Transcript Overview of the current evidence on male circumcision and

Overview of the current
evidence on male circumcision
and HIV prevention
Catherine Hankins
Associate Director,
Department of Policy, Evidence and Partnerships
Chief Scientific Adviser to UNAIDS
Strategies and Approaches for Male Circumcision
Programming
Geneva, Switzerland
5-6 December 2006
Acknowledgements
 Participants in the November 2005
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UNAIDS/WHO/SACEMA meeting on Modelling
Members of the background paper writing group
(Global trends and determinants of prevalence,
safety and acceptability)
UN Working Group on Male Circumcision;
Interagency Task Team; Steering Group on Male
Circumcision and HIV
Colleagues: academics, researchers, public health
practitioners, funders, technical support
providers, prevention activists
Special thanks to Bob Bailey
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Overview of the current evidence on male
circumcision and HIV prevention
• Male circumcision in the emerging HIV
prevention technology landscape
• Historical and epidemiological perspective
• Known benefits (non-HIV)
• Strength of the evidence for HIV
• Biological rationale
• Other issues: impact, resource needs,
acceptability, risk compensation, safety
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Prevention Research Landscape
Vaccines
PREP
HSV2/STI
Data in long term
future
DiaphragmIndex Microbicides
Partner
Rx
Circumcision
Data in “near” future
Data available
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Male circumcision: historical perspective
Male circumcision (MC) is associated
with various cultural factors:
• traditional or religious practices
• rites of passage into adulthood
• promotion of hygiene
The earliest documentary evidence
for circumcision is from Egypt. Tomb artwork from the Sixth
Dynasty (2345–2181 B.C.) shows circumcised men, and one relief
from this period (Ankh Mahor) shows the rite being performed
on standing adult males
Genesis (17:11) places the origin of the rite among the Jews in the
age of Abraham who lived around 2000 B.C.
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Male Circumcision: Background Information
• Globally, approximately 30% of men are
circumcised. In Africa, approximately 68%.
• A practice observed mostly for cultural and
religious reasons, less often for health
reasons.
• A simple procedure that confers benefits.
• A surgical procedure that entails risks
• The benefits of male circumcision must be
weighed against the potential harm.
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Benefits of Circumcision
Urinary tract infections in infants
 12 fold increased risk in uncircumcised boys
Syphilis
 1.5-3.0 fold increased risk in uncircumcised men
Chancroid
 2.5 fold increased risk in uncircumcised men
Human Papilloma Virus (HPV)
 63% reduction in circumcised men
Invasive penile cancer in men
 22 times more frequent in uncircumcised men
Cervical cancer in female partners
 2.0 – 5.8 times more frequent in women with
uncircumcised partners
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Studies of the Association Between
Circumcision and HIV Infection
• 4 ecological studies: HIV prevalence lower
with higher male circumcision prevalence
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
MALE CIRCUMCISION AND POPULATION BASED HIV
PREVALENCE IN AFRICA
Senegal
Sierra Leone
Guinea
Burkina Faso
Ghana
Cameroon
Kenya
High (>80%) male circumcision
Tanzania
Low (<20%) male circumcision
Zambia
Lesotho
Botswana
0
10
20
30
40
Sources: ORC/MACRO, 2005, USAID, 2002
MALE CIRCUMCISION AND HIV IN ASIA
Bangladesh
Pakistan
Philippines
Indonesia
0
0
0.1
0.1
High (>80%) male circumcision
0.1
Low (<20%) male circumcision
Fiji
China
Vietnam
0.30
0.60
PNG
India
0.91
1.2
Burma
Thailand
1.5
2.6
Cambodia
0
1
2
3
Sources: UNAIDS, 2004
Studies of the Association Between
Circumcision and HIV Infection
• 4 ecological studies: HIV prevalence lower
with higher male circumcision prevalence
• 35 cross-sectional studies: meta-analysis
– Overall Crude OR: 0.52 (95% CI: 0.40 to
0.68)
– Adjusted OR: 0.42 (95% CI: 0.34 to
0.54)
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Meta-analysis by Weiss et al.
AIDS 2000; 14:2361-2370
Geneva,
Dec 5, 2006
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.3 .4 .5
1
2
3
Evidence on male A
circumcision
and
HIV
prevention
d ju s te d O d d s R a tio
Strategies and Approaches for Male Circumcision Programming
4 5Hankins
UNAIDS
Studies of the Association Between
Circumcision and HIV Infection
• 4 ecological studies: HIV prevalence lower with
higher male circumcision prevalence
• 35 cross-sectional studies: meta-analysis
– Overall Crude OR: 0.52 (95% CI: 0.40 to 0.68)
– Adjusted OR: 0.42 (95% CI: 0.34 to 0.54)
• 14 prospective studies: adjusted relative risk of
HIV infection for circumcised men is 0.52 – 0.18
(i.e. at least half the probability of acquiring HIV)
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
HIV Acquisition among Male Partners of HIV +
Female Partners By Circumcision Status In Rakai
Acquisition/100py
30
25
27.7
Circumcised
Uncircumcised
27.7
20
15
8.2
10
5
0
0
0
0
<10,000
10,000-49,999
>50,000
Female viral load
40/137 uncircumcised men (16.7/100 py) vs. 0/50 of circumcised men became
infected after two+ years (p = 0.004).
