HIV and the female genital tract – what does it mean for HIV prevention?

Prevention in Focus PiF 2016 Fall

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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.

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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.

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

HIV prevention in the female genital tract

What strategies can women use to prevent HIV?

The HIV prevention toolbox continues to grow, offering multiple strategies to prevent the sexual transmission of HIV depending on a person’s needs and preferences. Many women are especially interested in the types of prevention methods which they can control for themselves. Recent biomedical advances have created new options for female-initiated HIV prevention; however, widespread access remains an issue, and more traditional or longstanding prevention strategies are still important to promote. The following prevention approaches are options that you should be prepared to discuss with clients:

Condoms

Internal (sometimes referred to as female) condoms and external (sometimes referred to as male) condoms are highly effective strategies for women to reduce their risk of sexual HIV transmission, when used consistently and correctly. For a long time, the internal condom was the only female-initiated HIV prevention option available to women. Unfortunately, uptake of internal condoms among women has been low due to lack of awareness about this method and how to use it, poor acceptability among some women, and the relatively high cost compared to external condoms .9,18 Furthermore, a woman’s ability to actually control this method is limited because it can’t be used covertly.

The use of internal and/or external condoms may be preferable to many women because they offer several advantages including effective pregnancy and STI prevention, and they do not involve side effects that may result from the use of antiretroviral drugs for prevention.9, 19

PrEP and PEP

Oral pre-exposure prophylaxis (PrEP) involves taking a pill containing antiretroviral drugs every day, starting before being exposed to HIV and continuing afterwards. Studies have shown that daily oral PrEP, when used consistently and correctly, is a highly effective strategy for reducing the risk of the sexual transmission of HIV in women.20,21 However, adherence to oral PrEP appears to be especially important for females having vaginal sex. There is some evidence showing that oral PrEP takes longer to reach maximum drug levels in vaginal tissues compared to rectal tissues and also that drug levels can decrease quickly in the vagina if PrEP is not taken every day.22,23,24

Post-exposure prophylaxis (PEP) involves the use of antiretroviral drugs after a single, unintended exposure to HIV. HIV-negative women can use PEP to reduce their risk of HIV transmission after a sexual encounter where there was a significant risk of HIV exposure. Some women may be offered PEP after a sexual assault.25 Guidelines recommend that PEP should be started as soon as possible after the exposure (within maximum 72 hours) and that pills must be taken every day for 28 days.26 PEP is more likely to work the earlier it is started and with greater adherence to the full course of pills.26

Both PrEP and PEP can be initiated by women and taken discreetly, if necessary. In some cases, it may be difficult to hide daily PrEP and/or PEP use from intimate partners, who may question its use. In addition, antiretroviral drugs may cause (usually temporary) side effects that can be difficult to tolerate or to hide from others. It is also important to note that PrEP and PEP do not offer any protection against STIs (such as herpes, chlamydia or gonorrhea) or pregnancy.  

Antiretroviral drugs are expensive and cost is a significant barrier to accessing PrEP and PEP because the drugs are not currently covered by all public and private health insurance plans in Canada.

Treatment to prevent HIV

The consistent and correct use of antiretroviral treatment (ART) by people living with HIV to achieve and maintain an undetectable viral load is a highly effective strategy to help prevent HIV transmission.19 In the case of sexual transmission, an HIV-positive partner will not pass HIV to their HIV-negative partner as long as the HIV-positive partner takes ART consistently and correctly and has a viral load that remains undetectable. A woman living with HIV could also use this approach to avoid passing HIV to her HIV-negative partner(s).

What about women who are trying to conceive?

An HIV-negative woman who wishes to conceive a child with an HIV-positive partner now has several options available to greatly reduce or eliminate the risk of getting HIV while trying to get pregnant. This may include treatment of their HIV-positive partner and timed natural intercourse, “sperm washing” with intrauterine insemination or in vitro fertilization, and PrEP. Serodiscordant couples who want to conceive a child should seek expert advice to tailor conception and HIV prevention approaches to their specific needs.27,28

Implications for HIV prevention in women

It is important for service providers who work with women to understand the biology of HIV transmission in females so that they can communicate this information to women while providing appropriate prevention counselling. 

