Abstract
BackgroundThe continued growth of the global HIV epidemic highlights the urgent need to develop novel prevention strategies to reduce HIV transmission. The development of topical microbicides is likely to take a number of years before such a product would be widely available. This has resulted in a call for the rapid introduction of simpler vaginal intervention strategies in the interim period. One suggested practice would be vaginal douching with natural products including lime or lemon juice. Here we present a comprehensive preclinical evaluation of lime juice (LiJ) as a potential intervention strategy against HIV.ResultsPre-treatment of HIV with LiJ demonstrated direct virucidal activity, with 10% juice inactivating the virus within 5 minutes. However, this activity was significantly reduced in the presence of seminal plasma, where inactivation required maintaining a 1:1 mixture of neat LiJ and seminal plasma for more than 5 minutes. Additionally, LiJ demonstrated both time and dose-dependent toxicity towards cervicovaginal epithelium, where exposure to 50% juice caused 75–90% toxicity within 5 minutes increasing to 95% by 30 minutes. Cervicovaginal epithelial cell monolayers were more susceptible to the effects of LiJ with 8.8% juice causing 50% toxicity after 5 minutes. Reconstructed stratified cervicovaginal epithelium appeared more resilient to LiJ toxicity with 30 minutes exposure to 50% LiJ having little effect on viability. However viability was reduced by 75% and 90% following 60 and 120 minutes exposure. Furthermore, repeat application (several times daily) of 25% LiJ caused 80–90% reduction in viability.ConclusionThese data demonstrate that the virucidal activity of LiJ is severely compromised in the presence of seminal plasma. Potentially, to be effective against HIV in vivo, women would need to apply a volume of neat LiJ equal to that of an ejaculate, and maintain this ratio vaginally for 5–30 minutes after ejaculation. Data presented here suggest that this would have significant adverse effects on the genital mucosa. These data raise serious questions about the plausibility and safety of such a prevention approach.
Highlights
The continued growth of the global Human immunodeficiency virus (HIV) epidemic highlights the urgent need to develop novel prevention strategies to reduce HIV transmission
Women are increasingly bearing the brunt of the global HIV epidemic, accounting for 50% of cases worldwide and >67% of cases in sub-Saharan Africa where three times more 15–24 year old women are infected than men [1]
A previous pilot study on a similar population of commercial female sex workers (FSW) has shown that the most common method of using lime juice (LiJ) is to mix the juice from 1–4 limes with 1–4 teaspoons of water and douche with the resulting solution, but practices range from mixing the juice of one lime with one cup of water to mixing the juice of four limes with one teaspoon of water [12]
Summary
The continued growth of the global HIV epidemic highlights the urgent need to develop novel prevention strategies to reduce HIV transmission. The development of topical microbicides is likely to take a number of years before such a product would be widely available This has resulted in a call for the rapid introduction of simpler vaginal intervention strategies in the interim period. The timelines for the development of an effective microbicide (5–10 years) have led some to question whether simpler strategies using readily available natural products such as limes or lemons, might allow a more rapid introduction of a vaginal intervention strategy that could prevent infection even if only partially effective. Limes are cheap and readily accessible throughout all tropical and temperate regions of the globe [5], and are probably accessible to the majority of the world's population They most likely fit the first three criteria of an effective intervention strategy (cheap, available, acceptable), little is known about the other criteria – safety and efficacy
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