The Cochrane review: Male circumcision for prevention of heterosexual HIV

[Guest guest]

The Cochrane Library, Issue 3, 2006. Chichester, UK: Wiley & Sons, Ltd. All rights reserved.

Male circumcision for prevention of heterosexual acquisition of HIV in men (Cochrane Review)

Siegfried N, Muller M, Volmink J, Deeks J, Egger M, Low N, Weiss H, S, on P

A substantive amendment to this systematic review was last made on 09 April 2003. Cochrane reviews are regularly checked and updated if necessary.

PLAIN LANGUAGE SUMMARY

Male circumcision for prevention of heterosexual acquisition of HIV in men

Circumcision in heterosexual men is associated with lower rates of HIV infection. This association is strongest in groups at high-risk of HIV infection. However there are no trials to show whether male circumcision as an intervention reduces HIV infection.

Male circumcision is the surgical removal of the foreskin of the penis. It is a common religious or traditional ritual, and is sometimes done for medical reasons. It is not known if the foreskin affects sexual transmission of infection. Circumcision may be an indicator of men affected by other religious or traditional practices which lower the risk of HIV. The review found that men who have already been circumcised have lower rates of HIV infection than uncircumcised men. However, there is no strong evidence of the effects of male circumcision to try to reduce the spread of HIV/AIDS. Trials are underway.

ABSTRACT

Background:

The findings from observational studies, reviews and meta-analyses, supported by biological theories, that circumcised men appear less likely to acquire human immunodeficiency virus (HIV) has contributed to the recent ground swell of support for considering male circumcision as a strategy for preventing sexually acquired infection. We sought to elucidate and appraise the global evidence from published and unpublished studies that circumcision can be used as an intervention to prevent HIV infection.

Objectives:

1) To assess the evidence of an interventional effect of male circumcision for preventing acquisition of HIV-1 and HIV-2 by men through heterosexual intercourse 2) To examine the feasibility and value of performing individual person data (IPD) meta-analysis

Search strategy:

We searched online for published and unpublished studies in The Cochrane Library (issue 2, 2002), MEDLINE (April 2002), EMBASE (February 2002) and AIDSLINE (August 2001). We also searched databases listing conference abstracts, scanned reference lists of articles and contacted authors of included studies.

Selection criteria:

We searched for randomized and quasi-randomized controlled trials of male circumcision or, in their absence, observational studies that compare acquisition rates of HIV-1 and HIV-2 infection in circumcised and uncircumcised heterosexual men.

Data collection and analysis:

Independent reviewers selected studies, assessed study quality and extracted data. We stratified studies based on study design and on whether they included participants from the general population or high-risk groups (such as patients treated for sexually transmitted infections). We expressed findings as crude and adjusted odds ratios (OR) together with their 95% confidence intervals (CI) and conducted a sensitivity analysis to explore the effect of adjustment on study results. We investigated whether the method of circumcision ascertainment influenced study outcomes.

Main results:

We identified no completed randomized controlled trials. Three randomized controlled trials are currently underway or commencing shortly. We found 35 observational studies: 16 conducted in the general population and 19 in high-risk populations. It seems unlikely that potential confounding factors were completely accounted for in any of the included studies. In particular, important risk factors, such as religion and sexual practices, were not adequately accounted for in many of the included studies.

General population study results:The single cohort study (N = 5516) showed a significant difference in HIV transmission rates between circumcised and uncircumcised men [OR = 0.58; 95% CI: 0.36 to 0.96]. Results for the 14 cross-sectional studies were inconsistent, with point estimates for unadjusted odds ratios varying between 0.28 and 1.73. Six studies had statistically significant results, four in the direction of benefit and two in the direction of harm. The test for heterogeneity between the cross-sectional studies was highly significant (chi-square = 77.59; df = 13; P-value < 0.00001). Nine studies reported adjusted odds ratios with eight in the direction of benefit, ranging from 0.26 to 0.80. Use of adjusted results tended to show stronger evidence of an association although they remained heterogenous (chi-square = 75.2; df = 13; P-value < 0.00001). Only one case-control study was found (N = 51) which had a non-significant result [OR = 1.90; 95% CI: 0.50 to 7.20].

