How AIDS Works


Introduction to How AIDS Works
According to the World Health Organization, approximately 36.7 million people were living with HIV at the end of 2016. BigFive Images/Getty Images

More than a century ago in Cameroon, around 1908 to be a bit more precise, a hunter brought down a chimpanzee with a well-aimed arrow. While gutting his kill, the hunter accidentally cut himself, bringing the chimp's blood directly into contact with his own. And in that moment, an unknown virus "spilled over." In other words, it jumped from one species to another. So begins the story of AIDS — perhaps.

The tale of the "cut hunter" is just a theory, but it's considered one of the most plausible scenarios for how a simian immunodeficiency virus jumped from chimps to humans and became HIV.

Remarkably, we do know for certain where the crossover happened because scientists can track it. Like all viruses, HIV mutates, and it does so at a constant rate. Scientists can use this rate of mutation to track the history and progress of the virus. Because of HIV's close resemblance to a simian immunodeficiency virus, researchers knew it must have originated as a virus carried by chimps. Through an exhaustive process of taking chimp stool samples all over Africa and measuring the rate of mutation in the viruses they found, scientists narrowed down the location of "spillover" to a remote corner of present-day Cameroon in the early 20th century.

What likely happened next is that the injured hunter traveled downriver to a nearby town where he unwittingly infected somebody else through sexual contact. The virus would then have worked its way from town to town until it reached Leopoldville, now Kinshasa, capital of the Democratic Republic of Congo. As Kinshasa's population exploded between the 1920s and the 1950s, Belgian colonial officials were conducting medical treatment campaigns that involved multiple injections with reusable syringes. This would have spread the virus more rapidly.

In 1960, the Belgians abandoned the Congo, and the Haitians who made up the bulk of Kinshasa's medical community returned to Haiti. At least one of them took HIV back with them. There, an American-run clinic was paying for blood plasma donations. The clinic's reusable needles helped spread the disease through Port-au-Prince, and, around 1969, some of that infected blood plasma made its way to the U.S. for use in hospitals or clinics. Once there, it spread among drug users via shared needles and among gay men via sexual contact [source: Lynch].

The virus, later named human immunodeficiency virus (HIV), causes the virulent condition known as auto-immune deficiency syndrome (AIDS). As of 2017, an estimated 35 million people have died of AIDS worldwide [source: WHO]. However, thanks to improved therapies and preventive measures, the number of deaths and new infections has declined steeply since peaking in 2005.

The Unusual Virus

The Unusual Virus
HIV can be transmitted through a variety of body fluids from infected individuals. Ian Cuming/Getty Images

AIDS has infected and killed so many people because of the way it works. Let's look at some of the features that make this disease so unusual.

HIV can be transmitted through a variety of body fluids from infected individuals, such as blood, breast milk, semen and vaginal secretions. But individuals cannot become infected through ordinary contact such as kissing, hugging, shaking hands, or sharing food or water. When compared with the many viruses that spread through the air, it would seem that the intimacy involved in the transmission of AIDS would be a limiting factor.

However, a person can be contagious for a decade or more before any visible signs of disease become apparent. And in that decade, an HIV carrier can potentially infect dozens of people, each of whom can infect dozens more, and so on.

HIV invades the cells of our immune system and reprograms them to become HIV-producing factories. Without treatment, the number of immune cells in the body dwindles and AIDS can develop. Once AIDS manifests, a person is susceptible to many different infections because HIV has weakened the immune system to the point where it can no longer fight back effectively.

In fact, HIV not only invades and weakens the immune system — the very system that would normally protect the body from a virus — it also destroys it. HIV has also shown the ability to mutate, which makes treating the virus very difficult. As the virus destroys and impairs the function of immune cells, infected individuals gradually become immunodeficient.

