Circumcision and HIV

From IntactiWiki
Jump to navigation Jump to search

This article discusses the relationship of male circumcision and HIV infection. For a discussion of circumcision and other sexually transmitted infections, see Circumcision and STDs.

Recently, circumcision has been heavily promoted as a method of preventing HIV. The World Health Organization (WHO), now known to be corrupted, hasitly endorsed male circumcision as a form of HIV prevention in 2007, based on three studies (2005) & (2007) conducted in Africa (Kenya, South Africa, and Uganda) which claim that male circumcision is supposed to "reduce the risk of HIV transmission by 60%."[1] This endorsement has lead to the institution of "mass circumcision campaigns" aimed at circumcising the majority of African men in a few countries,[2] and the promotion of male circumcision as a HIV-prevention method by the Centers for Disease Control[3][4][5]

Origin of the circumcision/HIV hypothesis

The idea that circumcision prevented HIV transmission was invented by Valiere Alcena, long before there was any "research" to substantiate the claim.[6] In 1986, California urologist Aaron J. Fink, (1926-1994) adopted this idea,[7] and vehemently promoted it,[8] without any kind of proof whatsoever.

In 1986, Fink sent a letter to the New England Journal of Medicine titled "A possible Explanation for Heterosexual Male Infection with AIDS," where he argued that the hard and toughened glans of the circumcised male resisted infection, while the soft and sensitive foreskin and glans mucosa of the intact male were ports of entry.[9] Fink proposed in his letter: "I suspect that men in the United States, who, as compared with those in Africa and elsewhere, have had less acquisition of AIDS, have benefited from the high rate of newborn circumcision in the United States," regardless of the fact that the United States has one of the highest circumcision rates, and one of the highest HIV rates, in the western (industrialized) world (compare with European countries, Canda, and Australia).[10]

Fink's proposal appeared in media throughout the US and Canada. Asked about his idea by a United Press reporter, Fink replied "This is nothing I can prove."[11] This didn't stop other physicians from conducting "research" leading to a steady stream of widely publicized articles arguing that circumcised men were less likely to contract HIV - with the result that prevention of HIV infection has now surpassed even cancer prevention as the most popular claim of circumcision advocates.

Fink's Own Words
This is nothing I can prove.
Aaron J. Fink ("This Little Operation". Marked in Your Flesh. p.206-208)

Fink abandoned the circumcision/HIV controversy in 1991, and he died in 1994. He left behind an indelible legacy nonetheless; the circumcision/HIV hypothesis continues to be supported by researchers and scientists that are adopting his assertions and writing studies based upon them, and the campaign to establish a causal link between HIV infection and the presence of the foreskin continues to this day.

Early research

Hrdy (1987) identified numerous African cultural practices other than circumcision or non-circumcision that would contribute to the spread of HIV infection. Such factors include:

  • Female circumcision and infibulation.
  • Promiscuity.
  • Homesexuality and anal intercourse.
  • Practices resulting in exposure to blood.
  • Practices involving the use of shared instruments.
  • Contact with non-human primates.[12]

Carael et al. (1988) studied HIV transmission among heterosexual couples in Central Africa. No difference was found between couples in which the male was circumcised and in which the male was intact.[13]

de Vincenzi & Mertens (1994) reviewed the literature regarding the alleged role of the foreskin in HIV transmission. They concluded:

The potential public-health benefits of male circumcision have been greatly discussed in the past 50 years, often in a passionate and emotional manner. However, relatively few studies have been carried out and those that have, present conflicting results. The major criticism of most of the studies preformed to date is the lack of attention given to potential confounding factors, which could be related to both circumcision status and risk of sexually transmitted infections, such as sexual behaviour or differences in hygienic practices, or differential use of specific health facilities. As Poland [48] noted, "We must remember that circumcision is not performed randomly."

Therefore, further efforts are still required to quantify the relative risk associated with the lack of male circumcision. Some of this can be achieved by using observational designs which better address the limitations discussed above. Laboratory and primate research might also continue to provide useful information.

As the safety, expected benefits, feasibility and acceptability of mass circumcision are all questionable, neither public-health interventions nor intervention studies appear to be defensible options before there is stronger evidence from observational studies in different settings that show lack of male circumcision may be a genuinely independent risk factor for the transmission of HIV.[14]

Darby (2002) examined the claims that circumcision is preventive of infection with HIV. He tabulated the prevalence of circumcision and HIV infection in various nations. He found no connection between the prevalence of circumcision and HIV infection. Darby also compared the nineteenth century British attempts to control syphilis (then a dreaded and incurable disease) with male circumcision, which was equally unsuccessful.[15]

Thomas et al. (2004) studied the incidence of HIV in circumcision and intact men in a United States Navy population. A slightly higher incidence of HIV infection was found in circumcised men (84.9%) as compared with intact men (81.8%). The authors concluded:

Although there may be other medical or cultural reasons for male circumcision, it is not associated with HIV or STI prevention in this U.S. military population.[16]

Confounding factors

Debunked ad-hoc hypotheses

Various hypotheses have been suggested in regards to the mechanism whereby circumcision prevents the tarnsmission of HIV. They have all been disproven, however, and all of the "studies" attempting to establish a causal link between circumcion and HIV transmission remain unsubstantiated by a working hypothesis.

Keratinization hypothesis

Perhaps the oldest hypothesis on the mechanism whereby circumcision prevents the transmission of HIV is the theory that suggests that the keratinized surface of the penis in circumcised male resists infection, while the mucosa of the glans and inner of the intact male are ports of entry, which was purported by Aaron J. Fink.

