Dr Shay Ganesh, Clinical Manager at medical Research Council in the HIV Prevention, Treatment and Wellness Unit presented on local and global HIV prevention efforts, focusing on previous, current and future programmes. Dr Ganesh  looked towards Pre-Exposure Prophylaxis as a possible future prevention programme and gave some insight into possible programmatic and public health challenges involved in rolling out new HIV prevention programmes.

1. HIV Prevention
Update
Presented By:
Dr. S.Ganesh
Medical Research Council( SA)
HIV Prevention Research Unit
Durban
HIV PREVENTION UPDATE

2. Discussion Focus
• Background
• Current prevention strategies
• Recent updates
• Roll out , Access and Challenges

3. A global view of HIV infection
2.4

4. Background
• Worldwide, an estimated 34 million people are living with HIV,
more than two thirds of whom live in sub-Saharan Africa.
• Since the epidemic began in the early 1980s, more than 60
million people have been infected with HIV and nearly 30 million
people have died of HIV-related causes.
• Even as inroads are made, as a global crisis, HIV/AIDS shows
few signs of slowing down
Ref: www.mtnstopshiv.org

5. In
• Approximately 2.7 million people were newly infected with HIV in
2010 – more than 7,000 every day.
• The number of new infections continues to outstrip advances in
treatment:
• For every person starting HIV treatment, there are two new
infections
• Ref: www.mtnstopshiv.org

6. Women and HIV
• Although the rate of new HIV infections is stabilizing or
decreasing in many countries around the world, the global
epidemic continues to have its greatest toll on sub-Saharan
Africa, a region that accounts for 67 percent of all new HIV
infections and 80 percent of the world‟s HIV-positive women.
Ref: www.mtnstopshiv.org

7. • Women account for 59 percent of adults with HIV in sub-Saharan
Africa, where unprotected heterosexual intercourse is the primary
driver of the epidemic.
• Young women are especially vulnerable. In southern Africa,
young women are up to five times more likely to become infected
with HIV than young men.
• Among both men and women aged 15-24 in sub-Saharan Africa,
71 percent are women.

8. MSM and HIV
• Throughout the globe, racial and ethnic minorities and men who
have sex with men are disproportionately affected.
• Men who have sex with men account for more than half of all
new HIV infections in the U.S. each year, as well as nearly half of
people living with HIV.
• This population bears the burden of the epidemic in many other
parts of the world, such as Europe, Latin America, Australia and
New Zealand.
Ref: www.mtnstopshiv.org

9. Importance of HIV prevention
• Antiretroviral treatment alone will not be able to stem this
epidemic
• No intervention is likely to be fully protective
• Need multiple approaches to HIV prevention (eg., male
circumcision, HSV-2 suppression, PrEP)
• Need short-term interventions while working towards effective
HIV vaccines and microbicides
• Need interventions that target reduced HIV infectiousness &
decreasing HIV susceptibility

10. Current HIV Prevention Modalities
• Biomedical Prevention
• Abstinence
• Condoms
• Behavioral modification
• Diagnosis and treatment of STIs
• HSV suppression
• PREP/PEP
• Circumcision
• Vaccines
• Microbicides

11. Microbicides
Needle exchange
programmes
Testing and
treatment of genital
infections (STIs)
Cervical Barriers:
vaginal diaphragms
HSV-2 Suppressive
therapy
Exposure prophylaxis
MTCT
PEP
PrEP
Immunisation:
Vaccines
Voluntary
Counselling and
Testing (VCT)
Behavioural
Intervention
Abstain
Be faithful
Condomise
HIV
PREVENTION
Male circumcision

12. Rationale for Chemoprophylaxis
for HIV Prevention
• Continuous oral prophylaxis works against malaria and HIV
PMTCT
• Efficacy demonstrated in animal models
• Can be combined with other prevention strategies
• Could be used by both genders
• Potentially could be effective against vaginal, anal, &
parenteral transmission

