Global AIDS - India
Uncircumcised Indian men have 8 times higher HIV risk
From: Bulletin@nam.org.uk
To: AIDS-INDIA@yahoogroups.com
October 15, 2003
Uncircumcised men have an 8 fold higher risk of becoming infected with
HIV compared to circumcised men, according to a study of 2298 Indian
men presented on Thursday at the 41st Annual Meeting of the Infectious
Diseases Society of America by Dr Steven Reynolds of Johns Hopkins University,
Baltimore.
The research was part of a larger study investigating risk factors for
HIV-1 infection based on men attending one of three STD clinics in Pune,
India. Between 1993 and 2000, 2,298 men who tested negative for HIV-1
were enrolled in the study. During subsequent visits (an average of
three visits in 11 months), 2 of 191 men who were circumcised and 165
of 2,107 who were uncircumcised tested positive for HIV.
Demographics, sexual risk behaviours (including having sex with a prostitute),
and condom use were remarkably similar between both groups, said Dr
Reynolds. Despite the similarity in risk profiles, researchers determined
the incidence rate of HIV-1 among circumcised men was 0.7 percent, whereas
among uncircumcised men it was 5.5 percent, an 8-fold increase. The
relative risk of infection among circumcised men, after adjusting for
calendar year, age group, level of education, marital status, living
with family, multiple sex partners, sex worker partners, condom use,
tattoos and medical injections, was 0.12 (p=0.003).
However, the study did not find circumcision to be protective against
other sexually transmitted diseases, including syphilis, genital herpes
and gonorrhoea.
The findings suggest the benefit of circumcision may be biological rather
than due to other factors, such as difference in behaviour between circumcised
and uncircumcised men, or the possibility that circumcision promotes
the acquisition of sexually transmitted infections, said Dr. Reynolds.
The inner surface of the foreskin is not as thickly "keratinised"
as the outside or other surfaces of the penis, meaning it has less of
a protective layer and may be more easily penetrated by HIV, he said.
It also has higher numbers of the cells that HIV infects, possibly contributing
to the reduced risk of HIV infection observed when the foreskin is removed.
There are other potential methods uncircumcised men may be able to use
to protect themselves against HIV, said Dr Reynolds. In the future,
a topical microbicide product might be applied to the foreskin before
sex to protect against HIV. Such products are in development.
Circumcision isn't totally protective and may not be culturally acceptable
or safe in some settings, so regular condom use is still the best way
of protecting against HIV and other sexually transmitted diseases, said
Dr Reynolds. Condom promotion remains a key strategy in the current
fight against the spread of AIDS, he said.
Circumcision as a potential prevention strategy requires confirmation
by randomised clinical trials, which are the gold standard in evaluating
medical interventions, he said. There currently are clinical trials
underway in Uganda, Kenya and South Africa.
Reference.
Reynolds SJ et al. Male circumcision is protective against HIV-1 but
not other common sexually transmitted infections in India.
41st Annual Conference of the Infectious Diseases Society of America,
San Diego, 2003.
http://www.aidsmap.com./news/newsdisplay2.asp?/newsId=2350
The following is the reply for a request for further details of this
study. Moderator
Dear Mr Thomas,
With regard to the article, Uncircumcised Indian men have 8 times higher
HIV risk, it has not been published and was presented at the IDSA meeting
last week. We will not be releasing further details prior to publication.
We may be able to provide more information after its publication.
Thank you,
Debra L.Gair
Senior Administrative Assistant
Johns Hopkins School of Medicine
Division of Infectious Diseases
1830 E. Monument Street, Room 458
Baltimore, MD 21287-0003
(443)287-4098-Ph (443) 287-6440-Fax
dgair1@jhmi.edu
The following was posted on the AIDS-INDIA eForum on October 17, 2003
Subject: AIDS-INDIA. Further Details: Circumcision and Risk of HIV/STIs
among Indian Men
Dear Dr. Thomas,
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 Johns
Hopkins University in Baltimore Maryland 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,
Walker S, Williamson 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
- 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
- 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,
Mary Shepherd
Research Associate
Johns Hopkins School of Medicine
Division of Infectious Diseases
1830 E. Monument Street
Baltimore, MD 21287-0003
E-mail: mes@jhmi.edu
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