Recent studies, however, disprove this hypothesis. One study found that there is "no difference between the keratinization of the inner and outer aspects of the adult male foreskin," and that "keratin layers alone were unlikely to explain why uncircumcised men are at higher risk for HIV infection."[17] Another study found that "no difference can be clearly visualized between the inner and outer foreskin."

Langerhans cell hypothesis

Recent circumcision studies in Africa were conducted under the hypothesis that the Langerhans cells were the prime port of entry for the HIV virus. According to the hypothesis, circumcision was supposed to prevent HIV transmission by removing the Langerhans cells found in the inner mucosal lining of the foreskin.

deWitte found that not only are Langerhans cells found all over the body and that their complete removal is virtually impossible, but furthermore, deWitte found that Langerhans cells that are present in the foreskin produce Langerin, a substance that has been proven to kill the HIV virus on contact, acting as a natural barrier to HIV-1 transmission by Langerhans cells.[18]

Bacterial environment hypothesis

This hypothesis attempts to identify the change in bacterial environment that results in the penis as a result of circumcision, as the mechanism whereby circumcision reduces the spread of HIV transmission. A desperate ad-hoc hypothesis, the explanation is rather farfetched. The argument is that the change in bacterial environment after circumcision makes it difficult for bacteria that cause diseases to live; there are less chances for penile inflammation, a condition that facilitates the transmission of viruses. The chances for penile inflammation are reduced, thereby reducing the chances of sexually transmitted viruses, such as HIV.[19]

Presenting this hypothesis presents a two-fold problem. First, it presents an irrelevant conclusion; the randomized control trials were measuring frequency in HIV transmission, not for frequency in penile bacterial inflamation, and whether said inflamation facilitated sexually transmitted HIV. And secondly, circumcision advocates give themselves the new burden of proving the newly introduced hypothesis, that change in bacterial infection does indeed result in a significant reduction of HIV transmission. A new study is needed to measure HIV transmission in men who have been circumcised, intact men with constant penile inflamations, and intact men who don't suffer constant penile inflammation. Unless the randomized controlled studies were limited to only intact men who suffered constant penile inflammation.

The immunological function of the foreskin

The foreskin's inner fold and the glans of the penis are comprised of mucous membrane tissue. These are also present in your eyes, mouth, and all other bodily orifices including the female genitals. These are the first line of immunological defense for the body's orifices. These mucous membranes perform many immunological and hygienic functions.

Certain components such as Langerhans cells,[20] plasma cells,[21] apocrine glands,[22] and sebaceous glands,[23][24][25][26], collectively secrete emollient lubricants.[27] Apocrine glands perform a crucial function by secreting enzymes such as lysosomal enzymes, cathepsin B, chymotrypsin, and neutrophil elastase.[28]

There is also some research to suggest that lysozyme may protect against HIV infection.[29] [30]

Apocrine glands also produce cytokine,[31] which is a very important non-antibody protein that generates immune response when in contact with specific agents. Plasma cells which increase in number in response to pathogens levels, secrete immunoglobulin.[21] It is also very important to note that Langerhans cells that are present in the foreskin produce Langerin, a substance that has been proven to kill human immunodeficency virus (HIV) on contact.[32]

All of these function to sequester and “digest” foreign pathogens. All these substances play an important role in protecting the penis from viral and bacterial pathogens. The immunological functions of the human prepuce have been extensively documented by respected researchers for quite some time.[30]

Circumcision destroys the natural immunological protections of the foreskin and results in increased risk of contracting infection.

African RCTs

Strong bias exists in the RCTs.[33][34][35][36][37] "These trials, designed to detect a minimum 50 percent reduction in HIV risk, should provide definitive evidence regarding the efficacy and safety of MC within three to five years."[38] By designing a trial to "detect" a minimum 50 percent reduction risk in HIV, these researchers might have artificially created the clinical setting to observe the effect they were looking to discover.

Boyle & Hill (2011) have shown these RCTs to be have significant methodological flaws and statistical errors that render their claims invalid. Although a 60 percent relative reduction in HIV was claimed, the absolute reduction was a statistically insignificant 1.3 percent.[39]

Concerns about the three randomized controlled clinical trials (RCCTs) in Africa (in South Africa, Uganda, and Kenya)[40][41][42]:

  • The three RCTs were terminated early because results had reached a signifıcent level showing reduced HIV infections in experimental compared with control groups; however, it was too soon to gauge long-term effectiveness.
  • The results have no relevance for women or for men who have sex with men.
  • Far more participants were lost to follow-up than were reported to have contracted HIV.
  • A substantial number of participants appeared to have contracted HIV from nonsexual sources: 23 of the 69 infections reported in the South African trial and 16 of the 67 in the Ugandan study.[43]
  • Participants received continuous counseling, free condoms, and monitoring for infection, which was unlikely in real-world campaigns.
  • The sanitary conditions of the surgeries would be diffıcult to replicate on a mass scale in many parts of Africa where HIV infection rates and prevalence are highest.[44][45]
  • Follow-up of any of these RCCTs is impossible. Study participants agreed to be circumcised when joining the study and were randomized into “circumcise now” and “circumcise later” groups.[46]

Real world data

Countries in Africa

According to demographic health studies performed in other countries in Africa, HIV transmission was prevalent in circumcised men in at least 6 different countries:

Cameroon

In Cameroon, where 91% of the male population is circumcised, the ratio of circumcised men vs. intact men who contracted HIV was 4.1 vs. 1.1. [47]

Ghana

In Ghana, the ratio is 1.6 vs 1.4 (95.3% circumcised). "...the vast majority of Ghanaian men (95 percent) are circumcised... There is little difference in the HIV prevalence by circumcision status..."[48]

