dec 11, '14 webinar - lubes, rings, films, fibers, and shots 4 hiv prevention
TRANSCRIPT
Welcome
Lubes, Rings, Films, Fibers, and Shots 4 HIV PreventionDecember 11, 2014 webinar
Exploring the Pipeline
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Slides available for download at www.myprepexperience.org
Housekeeping & questions
• Use the “questions” feature to ask questions OR
• Email [email protected]
• Can’t hear? Click the “audio” tab and dial the number and code
• Download the slides at www.myprepexperience.org
Housekeeping & questions
• Use the “questions” feature to ask questions OR
• Email [email protected]
• Can’t hear? Click the “audio” tab and dial the number and code
• Download the slides at www.myprepexperience.org
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PRE-TESTLET’S SEE WHAT WE KNOW
ARV-Based Prevention Pipeline (March 2014)
IPCP NIAID
Pop Council
Pop Council
CONRAD
Albert Einstein
CONRADGSK
IPM
CONRAD
Janssen
TaiMed
Pop Council
HPTN/ACTGIPM CONRAD IPM Gilead
IPM
IPM
IPM
IPM
IPM
IPM
Pop Council
RTI
Pop Council
Mintaka
PBS
ImQuest
ImQuest
Vaginal gel
Oral pills
Vaginal film
Vaginal tablet
Vaginal ringLong acting injectable
DELIVERY SYSTEM
Thin film polymer
Nano-fiberPhosphate buffered saline
PBS
RRectal gel
IPM
IPM
IPM
IPM
R
IPM
R
MVA
TDF/FTC
TFV/FTC
TMC 278
MIV 150
GRF
TFV
TDF
DAP
744
MAbMaraviroc
Tenofovir
GSK 744
Tenofovir disoproxil fumarate/emtricitabine
Dapivirine
Ripilvirine
MIV 150
Tenofovir disoproxil fumarate
Monoclonal antibody
Tenofovir/emtricitabine
Griffithsin
DS003 DS003 (BMS793)
DAR Darunavir
No drug tested currently
5P12 5P12-RANTES
IQP IQP-0528
TFV Tenofovir prodrug
ACTIVE DRUG
RAL Raltegravir
CDC
CONRAD
R
PRE-CLINICAL PHASE I PHASE II PHASE III PHASE IV
Adapted from AVAC Report 2013: Research & Reality. www.avac.org/report2013
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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
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OUR AGENDA
Multipurpose Technologies Interesting formulations Implementation
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Unrestricted educational grant from Janssen Therapeutics to AFC --- 2014
Learn about research &
development of new
prevention technologies
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EXPECTATIONS AND DISCLAIMERS
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THE ONLY DUMB QUESTION IS THE ONE YOU
DIDN’T ASK
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REVIEWTREATMENT, PEP, PREP
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SEISMIC CHANGES
PREVENTION REVOLUTION
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HOW DOES HIV TREATMENT ACT AS PREVENTION?
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2011: TREATMENT ISPREVENTION TOO
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WHAT IS POST-EXPOSURE PROPHYLAXIS (PEP)?
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WHAT IS PRE-EXPOSURE PROPHYLAXIS (PREP)?
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2010: PREP WORKS!
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tinyurl.com/CDCprepguidelines
2014: Clinical Guidelines
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Condomless is not “unprotected”
2014: Language Matters
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PREP ACCESS
THE DEVIL IS IN THE DETAILS
PREP WARM LINE
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Recently launched!
PrEPline, 855-448-7737The CCC Pre-Exposure Prophylaxis Service
11 a.m. – 6 p.m. EST
http://nccc.ucsf.edu/2014/09/29/introducing-the-ccc-prepline/
HANDY BROCHURE!
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Designed to help individuals talk to their doctors about PrEP
Before, during, after visitQuestions to askWeb resources
tinyurl.com/talkPrEPtoDr
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
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Insurance Medicaid
Devil in the details• Prior auth• Deductibles• Co-pays• Tiers• Confusion
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ACCESSING PREP— INSURANCE
Gilead support
programs
Medication Assistance Program
500% FPL
Co-pay program
$300/mo.
