HIVreport.de 02 2011 Pre-cum 2 Pre-cum – What’s that? 3 HIV in Pre-cum 4 Gonorrhoeae in Pre-cum 6 Conclusions for Prevention aidshilfe.de HIVreport 2/2011 Pre-cum Issue No. 02/2011 28/04/2011 Dear Readers, Pre-Cum Spring has arrived at the HIVreport’s editorial office. This issue introduces a fresh new look for the HIVreport and connects it more closely to the DAH website. All topics will now be easier to find and will offer links to our other information services. This is meant to increase the HIVreport’s usefulness while making it more exciting to read. The focus of the HIVreport’s current issue also happens to be on excitement, or more specifically, pre-ejaculate. Questions about what role this small drop of liquid has in HIV transmission have puzzled many experts. We decided to get to the bottom of this, all the way to the pelvic floor, where the pea-sized glands are located that produce pre-ejaculate. Bottom line: The established facts of HIV prevention still apply. Pre-ejaculate is of no concern in oral intercourse. Oral contact with pre-ejaculate is still considered “safer sex”. However, this is not the case with vaginal and anal intercourse, where preejaculate may well lead to an HIV infection (or pregnancy). The second topic is – once again – preexposure prophylaxis (PrEP): In the two previous HIVreports, we discussed the findings of the first phase-3 study. Unfortunately, we now have some unexpected bad news: A PrEP study on women from southern African countries was stopped. This is why, for the third time in a row, we are informing you about PrEP, which seems to become a prominent topic this year. Best regards, Armin Schafberger, Steffen Taubert PRE-CUM ............................................... 2 Pre-cum or Pre-ejaculate – What’s that? ........ 2 Where does it come from? ............................... 2 What’s in it, and why? ...................................... 2 A Comparison: Ejaculate ................................. 3 A Comparison: The boar .................................. 3 HIV in Pre-ejaculate ........................................... 3 A Comparison: HIV in ejaculate ....................... 3 Neisseria Gonorrhoeae in Pre-ejaculate .......... 4 Co m me n t a r y ................................................... 4 Conclusions for Prevention .............................. 6 Oral sex ............................................................ 6 HIV: Pre-ejaculate of no concern ................. 6 N. gonorrhoeae: Infection of the throat possible ........................................................ 6 Vaginal and anal sex ........................................ 6 Pre-ejaculate as HIV risk ............................. 6 NEWS BULLETIN .................................. 7 PrEP Study Stopped .......................................... 7 Competence Networks Ends HIV Cohort ........ 7 New Website for HIVreport................................ 7 REFERENCES ....................................... 7 IMPRINT ................................................. 8 1 HIVreport 2/2011 Pre-cum Pre-cum “I’ve heard that pre-cum contained an extreme concentration of HIV. Others say the exact opposite.” Questions like this are frequently asked in the Health Support section of the gay dating site Gayromeo as well as on other online advice sites. into the rear of the urethra. They are supported by the smaller Littré glands located in the penis along the urethra. What’s in it, and why? Pre-ejaculate serves as a natural lubricant during sex and subsequent ejaculation. It flushes out residual urine and changes the chemical environment in the urethra (from acidic to basic). This secretion thereby acts as a buffer in vaginal intercourse before any sperm enters the vagina’s acidic and rather “hostile” environment. Additionally, the secretion’s constituents are considered to have immune defence properties [2]. Pre-cum or Pre-ejaculate – What’s that? The clear fluid that is secreted by the urethra of a man’s penis after sexual arousal prior to ejaculation is referred to as pre-ejaculate, Cowper’s fluid, and colloquially as pre-cum. The amount varies from a few drops up to 5 ml [1]. In rare cases, the amount may be larger and is perceived by some men as uncomfortable or embarrassing. The secretion of the Cowper’s gland itself is free of sperm. Several authors have nevertheless found sperm