NHP Model to Evaluate CS impact of HIV Acquisition

Recipient Organization
UNIV OF CALIFORNIA (VET-MED)
(N/A)
DAVIS,CA 95616

Performing Department
COMPARATIVE MEDICINE

Non Technical Summary
The purpose of this study is to evaluate potential enhancement of SIV infection by repeated frequent exposure of the CV mucosa to CS. We will inoculate the monkeys and caluclate their IC50 in a standard in vitro assay. The animals will be pretreated prior to the inocuation with virus.

Animal Health Component

(N/A)

Research Effort Categories

Basic

50%

Applied

(N/A)

Developmental

50%

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
311	3899	1090	40%
305	3899	1101	30%
311	3899	1160	30%

Knowledge Area
311 - Animal Diseases; 305 - Animal Physiological Processes;

Subject Of Investigation
3899 - Other animals, general;

Field Of Science
1090 - Immunology; 1101 - Virology; 1160 - Pathology;

Keywords

siv infection, cv mucosa, cs, tcid50, sivmac251, cvl,

histophathology, immune infiltrate, phenotype and activation status,

bx, cytokine/ccs/innate factors, miltiplex, cell pellets, phenotype

Goals / Objectives
To evaluate potential enhancement of SIV infection by repeated frequent exposure of the CV mucosa to CS gel. 40 adult cycling female macaques. 2 arms (blinded cpds. Four active ingredients will be submitted prior to the start of the animal experimentation to verify their activity against the strain used to inoculate the monkeys and calculate their IC50 in a standard in vitro assay. To facilitate the study, it may be carried out in 4 series of 10 animals each.

Project Methods
Blood collections every 2 weeks (and week -3, -1 (prior to start Tx), day 0, day 7 and day 21 PC) = 14/animal CVLs (-3 and 01 weeks (prior to start Tx), 24h after last cpd dose and 1 week after the inoculation) = 5/animal vaginal biopsies (-3 weeks (3 weeks before gell Tx) and 24h after inoculation = 2/animal necropsy at 16-18 weeks PC

Progress 04/01/08 to 12/31/08

Outputs
OUTPUTS: The objective of this project was to test the effect of cellulose sulfate on vaginal transmission of 5000 50% Tissue Culture Infection Dose (TCID50) of SIVmac251. Animal experiments started on June 17, 2008 as scheduled. By May 29, 2009, animal experiments had been finished as per the protocol, assays were performed on all collected samples, data were compiled and results prepared for this report. All procedures are followed as per protocol with no changes. All data have been kept confidential. Because the gel assignment for each group has not been decoded, we reach final conclusions about the results. However, there were, no significant differences between the groups in nay parameter measured. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
This study did not recapitulate the results of the human clinical trial. Thus relatively simple study design used is not adequate to measure the effects of candidate microbicides on HIV transmission. To better predict the results of clinical trials, the design of future NHP studies should utilize a repeated low dose SIV challenge system combined with repeated microbicide /placebo exposure to better mimic human exposure/use patterns. In addition, as with clinical trails, these studies should be open ended with experimental endpoints determining when a study is halted. For instance if all the controls become infected, the study can be halted.

Publications

No publications reported this period