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HIV and the Female Genital Tract -- What Does It Mean for HIV Prevention?

Fall 2016

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Introduction

Although unprotected vaginal sex is a high risk activity for HIV transmission, the majority of exposures to HIV do not actually lead to infection. This is probably due to the innate protective defences of the female genital tract, which help to fight HIV infection. Still, the female genital tract is vulnerable to HIV, and research suggests that females are at higher risk for HIV transmission through penile-vaginal sex than males.

This article discusses the female genital tract's unique biological vulnerabilities to HIV and its protective defences against HIV. It also reviews HIV prevention approaches available to women and provides key messages for service providers who work with women at risk of HIV.

Note: This article discusses HIV transmission as it relates to the biology of the female genital tract, and this information may apply to both cisgender (non-trans) women and transmen.


The Female Genital Tract and the Sexual Transmission of HIV

Worldwide, the main way that females get infected with HIV is through sex with males. In Canada, 79% of new HIV infections among females were attributable to heterosexual sex in 2014.1 However, not all sexual exposures to HIV actually lead to infection.2 On average, there is about a 1 in 1,200 chance of females getting HIV when exposed to the virus through vaginal sex.3 The female genital tract has innate protective defences that can trap, inactivate or fight HIV before it causes infection, so that most exposures do not result in infection.

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For HIV to be transmitted sexually there needs to be an exposure to HIV that carries a risk of transmission. There are three necessary components for sexual transmission of HIV to occur: fluid, route and activity. First, there needs to be a bodily fluid from a person living with HIV that contains enough HIV to cause infection. Next, this fluid needs a route of entry into the body of an HIV-negative person. Finally, there needs to be an activity that brings the fluid and the route together. For example, vaginal sex is an activity that can bring a fluid -- such as semen or pre-ejaculate (pre-cum) -- from an HIV-positive person into contact with the lining of the female genital tract, which HIV uses as a route for infection.

The female genital tract includes the vulva, vagina, cervix, uterus, fallopian tubes and ovaries. In this article, use of the term "female genital tract" will refer to the vagina and cervix (including the ectocervix, which is the part of the cervix that is touchable and visible through the vagina, and the endocervix, which is the internal, canal-like part of the cervix that opens into the uterus). Research tells us that these are the main parts of the female genital tract that HIV uses to enter the body and cause infection. The female genital tract is lined with moist mucous membranes made up of epithelial cells that are tightly joined together to provide a partially protective barrier against HIV. This is known as the epithelial cell layer.

After the vagina and cervix of an HIV-negative person has been exposed to a fluid containing HIV, there are two important steps that HIV needs to take to cause an infection:

  1. HIV needs to cross the epithelial cell layer and enter the underlying tissue. HIV can pass through the epithelial cell layer on its own, but damage to the mucous membrane can further enhance HIV's ability to enter the body.
  2. After crossing the epithelial cell layer, HIV needs to replicate within the mucous membrane tissue for one to three days before it can spread throughout the body. It does this by infecting certain immune cells (known as target cells) in the tissue and replicating to produce more virus. This can lead to a permanent infection with HIV if the body's protective defences do not destroy the virus in time.


How Does the Female Genital Tract Defend Itself From HIV?

The female genital tract has several biological defences that naturally help to protect against HIV infection: mucous membranes, layers of epithelial cells, immune cells, and bacteria. While all of these biological defences can help protect the body against a permanent HIV infection, they are not always successful.

The mucous membranes that line the female genital tract act as an important line of natural defence against HIV and other germs.2,4 The layer of mucous produced by the vagina and cervix provides a natural physical barrier that can trap HIV and prevent it from crossing the epithelial cell layer and reaching the cells underneath.4,5 This mucous also lubricates the cell lining to protect against damage to the epithelial cell layer that can be caused by friction during sex. This is important because small tears or other damage can be used by HIV to cross the cell layer more easily.6

Underneath the mucous, the epithelial cells of the vagina and ectocervix, which make up most of the surface area of the female genital tract, are many layers thick. This provides a thicker barrier that offers greater protection against HIV, compared to the lining of the rectum, for example, which is only lined by a single layer of cells.

The female genital tract has a complex local immune system that can help fight and clear HIV from the body. This includes both antibodies and immune cells in the vaginal mucous and epithelial lining that can help to attack and inactivate HIV.

