Some sexual lubricants damage cells – but may not increase HIV risk

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An evaluation of 13 sexual lubricants has found that, while many are toxic to the cells that line the vagina and rectum, this does not lead to an increased rate of HIV infection – at least in test-tube experiments.

The researchers conclude that, while some of these commercially available compounds do cause damage to the epithelium (the layer of cells that lines the vagina and rectum), this may not in itself be sufficient to increase the likelihood of HIV infection. This means that although the 'lubes' that cause the most damage to cells are, in the main, water-based ones, they are unlikely to reduce the efficacy of the condoms they are designed to be used with. Some other water-based lubes, and the silicone-based ones, were not toxic to cells.

Summary of main findings

The researchers confirmed that the main reason some lubricants kill off tissue is because they contain more dissolved salts and other chemicals than the fluid inside cells: to use the technical term, they are hyperosmolar. This property means that they draw water out of the mucous membrane cells, drying them out and stripping them from the membrane surface.  Two lubes tested were hypo-osmolar, meaning that instead the cells drew water out of the lube, which makes them swell and burst; one of these gels was toxic to cells too.

In contrast, the two gels that were iso-osmolar, meaning with the same fluid/salt balance as body fluids, did not damage mucous membranes; nor did the two lubes that were silicone- rather than water-based, and one of the hypo-osmolar ones.

Glossary

rectum

The last part of the large intestine just above the anus.

toxicity

Side-effects.

hypo

Prefix meaning lower than usual.

microbicide

A product (such as a gel or cream) that is being tested in HIV prevention research. It could be applied topically to genital surfaces to prevent or reduce the transmission of HIV during sexual intercourse. Microbicides might also take other forms, including films, suppositories, and slow-releasing sponges or vaginal rings.

inflammation

The general term for the body’s response to injury, including injury by an infection. The acute phase (with fever, swollen glands, sore throat, headaches, etc.) is a sign that the immune system has been triggered by a signal announcing the infection. But chronic (or persisting) inflammation, even at low grade, is problematic, as it is associated in the long term to many conditions such as heart disease or cancer. The best treatment of HIV-inflammation is antiretroviral therapy.

While this property, osmolality, was the one most strongly associated with toxicity, preservatives found in some of the lubes were also toxic to cells, principally the compound chlorhexidine. This included K-Y Jelly, probably the most long-established lube and one that has been used as a ‘control’ in some microbicide trials. Chlorhexidine, and possibly other preservatives, also killed off some beneficial vaginal bacteria (Lactobacillus species) that guard against bacterial vaginosis and may protect against HIV infection.

Alarmingly, it found that the two lubes it tested that were oil-based – and specifically aimed at gay men who choose not to use condoms – were also likely to cause rectal membrane damage.

In the experiments, lubes did not prevent infection, but they also did not amplify infection – in other words, infected cells did not produce copies of HIV any faster than usual. This means that another process, such as active inflammation, may need to be there in order to increase the chance that a temporary, local infection of cells turns into a systemic, continuing one.

The research also found that cervicovaginal tissue was – contrary to what had previously been thought – just as likely to be damaged by some of the lubricants as rectal tissue.

Background

Lead researcher Charlene Dezzutti and colleagues from the University of Pittsburgh, which has pioneered microbicides studies, were one of two teams who, in different papers presented at the 2010 International Microbicides Conference, first announced findings suggesting that many lubricants used in sex were toxic to cells and might possibly increase the risk of HIV transmission.

Previously it had been assumed that most lubes were neutral or even beneficial in terms of HIV transmission, partly because they reduce injury and soreness, and also because some of their ingredients have shown anti-HIV activity in the test tube. Although results showing the spermicide nonoxynol-9 and the candidate microbicide cellulose sulphate actually increased HIV transmission, this was not thought to be the case for other lubes.

Dezzutti and colleagues’ research seemed to show that it was the water-based lubes that were particularly associated with cell damage, which put prevention advocates into a dilemma: should the standard safer-sex advice still include using a water-based lube with condoms? 

