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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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Challenge study design (Phase II).Lubricant was applied non-traumatically for three weeks, on two consecutive days per week. The animal was challenged with SHIVSF162p3 30 minutes after the sixth lubricant application (open triangle). To check for plasma viremia and virus shedding, samples were collected for at least 2 weeks post-peak viremia. Not shown are baseline blood draws that were performed before the first lubricant application to ensure that the animal is not infected.
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pone.0120021.g004: Challenge study design (Phase II).Lubricant was applied non-traumatically for three weeks, on two consecutive days per week. The animal was challenged with SHIVSF162p3 30 minutes after the sixth lubricant application (open triangle). To check for plasma viremia and virus shedding, samples were collected for at least 2 weeks post-peak viremia. Not shown are baseline blood draws that were performed before the first lubricant application to ensure that the animal is not infected.

Mentions: In order to determine whether the observed, lubricant-induced cytotoxicity may affect HIV risk, we used the cynomolgus macaque model to study rectal SHIVSF162P3 infection risk. Fig. 4 shows the study design; the lubricant was applied non-traumatically over three weeks, on two consecutive days per week, and virus challenges occurred 30 minutes after the sixth lubricant application since the cytokine levels peaked at 30 min post-application. We determined relative susceptibility to infection by comparing the SHIVSF162P3 doses (AID50) needed for infection in lubricant- or control buffer-treated macaques in two study arms. Macaques were first exposed to low doses of virus, and if they remained uninfected, they were rested, and then re-enrolled at higher doses until infection occurred. The virus exposure schedule for individual macaques can be seen in S1 Table. In total, 21 macaques were challenged with various doses until 15 infections occurred in a total of 51 exposures (controls = 7, lubricant = 8). Table 2 summarizes the number of virus exposures and outcomes. Unexpectedly, only two out of nine lubricant-treated animals were infected at doses >2,500 TCID50. In contrast, six of the seven macaques were infected in the control arm at those higher doses. In this study, we also used data from historical controls, i.e., from 11 macaques exposed to SHIVSF162P3 at 50 or 250 TCID50s, with one infection occurring at each dose.


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)

Challenge study design (Phase II).Lubricant was applied non-traumatically for three weeks, on two consecutive days per week. The animal was challenged with SHIVSF162p3 30 minutes after the sixth lubricant application (open triangle). To check for plasma viremia and virus shedding, samples were collected for at least 2 weeks post-peak viremia. Not shown are baseline blood draws that were performed before the first lubricant application to ensure that the animal is not infected.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0120021.g004: Challenge study design (Phase II).Lubricant was applied non-traumatically for three weeks, on two consecutive days per week. The animal was challenged with SHIVSF162p3 30 minutes after the sixth lubricant application (open triangle). To check for plasma viremia and virus shedding, samples were collected for at least 2 weeks post-peak viremia. Not shown are baseline blood draws that were performed before the first lubricant application to ensure that the animal is not infected.
Mentions: In order to determine whether the observed, lubricant-induced cytotoxicity may affect HIV risk, we used the cynomolgus macaque model to study rectal SHIVSF162P3 infection risk. Fig. 4 shows the study design; the lubricant was applied non-traumatically over three weeks, on two consecutive days per week, and virus challenges occurred 30 minutes after the sixth lubricant application since the cytokine levels peaked at 30 min post-application. We determined relative susceptibility to infection by comparing the SHIVSF162P3 doses (AID50) needed for infection in lubricant- or control buffer-treated macaques in two study arms. Macaques were first exposed to low doses of virus, and if they remained uninfected, they were rested, and then re-enrolled at higher doses until infection occurred. The virus exposure schedule for individual macaques can be seen in S1 Table. In total, 21 macaques were challenged with various doses until 15 infections occurred in a total of 51 exposures (controls = 7, lubricant = 8). Table 2 summarizes the number of virus exposures and outcomes. Unexpectedly, only two out of nine lubricant-treated animals were infected at doses >2,500 TCID50. In contrast, six of the seven macaques were infected in the control arm at those higher doses. In this study, we also used data from historical controls, i.e., from 11 macaques exposed to SHIVSF162P3 at 50 or 250 TCID50s, with one infection occurring at each dose.

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