There are several key messages that can be given to female clients about the risk of HIV transmission through vaginal sex:

  • A healthy female genital tract has protective defences that can fight HIV infection; however, it also has biological vulnerabilities that contribute to a greater risk of HIV infection compared to men.
  • Inflammation in the female genital tract is associated with an increased risk of HIV infection. Inflammation can be caused by STIs, vaginal conditions, friction during sex, and cleansing practices (such as douching), among other things.
  • STIs and other vaginal conditions (such as bacterial vaginosis) may increase risk, even if they are not symptomatic. Women should be tested for STIs regularly and treated if necessary.
  • Women with diverse needs and preferences have prevention options available to them for reducing their risk of getting HIV, including methods they can initiate themselves and those that require greater partner involvement.
  • Women in a serodiscordant relationship who want to conceive have several options for preventing HIV transmission within the relationship, and should seek expert medical advice to review these options.

When counselling women about their risk for HIV transmission through vaginal sex and their prevention options:

  • Provide women with information that helps them understand the biological factors that may increase their vulnerability to HIV in the female genital tract.
  • Counsel women about behaviours, practices and biological factors that may put them at increased risk of HIV, and encourage regular HIV and STI testing for women who are at high risk.
  • Inform women about the highly effective HIV prevention options that can help them to reduce their risk of HIV infection (condoms, PrEP and an undetectable viral load), and counsel them on the need for women to be highly adherent when taking daily oral PrEP.  
  • Discuss combination prevention options based on type and frequency of sex, personal preferences and desire to become pregnant (or not).
  • Discuss risk behaviours other than vaginal sex, recognizing that many women may also be at risk for HIV transmission through anal sex or other sexual practices, or through injection drug use.
  • Whenever possible, address other risk factors that may influence a woman’s risk of getting HIV and/or impact her ability to prevent HIV infection, such as food insecurity, housing instability or intimate partner violence. 
  • Be aware of other services and providers that female clients can be connected to as appropriate, to address other identified issues (for example, mental health and addiction services, housing assistance, etc.).

Resource list

Revised June 2018

 