in pre-ejaculate, sometimes even in almost half of their study subjects [3]. There are two possible explanations for this observation: It was either residual sperm from a previous ejaculation, or sperm from an imminent ejaculation that prematurely exited the urethra. Given the technically tricky “extraction” of pre-ejaculate, Where does it come from? Pre-ejaculate originates from glands whose existence and name is even unknown to many doctors. It is primarily produced by two pea-sized bulbourethral glands (also called Cowper’s glands) that are located below the prostate and release their secretions directly Male lower abdomen (cross-section) Intestine Groß wieof The size einethe a pea: Erbse: die Cowper’s Cowperglands Drüsen Urinary bladder Seminal duct Prostate Rectum Urethra Testis Epididymis 2 HIVreport 2/2011 Pre-cum line: Men drip before, boars drip after – and seal it off. it is almost impossible to distinguish between pre-ejaculate and ejaculate. Sperm found in inherently sperm-free pre-ejaculate is the main reason why coitus interruptus, i.e. the pull-out method, is not recommended for heterosexuals as a suitable method of contraception. sch HIV in Pre-ejaculate There are only two small-scale studies from 1992 that investigated whether pre-ejaculate contains HIV. Due to the difficult extraction of pre-ejaculate, there is no other available research known to us. A Comparison: Ejaculate Semen consists of various secretions produced by the epididymis (located behind the testes), the seminal vesicles (located behind the prostate), the prostate and the Cowper’s glands. The sperm cells originating from the testes only make up a very small part of the volume, with most of the ejaculate coming from the prostate. The study by Ilaria et al. [10] used DNA measurement 2 to detect the presence of HIV, while the study by Pudney et al. [11] employed HIV-antibody markers. Result: Immune cells 3 containing HIV were found in most of the 23 examined pre-ejaculate samples from HIV-positive subjects. A Comparison: The boar Humans and pigs have a fairly similar anatomy 1. There is, however, at least one difference between man and pig in the anatomy and function of the bulbourethral glands. Neither of the two studies provided any information about the detection of free viruses in pre-ejaculate. The studies did not offer any statements about concentration (referred to as viral load) or comparisons between the concentration of HIV in pre-ejaculate and ejaculate. The study findings have been interpreted to suggest that pre-ejaculatory fluid tends to contain less HIV than semen while still being potentially infectious. However, based on this research, it is not possible to determine if, and under what circumstances, preejaculatory exhibits a higher or lower concentration of HIV. It can be assumed (although not scientifically proved) that the concentration of HIV in preejaculatory fluid – as well as in blood and other secretions – is higher in the case of acute HIV infection and will be low or no longer detectable after several months of successful HIV treatment. photo: Ich-und-Du / pixelio.de A man’s bulbourethral gland is only pea-sized and produces hardly any secretion worth mentioning. A boar releases about 40 grams of fluid from a gland up to 20 cm (8 inches) in length during, but not before, the final thrust of ejaculation. This secretion reacts with the proteins of the seminal vesicles, forming a viscous gel that closes the cervix to prevent the semen previously ejaculated into the uterus from leaking back out [12]. Bottom A Comparison: HIV in ejaculate HIV is found in ejaculate as both a free virus and in immune cells (lymphocytes and mac- 2 HIV is an RNA virus. However, when the genetic material of HIV is integrated into the genetic material of the human cell, it must be present in the form of DNA – as in humans. This integrated HIV DNA can be measured. 1 This is why pigs are used as subjects in medical trials (e.g. testing new anaesthetic techniques) and as heart valve donors. The transplantation of other tissue from pigs to humans, such as pancreatic islet cells for the treatment of diabetes, is currently being researched. 3 HIV can be transferred by both free viruses and viruses in cells (cell-to-cell contact). 