Garenne
Stephen Strauss
Dr Petra
Matare
Kalichman
Myers
Sanger
Garenne again
van Howe and Storms
Boyle and Hill
Thornton

Correspondence
Male Circumcision and HIV Control in Africa
Michel Garenne

In a recent article, Auvert and colleagues present the results of their randomized controlled trial on male circumcision to prevent HIV transmission [1]. They conclude that male circumcision reduced the risk of HIV infection by some 60% (95% confidence interval, 32%–76%). The trial was certainly well conducted, and it nicely confirmed observational studies, which came to the same conclusion [2]. However, a number of their concluding statements deserve a comment.

Auvert and colleagues claim a “degree of protection equivalent to a vaccine of high efficacy” [1]. This is obviously overstated. 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. Furthermore, the analogy with vaccines appears misleading. 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 different: they show 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.

A closer analogy of the “reduced risk” offered by male circumcision is that offered by contraception. Modern and efficacious methods such as hormonal contraceptives (pill, injectables, implants) or intra-uterine devices (IUDs) do offer high protection, usually 99% or above for women who are exposed repeatedly (every month) to risk of pregnancy. Highly efficacious methods do protect these women against unwanted pregnancy. On the contrary, a less efficacious method such as rhythm method (periodic abstinence) reduces fecundity by some 50%, but offers little protection against unwanted pregnancy. Even though women using consistent rhythm methods will have a lower number of pregnancies over their lifetime than women who use no contraceptive methods at all, they will be unlikely to achieve their desired family size, as could women using highly effective methods.

Similarly, for persons who are highly exposed to risk of HIV infection, as are the young men of South Africa, a 60% reduction in annual risk will ultimately protect only a smaller proportion. Basic probability calculations show that in discordant couples exposed for 30 years, some 74% will contract the HIV virus if circumcised, compared with 97% if uncircumcised (with incidence of 11% per year)—a small reduction indeed if compared with a highly efficacious vaccine (comparable figures would be 4% versus 97% for children vaccinated against measles who are exposed between 1 and 15 years of age).

One could argue that the population effect could exceed the individual risk for a variety of reasons ranging from herd immunity to prevention of other sexually transmitted diseases (STIs). If all men are circumcised, then prevalence among women will be lower, and men will have lower risk of being exposed and infected. However, several natural experiments do not confirm this argument. For instance, Tanzania has some 110 ethnic groups, some groups using universal male circumcision, others not circumcising. After controlling for urbanization, there was no difference in male HIV prevalence between the two groups: in urban areas, HIV seroprevalence was 9.5% in circumcised groups and 9.7% in uncircumcised groups, and conversely, 4.6% and 5.2%, respectively, in rural areas—none of the differences being significant [3]. In South Africa, the KwaZulu-Natal province, where few are circumcised, has a higher HIV seroprevalence than other provinces, reaching 37% among antenatal clinic attendants in 2003. But, in the Eastern Cape, where circumcision is the rule, the dynamics of the epidemic are almost the same, simply lagging a few years behind, increasing from 4.5% in 1994 to 27% in 2003. Finally, it was argued that the large epidemic in Abidjan, Côte d'Ivoire, and surrounding areas in the late 1980s was largely due to the lack of male circumcision of the local ethnic groups. This, however, did not impede the rapid increase in HIV infection among migrant workers from Burkina Faso and Mali living in Abidjan, who were circumcised.

For highly exposed men, such as men living in southern Africa, the choice is either using condoms consistently, with extremely low risk of becoming infected, or being circumcised, with relatively high risk of becoming infected. This is quite similar to women's choice to either use a highly efficacious contraceptive method or use a folk method. Some women make the second choice for religious reasons, with the obvious consequences. Is there a rationale for promoting the idea of circumcision when better choices are available? Regular condom use was found to be protective at the individual level and also effective for stopping HIV epidemics, as in Thailand [4,5].

Concluding that “male circumcision should be regarded as an important public health intervention for preventing the spread of HIV” [1] appears overstated. Even though large-scale male circumcision could avert a number of HIV infections, theoretical calculations and empirical evidence show that it is unlikely to have a major public health impact, apart from the fact that achieving universal male circumcision is likely to be more difficult than universal vaccination coverage or universal contraceptive use.

