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Male circumcision and risk of HIV infection: Current epidemiological data. Helen Weiss London School of Hygiene & Tropical Medicine, UK. HIV seroprevalence in adults, end 2000. Systematic review, 1999. Inclusion criteria: Studies in Africa Female to male transmission of HIV-1

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male circumcision and risk of hiv infection current epidemiological data

Male circumcision and risk of HIV infection: Current epidemiological data

Helen Weiss

London School of Hygiene & Tropical Medicine, UK

systematic review 1999
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
slide5

RR<1

reduced risk of HIV

among circumcised men

RR=1 (no effect)

Barongo-all

Kelly

Population-based studies

Quigley

Serwadda

Urassa-2

Urassa-3

Bwayo

High risk studies

Cameron

Diallo

Mbugua

Sassan-Morokro

Simonsen

Tyndall

Other studies

Seed

Urassa-4

Combined

.1

.2

.3

.4

.5

1

2

3

4

5

Adjusted relative risk

slide6

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
studies included
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
slide8

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
slide9

Population-based studies - crude RRs

* Additional study - not included in published meta-analysis

slide10

Population based studies - adjusted RRs

* Additional study - not included in published meta-analysis

slide12

High risk groups - crude RRs

* Additional study - not included in published meta-analysis

slide13

High risk groups - adjusted RRs

* Additional study - not included in published meta-analysis

is the effect real
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
limitations
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
effect of age at circumcision
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
does mc affect risk of hiv transmission
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
m f transmission of hiv
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 study

Castilho et al; XIV AIDS conf. abstr. C10907

    • No effect of circumcision on HIV prevalence in female partners of 377 HIV positive men
slide21

STIs

Lack of circumcision

HIV

slide23

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
mc cervical cancer
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)
current research needs
Current research needs

Biological 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)

conclusions
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

what should we do now
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
summary of 2002 analysis
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