Talaromycosis in HIV Patients Responds Better to Initial Amphotericin B Treatment

Highlights:

• HIV patients in Southeast Asia, China and India are predisposed to a fungal infection called talaromycosis
• Current guidelines recommend the use of amphotericin B followed by itraconazole drug
• Researchers evaluated whether the replacement of amphotericin B with itraconazole will be an equally effective and safer option

Possible replacement of amphotericin B with the safer and oral drug itraconazole for a fungal infection called talaromycosis was evaluated in HIV patients, and found that it may not be a feasible option. The study was published in the New England Journal of Medicine.

Infection with the HIV (human immunodeficiency) virus reduces immunity and eventually results in a condition called AIDS. The immunity may reduce to such an extent that infections that do not affect people with normal immunity can cause life-threatening infection in HIV-infected patients. Examples of such infections include cryptococcosis and tuberculosis caused by Mycobacterium avium complex.

Another infection that only affects people with reduced immunity is talaromycosis, which is caused by a fungus called Talaromyces marneffei. The infection is particularly noted in HIV patients from or traveling to Southeast Asia, China, and India. It infects the lungs and can spread to multiple organs. The infection has a high death rate despite treatment with antifungal medications.

A clinician is often faced with the dilemma of choosing between the effectiveness and safety of medications. A highly effective medication may not be the safest option, and vice versa. The same issue arises during the treatment of talaromycosis. The current recommended treatment for talaromycosis is amphotericin B for 2 weeks followed by itraconazole for 10 weeks. Amphotericin B is associated with serious side effects related to the kidneys and blood, and is also quite expensive. It has to be given by an intravenous infusion, which increases the cost of the treatment. Some researchers felt that if amphotericin could be replaced with itraconazole even in the initial period, the patient could be at a risk for fewer complications and the treatment would have lesser financial implications, which is extremely important since poverty is not uncommon in the countries where the infection is prevalent.

In a study referred to as the Itraconazole versus Amphotericin B for Penicilliosis (IVAP) trial, (penicilliosis is the older name for talaromycosis), researchers compared the use of amphotericin B with itraconazole for the initial treatment of talaromycosis in 440 adults over a period of three years in Vietnam.

The patients were divided into two groups:

• One group received intravenous amphotericin B for 14 days
• The second group received 300 mg of itraconazole twice daily for the first three days, followed by a lower dose of 200 mg twice a day for the remaining 11 days.

Both the groups were hospitalized for these two weeks.

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After the first two weeks of treatment, both groups received 200 mg of itraconazole twice daily for 10 weeks, which was later reduced to 100 mg twice daily and administered until the CD4+ count was stabilized for at least 6 months. The CD4+ count is associated with the immunity of the patient.

The patients, in addition, received anti-HIV treatment and preventive treatment for Pneumocystis jiroveci pneumonia, another infection commonly noticed in AIDS patients.

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The research team found that:

In terms of effectiveness,

• The risk for death was lower in the amphotericin group as compared to the itraconazole group. Though this effect appeared to be similar in both the groups at the end of 14 days, in due course, i.e. at the end of 24 weeks, the risk was almost double in the itraconazole group.
• The healing was faster and the relapse rates were lower in the patients who received amphotericin
• Amphotericin B cleared the fungus from the blood almost four times as fast as itraconazole, as noted through laboratory tests on day 8 of the treatment

In terms of side effects:

• As expected, the side effects were more common in the amphotericin group and included infusion-related reactions, increase in creatinine levels (which indicates reduced kidney function), low blood potassium and magnesium levels, and anemia.
• Most of the side effects in the amphotericin group did not reach serious proportions. One possible reason could be the hydration and the electrolyte treatment that the patients on amphotericin B received before the treatment.

Thus, it appears, at least for now, that amphotericin B will remain the first choice for the initial treatment of talaromycosis. The researchers suggest that since amphotericin B clears the fungus from the blood in 8 days, treatment with amphotericin B for 8 days will probably be enough. More studies are needed to establish this.

Reference:

1. Le T et al. A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis. N Engl J Med 2017; 376:2329-2340; DOI: 10.1056/NEJMoa1613306

Source-Medindia