Michel Garenne
Institut Pasteur
Paris, France
E-mail: mgarenne@pasteur.fr

References

1. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R et al. (2005) Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 trial. PLoS Med 2: e298 DOI: 10.1371/journal.pmed.0020298. Find this article online
2. Weiss HA, Quigley MA, Hayes RJ (2000) Male circumcision and risk of HIV infection in sub-Saharan Africa: A systematic review and meta-analysis. AIDS 14: 2361–2370. Find this article online
3. Tanzania Commission for AIDS, National Bureau of Statistics, ORC Macro (2005) Tanzania HIV/AIDS indicator survey 2003-04. Calverton (Maryland): Tanzania Commission for AIDS, National Bureau of Statistics, ORC Macro. Available: http://www.measuredhs.com/pubs/pdf/FR162/00FrontMatter.pdf. Accessed 15 December 2005.
4. De Vicenzi I (1994) A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. N Engl J Med 331: 341–346. Find this article online
5. Zenilman JM (2005) Behavioral interventions: Rationale, measurement, and effectiveness. Infect Dis Clin North Am 19: 541–562. Find this article online

Citation: Garenne M (2006) Male Circumcision and HIV Control in Africa. PLoS Med 3(1):

STEPHEN STRAUSS: No shortcuts in circumcision
CBC News Viewpoint
November 21, 2005

Snippety, snip, snip. Could that be the sound of AIDS in retreat in Africa?

The auditory metaphor and its effect come to mind if you spend any time reflecting on a much-publicized South African study tying a dramatic decline in HIV infection rates to circumcision. But well might you think just the opposite if you were apprised of the sometimes putrid public health politics underlying publication of said study.

The facts seem straightforward on the surface. Some 3,000 young men - hardly any married - were selected from a semi-rural area near Johannesburg. Half were put in a group that got circumcisions, half in a non-circumcised group. After more than a year, 20 of the circumcised men had become HIV positive versus 49 of the uncircumcised men, this even though the circumcised men had more sexual encounters.

The scientists were jubilant. "The result is equivalent to saying that during the period [of the study] the intervention prevented six out of 10 potential infections," wrote the French and South African researchers who conducted the research, adding, "this provides a degree of protection against acquiring HIV infection equivalent to what a vaccine of high efficiency would have achieved."

The finding was so striking, the researchers stopped the trial before it was supposed to finish because the "protective effect of male circumcision was so high it would have been unethical to continue." That is to say, they thought there was no doubt that circumcision protected against HIV infection.

Finally, the effectiveness of circumcision led the scientists to argue that decision makers should herewith consider making circumcision of all African men a public health priority.

Wonderful, except for all the ethical and methodological mud splattered on the findings.

As a background you should know the project grew out of more than two decades of observation that places in Africa where circumcision was the norm had less AIDS than the uncut places. We are not, by the way, simply talking about Muslim Africa but also tribes where male circumcision is part of a rite of passage into adulthood.

While scientists have been able to come up with numbers of physical explanations for why what has sometimes been snidely called the "cut cure" works, nobody has been certain about the connection. This is because no previous studies have controlled for confounding factors - age at circumcision, number of sexual partners, safe sex practices - that could distort results. So the Johannesburg study was vital in translating anecdote and intimation into believable science.

However, there was a fundamental ethical problem with its methodology. The men were given HIV tests before the project began and 146 were found to be HIV positive, but - underline the following in lipstick red - they weren't told about their status as researchers "considered it unethical to inform participants of their HIV status without their permission."

Gasp. You don't tell people with a life-threatening, highly infectious disease they are both sick and dangerous to others because knowing somehow violates their sense of privacy?

To justify this position, French and South African scientists involved argued that they were just respecting a fear of AIDS stigma so intense that "many of these people prefer to be dead than rejected by their communities."

Gasp again. This is a public health position so obviously crazy - think in the Canadian context of not telling people with SARS they had it because they would be stigmatized and quarantined - it led the British journal The Lancet to reject the publishing of the AIDS paper on the grounds it was ethically flawed.

And there may be a worse confusion to come. Not everyone believes the HIV infection numbers in men who hadn't been circumcised were so conclusive they justified the trial being shut down early. Part of the concern was caused by two recent papers that suggest that clinical trials claiming huge, big, early effects from drugs or other treatments as often as not turn out to be statistical blips and not true results.

Could that be the case here?

"My sense is that the circumcision study may have been stopped too early and that there is a real danger we may be subjecting hundreds of thousands or millions of men to having circumcisions that may not have the benefit we assume," Jeremy Grimshaw, director of the Clinical Epidemiology Program at the University of Ottawa, warns me about the South African study.

Gasp a third time. So why stop a study when the number of people who had become infected wasn't even half as large as the number who had the disease to start with and weren't told they had it? My guess is a guilty conscience. The doctors wanted an excuse to tell all the infected of their condition, no matter the stigmatization, and the early, positive statistics gave them just such an out.