3 HIVreport 2/2011 Pre-cum People with living with HIV/AIDS who have a gonococcal infection of the urethra, have three times more often HIV in the urethra [13]. . This will increase the risk of HIV transmission through unprotected vaginal or anal sex. The diagnosis and treatment of gonorrhoea (and chlamydia) is therefore an important factor in preventing HIV rophages). While the sperm themselves are free of HIV, the virus is capable of attaching to the sperm’s surface. Sperm washing in assisted reproduction therefore makes it possible to obtain HIV-free sperm. HIV originates from all secretions of the ejaculate. However, it has yet to be determined which gland(s) are primarily responsible for the concentration of HIV in sperm, and to what extent immune cells (macrophages) in the lining of the urethra are able to release HIV [7]. sch Commentary A Safe Feeling, Flushed Down the Drain? A large part of the viruses in ejaculate appears to come from the prostate and the seminal vesicles [8]. This is supported by the fact that there is no noticeable decrease in the concentration of HIV in sperm after a vasectomy (severing the vas deferens from the testes and epididymis). Pre-cum encapsulates all the drama about safer sex. Answering questions about precum is the ultimate challenge in HIV/AIDScounselling. I’m not sure if anyone has ever noticed, but the penis is somehow reminiscent of gremlins: When it gets wet, it gets serious. According to an examination by Smith et al., the concentration of HIV in ejaculate may be even higher after a prostate massage (using a finger), at least in some of their male test subjects [9]. This may require a little explanation: “Gremlins” is a 1984 film about adorable little creatures that can quickly turn into vicious monsters. Whenever they come into contact with something wet, bad things are bound to happen. Neisseria Gonorrhoeae in Preejaculate We do know that a penis doesn’t bite when it comes into contact with…let’s say… saliva. But as soon as a drop of liquid comes out of it during oral sex, the performer often recoils in fear, because that drop can be bad news. This goes back to 30 years of HIV prevention telling us to “get out before it comes!” – Most people have really taken this advice to heart. As we have learned, anyone whose mouth comes into contact with semen is at risk of contracting HIV. In science and preventive medicine, Cowper’s fluid – as some like to call it – has always held a special status based on the belief that the concentration it contains is too low for HIV to be transmitted through oral sex. To rephrase this in a lyrical way: The first heralds of spring won’t give you sunburn. The bulbourethral glands are no strangers to gonorrhoea. Neisseria gonorrhoeae infect the urethra and its accessory glands 4. In chronic (untreated) gonorrhoea, they may persist in the bulbourethral glands for a long time. These glands are also a reservoir for bacteria. This means that in the event of a bacterial infection, the pre-ejaculate contains N. gonorrhoeae (or chlamydia) while also carrying the bacteria located in the urethra. Even when there is no contact with sperm during oral sex, N. gonorrhoeae may still infect the throat 5. The preliminary results of the recent PARIS study by the Robert Koch Institute indicate that one in twenty MSM had N. gonorrhoeae of the throat. Things could be so easy: sperm nay, preejaculate yay. But honestly, most of us never swallowed that message, or the liquid in question, without thinking twice about it. For many people, pre-cum is a turn-off. And it has always been the ultimate challenge in HIV/AIDS counselling, because this tiny drop of bodily fluid encapsulates the entire uni- 4 N. gonorrhoeae may also infect the throat (after oral sex), the rectum (after anal sex) and the cervix (after vaginal sex). They may also cause so-called ascending infections of upper organs, e.g. Fallopian tubes, prostate, spermatic cord, epididymis, … 5 Chlamydia appear to infect the throat less often that N. gonorrhoeae 4 HIVreport 2/2011 Pre-cum verse of safer sex, all knowledge about potential risks of infection, as well as all those nagging fears and uncertainties that affect so many people. Reliable information may not always be enough to overcome that fear entirely, but it will at least help keep it at bay. Fortunately, we know by now that even a whole mouthful of semen poses only a minor risk compared to unprotected