for example, heterosexual women account for 60% of HIV infections.  Young women and girls are especially vulnerable and are approximately 3 times more likely to be infected than males their age.  In the U.S., poor inner-city communities are a new area for concern.  A lack of good healthcare, persistent rumors and misinformation about the risks of unprotected sex are contributing factors.

Transmission

HIV is a relatively fragile virus and must be passed directly from host to host through exposure to infected bodily fluids containing the virus.  The virus only infects humans.  Transmission is increased when virus particles come in contact with torn, broken and inflamed mucous membranes (def).  The most common modes of transmission are through sexual intercourse, sharing of intravenous drug paraphernalia or mother to child transmission, which are all due to exposure either to infected semen, blood, vaginal secretions or breast milk.  Other bodily fluids like saliva, sweat and tears do contain low levels of viral particles, but infection through these routes is extremely difficult, if at all possible.  The most common strain is HIV-1, a highly infectious and rapidly replicating variant that is primarily responsible for the global pandemic.  HIV-2, the other recognized strain, is a much less virulent species of HIV and largely limited to Western Africa.  While these are the only major forms of HIV, the virus mutates extremely rapidly making it difficult for drugs or adaptive immunity to fully control infections.

Signs and Symptoms

Again while it appears throughout the body, the virus infects primarily the blood and lymphatic systems (def), specifically targeting CD4+ T-cells (def), dendritic cells (def), monocytes (def) and macrophages (def).  During the initial infection the virus spreads rapidly through the immune system and produces symptoms such as fatigue, rashes, fever and lymphadenopathy (def).  After several days or weeks, the body is typically able to fight the infection with CD8+ T-cells (def) and antibodies.  Viral load (def) drops and HIV is confined to the lymphatic system (def).  This latent period (def) may last anywhere from 2-20 years with an average of 10 years without any major signs or symptoms.  Over this period the virus spreads very slowly and CD4+ T-cell (def) counts drop steadily.

When CD4+ T-cell count drops below approximately 200/microliter (def) of blood, this typically signals progression of HIV infection to AIDS and the body becomes susceptible to a wide range of normally harmless opportunistic infections.  Initial symptoms include anemia, fatigue, wasting (def) and persistent or recurring candidiasis (def) of the throat, nails and genitals.  As the disease progresses more serious complications develop including most commonly pneumocystis pneumonia (PCP) (def) caused by the pathogenic yeast Pneumocystis jirovecii.  Other common opportunistic fungal pathogens include Cryptococcus neoformans and Histoplasma capsulatum.   Frequent bacterial infections include tuberculosis (def) and gastroenteritis (def) caused by Salmonella, Shigella or Listeria.  The protozoa, Toxoplasma gondii, may cause encephalitis (def) with symptoms of headache, confusion, fatigue and occasionally seizures.  Lastly, several secondary viral infections may also complicate AIDS and cause frequent fevers, malaise (def) and myalgia (def).  Several oncogenic (def) viruses including Human Papillomavirus (HPV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), and Kaposi's sarcoma-associated herpesvirus (KSHV) and are commonly found in AIDS patients and associated with increased risk of cancer and tumor development.  Kaposi’s sarcoma (def) caused by KSHV is a classic signs of AIDS.

Prevention and Treatment

In nearly every case, infection with HIV leads to AIDS followed by multiple opportunistic infections and death.  Current therapies can only attempt to slow the progression of the disease giving patients precious months or years, but are unable to completely clear the infection.  Highly Active AntiRetroviral Therapy (HAART) is currently the preferred treatment for AIDS.  Most patients take a cocktail of different classes of anti-retroviral drugs to help contain the rapidly mutating virus.  Treatment also commonly includes prophylaxis (def) against several common opportunistic pathogens.  Because AIDS destroys the body’s natural defenses, treatment is often as concerned with controlling and preventing secondary infections as it is with HIV itself.  In the end it is these secondary infections that become fatal.

Because of the difficulty in controlling HIV after infection, it is critical that prevention play an important role in efforts to stop the pandemic.  Especially in poorer nations where patients can’t afford antiretroviral drugs, it is important to focus efforts on prevention.  Educating the public, providing cheap HIV tests, clean needles and promoting condom use have all been important in slowing the spread of the virus.  A lot of effort has been expended over the last 30 years in developing a vaccine against HIV.  The highly variable nature of the virus and its ability to mutate rapidly has made HIV a particularly difficult antibody target.  Most vaccine trials have been unsuccessful at reducing infection rates and in one case vaccination actually seemed to increase the rate of infection.  However, recent vaccine trials in Thailand have finally brought some good news.  A combination of two unsuccessful vaccines was able to reduce the chance of catching HIV by 30%.  The results are still preliminary, but they are encouraging nonetheless.

Bibliography

"AIDS." Wikipedia. Wikimedia Foundation, Inc., 21 Apr 2010. Web. 21 Apr 2010.
"HIV." Wikipedia. Wikimedia Foundation, Inc., 21 Apr 2010. Web. 21 Apr 2010.
UNAIDS. AIDS Epidemic Update. Geneva: UNAIDS, 2009. Print.

McCutchan, Allen J. "Human Immunodeficiency Virus Infection." The Merck Manuals. Merck & Co., Oct 2008. Web. 21 Apr 2010. <http://www.merck.com/mmhe/sec17/ch199/ch199a.html?qt=HIV&alt=sh>.

"HIV/AIDS." CDC. Centers for Disease Control and Prevention, 15 Apr 2010. Web. 21 Apr 2010.

Bennett, Nicholas John, and Frederick Burton Rose. "HIV Disease." eMedicine. 20 Apr 2010. Web. 21 Apr 2010. <http://emedicine.medscape.com/article/211316-overview>.