It's time to talk top: the risk of insertive, unprotected anal sex
HIV Australia | Vol. 9 No. 3 | November 2011
This article describes the biological role of anal mucus and its association with the gastrointestinal immune system, which harbours a persistent reservoir of HIV that potentially leads to infectious anal mucus. ERIC GLARE argues that all HIV prevention discussions should highlight the role anal mucus plays in HIV transmission.
Strategic positioning, where an HIV-negative man takes the insertive role inunprotected anal intercourse with an HIV-positive partner in order to reduce his risk of infection, has been associated with an intermediate incidence of HIV in cohorts of Sydney men who have sex with men (MSM).1
Circumcision of the insertive partner and an undetectable blood plasma viral load in the receptive partner are two factors often cited as contributing to risk reduction in strategic positioning practices, despite there being a paucity of data on HIV transmission by anal intercourse in men who take the insertive role in male-to-male sex.2
Men who practise strategic positioning are attempting to take perceived risks into account to form personalised boundaries around anal intercourse but, until recently, a comprehensive understanding of HIV transmission through insertive unprotected anal intercourse has not been widely canvassed in research literature.
A 2008 study of risk factors associated with HIV seroconversion in gay men in England identified that some men taking the insertive role in anal intercourse contracted HIV because they did not perceive that they were at risk of infection.3 GMFA, a gay men’s health charity based in the UK, responded with a campaign called Arse Facts that identified anal mucus as a body fluid containing HIV at potentially infectious levels.4
Anal mucus is increasingly being mentioned in Australian campaigns as the infectious body fluid potentially infecting the insertive partner during unprotected anal intercourse.5, 6, 7 At times, the explanation of the role that anal mucus plays in transmitting HIV to the insertive partner has been relegated to in-depth discussions of topics such as risk reduction, but is frequently left out of more introductory information about HIV transmission (e.g. Whereversexhappens.com8),and some campaigns discuss the risk of insertive anal intercourse without mentioning any body fluids involved9.
Some campaigns warn that even if an HIV-positive person has an undetectable blood plasma viral load they might have higher viral load in anal mucus, particularly if they also have another STI.10, 11 However, it should also be noted that a recent study, looking at men who have sex with men, found that plasma and rectal viral load were correlated, and that STI in the rectum did not increase the likelihood of detecting HIV in anal mucus, including those that had low or undetectable levels of HIV in their blood.12 This study suggests that a lower HIV viral load in blood plasma would also mean a lower viral load in anal mucus.
The role of anal and gastrointestinal mucus
Anal mucus13 and, more generally, gastrointestinal mucus found throughout the length of the gut are the body fluids that protect the delicate inner lining of our gastrointestinal tract. Mucus lubricates, prevents drying and protects the mucous membranes that line our nose, mouth, lungs, eyes, inner ears, our urinary-genital organs and our gut. Mucus in the gastrointestinal tract forms a defensive divide between the fragile epithelial cells that absorb nutrients and the digesting slurry of acids, enzymes, food and commensal bacteria that transit our gut.
Studies in rats have shown that the mucus in the gastrointestinal tract consists of two constantly renewed layers that in the colon total 0.15mm thick.14 The outer layer that is most exposed is loose and moves with faecal material lubricating its passage down the gut (see Figure 1).The inner mucus layer is firmly pinned to the gut wall rather like pieces of paper on a noticeboard. The adherence of the inner mucus layer allows the outer mucus layer to slide over the inner layer as material moves down the gut. This ensures that the gastrointestinal wall from oesophagus to anus is always covered and protected by a layer of mucus.