How HIV Is Transmitted

How HIV Is Transmitted
A newborn in South Africa receives a dose of antiretroviral drug, nevirapine, shortly after birth. Her mother is HIV positive and has been enrolled in program that will increase the baby's chances of not getting the virus from her. Gideon Mendel/Corbis for UNICEF/Corbis via Getty Images)

When AIDS first came to public attention in the 1980s there were many misconceptions about how it spread. Thanks to ongoing awareness campaigns, these misconceptions have been dispelled.

People transmit HIV through a very specific list of bodily fluids: blood, semen, pre-seminal fluid, rectal fluids, vaginal fluids and breast milk. For the virus to transmit, these fluids must come in contact with damaged tissue or mucus membranes of another person, or be directly injected with a needle. There are mucus membranes in the mouth, anus, rectum, cervix, vagina, and the foreskin and urethra of the penis.

Here is a list of ways in which HIV can be transmitted:

  • Through sexual contact
  • Through sharing contaminated intravenous needles
  • From an infected mother to her child during pregnancy or birth
  • Through blood transfusions (this is rare in countries where blood is screened for HIV antibodies)

HIV also can be transmitted from mother to baby during breastfeeding. The risk of this form of transmission is so small that the World Health Organization now recommends that HIV-positive mothers continue to breastfeed their babies because of breast milk's overwhelming health benefits. WHO does recommend, however, that both the mother and the baby take antiretroviral therapy to help reduce the risk of transmission [source: WHO].

A fragile virus that can't survive outside the human body, HIV does not transmit through the air. It also can't be contracted like a cold or the flu from surface contact with, for instance, doorknobs or countertops. Its fragility makes the possibility of environmental transmission so remote that there are no recorded instances of it happening [source: Aidsmap].

Because of existing misinformation about how HIV can be transmitted, it's important to emphasize the ways in which it's not:

  • Saliva, tears and sweat: Saliva and tears contain only small amounts of the virus, and scientists haven't detected any HIV in the sweat of an infected person.
  • Insects: Studies show no evidence of HIV transmission through bloodsucking insects. This is true even in areas where there are many cases of AIDS and large populations of mosquitoes.
  • Using the same toilet seat
  • Swimming in the same pool
  • Touching, hugging or shaking hands
  • Eating in the same restaurant
  • Sitting next to someone

The HIV Life Cycle

The HIV Life Cycle
A man with AIDS is comforted by his wife as he lies in his bed at Zimbabwe's Matibi Mission Hospital, where at the time of the photo nearly 60 percent of the hospital's cases were AIDS related. Gideon Mendel/Getty Images

Like all viruses, HIV treads the fine line that separates living things from nonliving things. Viruses lack the chemical machinery that human cells use to support life. So, HIV requires a host cell to stay alive and replicate. To reproduce, the virus creates new virus particles inside a host cell, and those particles carry the virus to new cells. Fortunately the virus particles are fragile.

Viruses, including HIV, don't have cell walls or a nucleus. Basically, viruses are made up of genetic instructions wrapped inside a protective shell. An HIV particle, called a virion, is spherical and has a diameter of about one 10,000th of a millimeter.

HIV infects one particular type of immune system cell. This cell is called the CD4+T cell, a type of white blood cell also known as a T-helper cell. In fact, the virus only targets a subset of the T-helper cells: those that have already been exposed to infection. This is because, unlike "naive" cells, the experienced "memory" cells are in constant motion, and HIV uses that motion in a complex way to get inside them. Once infected, the T-helper cell turns into an HIV-replicating cell. T-helper cells play a vital role in the body's immune response. There are typically 1 million T-cells per 1 milliliter of blood. HIV will slowly reduce the number of T-cells until the person develops AIDS.

HIV is a retrovirus, which means it has genes composed of ribonucleic acid (RNA) molecules. Like all viruses, HIV replicates inside host cells. It's considered a retrovirus because it uses an enzyme, reverse transcriptase, to convert RNA into DNA [source: Lu et al.].

