www guscairns com Rectal microbicides An update Gus
www. guscairns. com Rectal microbicides An update Gus Cairns
www. guscairns. com Why now? Alternatives to condoms needed l Incidence in gay men is not going down l Vaginal microbicides may be available within two years l Safety concerns – and not just among gay men l Human trials – at last – about to start l
www. guscairns. com Alternatives to condoms needed l UK Gay HIV prevalence in London 2000, anon testing: 12. 8%. l GMSS, data collected 2004: 6. 5% UK-wide, 13. 2% London l Among STD clinic attendees, London, 2005: 20. 3% USA: l Annual incidence, anon testing: white gay men, Baltimore: 3%. Black gay men: 15% Asia: l MSM, Bangkok: prevalence, anon testing: 2003, 17%. 2005, 28%. l l l
www. guscairns. com Gay men try to protect themselves l Serosorting study, Seattle: l HIV diagnoses among men who: l “Did not have anal sex”: 0. 9% l “Did not have UAI”: 1. 5% (34% of testees) l “Only had UAI with other negative guys”: 2. 6% l Took no precautions: 4. 0% l About one in five gay men who have UAI try only to do it with concordant partners
www. guscairns. com Latest London gym study
www. guscairns. com …but appears to have no effect on incidence HPA anonymous testing programme, gay men attending STD clinics
www. guscairns. com We need biomedical interventions because: l l l They don’t rely on perceptions of risk They don’t require disclosure They could possibly be used well in advance of sex – of, if not, in a way that adds to pleasure They don’t rely on you preparing your ‘works’ when you’re ‘high’ They’re compatible with sexual dysfunction The more prevention tools we have the more they can be used ‘in combination’
www. guscairns. com Demand: Do Gay Men Want a Rectal Microbicide? >10, 000 from web PEP Heard of 21% Would consider 71% Home HIV 22% test Microbicide 23% 53% Vaccine 50% 66% 59% Terrence Higgins Trust 2003 Gay Men’s sex survey
www. guscairns. com An example of a successful biomedical intervention l Circumcision study, South Africa, 2005 l l Cohort study, Uganda, 2006 l l Reduced acquisition of HIV in circumcised men by 75% Female partners of circumcised men had 30% lower rate of HIV infection (and some STDs) Where’s the gay men’s study…. ?
www. guscairns. com …and is catching on l l l SWAZILAND: Circumcision Makes Comeback in AIDS-Hit Swaziland Reuters (02. 24. 06) - Tuesday, February 28, 2006 Circumcision has recently gained high regard in Swaziland in the wake of the first controlled study to show that circumcised men are about 60 percent less likely to contract HIV. Circumcision In the capitalhas recently, patients eager undergo the recently gained hightoregard in Swaziland in procedure almost rioted at an overbooked clinic where it is performed. "There was a stampede, " said Dr. Mark Mills, administrator at the private Mbabane Clinic. "There is not a family in Swaziland unaffected by HIV, and people are desperate. " Swazi mothers are a key factor in promoting circumcision. "I decided he needed to do it for safety and for the future, " said Phindile Maseko, a nurse at Mbabane whose 13 -year-old son was circumcised. "Swazi men have heard that it is a good thing and when you play with your partner the sex is good, " said Titus Shabangu, 36, who was recently circumcised. "That is why they come. " l The Mbabane Clinic is performing 10 circumcisions weekly, up from less than one a month prior to the study.
www. guscairns. com …and another one (at least in monkeys) l PREP study, CROI 2006 l l l Monkeys given tenofovir/FTC and then rectally challenged with SHIV 0/6 infected In control group 5/6 infected 1/6 infected when FTC was used alone Safety study (400 men) in USA ongoing Efficacy study (1200 men) in Peru [finally] soon to start. Results: 2009.
