23 June 2017

The anti-fungal medication amphotericin B is most effective in controlling the HIV-related fungal infections that occur frequently in South and Southeast Asia. If treated with this medication, the mortality from these infections is reduced by half compared to itraconazole, a frequently used alternative. Even though amphotericin is expensive and has many side effects, it should be more widely available. This was the conclusion of an article by an international research group, including Heiman Wertheim of Radboudumc, which was published on 17 June in the New England Journal of Medicine.

In South and Southeast Asia, an infection with a Talaromyces fungus is one of the most important HIV-related causes of death. According to international guidelines, infections with this fungus should be treated with amphotericin B. However, this medication is expensive, difficult to obtain and has significant side effects. An alternative is the cheaper anti-fungal medication itraconazole, which is easier to take and has fewer side effects. Previous studies concluded that these medications are equally effective, but a comparative clinical study had not been conducted. However, itraconazole is already being used on a large scale in South and Southeast Asia.
 
Comparing medications
During a three-year period, an international group of researchers from Vietnam, England, the Netherlands and the United States compared the effect of treatments with these anti-fungal medications at five Vietnamese hospitals. One group with 219 patients was given amphotericin, and a second group of 221 patients was given itraconazole. After two weeks, few differences were found between the groups. In the amphotericin group, 6.5% of the patients died, compared to 7.4% in the itraconazole group.
 
Effects differ after eight weeks
Six months after the treatment the difference between the groups suddenly became much greater: 11.3% of the amphotericin patients had died, compared to 21% of the patients who were given itraconazole. In addition, in the group that was given the alternative medication, it took longer before the patients were fungus-free, and these patients had more frequent relapses. On the other hand, the itraconazole group had fewer side effects. The effects of the two treatments began to differ only after eight weeks.
 
Long-term effect
An explanation for the difference between the medications can probably be found in the stronger effect of amphotericin. In patients who were given this medication, the quantity of fungus declined much faster. Heiman Wertheim: “It seems that the effect only becomes apparent in the long-term. This also explains why the previous non-comparative case studies, in which patients were tracked for a much shorter time, did not find any difference between the effectiveness of the medications.” Paul Verweij, head of the mycology laboratory at Radboudumc: “Worldwide, the disease burden of fungal infections is underestimated. This study is therefore an important step, and many patients in Asia will be able to benefit from these new findings”.
 
Better availability
Despite its disadvantages, the researchers concluded that the more expensive amphotericin was preferable to the cheaper alternative. For effective treatment of HIV-related fungal infections in Asia, amphotericin must become more widely available at a lower price.

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Marcel Wortel

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