Update on Lubricant Safety & Rectal Microbicide Research/Advocacy

CDC – TRIP – January 19, 2011 Jim Pickett AIDS Foundation of Chicago - Director of Prevention Advocacy and Gay Men’s Health - IRMA Chair 1

In our time together… •

Lube safety

– What do/don’t we know?

– What do we need to know?

– How do we make sense of it all?

– And how do we get there? •

Snapshot – rectal microbicide research and advocacy

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International Rectal Microbicide Advocates 3

Mission: support development of safe, effective, acceptable, and accessible rectal microbicides for all that need them

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IRMA, b.2005

4 people, 4 agencies, 2 countries

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rectalmicrobicides.org

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Lubricants used for anal sex 8

IRMA lube survey

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Why?

– Encourage researchers to conduct more research on lubricant safety – 100’s of lubricants – – Which are most widely used?

Other behaviors and practices 9

rectalmicrobicides.org

IRMA lube survey • Internet-based – Survey Monkey with e-promotion – Ran 29 weeks in 2007 – 6 languages (EN/FR/SP/POR/GER/TUR ) • 8,945 Responses from 107 countries – 6,273 reported AI within the past 6 months (70.1%) – 911 women, • 428 AI in past 6 mos.

• Analysis by UCLA 10

rectalmicrobicides.org

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IRMA lube survey 12

IRMA lube survey • • Well over 100 different lubes used 15 most commonly named, alpha – Astroglide (all types including original) – – Crisco, Durex Elbow Grease, Gun Oil – ID (all types, including Glide and Millennium) – K-Y (all types), Liquid Silk, Pjur Eros – Probe, spit/saliva, Swiss Navy – Trojan, Vaseline – Wet (all types, including Wet original and Wet Platinum) 13

IRMA lube survey • • Low condom use, but lube use relatively common • • High acceptability of RMs as lubes?

• No flavour, colour or smell Consistency: Both thick and liquid • Base: both water and silicone Take into account saliva, water and vaginal fluid 14

Lube safety – Welcome to Caveat City 15

Microbicides 2010

IRMA: Research on Lubricant Safety Very Past Due

"Some lubes are probably better than others, but we don't know where any of the currently available products fall along the spectrum from good to bad. While we push for a safe and effective rectal microbicide, we must ensure that existing lubes don't facilitate HIV transmission. People have a right to this kind of information, and it's very past due." 16

IRMA Steering Committee, and Lube Safety Working Group

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BASED ON CURRENT EVIDENCE:

•Unclear whether any particular type or brand of lube might increase, decrease, have no effect on acquiring HIV and/or rectal STIs •Using male or female condoms still considered best way to prevent acquiring HIV and STIs during AI

IRMA Steering Committee, and Lube Safety Working Group

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BASED ON CURRENT EVIDENCE:

•Condom-compatible lubes associated with decreased risk of condoms breaking, slipping •Not possible at this time to recommend for/against using lubes if having AI w/o condoms •Lube use on its own not proven method of HIV or STI prevention

IRMA Steering Committee, and Lube Safety Working Group

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WE NEED TO CONSIDER:

•Some level of inflammation occurs naturally in rectum, even w/o digestive or GI problems •AI itself, enemas, douching, cause temporary damage •Most of this damage repairs itself within minutes/hrs

IRMA Steering Committee, and Lube Safety Working Group

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WE NEED TO COMPARE:

•Because normal levels inflammation and cell damage occur naturally, we need to compare  Levels of inflammation and damage that are result of AI alone, without lubes  Levels of inflammation and damage that are a result of AI alone, with lubes

IRMA Steering Committee, and Lube Safety Working Group

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A sample of the science

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The science • Some studies tested lubes on rectal tissue in mice to see if they were toxic, irritating or caused damage.

– Sudol KM, Phillips DM. “Relative safety of sexual lubricants for rectal intercourse”, Sex Transm Dis. 2004 Jun; 31:346-9.