Whilst the outer layer functions in lubricating, the firmly adhered mucus layer functions more as a protective barrier from corrosive stomach acids and bacteria creating a stable microenvironment at the mucosal surface.15, 16 The gastrointestinal tract is home to ten times more bacteria than human gut cells; these bacteria are essential for healthy nutrition but are detrimental to our health if they get into other areas of the body. Bacteria are found in the outer mucus layer but not in the inner layer of mucus which forms a tight net-like structure lining the gut epithelium. The sub-microscopic molecular pores of the mucus ‘net’ allow nutrients to cross to the epithelium, and viruses to varying extents, but not bacteria (Figure 1).17
Anal mucus and HIV
From the early days of the epidemic, receptive anal sex with ejaculation has been known to carry the highest risk of sexual transmission of HIV, and this is dependent on HIV penetrating the mucus layers of the rectum. What has not been widely appreciated is that mucus in the rectum of infected people also contains infectious HIV19 – virus that has moved in the opposite direction from the gut wall into the mucus20.
HIV viral load in anal mucus is difficult to measure, but it is typically higher than in blood plasma or semen taken from the same person, even for those on highly active antiretroviral therapy (HAART).21 HIV replication in the gastrointestinal tract is responsive to HAART and blood plasma viral load reflects the overall amount of active viral replication in the body. In men who had undetectable viral load in blood plasma, HIV viral particles were rarely detected (2%) in rectal samples but plenty of HIV infected cells were still found in the mucosa.22
In a study measuring HIV shedding into the rectum, the presence of HIV-infected cells and local inflammation were the principle determinants of rectal HIV levels amongst individuals with a low plasma HIV viral load of less than 10,000 copies/mL, suggesting that the HIV was locally produced.23 When HIV-infected cells were present in the rectal wall, increased blood plasma HIV viral load did not increase the risk of shedding of HIV into the anal-rectal canal but inflammation from other STI – such as human papilloma virus (HPV) – did increase the amount of virus released. Although the act of taking samples could have stimulated release of HIV particles from the rectal wall or from the circulation by micro-bleeding, the trauma was likely to have been considerably less than that associated with anal intercourse.24
The gastrointestinal tract is the largest immune organ in the body.25 Approximately 70% of the immune system is found in the gastrointestinal tract in what is called gut-associated lymphoid tissue (GALT). The tonsils and adenoids at the back of the throat as well as a diffuse network of immune cells throughout the length of the gut are all part of the GALT.26, 27 The major sites of HIV replication in the body are the lymph nodes and the GALT of the gastrointestinal tract; relatively little HIV is produced in the blood.28
While mucus provides a physical barrier of protection, GALT harbours immune cells that can specifically target any microorganisms that penetrate the gut mucus. In healthy people,CD4 lymphocytes are found in their largest numbers in the gut and, due to their active surveillance role, they are often mature and activated bearing co-receptors such as CCR5,preferred for HIV infection.29 These CD4 cells are important both as the primary target of HIV infection following unprotected receptive anal sex and as the main source of HIV in rectal mucus that might infect subsequent insertive partners.30 The role of the mucus bilayer as the bi-directional frontier of the immune defence of the gut emphasises the importance of anal and rectal mucus in HIV transmission, whether through receptive or insertive anal intercourse.
CD4 counts in blood plasma drop over the months and years following infection, but CD4 cells in the gastrointestinal tract are depleted rapidly in the acute phase of HIV infection. In a group of 32 newly infected men (mean = 37 days from infection), CD4 cells in the gastrointestinal wall were greatly reduced within the first few weeks of infection.31 Impressively, the study included six men first sampled within 19 days of infection. The study found that gastrointestinal CD4 cells remained depleted at more than 50% of normal levels, even in people who had a relatively normal blood CD4 count due to long-term HAART.32
The enduring depletion of gastrointestinal CD4 cells indicates a failure of immune reconstitution of GALT in the gut despite active recruitment of effector and naive CD4 cells.33 This is currently an active area of research; it has been found that some of the CD4 cells are – as expected
– killed by cycles of HIV infection, but other uninfected CD4 cells are killed by inflammation as bystanders to the primary fight against HIV.34
From the earliest stages of infection of the many CD4 cells in the gastrointestinal mucosa, HIV causes a breakdown in the delicate balance protecting the gut wall from bacteria and their toxins. Epithelial cells struggle to maintain and repair junctions between cells, leading to impaired barrier function and increased permeability of the epithelium.35 This damage allows toxins and microbes to invade the gut wall and the circulation close-by. Bacterial products can be found in the bloodstream of people with HIV. Known as microbial translocation, this process triggers systemic immune activation.36 The immune response increases HIV replication increases activation of CD4 cells and their susceptibility to HIV infection, and induces immune cell death in the gastrointestinal tract. Essentially, the immune response against microbial translocation amplifies the damage caused by HIV in the gut, preventing effective immune reconstitution in many people.