Lesotho

In Lesotho, the ratio is 22.8 vs 15.2 (23% circumcised). "The relationship between male circumcision and HIV levels in Lesotho does not conform to the expected pattern of higher rates among uncircumcised men than circumcised men. The HIV rate is in fact substantially higher among circumcised men (23 percent) than among men who are not circumcised (15 percent). Moreover, the pattern of higher infection rates among circumcised men compared with uncircumcised men is virtually uniform across the various subgroups for which results are shown in thetable. This finding could be explained by the Lesotho custom to conduct male circumcision later in life, when the individuals have already been exposed to the risk of HIV infection. (Additional analysis is necessary to better understand the unexpected pattern in Table 12.9.)"[49]

An interesting defense of male circumcision, given the fact that the latest "studies," if they can even be called that, observed HIV transmission in men circumcised as adults. Then again, this demographic health survey was conducted in 2004, BEFORE the newer "studies" in 2006. None the less, the unproven assertion that "circumcision is only effective in reducing the risk of HIV when done in infancy" persists in some circles.
Malawi

DHS 2004 - 13.2 vs 9.5 (20% circumcised)

"The relationship between HIV prevalence and circumcision status is not in the expected

direction. In Malawi, circumcised men have a slightly higher HIV infection rate than men who were not circumcised (13 percent compared with 10 percent). In Malawi, the majority of men are not circumcised (80 percent).[50]

...where one would expect HIV to be the most rampant.
Rwanda

DHS 2005 - 3.8 vs 2.1 [51]

South Africa

Rosenberg et al. (2018) report that circumcised men in South Africa are more likely to be HIV infected than intact men.[52]

Swaziland

DHS 2006-2007 - 22 vs 20

"As Table 14.10 shows, the relationship between HIV prevalence and circumcision status is not in the expected direction. Circumcised men have a slightly higher HIV infection rate than men who are not circumcised (22 percent compared with 20 percent).[53]
Zambia

The prevalence of HIV infection among men aged 15-29 has not decreased despite several campaigns to perform male circumcision.

Garenne & Matthews (2019) report:

In a multivariate analysis, based on the 2013 DHS survey, circumcised men were found to have the same level of infection as uncircumcised men, after controlling for age, sexual behaviour and socioeconomic status. Lastly, circumcised men tended to have somewhat riskier sexual behaviour than uncircumcised men. This study, based on large representative samples of the Zambian population, questions the current strategy of mass circumcision campaigns in southern and eastern Africa.[54]

Malaysia

According to Malaysian AIDS Council vice-president Datuk Zaman Khan, more than 70% of the 87,710 HIV/AIDS sufferers in the country are Muslims. In Malaysia, most, if not all Muslim men are circumcised, whereas circumcision is uncommon in the non-Muslim community. 60% of the Malaysian population is Muslim, which means that HIV is spreading in the community where most men are circumcised at an even faster rate, than in the community where most men are intact.[55]

Interestingly enough, Malaysia is home to the TARA KLamp, a controversial circumcision device being marketed in KwaZulu Natal, Africa in the name of HIV prevention.

The Philippines

Tuli or male circumcision, a nearly compulsory cultural practice in the Philippine Islands, causes 93 percent of Filipino males to be circumcised. In the 2010 Global AIDS report released by UNAIDS in late November, the Philippines was one of seven nations in the world which reported over 25 percent in new HIV infections between 2001 and 2009, whereas other countries have either stabilized or shown significant declines in the rate of new infections. Among all countries in Asia, only the Philippines and Bangladesh are reporting increases in HIV cases, with others either stable or decreasing. [56]

The statistics suggest that removal of the protective foreskin by circumcision increases the risk of contracting HIV infection.

Israel

Despite circumcision being near-universal, HIV is an increasing problem in Israel.[57][58][59][60]

The United States

In America, the majority of the male population is circumcised, approximately 75%, while in most countries in Europe, circumcision is uncommon. One would expect for there to be a lower transmission rates in the United States, and for HIV to be rampant in Europe; HIV transmission rates are in fact higher in the United States, where most men are circumcised, than in various countries in Europe, where most men are intact.[61]

A common explanation given for this difference is the fact that sex education and instruction in the proper use of condoms is better executed in Europe than in the United States, where sex education is poor.

However, it is precisely these reasons given, that sex education and condoms aren't catching on in Africa, why circumcision advocates say "mass circumcision campaigns" should be promoted in Africa. What failed in the United States is somehow supposed to work miracles in Africa.

Studies with contrary conclusions

According to USAID, there appears no clear pattern of association between male circumcision and HIV prevalence—in 8 of 18 countries with data, HIV prevalence is lower among circumcised men, while in the remaining 10 countries it is higher.[62]

"Conclusions: We find a protective effect of circumcision in only one of the eight countries for which there are nationally-representative HIV seroprevalence data. The results are important in considering the development of circumcision-focused interventions within AIDS prevention programs."[63]

Results: ...No consistent relationship between male circumcision and HIV risk was observed in most countries."[64]

Findings

Male circumcision has been found not to decrease the risk of HIV and may in fact increase the risk of male to female transmission[65][66][67][68][69]

Follow-up studies

Using a population-based survey, Westercamp et al. (2010) examined the behaviors, beliefs, and HIV/HSV-2 serostatus of men and women in the traditionally non-circumcising community of Kisumu, Kenya prior to establishment of voluntary medical male circumcision services. A total of 749 men and 906 women participated. Circumcision status was not associated with HIV/HSV-2 infection nor increased high risk sexual behaviors. In males, preference for being or becoming circumcised was associated with inconsistent condom use and increased lifetime number of sexual partners. Preference for circumcision was increased with the belief that circumcised men are less likely to become infected with HIV.[70]

