male circumcision and risk of hiv infection: current epidemiological data helen weiss london school...
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![Page 1: Male circumcision and risk of HIV infection: Current epidemiological data Helen Weiss London School of Hygiene & Tropical Medicine, UK](https://reader031.vdocuments.mx/reader031/viewer/2022032521/56649d575503460f94a364ad/html5/thumbnails/1.jpg)
Male circumcision and risk of HIV infection:
Current epidemiological data
Helen Weiss
London School of Hygiene & Tropical Medicine, UK
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HIV seroprevalence in adults, end 2000HIV seroprevalence in adults, end 2000
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Systematic review, 1999
• Inclusion criteria:– Studies in Africa– Female to male transmission of HIV-1– Published papers only (up to April 1999)
– 28 studies identified
• Summary risk ratio (RR) obtained using random-effects meta analysis
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Adjusted relative risk
.1 .2 .3 .4 .5 1 2 3 4 5
Combined
Urassa-4
Seed
Tyndall
Simonsen
Sassan-Morokro
Mbugua
Diallo
Cameron
Bwayo
Urassa-3
Urassa-2
Serwadda
Quigley
Kelly
Barongo-all
Other studies
High risk studies
Population-based studies
RR<1reduced risk of HIVamong circumcised men
RR=1 (no effect)
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Updated analysis - Sep 2002
• Aim: To update the meta-analysis and include data from non-African countries with high HIV prevalence
• Inclusion criteria:– Published studies of F-M transmission in
developing countries– Abstracts from XIV AIDS conference included
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Studies included• 11 additional studies identified
– Published literature (9)– Abstracts from XIV International AIDS
conference (2)– 5 cohort studies– 2 non-African studies
• Total of 38 studies, of which 22 adjusted for confounding
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Study characteristics• 17 population-based
– 12 cross-sectional, 3 cohort, 2 case-control– 6 Mwanza, 4 Rakai, 3 Kenyan
• 18 high risk groups– STD clinic attendees, truck drivers, TB patients, discordant couples– 11 cross-sectional, 5 cohort, 3 case-control– 7 Nairobi studies
• 3 others - Volunteers, factory workers
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Population-based studies - crude RRs
* Additional study - not included in published meta-analysis
cor.1 .2 .3 .4 .5 1 2 3 4 5
Combined
*Kumwende *Kumwende
*Auvert *Agot
*4city-Nd *4city-Kis Wawer-2 Wawer-1 Urassa-3 Urassa-2
Serwadda Sataran Quigley
Pison Kelly
Carael Barongo-3 Barongo-2 Barongo-1
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Population based studies - adjusted RRs
* Additional study - not included in published meta-analysis
or2.1 .2 .3 .4 .5 1 2 3 4 5
Combined
*Kumwende
*Kumwende
*4city-Nd
*4city-Kis
Urassa-3
Urassa-2
Serwadda
Quigley
Kelly
Barongo-2
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Population-based studiesAnalysis 2000
analysis2002analysis
Crude NRR95% CI
120.930.71-1.21
190.760.59-0.99
Adjusted NRR95% CI
60.560.44-0.70
100.570.47-0.70
RR
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High risk groups - crude RRs
* Additional study - not included in published meta-analysis
cor.1 .2 .3 .4.5 1 2 3 4 5
Combined
*Quinn
*Mehendale
*McDonald
*Lavreys
Tyndall
Simonsen
Sassan-Morokro
Nasio-2
Nasio-1
Lankoande
Hira
Greenblatt
Gilks
Diallo
Cameron
Bwayo
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High risk groups - adjusted RRs
* Additional study - not included in published meta-analysis
or2.1 .2 .3 .4 .5 1 2 3 4 5
Combined
*Mehendale
*McDonald
*Lavreys
Tyndall
Simonsen
Sassan-Morokro
Mbugua
Diallo
Cameron
Bwayo
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High risk group studiesAnalysis 2000
analysis2002analysis
Crude NRR95% CI
120.270.22-0.33
160.300.23-0.40
Adjusted NRR95% CI
70.290.20-0.41
100.310.23-0.42
RR
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Analysis by type of studyAnalysis Cohort
studiesX-sectionalstudies
Crude NRR95% CI
90.460.27-0.78
240.510.39-0.66
Adjusted NRR95% CI
50.390.20-0.76
140.420.33-0.53
RR
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Is the effect real?• Strong, consistent effect
– very unlikely to be to due to random error
• Significant, strong effect in cohort studies (less susceptible to bias)
• Effect strengthens on adjustment for confounders– effect unlikely to be due to residual
confounding
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Limitations• Not a fully systematic review
– Strength of effect may be over-estimated as studies not finding an effect are more difficult to identify
– But - included studies found in recent Cochrane systematic review
• Observational studies only– Possibility of selection biases and residual confounding
• Significant heterogeneity between studies– Effect may differ in different populations
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Effect of age at circumcision• Many African tribes circumcise around
puberty. • Biologically plausible that MC has similar
effect irrespective of age at circumcision• Only 2 studies have examined HIV risk in
relation to age at circumcision– Kelly et al; AIDS 1999; 13:399-405– Quigley et al: AIDS 1997; 11:237-248
• Conflicting and inconclusive results
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Does MC affect risk of HIV transmission?