– Sudol KM, Wallace R, Ford BE, Phillips DM. “Relative safety of OTC lubricants for rectal intercourse,” Microbicides 2006 poster (unpublished).

Short answer – yes, for most lubes 23

The science • • Only one study has tested the effect of lubes on rectal tissue in humans – Fuchs EJ, et al. “Hyperosmolar sexual lubricant causes epithelial damage in the distal colon: potential implication for HIV transmission”, J Infect Dis. 2007 Mar 1; 195(5): 703 10.

Single rectal application of a hyperosmolar lube can cause damage to the rectal tissue 24

The science

Many water-based lubes are hyperosmolar

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The science

Osmolarity is a measure of the concentration of the soluble components—or solutes— present in a solution. Can be iso, hypo, or hyper

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The science

Iso-osmolar same osmolarity as normal cells products have

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The science

Hypo-osmolar bursting products tend to make cells swell up with water, can lead to cells

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The science

***Hyperosmolar products have a higher concentration of solutes than normal human cells. When in contact with rectal/vaginal cells, “suck” away water from inside cells, making them shrink in size

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The science • Some studies tested lubes in a laboratory to see if they killed HIV in vitro. – – – – Begay O, et al. “Preliminary evaluation of toxicity and antiviral properties of personal lubricants,” Microbicides 2010 poster (unpublished) Russo J, Dezzutti C, et al. “Safety and Anti-HIV Activity of Over-the-Counter Lubricant Gels,” Microbicides 2010 presentation (unpublished).

Nguyen D, Lee H, Poast J, Cloyd MW, Baron S. “Preventing sexual transmission of HIV: anti-HIV bioregulatory and homeostatic components of commercial sexual lubricants,” J Biol Regul Homeost Agents. 2004 Jul Dec; 18(3-4): 268-74.

Baron S, Poast J, Nguyen D, Cloyd MW. “Practical prevention of vaginal and rectal transmission of HIV by adapting the oral defense: use of commercial lubricants,” AIDS Res Hum Retroviruses. 2001 Jul 20; 17(11): 997-1002.

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The science • • • [Begay O, et al. “Preliminary evaluation of toxicity and antiviral properties of personal lubricants,” Microbicides 2010 poster (unpublished)] A total of 41 lubricants were examined, compared to Gynol II® and Carraguard® as positive and negative controls for toxicity, respectively Evaluated the in vitro toxicity, anti-HIV-1 activity, osmolality of popular lubes Most of the lubricants were found to be hyperosmolar 31

The science • • • [Begay O, et al. “Preliminary evaluation of toxicity and antiviral properties of personal lubricants,” Microbicides 2010 poster (unpublished)] Most commercial lubricants had little/no antiviral activity against 2 laboratory strains of HIV-1 (CCR5 and CXCR4 viruses) Four Astroglide lubricants (Astroglide® Liquid, Astroglide® Warming Liquid, Astroglide® Glycerin & Paraben-Free Liquid, Astroglide® Silken Secret™) enhanced HIV-1 infection in vitro More rigorous safety testing may need to be performed on these products 32

The science • Some studies have used human tissue (taken from the vagina or rectum) and tested lubes in vitro to see if they were toxic, irritating or caused damage to the tissue – Russo J, Dezzutti C, et al. “Safety and Anti-HIV Activity of Over-the-Counter Lubricant Gels,” Microbicides 2010 presentation (unpublished) 33

The science • • • • • [Russo J, Dezzutti C, et al. “Safety and Anti-HIV Activity of Over-the-Counter Lubricant Gels,” Microbicides 2010 presentation (unpublished)] KY Jelly is toxic to lactobacilli Elbow Grease, ID Glide, and KY Jelly have similar toxicity profiles for cells, cell lines, and tissues Astroglide is most toxic PRÉ and Wet Platinum appear safest None of the lubricants have anti-HIV activity 34

The science • Another study looked at link between the use of lubes during AI and some sexually transmitted infections (STIs) in rectum – Gorbach PM, et al. “Rectal lubricant use and risk of rectal STIs,” Microbicides 2010 presentation (unpublished).