Real-world

An analysis of HIV prevalence compared to circumcision status in sub-Saharan Africa concluded that male circumcision is not associated with reduced HIV prevalence.[71] Another study on circumcision prevalence compared to HIV in the general South African population concluded: “Circumcision had no protective effect on HIV transmission.”[72] When commercial sex worker patterns are controlled, male circumcision is not signifıcantly associated with lower HIV prevalence.[73] Mathematical impact modeling of circumcision, antiretroviral therapy (ART), and condom use for South Africa concluded: “Male circumcision was found to have considerably lower impact than condom use or anti-retroviral therapy on HIV infection rates and death rates.”[74] Both the U.S. and sub-Saharan Africa have relatively high incidence rates of HIV infection, considering that about 75% of U.S. men and about 70% of sub-Saharan African men are circumcised—higher percentages than in most other regions or countries with lower prevalence of HIV.[75]

There is no clear pattern of association between male circumcision and HIV prevalence. In 10 out of 18 countries, HIV prevalence is higher amongst circumcised men.[76] Furthermore, HIV prevalence was found to be higher amongst circumcised males and females for virgins and adolescents in Kenya, Lesotho, and Tanzania.[77]

David Gisselquist, Ph.D.[a 1], who has studied health care practices in sub-Saharan Africa, finds that much of health care, especially injection practices, in Africa is non-sterile, and is likely the cause of the high incidence of HIV infection. He notes that the consensus to make sex the primary cause of infection was determined in the 1980s and is likely to be inaccurate, because it does not give sufficient weight to medical transmission of HIV infection.[78] Gisselquist et al. argue strongly that statistical evidence indicates that 5/6s of the HIV infection in Africa is non-sexual.[79][80] Male circumcision has been proposed to reduce the incidence of sexual transmission of HIV. In reality, it actually increases the sexual transmission of HIV. Even if it did work, it would be ineffective against non-sexual transmission by unsafe health care. Furthermore, non-sterile health care could mean that the circumcision operation could transmit the HIV infection to the patient.[81]

Problems with promoting circumcision as HIV prevention policy

The fact that the World Health Organization is corrupt is now well-established:

Circumcision advocates use the latest African studies and WHO's endorsement based on them as proof "beyond reasonable doubt" that circumcision "reduces the risk of HIV." However, there are problems with the WHO's endorsement, as the studies on which it is based on suffer various flaws and confounding factors that bring their credibility in to question, many of which will be discussed in this article.

On their website, the WHO acknowledges that, "[m]ale circumcision provides only partial protection," and that it should be part of a "comprehensive HIV prevention package" that includes HIV testing and counseling services, treatment for STD infections, the promotion of safer sex practices and the provision of condoms and the promotion of their correct and consistent use.

Van Howe & Boyle (2018) pointed out numerous reasons that one should doubt the published results of the randomised clinical trials (RCTs)[82]

George C. Denniston, M.D.[a 2], M.P.H.[a 3], the president of Doctors Opposing Circumcision, in a letter to Ambassador Deborah L. Birx, M.D.[a 2], M.P.H.[a 3], (2020), the head of the President’s Emergency Plan for AIDS Relief (PEPFAR) has called on PEPFAR to suspend the provision of male circumcision because it is ineffective and may increase the reception of HIV infection due to the loss of immunological protections of the foreskin, and to focus on the provision of anti-retroviral therapy and condoms.[83]

Fish et al. (2020), speaking for the VMMC Experience Project, published an article that described the PEPFAR program to circumcise African men, as racist and neo-colonialist.[84]

September 2021

September 2021 saw the publication of two huge population studies on the relationship of circumcision and HIV infection.

Mayan et al. (2021) carried out a massive empirical study of the male population of the province of Ontario, Canada (569,950 males), of whom 203,588 (35.7%) were circumcised between 1991 and 2017. The study concluded that circumcision status is not related to risk of HIV infection.[85]

Morten Frisch and Jacob Simonsen (2021) carried out a large scale empirical population study in Denmark of 855,654 males regarding the alleged value of male circumcision in preventing HIV and other sexually transmitted infections in men. They found that circumcised men have a higher rate of STI and HIV infection overall than intact men.[86]

There now is credible evidence that the massive, expensive African circumcision programs have not been effective in preventing HIV infection.

Increased risk to women

A recent prospective study[87] showed that male circumcision offered no protection to women, and an RCCT[88] found that male circumcision actually increased the risk to women. Women also are placed at greater risk from unsafe sex practices when they, or their circumcised male partners, wrongly believe that with circumcision they are immune to HIV and therefore they choose not to use condoms.[89][90]

There are legitimate additional concerns about:

  • How male circumcision programs, or being circumcised, will influence human behavior.
  • The sidelining of women when considering male circumcision as a prevention method.
  • The tendency of both men and women to ascribe undue power to a technical fıx for what must remain a matter of human control, as in the use of condoms and other safe sex practices.[91]

Effective prevention

Estimated per act risk for acquisition
of HIV by exposure route (US only) [92]
Exposure Route Estimated infections
per 10,000 exposures
to an infected source
Blood Transfusion 9,000[93]
Childbirth (to child) 2,500[94]
Needle-sharing injection drug use 67[95]
Percutaneous needle stick 30[96]
Receptive anal intercourse* 50[97][98]
Insertive anal intercourse* 6.5[97][98]
Receptive penile-vaginal intercourse* 10[97][98][99]
Insertive penile-vaginal intercourse* 5[97][98]
Receptive oral intercourse 1[98]
Insertive oral intercourse 0.5[98]
* assuming no condom use
§ source refers to oral intercourse
performed on a man

The three main transmission routes of HIV are sexual contact, exposure to infected body fluids or tissues, and from mother to fetus or child during perinatal period. It is possible to find HIV in the saliva, tears, and urine of infected individuals, but there are no recorded cases of infection by these secretions, and the risk of infection is negligible.[100] Anti-retroviral treatment (ART) of infected patients also significantly reduces their ability to transmit HIV to others, by reducing the amount of virus in their bodily fluids to undetectable levels.[101] [83]

See also

External links

Abbreviations

  1. REFweb Doctor of Philosophy, Wikipedia. Retrieved 16 June 2021. (Also abbreviated as D.Phil.)
  2. a b REFweb Doctor of Medicine, Wikipedia. Retrieved 14 June 2021.
  3. a b REFweb Master of Public Health or Master of Philosophy in Public Health, Wikipedia. Retrieved 14 June 2021.

