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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e318291f331
Basic and Translational Science

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*,†

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Abstract

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.

© 2013 by Lippincott Williams & Wilkins

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