Quinn et al NEJM 2000
Need for Clinical Trials
• “Randomized clinical trials are needed to
determine the utility of circumcision as an HIV
preventive measure.”
• Reasons:
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Geneva,
Dec 5, 2006
All epidemiological studies had been observational
(cannot exclude residual confounding); not all
results were consistent
Risk of too early resumption of sexual activity after
circumcision or subsequent risk compensation could
counteract any protective effect
Risk of post-surgical complications must be
balanced against any protective effect
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Biological Determinants Affecting HIV Sexual Transmission
Infectiousness
Level of Blood Viral Load
Genital Viral Load
Stage of Infection
Lack of circumcision*
Genital ulcerations
Inflammatory STDs
Cervical ectopy
Viral Subtype
X4/R5 Phenotype
Antiretroviral therapy ( )
Geneva,
Dec 5, 2006
Acquisition
Viral Load in Index Case
Lack of circumcision*
Genital ulcers
Inflammatory STDs
Cervical ectopy
HLA Haplotype
Chemokines/Cytokines
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Biological Rationale for HIV link
Biological plausibility
– Inner mucosa of foreskin is rich in HIV target cells
– External foreskin/shaft keratinized and not
vulnerable
– After circumcision, only vulnerable mucosa is
meatus
Foreskin is retracted over shaft during
intercourse
– Large inner mucosal surface exposure
– Micro-tears, especially of frenulum
Intact foreskin associated with infections
– Genital ulcer disease
– Balanitis/phimosis
– Possible increased HIV entry or shedding
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Features of Three Clinical Trials
Orange
Farm
Rakai
Kisumu
Population
Semi-urban
Rural
Urban
MC Rate
20%
16%
10%
HIV incid.
1.6%
1.3%
1.8%
Age Range
18-24 yrs 15-49 yrs 18-24 yrs
Sample size
3,128
5,000
2784
Completion April, 2005 June, 2007 Sept, 2007
Interim DSMB
Geneva,
Dec 5, 2006
Nov, 2004
Dec, 2006
Dec, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Orange Farm Trial Results
Follow-up - 4664 person-years, mean 18 months
Intervention
(n=1538)
Control
(n=1590)
TOTAL
HIV seroconversions
M0–M3 M4–M12 M12–21 Total
2
7
9
18
9
15
27
51
11
22
36
69
Unadjusted RR: 0.40 (0.24–0.68);
p=0.00013
Controlling for behavioural factors: RR=0.39
Per protocol RR: 0.24 (0.14-0.46)
Geneva,
Dec 5, 2006
Hankins
Evidence on male circumcision and HIV prevention
UNAIDS
Strategies and Approaches for Male Circumcision Programming
Source: Auvert et al, 2005
Issues Still to be Addressed
• The impact on HIV prevalence at the population
level: modelling studies
• Resource needs (financial, human, facility),
cost effectiveness
• Acceptability
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Modelling the Impact of MC on HIV Prevalence &
Incidence
Williams et al., 2006
• 100% uptake of MC could avert 2.0 million new
infections and 0.3 million deaths over ten years in subSaharan Africa
• Could avert 5.7 million new infections over 20 years
Mesesan et al., 2006
• 50% uptake of MC could avert 32,000 – 53,000 new
infections in Soweto, SA over 20 yrs. Prevalence would
decline from 23% to 14%
Nagelkerke et al., submitted
• Prevalence in Nyanza Province, Kenya would decline
from 18% to 8% over 30 years with 50% uptake of
circumcision over 10 years
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
13 Acceptability Studies in Non-Circumcising
Communities (9 countries) Westercamp and Bailey 2006
• Perception that MC improves hygiene is
nearly universal.
• Perception that MC reduces risk of STI is
widespread
• Perception that MC reduces risk of HIV is
variable
• Biggest barriers to MC are cost, and
concerns about safety (risk of infection or
mutilation), and pain
• Most communities want safe, affordable
MC services to be available.
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Issues Still to be Addressed
• The impact on HIV prevalence at the population
level: modelling studies
• Resource needs (financial, human, facility),
cost effectiveness
• Acceptability
• Operational requirements
• Risk compensation – will circumcised men feel
they are protected and engage in more risky
behaviours? Will women assume they are
protected and not negotiate condom use?
• Safety
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Risk Compensation
If male circumcision is promoted as being
protective against HIV infection, will
circumcised men be more likely to engage in
higher risk behaviours?
