1. Welcome
Lubes, Rings, Films, Fibers, and Shots 4 HIV Prevention
December 11, 2014 webinar
Exploring the Pipeline

2. Use the question feature to ask questions
during the webinar
• All attendees are in listen-only
mode
• Everyone can ask questions
at any time using the
questions feature or by
emailing
ssemelka@aidschicago.org.
• During Q & A breaks, the
moderators will read
questions that have been
submitted

3. Can’t hear the audio?
• Use your telephone!
• Click on the “audio” tab
• Dial the telephone number,
access code, and PIN you
see on your computer

4. Slides available for download at
www.myprepexperience.org

5. Housekeeping & questions
• Use the “questions” feature to ask
questions OR
• Email ssemelka@aidschicago.org
• Can’t hear? Click the “audio” tab and
dial the number and code
• Download the slides at
www.myprepexperience.org

6. Housekeeping & questions
• Use the “questions” feature to ask
questions OR
• Email ssemelka@aidschicago.org
• Can’t hear? Click the “audio” tab and
dial the number and code
• Download the slides at
www.myprepexperience.org

7. PRE-TEST
LET’S SEE WHAT WE KNOW
7

8. 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

13. 13

14. 14

15. OUR AGENDA
 Quick review of treatment, PEP, PrEP
 Microbicide research
 Rectal products
 Vaginal products
 New PrEP
 New dosing strategies
 New oral drugs
 Long acting injectables
15

16. OUR AGENDA
 Multipurpose Technologies
 Interesting formulations
 Implementation
16

17. 17
Unrestricted
educational
grant from
Janssen
Therapeutics to
AFC
--- 2014
Learn about
research &
development
of new
prevention
technologies

18. EXPECTATIONS AND DISCLAIMERS
18

19. THE ONLY
DUMB QUESTION
IS THE ONE YOU
DIDN’T ASK
19

20. TREATMENT, PEP, PREP
REVIEW
20

21. PREVENTION REVOLUTION
SEISMIC CHANGES
21

22. HOW DOES HIV TREATMENT ACT AS PREVENTION?
22

23. 2011: TREATMENT IS
PREVENTION TOO
23

24. 24

25. 25

26. WHAT IS POST-EXPOSURE PROPHYLAXIS (PEP)?
26

27. WHAT IS PRE-EXPOSURE PROPHYLAXIS (PREP)?
27

28. 2010: PREP WORKS!
28

29. tinyurl.com/CDCprepguidelines
29
2014: Clinical Guidelines

30. Condomless is not “unprotected”
30
2014: Language Matters

31. THE DEVIL IS IN THE DETAILS
PREP ACCESS
31

33. PREP WARM LINE
33
Recently launched!
PrEPline, 855-448-7737
The CCC Pre-Exposure Prophylaxis Service
11 a.m. – 6 p.m. EST
http://nccc.ucsf.edu/2014/09/29/introducing-the-ccc-prepline/

34. HANDY BROCHURE!
34
Designed to help individuals talk to
their doctors about PrEP
Before, during, after visit
Questions to ask
Web resources
tinyurl.com/talkPrEPtoDr

35. 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
35

36. Insurance
Medicaid
Devil in the details
• Prior auth
• Deductibles
• Co-pays
• Tiers
• Confusion
36
ACCESSING PREP— INSURANCE

37. Gilead
support
programs
Medication
Assistance
Program
500% FPL
Co-pay
program
$300/mo.
37
NEWLY IMPROVED – OCTOBER 15, 2014

38. PREP UTILIZATION
38
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%

39. 39

40. www.hivresourcetracking.org

41. www.hivresourcetracking.org

42. STAGES OF CLINICAL TRIALS
42
Graphic courtesy International Partnership for Microbicides

43. PERSPECTIVE
43
Of 10,000 compounds that get
tested in the lab, 5 make it to
human trials and 1 makes it to
market.

44. THE PREVENTION PACKAGE
44
 Condoms – male and female
 Condom-compatible lubricant
 Information/education
 Counseling/risk reduction
 HIV testing
 STI testing/treatment
 HEP A and B vaccinations

45.  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!
45
MICROBICIDES

46. RECTAL GELS
MICROBICIDES
46

47. 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.

49. 49

50. 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

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

52. 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

53. 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

54. 017 ADHERENCE
PK monitoring, “real time” PK
RECTAL GEL
Layered approach to monitoring
•SMS (text messages)
• Product returns
• CASI (computer assisted self interview)

55. RECTAL GEL

56. RECTAL GEL

57. RECTAL GEL

58. RECTAL GEL

59. 59

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

61. 61

63. VAGINAL GELS AND RINGS
MICROBICIDES
63

64. 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

69. 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
69
VAGINAL GELS

70. 70
VAGINAL GELS

71. 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

72. 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

73. VAGINAL GELS
Courtesy of FACTS 001

74. 74
Courtesy of FACTS 001

75. 75
VAGINAL GELS
Courtesy of FACTS 001

76. 76
VAGINAL GELS
Courtesy of FACTS 001

77. 77
VAGINAL GELS
Courtesy of FACTS 001

78. VAGINAL RINGS
MICROBICIDES
78

79. 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

80. WHY AFRICA?
80

81. www.hivresourcetracking.org

82. FILMS AND FIBERS
MICROBICIDES
82

83.  International Partnership for Microbicides
 Early preclinical
 Maraviroc/tenofovir film
 Dapivirine/maraviroc film
 Phase I
 Dapivirine film
83
VAGINAL FILMS

84. 84
VAGINAL NANOFIBERS
NANO FIBERS

85.  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
85
VAGINAL NANOFIBERS
UNIVERSITY OF WASHINGTON
POPULATION COUNCIL

86. DOSING
PREP
86

87. 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
87
INTERMITTENT PREP

88. 88
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)

89. 89
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.

90. ORAL
PREP
90

91. 91
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)

92. LONG ACTING INJECTABLES
PREP
92

93. 93
Graphic courtesy AVAC
LONG ACTING INJECTABLES

94. 94
LONG ACTING INJECTABLES

95. 95
WE’RE IN THE
HOME STRETCH

96. COMBINATION PRODUCTS
MULTIPURPOSE
TECHNOLOGIES
(MPTS)
96

97. 97

98. Female Condoms: The Original MPT
• Several others beyond FC2 are
98
available outside of the US
• Scientists are developing new
options

99. 99
Graphic courtesy AVAC
MPTS

100. MPTS
100
Graphic courtesy AVAC

101. MAPPING PATHWAYS
IMPLEMENTATION
101

102. Published 1 April, 2014
mappingpathways.org

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

104. 104

105.  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

106. POST-TEST
LET’S SEE IF WE KNOW A LITTLE MORE
106

107.  ACCESS Grand Boulevard
 Aidsmap
 AVAC – Global Advocacy for HIV Prevention
 CORE Center
 FACTS
 HIV Prevention Trials Network
 HIV & Microbicides Resource Tracking
Working Group
 Howard Brown Health Center
 International Partnership for Microbicides
 Jessica Terlikowski/AFC
 Microbicide Trials Network
 Population Council
 Treatment Action Group
 University of Chicago
107
ACKNOWLEDGMENTS
Thank you

108. THANK YOU
108

109. CONTACT
JIM – JPICKETT@AIDSCHICAGO.ORG
JESSICA – TERLIKOWSKI@AIDSCHICAGO.ORG