My justification for this charge is that immediately after they closed down the trial, the researchers changed the rules so they could inform people of their disease, even if the people initially said they didn't want to know.

Maybe other, still ongoing trials will support the cut cure, but for the time being my faith in this one has gone snippety, snip, snip.

Dr Petra's Blog
January 7, 2007

You may remember before Christmas there was a lot of media attention to new research from Africa that suggested men who had been circumcised had lower HIV rates than men who had not undergone this procedure. I had a few questions about the research - particularly why it was a halted trial that went straight to media rather than being published anywhere.

Other colleagues working in the area of HIV have raised more specific concerns about the HIV/Circumcision research and the issues it raises. In particular there are worries that a population that’s not particularly health literate may interpret the study as circumcision gives immunity from HIV, and also that this research doesn’t include the health of women.

One such colleague, David Gisselquist*, has provided some thoughtful analysis of this latest research. He has kindly allowed me to reproduce his views on the HIV/Circumcision trial here:

“Three prospective studies report that circumcision protects African men from sexual acquisition of HIV. What is going on is not so clear. If circumcision is so protective, then why do CIRCUMCISED men in 6 of 10 African countries have HIGHER HIV prevalence than uncircumcised men in Demographic and Health Surveys (see attached table)? If circumcision protects men from sexual acquistion of HIV (and that may be so), then data on HIV prevalence suggests that most HIV in men in Africa is coming from something else.

Table showing HIV prevalence and circumcision

High HIV incidence and prevalence in women, especially young women, almost defines Africa’s HIV epidemic. So let’s look at HIV in women vs. male circumcision (see table above). If we consider countries in Southern Africa in a group, and all other countries in Africa as another group, we find:
(a) Southern Africa: Women in Lesotho have more HIV than women in Malawi, even though a much higher percentage of men are circumcised in Lesotho.
(b) Rest of Africa: The percentage of men circumcised ranges from 9% to 95%, while HIV prevalence in women ranges from 1.9% to 8.7%. The 3 countries with the highest HIV prevalence in women are (in order) Kenya, Uganda, and Tanzania with, respectively, 83%, 25%, and 69% of men circumcised.

The African AIDS literature is awash in fantasies about sugar daddies, and no doubt there are some. But what about risks during gynecological and antenatal care? If researchers in Europe had not looked at blood risks for groups of European women with 20%-50% HIV prevalence, but just winked and implied that the women were promiscuous (and lied about it), the researchers would be recognized as incompetent and probably anti-female. But AIDS experts get away with that sort of behavior in Africa.

Some specific questions that have been avoided for decades: Are multidose vials of tetanus contaminated? What happens to women when specula are reused without sterilization? Is equipment used to draw venous blood during antenatal care sterile? What about conditions during delivery?

When is safe health care for women in Africa going to be a priority in AIDS prevention? Circumcising men will not make women’s health care safe”.

*David is an anthropologist and economist and co-runs a listserve called RELASH (REporters and LAwyers for Safe Healthcare). RELASH is looking for reporters, lawyers, and others interested to share ideas about how to respond to unexplained HIV infections - to promote investigations, compensation and change.

January 7, 2007

I'm Dr Petra, and my blog covers sex and relationship issues that matter

Zimdaily
Monday January 29, 2007

Male Circumcision and HIV Prevention - The Great Controversy

PLoS Medicine, March 27, 2007

Circumcision for HIV Prevention: Failure to Fully Account for Behavioral Risk Compensation

Seth Kalichman, Lisa Eaton, Steven Pinkerton

... the protection of M[ale ]Circumcision] may be partially offset by increased HIV risk behavior, or “risk compensation,” especially reduction in condom use or increases in numbers of sex partners. Risk compensation occurs when individuals adjust their behavior in response to perceived changes in their vulnerability to a disease [6]. Risk compensation may be especially important for MC because avoiding the sexual dissatisfactions of condom use and the desire to have more sex partners are likely to be significant motivations for men to seek circumcision [7]. In South Africa, 73% of men between the ages of 15 and 24 report using condoms during the last time they had sex [8]. It is difficult to imagine a convincing public health message that effectively influences men to undergo circumcision and continue to consistently use condoms.

