The Biology of AIDS
Click on one of the links below to learn more about…
Human Immunodeficiency Virus (HIV) is the virus that causes Acquired ImmunodeficiencySyndrome (AIDS).
(back to top)
AIDS is the final stage of HIV disease. So, a person can have HIV without having AIDS. AIDS is characterized by a weakened immune system and certain types of infections and cancers. These include:
- a skin tumor called Kaposi’s sarcoma,
- infections and tumors in the central nervous system (the brain and spinal cord),
- cancers of the immune system (lymphomas)
- infections in the lungs,
- dementia,
- severe malnutrition,
- chronic diarrhea, and
- predominantly in the developing world: tuberculosis, malaria, and protozoal diseases.
These conditions are called “AIDS defining illnesses” and are eventually fatal.
(back to top)
HIV disease is characterized by a gradual weakening of the body’s immune system, mostly because the virus disables and destroys immune cells called CD4+ T cells (or “helper” T cells). Healthy people usually have between 800 and 1,200 CD4+ T cells per cubic millimeter of blood. When a person becomes infected with HIV, this number begins to drop. When T cell levels reach about 200 cells/mm3, the individual’s immune system is no longer strong enough to fight off secondary infections and cancers. At this point, the person has AIDS. There is no cure for AIDS. However, there are ways to slow the progression from HIV to AIDS.
(back to top)
HIV belongs to a family of viruses called “retroviruses.” Retroviruses have genes made up of ribonucleic acid (RNA) instead of deoxyribonucleic acid (DNA), which is what human genes are made of. When a retrovirus infects a cell, an enzyme called reverse transcriptase makes DNA copies of the virus’s RNA genes. These DNA copies can then be incorporated into the host cell’s DNA. This means that the viral genes are expressed when the host cell genes are expressed—this is how the virus makes new copies of itself inside the body.
HIV also belongs to the “lentivirus,” or “slow virus,” family. For these viruses, there is a long time between infection and when the person starts to show serious symptoms. In the case of HIV/AIDS, the symptoms of AIDS usually appear 10 to 12 years after HIV infection.
(back to top)
There are several ways a person can become infected with HIV:
- Through unprotected sexual intercourse with an infected partner. HIV can enter the body through the mucus membranes of the penis, vagina, rectum, and sometimes mouth. This is the most common cause of infection in adults.
- Through sharing needles with an infected person.
- Through a blood transfusion from an infected person (though this is now very rare in the US and Western Europe, where all blood is screened for HIV).
- Babies with HIV-positive mothers may become infected before or during birth through blood, or after birth through breast milk. The risk of infection is much smaller if the mother is being treated for HIV and if the baby also takes HIV medication after birth.
(back to top)
There are seven basic stages in the life cycle of HIV:
- Virus docking/entry: The proteins on the outside of the virus bind to CD4 receptors on the outside of CD4+ T cells like a key in a lock. This process is called “docking.” The membranes of the virus and the host cell then fuse, and the virus releases its RNA into the cytoplasm of the host cell.
- Reverse transcription: The enzyme reverse transcriptase in the host cell makes DNA copies of the virus’s RNA genes.
- Integration: The new viral DNA travels to the nucleus where another enzyme called HIV integrase helps it incorporate itself into the host cell’s DNA.
- Viral transcription: Cellular machinery from the host cell makes a messenger RNA (mRNA) copy of the DNA. This process is called transcription, and is part of the normal expression of the host cell’s DNA, but now the DNA being copied also contains viral DNA.
- Viral translation: More of the host cell’s own machinery creates proteins from the instructions encoded in the mRNA. This process is called translation, and is also part of the normal expression of the host cell’s DNA, but now proteins are also being created from the viral DNA.
- Virus replication: New viruses are created. They are made of viral RNA and the proteins just produced through transcription and translation of viral DNA.
- Virus release: The new viruses “bud” off from the host cell membrane and are released into the rest of the body where they can infect more cells and keep replicating.
(back to top)
Not yet. But current treatments can slow the progression from HIV to AIDS. If treated properly, people with HIV can often live healthy lives for many years after infection.
(back to top)
Right now, the most effective treatment for HIV is highly active antiretroviral therapy (HAART). HAART uses a combination of three or more antiretroviral drugs to stop or at least slow HIV replication once the virus is in the body. Antiretroviral drugs can help stop virus replication by blocking the entry of viral RNA into the host cell (fusion inhibitors), interfering with reverse transcription of viral RNA to DNA (reverse transcriptase inhibitors), and
denying new viruses the machinery they need to infect more cells (protease inhibitors). Most treatment regimens include at least two nucleoside reverse transcriptase inhibitors and a protease inhibitor. HAART’s goal is to decrease the amount of virus in the blood—the “viral load”—so that it is no longer detectable. Studies show that people with a lower viral load are less likely to develop AIDS symptoms than people with a higher viral load.
Once HIV progresses to AIDS, treatment must also include medications to fight the secondary infections and cancers associated with AIDS.
(back to top)
HAART treatment regimen is rigorous, and requires a lot of time and effort on the part of the patient. Antiretroviral drugs often have many unpleasant side effects, as do the drugs used to treat infections and cancers associated with AIDS. Antiretroviral drugs are not always effective in stopping or even slowing virus replication. This is because HIV can mutate very quickly and very often so that drugs that used to help lose their potency.
(back to top)
The mutable nature of HIV makes the virus difficult to target. Also, HIV can survive in resting T cells in a form that can replicate even when the virus cannot be detected in the blood. This makes it very hard to destroy the virus completely, even with intense antiretroviral treatment. So, efforts to find a cure demand a great deal of attention and funding.
(back to top)
In 1984, US Health and Human Services Secretary Margaret Heckler announced that an AIDS vaccine would be available within two years. Twenty-two years later, the world is still waiting. Although progress towards a vaccine lagged in the first two decades following AIDS’ discovery, recent progress has been promising. Currently, scientists in 19 countries on six continents are running human clinical trials on more than 30 candidate AIDS vaccines. Pharmaceutical companies, academic centers, and agencies from developing countries have all joined in the quest for an AIDS vaccine. A recent grant from the Bill and Melinda Gates foundation for $287 million has raised hope for future developments.
However, many challenges to vaccine development persist:
- No natural mechanism of recovery from AIDS exists for scientists to imitate
- There are many multiple subtypes of HIV, each quite distinct
- The nature of HIV infection (the virus destroys immune cells that are supposed to fight against it) makes vaccination challenging
- There is a lack of global consensus regarding how to best assess which vaccine candidates are deserving of large-scale trials
- Global spending on an AIDS vaccine remains low- less than 1% of global spending on all health product research and development
- Poor nations often lack the trained specialists and infrastructure necessary for vaccine trials
(back to top)
Download a pdf of this page to distribute as an informational handout!
