"Scientists have power by virtue of the respect commanded by the discipline. We may therefore be sorely tempted to misuse that power in furthering a personal prejudice or social goal -- why not provide that extra oomph by extending the umbrella of science over a personal preference in ethics or politics? But we cannot, lest we lose the very respect that tempted us in the first place."

- Stephen Jay Gould
Bully for Brontosaurus, pp 429-30

(But some, it seems, are willing to take that risk.)

It is not, of course, up to the media to decide what is good or bad science. The media was reporting what it heard from scientists [about cold fusion]. Only a tiny fraction of all scientific research is ever covered by the popular media, however, and most scientists go through their entire career without once encountering a reporter. New results and ideas are argued in the halls of research institutions, presented at scientific meetings, published in scholarly journals, all out of the public view. Voodoo science, by contrast, is usually pitched directly to the media, circumventing the normal process of scientific review and debate. ... The result is that a dispro­portionate share of the science seen by the public is flawed.

- "Voodoo Science" by Robert Park, pp26-7

Renal and Urology News August 19, 2009

"... circumcision must be combined with other techniques of HIV prevention, such as safe sex and voluntary testing. It is not sufficient to rely on circumcision alone to prevent HIV transmission."

- Ira Sharlip, MD, a specialist in sexual medicine at Pan Pacific Urology in San Francisco

A traveller came to a farmhouse and offered to make the occupants Nail Soup in return for a night's shelter. He threw a large nail in a pot of boiling water. But he said -
"A nail must be combined with other soup ingredients, such as onions, carrots, meat and seasonings. It is not sufficient to rely on the nail alone to make Nail Soup."

In the morning he went on his way, refreshed after a night in a comfortable bed, minus the nail, with some gold coins in his pocket and the thanks of the family ringing in his ears for the wonderful nail that made such delicious Nail Soup.

So it will be when mass circumcision has been "rolled out" and if there is any dent at all in HIV transmission.

Checklist to determine the relationship between alleged cause and outcome

• What could be other possible causes of an observation?
• Can they be ruled out?
• If not, could they act in concert with the alleged cause, or could they be part of a chain of events with the alleged cause?
• Is there a plausible mechanism linking the alleged cause and outcome?
• Do multiple studies link the alleged cause and outcome? Is the relationship consistent across studies?
• Has the relationship held up across different individuals, locations, and conditions, and over time? If not, is there a logical reason that the relationship does not exist in all cases?
• Are the data being used to describe the relationship statisti­cally significant, meaningful, free of confounding factors, and representative of reality rather than some quirk in the way the data were collected?
• Can the statistics be legitimately applied to the situation at hand?

Lies, Damned Lies and Science
by Sherry Seethaler
Pearson Education, NJ 2009, p110

(The Roman senator Cato was in the habit of ending every speech on any subject with those words - it helped that "must be destroyed" was a single splendid Latin word, "delenda". Eventually the Senate agreed to destroy Carthage, with disastrous consequences for Rome.)

• Any link between circumcision and HIV is statistically quite slight, so the protection would be quite inefficient compared to education in safe-sex practices and a culture of protected or otherwise safe(r) sex.
• The studies are trumpetted by their Relative Risk Reduction (RRR), currently running about 50-60%, but the corresponding Number Needed to Treat (NNT) is much less impressive. (In the latest Uganda study it is 56 circumcisions to prevent one HIV infection per year. That corresponds to 380 circumcisions/infection/year in the US, where AIDS is less prevalent.)
• As each new study corrects the errors of its predecessors, the protection claimed is less. When all the errors are corrected, what effect will be left?

In the case of randomised controlled trials (RCTs),

• While large numbers of men enter a trial, only a very small number are infected, making random errors high.
• The men were randomly assigned to be circumcised or left intact, but they were not a random sample of the population.
  • They were all HIV-negative, meaning they were more likely to have any natural immunity than the rest of the population
  • None were circumcised, meaning certain tribal groups had been selected out.
  • All were willing to be circumcised
  • They were significantly rewarded for taking part, skewing the socio-economic status of the sample
    It may have been impossible to correct for these (since humans are not lab rats), but they are issues none the less.
• Significant numbers of men dropped out of the trials (were "lost to study"). Only those who stay the distance should be counted.
• Those who are circumcised and contract HIV will be more likely to drop out than the others because
  1. they got what they came for but
  2. circumcision didn't protect them, so they would be disillusioned with the trial.
• The three RCTs were cut short: this has reduced their accuracy.
  • The control groups were then offered circumcision, making long-term follow-up impossible.
  • Ethical approval for better studies will be harder to get, making these studies the last word.
• The gold standard of medical testing is the double blind random controlled trial. Circumcision can not be concealed from the experimenter or the subject. The control groups were not given a placebo operation.
• The after-effects of the operation are likely to alter sexual behaviour.
• In an experimental environment, the subjects got counselling and safe-sex advice that would not be available in a mass circumcision campaign.
• The circumcised group had specific instructions to abstain from sex and use condoms that the intact control group does not.
  • Experimenter and circumcision advocate Robert Bailey has admitted that "repeated study visits and intensive behavioural counselling" of the circumcised men were needed to reduce risk behaviours.

If these results are acted on, with mass circumcision campaigns:

• Protection, if any, would be extended to a population, but it would be impossible to convince the average man that circumcision did not confer significant protection on him personally.
• The temptation would be irresistible - especially if he had submitted to a painful operation in adulthood - for a man to say "I'm circumcised, I'm safe".
  • He would be more likely to lean on partners for unprotected sex
  • This disempowers women
• Transmission from man to woman is easier than from woman to man. Circumcision has not been shown to protect women directly.
• Since circumcision desensitises the glans, men circumcised in adulthood would be less willing to use condoms than before.
• If they combine mass circumcision with Abstinence, Be faithful, Condoms, campaigns, as they propose, it will be impossible to tell what is responsible for the outcome: circumcision will be given the credit for any reduction, but will not have to take the blame for any lack of reduction.

National Prevention Information Network
September 17, 2008

'Snip' Protects Some Gay Men from HIV: Study

Findings reported at the Australasian Sexual Health Conference 2008 shed new light on male circumcision’s role in preventing HIV infection.

“We have shown for the first time that [men who have sex with men] who predominantly take on the insertive role in sex are less likely to contract HIV if they’ve been circumcised,” said Dr. David Templeton from the National Center for HIV Epidemiology and Clinical Research in Sydney.

He went on to note, however, “Most HIV infections are contracted in the receptive role, so what we’re talking about is a risk reduction for a small group of men who didn’t have a huge risk in the first place.” In the study, University of New South Wales researchers recruited 1,400 HIV-negative men, two-thirds of whom were circumcised. During the four-year study, 53 men acquired HIV. There was no evidence that circumcision reduced the HIV risk among gay men in general. But in looking at the men who predominantly took the insertive role in intercourse, there was an 85 percent reduction in the risk of HIV infection if they were circumcised. Only seven of the 53 HIV infections occurred among insertive partners; the study’s model indicated that five of these infections could have been avoided if the men had been circumcised.

[No figure for how many of the seven HIV infections were among circumcised insertive men. That's pathetically few to be drawing any statistical conclusions from, and then only of correlation, not causation. Were any of these men circumcised for religious reasons? Factors like that might selectively influence their behaviour, putting them at less risk.]

Templeton was quick to note, however, “That’s only 9 percent of all HIV infections overall that can be attributed to being uncircumcised, not enough to advocate throwing out condoms or advocating widespread circumcision.”

Indeed, the study’s model projected [by multiplying by thousands] that circumcising all Australian gay men would prevent 37 infections a year in the first decade and 57 per year by 2030, at a cost of $196 million (US $153 million) in the first two years.

[No studies have been done of insertive-to-receptive transmission, cut vs intact, but it seems likely the keratinised circumcised penis is more likely to tear the receptive anus or rectum, and there is much anecdotal evidence - and visual evidence from US vs European gay porn - that cut men are rougher, because their fewer nerve-endings need more stimulation. So circumcising insertive men could readily increase HIV transmission to their partners. Yet already this study is being touted as a reason for gay men to get circumcised.]

The study (Gray R et al. Male circumcision and the risks of female HIV and sexually transmitted infections acquisition in Rakai, Uganda. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 128, 2006.) was an attempt to find whether circumcised men were less likely to infect their female partners with HIV.

299 couples where the man was intact were compared with 44 where the man was circumcised. After 30 months (if the pattern of the rest of the study was followed), infection rates were 7 per 100 person-years for the wives of circumcised men and 10 for the wives of intact men. This may look like a protective effect, but in statistical terms, p=0.22, meaning no statistical significance. In real terms, it can be back-calculated that 8 of the wives of circumcised men were infected. If 11 had been, the rate would be the same for both, and that difference of three infections in 30 months is too few to be considered significant.

But the study was widely reported (by Reuters) as showing that all 299 wives of intact men were infected, compared with only 44 wives of circumcised men, as if these were just the small (infected) samples of two much larger and equal samples. This makes the supposed protective effect look much greater.

See the garbled report and the relevant part of a more accurate report.

Why, one wonders, was the study ever published, and why in this very misleading form?

Torture the data

If your results are bad, ask the computer to go back and see if any particular subgroups behaved differently. You might find that your drug works very well in Chinese women aged fifty-two to sixty-one. 'Torture the data and it will confess to anything,' as they say at Guantanamo Bay.

"Bad Science" by Ben Goldacre, Fourth Estate, London (2008), p 210

This is commonly called "data-mining" This cartoon illustrates the principle.

In the following study, the vast majority of the men showed no correlation between intactness and HIV. "Known risk" was defined by the experimenters and left only 50 intact men.

The Journal of Infectious Diseases (impact factor: 5.87). 01/2009; 199(1):59-65. DOI: 10.1086/595569

Male Circumcision and Risk of HIV Infection among Heterosexual African American Men Attending Baltimore Sexually Transmitted Disease Clinics

Lee Warner, Khalil G. Ghanem, Daniel R. Newman, Maurizio Macaluso, Patrick S. Sullivan, and Emily J. Erbelding

Background. Male circumcision has received international attention as an intervention for reducing HIV infection among high-risk heterosexualmen; however, few US studies have evaluated its association with the risk of HIV infection.

Methods. We analyzed visit records for heterosexual African American men who underwent HIV testing while attending sexually transmitted disease (STD) clinics in Baltimore, Maryland, from 1993 to 2000. We used multivariable binomial regression to evaluate associations between circumcision and the risk of HIV infection among visits by patients with known and unknown HIV exposure.

Results. Overall, 1096 (2.7%) of 40,571 clinic visits yielded positive HIV test results. Among 394 visits by [385] patients [fewer than 50 of whom were intact] with known HIV exposure, circumcision was significantly associated with lower HIV prevalence (10.2% vs. 22.0% [i.e. about 11 intact men compared to about 5 who might not have contracted HIV if they had been circumcised]; adjusted prevalence rate ratio [PRR], 0.49 [95% confidence interval [CI], 0.26–0.93]). [The question arises, how can you "adjust" {for age, STDs, year of visit, and clinic location} when you are dealing with only 385 men, and only 50 of them intact.] Conversely, among 40,177 visits by patients with unknown HIV exposure, circumcision was not associated with reduced HIV prevalence (2.5% vs. 3.3%; adjusted PRR, 1.00 [95% CI, 0.86 –1.15]), and age =>25 years old and diagnosis of ulcerative STD were associated with increased prevalence.

Conclusions. Circumcision was associated with substantially reduced HIV risk in patients with known HIV exposure, suggesting that results of other studies demonstrating reduced HIV risk for circumcision among heterosexual men likely can be generalized to the US context. [The suggestion does not follow from the evidence.]

[This study has generated a flurry of headlines like "Circumcision significantly cuts HIV infection risk in heterosexual men" but the key phrase "with known HIV exposure" was usually omitted. ]

A failed prediction is a very solid sign that a pattern is phony. A pattern allows you to make a prediction: ... A false pattern has no predictive power: it might seem to give you a lot of power to understand past data, but it completely breaks down when tested against new data.