www. guscairns. com US PREP trial
www. guscairns. com …and is catching on Study presented at IAS Conference, Rio, 2006 l People interviewed at gay festivals in Oakland, San Francisco, Baltimore, Detroit – only 75% of them gay/bisexual l 25% had heard of PREP l 7% had taken it – 9% in SF l
www. guscairns. com Microbicides l Creams, gels, enemas, or slow-release devices that: l 1 st generation: l l 2 nd generation: l l l Place a barrier between HIV and mucosal cells (1 st generation) Disrupt viral membranes (safety considerations – N 9) Change p. H of body cavities (Similar safety worries) Contain antiretroviral drugs (TMC 120, UC 781, tenofovir) And/or contain more sophisticated barrier chemicals/fusion inhibitors (cyanovirin-N) 3 rd generation: l Combination approaches plus genetic therapies (modified gut bacteria, etc)
www. guscairns. com Vaginal studies
www. guscairns. com Timelines… Carraguard/Population Council/Gates: Jan 2008 l Cellulose sulfate/CONRAD/USAID: September 2008 l PRO 2000/MRC: March 2009 l
www. guscairns. com Anal sex is heterosexual too Population N Prevalence of AI MSM in EXPLORE study 4295 48 – 54% High risk women 1268 32% Gross M et al. 2000 College students 210 20% Civic D 2000 3545 6 -8% Erickson PI et al. 1995 Californian residents Reference Koblin et al. 2003
www. guscairns. com Rectal microbicides… l More of a design and research challenge because… Less politically attractive for funders l Rectum/colon much more receptive to HIV so first-generation vaginal Mics. might not work l Also more fragile so increased safety issues l Coverage problem – large area so what formulation would work? l
www. guscairns. com Mucosal Transmission of HIV Infection Shattock and Moore 2003
www. guscairns. com Why volume is an issue… Without Coital Simulation With Coital Simulation 10 m. L HEC gel (1: 100 Gadolinium [Gd] label for MRI), subject supine B-bladder; SP-symphysis pubis; RA-rectal ampulla; A-anus; L 5 -5 th lumbar vertebra; S 1 -first sacral vertebra.
www. guscairns. com …or, a little goes a long way First Hour Post-Dose (0803 HRS) SPECT / CT Fusion CT: Gray scale SPECT: color scale Fourth Hour Post-Dose (1139 HRS) “Concentration” Subject F 003: Coital simulation with 5 m. L semen simulant @ 0734 HRS SPECT / CT Fusion
www. guscairns. com What’s happened so far Monkey studies l Toxicity studies l Acceptability studies l
www. guscairns. com Proof-of-concept: Cyanovirin-N Tsai et al. 2003
www. guscairns. com Toxicity studies We know virtually nothing about how gay men use LUBES or whether they are toxic l Exception: nonoxynol-9 l David Phillip, Population Council assessing safety of 13 lubes: results ready for Microbicides 2006 l
www. guscairns. com Cytotoxicity Compounds Methylcellulose Carraguard Viamor Vagisil Astroglide Delube KY- Plus Dilution (50% Cytotoxicity) Non cytotoxic (1: 1) 1: 1 1: 5 1: 32 1: 140 1: 330
www. guscairns. com Rectal protection – mice and HSV-2
www. guscairns. com Cell-sloughing (damage to rectum) Number cells/ml (1 x 108) 10 9 8 7 6 5 4 3 2 1 0
www. guscairns. com Acceptability study - solo
www. guscairns. com Acceptability study – in sex
www. guscairns. com Current microbicide development times Laboratory Testing 2 -6 Years Phase 1 1 Year Phase 2 2 Years Phase 3 3. 5 Years Phase 1 and 2 penile and rectal studies, HIV+, etc. 10 + Years Source: Tufts Center for the Study of Drug Development
www. guscairns. com UC-781 study
www. guscairns. com Why we need community preparedness NOW
www. guscairns. com Thanks to: l l l l Ian Mc. Gowan, Co-Director, UCLA Center for HIV & Digestive Diseases Craig W. Hendrix, Associate Professor of Medicine, Johns Hopkins University School of Medicine Alex Carballo-Diéguez, Associate Professor of Clinical Psychology, HIV center for clinical and behavioural studies, Columbia University Robin Shattock, Reader in Cell Biology of Infection, St George’s Hospital Medical School, London David M Phillips, Population Council, New York Alan Stone, Chair, International Working Group on Microbicides Caroline Haworth, Director of International programmes, Inter. ACT Worldwide Albert Liu, HIV Research Section, San Francisco Department of Public Health
www. guscairns. com And… l Kim Mulji, Executive Director, Naz Foundation International
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