This is a training on the research and development pipeline for new HIV prevention technologies - including PrEP, microbicides, and new male and female condoms. It was conducted by AIDS Foundation of Chicago's Jim Pickett in partnership with the Illinois Public Health Association, on Monday, September 29, 2014 in Bloomington, Illinois.

1. WELCOME
SEPTEMBER 29, 2014
IPHA – BLOOMINGTON
Exploring the Pipeline

2. PROJECT READY, SET, PREP – PLUS
EXPLORING
THE PIPELINE

3. 3

4. PRE-TEST
LET’S SEE WHAT WE KNOW
4

5. ARV-Based Prevention Pipeline (March 2014)
PRE-CLINICAL PHASE I PHASE II PHASE III PHASE IV
Pop Council
IPM
IPCP NIAID
Pop Council
R
IPM HPTN/ACTG CONRAD IPM Gilead
CONRAD
Albert Einstein
GSK CONRAD
IPM
CONRAD
Janssen
TaiMed
Pop Council
IPM
IPM
IPM
IPM
PBS
IPM
R
IPM
R
Pop Council
RTI
Pop Council
Mintaka
ImQuest
ImQuest
DELIVERY SYSTEM
Oral pills
Vaginal gel
Vaginal film
Vaginal tablet
Vaginal ring
Long acting
injectable
Thin film
polymer
Phosphate Nano-fiber
buffered saline
PBS
R
Rectal gel
IPM
IPM
IPM
IPM
TFV/
FTC
TDF/
FTC
MIV
150
TMC
278
MVA
DAR Darunavir
GRF
TFV
TDF
DAP
IQP IQP-0528
5P12 5P12-RANTES
744
Tenofovir
Tenofovir disoproxil
fumarate
MIV 150
Maraviroc MAb
GSK 744
Tenofovir disoproxil
fumarate/emtricitabine
Dapivirine
Ripilvirine
Monoclonal antibody
Tenofovir/
emtricitabine
Griffithsin
DS003 DS003 (BMS793)
No drug tested
currently
TFV Tenofovir
prodrug
ACTIVE DRUG
RAL Raltegravir
CDC
CONRAD
Adapted from AVAC Report 2013: Research & Reality. www.avac.org/report2013

10. 10

11. OUR AGENDA
 Quick review treatment, PEP, PrEP
 Video: The Rectal Revolution is Here:
An introduction to rectal microbicide
clinical trials
 Microbicide research
 Rectal products
 Vaginal products
11

12. OUR AGENDA
 New PrEP
 New dosing strategies
 New oral drugs
 Long acting injectables
 New male and female
(receptive) condoms
 Multipurpose Technologies
 Interesting formulations
 Implementation
12

13. 13
Unrestricted
educational
grant from
Janssen
Therapeutics to
AFC
- 2014
Learn about
research &
development
of new
prevention
technologies

14. EXPECTATIONS AND DISCLAIMERS
14

15. THE ONLY
DUMB QUESTION
IS THE ONE YOU
DIDN’T ASK
15

16. 16
Discussion
Learning
The only
“dumb”
question is
the one you
didn’t ask
OUR TIME
TOGETHER

17. 17
>>> WHY IS THIS RELEVANT TO ME?

18. TREATMENT, PEP, PREP
REVIEW
18

19. HOW DOES HIV TREATMENT ACT AS PREVENTION?
19

20. 20

21. 21

22. 22

23. U.S. HIV TREATMENT CASCADE

24. WHAT IS POST-EXPOSURE PROPHYLAXIS (PEP)?
24

25. WHAT IS PRE-EXPOSURE PROPHYLAXIS (PREP)?
25

26. THE DEVIL IS IN THE DETAILS
PREP ACCESS
26

27. ACCESSING PREP
Any medical provider who can write a
scrip can write one for Truvada as PrEP
Most HIV docs familiar with PrEP
Chicago:
 Research (Project PrEPare)
 UC and ACCESS Grand Blvd
 Howard Brown Health Center
 CORE Center – clinic coming soon
 Chicago PrEP Working Group
27

29. HANDY BROCHURE!
29
Designed to help individuals talk to
their doctors about PrEP
Before, during, after visit
Questions to ask
Web resources
tinyurl.com/talkPrEPtoDr