13. Male Circumcision: Clinical Trials
Population HIV Prevalence (%) Site Recruited End Date/Results
HIV (-) men 7.3 Kenya
(Kisumu)
2,784 53% reduction in
HIV acquisition
HIV (-) men 9 Uganda
(Rakai)
4,996 48% reduction in
HIV acquisition
HIV (-) men 4.5 South
Africa
3,274 60% protection
from HIV acquisition
Ref: Prof G. Ramjee ( 2006)
Challenges
Safety and Ethical Challenges
Cultural and religious acceptability
Effect on female partners
From evidence to public health action

14. Biological data on HIV risk reduction
 Removal of HIV target cells from foreskin
 Keratinisation of skin surface – rapid drying  STI
Epidemiological evidence
 HIV prevalence  in circumcised men
Meta analysis (Weiss et al, 2000)
 38 (mainly African) studies – circumcision  risk of HIV
Ref : Prof G Ramjee ( 2008)
Male Circumcision for HIV Prevention

15. Challenges for
HIV Vaccine Development
 Virus
HIV is hyper-variable
Which HIV antigens needed for protection?
No ideal animal model for HIV/AIDS
Multiple forms/routes for transmission
Replication cycle yields integration- permanently
 Host
Natural immunity doesn‟t eradicate HIV
Correlate of protection- undefined
Superinfection can occur
Ref Prof G Ramjee ( 2008)

16. Microbicides: A Promising Strategy
• Microbicides are products being developed to prevent or reduce
the sexual transmission of HIV or other sexually transmitted
infections (STIs) when used in the vagina or rectum.

17. What might a microbicide look like?
A microbicide could assume a number of different forms:
Gel or cream
Film
Suppository
Pre-loaded diaphragm or cervical cap
Sponge or vaginal ring slowly releasing active ingredient
What would be the ideal characteristics of a microbicide?
active against a range of sexually transmitted pathogens
not irritating to mucosal surfaces
available in both spermicidal and non-spermicidal formulations
effective over relatively long periods
acceptable to potential users (odor, color, taste, portability)
biodiffusible
bioadhesive
stable at high temperatures
able to maintain or enhance normal vaginal ecology; and
not be absorbed systemically
Tablet, capsule, film

18. • The idea for a microbicide-like product was first proposed more than 20
years ago by reproductive health specialists and advocates who
recognized the need for female-controlled HIV prevention methods.
• One of the first products considered was the spermicide nonoxynol-9
because researchers believed it might also be effective against HIV.
• Unfortunately, research showed it was neither safe nor effective against
HIV. Other trials of different so-called first generation microbicides also
proved unsuccessful.
• These included products intended to strengthen natural defenses in the
vagina or create a barrier to protect target cells in the vagina
Ref: www.mtnstopshiv.org

19. 
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South Africa
Zimbabwe
Malawi
Uganda Kenya
Cameroon
Benin
Nigeria
Tanzania
Zambia
Burkina Faso
 CARRAGUARD
CELLULOSE SULFATE
2% & 0.5% PRO2000
BUFFERGEL & 0.5% PRO2000
C31G (SAVVY)
1% TENOFOVIR GEL
Ref: Prof G Ramjee
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India
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Philadelphia,
USA
PHASE IIB/III MICROBICIDE TRIALS:
GLOBALLY

20. 
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CARRAGUARD
CELLULOSE SULFATE
2% & 0.5% PRO2000
BUFFERGEL & 0.5% PRO2000
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Durban
MtubatubaHlabisa
Johannesburg
Pretoria
Cape Town
Johannesburg: RHRU
Pretoria: MEDUNSA
Cape Town: UCT
Mtubatuba: Africa Centre
Durban/Hlabisa: MRC
Ref : Prof G Ramjee
PHASE IIB/III MICROBICIDE TRIALS:
SOUTH AFRICA

21. Earlier Clinical Trials of First-Generation Products
• MDP 301 – A Phase III trial of PRO 2000 that involved 9,395
African women. The study found no evidence that PRO 2000
reduced the risk of HIV. Conducted by the Microbicides
Development Programme, and reported in December 2009.
Ref: www.mtnstopshiv.org

