Further Details: Circumcision and Risk of HIV/STIs among Indian Men

[Guest guest]

Dear Dr. ,

The abstract for the presentation at the Infectious Disease Society of America

last week on circumcision and risk of HIV and other STIs can be found at the

following site under Session LB-10

http://www.idsociety.org/me/am2003/ABS_LatebreakerOral.pdf

The study is part of an ongoing, 10-year collaboration between s Hopkins

University in Baltimore land and the National AIDS Research Instititute in

Pune.

The association between lack of circumcision and incident HIV infection in this

study population has been previously reported in the Indian Journal of Medical

Research:

Mehendale SM, Shepherd ME, Divekar AD, Gangakhedkar RR, Kamble SS, Menon PA,

Yadav R, Risbud AR, Paranjape RS, Gadkari DA, Quinn TC, Bollinger RC, Rodrigues

JJ. Evidence for high prevalence & rapid transmission of HIV among individuals

attending STD clinics in Pune, India. Indian J Med Res 1996;104:327-35.

The IDSA presentation included a detailed examination of risk of acquision of

other STIs as well as HIV. While a protective trend was found for HSV-2,

Syphilis, and Gonorrhoea among circumcised men, the associations were not

statistically significant.

This study indicates that uncircumcised men may be more susceptible to infection

with HIV, given the same level of exposure, and highlights the need for

consistent condom use to protect the vulnerable cells in the foreskin.

Definitive evidence of a causal effect await the results of clinical trials

underway in 3 countries of Africa.

The 1996 IJMR article was included in a systematic review of Male Circumcision

for prevention of heterosexual acquisition of HIV in men just published in the

Cochrane Library in July 2003:

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). In: The Cochrane Library, Issue 3, 2003. Oxford:

Update Software.

I have included the abstract of the Cochrane review below:

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 34

observational studies: 16 conducted in the general population and 18 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.

Reviewers' 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.

With Kind Regards,

Shepherd

Research Associate

s Hopkins School of Medicine

Division of Infectious Diseases

1830 E. Monument Street

Baltimore, MD 21287-0003

E-mail: mes@...