Circumcised men in the ANRS 1265 trial reported 18% more sexual contacts at follow-up than did uncircumcised men, but no other sexual behavior differences were obtained [1]. However, for ethical reasons all men in MC RCTs receive ongoing risk-reduction counseling and free condoms, which reduces the utility of these trials for estimating the potential behavioral impact of MC when implemented in a natural setting. [Nor was the differential effect considered, of the experimental (circumcised) group but not the control (intact) group being given a painful and marking operation together with the counselling.] One model of the potential impact of MC did not take into account risk compensation [4], but noted that “increases in risk-taking behaviour among circumcised men could reduce the benefit of MC.” Based on the 18% difference in sexual contacts for circumcised and uncircumcised men in the ANRS 1265 trial and the assumption that “risk compensation might be higher in a nonresearch program scale-up,” Kahn et al. [5] adjusted the 60% effectiveness estimate obtained in this RCT downward to 50% to reflect a 25% increase in sexual risk behaviors among circumcised men. Although Kahn et al.'s model explicitly incorporated the increased risk of HIV acquisition associated with risk compensation, it did not consider the impact of risk compensation on the HIV transmission risk of HIV-infected circumcised men, or on circumcised men's risk for non-HIV sexually transmitted infections (STIs).

There is no evidence that circumcision increases or decreases the risk of HIV transmission by HIV-infected men. However, risk compensation by HIV-infected circumcised men will substantially increase the risk of transmission to their sex partners. This suggests that, in the short term at least, circumcision would reduce the incidence of HIV among men, but increase the incidence among women, translating to increased prevalence among women, which in turn translates to greater risk to men. Epidemiological models of MC should take this dynamic into account.

Countless studies have shown that ulcerative and non-ulcerative STIs account for at least some of the rapid increases in HIV transmission in southern Africa [9]. Non-HIV STIs are associated with a 2- to 5-fold increase in HIV transmission risk in countries with low and high rates of MC [9]. In areas with prevalent STIs, the relative increase in men's STI-associated HIV risk can be as high as 60% to 340% [10]. Circumcision likely reduces the risk of acquiring a non-HIV STI and may be partially responsible for the decreased HIV risk observed in circumcision RCTs [1]. Nevertheless, the failure of models to account for increased STI risk due to risk compensation likely inflates estimates of averted HIV infections. Estimates of HIV risks resulting from increased exposure to STIs that coincide with reductions in condom use have been included in previous models of the cost-effectiveness of HIV prevention interventions [11] and should be included in MC models.

Male circumcision - the new hope?

A Myers, J Myers

Before we rush to administer the 'silver bullet' of circumcision in the fight against HIV/AIDS, it is important to take a long cool look at the practice, and the historical and contemporary rationales for its use.

...

Caution and more research are needed

More research is needed into integrated HIV/AIDS maanagement that examines the long-term preventive effects of circumcison. Research should focus on the duration of sexual activity in men (as with the rhythm method of contraception over the reproductive years of women), the impact on female risk of acquiring HIV and on the issue of disinhibition in circumcised men. The impact on women is a key issue and recent research in Uganda shows that female partners of circumcised men appear twice as likely to contract HIV, while South African research shows that of the principal group at risk for HIV infection - 15-24 year olds - a massive 90% of those newly infected were women. In summary the evidence for preventative benefit of male circumcision is rather modest and does not warrent heroic policies or practices.

SAMJ [South African Medical Journal] May 2007, Vol 97, No 5, pp 338-341

African Journal of AIDS Research 2008, 7(1): 1–8
May, 2008

Long-term population effect of male circumcision in generalised HIV epidemics in sub-Saharan Africa

Michel Garenne
Institut Pasteur, Unité d’Epidémiologie des Maladies Emergentes, 25 Rue du Docteur Roux, 75724 Paris Cedex 15, France e-mail: mgarenne@pasteur.fr

Abstract: This paper examines the complex relationship between male circumcision and HIV prevalence and incidence in sub-Saharan African countries that have generalised epidemics. In South Africa, the mean yearly HIV incidence and an estimate of the net reproduction rate of the epidemic (R0) (in this case, the ratio of the number of HIV-infected persons between 1994 and 2004 to the number of persons infected in 1994 from which they were presumed to have become infected) were computed from antenatal clinic data for the period 1994–2004, and then compared, by province, to prevailing levels of male circumcision (high, medium and low). In South Africa, mean yearly HIV incidence and net reproduction rate of the epidemic were not lower in provinces with higher levels of male circumcision. For thirteen other countries where Demographic and Health Survey data were available, male HIV prevalence in circumcised and non-circumcised groups was compared. A meta-analysis of that data, contrasting male HIV seroprevalence according to circumcision status, showed no difference between the two groups (combined risk ratio [RR] = 0.99, 95% CI = 0.94–1.05). Individual case study analysis of eight of those countries showed no significant difference in seroprevalence in circumcised and uncircumcised groups, while two countries (Kenya and Uganda) showed lower HIV prevalence among circumcised groups, and three countries (Cameroon, Lesotho and Malawi) showed higher HIV prevalence among circumcised groups. In most countries with a complex ethnic fabric, the relationship between men’s circumcision status and HIV seroprevalence was not straightforward, with the exception of the Luo in Kenya and a few groups in Uganda. These observations put into question the potential long-term effect of voluntary circumcision programmes in countries with generalised HIV epidemics.

