Transcript Lessons from Global Research on HIV Prevention: “It Takes

New Approaches to HIV Prevention:
Present Status, Future Hopes
Willard Cates, Jr., MD, MPH
Family Health International
Contraceptive Technology Conference
March 31, 2007
Key Topics
• HIV prevention rationale
• HIV prevention approaches
• Current trials
• Future directions
HIV Prevention Research - Why
• Continued
spread of HIV
• Clear moral
imperative to
conduct
prevention
science
2007 – Do the HIV Math
• Major success in ART access
– 1.65 M on treatment, BUT
• 4.3 M new HIV infections
• We’re losing our fight against HIV
Interventions to Prevent HIV
Routes
•Sexual
•Blood
•Perinatal
HIV+
Rx OIs
Perinatal
Reduce High
Risk Behavior
Rx STDs
Newly HIV+
Rx HIV
HIV-
Block with
Barriers
Circumcision
Vaccine
ART PREP
Contraceptive Pregnancy Rates
Spermicides
Diaphragm w/spermicides
Female condom
Male condom
Oral Contraceptives
IUD (TCu-380A)
Rate during perfect use
Female/male sterilization
Rate during typical use
Implant/Depo-Provera
0
5
10
15
20
25
Percent of Women Pregnant in First Year of Use
Source: Trussell (2004); NCHS (2005)
HIV Prevention Tools Infection Rates
Abstinence
Microbicides
Diaphragm
Female condom
Male condom
Oral Acyclovir
Oral ARV
Rate during perfect use
Male circumcision
Rate during typical use
Vaccines
0
20
40
60
80
Percent of Persons Infected after a Decade of Use
Risk of HIV Transmission,
By Consistency of Condom Use,
Discordant Couples
HIV Incidence/ 100 PY
7
6.5
5.1
5
3
1
0
0.9
Always
Sometimes
“Consistent” “Inconsistent”
Never
“Nonuse”
Source: Davis and Weller (1999)
Male Circumcision –
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 urethral meatus
• Moist sub-preputial space increase HIV
survival
Male Circumcision – 3 RCTs
Orange Farm
Rakai
Kisumu
Semi-urban
Rural
Urban
MC Rate
20%
16%
10%
HIV Incidence
1.6%
1.0%
1.6%
Age Range
18-24 yrs
15-49 yrs
18-24 yrs
Sample size
3,128
4,996
2,784
Nov. 2004
Dec. 2006
Dec. 2006
Protex – ITT
60%
51%
53%
– As Rx’d
76%
55%
60%
Population
DMC Stopped
Complications from Circumcision
in Africa
• Orange Farm Trial (ages 18-24 yrs)
– Complication rate of 3.8%
• Kisumu (ages 18-24 yrs)
– Complication rate of 1.7%
• Bungoma, Kenya
– 17.5 % complication rate in medical settings
– 35% complication rate in traditional settings
Topical Microbicides –
Current Products
BufferGel
Carraguard
Pro2000
Tenofovir
Diaphragm
• RCT in Zimbabwe, S Africa
• Diaphragm plus lubricant gel
vs. condom
• 4,500 participants enrolled
• Results expected “soon”
Female Condoms
• Biologic plausibility similar to
male condoms
• If made available, lowers overall
level of unprotected acts
• Emerging evidence on STD
prevention when used consistently
Oral Acyclovir Prophylaxis
• Acquisition – HSV+, HIV- subjects
– HPTN 039 – USA and global
– 3,000 participants – MSM, MSW
– Results expected 2007
• Transmission – HSV+, HIV+ subjects
– Gates – US and global
– 3,600 HIV discordant couples
– Results expected 2009
Oral ARV Pre-exposure Prophylaxis
• Focus for prevention trial ethics/politics
• Studies in multiple populations globally
• Testing 3 transmission routes
• Different drugs and regimens
• West Africa TDF safety data – summer ’06,
International AIDS Meeting
West Africa TDF Conclusions
• Daily oral use of TDF in HIV-uninfected
women was not associated with
increased adverse events
• No evidence of risk compensation
• Acceptability of and adherence to TDF
regimen were possible
• Effectiveness could not be evaluated
conclusively
ARV Treatment as Prevention
• Viral load importance
• HPTN 052 – 8 sites, 5 countries
• Pilot phase completed
• Full trial – 1,760 discordant couples
Contraception as HIV Prevention
Willard Cates, Jr., MD, MPH
Family Health International
HIV Prevention Trials Conference
March 29, 2007
Contraception is HIV Prevention
Willard Cates, Jr., MD, MPH
Family Health International
HIV Prevention Trials Conference
March 29, 2007
WHO Four Element PMTCT Strategy
Prevention of
HIV in
uninfected
women,
especially
young
women
Prevention of
unintended
pregnancies
in HIVinfected
women
Prevention of
transmission
from an HIVinfected
woman to her
infant
Element 1
Element 2
Element 3
General Population
FP & Postnatal
Clinics
ANC Clinics
Support for
mother and
family
Element 4
HIV Care/
Treatment
Effect of Current Contraceptive
Use by HIV+ Women
•
577,000 unintended births averted annually
in HIV+ women – implications for orphanage
•
30% vertical transmission if no ARTs
•
173,000 HIV+ births prevented annually
•
If unmet need for contraception addressed,
this number could be doubled.
Source: Reynolds, et al., 2005
Contraception – The BEST KEPT
SECRET in HIV Prevention
• Effective contraception for HIV-infected
women who do not wish to become
pregnant
– Prevents more infants becoming
infected than NVP
– Decreases the number of future orphans
• Key Question – how best to promote
the SRH/HIV linkages?
SRH and HIV: Key Linkages
SRH
• Family Planning
• Maternal & infant
care
• Management of
sexually
transmitted
infections
• Management of
other SRH
problems
Key
Linkages
Learn HIV status
Promote safer sex
Optimize connection
between HIV/AIDS
and STI services
HIV/AIDS
• Prevention
• Treatment
• Care
• Support
Integrate HIV/AIDS
with maternal and
infant health
Source: WHO/UNAIDS, IPPF/UNFPA (2005)
Future Directions
• Acute HIV infection
• 3rd generation microbicides
• New formulations and
combinations
Transmission Efficiency
Simultaneous Prevention Interventions
in Early HIV Infection Interval
Pathway
Intervention
Biologic
ART to lower viral load
Behavioral
Individual counseling to
promote safer behaviors
Social
Structural interruption
of network processes
Topical Microbicides –
3rd Generation Products
ACID FORM
VivaGel
CAP
TMC 120
UC-781
Microbicides –
Regimens/Formulations
• Coitally – gel, film, suppository, oral
• Daily – gel, oral
• Longer Acting – vaginal ring, sponge
HIV Prevention - 2007
• HIV prevention regaining momentum
• Combination of methods necessary –
ABC…Z (The full alphabet)
• Current methods are working –
when used
• New methods being evaluated