 Orange Farm Trial Results
• Mean # sexual acts higher in circumcised men
• Behavioural factors had no influence on effect of MC
 Agot et al., 2006 Siaya, Kenya
• No difference in sexual risk behaviours of men who became
circumcised compared to controls
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Complications Due to Neonatal Male
Circumcision in the United States
• One study of 230,632 infants
• Complication rate of 0.2%
– Bleeding .13%
– Infection .06%
• One study of 5,521 infants
• Complication rate of 2.0%
– Bleeding 1.0%
– Infection 0.4%
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Complications from Circumcision in Africa
In East and southern Africa – circumcision
primarily of adolescents (ages 8 – 18 years)
 One study in Nigerian and Kenyan Hospitals: about
12%
 Kisumu UNIM randomized controlled trial (ages 1824yrs): complication rate of 1.7%
 Orange Farm Trial (ages 18-24yrs): 3.8%
Many anecdotal reports throughout Africa of
bleeding, infection, mutilation and death,
especially associated with traditional MC
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Background Study in Bungoma, Kenya
Bailey and Egesah 2006
• BaBukusu are an ethnic group that has
traditionally practiced MC for many
generations.
• Recently, Bukusu families have begun to shift
from traditional circumcision rites and rituals
toward medicalized circumcision.
• Reasons: cost, time away from school and
work, safety, HIV risk, “modernization”
• Presents an ideal natural experiment to
assess medical versus traditional MC
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Complications From Traditional Versus
Medical Circumcisions in Bungoma District,
Kenya (N=1010)
VARI
ABL
TRADITION
AL
MEDICAL
TOTAL
AE
N
%
N
%
N
%
Yes
156
35.2
99
17.7
255
25.4
OR
2.53*
No
287
64.8
460
82.3
747
74.6
Bailey & Egesah, 2006
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Most Common Complications Reported
• Profuse bleeding
• Infection requiring antibiotics
• Insufficient foreskin removed: recircumcision required
• Excessive pain
• Erectile dysfunction
• Torsion
• Urinary tract infections
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Adverse Events (AE) By Setting
FACILITY
#
NUMBER
AEs
Public Facility
111
11
10.1
Private
Facility
346
78
22.5
Traditional
426
146
34.3
Total
883
235
26.6
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
%
Hankins
UNAIDS
Summary of Bungoma Complication Study
• Traditional circumcisers and most medical practitioners
are not adequately trained
• Most facilities lack proper supplies and instruments
• Many AEs could be avoided if boys and parents are
adequately trained in post-operative wound care.
• Most Bukusu would in practice prefer medical
circumcision over traditional circumcision, but they
fear stigma and disapproval within the community.
• If medical circumcision were actively promoted, with
complete and correct information provided, many
Bukusu boys and parents would elect to be circumcised
by a medical professional.
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Needs Assessment Kisumu and Suba, Kenya
(Bialey, Onyango, Kanolloh, Westercamp)
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Almost all Medical Officers and Clinical Officers have
performed circumcisions
Almost all but MOs would need and desire additional
training
Cost, lack of resources and lack of trained health staff
are likely to be the major barriers to MC uptake
Communications to overcome cultural barriers necessary
Charges for MC are highly variable and this makes
clients suspicious
Most Health Centres and dispensaries require upgrading
of sterilization equipment and assistance with
consumables
Many facilities, especially private, are currently unable
to offer a comprehensive package of HIV prevention
services (e.g. MC plus VCT & STI treatment)
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Summary
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Evidence of the protective effect of MC on STIs
and HIV is compelling: observational, biological,
clinical trial
Modelling indicates that MC could avert millions of
new HIV infections in East and southern Africa,
and would be highly cost-effective.
Acceptability of MC in non-circumcising populations
is already high and growing.
The limited data on safety are alarming.
Safety is feasible, but will take resources.
Risk compensation must always be a concern.
Needs for training and resources are widespread
outside of hospitals
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Next Steps
Research
 Complete the clinical trials in Kenya and Uganda
 More research into immunohistochemistry of foreskin
and the keratinization process
 Operational research, monitoring and evaluation
 Sutureless techniques for adult circumcision
Action to respond safely to a growing need
 Establish national and regional task forces – include
women
 Rapid needs assessments
 Start pilot integrated programs NOW
Geneva,
Dec 5, 2006
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•
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To test different MC service modalities
To develop training programs and supply mechanisms
To learn what factors contribute to uptake
To monitor and address sources of adverse events
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS
Male Circumcision: an Opportunity
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Programmes that integrate safe male circumcision
services with other sexual and reproductive health
services:
Provide access to young men
 Offer HIV testing and counselling, provide behavioural counselling,
STI treatment, health education, gender sensitivity, parenting
(One Man Can)
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To reduce HIV incidence in men by 60-75%?
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To reduce HIV incidence in women?: fourth trial
reporting in 2008 on whether circumcision of men
with HIV infection reduces transmission to their
female partners
Geneva,
Dec 5, 2006
Evidence on male circumcision and HIV prevention
Strategies and Approaches for Male Circumcision Programming
Hankins
UNAIDS