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The science • • • [Gorbach PM, et al. “Rectal lubricant use and risk of rectal STIs,” Microbicides 2010 presentation (unpublished)] Women, men in two U.S. cities asked about lube use during AI, tested for STIs - gonorrhea and chlamydia Lube use during AI in past mo. = more likely to test positive for rectal STI than those who reported not using lubes during AI— condoms used or not Strong association between using lube and having a rectal STI – but… • Not designed to show if timing of lube use/acquiring rectal STI coincided • • Not designed to show whether lubes caused the higher rate of rectal STIs Didn’t indicate specific lubes used 36

The science [Gorbach PM, et al. “Rectal lubricant use and risk of rectal STIs,” Microbicides 2010 presentation (unpublished)] Frequency of Lube Use in Past Month n=380 Never Sometimes Always

N

73 170 137

%

20% 44% 36% 37

The science – what’s on tap • FC2 data – unpublished – Dezzutti – Does the FC2 lube effect tissue viability? NO – Does the FC2 lube impact the epithelium?

• • Evaluate permeability of stratified epitheilium NO Tissue histology NO – Does the FC2 lube have anti-HIV activity? NO • Gorbach – more analysis of existing lubricant data and new Project AWARE lube sub-study (part of a 9 U.S. clinic study on STDs) • Douche/enema data 38

Regulation 39

Regulation 40

Regulation Regulators in various countries classify lubes differently, depending on claims made by manufacturers Application of different sets safety criteria for exact same product in different countries

IRMA Lube Safety Working Group

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Regulation Safety criteria for medical devices usually stricter than cosmetics criteria U.S. simply requires data from studies that test whether lubes irritate rabbit vaginas IRMA – current criteria insufficient based on info from lube studies to date

IRMA Lube Safety Working Group

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Regulation In some contexts, some lubes are on the market w/out any regulatory approval Some regulatory agencies have little to no power or resources to:

IRMA Lube Safety Working Group

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Regulation Even in jurisdictions where : • Regulatory agencies have very clear and

stringent safety criteria

• Power and resources to enforce rigorously • May still be no requirement to

demonstrate safety for rectal use

• Manufacturers rarely indicate product

intended for that use IRMA Lube Safety Working Group

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Regulation – lack of clarity moment #1

Here’s the rub

• No clarity around safety tests to recommend, even if

regulations demanded them

• Regulators likely to be hesitant to enforce tests that would yield limited safety info

IRMA Lube Safety Working Group

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Lack of clarity moment #2

Even if/when we know which lubes are better than others…

How does that translate into HIV/STI risk?

IRMA Lube Safety Working Group

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What is IRMA doing?

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What is IRMA doing?

• • • Urge researchers to test lubes for rectal safety and to share findings Facilitate dialogue leading researchers/advocates in Lube Safety Working Group (wanna join?) Compile articles, studies, maintain background document 48

What is IRMA doing?

• • • • Make IRMA’s list of most widely used lubes available to anyone interested in testing lubes Monitor how regulatory agencies in various countries address lube safety Engage with lube manufacturers Keep IRMA membership updated 49

irma-rectalmicrobicides.blogspot.com

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Safety of lubricants for rectal use: A fact sheet for HIV educators and advocates

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Safety of lubricants for rectal use: Questions & Answers for HIV educators and advocates rectalmicrobicides.org

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Lube safety conclusions • • • • Water-based lubes don’t look great BASED ON THE TESTS CONDUCTED TO DATE We don’t know how this translates into real-world use, real-world risk Is there a commitment to find out?

Can we ever imagine advocating for AI without lubricant?