To understand how HIV infects the body, let's look at the virus's basic structure:

  • Viral envelope: This is the outer coat of the virus. It's composed of two layers of fatty molecules, called lipids. Embedded in the viral envelope are proteins from the host cell. There are also about 72 copies of so-called Env protein, which protrudes from the envelope surface. Env consists of a cap made of three or four molecules called glycoprotein (gp) 120 and a stem consisting of three to four gp41 molecules.
  • p17 protein: The HIV matrix protein lies between the envelope and core. It's a structural protein that plays multiple roles in the life cycle of the HIV virus, including viral replication and particle assembly. P17 also acts as a viral cytokine, a substance that helps cells communicate and move in a particular direction [source: Fiorentini et al.].
  • Viral core: Inside the envelope is the core, which contains 2,000 copies of the viral protein p24. These proteins surround two single strands of HIV RNA, each containing a copy of the virus's nine genes. Three of these genes — gag, pol and env — contain information needed to make structural proteins for new virions.

What HIV Does

What HIV Does
HIV infects one particular type of immune system cell, the CD4+T cell, a type of white blood cell also known as a T-helper cell. Wikimedia Commons

Once HIV enters the body, it heads for the lymphoid tissues, where it finds T-helper cells [source: The Body]. Let's look at how the HIV virus infects immune system cells and replicates.

Binding: First, HIV attaches to the immune cell when the virus's gp120 protein binds with the CD4 protein of the T-helper cell. The viral core enters the T-helper cell, and the virion's protein membrane fuses with the cell membrane.

Reverse transcription: The viral enzyme, reverse transcriptase, copies the virus's RNA into DNA.

Integration: The newly created DNA is carried into the cell's nucleus by the enzyme, viral integrase, and it binds with cell's DNA. HIV DNA is called a provirus.

Transcription: The viral DNA in the nucleus separates and creates messenger RNA (mRNA), using the cell's own enzymes. The mRNA contains the instructions for making new viral proteins.

Translation: The mRNA is carried back out of the nucleus by the cell's enzymes. The virus then uses the cell's natural protein-making mechanisms to make long chains of viral proteins and enzymes.

Assembly: RNA and viral enzymes gather at the edge of the cell. An enzyme called protease cuts the polypeptides into viral proteins.

Budding: New HIV particles pinch out from the cell membrane and break away with a piece of the cell membrane surrounding them. This is how enveloped viruses leave the cell. In this way, the host cell is not destroyed.

The newly replicated virions will infect other T-helper cells and, left untreated, cause the person's T-helper cell count to slowly dwindle. The lack of T-helper cells compromises the immune system. If a person's T-helper cell count drops below 200 cells per cubic millimeter of blood, he or she is considered to have AIDS. Untreated, a person with AIDS has a life expectancy of three years [source: CDC].

HIV infection follows three basic stages. Usually developing within two to four weeks, the first stage is known as acute HIV infection. The infected person can experience symptoms similar to the flu, including rashes, fevers and headaches. At this point, the virus is multiplying quickly throughout the body. It's during this stage that the infected person is the most contagious.

The second stage is called chronic HIV infection or asymptomatic HIV infection or clinical latency. The virus's rate of multiplying reduces to a low level, and symptoms often disappear. Untreated chronic HIV infection usually develops into AIDS within 10 to 12 years.

The third and final stage of HIV infection is AIDS itself, but no one dies from AIDS specifically. Instead, an AIDS-infected person dies from infections because the immune system has been dismantled. If left untreated, people with AIDS could die from the common cold as easily as from cancer.

World Impact of AIDS

World Impact of AIDS
The AIDS Memorial Quilt, seen here at the National Mall in Washington D.C., was first created to honor those who had died of AIDS. Chris Maddaloni/CQ Roll Call/Getty Images

In the years after the discovery and identification of HIV/AIDS, the syndrome was a terrible killer. Early treatments sometimes proved nearly as damaging as the disease itself. But starting in the mid-1990s, doctors began using a new treatment regimen that involved deploying an antiretroviral "cocktail" of several drugs simultaneously. The cocktail, called Antiretroviral Therapy, or ART, can't cure AIDS; rather, it controls viral replication, allowing the immune system to recover and strengthen. ART has turned out to be remarkably effective, transforming AIDS from a death sentence into a survivable and manageable disease. In fact, a person living with HIV who receives good treatment and lives a healthy lifestyle might live as long as a person without the virus [source: The Body].