anal sex. Perhaps this will help us make peace with pre-ejaculate? To put it another way: We know that nothing can happen – but does this mean we can all blow easy? If not, I recommend counselling projects ot the Deutsche AIDS-Hilfe. They know a lot about this subject. Here’s what happens in a real life situation: As long as we don’t see or taste anything, everything is fine, so a tiny drop of liquid is not going to kill us. But as soon as the thought of pre-ejaculate, no matter how little it may be, enters our mind, it can unleash a whole landslide of worries. Holger Wicht First of all, it’s not always just a drop; the amount of pre-cum can vary greatly. So what if it’s not a drop, but a trickle or even a stream – could this be the very exception to the safer sex rule? Wouldn’t this mean that those extremely few viruses per micro-litre all add up to exceed the risk threshold? Does that even qualify as pre-cum anymore? Or could that already be semen? There are men who produce a lot of pre-cum and there are those who produce little semen. Consistencies vary. Both fluids pass through the same opening in short succession. Preejaculate and ejaculate – practitioners only draw a fuzzy distinction between these two terms. And let’s be honest, saying that “a very low concentration of the virus is not enough to become infected” does not make for a very solid argument. To make things even more complicated, it’s also been reported that precum in the rectum may very well be dangerous after all. Any feeling of safety we may have had is flushed down the drain! Consider this: Last night I bit my tongue, this morning I sliced my gums with dental floss, and mucous membranes can’t be trusted anyway. Wouldn’t a situation like this leave the door wide open for HIV infection? The issue of pre-ejaculate fuels a flurry of irrational fears that are particularly difficult to cope with because there are also some reasonable doubts involved. That’s what safer sex is like: While striving for total commitment, we are secretly calculating the probabilities – and always expect the worst. The residual risk has to be taken, but we fool ourselves by blowing it out of proportion, because fear is one of the most skilled illusionists under the sun. 5 HIVreport 2/2011 Pre-cum Safer sex (“Get out before it comes”) does not provide protection against gonorrhoea during oral sex. Sexually active people who practice oral sex with various partners should consider the possibility of having contracted gonorrhoea – although that disease often progresses without any apparent symptoms. Only a routine test (throat swab to measure bacterial DNA = PCR) can provide clarity in this case. However, these examinations have so far been rarely performed in medical practices. Conclusions for Prevention Pre-ejaculate is no easy subject. When assessing the risk of HIV infection, it is not essential to know whether the concentration of HIV in pre-ejaculate is slightly lower or higher than in semen. What’s most important is the type of sex that was practiced and the mucous membrane that came into contact with the preejaculate. In the mouth, pre-ejaculate does not 6 pose a risk of HIV transmission. In the vagina, pre-ejaculate is very likely to pose a high risk of HIV transmission. Sex workers are advised to wear condoms also for oral sex to prevent gonococcal infections (and other STIs, e.g. syphilis). Oral sex Vaginal and anal sex HIV: Pre-ejaculate of no concern Pre-ejaculate as HIV risk In general, oral sex (including contact between mouth and semen) only poses a low risk of a HIV transmission [14,15,16]. To further reduce this low risk, the safe-sex message is to avoid taking ejaculate in the mouth. This message permits oral contact with preejaculate, and has been proved in millions of cases over a quarter of a century. The pull-out or withdrawal method (also called “coitus interruptus”) is often used with the intention to prevent pregnancy or HIV infection. Scientific studies have demonstrated the opposite: This method provides no protection against pregnancy or HIV. Preejaculate may have a significant role in this case. HIV is also a “problem of quantity”. The small quantity 7 of HIV in pre-ejaculate is not enough for oral (!) transmission. This is because the oral mucosa is much more resilient 8 than the genital and rectal mucous membranes, in