30. ACCESSING PREP— INSURANCE
FDA approval of
Truvada enables
private ins to cover
Truvada
on
Medicaid
formulary
Ins companies
covering, so far
ADAP
does not
cover
PrEP
30

31. Insurance
Medicaid
Devil in the details
• Prior auth
• Deductibles
• Co-pays
• Tiers
• Confusion
31
ACCESSING PREP— INSURANCE

32. PREP UTILIZATION
32
A total of 2,319 unique individuals who started
TVD for PrEP between 01 Jan 2012 and 30 Sep
2013 were included in the analysis.
• 48.8% of PrEP users were women.
• Mean age was 38.2 ± 12.2 years
• Males were significantly older (39.5 ±
12.0) than females (36.8 ± 12.3).
p<0.0001
• 12.3% of individuals were under 25 years old.
• The proportion of males under 25 was
8.0% (95% CI 6.5 – 9.5) significantly lower
than that of women 16.8% (95% CI 14.6 –
19.0). p<0.0001
Overall distribution of TVD for PrEP
prescriptions by prescriber specialty:
• Family Practice (18%)
• Internal Medicine (16%)
• Infectious Diseases (11%)
• Nurse Practitioners (9%)
• Physician Assistants (9%)
WY
CO
ND
SD MI
OK AR
 Uninfected individuals receiving TVD for PrEP were:
DE
– 1.8 times more likely to be female (95% CI 1.6 – 1.9)
– 1.4 times more likely to be younger than 25 years old (95% CI
1.3 – 1.7)
MA
– 3.6 times more likely to be treated by a non-ID physician (95%
CI 3.2 – 4.1).
WA
OR
CA
NV
ID
UT
AZ
MT
NM
NE
KS
WI
MN
IA
MO
IL IN OH
KY
ME
NH
VT
RI
NY
CT
NJ
PA NY
C,
LI
A
K
TX
LA
AL GA
SC
NC
WV
MD
MS
TN
VA
FL
Midwest
16%
Northeast
25%
South
32%
West
27%
Prescribers of TVD for PrEP are located in 49 of the 50 U.S. states
Overall Midwest Northeast South West
Unique PrEP users n (%) 2,319* 373 (16%) 570 (25%) 729 (32%) 604 (27%)
Mean age in years (SD) 38 (12) 37 (12) 37 (12) 40 (12) 38 (12)
Younger <25 y/o 12.3% 16.4% 12.3% 9.7% 12.4%
Female 48.8% 53.6% 51.4% 51.4% 39.2%
Medicaid 9.9% 15.3% 15.3% 6.6% 5.1%

33. Chicago PrEP
Working
Group
Researchers
Medical
providers
HIV planning
members
Advocates
CBOs
33

34. TAKING PREP IS
THOUGHTFUL
RESPONSIBLE
CAREFUL
34
AWARE
PRO-ACTIVE
DISCIPLINED

35. TAKING PREP IS
SAFER SEX
35

36. Name a common side
effect from taking PrEP.
Peace of mind.
Learn about PrEP – www.myprepexperience.org

37. INVESTMENT
NEEDED
INFRASTRUCTURE
TRAINING
SOCIAL MARKETING
HEALTH CARE ACCESS
BEST PRACTICES
POLICY/ADVOCACY
FEDERAL
STATE
LOCAL
PUBLIC
PRIVATE
37

38. MORE DATA, MORE ENERGY AND
MORE RESOURCES
38
WOMEN
TRANSGENDER
WOMEN AND MEN

39. CONTINUED
COLLABORATION
39
CHICAGO PREP WORKING GROUP
AVAC
FENWAY
PREP FACTS ON FACEBOOK
PROJECT INFORM
SAN FRANCISCO AIDS FOUNDATION
SISTERLOVE
+ MANY MORE

40. 40

41. VIDEO
THE RECTAL REVOLUTION IS HERE
AN INTRODUCTION TO RECTAL MICROBICIDE CLINICAL TRIALS
41

42. 42
tinyurl.com/RectalRevEnglish
tinyurl.com/RectalRevSpanish
youtube.com/IRMAadvocacy

