From Exposure to Infection: The Biology of HIV Transmission

One way HIV is transmitted is through sex -- but how does the virus infect someone after they have been exposed to HIV during sex?

In this article, we will follow the journey that HIV takes from the time someone is first exposed to the virus through to infection. Along the way, we will identify various factors that increase or decrease the chances that the virus will cause an infection.

It Begins With an Exposure ...

The journey begins with an exposure. For an HIV exposure to pose a risk of infection, specific bodily fluids from an HIV-positive person need to come into contact with specific body parts of an HIV-negative person. This can happen during anal, vaginal or oral sex.

We know that if a person is HIV-positive, only some of their bodily fluids contain enough virus to transmit HIV sexually -- these include semen, pre-cum, vaginal fluid and rectal fluid.¹ Blood also contains enough virus to transmit HIV, but it is not commonly involved in the sexual transmission of HIV.

The HIV in these fluids may cause infection if it enters the body of a sex partner. Most of the body's surfaces are "dry" skin (for example, on the arms and legs) -- these surfaces don't allow HIV to enter the body unless a cut or sore is present. However, other parts of the body are covered by "wet" skin, also known as mucous membranes, which are more vulnerable to HIV. The mucous membranes involved in the sexual transmission of HIV include the:

• foreskin and urethra on the penis
• cervix and vagina
• anus and rectum
• mouth and throat

A Closer Look at the Mucous Membranes

Let's take a closer look at the mucous membranes and find out why they are so vulnerable to HIV infection.

Whereas most of the skin on the body is covered with a protective layer of fibers that makes the skin "dry" and that HIV cannot cross unless there is a cut or sore, the mucous membranes are not covered with this protective layer of fibers because it would hinder their function. Without this protective layer, mucous membranes are more vulnerable and often the main "routes" that germs use to enter the body.

Vulnerable but Not Defenseless!

Infection isn't automatic if an exposure to HIV occurs. After a fluid containing HIV comes into contact with a mucous membrane, HIV still needs to complete a difficult journey before it can cause an infection. In some cases, HIV is not able to complete this journey and infection does not occur.

The mucous membranes are vulnerable but not defenseless. These membranes are covered with a layer of cells (called epithelial cells) that are tightly joined together. This helps to prevent germs from entering the body and causing an infection. Some mucous membranes (such as the rectum) have a single layer of cells while others (such as the foreskin, urethra, mouth and vagina) have multiple layers. The more layers, the more protection there is. The mucous itself also contains chemicals and antibodies that can kill germs.

Even if HIV manages to pass through the mucous and the layer of cells, there are still ways the body can prevent an HIV infection. Under the cell layer, a large concentration of immune cells is responsible for attacking and killing germs that manage to find their way past the cell layer.

To cause an infection after an exposure, HIV first needs to cross the cell layer and then avoid being destroyed by the immune cells below. If the virus overcomes these defenses, it can enter the body and then spread past the site of infection to other parts of the body, by entering the blood and lymphatic vessels in the mucous membrane tissue. Once HIV has spread throughout the body, the infection becomes permanent see Figure).^2-4 In some cases, HIV may not be able to either cross the cell layer or win its battle against the immune cells in the tissue below. This explains why some exposures to HIV do not lead to infection.

Crossing the Cell Layer

HIV can travel across the cell layer and enter the body on its own, but damage to the cell layer can make it easier for HIV to get across. Things that damage an intact cell layer and have the potential to increase the risk of infection include:

• Some sexually transmitted infections (STIs), such as herpes and syphilis, which can cause sores or ulcers ("holes") on the mucous membranes.⁵
• Tiny tears that can occur during sex due to friction. These "microtears" in the epithelial layer, which commonly occur during sex, can increase the risk of HIV infection. Some mucous membranes are more vulnerable to tearing, either because they are covered by a thinner cell layer or because they do not produce lubrication to reduce friction during sex. This partly explains why receptive anal sex (receiving the penis into the anus, also known as "bottoming" among gay men) with someone who is HIV-positive is generally the riskiest type of sex.⁶ The rectum's cell layer is thin and does not produce extra lubrication during sex.
• The mucous membranes can also be damaged in other ways, such as enemas, dental work, surgery, douching, brushing teeth and flossing.
• Although lubricants are often promoted to reduce the risk of tearing during sex, preliminary research suggests that some types of sexual lubricants may cause damage to the epithelial cell layer.⁷ More research is needed before we can change our recommendations regarding the use of lubricants.