addition to the diluting effect of the saliva and the short period of exposure before the fluid is swallowed. In a study on Canadian homosexual and bisexual men, Liviana Calzavara et al. [4] identified the delayed application of condoms during anal sex as a major HIV risk factor for the receptive partner. They assume that preejaculate may contribute to this increased risk. In two studies on Australian gay men, Jin et al. discovered a risk for the receptive partner during anal sex when the insertive partner withdrew before ejaculation [5]. The second study (see HIVreport 1/2010 for detailed information) found that unprotected anal sex without ejaculation was still half as risky as unprotected anal sex with ejaculation [6] – thus posing a high risk. N. gonorrhoeae: Infection of the throat possible A gonorrhoea infection of the throat is a previously underestimated or rather little-known condition. During oral sex (with ejaculation), these pathogens can be transmitted through contact with the urethra and pre-ejaculate. So far, it has not been possible to scientifically prove whether pre-ejaculate is the cause of that high HIV risk, or if there may be other reasons involved (unintentional ejaculation, small bleeding injuries on the partner’s penis, ulcers on the partner’s glans or foreskin leaking HIV-infected secretions). Small amounts of pre-ejaculate may, however, also pose a risk of HIV transmission, since the mucous 6 Nothing is 100% safe, neither medicine and prevention nor nuclear safety or air travel. In very rare cases, oral sex may lead to infection even if there was no oral contact with semen. 7 A man simply doesn’t have the tremendous secretion volume of a boar 8 After all, the oral mucosa has to withstand many things, including spicy foods, hot tea, acidic juices and distilled spirits. 6 HIVreport 2/2011 Pre-cum membranes of the cervix and the intestine are more susceptible than the mouth – even when there are only small amounts of HIVinfected secretions. Competence Networks Ends HIV Cohort Funding for the HIV/AIDS Competence Network ends in April 2011. Now that state funding has run out, the Competence Network for HIV/AIDS will have to give up its plans for a long-term patient database. All attempts to raise money for the continuation of the HIV cohort failed. The competence network plans to keep the collected data and biomaterial until June 2016 to allow for the completion of ongoing research projects and to give scientists the opportunity to continue working with the compiled material for a few more years. Is there even any point in preserving data for such a long time when there is only “old data” left anyway? How secure are the data and the biomaterial when there is no longer a funded administrative structure? Should study participants continue their participation, or would they be better advised to revoke their consent? This May, the DAH will provide a critical analysis and in-depth coverage of the developments in the competence network on „blog.aidshilfe.de” and “HIVreport.de” to shed some light on these questions. tau Armin Schafberger, Steffen Taubert News Bulletin PrEP Study Stopped On 18 April 2011, Family Health International (FHI) announced that it will stop the FEMPrEP HIV-prevention study, in which some 2,000 women from Kenya, South Africa and Tanzania participated. The study investigated whether a daily dose of Truvada can prevent HIV infection and reduce the number of HIV infections. Preliminary study results indicated that the group of women who received Truvada® (Tenofovir plus Emtricitabin) for several months had the same number of infections as the control group, suggesting that this PrEP was not able to reduce the number of HIV infections. The exact reasons for this are not yet known. It is unclear if the outcome may be due to low adherence to the study regimen, or interactions between Truvada and other drugs or foods, or a general ineffectiveness of PrEP in vaginal intercourse (a study among MSM in late 2010 indicated 44% protective efficiency), or if PrEP only failed to be effective in this particular study, or if it only happened to be effective in the iPrEx study among MSM. A final evaluation has yet to be made – leaving the matter open to speculation for now. New Website for HIVreport Over the next few months, the HIVreport website will be moving to be