High-risk group study results:The four cohort studies identified found a protective effect from circumcision with point estimates for unadjusted odds ratios varying from 0.10 to 0.39. Two of these studies had statistically significant results. Two studies reported adjusted odds ratios, both protective with one being significant. The chi-square test for between-study heterogeneity was not significant (chi-square = 5.21; df = 3; P-value = 0.16). All eleven cross-sectional studies reporting unadjusted results found benefit from circumcision, eight of which had statistically significant results. Estimates of effect varied from an unadjusted odds ratio of 0.10 to 0.66. Between-study heterogeneity was significant with the chi-square = 29.77; df = 10; P-value = 0.0009. Four of these studies reported adjusted odds ratios ranging from 0.20 to 0.59 and all were significant. One additional cross-sectional study only reported an adjusted odds ratio in the direction of benefit which was statistically significant. All three case-control studies found a protective effect of circumcision on HIV status, two being statistically significant. Point estimates varied from unadjusted odds ratios of 0.37 to 0.88. One reported an adjusted odds ratio showing a significant protective effect.

Adverse effects:No studies reported on the adverse effects of circumcision. In most studies, circumcision had taken place during childhood or adolescence before the studies commenced.

Authors' conclusions:

We found insufficient evidence to support an interventional effect of male circumcision on HIV acquisition in heterosexual men. The results from existing observational studies show a strong epidemiological association between male circumcision and prevention of HIV, especially among high-risk groups. However, observational studies are inherently limited by confounding which is unlikely to be fully adjusted for. In the light of forthcoming results from RCTs, the value of IPD analysis of the included studies is doubtful. The results of these trials will need to be carefully considered before circumcision is implemented as a public health intervention for prevention of sexually transmitted HIV.

Citation: Siegfried N, Muller M, Volmink J, Deeks J, Egger M, Low N, Weiss H, S, on P. Male circumcision for prevention of heterosexual acquisition of HIV in men (Cochrane Review). The Cochrane Database of Systematic Reviews 2003, Issue 3. Art. No.: CD003362. DOI:10.1002/14651858.CD003362.

This is an abstract of a regularly updated, systematic review prepared and maintained by the Cochrane Collaboration. The full text of the review is available in The Cochrane Library (ISSN 1465-1858).

http://www.update-software.com/Abstracts/AB003362.htm

[Guest guest]

Dear FORUM,

Thank you very much for sharing this cochrane review with the group.

Considering the heightened interest on this topic recently, it would be prudent

to share the consolidated reply of a query on this topic raised in the Solution

Exchange AIDS Community. I had quoted the same cochrane review there. There are

many other related resources and opinions as well on the topic contributed by

several people. There we can find a balanced and cautioned approach to the

subject and a call for more research with ethically compliant and scientifically

sound methodology. This consolidated reply was quoted in some other platforms as

well. Kindly share it with the group so that it might help those interested to

get a comprehensive account on the topic.

I am hereby appending the summary below.

Summary of Responses: New research has suggested the safety and effectiveness

of male circumcision in reducing the risk of sexual acquisition of HIV.

Therefore, the query on male circumcision as a potential and effective ‘tool’ to

stem HIV evoked considerable responses. Members discussed experiences and the

possibility of integrating male circumcision into HIV prevention strategies in

India.

Researchers have documented that circumcised males have lower rates of HIV.

However, until last year, no study had tested the effectiveness of circumcision

in preventing sexual transmission of HIV. In 2005, researchers published the

results of a trial in Orange Farm, South Africa, which studied 3,000 HIV

negative men and found that male circumcision significantly reduced the men’s

risk of sexually contracting HIV by 60%. In addition, a study published in March

2006 in Maharashtra found that uncircumcised men were more than six times likely

to acquire HIV. Trials in Zambia and Kenya also support the hypotheses that male

circumcision provides biological protection from HIV.

Members explained that in male circumcision with the removal of the foreskin of

the penis, there is keratinization or hardening of the skin surface. The inner

surface of the foreskin serves as an entry point for the virus. The removal

promotes rapid drying, reducing the risk of acquiring HIV through vaginal sex.

