Circumcision and HIV

From Intactipedia
Jump to: navigation, search
THIS ARTICLE IS UNDER CONSTRUCTION

Recently, circumcision has been heavily promoted as a method of preventing HIV. The World Health Organization (WHO) has endorsed male circumcision as a form of HIV prevention, based on three recent studies 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]

Contents

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.

--"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.

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.

Hardened Skin 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."[12] Another study found that "no difference can be clearly visualized between the inner and outer foreskin."[13]

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. 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.[14]

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 desparate 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 inflamation, a condition that facilitates the transmission of viruses. The chances for penile inflamation are reduced, thereby reducing the chances of sexually transmitted viruses, such as HIV.[15]

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, uncircumcised men with constant penile inflamations, and uncircumcised men who don't suffer constant penile inflamation. Unless the randomized controlled studies were limited to only uncircumcised men who suffered constant penile inflamation.

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. [16]

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..."[17]


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.)"[18]

An interesting defense of male circumcision, given the fact that the latest "studies," if they can even be called that, observed HIV trasmission 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).[19]

...where one would expect HIV to be the most rampant.
  • Rwanda - DHS 2005 - 3.8 vs 2.1 [20]
  • 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).[21]

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.[22]

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

The Philippines
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. [23]

Israel
Despite circumcision being near-universal, HIV is an increasing problem in Israel. [24] [25] [26] [27]

The United States
In America, the majority of the male population is circumcised, approximately 80%, 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. [28]

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. [29]

"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." [30]

Results: ...No consistent relationship between male circumcision and HIV risk was observed in most countries." [31]

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[32][33][34][35][36]

African RCT's

Strong bias exists in the RCT's.[37][38][39][40][41] "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."[42] By designing a trial to "detect" a minimum 50 percent reduction risk in HIV, these researchers might have artifically created the clinical setting to observe the effect they were looking to discover.

Concerns about the three randomized controlled clinical trials (RCCTs) in Africa (in South Africa, Uganda, and Kenya)[43][44][45]:

  • The three RCCTs were terminated early because results had reached signifıcance 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.[46]
  • 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.[47][48]
  • 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.[49]

Follow-up studies

Using a population-based survey, Westercamp et al. 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.[50]

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.[51] Another study on circumcision prevalence compared to HIV in the general South African population concluded: “Circumcision had no protective effect on HIV transmission.”[52] When commercial sex worker patterns are controlled, male circumcision is not signifıcantly associated with lower HIV prevalence.[53] 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.”[54] 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.[55]

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.[56] Furthermore, HIV prevalence was found to be higher amongst circumcised males and females for virgins and adolescents in Kenya, Lesotho, and Tanzania.[57]

Circumcision in real-world African settings will likely be a vector for transmitting the virus and is as such likely to worsen the pandemic.[58][59][60][61][62][63]

Problems with Promoting Circumcision as HIV Prevention Policy

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 indorsment, 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.

Even if the recent trials were accurate, circumcision would only reduce the relative risk of acquiring HIV between circumcised and uncircumcised men by 60% over a period of about one year. Circumcision is outperformed by condoms, which have an absolute reduction risk of acquiring HIV that's over 95% (closer to 100% when used properly). Even if a man is circumcised, he would still need to use condoms, and even the authors of the latest studies cannot stress this enough.

Increased Risk to Women

A recent prospective study[64] showed that male circumcision offered no protection to women, and an RCCT[65] 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.[66][67]

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.[68]

Effective Prevention

Estimated per act risk for acquisition
of HIV by exposure route (US only) [69]
Exposure Route Estimated infections
per 10,000 exposures
to an infected source
Blood Transfusion 9,000[70]
Childbirth (to child) 2,500[71]
Needle-sharing injection drug use 67[72]
Percutaneous needle stick 30[73]
Receptive anal intercourse* 50[74][75]
Insertive anal intercourse* 6.5[74][75]
Receptive penile-vaginal intercourse* 10[74][75][76]
Insertive penile-vaginal intercourse* 5[74][75]
Receptive oral intercourse 1[75]
Insertive oral intercourse 0.5[75]
* 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.[77] Anti-retroviral treatment 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.[78]