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IRMA Steering Committee, and Lube Safety Working Group

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Snapshot : rectal microbicide research and advocacy 54

RM research activities 55 Source: From Promise to Product: Advancing Rectal Microbicide Research and Advocacy

Rectal Specific Products

• CHARM Program – C ombination H IV A ntiretroviral R ectal M icrobicide P rogram – DAIDS IPCP Program – Tenofovir, [UC781, tenofovir + UC781] – Consortium • University of Pittsburgh • UCLA • Johns Hopkins • CONRAD PI: Ian McGowan MD PhD

Slide courtesy of Ian McGowan MD PhD 57

Slide courtesy of Ian McGowan MD PhD 58

Slide courtesy of Ian McGowan MD PhD 59

A two-site, Phase 1, partially-blinded, placebo-controlled safety, acceptability and pharmacokinetic trial of topical, vaginally-formulated tenofovir 1% gel applied rectally compared with oral 300 mg tenofovir disoproxil fumarate in HIV-1 seronegative adults RMP-02 / MTN-006 UCLA, MWRI, NIH, CONRAD, GILEAD

Trial completed an NIH IP/CP for Topical Microbicides

Boston, Pittsburgh, Birmingham Approx 50% enrolled

Project Gel [Microbicide Safety and Acceptability in Young Men] Pittsburgh, Boston, Puerto Rico

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

Stage 2

Phase 1 tenofovir rectal safety study 42 MSM 80% adherence in Stage 1B McGowan & Carballo-Dieguez 2009 62

Populations for RM studies Phase 2 studies • RAI sexually active men and women • Higher risk populations Phase 2B studies • 3% seroincidence MSM populations • North America • Latin America • Asia • Africa Ian McGowan MD PhD FRCP, Magee Womens Research Institute, University of Pittsburgh, USA

Slide courtesy of Ian McGowan MD PhD 64

iPrEx implications for rectal microbicides

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Acceptability of RMs • • • iPrEx – Only 50% of men took their pills regularly, if at all An ARV-based prevention option based on a lubricant or an enema could be more acceptable to these men Buffet approach!

Advocacy goals

Increase and diversify funding Increase research activities Increase knowledge, awareness

• Learn more about

heterosexual anal sex

• Anal sex practices • Anal health 67

Advocacy goals • Develop Global Rectal Microbicide Development Plan – Every R&D dollar/euro needs to be spent smartly, strategically – Find consensus on research priorities among stakeholders – Coordinate research activities, from discovery through Phase III – Monitor progress 68

Microbicides 2010

Address burden of HIV among gay men, MSM – particularly in developing world Recognise AI as important driver in HIV epidemic among gay men, MSM, heterosexuals

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Project ARM • Project ARM – Africa for Rectal Microbicides – Africa needs research and advocacy strategy specific to the continent – Stigma, criminalization, denial, homophobia – Until recently, vaginal-centric, hetero-centric – Incorporate anal health, LGBT rights, current prevention gaps, other contextual issues – Organizing, capacity building – Meeting at ICASA in December 2011 70

Advocacy goals • • Recruit researchers, advocates Recognize AI as important driver in the HIV epidemic • • • Address burden of HIV among gay men/MSM, particularly in developing world Promote anal health Determine safety of lubricants for rectal use 71

Advocacy goals

Increase and diversify funding

72 Source: From Promise to Product: Advancing Rectal Microbicide Research and Advocacy

Advocacy goals

Projected funding needs

73 Source: From Promise to Product: Advancing Rectal Microbicide Research and Advocacy

Microbicide funding in total Source: Microbicides: Ways Forward 74

NPT funding in total 75 Source: Microbicides: Way Forward

ringonit.org

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Intimacy Connection Pleasure Emotion

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Special thanks to IRMA supporters 79

Super special thanks 80

Questions?

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Thank you

• • • • Jim Pickett [email protected]

aidschicago.org

rectalmicrobicides.org

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