- Charles Seife, Proofiness, p56f

Elites TV
December 18, 2010

Male Circumcision in the General Population of Kisumu, Kenya: Beliefs about Protection, Risk Behaviors, HIV, and STIs

Using a population-based survey we 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 understanding [i.e. indoctrination] that circumcised men are less likely to become infected with HIV.

[The study, by Robert Bailey et al. writes off the lack of association to "possible ... limitations in sample size and prevalence." 108 men with sexual experience out of 749 tested HIV+. The circumcision rate was 25% by self-report and 28% by examination. Raw figures for circumcision vs HIV are not given.]

A total of 2585 males over the age of 15 were administered questionnaires and provided specimens for HIV testing. 916 (35.4%) of them said they were circumcised. HIV prevalence among circumcised males was 10.7% and among uncircumcised males was 12.1%, p = 0.9 [i.e. no statistical significance]. Blacks were less likely to be circumcised (28.8%) compared to other racial groups, 42.6%, p = 0.002. When the data was stratified by racial group, circumcised Blacks showed similar rates of HIV as uncircumcised Blacks, (OR: 0.8, p = 0.4) however other racial groups showed a strong protective effect, (OR: 0.3, p = 0.01) [or rather, a correlation]. When the data are further stratified by age of circumcision, there is a slight protective effect [correlation] between early circumcision and HIV among Blacks, OR: 0.7, p = 0.4.
Conclusion In general, circumcision offers slight protection. The effect is much stronger in other racial groups than in blacks. This racial difference cannot be explained by age of circumcision.

HIV and circumcision in South Africa
C.A. Connolly, O. Shisana, L. Simbayi, M. Colvin.
Poster at the XV AIDS Conference in Bangkok [MoPeC3491]

South African Medical Journal, October 2008, Vol. 98, No. 10

Male circumcision and its relationship to HIV infection in South Africa: Results of a national survey in 2002

Catherine Connolly, Leickness C Simbayi, Rebecca Shanmugam, Ayanda Nqeketo

Objective. To investigate the nature of male circumcision and its relationship to HIV infection. Methods. Analysis of a sub-sample of 3 025 men aged 15 years and older who participated in the first national population-based survey on HIV/AIDS in 2002. Chi-square tests and Wilcoxon rank sum tests were used to identify factors associated with circumcision and HIV status, followed by a logistic regression model.

Results. One-third of the men (35.3%) were circumcised. The factors strongly associated with circumcision were age >50, black living in rural areas and speaking SePedi (71.2%) or IsiXhosa (64.3%). The median age was significantly older for blacks (18 years) compared with other racial groups (3.5 years), p <0.001. Among blacks, circumcisions were mainly conducted outside hospital settings. In 40.5% of subjects, circumcision took place after sexual debut; two-thirds of the men circumcised after their 17th birthday were already sexually active. HIV and circumcision were not associated (12.3% HIV positive in the circumcised group v. 12% HIV positive in the uncircumcised group). HIV was, however, significantly lower in men circumcised before 12 years of age (6.8%) than in those circumcised after 12 years of age (13.5%, p=0.02). When restricted to sexually active men, the difference that remained did not reach statistical significance (8.9% v. 13.6%, p=0.08.). There was no effect when adjusted for possible confounding.

Conclusion. Circumcision had no protective effect in the prevention of HIV transmission. This is a concern, and has implications for the possible adoption of the mass male circumcision strategy both as a public health policy and an HIV prevention strategy.

A 2001 study by Bertran Auvert et al (who also ran the 2005 Random Controlled Study) of HIV infection among youth in a South African mining town found it is associated with the Herpes simplex 2 virus

It was "a community-based, cross-sectional study" of a random sample of men (n = 723) and women (n = 784) living in a township in the Carletonville district of South Africa.
Risk factors associated with HIV were recorded by questionnaire and biological tests were performed on serum and urine.
It found that women were much more likely to have HIV (34%) than men (9%) and HSV-2 (53% vs 17%) Two thirds of the 24-year-old women had HIV. Of the men,

Thus, the circumcised men in the study were more likely to be HIV+, but the difference was not statistically significant (the 95% CI straddles 1.0 - in real terms, 10 of the 61 circumcised men had HIV, three more than would be expected if they had the same rate as the intact men) But it certainly casts doubts on the claim that circumcision protects against HIV infection. Typically, Auvert expresses this cautiously, in terms of the prevailing mythology - which he has done so much to promote: "No protective effect of circumcision on HIV prevalence was shown."

Circumcision status and HIV infection among MSM:
reanalysis of a Phase III HIV vaccine clinical trial.

Gust DA, Wiegand RE, Kretsinger K, Sansom S, Kilmarx PH, Bartholow BN, Chen RT.

OBJECTIVE: Determine whether male circumcision would be effective in reducing HIV transmission among men who have sex with men (MSM).

DESIGN: Retrospective analysis of the VAXGen VAX004 HIV vaccine clinical trial data. [Since the men were all volunteers in a vaccine trial, they were not a random sample of the population.]

METHODS: Survival analysis was used to associate time to HIV infection with multiple predictors. Unprotected insertive and receptive anal sex predictors were highly correlated, thus separate models were run.

RESULTS: Four thousand eight hundred and eighty-nine participants were included in this reanalysis; 86.1% were circumcised. Three hundred and forty-two (7.0%) men became infected during the study; 87.4% [4209] were circumcised. [So 680 were intact, of whom only 43 became HIV+, according to this news item, or 6.3%. And the rate among the circumcised men is (342-43)/4209 or 7.1% ] Controlling for demographic characteristics and risk behaviors, in the model that included unprotected insertive anal sex, being uncircumcised was not associated with incident HIV infection [adjusted hazards ratio (AHR) = 0.97, confidence interval (CI) = 0.56-1.68]. Furthermore, while having unprotected insertive (AHR = 2.25, CI = 1.72-2.93) or receptive (AHR = 3.45, CI = 2.58-4.61) anal sex with an HIV-positive partner were associated with HIV infection, the associations between HIV incidence and the interaction between being uncircumcised and reporting unprotected insertive (AHR = 1.78, CI = 0.90-3.53) or receptive (AHR = 1.26, CI = 0.62-2.57) anal sex with an HIV-positive partner were not statistically significant. Of the study visits when a participant reported unprotected insertive anal sex with an HIV-positive partner, HIV infection among circumcised men was reported in 3.16% of the visits (80/2532) and among uncircumcised men in 3.93% of the visits (14/356) [relative risk (RR) = 0.80, CI = 0.46-1.39]. [This is data-mining. The number who knew the HIV+ status of their partners would be a small and random fraction of the total, as the wide Confidence Intervals indicate.]

CONCLUSIONS: Among men who reported unprotected insertive anal sex with HIV-positive partners, being uncircumcised did not confer a statistically significant increase in HIV infection risk [The possiblity that circumcision increases the risk is not considered, even though the figures "trend" that way.]. Additional studies with more incident HIV infections or that include a larger proportion of uncircumcised men may provide a more definitive result.

PMID: 20168206 [PubMed - as supplied by publisher]

"Our finding that 17% of homosexual men with newly acquired HIV infection reported insertive UAI [unprotected anal intercourse] as their highest risk activity suggests that insertive UAI is an important means of HIV transmission in this population. However, we found no association between circumcision status and infection by insertive UAI. In addition, men who had seroconverted despite no reported event of UAI were also no more likely to be uncircumcised. These data strongly suggest that the foreskin is not the main source of HIV infection in homosexual men who become infected by insertive UAI, and that other sites, such as the distal urethra, must be important in HIV infection.

"Our data showing that there is no difference in the circumcision status of men infected by receptive or insertive UAI, in a population with a circumcision prevalence of approximately 75%, suggests that circumcision is not strongly protective against HIV infection in homosexual men. Larger studies, preferably of prospective design, are needed to confirm the absence of a relationship between circumcision and HIV infection risk in gay men. In the meantime, educational messages to homosexual men should continue to emphasize that insertive anal sex is a high-risk activity for HIV transmission whether or not the insertive partner is circumcised."

- Grulich AE, Hendry O, Clark E, Kippax S, Kaldor JM.
Circumcision and male-to-male sexual transmission of HIV.
AIDS 2001 Jun 15;15(9):1188-1189.

A longer-term study of the same men did find significantly less HIV in strictly insertive men ("tops") who were circumcised, but it is based on

"As the minority of HIV infections in H[ealth] I[n ]M[en -a prospective cohort study of homosexual men in Sydney] occurred in those reporting no receptive U[unprotected ]A[mal ]Intercourse ], and most Australian men are circumcised, circumcision is unlikely to have a major impact on HIV incidence in homosexual men in Australia. Nonetheless, 'strategic positioning' when HIV-negative gay men adopt the insertive role in UAI to reduce their HIV risk is occurring commonly among Sydney gay men. This coupled with a rapidly declining prevalence of circumcision in Australian and US homosexual men means circumcision could play a more important role in reducing gay men's susceptibility to HIV infection in the future. Randomized trials are warranted before recommendations can be made regarding circumcision as an HIV prevention intervention among MSM populations, but the design of such studies is challenging. [A Tuskegee-style study would be required] Study populations would require high HIV incidence, low baseline circumcision prevalence and large numbers of participants exclusively or predominantly practising the insertive role. Such attributes are necessary for sufficient study power to detect an association of circumcision status with the relatively infrequent outcome measure of HIV acquisition via insertive anal intercourse."

- Templeton DJ, Jin F, Mao L, Prestage GP, Donovan B, Imrie J, Kippax S, Kaldor JMa, Grulich AE
Circumcision and risk of HIV infection in Australian homosexual men
AIDS 2009 Nov 13:23(17): 2347-2351.

Arch Sex Behav. 2013 Jan 29. [Epub ahead of print]

Circumcision and HIV Infection among Men Who Have Sex with Men in Britain: The Insertive Sexual Role.

Doerner R, McKeown E, Nelson S, Anderson J, Low N, Elford J.

Abstract
The objective was to examine the association between circumcision status and self-reported HIV infection among men who have sex with men (MSM) in Britain who predominantly or exclusively engaged in insertive anal intercourse. In 2007-2008, a convenience sample of MSM living in Britain was recruited through websites, in sexual health clinics, bars, clubs, and other venues. Men completed an online survey which included questions on circumcision status, HIV testing, HIV status, sexual risk behavior, and sexual role for anal sex. The analysis was restricted to 1,521 white British MSM who reported unprotected anal intercourse in the previous 3 months and who said they only or mostly took the insertive role during anal sex. Of these men, 254 (16.7 %) were circumcised. Among men who had had a previous HIV test (n = 1,097), self-reported HIV seropositivity was 8.6 % for circumcised men (17/197) and 8.9 % for uncircumcised men (80/900) (unadjusted odds ratio [OR], 0.97; 95 % confidence interval [95 % CI], 0.56, 1.67). In a multivariable logistic model adjusted for known risk factors for HIV infection, there was no evidence of an association between HIV seropositivity and circumcision status (adjusted OR, 0.79; 95 % CI, 0.43, 1.44), even among the 400 MSM who engaged exclusively in insertive anal sex (adjusted OR, 0.84; 95 % CI, 0.25, 2.81). Our study provides further evidence that circumcision is unlikely to be an effective strategy for HIV prevention among MSM in Britain.

Sex Transm Dis. 2009 Nov 6. [Epub ahead of print]

The [Lack of] Association Between Lack of Circumcision and HIV, HSV-2, and Other Sexually Transmitted Infections Among Men Who Have Sex With Men.

Jameson DR, Celum CL, Manhart L, Menza TW, Golden MR. BACKGROUND:: Observational studies evaluating the association of circumcision and HIV infection among men who have sex with men (MSM) have yielded mixed results. We examined the relationship between circumcision and HIV, herpes simplex virus type-2 (HSV-2), syphilis, urethral gonorrhea, and urethral chlamydia among MSM stratified by anal sexual role.

METHODS:: Between October 2001 and May 2006, 4749 MSM who reported anal intercourse in the previous 12 months attended the Public Health-Seattle and King County STD clinic for 8337 evaluations. Clinicians determined circumcision status by examination and anal sexual role in the previous year by interview. Blood samples were used to test HIV, syphilis, and HSV-2 serostatus. Urethral gonorrhea and chlamydia were tested by culture or nucleic acid amplification. We used generalized estimating equations to evaluate the association between circumcision and specific diagnoses, adjusted for race/ethnicity and age.