integrated into the website of Deutsche AIDS-Hilfe. This will connect the contents of the HIVreport even more closely to the DAH’s other media. The search function on aidshilfe.de will then make it possible to conveniently list all contents of the HIVreport. The “old” web address will remain available for the transition period. Subscribers to the HIVreport will from now on receive their PDF file from “aidshilfe.de”. tau These results are not expected to mean “the end” for PrEP. Although the FEM-PrEP was stopped, there are still other ongoing PrEP studies whose results are expected to be released in the next few years (overview in HIVreport of December 2010, further information on the MSM-PrEP study). In February 2011, the U.S. Centers for Disease Control published guidelines for the use of PrEP among MSM in response to the iPrEx study findings: That move may have been premature (see HIVreport 1/2011). sch 7 HIVreport 2/2011 Pre-cum [15] Romero J et al: Evaluating the risk of HIV transmission through unprotected orogenital sex. AIDS 2002, Vol 16, No 9 References [1] Chudnovsky A, Niederberger C: Copious Pre-Ejaculation: Small Glands - Major Headaches. Journal of Andrology, Vol. 28, No.3, May/June 2007 [2] Chughtai B et al: A neglected gland: a review of Cowper gland. Int J Androl. 2005; 28:7477 [16] Baggaley RF et al.: Systematic review of orogenital HIV-1 transmission probabilities. Int Journal of Epidemiology 2008; 37: 1255-1265 Imprint Publisher [3] Killick SR: Sperm content of preejaculatory fluid. Hum Fertil (Camb). 2011 Mar; 14(1):48-52 Deutsche AIDS-Hilfe e.V., Wilhelmstr. 138 10963 Berlin Tel: (030) 69 00 87- 0 , Fax: (030) 69 00 87- 42 www.aidshilfe.de [4] Calzavara L: Delayed Application of Condoms is a Risk Factor for HIV Infection among Homosexual and Bisexual Men. Am J Epidemiol 2003; 157:210-217 Responsible in the sense of the German "Pressegesetz" (law on publishing/news): Steffen Taubert (tau) Armin Schafberger (sch) [5] Jin F et al: Unprotected anal intercourse, risk reduction behaviours, and subsequent HIV infection in a cohort of homosexual men. AIDS 2009; 23:243-252 Texts Armin Schafberger, Holger Wicht, Steffen Taubert [6] Jin F et al: Per-contact probability of HIV Transmission in homosexual men in Sydney in the era of HAART. AIDS 2010; 24:907-913 German-English Translation: Macfarlane International Business Services GmbH & Co. KG [7] Coombs RW et al: Lower Genitourinary Tract Sources of Seminal HIV. JAIDS 2006; 41:430-438 Order new and download older sues: www.hivreport.de [8] Le Tortorec A, Dejucq-Rainsford N: HIV infection of the male genital tract - consequences for sexual transmission and reproduction. Int Journal of Andrology 33 (2010), e98-e108 Donations account of Deutsche AIDS-Hilfe e.V Account no. 220 220 220 Berliner Sparkasse Sort code 100 500 00 [9] Smith DM et al: The Prostate as a reservoir for HIV-1. AIDS 2004, Vol 18 No 11, 16001602 Notice The procedures, medication, constituents and generic drugs are communicated regardless of the existing patent situation. Protected product names (trademarks) are not always marked as such; however, this must not give rise to the assumption that the designations used are non-proprietary names. Deutsche AIDS-Hilfe accepts no liability for the correctness of the information provided as well as for any damage caused by possible errors. We recommend that our readers refer to the manufacturers’ summary of product characteristics and package inserts. [10] Ilaria G et al.: Detection of HIV-1 DNA sequences in pre-ejaculatory fluid. The Lancet, Volume 340, Issue 8833, 12 December 1992, Page 1469 [11] Pudney J et al.: Pre-ejaculatory fluid as potential vector for sexual transmission of HIV-1 The Lancet, Volume 340, Issue 8833, 12 December 1992, Page 1470 [12] Busch W, Holzmann A.: Veterinärmedizinische Andrologie: Physiologie und Pathologie der Fortpflanzung bei männlichen Tieren. Schattauer Verlag, 2001 [13] Moss GB et al: Human Immundeficiency Virus DNA in Urethral Secretions in Men: Association with Gonococcal Urethritis and CD4 Cell Depletion. The Journal of Infectious Diseases 1995; 172:1469-74 The translation of this issue was made possible by the support of [14] Campo J et al: Oral transmission of HIV. Reality or fiction. Review. Oral Diseases, 2006, 12, 219–228. 8
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