Three million people were dying of AIDS every year in 2005, but 12 years later, that number had dropped to 1 million. As of 2017, the number of people living with HIV hovers just below 37 million, but the number of new infections has dropped from by 39 percent between 2000 and 2016. And HIV-related deaths fell by one third during that same period thanks in part to ART. Today 54 percent of adults and 43 percent of children living with HIV are currently receiving lifelong ART drugs [source: WHO].

However, current treatments are less than ideal. ART can have long-term side effects such as chronic inflammation leading to organ damage and premature aging [source: Groopman]. It's also expensive, making it difficult to extend treatment to low-income people in general or to people in countries with underdeveloped medical infrastructures. Because the majority of AIDS cases persist in some of the world's poorest countries, this is a serious problem.

According to WHO, of the more than 36 million people estimated to be living with HIV as of 2017, 25.6 million of those live in the African region, and the area also accounts for almost two thirds of the global total of new HIV infections. Another factor is that researchers estimate only 70 percent of people with HIV are actually aware of their status, which means testing needs to be easier and more accessible [source: WHO].

HIV is a latent virus, meaning that not only can it lie dormant for years before developing into full-blown AIDS, but it can also go into hiding when a patient is receiving treatment. This makes it incredibly difficult to eradicate. In fact, only one person in the world is known to have been fully cured of HIV. Scientists are studying his case to better understand how a cure might be effected.

The key, it seems, will be to develop a safe and affordable way of eradicating the viral reservoir that can lie dormant, unfazed by ART. Approaching the problem from multiple angles, some researchers are looking for ways to use the body's immune system to do the job; some are experimenting with genetically engineered stem cells; and others are developing "shock and kill" drug therapies. All are optimistic that AIDS can eventually be cured outright, with one researcher suggesting this could happen within 10 to 20 years [source: Groopman].

Prevention, as they say, is the best medicine. Those who are at a high risk of contracting HIV/AIDS can take a pill called pre-exposure prophylaxis, or PrEP, which combines two types of medications. When taken consistently every day, PrEP can reduce the risk of HIV infection by 92 percent [source: CDC]. Teaching and practicing safe sex is also key to preventing and spreading the HIV virus.

Meanwhile, the search for an AIDS vaccine is ongoing. In 2015, Michael Farzan, an infectious disease specialist at the Scripps Research Institute in Florida, announced a promising new possibility.

Structurally, HIV has spikes called glycoproteins, each equipped with two sites that attach to immune cells. Farzan described a compound that prompts muscles to produce a special protein that, unlike most antibodies, has both a head and a tail. The head of the protein blocks one site on an HIV spike, and the tail blocks the other, making it impossible for the virus to attach to an immune cell. Deprived of a home, the virus wanders off and is eventually destroyed by the immune system. So far, four monkeys have been completely protected against repeated exposure to HIV for a year [source: McNeil].

In September 2015, the Scripps Research Institute announced that the Bill & Melinda Gates Foundation had given Farzan $6 million to develop his compound into an HIV vaccine for humans [source: Scripps].

Author's Note: How AIDS Works

When I was in high school in the 1980s, AIDS was the boogeyman. As a shared national anxiety, it loomed as large as nuclear Armageddon. While in university in the early 1990s I befriended a returning student who'd lost all of his close friends and lovers to AIDS in the previous decade. But then things changed. While living in San Francisco in the mid-1990s I met a young man who was dying of AIDS. Emaciated and pale, he looked desperately ill. I thought I would probably never see him again. A few months later an energetic young person bounded up to me on the sidewalk and shook my hand, reminding me that we'd already met. It was the same person who'd been dying. His doctor had put him on the new antiretroviral therapy, and it had saved his life. – O.C.

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More Great Links

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