RESULTS:: Among the 3828 men whose circumcision status was assessed, 3241 (85%) were circumcised and 587 (15%) were not. The proportion of men newly testing HIV-positive or with previously diagnosed HIV did not differ by circumcision status when stratified by men's anal sexual role in the preceding year, even when limited to men who reported only insertive anal intercourse in the preceding 12 months (OR = 1.45; 95% CI: 0.30, 7.12). Similarly, we did not observe a significant association between circumcision status and the other sexually transmitted infections (STI).

CONCLUSIONS:: Our findings suggest that male circumcision would not be likely to have a significant impact on HIV or sexually transmitted infections acquisition among MSM in Seattle. PMID: 19901865 [PubMed - as supplied by publisher]

AIDS Patient Care and STDs

Relations Between Circumcision Status, Sexually Transmitted Infection History, and HIV Serostatus Among a National Sample of Men Who Have Sex with Men in the United States

Kristen Jozkowski, Joshua G. Rosenberger, Vanessa Schick, Debby Herbenick, David S. Novak, Michael Reece. AIDS Patient Care and STDs. August 2010, 24(8): 465-470.

Abstract
Circumcision's potential link to HIV/sexually transmitted infections (STI) has been at the center of recent global public health debates. However, data related to circumcision and sexual health remain limited, with most research focused on heterosexual men. This study sought to assess behavioral differences among a large sample of circumcised and noncircumcised men who have sex with men (MSM) in the United States. Data were collected from 26,257U.S. MSM through an online survey. [An online survey is a population sample of unknown randomness.] Measures included circumcision status, health indicators, HIV/STI screening and diagnosis, sexual behaviors, and condom use. Bivariate and regression analyses were conducted to determine differences between HIV/STI status, sexual behaviors, and condom use among circumcised and noncircumcised men. Circumcision status did not significantly predict HIV testing (p>0.05), or HIV serostatus (p>0.05), and [there were no significant differences based on circumcision status for most STI diagnosis [syphilis, gonorrhea, chlamydia, human papilloma virus (HPV)]. Being noncircumcised was predictive of herpes-2 diagnosis, however, condom use mediated this relationship.] [That is, circumcised men were more likely to use condoms, and it was this that protected them from herpes, not being circumcised. This suggests that being circumcised increased their risk of the other STIs.] These data provide one of the first large national assessments of circumcision among MSM. While being noncircumcised did not increase the likelihood of HIV and most STI infections, results indicated that circumcision was associated with higher rates of condom use, suggesting that those who promote condoms among MSM may need to better understand condom-related behaviors and attitudes among noncircumcised men to enhance the extent to which they are willing to use condoms consistently.

JAIDS
December 15, 2007

Circumcision Status and HIV Infection Among Black and Latino Men Who Have Sex With Men in 3 US Cities.

Millett, Gregorio A; Ding, Helen; Lauby, Jennifer; Flores, Stephen; Stueve, Ann; Bingham, Trista; Carballo-Dieguez, Alex; Murrill, Chris; Liu, Kai-Lih; Wheeler, Darrell; Liau, Adrian; Marks, Gary

Abstract:
Objective: To examine characteristics of circumcised and uncircumcised Latino and black men who have sex with men (MSM) in the United States and assess the association between circumcision and HIV infection.

Methods: Using respondent-driven sampling, 1154 black MSM and 1091 Latino MSM were recruited from New York City, Philadelphia, and Los Angeles. A 45-minute computer-assisted interview and a rapid oral fluid HIV antibody test (OraSure Technologies, Bethlehem, PA) were administered to participants.

Results: Circumcision prevalence was higher among black MSM than among Latino MSM (74% vs. 33%; P < 0.0001). Circumcised MSM in both racial/ethnic groups were more likely than uncircumcised MSM to be born in the United States or to have a US-born parent. Circumcision status was not associated with prevalent HIV infection among Latino MSM, black MSM, black bisexual men, or black or Latino men who reported being HIV-negative based on their last HIV test. Further, circumcision was not associated with a reduced likelihood of HIV infection among men who had engaged in unprotected insertive and not unprotected receptive anal sex. [Yet the protection claim is made exclusively about insertive {vaginal} sex.]

Conclusions: In these cross-sectional data, there was no evidence that being circumcised was protective against HIV infection among black MSM or Latino MSM.

JAIDS Journal of Acquired Immune Deficiency Syndromes. 46(5):643-650, December 15, 2007.

Sex Transm Infect. 2010 Jun 30

Circumcision among men who have sex with men in Scotland: limited potential for HIV prevention. McDaid LM, Weiss HA, Hart GJ.

Abstract
Objective Male circumcision has been shown to reduce the risk of HIV acquisition among heterosexual men but the impact among men who have sex with men (MSM) is not known. In this paper, we explore the feasibility of research into circumcision for HIV prevention among MSM in Scotland.
Methods Anonymous, self-complete questionnaires and Orasure oral fluid collection kits were distributed to men visiting the commercial gay scenes in Glasgow and Edinburgh.
Results 1508 men completed questionnaires (70.5% response rate) and 1277 provided oral fluid samples (59.7% response rate). Overall, 1405 men were eligible for inclusion in the analyses. 16.6% reported having been circumcised. HIV prevalence was similar among circumcised and uncircumcised men (4.2% and 4.6%, respectively). Although biologically, circumcision is most likely to protect against HIV for men practising unprotected insertive anal intercourse (UIAI), only 7.8% (91/1172) of uncircumcised men reported exclusive UIAI in the past 12 months. Relatively few men reported being willing to participate in a research study on circumcision and HIV prevention (13.9%), and only 11.3% of uncircumcised men did so. Conclusion The lack of association between circumcision and HIV status, low levels of exclusive UIAI, and low levels of willingness to take part in circumcision research studies suggest circumcision is unlikely to be a feasible HIV prevention strategy for MSM in the UK. Behaviour change should continue to be the focus of HIV prevention in this population.

PMID: 20595141

The Lancet, Volume 374, Issue 9685, Pages 229 - 237, 18 July 2009

Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial

Dr, Prof Maria J Wawer MD, Frederick Makumbi PhD, Godfrey Kigozi MBChB, David Serwadda MMed, Stephen Watya MMed, Fred Nalugoda MHS, Dennis Buwembo MBChB, Victor Ssempijja ScM, Noah Kiwanuka MBChB, Prof Lawrence H Moulton PhD, Nelson K Sewankambo MMed, Steven J Reynolds MD, Thomas C Quinn MD, Pius Opendi MBChB, Boaz Iga MSc, Renee Ridzon MD, Oliver Laeyendecker MBA, Prof Ronald H Gray MD

Summary
Background
Observational studies have reported an association between male circumcision and reduced risk of HIV infection in female partners. We assessed whether circumcision in HIV-infected men would reduce transmission of the virus to female sexual partners.

Methods
922 uncircumcised, HIV-infected, asymptomatic men aged 15-49 years with CD4-cell counts 350 cells per ?L or more were enrolled in this unblinded, randomised controlled trial in Rakai District, Uganda. Men were randomly assigned by computer-generated randomisation sequence to receive immediate circumcision (intervention; n=474) or circumcision delayed for 24 months (control; n=448). HIV-uninfected female partners of the randomised men were concurrently enrolled (intervention, n=93; control, n=70) and followed up at 6, 12, and 24 months, to assess HIV acquisition by male treatment assignment (primary outcome). A modified intention-to-treat (ITT) analysis, which included all concurrently enrolled couples in which the female partner had at least one follow-up visit over 24 months, assessed female HIV acquisition by use of survival analysis and Cox proportional hazards modelling. This trial is registered with ClinicalTrials.gov, number NCT00124878.

Findings
The trial was stopped early because of futility. [That is, it failed to find any protection. It might have shown increased risk, but they weren't interested in that.] 92 couples in the intervention group and 67 couples in the control group were included in the modified ITT analysis. 17 (18%) women in the intervention group and eight (12%) women in the control group acquired HIV during follow-up (p=0.36). Cumulative probabilities of female HIV infection at 24 months were 21.7% (95% CI 12.7-33.4) in the intervention group and 13.4% (6.7-25.8) in the control group (adjusted hazard ratio 1.49, 95% CI 0.62-3.57; p=0.368).

Interpretation
Circumcision of HIV-infected men did not reduce HIV transmission to female partners over 24 months; longer-term effects could not be assessed. Condom use after male circumcision is essential for HIV prevention.

Funding
Bill & Melinda Gates Foundation with additional laboratory and training support from the National Institutes of Health and the Fogarty International Center.

A YouTube video of Maria Wawer describing the experiment

Author: Turner AN | Morrison CS | Padian NS | Kaufman JS | Salata RA

Source: AIDS. 2007 Aug 20;21(13):1779-1789.

Abstract: The objective was to assess whether male circumcision of the primary sex partner is associated with women's risk of HIV. Data were analyzed from 4417 Ugandan and Zimbabwean women participating in a prospective study of hormonal contraception and HIV acquisition. Most were recruited from family planning clinics; some in Uganda were referred from higher-risk settings such as sexually transmitted disease clinics. Using Cox proportional hazards models, time to HIV acquisition was compared for women with circumcised or uncircumcised primary partners. Possible misclassification of male circumcision was assessed using sensitivity analysis. At baseline, 74% reported uncircumcised primary partners, 22% had circumcised partners and 4% had partners of unknown circumcision status. Median follow-up was 23 months, during which 210 women acquired HIV (167, 34, and 9 women whose primary partners were uncircumcised, circumcised, or of unknown circumcision status, respectively). Although unadjusted analyses indicated that women with circumcised partners had lower HIV risk than those with uncircumcised partners, the protective effect disappeared after adjustment for other risk factors [hazard ratio (HR), 1.03; 95% confidence interval (CI), 0.69-1.53]. Subgroup analyses suggested a non-significant protective effect of male circumcision on HIV acquisition among Ugandan women referred from higher-risk settings: adjusted HR 0.16 (95% CI, 0.02-1.25) but little effect in Ugandans (HR, 1.33; 95% CI, 0.72-2.47) or Zimbabweans (HR, 1.12; 95% CI, 0.65-1.91) from family planning clinics. After adjustment, male circumcision was not significantly associated with women's HIV risk. The potential protection offered by male circumcision for women recruited from high-risk settings warrants further investigation. (author's)

Date Posted: 3 September 2007

AIDS. 2009 Dec 29. [Epub ahead of print]

Male circumcision and risk of male-to-female HIV-1 transmission: a multinational prospective study in African HIV-1-serodiscordant couples.

Baeten JM, Donnell D, Kapiga SH, Ronald A, John-Stewart G, Inambao M, Manongi R, Vwalika B, Celum C; for the Partners in Prevention HSV/HIV Transmission Study Team.

OBJECTIVE:: Male circumcision reduces female-to-male HIV-1 transmission risk by approximately 60%. Data assessing the effect of circumcision on male-to-female HIV-1 transmission are conflicting, with one observational study among HIV-1-serodiscordant couples showing reduced transmission but a randomized trial suggesting no short-term benefit of circumcision.

[Suggesting an increased risk, actually]

DESIGN/METHODS:: Data collected as part of a prospective study among African HIV-1-serodiscordant couples were analyzed for the relationship between circumcision status of HIV-1-seropositive men and risk of HIV-1 acquisition among their female partners. Circumcision status was determined by physical examination. Cox proportional hazards analysis was used.

RESULTS:: A total of 1096 HIV-1-serodiscordant couples in which the male partner was HIV-1-infected were followed for a median of 18 months; 374 (34%) male partners were circumcised. Sixty-four female partners seroconverted to HIV-1 (incidence 3.8 per 100 person-years). [It would be useful to know the raw figures, circumcised vs intact partners, at this point.] Circumcision of the male partner was associated with a nonstatistically significant approximately 40% lower risk of HIV-1 acquisition by the female partner (hazard ratio 0.62, 95% confidence interval 0.35-1.10, P = 0.10). [Translation: no protection.] The magnitude of this effect was similar when restricted to the subset of HIV-1 transmission events confirmed by viral sequencing to have occurred within the partnership (n = 50, hazard ratio 0.57, P = 0.11), after adjustment for male partner plasma HIV-1 concentrations (hazard ratio 0.60, P = 0.13), and when excluding follow-up time for male partners who initiated antiretroviral therapy (hazard ratio 0.53, P = 0.07). [Translation: data-mining failed to find an effect.]