References

  1. "Male circumcision for HIV prevention". World Health Organization. 2011. http://www.who.int/hiv/topics/malecircumcision/en/. Retrieved 2011-05-06. 
  2. Mazzotta, Meredith (2011-03-04). "Swaziland embarks on ambitious plan to circumcise 80 percent of men 18 to 49 this year". Science Speaks: HIV & TB News. http://sciencespeaksblog.org/2011/03/04/swaziland-embarks-on-ambitious-plan-to-circumcise-80-percent-of-men-18-to-49-this-year/. Retrieved 2011-05-06. "The emphasis is on reaching 80 percent coverage with the Soka Uncobe campaign..." 
  3. "Male Circumcision and Risk for HIV Transmission and Other Health Conditions: Implications for the United States". February 2008. http://www.cdc.gov/hiv/resources/factsheets/circumcision.htm. Retrieved 2011-06-01. 
  4. "Success Stories: Male Circumcision: A Question and Answer Session". March 2007. http://www.cdc.gov/botusa/Success-Stories/0307-MaleCircumcision-Botswana.htm. Retrieved 2011-06-01. 
  5. "Funding". 9/1/2011. http://www.cdcnpin.org/Display/FundDisplay.asp?FundNbr=4285. Retrieved 2011-06-01. 
  6. Alcena, Valiere (October 2006). "AIDS in Third World Countries". PLoS Medicine: [online]. doi:10.1371/journal.pmed.0020298#r1326. http://medicine.plosjournals.org/perlserv/?request=read-response&doi=10.1371/journal.pmed.0020298#r1326. 
  7. Glick, Leonard (2005). ""This Little Operation", Jewish American Physicians and Twentieth-Century Circumcision Advocacy". Marked in Your Flesh. New York, New York: Oxford University Press. pp. 206. ISBN 0-19-517674-X. "What if circumcision protected against infection with HIV..." 
  8. Weiss, Helen A; Quigley, Maria A.; Hayes, Richard J. (October 2000). "Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis". AIDS 14 (15): 2361–2370. doi:10.1097/00002030-200010200-00018. PMID 11089625. http://www.aidsonline.com/pt/re/aids/fulltext.00002030-200010200-00018.htm. 
  9. Fink, Aaron J. "A possible Explanation for Heterosexual Male Infection with AIDS." New England Journal of Medicine 315, 18 (1986): 1167
  10. WHO/UNAIDS (2004). "A global view of HIV infection". World Health Organization. http://www.who.int/hiv/facts/hiv2003/en/. Retrieved 2011-02-27. 
  11. Glick, Leonard (2005). ""This Little Operation", Jewish American Physicians and Twentieth-Century Circumcisoin Advocacy". Marked in Your Flesh. New York, New York: Oxford University Press. pp. 207. ISBN 0-19-517674-X. "This is nothing I can prove." 
  12. Dinh, MH; McRaven MD, Kelley Z, Penugonda S, Hope TJ (2010-03-27). "Keratinization of the adult male foreskin and implications for male circumcision.". AIDS 24 (6): 899-906. PMID 20098294. http://www.ncbi.nlm.nih.gov/pubmed/20098294. Retrieved 2011-06-28. "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.". 
  13. Dinh, Minh H; Sheila M Barry, Meegan R Anderson, Scott G McCoombe, Shetha A Shukair, Michael D McRaven, Thomas J Hope (2009-12-06), "HIV-1 Interactions and Infection in Adult Male Foreskin Explant Cultures" (PDF), 16th Conference on Retroviruses and Opportunistic Infections, Montreal, Canada, http://retroconference.org/2009/PDFs/502.pdf, retrieved 2011-06-28, "No difference can be clearly visualized between the inner and outer foreskin." 
  14. de Witte, Lot; Alexey Nabatov, Marjorie Pion, Donna Fluitsma, Marein AW P de Jong, Tanja de Gruijl, Vincent Piguet, Yvette van Kooyk, Teunis B H Geijtenbeek (2007-03-04). "Langerin is a natural barrier to HIV-1 transmission by Langerhans cells" (PDF). Nature Medicine. doi: 10.1038/nm1541. http://www.circumcisionandhiv.com/files/de_Witte_2007.pdf. Retrieved 2011-06-28. 
  15. Price, Lance B.; Cindy M. Liu, Kristine E. Johnson, Maliha Aziz, Matthew K. Lau, Jolene Bowers, Jacques Ravel, Paul S. Keim, David Serwadda, Maria J. Wawer, Ronald H. Gray (2010). "The Effects of Circumcision on the Penis Microbiome". PLoS ONE 5 (1). doi: 10.1371/journal.pone.0008422. http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0008422. Retrieved 2011-06-29. "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.". 
  16. Mosoko, Jembia J.; Affana, Gislaine A. N. (2005). "16". In Calverton, MD, USA. Prévalence du VIH et facteurs associés. Cameroon: DHS. pp. 309. http://www.measuredhs.com/pubs/pdf/FR163/16chapitre16.pdf. Retrieved 2011-06-02. "Contrairement aux résultats trouvés dans d’autres pays, notamment le Kenya..." 