43. 43
rectalmicrobicides.org

44. SHOWTIME…
44

45. DISCUSSION
45

46. BREAK TIME
46

47. STAGES OF CLINICAL TRIALS
47
Graphic courtesy International Partnership for Microbicides

48. PERSPECTIVE
48
Of 10,000 compounds that get
tested in the lab, 5 make it to
human trials and 1 makes it to
market.

49. THE PREVENTION PACKAGE
49
 Condoms – male and female
 Condom-compatible lubricant
 Information/education
 Counseling/risk reduction
 HIV testing
 STI testing/treatment
 HEP A and B vaccinations

50. Graphic courtesy AVAC

51.  A PRODUCT APPLIED TOPICALLY IN THE VAGINA OR THE
RECTUM THAT CAN OFFER PROTECTION AGAINST HIV AND,
IDEALLY, OTHER STIs
 IDEALLY WOULD HAVE A CONTRACEPTIVE VERSION, AND
ANOTHER TO ALLOW FOR PREGNANCY – ARV/NON-ARV
 FORMULATED AS A GEL/LUBRICANT, FILM, FIBER, VAGINAL
RING
 A RECTAL MICROBICIDE MIGHT BE DELIVERED VIA
GEL/LUBRICANT, DOUCHE/ENEMA, OR …
 MICROBICIDES ARE STILL IN DEVELOPMENT
 THEY ARE NOT AVAILABLE YET!
51
MICROBICIDES

52. RECTAL GELS
MICROBICIDES
52

53. An act of unprotected anal
intercourse is 10 to 20 times more
likely to result in HIV transmission
compared to an act of
unprotected vaginal intercourse.

54. Slide courtesy of the Microbicide Trials Network

56. 56

57. MTN 017
RECTAL GEL
A Phase 2 Randomized Sequence
Open Label Expanded Safety and
Acceptability Study of Oral
Emtricitabine/Tenofovir Disoproxil
Fumarate Tablet and Rectally-Applied
Tenofovir Reduced-Glycerin 1% Gel

58. N = 192
RECTAL GEL
[Sept ’13 – June ‘16 ]
Participants
Gay/MSM,
transgender
women
Study sites
• US (4)
• Thailand (2)
• RSA (1)
• Peru (1)

59. 017 IN BRIEF
Study regimens include:
RECTAL GEL
• Rectal tenofovir gel used daily
• Rectal tenofovir gel used before and after sex
• Truvada tablets taken daily
Each participant will follow all of the study regimens for
eight weeks, with a weeklong break between regimens
when no product will be used
• The order in which participants follow study regimens will be based on
random assignment
All participants receive standard HIV prevention package

60. Product
Sequence
N Period 1
(8 weeks)
Product Break
(1 week)
017 STUDY DESIGN
Period 2
(8 weeks)
Product
Break
(1 week)
Period 3
(8 weeks)
1 31 Daily Truvada
Daily rectal gel
Rectal gel before and
after sex
2 31 Rectal gel before and
after sex Daily Truvada Daily rectal gel
3 31
Daily rectal gel
Rectal gel before and
after sex Daily Truvada
4 31
Daily rectal gel Daily Truvada
Rectal gel before and
after sex
5 31
Daily Truvada
Rectal gel before and
after sex Daily rectal gel
6 31 Rectal gel before and
after sex Daily Rectal gel Daily Truvada
Slide courtesy of Dr. Ross D. Cranston, 017 Principal Investigator
RECTAL GEL

61. 017 ADHERENCE
PK monitoring, “real time” PK
RECTAL GEL
Layered approach to monitoring
•SMS (text messages)
• Product returns
• CASI (computer assisted self interview)

62. RECTAL GEL

63. RECTAL GEL

64. RECTAL GEL

65. RECTAL GEL

66. RECTAL GELS
 Combination HIV Antiretroviral Rectal
Microbicide Program (CHARM)
 Phase I
 Maraviroc gel
 Microbicide Trials Network
 Phase I – in development
 Dapivirine gel