Circumcision also has other potential benefits in terms of HIV prevention,

members noted. A circumcised HIV positive man is less likely to transmit the

infection to a female partner. Male circumcision is associated with protecting

against some sexually transmitted infections, penile cancer, and cervical

cancer.

However, members pointed out that these benefits are dependent on the timing and

type of circumcision. They mentioned that Lesotho is a classic example of a

country with high rates of HIV infection in spite of nearly 50% of its males

having undergone circumcision. This is due to incomplete circumcision that is

traditionally performed.

Members warned that circumcision could be risky if performed in non-sterile

conditions. It can lead to infection, bleeding, permanent injury, or HIV. Every

year the authorities in South Africa report serious complications from

circumcisions of young boys carried out by traditional healers. Members felt

there is a need for more trained staff to perform circumcision to prevent people

from going to unqualified practitioners.

To address this problem, WHO has produced a technical manual to help countries

improve the safety of their circumcision procedures. UN has developed rapid

assessment tools to evaluate key concerns related to the issue of male

circumcision. In addition, to developing awareness, one could reach the youth in

schools, before they become sexually active. Members also stressed on an IEC

campaign for general public and providing incentives to encourage circumcision.

Members also voiced their concerns regarding using male circumcision as

prevention strategy, especially considering that:

The results from studies in Tanzania and Australia show that the protective

effect from male circumcision is not fully understood and may not apply to all

forms of sex

Neonatal circumcision could be considered a violation of the rights of children

If introduced now, by the time the infants circumcised in 2006 would be sexually

active, a HIV vaccine is likely to be available

Circumcision may not really be the reason for reduced risk of infection, the

sexual norms within communities that practice circumcision might be the real

reason

The male foreskin may have sexual value and circumcised males, perhaps because

of reduction of sensation, may be disinclined to use condoms

Additionally, members’ worried promotion of circumcision as ‘prevention method’

could provide a false sense of security. This can lead to circumcised males

indulging in risky sexual behavior. It is important, they argued, to communicate

clearly that male circumcision reduces risk but does not prevent HIV and is only

an additional prevention tool. Therefore, they contended that it must be

encouraged in tandem with other preventive methods, including correct and

consistent condom use, behavior change and voluntary counseling and testing.

Respondents cautioned against immediate launching of circumcision programmes in

India. They argued that before advocacy, the acceptability, safety, cost, and

education of the public on its benefits, needs serious consideration. Cultural

acceptance of male circumcision is vital. Around 20% of men globally and 35% in

developing countries are circumcised for religious, cultural, and medical

reasons. For example, in Botswana, it has proved socially acceptable. In India,

members noted, male circumcision is done for religious and cultural reasons. To

overcome socio-cultural barriers to make circumcision a more widespread

practice, policy makers and program planners would have to proceed carefully.

Members concluded that it is premature to recommend male circumcision as part of

any HIV prevention program. What is required is more research to clarify the

relationship between male circumcision and HIV in different social, ethical,

cultural, and national contexts. They felt individuals can opt for safe

circumcision, but a policy decision on whether to promote it needs to wait until

the results of the Kenya and Uganda trials are available.

Thanking You,

With Regards,

Nabeel.

Dr.Nabeel.M.K.

Alliance for Social Health Action (ASHA)

Academy of Medical Sciences,

Kannur, Kerala

e-mail: <drnabeelmk@...>

[Guest guest]

Dear FORUM,

I found Dr Nabeel word of caution very appropriate. We have to be careful with

statistics, because the causality is not often proven. Lethoto and Botswana have

the highest rates of HIV worldwide alongside

high rates of circumcision.

In many Jewish or Muslim communities, circumcised men would never 'touch' a

menstruating woman, unlike Christian communities where such taboos are not as

frequent.

I am very amazed that nearly all the studies I have read on circumcision and HIV

do not examine this aspect, that a higher proportion of circumscised men may not

have contact with BLOOD of an HIV positive partner. In a serodiscordant couple,

this would delay contamination.

We should never forget that HIV is a bloodborn retrovirus.

I recall a Polish scientist who wrote a fun article on misuse of medical

statistics, he gave an example: " Most people die in their bed -

conclusion, to reduce chances of dying: never sleep in your own bed. "

The stats on circumcision are of the same type.

Nance

e-mail: <g_upham@...>