1 / 11

Ellen Kersh, PhD Microbiologist, Preclinical Evaluation Team,

Acute Cytotoxicity but No Increased SHIV Infection Risk after Rectal Application of a Highly Osmolar Personal Lubricant in an Animal Model. Ellen Kersh, PhD Microbiologist, Preclinical Evaluation Team, Laboratory Branch, DHAP, NCHHSTP, CDC IRMA Webinar, June 4, 2014.

laken
Download Presentation

Ellen Kersh, PhD Microbiologist, Preclinical Evaluation Team,

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Acute Cytotoxicity but No Increased SHIV Infection Risk after Rectal Application of a Highly Osmolar Personal Lubricant in an Animal Model Ellen Kersh, PhD Microbiologist, Preclinical Evaluation Team, Laboratory Branch, DHAP, NCHHSTP, CDC IRMA Webinar, June 4, 2014 National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Division of HIV/AIDS Prevention Disclaimer: The findings and conclusions in this presentation are those of the presenter and do not necessarily represent the views of the CDC. 1

  2. Study Goal and Design • Goal: • To determine whether a commercially available lubricant causes rectal cytotoxicity and increases HIV/ SHIV risk in a macaque model. • Design: • Purchased a lubricant with osmolality of 8,064 mOsm/kg, pH of 4.4, poly-quaternium 15+ • Phase I: cytotoxicity evaluation in n=9 cynomolgus macaques • Phase II: SHIV infection risk evaluation in n=21 macaques 2

  3. Phase I: Cytotoxicity Evaluation • Goals: • To develop animal model • To determine rectal cytotoxicity, i.e., inflammation, bleeding, tissue damage • To establish time course of lube effects biopsy Lube applications Specimen collections 15m 30m 2hrs 4hrs 24hrs 48hrs week 1 2 3 4 5 6 7 • Experimental Details: • Non-traumatic rectal lube; 3 mL internal + 2 mLexternal • Specimens: rectal swabs (cytokines, pH, bacteria), washes (sloughing, blood); biopsies (tissue architecture, infiltration) 3

  4. Result: Inflammation 30 min after lubricant use Example: Pro-inflammatory cytokine IL-6 in rectal secretions Control buffer Lubricant * * 40 40 Specimens *p<0.0001 Wilcoxon rank- sum test Lube IL-6 (pg/mg) 20 20 “acute” specimens only median 0 0 BL 15 m 30 m 2 h 4 h 24 h 48 h BL 15 m 30 m 2 h 4 h 24 h 48 h • Inflammation observed • Peak of inflammation 30 minutes after lube; subsided • Other cytokines upregulated as well • Detailed analysis reported at CROI ‘14 4

  5. Other Results • Tissue sloughing: Rectal washes had epithelial tissue pieces, associated with blood • No change in pH • No striking changes in bacterial microflora • Biopsies showed limited inflammatory cell infiltrates at 30 minutes post lube • Biopsies also showed healing within 7 days Control buffer Lubricant after 6 applications week 3 5

  6. Phase II: SHIV risk after lube use SHIVSF162P3 Infection? Virus Shedding? • Goals: • To determine SHIV risk of rectal lube use at a time point with demonstrated inflammation (30 min) • Design: • Compared SHIV infection risk in n=21 macaques, in lube and control buffer groups • Determined virus dose with 50% of animals infected (AID-50); Hypothesis: AID50 (ctrl) > AID50 (lube) 30 min Lube study week 1 2 3 4 5 6 6

  7. SHIV Risk Results + one animal exposed, infected - one animal exposed, uninfected AID50 (control) =1,721 TCID50(95% CI 414, 7165) AID50 (lube)=196,336 TCID50 (95% CI 1.0, 4.5x1010) Not different (p = 0.4467; logistic regression models) 7

  8. Continued Lube treatment does not affect infection course Controls Lube-treated Plasma SHIVSF162P3 Rectal SHIV shedding 10 5 8 4 log10RNA copies/mL 6 3 4 2 2 1 0 0 0 +1 +2 0 5 10 0 5 10 Weeks relative to peak viremia 8

  9. Summary • One hyperosmolar, low pH lubricant induced short-lived rectal cytotoxicity in an animal model • This was not associated with increased SHIV infection risk • Study limitations: • Only one product • Only non-traumatic lube application • Animal models for increased risk testing have limits in sensitivity 9

  10. Discussion, Future Directions • Results from the infection risk study were unexpectedbecause of cytotoxicity • More data could clarify the real-world effects of lubricant use • The employed non-human primate model may not have been sufficiently suitable for detecting enhanced infection risk. • We plan to evaluate additional lubricants in additional cytotoxicity and risk models. 10

  11. Co-authors: Sundaram A Vishwanathan Richard J Wolitski Wei Luo Charles E Rose Dianna M Blau Monica R Morris Theodros Tsegaye Tara C Henning Sherif R Zaki David A Garber Leecresia T Jenkins Dorothy L Patton, University of Washington R. Michael Hendry Janet M McNicholl Disclaimer: The findings and conclusions in this presentation are those of the presenter and do not necessarily represent the views of the CDC. 11

More Related