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As mentioned earlier in this issue of TreatmentUpdate, research strongly suggests that in HIV-positive people fungi and/or fungal products leak across the intestine into the blood. Scientists call this transfer of fungi and/or fungal products from the gut to the blood “fungal translocation.” Once in the blood, these fungi and/or their products, such as beta-D-glucan (BDG), circulate throughout the body and may contribute to the issue of HIV-related excess immune activation and inflammation. This problem is not reduced by taking ART.
Scientists in the U.S. have tested the antifungal drug fluconazole (Diflucan, Diflucan One) in a small placebo-controlled study with HIV-positive people. These people all had problems with memory and thinking clearly (collectively called neurocognitive impairment). Fluconazole did not improve their condition.
However, fluconazole only has a limited spectrum of activity against the fungi that normally live in the gut. Physician-scientist and fungus expert Martin Hoenigl, MD, from the University of California at San Diego suggests that different antifungal agents be tested for their potential to reduce excess HIV-related immune activation and inflammation. In an editorial in the journal Clinical Infectious Diseases, Dr. Hoenigl states that such antifungal drugs should have the following properties:
Although broad-spectrum antifungals such as posaconazole (Posanol, Noxafil) may be considered for future studies of fungal translocation, Dr. Hoenigl noted that emerging antifungal drugs are likely “better tolerated and/or allow for once weekly [dosing].” Such antifungal drugs are currently in phase II or phase III clinical trials and include the following:
Fungal translocation is an emerging idea in HIV research and it may take some time before more scientists accept it. The exact cause of the excess immune activation and inflammation seen in HIV-positive people is not clear. Nevertheless, if regulatory authorities in high-income countries eventually license drugs such as ibrexfungerp and rezafungin, it is likely that at least pilot studies on fungal translocation will be done in the future. Although the evidence for fungal translocation is growing, scientists working on interfering with bacterial translocation need to continue their efforts.
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—Sean R. Hosein
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