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NEWLY IMPROVED – OCTOBER 15, 2014
PREP UTILIZATION
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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%)
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
Uninfected individuals receiving TVD for PrEP were: – 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) – 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
CO
WYNE
KS
ND
SD MIWI
MN
IA
MOINIL OH
KY
ME
NHVT
RINY
CTNJ
MA
PA NYC, LI
AK
TX
OK AR
LAAL GA
SCNC
WVMDDE
MS
TN
VA
FL
Midwest16%
Northeast25%
South32%
West27%
Prescribers of TVD for PrEP are located in 49 of the 50 U.S. states
Overall Midwest Northeast South WestUnique 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%
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www.hivresourcetracking.org
www.hivresourcetracking.org
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STAGES OF CLINICAL TRIALS
Graphic courtesy International Partnership for Microbicides
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PERSPECTIVE
Of 10,000 compounds that get tested in the lab, 5 make it to human trials and 1 makes it to market.
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THE PREVENTION PACKAGE
Condoms – male and female Condom-compatible lubricant Information/education Counseling/risk reduction HIV testing STI testing/treatment HEP A and B vaccinations
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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!
MICROBICIDES
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MICROBICIDES
RECTAL GELS
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.
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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
MTN 017
RECTAL GEL
N = 192Participants Gay/MSM,
transgender women
Study sites• US (4)
• Thailand (2)• RSA (1)• Peru (1)
[Sept ’13 – June ‘16 ]
RECTAL GEL
017 IN BRIEFStudy regimens include:
• 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
RECTAL GEL
017 STUDY DESIGNProduct Sequence
N Period 1(8 weeks)
Product Break(1 week)
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 31Daily rectal gel
Rectal gel before and after sex
Daily Truvada
4 31Daily rectal gel
Daily Truvada
Rectal gel before and after sex
5 31Daily 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
017 ADHERENCE
PK monitoring, “real time” PK
Layered approach to monitoring• SMS (text messages)• Product returns• CASI (computer assisted self interview)
RECTAL GEL
RECTAL GEL
RECTAL GEL
RECTAL GEL
RECTAL GEL
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RECTAL GELS
Combination HIV Antiretroviral Rectal Microbicide Program (CHARM) Phase I
Maraviroc gel
Microbicide Trials Network Phase I – in development
Dapivirine gel
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MICROBICIDES
VAGINAL GELS AND RINGS
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
80% + adherence
= 54% efficacy
The trial achieved a
95% retention
rate
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
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VAGINAL GELS
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VAGINAL GELS
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
VOICE C, D
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
VAGINAL GELS
Courtesy of FACTS 001
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VAGINAL GELS Courtesy of FACTS 001
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VAGINAL GELS Courtesy of FACTS 001
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VAGINAL GELS Courtesy of FACTS 001
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MICROBICIDESVAGINAL RINGS
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
Monthly vaginal ring with Dapivirine
Slide courtesy AVAC
VAGINAL RINGSTWO TRIALS
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WHY AFRICA?
www.hivresourcetracking.org
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MICROBICIDES
FILMS AND FIBERS
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International Partnership for Microbicides Early preclinical
Maraviroc/tenofovir film Dapivirine/maraviroc film
Phase I Dapivirine film
VAGINAL FILMS
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VAGINAL NANO FIBERS
NANO FIBERS
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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
VAGINAL NANO FIBERS
UNIVERSITY OF WASHINGTONPOPULATION COUNCIL
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PREP
DOSING
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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
INTERMITTENT PREP
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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)
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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.
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PREP
ORAL
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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)
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PREP
LONG ACTING INJECTABLES
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Graphic courtesy AVAC
LONG ACTING INJECTABLES
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LONG ACTING INJECTABLES
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WE’RE IN THE HOME STRETCH
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MULTIPURPOSE TECHNOLOGIES(MPTS)
COMBINATION PRODUCTS
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Female Condoms: The Original MPT
• Several others beyond FC2 are available outside of the US
• Scientists are developing new options
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Graphic courtesy AVAC
MPTS
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Graphic courtesy AVAC
MPTS
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IMPLEMENTATION
MAPPING PATHWAYS
Published 1 April, 2014mappingpathways.org
What is most striking is that [the] future is not driven by the science, it is driven by communities and the needs of implementation.
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ADVOCACY
INTERNATIONAL RECTAL MICROBICIDE ADVOCATES 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
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POST-TESTLET’S SEE IF WE KNOW A LITTLE MORE
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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
ACKNOWLEDGMENTS
Thank you
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THANK YOU
