Recent advances in the development of antiretrovirals have significantly extended life-spans and positively impacted morbidity of HIV-seropositive patients. While effective, antiretrovirals are associated with complex medication regimens, large pill burdens, and significant side effects which may impact quality of life. Researchers continue to examine various chemical entities in their search for agents with anti-HIV activity. Ideal agents would be efficacious, easily dosed and administered, inexpensive, and with few adverse effects. Chloroquine and its analog hydroxychloroquine are two inexpensive agents that are widely used for the treatment of malaria and have been shown to achieve some level of anti-HIV activity. The exact mechanism of chloroquine and hydroxychloroquine's anti-HIV activity has not yet been discerned but may be related to effects on HIV's surface envelope glycoprotein 120. If found efficacious, both drugs would offer significant advantages to current therapy including a unique mechanism of action, lack of cross-resistance with other antiretrovirals, and low cost. Early and limited in vitro and in vivo data have demonstrated modest anti-HIV efficacy as indicated by measures of viral burden. Effects on CD4+ cell counts have not been as pronounced. It is premature to advocate the use of either of these agents in the management of routine HIV disease; however; the drugs should be further studied to determine their benefit in the treatment of patients who have exhausted all standard treatments. Larger, well-controlled trials are needed to discern the potential role of chloroquine and hydroxychloroquine in the management of HIV.
Density-dependent cell-cell communication, or quorum sensing (QS), has been demonstrated in numerous species of bacteria. The basic function of QS is likely to confer a nutritional advantage, particularly in a highly populated, mixed-species environment. QS also has ramifications on the production of colonization and virulence factors. Pheromone-like substances secreted into the extracellular milieu appear to govern many of the transcription products in these bacteria. At a high cell density, the QS systems are triggered, and the transcription of the colonization factors are suppressed and replaced by the expression of virulence factors. Major pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, have evolved with numerous QS circuits, which modulate the production of various toxins and regulate parallel QS systems. Several QS-modulating therapies, such as macrolide antibiotics, QS vaccines, and competitive QS inhibitors, have been investigated and may prove to be helpful in diminishing the translation of QS-directed toxins or by prematurely activating the QS response to alert the immune system to bacteria hiding in a low cell density. QS represents a recently discovered method of bacterial communication and population control, which may prove to be a unique mechanism to prevent, suppress, and/or treat infectious diseases.
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