Amphotericin B, an antifungal agent commonly used in Aids patients with cryptococcal meningitis, can be used safely in conjunction with tenofovir (TDF) antiretroviral therapy (ART), according to a study presented at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015).
“Amphotericin B is a drug of choice for treatment of cryptococcal meningitis, a life-threatening fungal infection common among patients with advanced HIV/Aids,” said Dr David Boulware, University of Minnesota, Minneapolis, Minnesota. “Although both amphotericin and TDF are independently known to cause kidney damage and there is concern about their coadministration, there was no scientific evidence to show that when these drugs are used together during the management of cryptococcal meningitis among patients with HIV, there is increased kidney toxicity,” Boulware explained.
To investigate whether the co-administration of amphotericin and TDF leads to increased renal toxicity, Boulware and colleagues assessed kidney function during cryptococcal meningitis treatment and at 4 weeks post-diagnosis in 160 patients receiving concomitant amphotericin and TDF. The patients were enrolled in a clinical trial comparing the effects of adjunctive sertraline treatment and standard antifungal therapy for the treatment of cryptococcal meningitis in Uganda. Participants were classified at diagnosis as not receiving ART, receiving non-TDF ART, or receiving ART including TDF.
Patients’ creatinine concentrations were measured on days 1, 3, 7, 10, 14, and 28 of follow-up, and kidney function was classified according to the National Institute of Allergy and Infectious Diseases (NIAID) Division of Aids (DAIDS) adverse events grading system.
At the time of meningitis diagnosis, 17% (27) of the patients were being treated with non-TDF ART, 26% (42) were on ART with TDF, and 57% (91) were not on ART. The incidence of kidney-related adverse events was similar across the 3 groups for up to 4 weeks after amphotericin initiation. For example, the cumulative incidence of grade 2 to 4 renal adverse events at 1 month was 0.18, 0.19, and 0.16 in the no-ART, ART with no TDF, and ART with TDF groups, respectively (P = .85).
According to Boulware, these results suggest that amphotericin and tenofovir can be used together and that mandatory switching of ART regimens containing tenofovir is not necessary.