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HIV-1 Infection of Female Genital Tract Tissue for Use in Prevention Studies

Dezzutti, Charlene S. PhD*,†; Uranker, Kevin BS; Bunge, Katherine E. MD*; Richardson-Harman, Nicola PhD; Macio, Ingrid PA-C§; Hillier, Sharon L. PhD*,†

JAIDS Journal of Acquired Immune Deficiency Syndromes: 15 August 2013 - Volume 63 - Issue 5 - p 548–554
doi: 10.1097/QAI.0b013e318291f331
Basic and Translational Science

Objective: Ex vivo HIV-1 challenge has been proposed as a bioindicator of microbicide product effectiveness. The objective of this study was to establish optimal parameters for use of female genital tract tissue in this model.

Design: Ex vivo challenge involves in vivo product use, followed by tissue biopsy, and exposure of the tissue to HIV-1 in the laboratory.

Methods: Paired ectocervical and vaginal biopsies were collected from 42 women, and 28 women had additional biopsies from each site collected after 5% lidocaine (n = 14) or chlorhexidine (n = 14) treatment. Tissues were transported immediately to the laboratory and exposed to HIV-1. HIV-1 infection was followed by p24 enzyme-linked immunosorbent assay on culture supernatants and at study end after weighing and fixing the tissue for immunohistochemistry to detect p24 expressing cells.

Results: Although both tissue types were equally infected with HIV-1 based on the immunohistochemistry results, ectocervical tissues had significantly higher HIV-1 replication than vaginal tissues (P < 0.005). Lidocaine and chlorhexidine had minimal impact on HIV-1 infection and replication. Point estimates for p24 levels were defined for 95% probability of p24-positive tissues and were 3.43 log10 for ectocervical tissue and 2.50 log10 for vaginal tissue based on the weight-adjusted cumulative p24 end points.

Conclusions: Although similar proportions of ectocervical and vaginal tissues support HIV-1 infection, higher levels of HIV-1 replication were observed in ectocervical tissues. Defining point estimates for HIV-1 infection in fresh ectocervical and vaginal tissues provides valuable information for the evaluation of HIV-1 preventative treatments during early clinical studies.

*Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA;

Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA;

Alpha StatConsult, LLC, Damascus, MD; and

§University of Pittsburgh Medical Center, Pittsburgh, PA.

Correspondence to: Charlene S. Dezzutti, PhD, Magee-Womens Research Institute, University of Pittsburgh, 204 Craft Avenue, Rm B503, Pittsburgh, PA 15213 (e-mail: cdezzutti@mwri.magee.edu).

Supported by the Film Antiretroviral Microbicide Evaluation program, which received funding from the National Institutes of Health, Division of AIDS (U19 AI082639). The work was also supported in part by a subcontract with Advanced BioScience Laboratories, Inc., Rockville, MD, through an NIH/NIAID/DAIDS contract: Comprehensive Resources for HIV Microbicides and Biomedical Prevention (#HHSN272201000001C).

Presented in part at the International Microbicides 2012 Meeting, April 15–18, 2012, Sydney, Australia (Abstract #14).

The authors have no conflicts of interest to disclose.

C. S. D., K. E. B., and S. L. H. planned the experiments. K. E. B. and I. M. recruited the participants and collected the tissue. K. U. performed the HIV-1 infection experiments. N. R.-H. performed the data analyses. C. S. D., K. E. B., N. R.-H., and S. L. H. wrote the manuscript.

Received January 15, 2013

Accepted March 13, 2013

© 2013 by Lippincott Williams & Wilkins