CONCLUSION:: Among HIV-1-serodiscordant couples in which the HIV-1-seropositive partner was male, we observed no increased risk and potentially decreased risk from circumcision on male-to-female transmission of HIV-1.

[An attempt to snatch victory from the jaws of defeat. The risk was not decreased.]

PMID: 20042848 [PubMed - as supplied by publisher]

Int J Epidemiol. 1994 Apr;23(2):371-80.

Risk factors associated with prevalent HIV-1 infection among pregnant women in Rwanda.
National University of Rwanda-Johns Hopkins University AIDS Research Team.
Chao A, Bulterys M, Musanganire F, Habimana P, Nawrocki P, Taylor E, Dushimimana A, Saah A.
Department of Epidemiology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205.

Abstract: This study evaluated risk factors associated with prevalent HIV-1 infection among pregnant women in a semi-rural but densely populated area surrounding the town of Butare in Rwanda. Overall seroprevalence was 9.3% in 5690 pregnant women who sought antenatal care at one of five health centres. Factors associated with higher seroprevalence of HIV-1 included history of multiple sexual partners, history of at least one sexually transmitted disease (STD), relatively high socioeconomic status (SES), being unmarried, young age at first pregnancy, and low gravidity. Women who had used oral contraceptives, smoked more than one cigarette per day, whose partners were circumcised, and had had sex to support themselves were also at higher risk of being infected. A history of blood transfusion in the past 5 years was not associated with HIV-1 infection. History of multiple sexual partners, history of STD, high household income, partner circumcision, and past oral contraceptive use remained strongly associated with HIV-1 infection even when simultaneously controlling for other covariates. Among legally married women who lacked sexual behaviour risk factors, history of STD, high SES, young age at first pregnancy, and low gravidity were significantly associated with HIV-1 seroprevalence.

PMID: 8082965 [PubMed - indexed for MEDLINE]

International AIDS Society

Prevalence of male circumcision and its association with HIV and sexually transmitted infections in a U.S. navy population
A G Thomas, L N Bakhireva, S K Brodine, R A Shaffer
Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. TuPeC4861.

Background: Lack of male circumcision has been found to be a risk factor for HIV and sexually transmitted infection (STI) in several studies performed in developing countries. However, the few studies conducted in developed nations have yielded inconsistent results. Policy regarding circumcision of male infants as a prevention measure against HIV/STI remains a controversial topic. This study describes the prevalence of circumcision and its association with HIV and STI in a U.S. military population.

Methods: This is a case-control study of male HIV infected U.S. military personnel (n= 232) recruited from 7 military medical centers and male U.S. Navy controls (n=516) from a general aircraft carrier population. Cases and controls completed similar self-administered HIV behavioral risk surveys. Case circumcision status was abstracted from medical charts while control status was reported on the survey. Cases and controls were frequency matched on age. Multiple logistic regressions were constructed separately to evaluate the role of circumcision in the acquisition of HIV and STI.

Results: The proportion of circumcised men did not significantly differ between cases (84.9%) and controls (81.8%). Prevalence of circumcision among men born in the U.S. was higher (85.0%) than those born elsewhere (58.1%). After adjustment for demographic and behavioral risk factors lack of circumcision was not found to be a risk factor for HIV (OR = 0.9; 95% CI: 0.51, 1.7) or STI (OR = 1.08; 95% CI 0.52, 2.26). The odds of HIV infection were 2.6 higher for irregular condom users, 5 times as high for those reporting STI, 6.2 times higher for those reporting anal sex, 2.8-3.2 times higher for those with 2-7+ partners, nearly 3 times higher for Blacks, and 3.5 times as high for men who were single or divorced/separated.

Conclusions: 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.

J Acquir Immune Defic Syndr. 2007 Aug 1;45(4):371-9.
The protective effect of circumcision on HIV incidence in rural low-risk men circumcised predominantly by traditional circumcisers in Kenya: two-year follow-up of the Kericho HIV Cohort Study.
Shaffer DN, Bautista CT, Sateren WB, Sawe FK, Kiplangat SC, Miruka AO, Renzullo PO, Scott PT, Robb ML, Michael NL, Birx DL.
US Army Medical Research Unit, Walter Reed Project HIV Program, Kericho, Kenya. dshaffer@wrp-kch.org

BACKGROUND: Three randomized controlled trials (RCTs) have demonstrated that male circumcision prevents female-to-male HIV transmission in sub-Saharan Africa. Data from prospective cohort studies are helpful in considering generalizability of RCT results to populations with unique epidemiologic/cultural characteristics.

METHODS: Prospective observational cohort sub-analysis. A total of 1378 men were evaluated after 2 years of follow-up. Baseline sociodemographic and behavioral/HIV risk characteristics were compared between 270 uncircumcised and 1108 circumcised men. HIV incidence rates (per 100 person-years) were calculated, and Cox proportional hazards regression analyses estimated hazard rate ratios (HRs).

RESULTS: Of the men included in this study, 80.4% were circumcised; 73.9% were circumcised by traditional circumcisers. Circumcision was associated with tribal affiliation, high school education, fewer marriages, and smaller age difference between spouses (P < 0.05). After 2 years of follow-up, there were 30 HIV incident cases (17 in circumcised and 13 in uncircumcised men). Two-year HIV incidence rates were 0.79 (95% confidence interval [CI]: 0.46 to 1.25) for circumcised men and 2.48 (95% CI: 1.33 to 4.21) for uncircumcised men corresponding to a HR = 0.31 (95% CI: 0.15 to 0.64). In one model controlling for sociodemographic factors, the HR increased and became non-significant (HR = 0.55; 95% CI: 0.20 to 1.49).

CONCLUSIONS: Circumcision by traditional circumcisers offers protection [That's not what "non-significant" means.] from HIV infection in adult men in rural Kenya. Data from well-designed prospective cohort studies in populations with unique cultural characteristics can supplement RCT data in recommending public health policy. PMID: 17558336 [PubMed - indexed for MEDLINE]

Declining Rates in Male Circumcision amidst Increasing Evidence of its Public Health Benefit

Mor Z, Kent CK, Kohn RP, Klausner JD (2007) Benefit. PLoS ONE 2(9):

The study objective was to describe male circumcision trends among men attending the San Francisco municipal STD clinic, and to correlate the findings with HIV, syphilis and sexual orientation.
Methods and Findings. A cross sectional study was performed by reviewing all electronic records of males attending the San Francisco municipal STD clinic between 1996 and 2005. The prevalence of circumcision over time and by subpopulation such as race/ethnicity and sexual orientation were measured. The findings were further correlated with the presence of syphilis and HIV infection. Circumcision status was determined by physical examination and disease status by clinical evaluation with laboratory confirmation.

Among 58,598 male patients, 32,613 (55.7%, 95% Confidence Interval (CI) 55.2–56.1) were circumcised. Male circumcision varied significantly by decade of birth (increasing between 1920 and 1950 and declining overall since the 1960’s), race/ethnicity (Black: 62.2%, 95% CI 61.2–63.2, White: 60.0%, 95% CI 59.46– 60.5, Asian Pacific Islander: 48.2%, 46.9–49.5 95% CI, and Hispanic: 42.2%, 95% CI 41.3–43.1), and sexual orientation (gay/ bisexual: 73.0%, 95% CI 72.6–73.4; heterosexual: 66.0%, 65.5–66.5).

Male circumcision may [or, equally, may not] have been modestly protective against syphilis in HIV-uninfected heterosexual men (PR 0.92, 95% C.I. 0.83–1.02, P = 0.06) . [No correlations were found between circumcision and HIV or syphilis in any of the groups of men studied, but the paper tries its best to make it look as if they were]

From the Results:

Table 2. Percent circumcised in those with and without syphilis infection by HIV status and sexual orientation, as determined during male patient visits, San Francisco municipal STD clinic, 1996-2005.
Sexual orientation	Syphilis infection	HIV-infected				HIV-uninfected
		Circumcised %	(n/N)	PR*	(95% CI)	Circumcised %	(n/N)	PR	(95% CI)
Heterosexual	Yes	62.5	(10/16)	0.85	(0.40-1.56)	66.7	(384/576)	0.92	(0.83-1.02)
	No	73.8	(1,050/1,423)	Ref.		72.4	(36,290/50,128)	Ref.
Gay/ bisexual	Yes	75.8	(214/282)	1.0	(0.87-1.15)	72.7	(384/528)	0.98	(0.88-1.08)
	No	75.4	(15,910/21,090)	Ref.		74.6	(34,210/45,869)	Ref.
*PR = Prevalence ratio of circumcision status by syphilis infection (Yes/No) Table 2 shows the proportion of visits by circumcised men at the San Francisco municipal STD clinic from 1996 through 2005 by sexual orientation, syphilis and HIV infection status. There was a trend towards a protective effect of circumcision for syphilis infection in heterosexual HIV-uninfected men and in a lesser extent in HIV-infected men. Among gay/bisexual men, no such protective effect was seen and also no association was found between circumcision status and HIV infection (71.1% circumcised versus 72.2%, PR = 0.97, 95% CI 0.90-1.0, P =0.52).

Conclusions. Male circumcision was common among men seeking STD services in San Francisco but has declined substantially in recent decades. Male circumcision rates differed by race/ethnicity and sexual orientation. Given recent studies suggesting the public health benefits of male circumcision, a reconsideration of national male circumcision policy is needed to respond to current trends.

[And therefore Carthage must be destroyed. The conclusion does not follow at all from the data.

"A trend towards a protective effect" is weasel wording for no correlation.

However, none of the ratios is statistically significant.

Considering HIV, in every row except the first, the percentage on the right (circumcised men with HIV) is greater than the percentage on the left (intact men with HIV), and in the first row, there are only six intact (heterosexual) men with HIV (and syphilis). Here is a different presentation of the same data:

In all classes except the first, men with HIV are very slightly more likely to be circumcised than men without HIV, but in no class does the difference reach statistical significance. (And in the first class - because only six of the men with HIV were intact - if one more HIV+ man had been circumcised, that ratio would also have been greater than 1:1.)

There are other problems with this paper. According to its Table 1 there were 15,515 intact men, while according to Table 2 intact men paid only 14,409 visits to the clinic.

A published response to the paper

Circumcision Among Men Who Have Sex with Men in London, United Kingdom: An Unlikely Strategy for HIV Prevention

Abstract

Male circumcision is unlikely to be a workable HIV prevention strategy among London MSM, the current study suggests. The team undertook the research to explore attitudes about circumcision among MSM in London and to assess the feasibility of conducting research on circumcision and HIV prevention among these men. In May and June 2008, a convenience sample of MSM visiting gyms in central London completed a confidential, self-administered questionnaire. The information collected included demographic characteristics, self-reported HIV status, sexual behavior, circumcision status, attitudes about circumcision, and willingness to take part in research on circumcision and HIV prevention. Among the 653 participants, 29 percent reported they were circumcised. HIV prevalence among the MSM was 23.3 percent and did not differ significantly between circumcised (18.6 percent) and uncircumcised (25.2 percent) men (adjusted odds ratio=0.79; 95 percent confidence interval: 0.50-1.26). The proportion of participants reporting unprotected anal intercourse in the past three months was similar in the circumcised (38.8 percent) and uncircumcised (36.7 percent) groups (AOR=1.06; 95 percent CI: 0.72-1.55). The uncircumcised MSM were [much] less likely to think there were benefits to being circumcised compared to the circumcised men (31.2 percent vs. 65.4 percent, P<0.001). Just 10.3 percent of the uncircumcised men indicated a willingness to take part in research on circumcision as a strategy to prevent HIV transmission.

“Most uncircumcised MSM in this London survey were unwilling to participate in research on circumcision and HIV prevention,” the authors concluded. “Only a minority of uncircumcised men thought that there were benefits of circumcision. It is unlikely that circumcision would be a feasible strategy for HIV prevention among MSM in London.”