Lastly, the vagina is colonized by bacteria that help play a role in protecting against HIV infection. These "friendly" bacteria in the vagina produce lactic acid that helps to maintain a low pH (an acidic environment) in the vaginal lining, which research has found can trap and inactivate HIV.7


Inherent Vulnerabilities Also Exist

Unfortunately, we know that HIV can sometimes overcome the protective defences of the female genital tract. On average, the risk of HIV transmission through vaginal sex may be about two times higher for females than for males.3 There are several inherent biological factors that may explain an increased vulnerability to HIV infection in the female genital tract, including physical characteristics and the immune system.

First, the vagina and ectocervix have a much larger surface area than the foreskin and urethra, where HIV transmission can occur in the male genital tract. With a larger surface area there is a higher likelihood that HIV can find a way to cross the epithelial cell layer and cause infection.6,8

In addition, the female genital tract may be exposed to a greater volume of HIV-infected fluid compared to the penis. This fluid (semen) can remain in prolonged contact with the female genital tract after ejaculation. Prolonged contact with this greater volume of HIV-infected fluid can increase the chances of HIV finding a way across the vaginal or cervical epithelial lining and causing infection.

Finally, although the immune system is meant to protect the body from infection, the immune cells located in the female genital tract may also play a role in increasing vulnerability to HIV infection, because HIV can attack immune cells in the vaginal mucous and epithelial lining.8,9


Factors That Can Alter Susceptibility to HIV Infection in the Female Genital Tract

The female genital tract is a dynamic environment that can be altered by internal and external factors, creating biological changes that may increase or decrease vulnerability to HIV infection among females.


Inflammation

Inflammation in the mucous membranes of the female genital tract can increase HIV risk.10 Inflammation is the body's natural immune system response to something harmful, such as tissue damage or "unfriendly" bacteria. The inflammatory response brings immune cells to the affected area and activates these immune cells to help repair tissue damage or fight harmful organisms.2 HIV prefers to target these activated immune cells, so inflammation supplies a high volume of vulnerable cells for HIV to infect and replicate within.

Conditions that may cause inflammation in the female genital tract include sexually transmitted infections (STIs, such as herpes or syphilis) and certain vaginal conditions (such as bacterial vaginosis or yeast infections). Additionally, friction caused during sex, vaginal cleansing practices such as douching, and some lubricants can cause tissue damage leading to inflammation.


Sexually Transmitted Infections

Inflammation is not the only reason why having an STI can increase the risk of getting HIV. In addition, some STIs, such as genital herpes or syphilis, cause sores which can damage the epithelial layer of the vagina or cervix, increasing the ability of HIV to pass through the cell lining.4,5 Having genital herpes in particular has been associated with a very high risk of getting HIV11,12 even when there are no sores present.13


Bacterial Vaginosis

Bacterial vaginosis is an infection that occurs when the balance of "friendly" bacteria in the vagina is upset by an overgrowth of "harmful" bacteria. Research suggests that bacterial vaginosis may increase HIV risk by up to two to three times because it can cause inflammation, disturb the protective low pH of normal "friendly" bacteria, and damage the vaginal lining.14,15


Hormonal Changes

Hormonal fluctuations happen naturally throughout the menstrual cycle, so it is possible that the risk of HIV infection may change over the course of a female's menstrual cycle. Hormone levels also change during menopause and pregnancy, and with the use of hormonal contraceptives.

Higher levels of progesterone may cause physical changes that can increase vulnerability to HIV infection, while higher levels of estrogen may offer a protective effect. Some research suggests that higher levels of progesterone can thin the cervical and vaginal linings, reduce the amount of healthy bacteria, decrease the protective immune function of the female genital tract, and increase the number of HIV target cells in the area.4 As a result, the female genital tract may be more vulnerable to HIV infection when progesterone levels in the body are high. On the other hand, research suggests that higher levels of estrogen can increase the thickness of the vaginal lining, increase the levels of healthy bacteria, and increase the production of cervical mucous, all of which can help to protect against HIV.4

Some research has found that certain types of hormonal contraceptives may increase the risk of HIV infection in females who are taking them to prevent pregnancy. Several studies have found that Depo-Provera, an injectable contraceptive containing progesterone only, may increase the risk of HIV infection, however the evidence is not conclusive at this time.16,17

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