References

  1. Public Health Agency of Canada. Summary: Estimates of HIV Prevalence and Incidence in Canada, 2014. Surveillance and Epidemiology Division, Professional Guidelines and Public Health Practice Division, Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, 2015. Available from: https://www.canada.ca/content/dam/canada/health-canada/migration/healthy-canadians/publications/diseases-conditions-maladies-affections/hiv-aids-estimates-2014-vih-sida-estimations/alt/hiv-aids-estimates-2014-vih-sida-estimations-eng.pdf
  2. a. b. c. Kaul R, Pettengell C, Sheth PM, et al. The genital tract immune milieu: an important determinant of HIV susceptibility and secondary transmission. Journal of Reproductive Immunology. 2008;77:32–40.
  3. a. b. Boily M-C, Baggaley RF, Wang L, et al. Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies. Lancet Infectious Diseases. 2009 Feb;9(2):118–29.
  4. a. b. c. d. e. Petrova MI, Van den Broek M, Balzarini J, et al. Vaginal microbiota and its role in HIV transmission and infection. FEMS Microbiology Reviews. 2013 Sept 1;37(5):762–92.
  5. a. b. Wira CR, Rodriguez-Garcia M, Patel MV. The role of sex hormones in immune protection of the female reproductive tract. Nature Reviews Immunology. 2015 Mar 6;15(4):217–30.
  6. a. b. Hladik F and McElrath MJ. Setting the stage: Host invasion by HIV. Nature Reviews Immunology. 2008 Jun 1;8(6):447-57.
  7. Lai SK, Hida K, Shukair S, et al. Human Immunodeficiency Virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus. Journal of Virology. 2009 Nov 1;83(21):11196–200.
  8. a. b. Griesbeck M and Altfeld M. “Sex Differences in the Manifestations of HIV-1 Infection.” In Sex and Gender Differences in Infection and Treatments for Infectious Diseases, 103–81. Springer, 2015. Available from: http://link.springer.com/chapter/10.1007/978-3-319-16438-0_5.
  9. a. b. c. Adimora AA, Ramirez C, Auerbach JD, et al. Preventing HIV infection in women. Journal of Acquired Immune Deficiency Syndromes. 2013 Jul 1;63 Suppl 2:S168-73.
  10. Masson L, Passmore JS, Liebenberg LJ, et al. Genital inflammation and the risk of HIV acquisition in women. Clinical Infectious Diseases. 2015 Jul 15;61(2):260–69.
  11. Brown JM, Wald A, Hubbard A, et al. Incident and prevalent herpes simplex virus type 2 infection increases risk of HIV acquisition among women in Uganda and Zimbabwe. AIDS. 2007;21:1515–23.
  12. Freeman EE, Weiss HA, Glynn JR, et al. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS. 2006;20:73–83.
  13. Shannon B, Yi TJ, Thomas-Pavanel J, et al. Impact of asymptomatic herpes simplex virus type 2 infection on mucosal homing and immune cell subsets in the blood and female genital tract. The Journal of Immunology. 2014 Jun 1;192(11):5074–82.
  14. Thurman AR, Doncel G. Innate immunity and inflammatory response to trichomonas vaginalis and bacterial vaginosis: Relationship to HIV acquisition. American Journal of Reproductive Immunology. 2011;65:89–98.
  15. Thurman AR, Kimble T, Herold B, et al. Bacterial vaginosis and subclinical markers of genital tract inflammation and mucosal immunity. AIDS Research and Human Retroviruses. 2015 July 23;31(11):1139–52.
  16. Morrison CS, Chen P, Kwok C, et al. Hormonal contraception and the risk of HIV acquisition: An individual participant data meta-analysis. PLoS Medicine. 2015 Jan;12(1):e1001778. Available from: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001778.
  17. Polis CB, Phillips SJ, Curtis KM, et al. Hormonal contraceptive methods and risk of HIV acquisition in women: A systematic review of epidemiological evidence. Contraception. 2014 Oct 1;90(4):360–90.
  18. Weeks M. Female condom use and adoption among men and women in a general low-income urban U.S. population. AIDS and Behavior. 2015 Sept 1;19(9):1642–54.
  19. a. b. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. New England Journal of Medicine. 2011 Aug 11;365(6):493–505.
  20. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. New England Journal of Medicine. 2012 Aug 2;367(5):399–410.
  21. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. New England Journal of Medicine. 2012 Aug 2;367(5):423–34.
  22. Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African Women. New England Journal of Medicine. 2015 Feb 5;372(6):509–18.
  23. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. New England Journal of Medicine. 2012 Aug 2;367(5):411–22.
  24. Cottrell ML, Yang KH, Prince H, et al. A translational pharmacology approach to predicting HIV pre-exposure prophylaxis outcomes in men and women using tenofovir disproxil fumarate + emtricitabine. Journal of Infection Diseases. 2016; in press.
  25. Loutfy MR, Macdonald S, Myhr T, et al. Prospective cohort study of HIV post-exposure prophylaxis for sexual assault survivors. Antiviral Therapy. 2008 Jan;13:87–95.
  26. a. b. Sultan B, Benn P, Waters L. Current perspectives in HIV post-exposure prophylaxis. HIV/AIDS – Research and Palliative Care. 2014;6:147–58.
  27. U.S. Centers for Disease Control and Prevention. Provider Information Sheet – PrEP During Conception, Pregnancy, and Breastfeeding. Available from: http://www.cdc.gov/hiv/pdf/prep_gl_clinician_factsheet_pregnancy_english.pdf.
  28. Loutfy MR, Margolese S, Money DM, et al. Canadian HIV Pregnancy Planning Guidelines. SOGC Clinical Practice Guideline. Jun 2012; No.278. Available from: http://sogc.org/wp-content/uploads/2012/09/gui278CPG1206E1.pdf.

 

About the author(s)

Camille Arkell is CATIE’s Knowledge Specialist, Biomedical Science of Prevention. She has a Master’s of Public Health degree in Health Promotion from the University of Toronto and has been working in HIV education and research since 2010.