  17. Marum; L.; J. Muttunga; F. Munene (2003). "13". HIV Prevalence and Associated Factors. Nairobi, Kenya: Central Bureau of Statistics. pp. 250-251. http://www.measuredhs.com/pubs/pdf/FR152/13Chapter13.pdf. Retrieved 2011-06-02. "...the vast majority of Ghanaian men (95 percent) are circumcised... There is little difference in the HIV prevalence by circumcision status..." 
  18. Ministry of Health and Social Welfare; Bureau of Statistics (2005). HIV PREVALENCE AND ASSOCIATED FACTORS. Calverton, Maryland: Ministry of Health and Social Welfare. pp. 13. http://www.measuredhs.com/pubs/pdf/FR171/12Chapter12.pdf. Retrieved 2011-06-02. 
  19. Chipeta, John; Schouten, Erik; Aberle-Grasse, John (2005). "12". HIV PREVALENCE AND ASSOCIATED FACTORS. Calverton, Maryland: National Statistical Office. pp. 234. http://www.measuredhs.com/pubs/pdf/FR175/12Chapter12.pdf. Retrieved 2011-06-02. 
  20. http://www.measuredhs.com/pubs/pdf/FR183/15Chapter15.pdf p. 10
  21. http://www.measuredhs.com/pubs/pdf/FR202/FR202.pdf P. 256
  22. http://www.mmail.com.my/content/39272-72-percent-aidshiv-sufferers-malaysia-are-muslims-says-council
  23. http://globalnation.inquirer.net/news/breakingnews/view/20110102-312124/Philippines-HIVAIDS-problem-worries-UN
  24. http://www.haaretz.com/print-edition/opinion/failing-the-aids-test-1.249088
  25. http://www.haaretz.com/print-edition/features/israeli-gays-shun-condoms-despite-worrying-rise-in-aids-1.249372
  26. http://www.haaretz.com/news/has-the-aids-cocktail-worked-too-well-in-israel-1.258520
  27. http://www.haaretz.com/print-edition/news/hiv-diagnoses-in-israel-climb-new-cases-among-gays-up-sharply-1.248651
  28. http://data.unaids.org/pub/Report/1998/19981125_global_epidemic_report_en.pdf
  29. http://www.measuredhs.com/pubs/pdf/CR22/CR22.pdf
  30. http://www.iasociety.org/Default.aspx?pageId=11&abstractId=2197431
  31. "http://apha.confex.com/apha/134am/techprogram/paper_136814.htm
  32. Castilho EA, Boshi-Pinto C, Guimaraes MDG. Male circumcision and HIV heterosexual transmission. XIV World AIDS Conference. 2002.
  33. 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):1362-8.
  34. Guimaraes M, Castilho E, Ramos-Filho C, et al. Heterosexual transmission of HIV-1: a multicenter study in Rio de Janeiro, Brazil. VII Intl Conf on AIDS. 1991.
  35. Changedia SM, Gilada IS. Role of male circumcision in HIV transmission insignificant in Conjugal relationship. XIV World AIDS Conference. 2002.
  36. Circumcision protects men from AIDS but might increase risk to women, early results suggest.International Herald Tribune, Tuesday, 6 March 2007.
  37. Green LW et al. Male circumcision is not the HIV 'vaccine' we have been waiting for! Future HIV Ther. (2008) 2(3), 193–199.
  38. Montori VM, Devereaux PJ, Adhikari NKJ, et al. Randomized trials stopped early for benefit: a systematic review. JAMA. 2005;294:2203-2209.
  39. Ioannidis JP. Contradicted and initially stronger effects in highly cited clinical research. JAMA. 2005;294:218-228.
  40. 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.
  41. Slutsky AS, Lavery JV. Data safety and monitoring boards. N Engl J Med. 2004;350:1143-1147.
  42. "Male Circumcision: Current Epidemiological and Field Evidence", Program and Policy Implications For HIV Prevention and Reproductive Health, USAID, September 18 and 19, 2002, http://www.path.org/publications/detail.php?i=1048, retrieved 2011-07-07, "designed to detect a minimum 50 percent reduction in HIV risk" 
  43. 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.
  44. 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):643–56.
  45. 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– 66.
  46. Gisselquist D. Points to consider: responses to HIV/AIDS in Africa, Asia, and the Caribbean. London: Adonis and Abbey, 2008, chapter 7.
  47. 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;14:2361–70.
  48. 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;5:165–73.
  49. Slutsky AS, Lavery JV. Data safety and monitoring boards. N Engl J Med. 2004;350:1143-1147.
  50. Westercamp, M; Bailey RC, Bukusi EA, Montandon M, Kwena Z, et al. (2010). "Male Circumcision in the General Population of Kisumu, Kenya: Beliefs about Protection, Risk Behaviors, HIV, and STIs". PLoS ONE 5 (12). doi: 10.1371/journal.pone.0015552. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015552. 
  51. Garenne M. Long-term population effects of male circumcision in generalized HIV epidemics in sub-Saharan Africa. Afr J AIDS Res 2008;7(1):1– 8.
  52. 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. S Afr Med J 2008;98:789 –94.