Source http://www.stdjournal.com Date of Publication 10//2011

Author

Alicia C. Thornton; Samuel Lattimore; Valerie Delpech; Helen A. Weiss; Jonathan Elford

-

The Bagisu people of Eastern Uganda circumcise boys aged 12-18 years. The cultural practices associated with circumcision are a risk to HIV transmission. HIV transmission awareness programmes have been running in the local media but the message is mainly perceived by urban, literate people. The researchers found it is hard to change the attitude of the Bagisu towards their cultural circumcision practices despite the risks.

A. Kataami Moiti. Joint Clinical Research Centre, Kampala, Uganda
The Importance of education in addressing risk factors associated with cultural circumcision practices among Bagisu community, Uganda
Poster at the XV AIDS Conference in Bangkok, July 2004 [ThPeC7544]

WebmedCentral EPIDEMIOLOGY 2011;2(9):WMC002206

Scarification and Male Circumcision Associated with HIV Infection in Mozambican Children and Youth

By Dr. Devon D Brewer

Abstract

Background: In sub-Saharan Africa, significant numbers of children with seronegative mothers are HIV infected. Similarly, substantial proportions of African youth who have not had sex are infected with HIV. These findings imply that some African children and youth acquire HIV through blood exposures in unhygienic healthcare, cosmetic care, and rituals. In prior research, male and female Kenyan, Lesothoan, and Tanzanian adolescents and virgins who were circumcised were more likely to be infected with HIV than their uncircumcised counterparts.

Methods: I examined the association between male circumcision, scarification, and HIV infection in Mozambican children and youth with data from the 2009 Mozambique AIDS Indicator Survey. I excluded from analysis children under age 12 who had HIV seropositive biological mothers. I coded children and youth as exposed to circumcision or scarification only if it had occurred within the prior 10 years.

Results: Circumcised and scarified children and youth were two to three times more likely to be infected with HIV than children and youth who had not been circumcised or scarified, respectively. Circumcision and scarification were each associated with HIV infection for both virgins and sexually experienced youth. Males circumcised by medical doctors were almost as likely to be infected as those circumcised by traditional circumcisers. Circumcision and scarification were also independently associated with HIV infection in males.

Conclusions: To determine modes of HIV transmission with confidence, researchers must employ more rigorous research designs than have been used to date in sub-Saharan Africa. In the meantime, Mozambicans and other Africans should be warned about all risks of blood-borne HIV transmission, including scarification and medical and traditional circumcision, and informed about how these risks can be avoided.

-

Australian and New Zealand Journal of Public Health, 35: 459–465.
doi: 10.1111/j.1753-6405.2011.00761.x

Not a surgical vaccine: there is no case for boosting infant male circumcision to combat heterosexual transmission of HIV in Australia
Robert Darby, Robert Van Howe

Abstract

Objective: To conduct a critical review of recent proposals that widespread circumcision of male infants be introduced in Australia as a means of combating heterosexually transmitted HIV infection.

Approach: These arguments are evaluated in terms of their logic, coherence and fidelity to the principles of evidence-based medicine; the extent to which they take account of the evidence for circumcision having a protective effect against HIV and the practicality of circumcision as an HIV control strategy; the extent of its applicability to the specifics of Australia's HIV epidemic; the benefits, harms and risks of circumcision; and the associated human rights, bioethical and legal issues.

Conclusion: Our conclusion is that such proposals ignore doubts about the robustness of the evidence from the African random-controlled trials as to the protective effect of circumcision and the practical value of circumcision as a means of HIV control; misrepresent the nature of Australia's HIV epidemic and exaggerate the relevance of the African random-controlled trials findings to it; underestimate the risks and harm of circumcision; and ignore questions of medical ethics and human rights. The notion of circumcision as a ‘surgical vaccine’ is criticised as polemical and unscientific.

Implications: Circumcision of infants or other minors has no place among HIV control measures in the Australian and New Zealand context; proposals such as these should be rejected.

J Sex Med. 2012 Aug 15. doi: 10.1111/j.1743-6109.2012.02871.x. [Epub ahead of print]

More than Foreskin: Circumcision Status, History of HIV/STI, and Sexual Risk in a Clinic-Based Sample of Men in Puerto Rico.

Rodriguez-Diaz CE, Clatts MC, Jovet-Toledo GG, Vargas-Molina RL, Goldsamt LA, García H.

Abstract

Introduction. Circumcision among adult men has been widely promoted as a strategy to reduce human immunodeficiency virus (HIV) transmission risk. However, much of the available data derive from studies conducted in Africa, and there is as yet little research in the Caribbean region where sexual transmission is also a primary contributor to rapidly escalating HIV incidence.

Aim. In an effort to fill the void of data from the Caribbean, the objective of this article is to compare history of sexually transmitted infections (STI) and HIV diagnosis in relation to circumcision status in a clinic-based sample of men in Puerto Rico.

Methods. Data derive from an ongoing epidemiological study being conducted in a large STI/HIV prevention and treatment center in San Juan in which 660 men were randomly selected from the clinic's waiting room.

Main Outcome Measures. We assessed the association between circumcision status and self-reported history of STI/HIV infection using logistic regressions to explore whether circumcision conferred protective benefit.

Results. Almost a third (32.4%) of the men were circumcised (CM). Compared with uncircumcised (UC) men, CM have accumulated larger numbers of STI in their lifetime (CM = 73.4% vs. UC = 65.7%; P = 0.048), have higher rates of previous diagnosis of warts (CM = 18.8% vs. UC = 12.2%; P = 0.024), and were more likely to have HIV infection (CM = 43.0% vs. UC = 33.9%; P = 0.023). Results indicate that being CM predicted the likelihood of HIV infection (P value = 0.027).

...

Risk factors for HIV infection among circumcised men in Uganda: a case-control study
Michael Ediau, Joseph KB Matovu, Raymond Byaruhanga, Nazarius M Tumwesigye, Rhoda K Wanyenze
[None of the usual suspects for Uganda, Bailey, Quinn or Wawer]

Abstract

Introduction: Male circumcision (MC) reduces the risk of HIV infection. [Om mane padme hum] However, the risk reduction effect of MC can be modified by type of circumcision (medical, traditional and religious) and sexual risk behaviours post-circumcision. Understanding the risk behaviours associated with HIV infection among circumcised men (regardless of form of circumcision) is critical to the design of comprehensive risk reduction interventions. This study assessed risk factors for HIV infection among men circumcised through various circumcision approaches.

Methods: This was a case-control study which enrolled 155 cases (HIV-infected) and 155 controls (HIV-uninfected), all of whom were men aged 18–35 years presenting at the AIDS Information Center for HIV testing and care. The outcome variable was HIV sero-status. Using SPSS version 17, multivariable logistic regression was performed to identify factors independently associated with HIV infection.

Results: Overall, 83.9% among cases and 56.8% among controls were traditionally circumcised; 7.7% of cases and 21.3% of controls were religiously circumcised while 8.4% of cases and 21.9% of controls were medically circumcised. A higher proportion of cases than controls reported resuming sexual intercourse before complete wound healing (36.9% vs. 14.1%; p<0.01). Risk factors for HIV infection prior to circumcision were:being in a polygamous marriage (AOR: 6.6, CI: 2.3–18.8) and belonging to the Bagisu ethnic group (AOR: 6.1, CI: 2.6–14.0). After circumcision, HIV infection was associated with: being circumcised at >18 years (AOR: 5.0, CI: 2.4–10.2); resuming sexual intercourse before wound healing (AOR: 3.4, CI: 1.6–7.3); inconsistent use of condoms (AOR: 2.7, CI: 1.5–5.1); and having sexual intercourse under the influence of peers (AOR: 2.9, CI: 1.5–5.5). Men who had religious circumcision were less likely to have HIV infection (AOR: 0.4, 95% CI: 0.2–0.9) than the traditionally circumcised but there was no statistically significant difference between those who were traditionally circumcised and those who were medically circumcised (AOR: 0.40, 95% CI: 0.1–1.1). [So much for the claim that medical genital cutting protects more than traditional - which was used to explain the complete lack of connection between cutting and HIV that USAID found.]

Conclusions: Being circumcised at adulthood, resumption of sexual intercourse before wound healing, inconsistent condom use and having sex under the influence of peers were significant risk factors for HIV infection. Risk reduction messages should address these risk factors, especially among traditionally circumcised men.

[Why especially them? They've just established that traditional cutting is no different from medical cutting! Or are they admitting that it's the accidental circumstances around medical cutting, the setting, the indoctrination, the "medical ritual" that impresses the safe sex message on those men, and it is really acting on that message that protects them, and not the cutting itself?]

PLOS Medicine

HIV Shedding from Male Circumcision Wounds in HIV-Infected Men: A Prospective Cohort Study

Aaron A. R. Tobian, Godfrey Kigozi, Jordyn Manucci, Mary K. Grabowski, David Serwadda, Richard Musoke, Andrew D. Redd, Fred Nalugoda, Steven J. Reynolds, Nehemiah Kighoma, Oliver Laeyendecker, Justin Lessler, Ronald H. Gray, [ ... ],

Published: April 28, 2015

DOI: 10.1371/journal.pmed.1001820

Abstract

Background
A randomized trial of voluntary medical male circumcision (MC) of HIV—infected men reported increased HIV transmission to female partners among men who resumed sexual intercourse prior to wound healing. We conducted a prospective observational study to assess penile HIV shedding after MC.

Methods and Findings
HIV shedding was evaluated among 223 HIV—infected men (183 self—reported not receiving antiretroviral therapy [ART], 11 self—reported receiving ART and had a detectable plasma viral load [VL], and 29 self—reported receiving ART and had an undetectable plasma VL [<400 copies/ml]) in Rakai, Uganda, between June 2009 and April 2012. Preoperative and weekly penile lavages collected for 6 wk and then at 12 wk were tested for HIV shedding and VL using a real—time quantitative PCR assay. Unadjusted prevalence risk ratios (PRRs) and adjusted PRRs (adjPRRs) of HIV shedding were estimated using modified Poisson regression with robust variance. HIV shedding was detected in 9.3% (17/183) of men not on ART prior to surgery and 39.3% (72/183) of these men during the entire study. Relative to baseline, the proportion shedding was significantly increased after MC at 1 wk (PRR = 1.87, 95% CI = 1.12–3.14, p = 0.012), 2 wk (PRR = 3.16, 95% CI = 1.94–5.13, p < 0.001), and 3 wk (PRR = 1.98, 95% CI = 1.19–3.28, p = 0.008) after MC. However, compared to baseline, HIV shedding was decreased by 6 wk after MC (PRR = 0.27, 95% CI = 0.09–0.83, p = 0.023) and remained suppressed at 12 wk after MC (PRR = 0.19, 95% CI = 0.06–0.64, p = 0.008). Detectable HIV shedding from MC wounds occurred in more study visits among men with an HIV plasma VL > 50,000 copies/ml than among those with an HIV plasma VL < 400 copies/ml (adjPRR = 10.3, 95% CI = 4.25–24.90, p < 0.001). Detectable HIV shedding was less common in visits from men with healed MC wounds compared to visits from men without healed wounds (adjPRR = 0.12, 95% CI = 0.07–0.23, p < 0.001) and in visits from men on ART with undetectable plasma VL compared to men not on ART (PRR = 0.15, 95% CI = 0.05–0.43, p = 0.001). Among men with detectable penile HIV shedding, the median log10 HIV copies/milliliter of lavage fluid was significantly lower in men with ART—induced undetectable plasma VL (1.93, interquartile range [IQR] = 1.83–2.14) than in men not on ART (2.63, IQR = 2.28–3.22, p < 0.001). Limitations of this observational study include significant differences in baseline covariates, lack of confirmed receipt of ART for individuals who reported ART use, and lack of information on potential ART initiation during follow—up for those who were not on ART at enrollment.

Conclusion
Penile HIV shedding is significantly reduced after healing of MC wounds. Lower plasma VL is associated with decreased frequency and quantity of HIV shedding from MC wounds. Starting ART prior to MC should be considered to reduce male-to-female HIV transmission risk. Research is needed to assess the time on ART required to decrease shedding, and the acceptability and feasibility of initiating ART at the time of MC.