It is not known what happens to the mucus bilayer during microbial translocation but it is likely that it is disorganised and not efficient at protecting the gut wall.
The implication of the failed immune reconstitution in the gastrointestinal tract is that the gut is a major reservoir of HIV persistence – even in people receiving HAART.37 This, in turn, suggests that anal mucus might be the body fluid most capable of returning to infectious levels of HIV, albeit momentarily, in people on well-maintained HAART.
Interestingly, a Sydney study of men who have sex with men conducted from 2001 to 2007 found that the per-contact probability of HIV transmission due to unprotected anal intercourse, both insertive and receptive, was similar to estimates from developed countries in the pre-HAART era.38 This was despite the more recent cohort having a high proportion of HIV-infected men who were on HAART and had an undetectable blood plasma viral load.
The immunobiology of the anus and rectum strongly implicates anal mucus in HIV transmission; it is not known to what extent blood contributes to transmission, although micro-bleeding is thought to occur during anal intercourse. In the absence of a major bleed from conditions such as haemorrhoids, fissures, tears and trauma, the predominant body fluid by volume is likely to be mucus, although this has not yet been confirmed by specific data.
Implications for HIV education
From an educational point of view, talking about anal mucus makes sense. Anal mucus is macroscopic, it is visible particularly with diarrhoea or after douching, and people can feel its moistness; microscopic invisible blood has none of these associations. Anal mucus is well known to people who practise fisting, where keeping individualised aliquots of lubricant from cross-contamination with body fluids is central to play-etiquette.39 Anal mucus can vary in appearance from clear to white, or brown. Because people can see and feel mucus, they can understand the role it plays in HIV transmission through their own personal association with the body fluid. Mucus provides a more powerful, less mysterious mechanism for transmission than microscopic blood.
Vaginal mucus is directly analogous to anal mucus in HIV transmission and whilst blood is likely to be a factor and a plausible mechanism of vaginal-penile transmission, in prevention education vaginal mucus is said to be the infectious body fluid. The rectum is much more susceptible to trauma than the vagina, as the rectal wall is very thin compared to the vagina and more easily damaged, and there is a much bigger stigma against anal intercourse that jointly might account for the comparative lack of anal mucus in many explanations of transmission.
In both vaginal and anal intercourse, blood resulting from rough sex, binge sex, large toys and fisting is seen as an amplifier of the risk of transmission
(e.g. see Wherever sex happens40). Talking about anal mucus counters stigma that says anal sex is not natural and causes tissue damage which facilitates transmission. This conversation makes HIV transmission seem a more normal biological process because it does not rely solely on the explanation of damage to the rectum to facilitate transmission; HIV is present in mucus in the rectum, not just further away in the circulation.
During anal sex, HIV can be transmitted to the insertive partner when a bodily fluid containing HIV from the receptive partner, such as anal mucus, enters the body of the insertive partner. This can occur through the foreskin and surrounding areas, the eye of the penis to the urethra (also a mucous membrane), or through tiny (often invisible) breaks in the skin of the penis.
HIV prevention discussions that neglect to explain how the insertive partner in anal sex is infected leave a hole in the discourse as well as a gap in the understanding of how HIV is transmitted during anal sex. Explaining the potential roles of both anal mucus and blood is a direct rebuttal to the taboo of talking about the specifics of anal sex. This must be good for prevention.
