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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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Related in: MedlinePlus

Epithelial sloughing and blood.A. Lubricant induces rectal shedding of epithelial cells. Examples of epithelial sloughing in a control- (top left) and lubricant-treated animal (top right). The lower panel shows a representative H&E stain of sloughed rectal epithelial cells (20x); B. Blood associated with rectal washes; photographs of microfuges containing rectal lavages; C,D. Epithelial sloughing measured at acute time points collected after the 2nd weekly lubricant application (C), and those measured over the entire study (D). The panel D in this figure shows three collections per week (day 1, pre-lubricant; day 2 pre-lubricant; day 2 post-lubricant), as indicated in Fig. 1.
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pone.0120021.g002: Epithelial sloughing and blood.A. Lubricant induces rectal shedding of epithelial cells. Examples of epithelial sloughing in a control- (top left) and lubricant-treated animal (top right). The lower panel shows a representative H&E stain of sloughed rectal epithelial cells (20x); B. Blood associated with rectal washes; photographs of microfuges containing rectal lavages; C,D. Epithelial sloughing measured at acute time points collected after the 2nd weekly lubricant application (C), and those measured over the entire study (D). The panel D in this figure shows three collections per week (day 1, pre-lubricant; day 2 pre-lubricant; day 2 post-lubricant), as indicated in Fig. 1.

Mentions: Tissue damage was examined by determining epithelial sloughing and associated blood in rectal lavages. Fig. 2, A shows photographs of epithelial sheets with size >3mm in any dimension, harvested from the rectum of a lubricant-treated macaque. The size of the sloughed cellular material varied from 3mm to 20mm. Controls exhibited a lesser degree of epithelial shedding (<3mm in any dimension), which is considered normal [18]. Histological examination showed that the sloughed material was of cellular origin, consistent with the shedding of epithelium (Fig. 2, A; lower panel). Blood associated with sloughed tissues was documented by visual and microscopic examination of lavages (Fig. 2, B). Blood was only associated with epithelial sheets following lubricant application, and not in control animals. Fig. 2, C and D display the frequency of detected tissue fragments > 3mm in all evaluated macaques. Sloughing occurred in five of six macaques 2 hours post-lubricant treatment, while only one of the three control macaques had signs of this type of tissue sloughing at any acute time point. The difference in sloughing at acute time points (Fig. 2, C) in the two study arms was not statistically significant (p = 0.1379; 2-tailed Fisher’s exact probability test). Fig. 2, D that displays all times points of collection (longitudinal) shows that sloughing did not increase over time. However maximum shedding of epithelium was seen in week 3 where all three collection points (over two days) showed sloughing in up to 5 out of 6 lubricant-treated animals. At this point, sloughing was seen on day 1 (pre-lubricant) and day 2 (post-lubricant) in only 1 out of 3 controls. The sloughing was also evident in week 4 but in fewer macaques. S1 Fig. shows the time course of visually observed blood associated with shed tissue fragments. Bleeding was first noted in some animals after week 1. Following repeated lubricant applications (weeks 4–6), blood in some lavage samples became discernible by eye. It peaked at 4h post-application and was detected in 67% of lubricant animals, and in none of the controls.


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)

Epithelial sloughing and blood.A. Lubricant induces rectal shedding of epithelial cells. Examples of epithelial sloughing in a control- (top left) and lubricant-treated animal (top right). The lower panel shows a representative H&E stain of sloughed rectal epithelial cells (20x); B. Blood associated with rectal washes; photographs of microfuges containing rectal lavages; C,D. Epithelial sloughing measured at acute time points collected after the 2nd weekly lubricant application (C), and those measured over the entire study (D). The panel D in this figure shows three collections per week (day 1, pre-lubricant; day 2 pre-lubricant; day 2 post-lubricant), as indicated in Fig. 1.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0120021.g002: Epithelial sloughing and blood.A. Lubricant induces rectal shedding of epithelial cells. Examples of epithelial sloughing in a control- (top left) and lubricant-treated animal (top right). The lower panel shows a representative H&E stain of sloughed rectal epithelial cells (20x); B. Blood associated with rectal washes; photographs of microfuges containing rectal lavages; C,D. Epithelial sloughing measured at acute time points collected after the 2nd weekly lubricant application (C), and those measured over the entire study (D). The panel D in this figure shows three collections per week (day 1, pre-lubricant; day 2 pre-lubricant; day 2 post-lubricant), as indicated in Fig. 1.
Mentions: Tissue damage was examined by determining epithelial sloughing and associated blood in rectal lavages. Fig. 2, A shows photographs of epithelial sheets with size >3mm in any dimension, harvested from the rectum of a lubricant-treated macaque. The size of the sloughed cellular material varied from 3mm to 20mm. Controls exhibited a lesser degree of epithelial shedding (<3mm in any dimension), which is considered normal [18]. Histological examination showed that the sloughed material was of cellular origin, consistent with the shedding of epithelium (Fig. 2, A; lower panel). Blood associated with sloughed tissues was documented by visual and microscopic examination of lavages (Fig. 2, B). Blood was only associated with epithelial sheets following lubricant application, and not in control animals. Fig. 2, C and D display the frequency of detected tissue fragments > 3mm in all evaluated macaques. Sloughing occurred in five of six macaques 2 hours post-lubricant treatment, while only one of the three control macaques had signs of this type of tissue sloughing at any acute time point. The difference in sloughing at acute time points (Fig. 2, C) in the two study arms was not statistically significant (p = 0.1379; 2-tailed Fisher’s exact probability test). Fig. 2, D that displays all times points of collection (longitudinal) shows that sloughing did not increase over time. However maximum shedding of epithelium was seen in week 3 where all three collection points (over two days) showed sloughing in up to 5 out of 6 lubricant-treated animals. At this point, sloughing was seen on day 1 (pre-lubricant) and day 2 (post-lubricant) in only 1 out of 3 controls. The sloughing was also evident in week 4 but in fewer macaques. S1 Fig. shows the time course of visually observed blood associated with shed tissue fragments. Bleeding was first noted in some animals after week 1. Following repeated lubricant applications (weeks 4–6), blood in some lavage samples became discernible by eye. It peaked at 4h post-application and was detected in 67% of lubricant animals, and in none of the controls.

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