Editors' Summary

Background
About 35 million people are currently infected with HIV, the virus that causes AIDS by destroying immune system cells, and every year, 2 million more people become HIV-positive. Antiretroviral therapy (ART) can keep HIV in check, but there is no cure for AIDS. Consequently, prevention of HIV acquisition and transmission is an important component of efforts to control the AIDS epidemic. Because HIV is most often spread through unprotected sex with an infected partner, individuals can reduce their risk of becoming HIV-positive by abstaining from sex, by having only one or a few partners, and by using male or female condoms. In addition, three trials undertaken in sub-Saharan Africa a decade ago showed that male circumcision—the surgical removal of the foreskin, a loose fold of skin that covers the head of the penis—can halve the HIV acquisition rate in men. Thus, since 2007, the World Health Organization (WHO) has recommended voluntary medical male circumcision for individuals living in countries with high HIV prevalence as part of its HIV prevention strategy.

Why Was This Study Done?
With the rollout of voluntary medical male circumcision programs, circumcision has become more normative (regarded as acceptable), and HIV-positive men are increasingly requesting circumcision because they want to avoid any stigma associated with being uncircumcised and because circumcision provides health benefits. WHO recommends that, although circumcision should not be promoted for HIV-positive men, voluntary circumcision programs should operate on HIV-positive men if they request circumcision. However, in a trial of circumcision of HIV-infected men, HIV transmission to their female partners increased if the couples had sexual intercourse before the circumcision wound had healed. Moreover, in studies of current male circumcision programs, two-thirds of married men and a third of all men reported that they resumed sexual intercourse before their circumcision wounds had healed. Thus, better understanding of how male circumcision increases HIV transmission to female partners is essential, and improved ways to prevent transmission in the post-surgical period are needed. Here, in a prospective observational study (an investigation that collects data over time from people undergoing a specific procedure), the researchers assess HIV shedding from the penis after circumcision.

What Did the Researchers Do and Find?
The researchers evaluated penile HIV shedding among 223 HIV-infected men (183 men who self-reported not being on ART and 40 men who self-reported being on ART, 29 of whom had no detectable virus in their blood) living in Rakai, Uganda, by examining preoperative and postoperative penile lavage (wash) samples. Viral shedding was detected in 9.3% of the men not on ART before surgery and in 39.3% of these men during the entire study. Relative to baseline, a greater proportion of men shed virus at one, two, and three weeks after circumcision, but a lower proportion shed virus at six and twelve weeks after circumcision. HIV shedding was more frequent among men with a high amount of virus in their blood (a high viral load) than among men with a low viral load. Moreover, the frequency of HIV shedding was lower in visits from men with healed circumcision wounds than in visits from men with unhealed wounds, and in visits from men on ART with no detectable virus in their blood than in visits from men not on ART men. Finally, among men with detectable penile HIV shedding, men on ART with no detectable virus in their blood shed fewer copies of virus than men not on ART.

What Do These Findings Mean?
The findings suggest that healed circumcision wounds are associated with reduced penile HIV shedding in HIV-positive men compared to unhealed circumcision wounds and HIV shedding prior to circumcision. [They only consider male HIV shedding in transmission to women, not any possible effect of the keratinised glans rubbing over the vaginal surface on HIV reception.]  In addition, they suggest that a lower HIV viral load in the blood is associated with a decreased frequency and quantity of HIV shedding from circumcision wounds. Because this was an observational study, these findings cannot prove that healed wounds or reduced blood viral load actually caused reduced penile HIV shedding. Moreover, the accuracy of these findings may be affected by the lack of information on ART initiation during follow-up among men not initially on ART and by reliance on ART self-report. Nevertheless, these findings highlight the importance of counseling HIV-positive men undergoing circumcision to avoid sexual intercourse until their circumcision wound heals. In addition, these findings suggest that it might be possible to reduce HIV transmission among HIV-positive men immediately after circumcision by starting these individuals on ART before circumcision. Further research is needed to assess how long before circumcision ART should be initiated and to assess the acceptability and feasibility of initiating ART concurrent with circumcision.

[But never for a moment do they consider NOT CUTTING HIV-POSITIVE MEN! It is TOO LATE to protect them. One reason they have given for doing so is that they do not want the men to be stigmatised as HIV-positive if they are not cut. But if people refuse to have sex with them, that too will help to prevent the spread of HIV. The question arises "What is their true motivation - to prevent the spread of HIV, or to promote the spread of male genital cutting?]

A Cochrane Review of HIV-circumcision studies finds:

Another Cochrane review cautiously supported a protective effect:

Siegfried N, Muller M, Deeks JJ, Volmink J. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD003362. DOI: 10.1002/14651858.CD003362.pub2

While the Cochrane reviews are highly regarded, this one appears to have done no more than added in, at face value, the three RCTs, whose faults are detailed on another page.

BMC Medical Research Methodology 2011, 11:34 doi:10.1186/1471-2288-11-34

What counts as reliable evidence for public health policy: the case of circumcision for preventing HIV infection

Reidar K Lie and Franklin G Miller

Abstract (provisional)
Background
There is an ongoing controversy over the relative merits of randomized controlled trials (RCTs) and non-randomized observational studies in assessing efficacy and guiding policy. In this paper we examine male circumcision to prevent HIV infection as a case study that can illuminate the appropriate role of different types of evidence for public health interventions.

Discussion
Based on an analysis of two Cochrane reviews, one published in 2003 before the results of three RCTs, and one in 2009, we argue that if we rely solely on evidence from RCTs and exclude evidence from well-designed non-randomized studies, we limit our ability to provide sound public health recommendations. Furthermore, the bias in favor of RCT evidence has delayed research on policy relevant issues.

Summary
This case study of circumcision and HIV prevention demonstrates that if we rely solely on evidence from RCTs and exclude evidence from well-designed non-randomized studies, we limit our ability to provide sound public health recommendations.

[The authors are at (excessive?) pains not to challenge the circumcision-HIV claims, but they point to many of the same holes in the RCTs that Intactivists do, and make the point that the second Cochrane review simply ignored all studies prior to the RCTs and hence the negative conclusion of the first Cochrane review.]

Country

% of men
circumcised

% HIV prevalence in

Adults

Circumcised
men

Uncircumcised
men

Burkina Faso

88

1.8

1.8

2.9

Cameroon

93

5.5

4.1

1.1

Cote d'Ivoire

96

4.7

2.8

3.8

Ethiopia*

91

1.4

0.9

1.1

Ghana

95

2.2

1.6

1.4

Kenya

83

6.7

3.0

12.6

Lesotho

49

23.5

22.8

15.2

Malawi

20

11.8

13.2

9.5

Rwanda

9

3.0

3.5 (2010 2.5)

2.1 (2010 2.2)

Swaziland

8.1

25.9

21.8

19.5

Tanzania

69

7.0

6.5

5.6

Uganda

25

6.4

3.8

5.6

Source: National surveys, available at: www.measuredhs.com/countries/

United States Agency for International Development (USAID)
February 2009

LEVELS AND SPREAD OF HIV SEROPREVALENCE AND ASSOCIATED FACTORS: EVIDENCE FROM NATIONAL HOUSEHOLD SURVEYS
DHS COMPARATIVE REPORTS 22

There appears to be no clear pattern of association between male circumcision and HIV prevalence. In 8 of 18 countries with data, as expected, HIV prevalence is lower among circumcised men, while in the remaining 10 countries HIV prevalence is higher among circumcised men ...

Findings from the 18 countries with data present a mixed picture of the association between male circumcision and HIV prevalence (Table 9.3). In eight of the countries (Burkina Faso, Cambodia, Côte d'Ivoire, Ethiopia, Ghana, India, Kenya, and Uganda), HIV prevalence is higher among men who are not circumcised, although the difference between circumcised and non-circumcised men is slight, except in Kenya, where the difference is substantial (HIV prevalence of 11.5 percent for non-circumcised men compared with 3.1 percent for circumcised men) (Figure 9.1). In 10 of the countries (Cameroon, Guinea, Haiti, Lesotho, Malawi, Niger, Rwanda, Senegal, Tanzania, and Zimbabwe) HIV prevalence is higher among circumcised men.

p123

... data has since become available for Mozambique and Zambia. In both cases, HIV prevalence is higher among those uncircumcised. Data also became available for Swaziland, which showed that HIV prevalence is higher among those who are circumcised.

Second, in the case of Tanzania, the earlier USAID report states that prevalence is higher among those who are circumcised. A more recent study indicates the opposite, with HIV prevalence being 3.7% among the circumcised and 6.4% among the uncircumcised.

Third, of the 14 countries where male circumcision is being promoted (Botswana, Ethiopia, Kenya, Lesotho, Malawi, Mozambique, Namibia, Rwanda, South Africa, Swaziland, Tanzania, Uganda, Zambia and Zimbabwe), there is no recent DHS data about male circumcision and HIV prevalence for 3 of them (Botswana, South Africa and Namibia). Of the 11 countries where there is data, 5 of them have higher HIV prevalence among the circumcised (Lesotho, Malawi, Rwanda, Swaziland and Zimbabwe) and 6 have higher HIV prevalence among the uncircumcised (Ethiopia, Kenya, Mozambique, Tanzania, Uganda and Zambia).

Those who support circumcision argue that at least in Lesotho and Malawi, partial circumcision is practiced, which may explain the results in those two countries. Also in Rwanda, the data indicates that if you look only in urban areas, circumcision is actually partially protective (even though in the country as a whole, it appears not to be). [More data-mining.]

- LSTM1 in ZimEye, December 29, 2011

[Clearly the results are still mixed, with nothing like the clear correlations you would expect if circumcision really did reduce HIV by anything like "60%"]

"Circumcision status should be viewed as a proxy for other aspects of human behavior. Unless one can control for these aspects, one cannot draw reliable conclusions about the causative status of the presence or absence of a foreskin on the course of medical disease processes."

- Dr Anne Laumann
in a letter to Archives of Dermatology

J Med Ethics 2010;36:798-801
doi:10.1136/jme.2010.038695
HIV/AIDS and circumcision: lost in translation
Marie Fox and Michael Thomson

Abstract
In April 2009 a Cochrane review was published assessing the effectiveness of male circumcision in preventing acquisition of HIV. It concluded that there was strong evidence that male circumcision, performed in a medical setting, reduces the acquisition of HIV by men engaging in heterosexual sex. Yet, importantly, the review noted that further research was required to assess the feasibility, desirability and cost-effectiveness of implementation within local contexts. This paper endorses the need for such research and suggests that, in its absence, it is premature to promote circumcision as a reliable strategy for combating HIV. Since articles in leading medical journals as well as the popular press continue to do so, scientific researchers should think carefully about how their conclusions may be translated both to policy makers and to a more general audience. The importance of addressing ethico-legal concerns that such trials may raise is highlighted. The understandable haste to find a solution to the HIV pandemic means that the promise offered by preliminary and specific research studies may be overstated. This may mean that ethical concerns are marginalised. Such haste may also obscure the need to be attentive to local cultural sensitivities, which vary from one African region to another, in formulating policy concerning circumcision.

Australian Doctor
November, 2005

Circumcision equal to a vaccine for HIV

by Rebecca Jenkins

CIRCUMCISION offers the same level of protection against HIV infection in heterosexual men as a highly effective vaccine, according to a landmark study. In the first randomised controlled trial of its kind, researchers found circumcision provided 60% protection against the virus, confirming the results of a large body of observational studies.

A vaccine of high efficacy is expected to offer long-term protection of 95% or above. Smallpox was eradicated with such a highly efficient vaccine. If control of tetanus, measles, and poliomyelitis has been largely achieved in the world, it has been a result of high-efficacy vaccines. ... A 96%-efficient measles vaccine means that 96% of vaccinated persons exposed to measles are indeed protected against infection. Protection lasts for many years, and revaccination permits dealing with loss of immunity over time. What Auvert and colleagues show is ... a 60% reduction in disease incidence over an 18-month period among circumcised men compared with uncircumcised men with similar exposure. To our knowledge, this does not mean that those men are really "protected" against HIV, especially in the case of repeated exposure. It simply means "reduced risk," or reduced probability of contamination.