67. 67

69. 69

70. 70

71. VAGINAL GELS AND RINGS
MICROBICIDES
71

72. South Africa -
2 sites in
KwaZulu-Natal
Phase IIB - 889
HIV- women,
18 – 40
Enrolled May
2007 – Jan.
2009
Vaginally
formulated
tenofovir gel
Results July
20, 2010 –
AIDS 2010

73. CAPRISA 008
 Implementation study
underway
 HIV-negative CAPRISA 004
participants
 Effectiveness/sustainability
in rural and urban clinics
 Oct ‘12 – Mar ’15
VOICE [MTN]
 Phase 2B, randomized, double-blind,
placebo-controlled, 5-arm
trial
 5029 women in trial – Uganda,
S. Africa, Zimbabwe
 Studied daily use of following :
 Vaginal tenofovir 1% gel
 Oral tenofovir
 Oral Truvada
 Results announced March 2013
73
VAGINAL GELS

74. 74
VAGINAL GELS

75. VOICE
C, D
Why women didn’t take study product
Asked participants, partners, community members
• Lack of social support
• Hearing that other women were not using
product
• Ambivalence about not knowing if placebo or
active drug
• Concerns about side effects, lack of side effects
• Stigma of using drug used by PLWHIV

76. VAGINAL GELS
Phase III trial of tenofovir gel
BAT24 dosing – hope to confirm
CAPRISA 004
2600 women, age 18-30, South Africa,
10 sites
Oct 2011 ~ late 2014
Results 2015

77. VAGINAL GELS
Courtesy of FACTS 001

78. 78
Courtesy of FACTS 001

79. 79
VAGINAL GELS
Courtesy of FACTS 001

80. 80
VAGINAL GELS
Courtesy of FACTS 001

81. 81
VAGINAL GELS
Courtesy of FACTS 001

82. VAGINAL RINGS
MICROBICIDES
82

83. VAGINAL RINGS
Monthly vaginal ring with Dapivirine
The Ring Study/IPM 023
• Phase III
• 1650 women
• South Africa, Rwanda
• Apr 2012 ~ mid 2015
ASPIRE/MTN 027
• Phase III
• 3500 women
• Malawi, SA, Uganda, Zambia,
Zimbabwe
• July 2012 ~ end 2014
Slide courtesy AVAC
TWO TRIALS

84. WHY AFRICA?
84

85. FILMS AND FIBERS
MICROBICIDES
85

86.  International Partnership for Microbicides
 Early preclinical
 Maraviroc/tenofovir film
 Dapivirine/maraviroc film
 Phase I
 Dapivirine film
86
VAGINAL FILMS

87. 87

89. 89
VAGINAL NANOFIBERS
PSEUDO TAMPON

90.  Weave maraviroc into water-soluble nano fibers
 200 times thinner than strand of human hair
 After insertion into vagina, fibers can dissolve
and release an effective dose in about 6 min
 Intercourse could further disperse drug
throughout the vagina
90
VAGINAL NANOFIBERS
VIA UNIVERSITY OF WASHINGTON

91. 91

92. 92

93. BREAK TIME
93

94. DOSING
PREP
94

95. Alternative Dosing to Augment
Pre-Exposure Prophylaxis Pill Taking
540 HIV-negative volunteers, randomized to 3 arms
Gay men, transgender women, cisgender women
Bangkok, Cape Town, New York City
Began late 2011, ongoing
95
INTERMITTENT PREP

96. 96
INTERMITTENT PREP
Intervention Préventive de l'Exposition aux Risques avec et pour les
hommes Gays
Action to Prevent Risk Exposure By and For Gay Men
Randomized, placebo controlled, pilot study to assess adherence and
feasibility.
France Jan ‘12, Quebec July ’13
Gay men, Canada (50) and France (300) – haven’t used condoms for
anal w/at least 2 partners in past 6 mos
Controversial study design
AIDS 2014 – good adherence (CASI, pill counts, plasma, hair)

97. 97
INTERMITTENT PREP
Regimen = Two Truvada 2 to 24 hours before sex, one tablet
within 24 hours after sex, and another tablet within 48 hours
after sex.