• Difficult to assess epidemiologically– Women may have more than one partner– More scope for misclassification
• Biologically less plausible than effect of acquisition of HIV
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M-F transmission of HIV• Uganda - cohort study of discordant couples
Quinn et al; NEJM 2000; 342:921-9– Some evidence of reduced transmission among
circumcised males– RR=0.41, 95% CI 0.1-1.1
• Brazil - cross sectional couples studyCastilho et al; XIV AIDS conf. abstr. C10907– No effect of circumcision on HIV prevalence in female
partners of 377 HIV positive men
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Lack of circumcision
HIV
STIs
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Male circumcision & other STIs
Infection Protectiveeffect?
GUD (syphilis, chancroid)
Herpes simplex virus
Gonorrhoea
Non-gonococcal urethritis X
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MC & cervical cancer• Most common cancer in many developing countries
• HPV infection - major cause
• Geographically clusters with penile cancer – Both cancers associated with HPV infection– Lower risk of HPV infection among circumcised men– Lower risk of penile ca. among circumcised men
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MC & cervical cancer
• Multi-country analysis of 1913 couples Castellsague et al: NEJM 2002:346:1105-12
– Brazil, Colombia, Thailand, Philippines, Spain• Adjusted OR = 0.72, 95% CI 0.49-1.04
– In monogamous women: • Adjusted OR = 0.75, 95% CI 0.49-1.14
– Penile HPV infection in male partner:– Adjusted OR = 0.37 (95% CI 0.2-0.9)
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Current research needsBiological mechanism
Attitudes & feasibility of introducing MC among non-circumcising communities
Effect of age at circumcision
Effect of hygiene practices
? Classification of circumcision through physical examination rather than self-report
Data on safety of current MC practices
? Effect of MC among MSM
? Male-female transmission
? Effect of MC on other viral infections of public health importance (e.g. HPV, HSV)
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Conclusions• Observational evidence for a protective effect
of MC on risk of HIV infection is strong and consistent
• BUT cannot exclude selection biases and residual confounding in observational studies
• RCTs will address many of these limitations
Probably not ready to actively promote MC as an HIV prevention measure
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What should we do now?• Disseminate current evidence• Continue studies of acceptability & feasibility of MC in
non-circumcising populations with high incidence of HIV• Assess safety of current circumcising procedures• Develop affordable services for safe voluntary MC• Develop educational materials that:
– emphasise that MC may reduce but not eliminate risk of HIV infection
– Separate out issues of male and female circumcision
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Summary of 2002 analysis• All studies (n=38)
– crude RR=0.52; 95% CI: 0.42 to 0.64– adjusted RR=0.44; 95% CI: 0.37 to 0.53
• Population-based studies - adjusted (n=10)– RR=0.57; 95% CI: 0.47 to 0.70
• High risk groups - adjusted (n=10)– RR=0.31; 95% CI: 0.23 to 0.42