References

  1. REFweb (2007). Male circumcision for HIV prevention, World Health Organization. Retrieved 6 May 2011.
  2. REFnews Mazzotta, Meredith (4 March 2011)."Swaziland embarks on ambitious plan to circumcise 80 percent of men 18 to 49 this year". Retrieved 6 May 2011. "The emphasis is on reaching 80 percent coverage with the Soka Uncobe campaign..."
  3. REFweb (February 2008). Male Circumcision and Risk for HIV Transmission and Other Health Conditions: Implications for the United States. Retrieved 1 June 2011.
  4. REFweb (March 2007). Success Stories: Male Circumcision: A Question and Answer Session, CDC. Retrieved 1 June 2011.
  5. REFweb (9 January 2011). Funding. Retrieved 1 June 2011.
  6. REFjournal Alcena V. AIDS in Third World Countries. N Y State J Med. October 2006; 8: 446. PMID. DOI. Retrieved 28 May 2020.
  7. REFbook Glick LB (2005): "This Little Operation", Jewish American Physicians and Twentieth-Century Circumcision Advocacy, in: Marked in Your Flesh. p. 206. New York, New York: Oxford University Press. Quote: What if circumcision protected against infection with HIV.... ISBN 0-19-517674-X. Retrieved 19 February 2011.
  8. REFjournal Weiss HA, Quigley MA, Hayes RJ. Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis. AIDS. October 2000; 14(15): 2361-2370. PMID. DOI.
  9. REFjournal Fink AJ. A possible Explanation for Heterosexual Male Infection with AIDS. New England Journal of Medicine. 315(18): 1167. PMID.
  10. REFweb WHO/UNAIDS (2004). A global view of HIV infection, World Health Organization. Retrieved 27 February 2011.
  11. REFbook Glick LB (2005): "This Little Operation", Jewish American Physicians and Twentieth-Century Circumcision Advocacy, in: Marked in Your Flesh. p. 207. New York, NY: Oxford University Press. Quote: This is nothing I can prove.. ISBN 0-19-517674-X. Retrieved 19 February 2011.
  12. REFjournal Hrdy DB. Cultural practices contributing to the transmission of human immunodeficiency virus in Africa. Rev Infect Dis. November 1987; 9(6): 1109-19. PMID. DOI. Retrieved 12 May 2021.
  13. REFjournal Carael M, Van de Perre PH, LePage PH, Allen S, et al. Human immunodeficiency virus transmission among heterosexual couples in Central Africa. AIDS. June 1988; 2(3): 201-5. PMID. Retrieved 28 May 2020.
  14. REFjournal de Vincenzi I, Mertens T. Male circumcision: a role in HIV prevention?. AIDS. 1994; 8(2): 153-60. PMID. Retrieved 29 May 2020.
  15. REFjournal Darby R. Been There, Done That: Thoughts on the proposition that yet more circumcision can save the world from AIDS. Australian Quarterly. September 2002; 74(5): 26-35. Retrieved 8 May 2021.
  16. Thomas AG, Bakhireva LN, Brodine SK, Shaffer RA. Prevalence of male circumcision and its association with HIV and sexually transmitted infections in a U.S. Navy population. Abstract no. TuPeC4861. Presented at the XV International AIDS Conference, Bangkok, Thailand, July 11-16, 2004.
  17. REFjournal Dinh MH, McRaven MD, Kelley Z, Penugonda S, Hope TJ. Keratinization of the adult male foreskin and implications for male circumcision. AIDS. 27 March 2010; 24(6): 899-906. PMID. Retrieved 28 June 2011. Quote: We found no difference between the keratinization of the inner and outer aspects of the adult male foreskin. Keratin layers alone are unlikely to explain why uncircumcised men are at higher risk for HIV infection.
  18. REFjournal de Witte L, Nabatov A, Pion M, Fluitsma D, de Jong MAWP, de Gruijl T, Piguet V, van Kooyk Y, Geijtenbeek TBH. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells PDF. Nature Medicine. 4 March 2007; 13(3): 367-71. PMID. PMC. DOI. Retrieved 2 July 2020.
  19. REFjournal Price LB, Liu CM, Johnson KE, Aziz M, Lau MK, Bowers J, Ravel J, Keim PS, Serwadda D, et al. The Effects of Circumcision on the Penis Microbiome. PLoS ONE. 2010; 5(1) DOI. Retrieved 29 June 2011. Quote: The anoxic microenvironment of the subpreputial space may support pro-inflammatory anaerobes that can activate Langerhans cells to present HIV to CD4 cells in draining lymph nodes. Thus, the reduction in putative anaerobic bacteria after circumcision may play a role in protection from HIV and other sexually transmitted diseases.
  20. REFjournal Weiss GN, Sanders M, Westbrook KC. The distribution and density of Langerhans cells in the human prepuce: site of diminished immune response?. Isr J Med Sci. January 1993; 29(1): 42-43. Retrieved 20 October 2019.
  21. a b REFjournal Flower PJ, Ladds PW, Thomas AD, Watson DL. An immunopathologic study on the bovine prepuce. Vet Pathol. March 1983; 20(2): 189-201. Retrieved 20 October 2019.
  22. REFjournal Ahmed A, Jones AW. Apocrine Cystadenoma: a report of two cases occurring on the prepuce. Br J Dermatol. December 1969; 81(12): 899-901. Retrieved 20 October 2019.
  23. REFjournal Hyman AB, Brownstein MH. Tyson's "glands": ectopic sebaceous glands and papillomatosis penis. Arch Dermatol. January 1969; 99(1): 31-36. Retrieved 20 October 2019.
