Single high-dose liposomal amphotericin B safe for HIV-associated fungal infections

For patients with HIV-associated fungal infections, single high-dose liposomal amphotericin B (LAmB) has the lowest risk for life-threatening adverse events (AEs) when compared with other amphotericin B-based treatment options. These findings, from a systematic review and meta-analysis, were published in Open Forum Infectious Diseases.

In 2022, the World Health Organization recommended single high-dose LAmB as first-line induction therapy for HIV-associated cryptococcal meningitis.

To better understand how LAmB compares with other amphotericin B-based treatment options in regard to severe AE occurrence, researchers at Dartmouth Hitchcock Medical Center in New Hampshire searched publication databases through April 2023 for relevant studies.

A total of 3 randomized controlled trials (N=946) were included in the review, of which 1 (published in 2020) was designed to compare single high-dose LAmB with amphotericin B deoxycholate (DAmB), and 2 (published in 2019 and 2023) were designed to compared single high-dose LAmB with 14 days of LAmB therapy.

In the studies published in 2019 in and 2023, 16 and 34 patients received single high-dose LAmB and 17 and 37 received 14 days of LAmB, respectively. In the study published in 2022, 420 patients received single high-dose LAmB and 422 received DAmB.

Pooled analyses of the 3 treatment options showed that single high-dose LAmB was significantly associated with the lowest risk for grade 4 kidney events (risk ratio [RR], 0.43; 95% CI, 0.20-0.94; I², 3%; P =.03), grade 4 hematologic events (RR, 0.46; 95% CI, 0.32-0.65; I², 27%; P <.0001), and grade 4 AEs (RR, 0.68; 95% CI, 0.55-0.86; I², 0%; P =.0010).

Further analysis of the 3 treatment options also indicated that patients who received single high-dose LAmB were less likely to develop grade 3 and grade 4 kidney events (RR, 0.49; 95% CI, 0.33-0.72; I², 0%; P =.0004).

However, single high-dose LAmB did not differ significantly from that of comparator treatments in regard to the combined outcomes of grades 3 or 4 hematologic events (RR, 0.62; 95% CI, 0.36-1.07; I², 30%; P =.09) or grades 3 or 4 AEs (RR, 0.75; 95% CI, 0.53-1.06; I², 26%; P =.10). It also was associated with the lowest risk for infusion-related AEs of any severity (RR, 0.78; 95% CI, 0.15-3.99; I², 83%; P =.76).

The 3 treatment options did not significantly differ in regard to the risk for 10-week mortality (RR, 0.89; 95% CI, 0.72-1.10; I², 0%; P =.29).

This analysis may have been biased as the majority of data were sourced from the trial in which DAmB was used as the comparator. Other limitations include potential heterogeneity as single high-dose LAmB was either used alone or in combination with 1 to 2 antifungal agents as induction therapy in all 3 RCTs.

According to the researchers, “Single high-dose LAmB is safer than traditional amphotericin-B based regimen when used for induction therapy to treat cryptococcal meningitis and histoplasmosis in people living with HIV.”

By Jessica Nye, PhD

References:

Kang HE, Uy JP, Ho CC, et al. Safety of single high-dose liposomal amphotericin B for induction treatment of cryptococcal meningitis and histoplasmosis in people living with HIV: a systematic review and meta-analysis. Open Forum Infect Dis. Published online September 20, 2023. doi:10.1093/ofid/ofad472