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Rectal application of a highly osmolar personal lubricant in a macaque model induces acute cytotoxicity but does not increase risk of SHIV infection.

Vishwanathan SA, Morris MR, Wolitski RJ, Luo W, Rose CE, Blau DM, Tsegaye T, Zaki SR, Garber DA, Jenkins LT, Henning TC, Patton DL, Hendry RM, McNicholl JM, Kersh EN - PLoS ONE (2015)

Bottom Line: Lubricant increased pro-inflammatory cytokines and tissue sloughing while control buffer (phosphate buffered saline; PBS) did not.However, the estimated AID50 (50% animal infectious dose) was not different in lubricant- and control buffer-treated macaques (p = 0.4467; logistic regression models).This study constitutes a first step in the in vivo evaluation of lubricants with regards to HIV transmission.

View Article: PubMed Central - PubMed

Affiliation: National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Atlanta, Georgia, United States of America.

ABSTRACT

Background: Personal lubricant use is common during anal intercourse. Some water-based products with high osmolality and low pH can damage genital and rectal tissues, and the polymer polyquaternium 15 (PQ15) can enhance HIV replication in vitro. This has raised concerns that lubricants with such properties may increase STD/HIV infection risk, although in vivo evidence is scarce. We use a macaque model to evaluate rectal cytotoxicity and SHIV infection risk after use of a highly osmolar (>8,000 mOsm/kg) water-based lubricant with pH of 4.4, and containing PQ15.

Methods: Cytotoxicity was documented by measuring inflammatory cytokines and epithelial tissue sloughing during six weeks of repeated, non-traumatic lubricant or control buffer applications to rectum and anus. We measured susceptibility to SHIVSF162P3 infection by comparing virus doses needed for rectal infection in twenty-one macaques treated with lubricant or control buffer 30 minutes prior to virus exposure.

Results: Lubricant increased pro-inflammatory cytokines and tissue sloughing while control buffer (phosphate buffered saline; PBS) did not. However, the estimated AID50 (50% animal infectious dose) was not different in lubricant- and control buffer-treated macaques (p = 0.4467; logistic regression models).

Conclusions: Although the test lubricant caused acute cytotoxicity in rectal tissues, it did not increase susceptibility to infection in this macaque model. Thus neither the lubricant-induced type/extent of inflammation nor the presence of PQ15 affected infection risk. This study constitutes a first step in the in vivo evaluation of lubricants with regards to HIV transmission.

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Hematoxylin and eosin stain (20x) of rectal biopsies.Showing biopsies from one animal (ID: 604962) collected before lubricant application (A) and 30 minutes after (B) product application; B shows focal infiltrates of inflammatory cells (square box), predominately mononuclear, seen in the lamina propria; there is no disruption of architecture. C is a magnified section (30x) of the square box with the green arrows showing mononuclear cells.
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pone.0120021.g003: Hematoxylin and eosin stain (20x) of rectal biopsies.Showing biopsies from one animal (ID: 604962) collected before lubricant application (A) and 30 minutes after (B) product application; B shows focal infiltrates of inflammatory cells (square box), predominately mononuclear, seen in the lamina propria; there is no disruption of architecture. C is a magnified section (30x) of the square box with the green arrows showing mononuclear cells.

Mentions: Rectal biopsies were taken from one animal 30 min after the final lubricant application, and they showed focal infiltrates of inflammatory cells (Fig. 3), predominantly mononuclear, seen in the lamina propria; there was no disruption of architecture. Biopsies collected in one animal a week after final lubricant application did not demonstrate significant tissue damage or inflammatory cell infiltration (H&E and IHC staining with CD3, CD6 or CD79) in lubricant-treated macaques (data not shown)


Rectal application of a highly osmolar personal lubricant in a macaque model induces acute cytotoxicity but does not increase risk of SHIV infection.

Vishwanathan SA, Morris MR, Wolitski RJ, Luo W, Rose CE, Blau DM, Tsegaye T, Zaki SR, Garber DA, Jenkins LT, Henning TC, Patton DL, Hendry RM, McNicholl JM, Kersh EN - PLoS ONE (2015)

Hematoxylin and eosin stain (20x) of rectal biopsies.Showing biopsies from one animal (ID: 604962) collected before lubricant application (A) and 30 minutes after (B) product application; B shows focal infiltrates of inflammatory cells (square box), predominately mononuclear, seen in the lamina propria; there is no disruption of architecture. C is a magnified section (30x) of the square box with the green arrows showing mononuclear cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390343&req=5

pone.0120021.g003: Hematoxylin and eosin stain (20x) of rectal biopsies.Showing biopsies from one animal (ID: 604962) collected before lubricant application (A) and 30 minutes after (B) product application; B shows focal infiltrates of inflammatory cells (square box), predominately mononuclear, seen in the lamina propria; there is no disruption of architecture. C is a magnified section (30x) of the square box with the green arrows showing mononuclear cells.
Mentions: Rectal biopsies were taken from one animal 30 min after the final lubricant application, and they showed focal infiltrates of inflammatory cells (Fig. 3), predominantly mononuclear, seen in the lamina propria; there was no disruption of architecture. Biopsies collected in one animal a week after final lubricant application did not demonstrate significant tissue damage or inflammatory cell infiltration (H&E and IHC staining with CD3, CD6 or CD79) in lubricant-treated macaques (data not shown)

Bottom Line: Lubricant increased pro-inflammatory cytokines and tissue sloughing while control buffer (phosphate buffered saline; PBS) did not.However, the estimated AID50 (50% animal infectious dose) was not different in lubricant- and control buffer-treated macaques (p = 0.4467; logistic regression models).This study constitutes a first step in the in vivo evaluation of lubricants with regards to HIV transmission.

View Article: PubMed Central - PubMed

Affiliation: National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Atlanta, Georgia, United States of America.

ABSTRACT

Background: Personal lubricant use is common during anal intercourse. Some water-based products with high osmolality and low pH can damage genital and rectal tissues, and the polymer polyquaternium 15 (PQ15) can enhance HIV replication in vitro. This has raised concerns that lubricants with such properties may increase STD/HIV infection risk, although in vivo evidence is scarce. We use a macaque model to evaluate rectal cytotoxicity and SHIV infection risk after use of a highly osmolar (>8,000 mOsm/kg) water-based lubricant with pH of 4.4, and containing PQ15.

Methods: Cytotoxicity was documented by measuring inflammatory cytokines and epithelial tissue sloughing during six weeks of repeated, non-traumatic lubricant or control buffer applications to rectum and anus. We measured susceptibility to SHIVSF162P3 infection by comparing virus doses needed for rectal infection in twenty-one macaques treated with lubricant or control buffer 30 minutes prior to virus exposure.

Results: Lubricant increased pro-inflammatory cytokines and tissue sloughing while control buffer (phosphate buffered saline; PBS) did not. However, the estimated AID50 (50% animal infectious dose) was not different in lubricant- and control buffer-treated macaques (p = 0.4467; logistic regression models).

Conclusions: Although the test lubricant caused acute cytotoxicity in rectal tissues, it did not increase susceptibility to infection in this macaque model. Thus neither the lubricant-induced type/extent of inflammation nor the presence of PQ15 affected infection risk. This study constitutes a first step in the in vivo evaluation of lubricants with regards to HIV transmission.

Show MeSH
Related in: MedlinePlus