The prevalence of receptive anal intercourse among men and women the world over requires the research and development of safe, effective and acceptable microbicides designed specifically for the rectum as well.

Today at CROI 2009, two interesting Poster Discussions were held of special interest to IRMA members.

You can access the abstracts and actual posters for each of these.

IRMA asked Drs. Peter Anton and Ian McGowan for their thoughts regarding these important findings. You can read their remarks below.

A Phase 1 Safety and Acceptability Study of the UC781 Microbicide Gel Applied Rectally in HIV Seronegative Adults: A First in Field

Peter Anton, A Adler, E Khanuknova, J Elliott, W Cumberland, Y Zhou, A Ventuneac, A Carballo-Dieguez, C Mauck, and I McGowan

Representing David Geffen Sch of Med, Univ of California, Los Angeles, US; Translational Sci Corp, Mill Valley, CA, US; Univ of California, Los Angeles Sch of Publ Hlth, US; HIV Ctr for Clinical and Behavioral Studies, New York, NY, US; CONRAD, Arlington, VA, US; and Magee-Womens Res Inst, Pittsburgh, PA, US

Click here for the abstract.

Click here for the PDF of the poster.

Strong Ex-Vivo Suppression of HIV-1 Infection of Colorectal Explants from In-Vivo Rectal Application of UC781 Gel: A Novel Endpoint In A Phase 1 Trial

Peter Anton, J Elliott, I McGowan, A Adler, K Tanner, EJ Johnson, T Saunders, C Siboliban, E Khanukova, Y.Zhou.

Representing David Geffen School of Medicine, Los Angeles, CA,
Magee-Women’s Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA

Click here for the abstract.

Click here for the PDF of the poster.

Dr. Peter Anton – “The Phase I rectal safety trial of the vaginal gel formulation of UC781 was historic in that it was the first of its kind in the field. While we determined that the gel appeared safe, well tolerated and acceptable among trial participants, it is noteworthy that we also observed signs of efficacy. Namely, this type of test could be an important new protocol the entire microbicide field might adopt as a way to help evaluate which products move forward in the pipeline.

“This Phase 1 rectal safety study for microbicides, using CONRAD’s UC781 lays the foundation for the many necessary trials to follow. This study required close, active collaboration with CONRAD, NIH and the FDA, as well as the academic research institutions (UCLA, U Pittsburgh/McGee Women’s Hospital and Columbia University).

“So, the first point is that this study has forged new territory in beginning to define relevant procedures, definitions of risk and mucosal injury.

“Second, the study itself showed great results for Phase 1: the drug and formulation appears safe by all indices measured. This bodes well for its advancing and also assisting an FDA application for vaginal use (should that prove possible) by already having a rectal safety study completed.

“Thirdly, and of great interest for future trials, were the remarkable results from the novel “explant study”, which saw a strong suppression of HIV replication (HIV was applied to tissue biopsies in the laboratory) from study subjects who had received the study drug (in vivo) 30 minutes before biopsy.

“This is the closest we can come to testing real, human, sexually-exposed tissue, already treated with a microbicide to determine if it helps to resists HIV infection. In this study, it did….a remarkable result that even we did not anticipate to this degree.

“With limited resources and the clear necessity for both vaginal and rectal microbicides, we need sophisticated tools to make the best decisions earlier about the viability of any candidate microbicide and which ones to advance to more expensive, longer studies. This is not yet an actual early marker of eventual efficacy, but it is an exciting start.”

Dr. Ian McGowan – “The results of the UC781 trial, in which we observed both safety and efficacy signals after testing the vaginal gel formulation of an NNRTI, are encouraging for the field of rectal microbicides.

“Later this year, the Microbicide Trials Network will launch a new Phase I safety trial to determine the safety and acceptability of Tenofovir vaginal gel applied rectally and will co-sponsor a parallel Phase 1 trial using tenofovir gel and oral formulations with NIH’s Integrated Preclinical-Clinical Program (IPCP) for microbicides.

“There is an associated 10-20 fold increased risk of HIV transmission during unprotected anal intercourse compared to unprotected vaginal intercourse. Anal intercourse among gay men, men who have sex with men, and between heterosexual men and women is common globally. We know that much of this behavior is unprotected.

“Therefore, we need two things. first, we must have rectal safety data on all vaginal microbicides in the pipeline, because we know they will be used vaginally and rectally.

“And secondly, the prevalence of receptive anal intercourse among men and women the world over requires the research and development of safe, effective and acceptable microbicides designed specifically for the rectum as well.”