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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

Plasma and rectal SHIV RNA.A. Plasma SHIV RNA levels measured in control buffer-treated (black symbols; solid lines) and lubricant-treated (grey symbols; broken lines) animals. B. SHIV RNA levels measured in rectal secretions, in control buffer-treated (open symbols) and lubricant-treated (closed symbols) animals; 0 = time of peak plasma viremia.
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pone.0120021.g005: Plasma and rectal SHIV RNA.A. Plasma SHIV RNA levels measured in control buffer-treated (black symbols; solid lines) and lubricant-treated (grey symbols; broken lines) animals. B. SHIV RNA levels measured in rectal secretions, in control buffer-treated (open symbols) and lubricant-treated (closed symbols) animals; 0 = time of peak plasma viremia.

Mentions: After infection, and as shown in the study design (Fig. 4), we continued to apply lubricant for at least 2 weeks to determine any effects on the course of SHIV infection and on genital shedding of virus. Fig. 5 displays the course of SHIVSF162P3 infection over time. The median peak plasma viremia was 3.5 x107 viral copies/mL in the control arm and 1x106 viral copies/mL in the lubricant arm, and was not significantly different (p = 0.1206; unpaired, two-tailed Mann-Whitney test). Additionally, viral RNA levels in the two arms were compared at a subsequent time point post-virus challenge when data points from all animals were available (5 weeks). Again, we found the viral RNA levels did not differ significantly (p = 0.9551; unpaired, two-tailed Mann-Whitney test). Virus shedding in rectal secretions is shown in Fig. 5, B at the time of peak plasma viremia and during the ensuing two weeks during continued rectal lubricant application. No statistically significant differences in rectal virus shedding were observed (two-tailed Mann-Whitney test) at these time points.


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)

Plasma and rectal SHIV RNA.A. Plasma SHIV RNA levels measured in control buffer-treated (black symbols; solid lines) and lubricant-treated (grey symbols; broken lines) animals. B. SHIV RNA levels measured in rectal secretions, in control buffer-treated (open symbols) and lubricant-treated (closed symbols) animals; 0 = time of peak plasma viremia.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0120021.g005: Plasma and rectal SHIV RNA.A. Plasma SHIV RNA levels measured in control buffer-treated (black symbols; solid lines) and lubricant-treated (grey symbols; broken lines) animals. B. SHIV RNA levels measured in rectal secretions, in control buffer-treated (open symbols) and lubricant-treated (closed symbols) animals; 0 = time of peak plasma viremia.
Mentions: After infection, and as shown in the study design (Fig. 4), we continued to apply lubricant for at least 2 weeks to determine any effects on the course of SHIV infection and on genital shedding of virus. Fig. 5 displays the course of SHIVSF162P3 infection over time. The median peak plasma viremia was 3.5 x107 viral copies/mL in the control arm and 1x106 viral copies/mL in the lubricant arm, and was not significantly different (p = 0.1206; unpaired, two-tailed Mann-Whitney test). Additionally, viral RNA levels in the two arms were compared at a subsequent time point post-virus challenge when data points from all animals were available (5 weeks). Again, we found the viral RNA levels did not differ significantly (p = 0.9551; unpaired, two-tailed Mann-Whitney test). Virus shedding in rectal secretions is shown in Fig. 5, B at the time of peak plasma viremia and during the ensuing two weeks during continued rectal lubricant application. No statistically significant differences in rectal virus shedding were observed (two-tailed Mann-Whitney test) at these time points.

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