98. ORAL
PREP
98

99. 99
ORAL MARAVIROC
Phase II safety and tolerability study – June ‘12 – July ‘15
600 HIV-negative individuals – women and gay men
All U.S. sites
Comparing 4 regimens
• Maraviroc
• Maraviroc + Emtricitabine (FTC)
• Maraviroc + Tenofovir (TDF)
• Truvada (TDF +FTC)

100. LONG ACTING INJECTABLES
PREP
100

101. 101
Graphic courtesy AVAC
LONG ACTING INJECTABLES

102. 102
LONG ACTING INJECTABLES

103. 103

104. MALE AND FEMALE (RECEPTIVE)
NEW CONDOMS
104

105. The Woman’s Condom
• Polyurethane with dissolving capsule
applicator
• Held in place by foam shapes
• Trials demonstrate safe, acceptable, and easy
to use, and has comparable functionality to
FC2
• Additional studies, including contraceptive
efficacy, are in process
• Received CE marking
• Commercially available in China and South
Africa
FEMALE CONDOMS

106. • Cupid
 Latex, inner sponge that aids insertion
 Outer ring helps keep it in place during sex
 Available in India, Brazil, Indonesia, The Netherlands, South
Africa, Mozambique, and Kyrgyz Republic
 Pre-qualified by WHO/UNFPA, enabling bulk procurement
 Safe, acceptable, and comparable functionality to FC2
 CE marking
• Cupid 2
 Same construction, thinner sponge
 Under evaluation for functionality
FEMALE CONDOMS

107. • Panty Condom
• Polyethylene sheath pre-lubricated w/
Vaseline
• Limited distribution in Colombia, under
review for WHO pre-qualification
• Phoenurse
• Polyurethane, silicone lubricated
• Insertion tool
• Limited availability in China & Brazil, under
review for WHO pre-qualification
FEMALE CONDOMS

108. FEMALE CONDOMS
• Origami
• Silicone, accordion-like folding
• Assessed acceptability and performance with 20 HIV-negative
hetero San Fran couples

109. ANAL CONDOM
 Origami
BOOTY SPECIFIC
 First condom designed specifically for receptive anal sex
 Silicone
 Fenway conducting Phase 1 safety trials with gay men

110. 110
GATES FOUNDATION CONDOM CHALLENGE

111. 111
GATES FOUNDATION CONDOM CHALLENGE
The common analogy is that wearing a
condom is like taking a shower with a
raincoat on. A redesigned condom that
overcomes inconvenience, fumbling, or
perceived loss of pleasure would be a
powerful weapon in the fight against
poverty.
– Dr. Papa Salif Sow, senior program
officer, Gates Foundation

112. 112
GATES FOUNDATION CONDOM CHALLENGE
CONCEPTS IN DEVELOPMENT
• Air-Infused Female Condom
• Uses air pressure to insert
• Polyurethane
• Female Pleasure Condom
• Elliptical opening
• Ribbed exterior
• Pleasure focus
• Non-Gender Specific Internal Silicone Condom
• Refining silicone Origami condoms
• Intended for both vaginal and anal
intercourse

113. COMBINATION PRODUCTS
MULTIPURPOSE
TECHNOLOGIES
(MPTS)
113

114. 114

115. 115
Graphic courtesy AVAC
MPTS

116. MPTS
116
Graphic courtesy AVAC

117. IMPLEMENTATION
117

118. DBS TFV-DP levels at Week 4, by study site
5.4
10.8
27
60
50
40
30
20
10
Miami
DC
SF
60% (557/922) of potentially eligible
participants enrolled, indicating strong
interest in PrEP use
Patients were more likely to enroll if they:
• Had prior PrEP awareness
• Were at higher risk (2-5 or >5 episodes
of anal sex with HIV+ partner in the last
12 months)
98% (n=136) of those with drug levels at
Week 4 had TFV-DP detected
• Most participants (77%) had TFV-DP
level consistent with taking ≥4
doses/week
Interest in FTC/TDF for PrEP and adherence as measured by drug levels
were high in this demonstration research project
43.2
13.6
2 2
18.4
42.9
34.7
0
4 4
40
52
0
BLQ <250 250-550 >550-950 >950
(<2 doses/wk) (2 doses/wk) (4 doses/wk) (daily dosing)
Samples, %
DBS TFV-DP level, in fmol/punch (estimated dosing)
PrEP Demonstration Project
PREP IMPLEMENTATION IN STD CLINICS:
HIGH UPTAKE AND DRUG DETECTION AMONG MSM
48-week, open-label PrEP demonstration project in MSM and transgender women
in San Francisco, Miami and Washington, DC (N=557); Sept 2012 – Jan 2014
Cohen S, et al, CROI 2014; Boston. # 954
IMPLEMENTATION

