Background and Importance In Spain, leishmaniasis is caused by Leishmania infantum, whose main reservoirs are dogs or small mammals, transmitted through the bite of dipterian insects of the genus Phlebotomus. Leishmania infection causes disease ranging from localised cutaneous to visceral leishmaniasis (VL), the most severe form, affecting frequently to profoundly immunocompromised individuals, such as late-stage HIV-infected patients, with high rates of treatment failure, relapses, and mortality.

Liposomal amphotericin B (LAB) is the VL treatment of choice, with an induction regimen followed by maintenance (3–5mg/kg/monthly). Published data¹ suggests that sargramostim, a recombinant human granulocyte-macrophage colony-stimulating factor, has potential as co-adjuvant treatment to LAB in VL-HIV to augment immune responses and clinical control.

Aim and Objectives To report a case of VL-HIV co-infection successfully treated with monthly LAB and sargramostim for 12 weeks.

Material and Methods A 47-year-old male, diagnosed with HIV infection in 2017 (CD4 T cell count: 14/µl; viral load: 1380000 copies/mL. Pneumocystis jirovecii pneumonia and esophageal candidiasis). Despite a continuous undetectable viral load with antiretroviral treatment, CD4 count remained ≤75–100/µL. In December 2020, he presented a mixed cryoglobulinemic membranoproliferative glomerulonephritis secondary to VL. Despite having received a complete induction regimen with LAB, febricula, systemic symptoms and positive Leishmania PCR persisted, therefore monthly LAB 3mg/kg were administered until March 2023.

Off-label use of sargramostim 150 mcg subcutaneously every two weeks for 3 months was requested as co-adjuvant treatment to LAB 3mg/kg/monthly, was approved by the off-label Pharmacy committee and authorised by national spanish drug regulator (AEMPS). Success of the treatment was defined as the discontinuation of LAB without clinical relapse.

Results After having completed 3 months of sargramostim plus LAB, the patient was asymptomatic, HIV viral load was undetectable and Leishmania PCR in bone marrow was still positive, but microscopically negative. LAB and sargramostim were discontinued and the patient was monthly evaluated. Four months later, the patient remained completely asymptomatic, awaiting further evaluation.

Regarding sargramostim safety, the patient presented fever after two doses, requiring a dose reduction by half. Treatment was afterwards well tolerated and completed with full sargramostim dose.

Conclusion and Relevance Sagramostim co-adjuvant treatment with LAB may be effective for the treatment of VL-HIV co-infected patients, although further long-term revaluation is needed.

References and/or Acknowledgements 1. https://pubmed.ncbi.nlm.nih.gov/15711134/

Conflict of Interest No conflict of interest.