amfar Funding for rectal HIV transmission and microbicides research Rowena Johnston, Ph.D.

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1 amfar Funding for rectal HIV transmission and microbicides research Rowena Johnston, Ph.D.

2 Research mission: Develop means to reduce - perhaps prevent - new HIV infections Develop means to better treat - perhaps cure - existing HIV infections

3 Rectal HIV transmission: Who s doing it? What influences it? What happens in the intestine? What are the effects on the tissues? How to ramp up rectal M development? How to deliver them once they exist?

4 Who s s doing it? By extension: Whom are we hoping to protect? Ultimately, what effect might rectal Ms have on the epidemic?

5 Marjan Javanbakht,, Ph.D. UCLA 2 years - $112,193 Anal intercourse, STIs, and HIV among STD clinic clients Male clients (MSMW) attending a public STD clinic in LA i.e. bridge between MSM and heterosexual populations Analysis of data gathered during clinic visit: Gender of sex partners? Anal sex with those partners? Substance use? Anonymous sex partners? History of STIs? Goals: Tailor intervention programs Math model of AI contribution to HIV in LA County/ effect of microbicides

6 Joanne Mantell,, Ph.D. Research Foundation for Mental Hygiene, Inc., New York, NY 1 year - $119,946 Anal sex practices in high-risk South African women and men Prevalence and factors associated with AI in heterosexually active men and women Male and female clients at STI clinics in Cape Town Research: culturally sensitive interviews prevalence and frequency of AI vs. vaginal frequency of condom use with A vs. V demographic, attitudinal and behavioral correlates of AI Goals: develop messages re risks of AI design RMs/other interventions for hetero men and women

7 What influences AI? Under which circumstances do people engage in AI? Which interpersonal factors might influence HIV risk during AI?

8 Hongjie Liu, Ph.D. Wayne State University, Detroit 1 years - $119,988 Mediation effects of network function on HIV risk behavior among Chinese MSM To what extent do MSM in China engage in UA/VI with men/women? Influence of social networks and collectivist culture Research: 250 MSM, respondent-driven sampling knowledge and self-risk assessment discrimination experienced components and characteristics of social and risk networks how networks influence involvement in UAI Goals: develop HIV intervention program

9 Getting to the bottom of it What damage is done to colon/rectum during AI?

10 Craig Hendrix, M.D. Johns Hopkins U School Medicine 1 year - $120,000 Epithelial injury and HIV penetration after simulated ejaculation Where does HIV-infected semen land following ejaculation? What does semen and/or coital trauma contribute to colonic injury? Research: labeled lymphocytes and pseudo virions mixed with autologous seminal plasma simulated anal intercourse and ejaculation SPECT, endoscope measure migration and penetration of cells/virions Goals: help interpret toxicity data from M clinical trials

11 Effects on tissues What is happening at the cellular level in HIV infection? Might microbicides affect this process?

12 Charlene Dezutti,, Ph.D. Magee-Womens Research Institute and Foundation, Pittsburgh 1 years - $120,000 Colorectal explants to study HIV transmission and microbicides Can we expect differences between female genital tract and rectal mucosa in terms of HIV transmission and microbicide efficacy? Research: rectal explants, 5 areas of colorectum plus hemorrhoids differences in susceptibility and M efficacy depending on tissue location and type? differences in initial cell types infected? differences in ability to infect based on CoR type? Goals: elucidate rectal HIV transmission and evaluation of topical microbicides

13 Carolina Herrera, Ph.D. St. George s University of London, UK 2 years - $125,000 Colorectal responses to HIV-1 and modulation by microbicides What are the cellular responses to HIV that may influence trafficking through mucosal epithelium? Research: rectal explants analyze cytokine profiles and chemokine receptors 1) in response to HIV 2) responses dependent on whether infection is established? 3) responses modulated by microbicide candidates? Goals: establish scientific basis for rational development of rectal M

14 Ramping up rectal M research Need animal model to conduct studies between test tubes and humans

15 Roberto Speck, M.D. University Hospital of Zurich, Switzerland 1 year - $119,822 Rectal transmission of HIV-1 in a novel mouse model Established novel HIV mouse model by intrahepatic transplantation of human CD34+ hematopoietic stem cells into newborn immunodeficient Rag2-/-γc-/- mice (lack B, T, and NK cells) Colonization of gut by human lymphoid cells Research: cell-associated vs. cell-free transmission co-receptor dependency of transmitted strains identification of HIV target cells is gut endothelial disruption necessary for transmission? Goals: more fully describe mouse model for use in pathogenesis and microbicide studies

16 Delivery Must have safe, effective delivery device Useful for standardizing between studies

17 Alex Carballo-Dieguez Dieguez,, Ph.D. Pic 3. Rectal douches. Excessive volume Columbia University, NYC 1 year - $119,992 Development of a standard rectal microbicide delivery device Use of rectal M will depend to large degree on acceptability of applicator Need for inexpensive, standard device to use across rectal M trials Research: determine appropriate design specifications identify manufacturers to develop prototypes ease of use, comfort and overall acceptability in men and women engaging in RAI Goals: develop devise to use in rectal M trials to standardize procedures Picture 1. Syringes used for rectal administration of a gel. Unappealing.

18 Funding process amfar issues request for proposals Applicants submit LOI Full applications invited by amfar Grant (1 year) $120,000 Fellowship (2 years) $125,000

19 Research Applications Applications and instructions at: /rfp

20 amfar Research Funding There are NO RESTRICTIONS on: Citizenship Country from which the application is received Age, color, creed, gender, medical condition, handicap, national origin, parental status, political affiliation, race, religion, marital status, sexual orientation

21 amfar Research Funding

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