Journal of Public Health in Africa 2011; 2:e4
doi:10.4081/jphia.2011.e4 April 2011

How the circumcision solution in Africa will increase HIV infections

Robert S. Van Howe, Michelle R. Storms

Abstract

The World Health Organization and UNAIDS have supported circumcision as a preventive for HIV infections in regions with high rates of heterosexually transmitted HIV; however, the circumcision solution has several fundamental flaws that undermine its potential for success. This article explores, in detail, the data on which this recommendation is based, the difficulty in translating results from high risk adults in a research setting to the general public, the impact of risk compensation, and how circumcision compares to existing alternatives. Based on our analysis it is concluded that the circumcision solution is a wasteful distraction that takes resources away from more effective, less expensive, less invasive alternatives. By diverting attention away from more effective interventions, circumcision programs will likely increase the number of HIV infections.

Journal of Law and Medicine (Australia), 2011;19:316-34

Sub-Saharan African randomised clinical trials into male circumcision and HIV transmission: Methodological, ethical and legal concerns

Gregory J Boyle and George Hill

Abstract

In 2007, WHO/UNAIDS recommended male circumcision as an HIV-prevention measure based on three sub-Saharan African randomised clinical trials (RCTs) into female-to-male sexual transmsission. A related RCT investigated male-to-female transmission. However, the trials were compromised by inadequate equipoise; selection bias; inadequate blinding; problematic randomisation; trials stropped early with exaggerated treatment effects; and not investigating non-sexual transmission. Several questions remain unanswered. Why were the trials carried out in countries where more intact men were HIV-positive than in those where more circumcised men were HIV-positive? Why were men sampled from specific ethnic subgroups? Why were so many participants lost to follow-up? Why did men in the male circumcision group receive additional counselling on safe sex practices? While the absolute reduction associated with male circumcision across the three female-to-male trials was only about 1.3%, relative reduction was reported as 60%, but, after correction for lead-time bias, averaged 49%. In the Kenyan trial, male circumcision appears to have been associated with four new incident infections. In the Ugandan male-to-female trial, there appears to have been a 61% relative increase in HIV infection among female partners of HIV-positive circumcised men. Since male circumcision diverts resources from known preventive measures and increases risk-taking behaviours, any long-term benefit in reducing HIV transmission remains uncertain.

Ripe Tomatoes, September 13, 2013

Circumcision and HIV

Two out of three key trials registered late

Does circumcision of adult men reduce HIV transmission? Initial scepticism, surely the foreskin reduces friction between penis and vagina, and prevents abrasions and blood transfer, and conflicting observational data, were eventually overcome by three randomised trials, one each from South Africa (click here), Kenya (click here) and Uganda (click here). In each trial men were randomly allocated to immediate circumcision or to wait for two years. All three trials showed about half the number of new HIV infections in the immediate circumcision group. The relevant Cochrane review (click here) summarises them as follows:

“The resultant incidence risk ratio (IRR) was 0.50 at 12 months with a 95% confidence interval (CI) of 0.34 to 0.72; and 0.46 at 21 or 24 months (95% CI: 0.34 to 0.62). These IRRs can be interpreted as a relative risk reduction of acquiring HIV of 50% at 12 months and 54% at 21 or 24 months following circumcision.”

The Cochrane reviewers judged “the potential for significant biases affecting the trial results [as] low to moderate”. Referring to selective reporting they wrote “All three trials clearly stated in their protocols that the primary outcome was HIV incidence. The risk of bias due to incomplete outcome reporting is therefore low in all three trials.”

The trial protocols have not been published so we have to trust that the Cochrane reviewers interpreted them correctly. But if they relied on trial registration documents (click here, for South Africa, here for Kenya and here for Uganda) they would have been misled. They they all indicate more of less the same primary outcomes and planned sample sizes as in the respective papers. But according to the date of first entry, only the Kenyan trial was prospectively registered. The South African trial was registered a year and a half after recruitment ended and seven days before the results were published! The Ugandan one a month after recruitment ended,and a month before publication.

It looks like PLOS One and The Lancet wanted to publish sexy high impact trials, found they weren’t registered, so got the authors to do it retrospectively, and hoped no-one would notice! All three trials were funded by the public sector.

Jim Thornton (Professor of Obstetrics and Gynaecology at Nottingham University)