Jim Pickett, AFC/IRMALos Angeles Biomedical Forum May 31, 2013

The Present and Future of Microbicides

Our time together…• Microbicides

– What are they?– Vaginal microbicide research – Rectal microbicide research

• IRMA– Who is she?– Rectal microbicide advocacy

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Microbicides

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What is a microbicide?

• A product applied topically in the vagina or the rectum that can offer protection against HIV and, ideally, other STI pathogens

• Ideally would have a contraceptive version, and another to allow for pregnancy – ARV/non-ARV (MPTs)

• Formulated as a gel/lubricant, film, or vaginal ring • A rectal microbicide might be delivered via

gel/lubricant, douche/enema, or …Microbicides are still in development

they are not available yet!

McGowan I, Biologicals, 2006Slide courtesy Dr. Ian McGowan

How a microbicide works

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CAPRISA 004

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Vaginal microbicide research

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% + compliance = 54% efficacy

The trial achieved a

95% retention rate

Vaginal microbicide research

• CAPRISA 004 – HUZZAH!

– CAPRISA 008 • Implementation study underway• Effectiveness/sustainability in rural

and urban clinics• HIV-negative CAPRISA 004

participants

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Vaginal microbicide research• VOICE• Phase 2B, randomized, double-blind,

placebo-controlled, 5-arm trial• 5029 women in trial – Uganda, South

Africa and Zimbabwe• Studied daily use of following :

– Vaginal tenofovir 1% gel – Oral tenofovir– Oral Truvada

• Results announced March 2013 CROI 12

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The Big 3 – Effectiveness Trials• Phase III trial of tenofovir gel• BAT24 dosing – hope to confirm CAPRISA 004• 2600 women, age 18-30, SA 10 sites• Oct 2011 ~ mid 2014

IPM 023/The Ring Study• Phase III• 1650 women• South Africa, Rwanda• Apr 2012 ~ mid 2015

ASPIRE/MTN 027, P III• Phase III• 3500 women• Malawi, SA, Uganda,

Zambia, Zimbabwe• July 2012 ~ end 2014

Monthly vaginal ring with Dapivirine – 2 trials

Slide courtesy AVAC

Anal intercourse is a human behavior.

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

Rectal microbicide research

• RMP 01 – UC-781

• MTN 006 – tenofovir• MTN 007 – modified

tenofovir

• Project Gel, CHARM SOON MTN 017

• 36 men/women U.S.

• 18 m/w U.S.

• 65 m/w U.S.

• 186 Peru, RSA, Thailand, U.S., PR (gay, MSM, TG women)

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NICHD R01: Ian McGowan & Alex Carballo-Dieguez

RM Safety, Acceptability /Young Men

Stage 1A

Screening

240 MSM

Consensual RAI in last month

URAI in last year

Stage 1B

3 month Acceptability & Adherence study with

placebo gel

120 MSM

RAI in last 3 months

STI negative

R01 HD059533Slide courtesy Dr. Ian McGowan

Stage 2

Phase 1 Tenofovirrectal

safety study

24 MSM

CHARM Program

• Combination HIV Antiretroviral Rectal Microbicide Program

• Development of rectal specific ARV microbicides

• Humanized mouse model• Phase 1 studies

– Tenofovir– Maraviroc– Tenofovir & Maraviroc

Slide courtesy Dr. Ian McGowan, pic from the IRMA collection

• Phase 1 rectal safety study

• Tenofovir 1% gel– Original formulation

(3,111)– Reduced glycerin

formulation (846)– Rectal specific

formulation (479)

• Endpoints– Safety, – Acceptability, – PK/PD

• N = 18• Sites

– Pittsburgh– UCLA

• Q1 2013

CHARM 01

Slide courtesy Dr. Ian McGowan

• Phase 1 rectal safety study

• Safety in the presence or absence of simulated coitus

• Endpoints– Safety – PK– Product distribution

• N = 9• Sites

– Johns Hopkins• Q1 2013

CHARM 02

Slide courtesy Dr. Ian McGowan

• Phase 1 rectal safety study

• Maraviroc• CCR5 antagonist

(Selzentry®)• Study products

– Maraviroc 0.1%– Maraviroc 1.0 %– Maraviroc + tenofovir

• Endpoints– Safety, – Acceptability, – PK/PD

• N = 24• Sites

– Pittsburgh– UCLA– Johns Hopkins

• Q1 2014

CHARM 03

Slide courtesy Dr. Ian McGowan

MTN-017 – Any day now…

8 weeks 8 weeks 8 weeksGel Daily

Gel With Sex

OralTruvada

Gel With Sex

Gel Daily

OralTruvada

OralTruvada

Gel With Sex

Gel Daily

Slide courtesy Dr. Ian McGowan

Real-time PK monitoring

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To enjoy (the gel)

first you need

to use it

Who is IRMA?

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4 people, 4 agencies, 2 countries

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IRMA, b.2005

1200+ advocates,

scientists, funders, policymakers from

6 continents

29AIDS Foundation of Chicago is the IRMA secretariat

Mission: support development of safe, effective,

acceptable, and accessible

rectal microbicides for all that need them

30AIDS Foundation of Chicago is the IRMA secretariat

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Highly active moderated

listserv

Website

Blog, Facebook, Twitter,

YouTube

Global teleconferences

Materials and Presentations

Focused projects in

Africa, S. America

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Highly active moderated

listserv

You haven’t lived if you’re

not on the IRMA list.

Linda-Gail Bekker, Desmond Tutu HIV Foundation

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irma-rectalmicrobicides.blogspot.com

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YouTubetinyurl.com/RectalRevEnglish tinyurl.com/RectalRevSpanish

tinyurl.com/RectalRevThai

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rectalmicrobicides.org

Monograph being published by RAND – coming to you soon electronically, and featuring a forward by Archbishop Desmond Tutu.

Visit www.mappingpathways.blogspot.com

Thanks to our supporters

• AIDS Foundation of Chicago• amfAR – The Foundation for AIDS Research

• Broadway CARES /Equity Fights AIDS• Elton John AIDS Foundation

• New Venture Fund• NIH Office of AIDS Research

• AVAC • MAC AIDS Foundation

• Microbicide Trials Network• Population Council

• Individuals - like my partner

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Don’t be a stranger

jpickett@aidschicago.org

Thank you xxoo

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Questions/comments?