- Michel Garenne, Male Circumcision and HIV Control in Africa

In a text for upper division and/or graduate study of immunology, a table gives the percentage of reduction obtained by vaccines for the diseases modern societies associate with successful immunization programs.

Smallpox, diphtheria, and polio vaccinations resulted in 100% reduction of incidence. Vaccination against measles, Mumps, and rubella (German measles) resulted in >99% reduction of incidence. Tetanus (lockjaw) was reduced by more than 98%; Pertussis (whooping cough) by more than 87%.

(No vaccines that reduced incidence by as little as 70% were included in the table.)

- Kindt, Thomas J, Goldsby, R.A., and Osborne, B.A.
(Kuby) Immunology (6th Ed), New York: W.H. Freeman, 2007.
[Kindt - NIH, Goldsby - Amherst College, Osborne - UMass, Amherst]

"...even assuming that reducing the risk of HIV transmission could be a justification for infant male circumcision, this justification would not be available until it became at least more likely than not that circumcision would reduce the risk of HIV transmission.

"...even assuming that circumcision could help to protect against HIV infection, it would not be necessary to carry it out on unconsenting infants. One could wait until the person was about to become sexually active and could decide for himself.

"...one is ethically required to use the least harmful, least invasive means of achieving a good, the achievement of which involves harm. Consequently, a surgical intervention aimed at preventing the spread of HIV could only be justified if there were no other reasonable way to achieve this. And, even if circumcision helped to protect people in developing countries from the spread of HIV, we would not be justified in carrying this out for this purpose in developed countries, where other, better means of protection are much more readily available."

- The Gazette, Montreal, October 24, 1998, pB6

Models of Protection Against HIV/SIV: Avoiding AIDS in Humans and Monkeys

Edited by Gianfranco Pancino, Guido Silvestri and Keith Fowke

Chapter 5 – The Genital Mucosa, the Front Lines in the Defense Against HIV

T. Blake Ball, Kristina Broliden

Summary
Mucosal sexual transmission of HIV now accounts for the majority of transmission worldwide, and occurs at the genital tract. However, relative to what is known about systemic correlates of protection, less is known about innate and adaptive immune responses capable of affecting HIV transmission at this site. The protective efficacy of immune mechanisms at the genital tract, especially the female genital tract, has been estimated to stop the vast majority of HIV transmission across an intact and uninflamed mucosal surface, indicating a protective efficacy of almost 99 percent – much greater than any biomedical intervention described to date. There is considerable evidence that individuals who appear to be naturally protected from HIV infection may be protected from HIV infection at this site. In this chapter we will discuss the physiologic features of the genital mucosa, the underlying cells susceptible to HIV transmission and replication, and the role of innate and adaptive immune responses at this site in protecting against HIV infection in highly HIV-exposed, uninfected subjects.

Have WHO and UNAIDS gotten the wrong message from studies of circumcision to reduce men's risk for HIV?

By David Gisselquist

In 2003-06, a study team funded by the US National Institutes of Health (NIH) recruited HIV-negative intact (uncircumcised) men in Rakai, Uganda, circumcised some, and then followed and retested both circumcised and intact men to see who got HIV.[1] The most widely reported data from this study say that men in the intervention (circumcised) group got HIV at the rate of 0.66% per year vs. 1.33% per year for men in the control (intact) group. These data have been used to motivate efforts to circumcise 20 million African adults by 2015 as well as to introduce routine infant circumcision.

Circumcise vs. wait and wipe
However, other data from the same study show a more effective, less dangerous, less culturally intrusive, and less expensive option for intact men to protect themselves from HIV after sexual contact – simply waiting at least 10 minutes after coitus before doing anything to clean one’s penis, and then just wiping it with a dry cloth, without water (Table). (Condom use reliably protects men from acquiring HIV from sexual partners; this note discusses waiting and wiping as an alternative to circumcision, not as an alternative to condom use.)

Abstract: Female circumcision and HIV infection in Tanzania: for better or for worse? Stallings R.Y, Karugendo E. (PowerPoint)

Introduction: ...The authors sought to explain an unanticipated significant crude association of lower HIV risk among circumcised women [R{isk} R{atio}=0.51; 95% C{onfidence} I{nterval} 0.38,0.70] in a recent survey by examining other factors which might confound this crude association.

Methods: Capillary blood was collected ... from a nationally representative sample of women age 15 to 49 during the 2004 Tanzania Health Information Survey. Eighty-four percent of eligible women gave consent for their blood to be anonymously tested for HIV antibody. Interview data was linked ... to final test results for 5753 women. The chi-square test of association was used to examine the bivariate relationships between potential HIV risk factors with both circumcision and HIV status. Restricting further analyses to the 5297 women who had ever had sexual intercourse, logistic regression models were then used to adjust circumcision status for other factors found to be significant.

Results: By self-report, 17.7 percent of women were circumcised. Circumcision status varied significantly by region, household wealth, age, education, years resident, religion, years sexually active, union status, polygamy, number of recent and lifetime sex partners, recent injection or abnormal discharge, use of alcohol and ability to say no to sex. In the final logistic model, circumcision remained highly significant [O{dds} R{atio}=0.60; 95% C{onfidence} I{nterval} 0.41,0.88] while adjusted for region, household wealth, age, lifetime partners, union status, and recent ulcer.

Conclusions: A lowered risk of HIV infection among circumcised women was not attributable to confounding with another risk factor in these data. Anthropological insights on female circumcision as practiced in Tanzania may shed light on this conundrum.

Will there be Randomised Controlled Trials of 3000 HIV-negative women, where 1500 are circumcised and they see how many seroconvert - followed by calls for mass circumcision of women to prevent the spread of HIV? Of course not.

Kanki et al. reported that, in Senegalese prostitutes, women who had undergone female genital cutting had a significantly decreased risk of HIV-2 infection when compared to those who had not.

Kanki P, M'Boup S, Marlink R, et al. "Prevalence and risk determinants of human immunodeficiency virus type 2 (HIV-2) and human immunodeficiency virus type 1 (HIV-1) in west African female prostitutes Am. J. Epidemiol. 136 (7): 895-907. PMID

Remarkably, there is consistent evidence that female-to-male HIV transmission, compared with male-to-female transmission, is much higher in Europe than in the USA . . . Data from the European Multicenter Partners Study and comparable research from the USA suggest that the ratio of female-to-male transmission (compared with male to female transmission) is about 10 fold higher in Europe.³

[3 De Vincenzi I. Heterosexual transmission of HIV. JAMA 1992; 267: 1919.]

"Russian Roulette with two bullets rather than three"

Male circumcision and HIV infection

For several years, researchers have been debating the relationship between male circumcision and HIV. Several studies have indicated that circumcised men are less likely to become infected with HIV than uncircumcised men. However, because circumcision is usually linked to culture or religion, it has been argued that the apparent protective effect of the procedure is likely to be related not to removal of the foreskin but to the behaviours prevalent in the ethnic or religious groups in which male circumcision is practised. In addition, some researchers have assumed that any association between circumcision and HIV must be complicated by the presence of other sexually transmitted infections, which have been found to be more common among uncircumcised men.

Clearly, the correlations are not straightforward. In the higher income countries, the rates of HIV infection among men who have sex with men do not vary greatly even though the circumcision rates do: few men in Europe and Japan but four-fifths of men in the United States are circumcised. In Africa, however, circumcision seems to confer some protection. A study in Nyanza Province, Kenya, among men from the same ethnic group, the Luo, found that one-quarter of uncircumcised men were infected with HIV, compared with just under one-tenth of circumcised men. The protective effect remained even after other factors, such as sexual behaviour and sexually transmitted infections, had been taken into account. A study of over 6800 men in rural Uganda has suggested that the timing of circumcision is important: HIV infection was found in 16% of men who were circumcised after the age of 21 and in only 7% of those circumcised before puberty. A recent review of 27 published studies on the association between HIV and male circumcision in Africa found that, on average, circumcised men were half as likely to be infected with HIV as uncircumcised men. When African men with similar socio-demographic, behavioural and other factors were compared, circumcised men were nearly 60% less likely than uncircumcised men to be infected with HIV.

Even though the weight of evidence increasingly suggests that circumcising men before they become sexually active does provide some protection against HIV, the practical implications for AIDS prevention are not obvious. Circumcision, where it is practised, usually has links to religious or ethnic identities and life-cycle ceremonies, and may customarily be done after puberty. If the same scalpel were used without sterilization on a number of boys, this could actually contribute to the transmission of HIV. Finally, if circumcision were promoted as a way of preventing HIV infection, people might abandon other safe sexual practices, such as condom use. This risk is far from negligible - already, rumours abound in some communities that circumcision acts as a "natural condom". A sex worker interviewed in the city of Kisumu in Kenya summed up this misconception, saying: "I can sleep with circumcised men without a condom because they don't carry a lot of dirt on their penis". While circumcision may reduce the likelihood of HIV infection, it does not eliminate it. In one study in South Africa, for example, two out of five circumcised men were infected with HIV, compared with three out of five uncircumcised men. Relying on circumcision for protection is, in these circumstances, a bit like playing Russian roulette with two bullets in the gun rather than three. [...assuming the gun has only five chambers - or, if it had the more usual six, 2.4 bullets rather than 3.6.]

- Report on the global HIV/AIDS epidemic
UNAIDS, June 2000
A large file, >275KB.

In the wake of three incomplete Random Controlled Tests of circumcision, the head of UNAIDS, Dr Peter Piot, has chosen to forget these wise words.

Know
the
score

Findings from
the National
Gay Men’s
Sex Survey
2001

David Reid
Peter Weatherburn
Ford Hickson
Michael Stephens

...

Introduction and methods

1.1 CONTENT OF THE REPORT

This research report outlines the main findings of Vital Statistics 2001 – which was the fifth annual national Gay Men’s Sex Survey (henceforth GMSS). The survey was carried out during the summer of 2001 by Sigma Research in partnership with 73 health promotion agencies across England and Wales.

...

Chapter 2 gives a brief description of the sample of 14,616 men living in England and Wales who either had sex with another man in the last year or expected to have sex with a man in the future.

...

1.2 BACKGROUND TO THE FIFTH NATIONAL GAY MEN’S SEX SURVEY
The Gay Men’s Sex Survey uses a short self-completion questionnaire to collect a limited amount of information from a substantial number of men. ...

1.3 PRIDE EVENTS: RECRUITMENT DATES, EVENTS AND RETURNS
Recruitment occurred at seven community-based events in the summer of 2001. ...

4.5 CIRCUMCISION
It has been suspected for some time that when uninfected men are insertive in UAI with positive men, whether or not the uninfected man is circumcised has a bearing on the probability of HIV transmission occurring. The hypothesis is that the cells of the fore-skin are more susceptible to infection by HIV and therefore circumcision has a protective function.

Men were asked Are you circumcised? and were asked to tick No, Yes or Don’t Know. Overall, 0.9% said Don’t know by which we think they mean they do not know the word rather than not knowing whether they have a foreskin. Excluding this small group, 22.1% of men indicated that they were circumcised. The proportion rose with increasing age, from 16.1% among the under 20s, through 18.8% (in the 20s), 21.3% (in the 30s), 24.8% (in the 40s) and 40.2% among the over 50s.

Circumcision also significantly varied by ethnicity, being highest among Bangladeshi men (100%, 5/5), Pakistani men (97.5%, 39/40), other Asian men (77.3%, 68/88) and Black African men (76.1%, 35/46). Of all sixteen ethnic groups, White British men had the lowest level of circumcision (18.7%, 2201/11764).

If circumcised men are less likely to acquire HIV than men with foreskins, then we should expect fewer of the circumcised men to have tested positive than the men with a foreskin. However, more of the circumcised men had tested positive for HIV (6.1%) than had those with a foreskin (5.0%). This small but significant difference is in the opposite direction than predicted if foreskins are contributing to transmission, and was observed in all ethnic groups and across the age range.

The survey found no evidence to support the adoption of ‘the proportion of HIV uninfected men who are not circumcised’ as a population level target for HIV prevention programmes for gay and bisexual men. [... let alone evidence to support the promotion of circumcising anyone]

[The only possible confounder remaining is selection bias. The results would not reflect the actual position if circumcised men who have HIV (and know it), or intact men who don't, are more likely to take the survey than intact men who have HIV (and know it) or circumcised men who don't, but it is very hard to see why that might be.