1 Jin, F., Crawford, J., Prestage, G., et al. (2009). HIV risk reduction behaviours in gay men: unprotected anal intercourse, risk reduction behaviours, and subsequent HIV infection in a cohort of homosexual men. AIDS, 23(2), 243–252. doi:10.1097/ QAD.0b013e32831fb51a
2 Jin, F., Jansson, J., Law, M., Prestage, G., et al. (2010). Per-contact probability of HIV transmission in homosexual men in Sydney in the era of HAARt. AIDS, 24(6), 907–913. doi:10.1097/ QAD.0b013e3283372d90 Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852627/
3 INSIGHT case-control study findings: Elam G., Macdonald, N., Hickson, F., et al. (2008). Risky sexual behaviour in context: qualitative results from an investigation into risk factors for seroconversion among gay men who test for HIV. Sex Transm Infect, 84(6), 473–7. doi:10.1136/ sti.2008.031468 See also: Macdonald, N., et al. (2008). Factors associated with HIV seroconversion in gay men in England at the start of the 21st century. Sex Transm Infect, 84(1), 8–13.
4 GMFA – the gay men’s health charity. (2008). Arse Facts. Available at: http://www.gmfa.org.uk/londonservices/adcampaigns/gmfa#arse-facts (accessed 5 October 2011).
5 ACON. (2007). HIV & AIDS – The Basics: A safe sex guide for gay men. Available at: http://www.acon.org.au/sites/default/files/Safe-Sex-Basics_0.pdf (accessed 29 September 2011).
6 Australian Federation of AIDS Orgnaisations (AFAO). (2002). HIV+ Gay Sex: A booklet about being gay, having HIV and sex. AFAO, Sydney. Available at: http://www.afao.org.au/__data/assets/pdf_file/0005/6953/HIV_Positive_Gay_Sex.pdf (accessed 29 September 2011).
7 Australian Federation of AIDS Orgnaisations (AFAO). 2008. the Drama Downunder. [Online] (See specifically: Introduction/STIs and HIV transmission HIV/How do you get it?) Available at: http://thedramadownunder.info. (accessed 29 September 2011).
8 Victorian AIDS Council/Gay Mens Health Centre (VAC/GMHC). Wherever sex happens. (see specifically: risk reduction: tops and bottoms) [Online] Available at: http://whereversexhappens.com/ (accessed 5 October 2011).
9 Victorian AIDS Council/Gay Men’s Health Centre (VAC/GMHC). (2010). Staying Negative. [Online]. (See specifically: HIV/AIDS and safe sex: bottom or passive partner). Available at: www.stayingnegative.net.au (accessed 5 October 2011).
10 AFAO 2008, op. cit. (See specifically: Introduction/STIs and HIV transmission/HIV-positive men and STIs).
11 VAC/GMHC Wherever sex happens, op. cit. (See specifically: risk reduction:sections ‘undetectable viral load’ and ‘tops and bottoms’).
12 Kelley C. F., Haaland R. E., Patel P., Evans-Strickfaden T., Farshy C., Hanson D., et al. (2011) HIV-1 RNA rectal shedding is reduced in men with low plasma HIV-1 RNA viral loads and is not enhanced by sexually transmitted infections in the rectum. J Infect Dis., 205(5), 761–67. doi:10.1093/infdis/jir400
13 Mucus (noun) is the secretion produced by mucous (adjective) membranes. Anal mucus is used elsewhere and here for simplicity, particularly for people who do not have English as their first language. Much of the research refers to rectal mucus because that is where the fluid was sampled; also referred to as mucosal secretions or rectal secretions. Anorectal mucus is probably the most accurate name for the body fluids involved in HIV transmission but this has not been confirmed by specific data to date.
