Identification of Personal Lubricants That Can Cause Rectal Epithelial Cell Damage and Enhance HIV Type 1 Replicationin Vitro

Abstract

Over-the-counter personal lubricants are used frequently during vaginal and anal intercourse, but they have not been extensively tested for biological effects that might influence HIV transmission. We evaluated the in vitro toxicity anti-HIV-1 activity and osmolality of popular lubricants. A total of 41 lubricants were examined and compared to Gynol II and Carraguard as positive and negative controls for toxicity, respectively. Cytotoxicity was assessed using the XTT assay. The MAGI assay with R5 and X4 HIV-1 laboratory strains was used to evaluate antiviral activity. The effect of the lubricants on differentiated Caco-2 cell monolayers (transepithelial electrical resistance, TEER) was also measured. None of the lubricants tested showed significant activity against HIV-1. Surprisingly, four of them, Astroglide Liquid, Astroglide Warming Liquid, Astroglide Glycerin & Paraben-Free Liquid, and Astroglide Silken Secret, significantly enhanced HIV-1 replication (p<0.0001). A common ingredient in three of these preparations is polyquaternium-15. In vitro testing of a chemically related compound (MADQUAT) confirmed that this similarly augmented HIV-1 replication. Most of the lubricants were found to be hyperosmolar and the TEER value dropped approximately 60% 2 h after exposure to all lubricants tested. Cells treated with Carraguard, saline, and cell controls maintained about 100% initial TEER value after 2-6 h. We have identified four lubricants that significantly increase HIV-1 replication in vitro. In addition, the epithelial damage caused by these and many other lubricants may have implications for enhancing HIV transmission in vivo. These data emphasize the importance of performing more rigorous safety testing on these products.

A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo

“…The assay was performed as previously described (9), except that the medium was replaced on the day of the assay with fresh Dulbecco's modified Eagle's medium (DMEM) without phenol red (Invitrogen, Grand Island, NY) and supplemented with MITOϩ Serum Extender (BD Biosciences). All formulations were diluted 1:10 in the media described above, and 300 l was applied in triplicate in the upper chambers.…”

An Event-Level Comparison of Risk-Related Sexual Practices Between Black and Other-Race Men Who Have Sex with Men: Condoms, Semen, Lubricant, and Rectal Douching

“…25 Despite the enhanced comfort and pleasure lubricants afford, recent literature has highlighted the enhanced risk they may also confer. 22 Laboratory research has shown that many of these agents compromise the integrity of the epithelial lining of the rectum and colon, which could increases susceptibility to infection, 20,21,24,39 and that several products even amplify HIV replication in vitro. 20 Notably, research to date exploring lubricant as a mechanism of HIV/STI transmission has largely focused on PAI risk as it pertains to the receptive partner, and it is therefore unknown whether lubricants enhance susceptibility of the insertive partner's penis to infection.…”

“…22 Laboratory research has shown that many of these agents compromise the integrity of the epithelial lining of the rectum and colon, which could increases susceptibility to infection, 20,21,24,39 and that several products even amplify HIV replication in vitro. 20 Notably, research to date exploring lubricant as a mechanism of HIV/STI transmission has largely focused on PAI risk as it pertains to the receptive partner, and it is therefore unknown whether lubricants enhance susceptibility of the insertive partner's penis to infection. Moreover, it is conceivable that by reducing friction between the penis and anus, lubricants may decrease the likelihood of the receptive partner experiencing anal tearing or bleeding, potentially reducing exposure of the insertive partner to blood-borne pathogens (e.g., HIV).…”

“…18 Moreover, documentation of condom use often relies on aggregate retrospective self-reports, which have proven vulnerable to distortion, with MSM more commonly underestimating than overestimating unprotected PAI. 19 Additionally, Black MSM's participation in other behavioral practices known or suspected to influence vulnerability to HIV and other STIs, including lubricant use [20][21][22][23][24] and precoital rectal douching or enema use, [25][26][27][28][29][30] has received insufficient attention in the literature.…”

Pharmacokinetic and Pharmacodynamic Evaluation following Vaginal Application of IQB3002, a Dual-Chamber Microbicide Gel Containing the Nonnucleoside Reverse Transcriptase Inhibitor IQP-0528 in Rhesus Macaques

“…In addition, a recent metaanalysis demonstrated that the estimated per-act human immunodeficiency (HIV) transmission risk (per 10,000 exposures) for RAI is 138, compared to 11, 8, and 4 for insertive anal intercourse, receptive penile-vaginal intercourse, and insertive penile-vaginal intercourse, respectively (10). The risk of HIV acquisition via unprotected RAI may be further exacerbated through the improper use of vaginal microbicide gels or high osmolality personal lubricants in the rectal compartment, which have been shown to cause cellular inflammation and epithelial damage (11)(12)(13)(14)(15)(16)(17)(18)(19). These studies collectively highlight a need for a microbicide formulation that is specifically designed for safe application in both the vaginal and rectal compartments and that may also serve as a lubricant.…”