Study details

In the study, Charlene Dezzutti’s team took 14 lubricants commercially available in the USA and performed a number of tests on them. 

Amongst the research team were Jim Pickett and Marc-André LeBlanc from International Rectal Microbicide Advocates (IRMA), who have urged more research into lubes. See here for IRMA's release on the study.

The lubes used in the present study were:

  • Gynol 2: a 'positive control' spermicide, already known to be likely to increase vulnerability to HIV as it includes the substance nonoxynol-9.
  • Astroglide, ID Glide, K-Y Jelly, Replens, Elbow Grease: hyperosmolar water-based lubes.
  • PRÉ and Good Clean Love (GCL):  iso-osmolar water-based lubes.
  • Slippery Stuff and Sliquid Organic: hypo-osmolar water-based lubes.
  • Boy Butter H2O and Boy Butter Original: oil-based lubes.
  • FC2 and Wet Platinum: silicone-based lubes.

The researchers conducted a variety of tests:

  • The lubes were assessed for osmolality, viscosity (at room temperature and body temperature) and acidity.
  • They were tested for toxicity against two Lactobacillus species.
  • They were tested for toxicity against epithelial cells that line mucous membranes, in suspension and against a single-cell layer of cultured cells.
  • They were tested for toxicity against explants, actual biopsies of tissue taken from vaginal and rectal walls.
  • They were tested for anti-HIV activity in the test tube.
  • They were tested for their ability to stop or slow down HIV infection of cells.
  • These cells thus infected were then tested to see if they productively reproduced HIV viruses, the lubes being compared in this case with EDTA, a substance already known to increase the likelihood of productive infections.

The most important results were:

  • Gynol 2, Astroglide (the most hyperosmolar gel) and Replens killed off one or more species of Lactobacillus.
  • All the hyperosmolar gels and one of the hypo-osmolar ones (Sliquid Organic) killed off epithelial cells in the test tube and in a monolayer. The iso-osmolar gels and the other hypo-osmolar one (Slippery Stuff) were non-toxic and the silicone-based and oil-based lubes only marginally so.
  • The hyper-osmolar lubes were also in most cases toxic to explant tissue and their toxicity was correlated with their osmolality. Iso- and hypo-osmolar lubes were in general not toxic to explants. The oil-based lubes were specifically toxic to rectal tissue and not vaginal – a worrying finding as they are targeted at gay men who don’t use condoms.
  • Replens, PRÉ and Good Clean Love showed evidence of some degree of anti-HIV activity in the test tube (but not Sliquid Organic, which contains green tea extract, often cited as an anti-HIV substance).
  • It took longer to infect cells treated with Astroglide, Replens and Good Clean Love, compared with untreated cells (though they did not stop infection); lubes did not appear to influence the subsequent rate of HIV infection, except when it was due to cellular damage caused by the lubes.

Conclusions

This research shows that the initial hunch that osmolality might be the cause of cellular toxicity was correct and that iso-osmolar water-based lubes and silicone-based ones are not toxic to vaginal or rectal cells.

It shows that, in the test tube at least, none of the lubes appear to increase the likelihood of HIV infection or replication, which is good news, but none decrease it either.

For obvious reasons, however, these studies cannot mimic whether lubes have protective or harmful effects when actually used in sex; explants are not the same as live tissue and no test can show whether lubes protect against HIV infection by protecting against the soreness, friction or injuries that might have occurred without them.

“Despite the lack of increased HIV infection in ... tissue,” the researchers write, “these results convey the importance of using condoms in conjunction with compatible lubricants.”

Charlene Dezzutti commented: “Much more work needs to be done to explore the safety of lubes. This was an early study; the jury is still out as to whether hyperosmolar lubes cause damage to the epithelium that, in conjunction with other processes like inflammation, could increase susceptibility to HIV.”

References

Dezzutti CS et al. Is wetter better? An evaluation of over-the-counter personal lubricants for safety and anti-HIV-1 activity. PLoS ONE 7(11): e48328, doi:10.1371/journal.pone.0048328, 2012. See open-access paper here.