HIV-1 infection of female genital tract tissue for use in prevention studies
CS Dezzutti, K Uranker, KE Bunge… - JAIDS Journal of …, 2013 - journals.lww.com
CS Dezzutti, K Uranker, KE Bunge, N Richardson-Harman, I Macio, SL Hillier
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2013•journals.lww.comObjective: 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 …
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 …
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 log 10 for ectocervical tissue and 2.50 log 10 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.
Lippincott Williams & Wilkins