119. U.S. CITIES INVOLVED IN DEMONSTRATION PROJECTS
San Francisco (2)
Boston (2)
Miami
D.C.
Chicago (2)
Los Angeles (2)
San Diego
Rochester
NYC (2)
Oakland
Birmingham
Orlando
Philadelphia (2)
Memphis
Nashville
New Orleans
Houston(2)
Detroit
Baltimore
Aurora
* NYC = Manhattan, Harlem, Bronx and Brooklyn
Chapel Hill
Jackson
Providence
Newark
Seattle (2)
Cleveland
Atlanta
Dallas
Tampa
Bethesda
Annandale
UPDATED
Demonstration and Implementation projects have a
planned enrollment of approximately 8,000 participants.
119
IMPLEMENTATION

120. SELECTED POST-APPROVAL DEMO/IMPLEMENTATION PROJECTS

121. CHICAGO
IMPLEMENTATION
121

122. 122
SHIPP [SUSTAINABLE HEALTH CENTER
IMPLEMENTATION PREP PILOT]
 June 1. 2014
 Implementation project examining PrEP use in
primary care settings in Chicago, Newark, Houston,
and Philadelphia
 Serves women and men
 Access Grand Boulevard Specialty Clinic
 5401 South Wentworth Avenue
PS-PREP
 Jan 1, 2015
 Randomized clinical trial of
PrEP linkage program by DIS
staff, UC and CDPH
CHICAG0 IMPLEMENTATION

123. 123
PROJECT PREPARE II
CHICAG0 IMPLEMENTATION
 Open label demo project AND safety study of PrEP in
young gay/MSM ages 15-22
 Actively enrolling 300 youth in 13 US sites, Chicago
 Evaluating:
 Safety of PrEP use among young HIV-neg gay/MSM
 Acceptability, patterns of use, adherence
 Risk patterns
 Texting to encourage adherence
 Demographic and/or behavioral difs among youth
 Interested in PrEP study
 Who stays on PrEP

124. 124
CHICAG0 IMPLEMENTATION
HOWARD BROWN HEALTH CENTER
 Evaluating PrEP in community
health center setting
 Collects info on why patient AND
provider are considering PrEP
 Data quality can be monitored by
visit types, provider, and testing
location
 Process enabling improved
communication and tracking of
those interested in PrEP, on PrEP,
discontinuing PrEPages 15-22

125. 125

126. MAPPING PATHWAYS
IMPLEMENTATION
126

127. 127
WE’RE IN THE
HOME STRETCH

128. Published 1 April, 2014
mappingpathways.org

129. What is most striking is
that [the] future is not
driven by the science, it
is driven by communities
and the needs of
implementation.

130. 130

131. 131
>>> HOW CAN I MAKE THIS
RELEVANT TO THOSE I SERVE?

132.  INTERNATIONAL RECTAL MICROBICIDE ADVOCATES
ADVOCACY
 rectalmicrobicides.org
 MAPPING PATHWAYS
 mappingpathways.org
 MY PREP EXPERIENCE
 myprepexperience.org
 CHICAGO FEMALE CONDOM COALITION
 chicagofemalecondom.org
 AVAC – GLOBAL ADVOCACY FOR HIV PREVENTION
 avac.org
 PREP WATCH
 prepwatch.org

133. POST-TEST
LET’S SEE IF WE KNOW A LITTLE MORE
133

134.  Aidsmap
 AVAC – Global Advocacy for HIV Prevention
 FACTS
 HIV Prevention Trials Network
 International Partnership for Microbicides
 Jessica Terlikowski/AFC
 Microbicide Trials Network
 Population Council
 Treatment Action Group
134
ACKNOWLEDGMENTS
Thank you

135. THANK YOU
135

136. CONTACT
JPICKETT@AIDSCHICAGO.ORG