  53. Talbott JR. Size matters: the number of prostitutes and the global HIV/AIDS pandemic. PloS One 2007;2(6):e543. www.plosone. org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0000543.
  54. Lima V, 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. 5th IAS Conference on HIV Treatment, Pathogenesis and Prevention, Cape Town, abstract WECA105, 2009.
  55. 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. 2010 Nov;39(5):479-82. Department of Epidemiology and Biostatistics, University of California at San Francisco, USA. PMID: 20965388
  56. "Levels and spread of HIV seroprevalence and associated factors: Evidence from national household surveys" (PDF), DHS Comparative Reports 22, Measre DHS, pp. 103, http://www.measuredhs.com/pubs/pdf/CR22/CR22.pdf 
  57. Brewer, PhD, Devon D.; John J. Potterat, BA, John M. Roberts Jr., PhD, Stuart Brody, PhD (March 2007). "Male and Female Circumcision Associated With Prevalent HIV Infection in Virgins and Adolescents in Kenya, Lesotho, and Tanzania". Annals of Epidemiology 17 (3): 217.e1-217.e12. http://www.annalsofepidemiology.org/article/S1047-2797%2806%2900265-1/abstract. Retrieved 2011-06-02. 
  58. Brewer DD, Brody S, Drucker E, Gisselquist D, Minkin SF, Potterat JJ, Rothenberg RB, Vachon F. Mounting anomalies in the epidemiology of HIV in Africa: cry the beloved paradigm. Int J STD AIDS. 2003; 14(3):144-7.
  59. Gisselquist D, Potterat JJ, Brody S, Vachon F. Let it be sexual: how health care transmission of AIDS in Africa was ignored. Int J STD AIDS. 2003; 14:148-61.
  60. Gisselquist D, Potterat JJ, Brody S. Running on empty: sexual co-factors are insufficient to fuel Africa's turbocharged HIV epidemic. Int J STD AIDS. 2004; 15(7):442-52.
  61. Gisselquist D, Potterat JJ. Heterosexual transmission of HIV in Africa: an empiric estimate. Int J STD AIDS. 2003; 14:162-73.
  62. 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.
  63. Nyindo M. Complementary factors contributing to the rapid spread of HIV-I in sub-Saharan Africa: a review. East Afr Med J. 2005; 82(1):40-6.
  64. 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;21:1779–89.
  65. 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;374:229 –37.
  66. Nyakairu F. Uganda turns to mass circumcision in AIDS fıght. Reuters Africa 2008, Aug 13. www.reuters.com/article/idUSLD 23235720080813
  67. Irin, Swaziland: Circumcision gives men an excuse not to use condoms. UN Offıce for the Coordination of Humanitarian Affairs, 2008 Jul. www.irinnews.org/Report.aspx?ReportId�79557
  68. 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. 2010 Nov;39(5):479-82. Department of Epidemiology and Biostatistics, University of California at San Francisco, USA. PMID: 20965388
  69. Smith DK, Grohskopf LA, Black RJ, et al. (2005). "Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States". MMWR 54 (RR02): 1–20. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5402a1.htm#tab1. Retrieved 2009-03-31. 
  70. Donegan E, Stuart M, Niland JC, et al. (1990). "Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations". Ann. Intern. Med. 113 (10): 733–739. PMID 2240875. 
  71. Coovadia H (2004). "Antiretroviral agents—how best to protect infants from HIV and save their mothers from AIDS". N. Engl. J. Med. 351 (3): 289–292. doi:10.1056/NEJMe048128. PMID 15247337. 
  72. Kaplan EH, Heimer R (1995). "HIV incidence among New Haven needle exchange participants: updated estimates from syringe tracking and testing data". J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 10 (2): 175–176. PMID 7552482. 
  73. Bell DM (1997). "Occupational risk of human immunodeficiency virus infection in healthcare workers: an overview.". Am. J. Med. 102 (5B): 9–15. doi:10.1016/S0002-9343(97)89441-7. PMID 9845490. 
  74. 74.0 74.1 74.2 74.3 European Study Group on Heterosexual Transmission of HIV (1992). "Comparison of female to male and male to female transmission of HIV in 563 stable couples". BMJ. 304 (6830): 809–813. doi:10.1136/bmj.304.6830.809. PMID 1392708. 
  75. 75.0 75.1 75.2 75.3 75.4 75.5 Varghese B, Maher JE, Peterman TA, Branson BM,Steketee RW (2002). "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. 29 (1): 38–43. PMID 11773877. 
  76. Leynaert B, Downs AM, de Vincenzi I (1998). "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. 148 (1): 88–96. PMID 9663408. 
  77. "Facts about AIDS & HIV". avert.org. http://www.avert.org/aids.htm. Retrieved 2007-11-30. 
  78. NPR.org

Personal tools