  24. REFjournal Delbanco E. Über das gehäufte Auftreten von freien Talgdrüsen an der Innenfläche des Präputiums [About the increased occurrence of free sebaceous glands on the inner surface of the prepuce] (German). Monatshefte für praktische Dermatologie. 1904; 38: 536-538. Retrieved 20 October 2019.
  25. REFjournal Piccinno R, Carrel CF, Menni S, et al. sebacous glands mimicking molluscum contagiosum. Acta Derm Venerol. 1990; 70: 344-345.
  26. REFjournal Krompecher S. Die Histologie der Absonderung des Smegma praeputii [Histology of allocation of a smegma praeputii] (German). Anatomischer Anzeiger. 1932; 75: 170-176.
  27. REFjournal Parkash S, Jeykumar S, Subramanyan K, Chaudhuri S. Human subpreputial collection: its nature and formation. J Urol. August 1973; 110(2): 211-212. Retrieved 20 October 2019.
  28. REFjournal Frohlich E, Shamburg-Lever G, Klesses C. Immunelectron microscopic localization of cathepsin B in human apocrine glands. J Cutan Pathol. February 1993; 20(1): 54-60.
  29. REFweb Hill, George (7 September 2003). Summary of evidence that the foreskin and lysozyme may protect against HIV infection. Retrieved 20 October 2019.
  30. a b REFjournal Fleiss PM, Hodges FM, Van Howe RS. Immunological functions of the human prepuce. Sex Trans Infect. October 1998; 74(5): 364-67. PMID. Retrieved 27 October 2021.
  31. REFjournal Ahmed AA, Nordlind K, Schultzberd M, Liden S. Immunohistochemical localization of IL-1 alpha-, IL-1 beta-, IL-6- and TNF-alpha-like immunoreactivities in human apocrine glands. Arch Dermatol Res. 1995; 287(8): 764-766. Retrieved 20 October 2019.
  32. REFjournal de Witte L, Nabatov A, Pion M, et al. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nat Med. March 2007; 13(3): 367-371. Retrieved 20 October 2019.
  33. REFjournal Green LW, et al. Male circumcision is not the HIV 'vaccine' we have been waiting for! PDF. Future HIV Ther. 2008; 2(3): 193–199.
  34. REFjournal Montori VM, Devereaux PJ, Adhikari NKJ, et al. Randomized trials stopped early for benefit: a systematic review. JAMA. 2005; 294: 2203-2209.
  35. REFjournal Ioannidis JP. Contradicted and initially stronger effects in highly cited clinical research PDF. JAMA. 2005; 294: 218-228.
  36. REFjournal Wheatley K, Clayton D. Be skeptical about unexpected large apparent treatment effects: the case of an MRC AML12 randomization. Control Clin Trials. 2003; 24: 66-70.
  37. REFjournal Slutsky AS, Lavery JV. Data safety and monitoring boards. N Engl J Med. 2004; 350: 1143-1147.
  38. REFdocument Program and Policy Implications For HIV Prevention and Reproductive Health PDF, Contribution: Male Circumcision: Current Epidemiological and Field Evidence, USAID. (January 2002). Retrieved 29 September 2019.
    Quote: designed to detect a minimum 50 percent reduction in HIV risk
  39. REFjournal Boyle GJ, Hill G. Sub-Saharan African randomised clinical trials into male circumcision and HIV transmission: Methodological, ethical and legal concerns PDF. Thompson Reuter. December 2011; 19(2): 316-34. PMID. Retrieved 30 December 2020.
  40. REFjournal Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 trial. PLoS Med. 2005; 2(11): e298.
  41. REFjournal Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: A randomised controlled trial. Lancet. 2007; 369(9562): 643–656.
  42. REFjournal Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: A randomised trial. Lancet. 2007; 369(9562): 657-666.
  43. REFbook Gisselquist D (2008): 7, in: Points to consider: responses to HIV/AIDS in Africa, Asia, and the Caribbean. London: Adonis and Abbey.
  44. REFjournal Weiss HA, Quigley MA, Hayes RJ. Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis. AIDS. 2000; 14: 2361–2370.
  45. REFjournal Siegfried N, Muller M, Deeks J, et al. HIV and male circumcision — a systematic review with assessment of the quality of studies. Lancet Infect Dis. 2005; 5: 165–173.
  46. REFjournal Slutsky AS, Lavery JV. Data safety and monitoring boards. N Engl J Med. 2004; 350: 1143-1147.
  47. REFbook Mosoko JJ, Affana GAN (2005): 16, in: Prévalence du VIH et facteurs associés. Calverton, MD, USA (ed.). Edition: Enquête Démographique et de Santé du Cameroun. p. 309. Cameroon: DHS. Quote: Contrairement aux résultats trouvés dans d’autres pays, notamment le Kenya.... Retrieved 2 June 2011.
  48. REFbook Marum L, Muttunga J, Munene F (Central Bureau of Statistics): 13, in: HIV Prevalence and Associated Factors. Work: Kenya: Demographic and Health Survey 2003. pp. 250-251. Nairobi, Kenya: Central Bureau of Statistics. Quote: ...the vast majority of Ghanaian men (95 percent) are circumcised... There is little difference in the HIV prevalence by circumcision status....
  49. REFbook (2005) HIV Prevalence and Associated Factors. Work: Lesotho Demographic and Health Survey 2004. p. 13. Calverton, Maryland: Ministry of Health and Social Welfare. Retrieved 2 June 2011.
