1. UNIVERSITY OF GONDAR
COLLEGE OF MEDCINE & HEALTH SCIENCES
SCHOOL OF BIOMEDICAL & LABORATORY
SCIENCES
DEPARTMENT OF MEDICAL MICROBIOLOGY
TOPIC: Microbicide drug candidates: A New hope for
HIV prevention
By: Setegn Eshetie (1st year MSc student)

2. Outline
Introduction
Rationale for devt of microbicide
Microbicide classification & features
Stages in microbicide devt
Current status of microbicide trials
Challenges in microbicide devt
Conclusion, recommendation, references, &
acknowledgment

3. Introduction
Burden of HIV/AIDS
 Sub-Saharan Africa - 22.5 million people
 South East Asia - 4.1 million people
Women
 Globally = 52 %
 Sub-Saharan Africa= 60 %
 Asia ,approximately 35 %
(UNAID, 2008)

4. Vaccines
Male and female condoms
PrEP
PEP
Microbicides
PMTCT
HIV
Prevention
Cervical barriers:
vaginal diaphragms
Male
circumcision
Clean injecting
equipment
Voluntary
counselling and
testing
Source: www.global-campaign.org.

5. Mechanism of spread
Direct
Indirect
CD4 cells
Dendiritic cells
CD4 cells

6. Rationale for development of
Microbicide
 Insufficiency of other prevention methods
 Acceptability issues
 User initiated vs partner initiated
 Maintains skin on skin intimacy
 HIV infection is higher among women
 Women failure to comply to the use of condoms

7. Microbicide, Classification &
features
 A substance that can reduce the transmission of HIV
and other STI pathogens when applied topically to
genital mucosal surfaces - vaginally
and, possibly, rectally.
available.
They are not yet

8. Microbicide could be…
 Contraceptive Vs non- contraceptive
 Broad activity
 Safe, stable, cheaper/available
 Can applied vaginally/rectally
 Can be utilized in HIV positive individuals
 Effective cell free/cell associated virus

9. How microbicides work?
Membrane
disruptor
• N-9
• C31G
• SLS
Milieu protector
• Buffer gel
• Acidform/lime juice
• Probiotic agents
Entry inhibitor
• Attachment inhibitor
• Fusion inhibitor
After entry
inhibitor
• 1% tenofovir gel
• TMC120. UC781
Unknown
mechanism
• Praneem
• Saponin

10. 1. boosts vagina’s natural
defenses - Buffergel
2. surfactants
4. anti-retrovirals
3. entry inhibitors =
=Tenofovir, UC781, TMC120
CS, Carraguard, Pro2000
Source: Shattock, R.; Moore, J. Inhibiting Sexual Transmission of HIV-1 Infection. Nature Reviews Microbiology. Vol 1, October 2003.

11. Microbicide development
• Toxicity
• potency
Preclinical
evaluation
Phase I
• Safety
• 25 – 40
peoples
• Safety
• efficacy
• 200 – 400
Phase II
Phase III
• Efficacy
• 3,000 –
10,000

12. Current status of clinical trials
 Outcome trials
Study trial
Location
Investigator
Efficacy
N-9
Kenya, Cameroon,
Benin, SA, …
Kreiss et al.
Roddy et al.
Van Damme et al
Nil/↑risk
Buffer gel
SA, Malawi,
Zambia..
Abdool Karimet al
Nil
0.5% PRO 2000
SA, USA, …
Abdool Karimet al
36% pre protocol
analysis.
1% Tenofovir gel
SA
Abdool Karimet al
40% protective
Source: www.avac.org.

13. Some of ongoing & planned trials
Trial name
Study pon/area
Phase
Expected
completion
IPM027
1650 women/SA,
Rwanda
III
2015
CAPRISA008
700 women/SA
III
2015
MTN014
28 women/SA
I
2014
CONRAD118
54 women/USA
I
Late 2013
Effects of
Tenofovir
on CAPRISA
samples
TBD
Preclinical
planned
Zinc salt gel study
TBD
Preclinical
planned
Source: www.avac.org.

14. Challenges in Microbicide dev’t
 Variation of vitro vs vivo efficacy
 Lack of validated animal model
 Absence of markers
 Time, cost
 Ethical issues
 Need of large scale study

15. Conclusion
 Microbicides are an option to prevent HIV
 Various mechanism of microbicide activity
 Marjory women based prevention strategies
 Promising trial results like 1% tenofovir gel
 Ethical, methodological & implementation challenges

16. Recommendation
 Need of continuous effort for the promise to be
realized
Governmental institution
Public institution
Private sectors
GAO like UNAIDS
 need of continuous researches on this optimistic area

17. References
 De Cock KM, Jaffe HW, Curran JW. The evolving
epidemiology of HIV/AIDS. AIDS. 2012;26(10):1205-13.
 Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta
R, Puren A. Randomized, controlled intervention trial of
male circumcision for reduction of HIV infection risk: the
ANRS 1265 Trial. PLoS medicine. 2005;2(11):e298.
 Young MR, Odoyo-June E, Nordstrom SK, Irwin
TE, Ongong’a DO, Ochomo B, et al. Factors associated with
uptake of infant male circumcision for HIV prevention in
Western Kenya. Pediatrics. 2012;130(1):e175-e82.
 And more!!!

18. Acknowledment
 To
Dr. Feleke Moges
Mr. Yitayal Shiferaw
Mr. Abate Assefa
SBMLS, DMM

19. Thank you !!!