22. HPTN 035
• A Phase IIb trial of PRO 2000 and BufferGel that involved more
than 3,000 women in Africa and the United States. Reported in
February 2009, the results found PRO 2000 was 30 percent
effective compared to a placebo, although this was not
statistically significant. BufferGel was found to have no protective
effect. Conducted by the MTN.
Ref: www.mtnstopshiv.org

23. Savvy (C-31G)
• Two Phase III trials of Savvy closed, the first in 2005 and the
second in 2006, after interim reviews indicated little convincing
evidence that Savvy protected against HIV. Both studies were
conducted by FHI 360.
Ref: www.mtnstopshiv.org

24. Cellulose Sulfate
• In 2007, two Phase III trials of cellulose sulfate were closed early
after a Data Safety and Monitoring Board (DSMB) review of the
study conducted by CONRAD suggested an increased risk of HIV
infection among women using the gel. As a precaution, the
second study, conducted by FHI 360, was also closed, although
its DSMB review found no evidence of increased risk.
Ref: www.mtnstopshiv.org

25. Carraguard
• A Phase III trial of Carraguard, a microbicide developed from
carrageenan, a derivative of seaweed, that showed the product
was safe and acceptable to women, but did not reduce their risk
of acquiring HIV. Conducted by the Population Council
Ref: www.mtnstopshiv.org

26. The State of the Field: Clinical Trials of ARV-Based Vaginal
Microbicides
• CAPRISA 004 – A Phase IIb trial that assessed the safety
and effectiveness of tenofovir gel used before and after
vaginal sex.
• The study, which involved 889 women from South Africa,
found tenofovir gel reduced the risk of HIV by 39 percent
compared to a placebo.
• However, results, which were reported in July 2010, also
indicated that the true level of effectiveness of tenofovir gel –
when used before and after sex – could be anywhere
between 6 and 60 percent.
• CAPRISA 004 provided the first proof of concept that a
microbicide can help prevent HIV, a finding that was
considered a major milestone for the field.
Ref: www.mtnstopshiv.org

27. VOICE (MTN-003)
• Vaginal and Oral Interventions to Control the Epidemic – is a major HIV
prevention trial designed to evaluate the safety and effectiveness of two
different ARV-based approaches for preventing sexual transmission of
HIV in women: daily use of an ARV tablet (tenofovir or Truvada) or daily
use of an ARV-based vaginal gel (tenofovir gel).
• The study began in September 2009 and enrolled 5,029 women in
Uganda, South Africa and Zimbabwe.
• Testing of tenofovir tablets was halted after an independent review of
study data in September 2011 concluded that although the tablets were
safe they were no more effective than placebo in preventing HIV.
• Similarly, a November 2011 routine review indicated that tenofovir gel
was safe but not effective among the women in the study. VOICE
continues to evaluate Truvada.
• Final results are due in early 2013.
Ref: www.mtnstopshiv.org

28. FACTS 001
• A Phase III study testing the same regimen as in CAPRISA 004,
in which women use tenofovir gel before and after sex. FACTS
001 was launched October 2011 and seeks to enroll a minimum
of 2,200 women at nine sites in South Africa. Being conducted by
the Follow-on Africa Consortium for Tenofovir Studies. Results
are expected in 2014
Ref: www.mtnstopshiv.org

29. CAPRISA 008
• A proposed three-year follow-up study of former participants from
CAPRISA 004 that will test the feasibility and effectiveness of
providing tenofovir gel in family planning clinics.
Ref: www.mtnstopshiv.org