  50. REFbook Chipeta J, Schouten E, Aberle-Grasse J (2005): 12, in: HIV Prevalence and Associated Factors. Work: Malawi Demographic and Health Survey 2004. p. 234. Calverton, Maryland: National Statistical Office. Retrieved 2 June 2011.
  51. http://www.measuredhs.com/pubs/pdf/FR183/15Chapter15.pdf p. 10
  52. REFjournal Rosenberg MS, Gómez-Olivé FX, Ronr JK, Kahn K, Bärnighausen TW. Are circumcised men safer sex partners? Findings from the HAALSI cohort in rural South Africa. PLOS ONE. 1 August 2018; 13(8): e0201445. PMID. PMC. DOI. Retrieved 20 October 2019.
  53. http://www.measuredhs.com/pubs/pdf/FR202/FR202.pdf P. 256
  54. REFjournal Garenne M, Matthews A. Voluntary medical male circumcision and HIV in Zambia: expectations and observations. J Biosoc Sci. 14 October 2019; Epub ahead of print: 1-13. PMID. DOI. Retrieved 19 October 2019.
  55. http://www.mmail.com.my/content/39272-72-percent-aidshiv-sufferers-malaysia-are-muslims-says-council
  56. http://globalnation.inquirer.net/news/breakingnews/view/20110102-312124/Philippines-HIVAIDS-problem-worries-UN
  57. REFweb (4 July 2008). Failing the AIDS Test. Retrieved 5 January 2020.
  58. REFweb (9 July 2008). Israeli Gays Shun Condoms Despite Worrying Rise in AIDS. Retrieved 5 January 2020.
  59. REFweb (30 November 2008). Has the AIDS Cocktail Worked Too Well in Israel?. Retrieved 5 January 2020.
  60. REFweb (27 June 2008). HIV Diagnoses in Israel Climb; New Cases Among Gays Up Sharply. Retrieved 5 January 2020.
  61. http://data.unaids.org/pub/Report/1998/19981125_global_epidemic_report_en.pdf
  62. http://www.measuredhs.com/pubs/pdf/CR22/CR22.pdf
  63. http://www.iasociety.org/Default.aspx?pageId=11&abstractId=2197431
  64. "http://apha.confex.com/apha/134am/techprogram/paper_136814.htm
  65. REFconference Castilho, E.A., with: Boshi-Pinto C., Guimaraes M.D.G.: Male circumcision and HIV heterosexual transmission (2002). XIV World AIDS Conference.
  66. REFjournal Guimaraes MD, Vlahov D, Castilho EA. Postcoital vaginal bleeding as a risk factor for transmission of the human immunodeficiency virus in a heterosexual partner study in Brazil (Rio de Janeiro Heterosexual Study Group). Arch Intern Med.. 1997; 157(12): 1362-1368.
  67. REFconference Guimaraes, M., with: Castilho E., Ramos-Filho C., et al.: Heterosexual transmission of HIV-1: a multicenter study in Rio de Janeiro, Brazil (1991). VII Intl Conf on AIDS.
  68. REFconference Changedia, S.M., with: Gilada I.S.: Role of male circumcision in HIV transmission insignificant in Conjugal relationship (2002). XIV World AIDS Conference.
  69. REFweb (6 March 2007). Circumcision protects men from AIDS but might increase risk to women, early results suggest, International Herald Tribune.
  70. REFjournal Westercamp M, Bailey RC, Bukusi EA, Montandon M, Kwena Z, et al. Male Circumcision in the General Population of Kisumu, Kenya: Beliefs about Protection, Risk Behaviors, HIV, and STIs. PLoS ONE. 2010; 5(12) DOI.
  71. REFjournal Garenne M. Long-term population effects of male circumcision in generalized HIV epidemics in sub-Saharan Africa PDF. Afr J AIDS Res. 2008; 7(1): 1-8.
  72. REFjournal Connolly C, Simbayi LC, Shanmugam R, Nqeketo A. Male circumcision and its relationship to HIV infection in South Africa: results of a national survey in 2002 PDF. S Afr Med J. 2008; 98: 789-794.
  73. REFjournal Talbott JR. Size matters: the number of prostitutes and the global HIV/AIDS pandemic. PloS One. 2007; 2(6): e543.
  74. REFconference Lima, V., with: Anema A., Wood R., et al.: The combined impact of male circumcision, condom use and HAART coverage on the HIV-1 epidemic in South Africa: a mathematical model, Cape Town (2009). 5th IAS Conference on HIV Treatment, Pathogenesis and Prevention (abstract WECA105).
  75. REFjournal Green LW, Travis JW, McAllister RG, Peterson KW, Vardanyan AN, Craig A. Male circumcision and HIV prevention insufficient evidence and neglected external validity. Am J Prev Med (Department of Epidemiology and Biostatistics, University of California at San Francisco, USA). November 2010; 39(5): 479-482. PMID.
  76. REFdocument DHS Comparative Reports 22, Contribution: Levels and spread of HIV seroprevalence and associated factors: Evidence from national household surveys, Measre DHS. Retrieved 29 September 2019.
  77. REFjournal Brewer DD, Potterat JJ, Roberts Jr JM, Brody S. Male and Female Circumcision Associated With Prevalent HIV Infection in Virgins and Adolescents in Kenya, Lesotho, and Tanzania PDF. Annals of Epidemiology. 17(3): 217.e1-217.e12. Retrieved 2 June 2011.
  78. REFjournal Gisselquist D, Rothenberg R, Potterat J, Drucker E. Non-sexual transmission of HIV has been overlooked in developing countries. Br Med J. 2002; 324(7331): 235.