14 Atuma, C., Strugala, V., Allen, A., and Holm, L. (2001). the adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am J Physiol Gastrointest Liver Physiol, 280(5), G922–9. Available at: http://ajpgi.physiology.org/content/280/5/G922.full.pdf
16 Phillipson, M., Johansson, M., Henriksnäs, J., et al. (2008). the gastric mucus layers: constituents and regulation of accumulation. Am J Physiol Gastrointest Liver Physiol, 295(4), G806–12. doi: 10.1152/ajpgi.90252.2008 Link: http://ajpgi.physiology.org/content/295/4/G806.full.pdf
17 Johansson, M., Phillipson, M., Petersson, J., et al. (2008). the inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci USA, 105(39), 15064–9. doi:10.1073/ pnas.0803124105
19 Zuckerman, R., Whittington, W., Celum, C, et al. (2004). Higher Concentration of HIV RNA in Rectal Mucosa Secretions than in Blood and Seminal Plasma, among Men Who Have Sex with Men, Independent of Antiretroviral therapy. The Journal of Infectious Diseases, 190(1), 156–61. doi: 10.1086/421246
20 Kiviat N., Critchlow C., Hawes S., et al. (1998). Determinants of Human Immunodeficiency Virus DNA and RNA Shedding in the Anal-Rectal Canal of Homosexual Men. The Journal of Infectious Diseases, 177(3), 571–8. doi:10.1086/514239 Link: http://jid.oxfordjournals.org/content/177/3/571.long
21 Zuckerman, R. et al., op. cit.
22 The mucosa is the mucous membrane layers forming the inner surface of organs such as the gastrointestinal tract; includes the epithelium and aggregates of immune cells in GALT follicles. In: Lampinen, T. M., Critchlow, C. W., Kuypers, J., et al. (2000). Association of antiretroviral therapy with detection of HIV-1 RNA and DNA in the anorectal mucosa of homosexual men. AIDS, 14(5), F69–75. Available at: http://journals.lww.com/aidsonline/Fulltext/2000/03310/Association_of_antiretroviral_therapy_with.1.aspx (accessed 4 October 2011).
23 Kiviat, N. B., et al., op. cit.
25 Janeway, C., Travers, P., Walport, M., and Shlomchik, M. (2001). Mucosal Immunity. In: Janeway, C., Travers, P., Walport, M., and Shlomchik, M. J. (eds.), Immunobiolgy, 5th Edition: The immune system in health and disease. Garland Science, New York, 10.13–10.20. Available at www.ncbi.nlm.nih.gov/books/NBK27169/ (accessed 4 October 2011).
27 Spahn, T. and Kucharzik, T. (2004). Modulating the intestinal immune system: the role of lymphotoxin and GALT organs. Gut, 53(3), 456–65. doi:10.1136/gut.2003.023671
28 Mehandru, S., Poles, M., Tenner-Racz, K., et al. (2007). Mechanisms of gastrointestinal CD4+ T-cell depletion during acute and early human immunodeficiency virus type 1 infection. J Virol, 81(2), 599–612. doi:10.1128/JVI.01739-06
29 Brenchley, J., Schacker, T., Ruff, L.,et al. (2004). CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med, 200(6), 749–59. doi:10.1084/jem.20040874
30 Kiviat, N. et al. op. cit.
31 Mehandru, S. et al. (2007)., op. cit.
32 Mehandru, S., Poles, M., Tenner-Racz,K., et al. (2006). Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection. PLoS Med, 3(12), e484. doi:10.1371/journal. pmed.0030484
33 Hofer, U., and Speck, R. (2009). Disturbance of the gut-associated lymphoid tissue is associated with disease progression in chronic HIV infection. Semin Immunopathol, 3 (2), 257–66. doi:10.1007/s00281-009-0158-3
35 Shacklett, B. and Anton, P. (2010). HIV infection and gut mucosal immune function: Updates on pathogenesis with implications for management and intervention. Curr Infect Dis Rep., 12(1), 19-27. doi:10.1007/s11908-009-0072-9
36 Hofer, U. and Speck, R., op. cit.
37 Shacklett, B. and Anton, P. op. cit.
38 Jin, F. et al. (2010), op. cit.
39 Herrman, B. (1991). Trust the hand book: A guide to the sensual and spiritual art of handballing. Alamo Square Press, San Francisco.
40 VAC/GMHC Wherever sex happens, op. cit. (see specifically: Drug use/decreased physical awareness and Risk reduction/tops and bottoms/there are other risk factors/point 5)
Eric Glare (PhD) is a PLHIV speaker and educator with the Positive Speakers Bureau, People Living With HIV/AIDS Victoria. He did his PhD studies on PCR technology and the gene expression of CD4 cells in asthma and allergy and is now retired as a biomedical researcher.
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