30. NEW PRODUCTS
• Vaginal Rings
• ASPIRE (MTN-020) – A Study to Prevent Infection with a Ring
for Extended Use (ASPIRE) - is a Phase III effectiveness trial of a
vaginal ring containing dapivirine. It is the first Phase III trial of a
vaginal ring for preventing HIV. The study, being led by the MTN,
is expected to be launched at several sites in Africa beginning
mid-2012. About 3,476 women will be enrolled, who will be
randomly assigned to insert either the dapivirine ring or a placebo
ring every four weeks for at least one year. The dapivirine ring
was developed by the International Partnership for Microbicides
(IPM).
Ref: www.mtnstopshiv.org

31. • The Ring Study (IPM 027) – As part of its strategy to license the
dapivirine ring, IPM plans to conduct The Ring Study in parallel
with ASPIRE, the study will collect long-term safety and efficacy
data among approximately 1,650 women at multiple research
centers in Africa. IPM expects to begin enrolling women into The
Ring Study in the first quarter of 2012
Ref: www.mtnstopshiv.org

32. Challenges with HIV Prevention?
• HIV Prevention at the Cross-Roads
• Critically need evidence-based prevention strategies
• Behavior change can be effective
• Increased condom use among serodiscordant couples
• Need to understand role of & interventions for multiple, concurrent
partnerships
• Biomedical interventions that have partial efficacy
• Male circumcision of HIV-negative heterosexual men (clinical trial data)
• ART (based on observational & ecologic data)
• New biologic interventions being tested for efficacy
• PrEP, microbicides (tenofovir gel), HIV vaccines, ART at higher CD4 (HPTN
052)
• No single strategy will work alone
• Multi-component, integrated, partially effective biomedical & behavioral
interventions
• Evidence-based approach to design of combination HIV prevention &
testing effectiveness of a package

33. Combination Prevention?
• Principles of Combination HIV Prevention
• 1) Important to “know one‟s HIV epidemic”
• HIV prevalence & incidence
• Populations at highest risk
• Whether they know they‟re at risk & their HIV serostatus
• Modifiable risk factors (community & individual levels)
• Evidence for different prevention interventions
• 2) To slow HIV epidemic (Ro<1), need interventions with demonstrated
efficacy to reduce infectiousness & susceptibility
• ART for HIV+, MC for HIV- men at high risk (eg., in discordant couples)
• Consider synergy, redundancy & antagonism when combine
interventions
• 3) Consider coverage, efficacy & cost-effectiveness in „scaling up‟
interventions

34. From Research to roll out
Research to Rollout A schematic road
map
Clinical Trial Safety and
Efficacy Real-world Effectiveness

35. Successes from 2011
What Works in HIV prevention, 2/12
Study
Effect size
(CI)
Prime-boost Vaccine
(Thai RV144, 2009)
1% tenofovir gel
(CAPRISA 004, 2010)
TDF/FTC oral PrEP
(iPrEx, 2010)
Medical male circumcision
(Orange Farm, 2005; Rakai, Kisumu, 2007)
TDF/FTC oral PrEP
(TDF2, CDC, 2011)
TDF oral PrEP
(Partners PrEP, 2011)
TDF/FTC oral PrEP
(Partners PrEP, 2011)
Immediate ART for HIV+ partner
(HPTN 052, 2011)
31% (1, 51)
39% (6, 60)
44% (15, 63)
57% (42, 68)
63% (22, 83)
62% (34, 78)
73% (49, 85)
96% (82, 99)
0% 10 20 30 40 50 60 70 80 90 100% Efficacy

36. Access and Programmatic issues: Challenges and questions?
• Who will receive HIV prevention?
• How will they be monitored?
• How often should HIV testing be done?
• Side effects and tolerability?
• Cost effectiveness?

37. To conclude……
• We now have an unprecedented opportunity ,based on solid
scientific data to control and ultimately end the AIDS
pandemic.(Tony Fauci ,NIH, 2011)

38. To conclude……..
• Our efforts have helped set the stage for the historic opportunity
the world has today: To change the course of this pandemic and
usher in an AIDS- free generation.“ ( Hillary Clinton,2011)

39. ACKNOWLEDGMENTS
• Prof G Ramjee
• Microbicides Trials Network

40. Thank You