  79. REFjournal Gisselquist D, Potterat JJ. Heterosexual transmission of HIV in Africa: an empiric estimate PDF. Int J STD AIDS. 2003; 14: 162-73.
  80. REFjournal Gisselquist D, Potterat JJ, Brody S. Running on empty: sexual co-factors are insufficient to fuel Africa's turbocharged HIV epidemic PDF. Int J STD AIDS. 2004; 15(7): 442-52.
  81. REFjournal Nyindo M. Complementary factors contributing to the rapid spread of HIV-I in sub-Saharan Africa: a review. East African Medical Journal. 2005; 82(1): 40-46.
  82. REFjournal Van Howe RS, Boyle GJ. Meta-analysis of HIV-acquisition studies incomplete and unstable. BJU Int. 31 October 2018; Retrieved 5 September 2020. Quote: Given the effectiveness of condoms, the lack of consistent findings on national levels, the methodologically flawed RCTs, the lack of translational research, and the impressive potential uptake and effectiveness of pre-exposure prophylaxis, circumcision as an intervention to prevent HIV infection should be treated with greater scepticism.
  83. a b REFdocument Denniston, George C.: World Health Organization, HIV, and male circumcision, Doctors Opposing Circumcision. (29 June 2020). Retrieved 2 September 2020.
  84. REFjournal Fish, Max, Shavisi, Arianne, Gwaambuka, Tatenda, Tangwa, Godfrey B., Ncayiyana, Daniel, Earp, Brian D. A new Tuskegee? Unethical human experimentation and Western neocolonialism in the mass circumcision of African men. Developing World Bioeth. 9 September 2020; 00: 1-16. PMID. Retrieved 7 April 2021.
  85. REFjournal Mayan, Madhur, Hamilton, Robert J., Juurlink, David N., Austin, Peter C., Jarvi, Keith A.. Circumcision and Risk of HIV Among Males From Ontario, Canada. J Urol. 23 September 2021; PMID. DOI. Retrieved 2 October 2021. Quote: We found that circumcision was not independently associated with the risk of acquiring HIV among men from Ontario, Canada.
  86. REFjournal Frisch, Morten, Simonsen, Jacob. Non-therapeutic male circumcision in infancy or childhood and risk of human immunodeficiency virus and other sexually transmitted infections: national cohort study in Denmark. Eur J Epidemiol. 26 September 2021; Published online ahead of print PMID. DOI. Retrieved 20 October 2021.
  87. REFjournal Turner AN, Morrison CS, Padian NS, et al. Men’s circumcision status and women’s risk of HIV acquisition in Zimbabwe and Uganda. AIDS. 2007; 21: 1779–1789.
  88. REFjournal Wawer MJ, Makumbi F, Kigozi G, et al. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet. 2009; : 229-237.
  89. REFweb Nyakairu, F. (13 August 2008). Uganda turns to mass circumcision in AIDS fıght, Reuters Africa.
  90. REFweb (July 2008). Circumcision gives men an excuse not to use condoms, The New Humanitarian (formerly IRIN News), UN Offıce for the Coordination of Humanitarian Affairs. Retrieved 5 January 2020.
  91. REFjournal Green LW, Travis JW, McAllister RG, Peterson KW, Vardanyan AN, Craig A. Male circumcision and HIV prevention insufficient evidence and neglected external validity PDF. Am J Prev Med (Department of Epidemiology and Biostatistics, University of California at San Francisco, USA). November 2010; 39(5): 479-482. PMID.
  92. REFjournal Smith DK, Grohskopf LA, Black RJ, et al. Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States. MMWR. 2005; 54(RR02): 1-20. Retrieved 31 March 2009.
  93. REFjournal Donegan E, Stuart M, Niland JC, et al. Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations. Ann. Intern. Med.. 1990; 113(10): 733-739. PMID.
  94. REFjournal Coovadia H. Antiretroviral agents—how best to protect infants from HIV and save their mothers from AIDS. N. Engl. J. Med.. 2004; 351(3): 289-292. PMID. DOI.
  95. REFjournal Kaplan EH, Heimer R. HIV incidence among New Haven needle exchange participants: updated estimates from syringe tracking and testing data. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol.. 1995; 10(2): 175-176. PMID.
  96. REFjournal Bell DM. Occupational risk of human immunodeficiency virus infection in healthcare workers: an overview. Am J Med. 1997; 102(5B): 9-15. PMID. DOI.
  97. a b c d REFjournal European Study Group on Heterosexual Transmission of HIV. Comparison of female to male and male to female transmission of HIV in 563 stable couples. BMJ. 304(6830): 809-813. PMID. PMC. DOI.
  98. a b c d e f REFjournal Varghese B, Maher JE, Peterman TA, Branson BM, Steketee RW. Reducing the risk of sexual HIV transmission: quantifying the per-act risk for HIV on the basis of choice of partner, sex act, and condom use. Sex Transm Dis. 2002; 29(1): 38-43. PMID.
  99. REFjournal Leynaert B, Downs AM, de Vincenzi I. Heterosexual transmission of human immunodeficiency virus: variability of infectivity throughout the course of infection. European Study Group on Heterosexual Transmission of HIV. Am J Epidemiol. 1998; 148(1): 88-96. PMID.
  100. REFweb Facts about AIDS & HIV, avert.org. Retrieved 30 November 2007.
  101. NPR.org