Only a small proportion of these men with HIV would have been infected trans-penilely, compared to the proportion infected tran-anally, so the small surplus of those HIV-positive men who are circumcised should not be taken as suggesting that circumcision makes HIV-infection more likely.]

"Scientists must constantly be on guard against this sort of self-deception [picking and choosing data to agree with the preconception that electromagnetic fields, as from power lines, cause leukaemia]. Unless studies are carefully designed to avoid it, the biases of the epidemiologist have a way of creeping into the results. To minimize the opportunity for bias, scientists rely on double-blind studies. An independent researcher might be given a list in­cluding both the homes of victims of childhood leukemia and an equal number of addresses of nonvictim children matched in age, gender, race, family income, etc., but without any indication of which are which. Without knowing which were the homes of vic­tims and which were "controls," the researcher would rate them by whatever criteria were used to estimate the field strength. Some­one else would then apply the key after the judgments were made.

[Double-blinding a study involving circumcision is hardly practicable, but much more could have been done to make the circumcised experimental groups and the intact control groups equivalent.]

But even if the study had been double blind, a "risk ratio" of only three for a rare disease such as childhood leukemia would be regarded by many epidemiologists as barely credible. The risk ratio for lung cancer from smoking, for example, is well over thirty^ that is, a 3,000 percent increase in the incidence of lung cancer among smokers. Yet it took years of checking and rechecking the figures, as well as a highly plausible mechanism in terms of known carcinogens in tobacco smoke and, finally, confirming laboratory studies on animals before the cancer link was firmly nailed down."

- "Voodoo Science" by Robert Park, pp 150-1

"The estimated reduction in the relative risk of infection with HIV [between circumcised and intact men in the Kenyan and Ugandan trials] was 51% (unadjusted modified intention-to-treat analysis) to 55% (as-treated analysis)."

Editorial comment in The Lancet.

To the Editor:

Largely ignored in the report by Quinn et al. of their study of the heterosexual transmission of human immunodeficiency virus type 1 (HIV-1) in Uganda (March 30 issue) (1) is the finding that of 137 uncircumcised men who were negative for HIV-1, 40 seroconverted, whereas 0 of 50 circumcised men seroconverted. This finding suggests that male circumcision is at least as protective against female-to-male transmission of HIV-1 as low viral load in the female partner. Yet the authors do not consider male circumcision among their list of possible strategies for the prevention of HIV-1 infection.

There are now more than 30 epidemiologic studies from sub-Saharan Africa dating back to 1987 that report a significant protective effect of male circumcision against HIV-1 infection. (2) Is it not time for those in Rakai, Uganda (where Quinn et al. conducted their study), as well as others, to benefit from these studies? The feasibility of offering information on voluntary male circumcision and circumcision services to this community with a high prevalence of HIV-1 infection could at least be investigated. Justice and scientific evidence demand it.

Robert C. Bailey, Ph.D., M.P.H.
University of Illinois School of Public Health
Chicago, IL 60302

References

1. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med 2000;342:921-9.

2. Halperin DT, Bailey RC. Male circumcision and HIV infection: 10 years and counting. Lancet 1999;354:1813-5.

[...a letter on another topic here...]

The authors reply:

To the Editor:

Bailey comments on the association between circumcision and reduced rate of acquisition of HIV-1 in male subjects in our study of couples discordant for HIV-1 status. Although circumcision was strongly associated with reduced acquisition of HIV-1 in these highly exposed couples, additional analyses suggest that generalization to the whole population is complicated by confounding. (1) In our representative population in Rakai, we found that circumcision was associated with a reduced rate of HIV-1 acquisition; this was particularly true for circumcision performed before puberty. However, this effect was mainly due to the lower incidence of HIV-1 among Muslims, who constitute the largest group of circumcised males. Circumcision was not significantly protective among non-Muslim men or in couples in which both partners were HIV-1-negative. (1) The 30 African epidemiologic studies mentioned by Bailey are mainly cross-sectional investigations with inconsistent findings and inadequate control for potential confounding. These observational data are difficult to interpret, and clinical trials are needed before circumcision can be promoted as a means of preventing HIV infection.

[...]

Thomas C. Quinn, M.D.
National Institute of Allergy and Infectious Diseases
Bethesda, MD 21205

Maria J. Wawer, M.D.
Columbia University
New York, NY 10032

Nelson K. Sewankambo, M.B., Ch.B.
Makerere University
Kampala, Uganda

References

1. Gray RH, Kiwanuka N, Quinn TC, et al. Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda. AIDS (in press).

[...]

No relationship to circumcision status (13 studies):

1. Hira SK, Kamanga J< Mcuacua R, et al. Genital ulcers and male circumcision as risk factors for acquiring HIV-1 in Zambia. J Infect Dis 1990;161:584-5.

2. Pépin J, Quigley M, Todd J, et al. Association between HIV-2 Infection and genital ulcer diseases among male sexually transmitted disease patients in The Gambia. AIDS 1992;6:489-93.

3. Bollinger RC, Brookmeyer RS, Mehendale SM,l et al. Risk factors and clinical presentation of acute primary HIV infection in India. JAMA 1997; 278:2085-9.

4. Chiasson M, Stoneburner RL, Hildebrandt DS, et al. Heterosexual transmission of HIV-1 associated with use of smokable freebase cocaine (crack). AIDS 1991;5:1121.

5. Carael M, Van De Perre, PH, Lepage PH, et al. Human immunodeficiency virus transmission among heterosexual couples in Africa. AIDS 1988;2:201-5.

6. Moss GB, Clemerson D, D'Costa L, et al. Association of cervical ectopy with heterosexual transmission of human immunodeficency virus: results of a study of couples in Nairobi, Kenya. J Infect Dis 1991;164:588-91.

7. Allen S, Lindan C, Serufilira A, et al. Human immunodeficiency virus infection in urban Rwanda: demographic and behavioral correlate in a representative sample of childbearing women. JAMA 1991; 266:1657-63.

8. Seidlin M, Vogler M, Lee E, et al. Heterosexual transmission of HIV in a cohort of couples in New York City. AIDS 1993;7:1247-54.

9. Konde-Lule JK. Bergley SF, Downing R. Knowledge attitudes and practices concerning AIDS in Ugandans. AIDS 1989;3:513-18.

10. Van de Perre P, Clumeck N, Steens M, et al. Seroepidemiological study on sexully transmitted diseases and hepatitis B in African promiscuous heterosexuals in relation to HTLV-III infection. Eur J Epidemiol 1987;3:14-8.

11. Quigley M, Munguti K, Grosskurth H, et al. Sexual behavior patterns and other risk factors for HIV infection in rural Tanzania: a case control study. AIDS 1997;11:237-48.

12. Hudson CP, Hennis AJM, Kataaha P, et al. Risk factors for the spead of AIDS in rural Africa, hepatitis B and syphilis in southwestern Uganda AIDS 1988; 2: 255-60.

13. Laumann EO, Masi CM, Zuckerman EW. Circumcision in the United States: prevalence, prophylactic effects, and sexual practice. JAMA 1997;277:1052-7.

A higher risk in circumcised men (4 studies):

1. Barongo LR, Borgdorff W, Mosha FF, et al. The epidemiology of HIV-1 infection in rural areas, roadside settlements and rural villages in Mwanza Region, Tanzania. AIDS 1992;6:1521-8.

2. Grosskurth H, Mosha F, Todd J, et al. A community trial of the impact of improved sexually transmitted disease treatment on the HIV epidemic in rural Tanzania: 2. Baseline survey results. AIDS 1995;9:927-34.

3. Chao A, Bulterys M, Musanganire F, et al.Risk factors associated with prevalent HIV-1 infection among pregnant women in Rwanda. National University of Rwanda-Johns Hopkins University AIDS Research Team. Int J Epidemiol 1994;23:371-380.

4. Urassa M, Todd J, Boerra JT, et al. Male circumcision and susceptibility to HIV infection among men in Tanzania. AIDS 1997;11:73-80. [study 1]

http://ije.oupjournals.org/cgi/reprint/dyh127v1.

Int J Epidemiol. 2004 Mar 24 [Epub ahead of print]

Trends in antenatal human immunodeficiency virus prevalence in Western Kenya and Eastern Uganda: evidence of differences in health policies?

Moore DM, Hogg RS.

Department of Health Care and Epidemiology, University of British Columbia, Vancouver, BC, Canada.

OBJECTIVE: To observe recent trends in human immunodeficiency virus (HIV) prevalence in antenatal clinic attendees to determine if previously noted falls in HIV prevalence are occurring on both sides of the Kenyan-Ugandan border. Design An ecologic study was conducted at the district level comparing HIV prevalence rates over time using data available through reports published by the Kenyan and Ugandan Ministries of Health and UNAIDS.

METHODS: Sentinel sites were compared with respect to population, ethnicity, language group, and the prevalence of circumcision practice. The prevalence of HIV found at each sentinel site was recorded for the years 1990-2000 and analysed visually and by conducting bivariate correlations.

RESULTS: Ethnographic analysis revealed a wide mix of ethnic and language groups and circumcision rates on both sides of the border. All sentinel surveillance sites in Uganda showed trends towards decreasing HIV prevalence, with three of five sites showing statistically significant declines (r = -0.87, -0.85, -0.86, P < 0.05). In contrast, all of the surveillance sites in Kenya showed trends toward increasing HIV prevalence, with two of the five sites showing statistically significant increases (r = 0.62, 0.84, P < 0.05).

CONCLUSIONS: The declines in HIV prevalence occurring in Uganda are not being seen in geographically proximal districts of Kenya. No obvious differences in ethnic groupings or their associated prevalence of circumcision appeared to explain these differences. This suggests that decreasing HIV prevalence in Uganda is not due to the natural course of the epidemic but reflects real success in terms of HIV control policies.

PMID: 15044420 [PubMed - as supplied by publisher]

http://www.ias2007.org/pag/Abstracts.aspx?SID=55&AID=2465

Circumcision status and risk of HIV seroconversion in the HIM cohort of homosexual men in Sydney
Presented by David James Templeton, Australia.

Templeton D.J.1, Jin F.1, Prestage G.P.1, Donovan B.1, Imrie J.2, Kippax S.C.2, Kaldor J.M.1, Grulich A.E.1
1National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Darlinghurst, Australia, 2National Centre in HIV Social Research, University of New South Wales, Randwick, Australia

Objectives: Circumcision substantially lowers the risk of HIV acquisition among heterosexual African men, but there are few data addressing circumcision status as a risk factor for HIV among homosexual men. We examined circumcision status as an independent risk factor for HIV seroconversion in the community-based Health in Men (HIM) cohort of homosexual men in Sydney, Australia.
Methods: Between 2001 and 2004, 1,427 initially HIV-negative men were enrolled. Circumcision status was self-reported at baseline and was validated by clinical examination during study visits in a sub-sample of participants. All participants were tested annually for HIV and offered testing for other sexually transmitted infections (STIs). Demographic information was collected at baseline and detailed information on sexual risk behaviours was collected every 6 months. Results: At baseline, 66% of participants reported being circumcised; mostly as infants. There were 49 HIV seroconversions through 2006, an incidence of 0.80 per 100PY. On multivariate analysis controlling for non-concordant unprotected anal intercourse (UAI), anorectal STIs and age, being circumcised was not associated with HIV seroconversion (RR = 0.88, 95% CI 0.45-1.74). Among men who reported no receptive UAI, there were nine seroconversions, an incidence of 0.35 per 100PY. When analyses were restricted to this group, there was also no association with HIV seroconversion (RR = 0.99, 95% CI 0.25-3.96).
Conclusion: Circumcision status was not associated with HIV seroconversion in this cohort. Although statistical power was limited, among men who were more likely to acquire HIV by insertive UAI, there was also no relationship. As most HIV infections in homosexual men occur after receptive anal sex, circumcision is unlikely to be an effective HIV prevention intervention in Australian gay men. However, further research in populations where there is more separation into exclusively receptive or insertive sexual roles by homosexually active men is warranted.