Case Report: No Response to Liposomal Daunorubicin in a Patient with Drug-Resistant HIV-Associated Visceral Leishmaniasis

Visceral leishmaniasis (VL) in patients with HIV co-infection presents a significant therapeutic challenge due to the lessened chance of achieving long-term cure. We report a case of VL in a 60-year-old man with HIV infection who became refractory to anti-leishmania treatment due to multi-drug resistance. In the face of a worsening clinical situation, and with no other options available, he was treated with an experimental regimen of liposomal daunorubicin, which has previously been shown to have in vitro activity against Leishmania donovani and to be effective treatment of VL in animal studies. To our knowledge, he was the first patient with VL and HIV co-infection to have this treatment evaluated. We report on the lack of response to this treatment and possible causes for its failure.

[1]  M. Keighobadi,et al.  Hypothesis: The potential application of doxorubicin against cutaneous leishmaniasis , 2015, Tropical parasitology.

[2]  L. Lynen,et al.  Visceral Leishmaniasis and HIV Coinfection in East Africa , 2014, PLoS neglected tropical diseases.

[3]  D. Schürmann,et al.  Macrophages accumulate in the gut mucosa of untreated HIV-infected patients. , 2014, The Journal of infectious diseases.

[4]  Douglas E. Jones,et al.  Programmed Death 1–Mediated T Cell Exhaustion during Visceral Leishmaniasis Impairs Phagocyte Function , 2013, The Journal of Immunology.

[5]  P. Mishra,et al.  Development of doxorubicin loaded novel core shell structured nanocapsules for the intervention of visceral leishmaniasis , 2013, Journal of microencapsulation.

[6]  M. D. de Sousa,et al.  Efficacy of Anti-Leishmania Therapy in Visceral Leishmaniasis among HIV Infected Patients: A Systematic Review with Indirect Comparison , 2013, PLoS neglected tropical diseases.

[7]  D. Lockwood,et al.  Clinical aspects of visceral leishmaniasis in HIV infection , 2013, Current opinion in infectious diseases.

[8]  P. Dwivedi,et al.  Development of nanocapsules bearing doxorubicin for macrophage targeting through the phosphatidylserine ligand: a system for intervention in visceral leishmaniasis. , 2012, The Journal of antimicrobial chemotherapy.

[9]  R. López-Vélez,et al.  The Relationship between Leishmaniasis and AIDS: the Second 10 Years , 2008, Clinical Microbiology Reviews.

[10]  J. Drevs,et al.  Pharmacokinetics of liposomal doxorubicin (TLC-D99; Myocet) in patients with solid tumors: an open-label, single-dose study , 2004, Cancer Chemotherapy and Pharmacology.

[11]  S. Karmakar,et al.  Targeting of parasite-specific immunoliposome-encapsulated doxorubicin in the treatment of experimental visceral leishmaniasis. , 2004, The Journal of infectious diseases.

[12]  J. M. Pérez-Victoria,et al.  Alkyl-Lysophospholipid Resistance in Multidrug-Resistant Leishmania tropica and Chemosensitization by a Novel P-Glycoprotein-Like Transporter Modulator , 2001, Antimicrobial Agents and Chemotherapy.

[13]  E. Bouza,et al.  Visceral Leishmaniasis in Human Immunodeficiency Virus (HIV)-Infected and Non-HIV-Infected Patients: A Comparative Study , 2001, Medicine.

[14]  J. V. Von Roenn,et al.  Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  D. Wirth,et al.  Multidrug resistance in Leishmania donovani is conferred by amplification of a gene homologous to the mammalian mdr1 gene , 1992, Molecular and cellular biology.

[16]  P. K. Das,et al.  Potential of doxorubicin as an antileishmanial agent. , 1992, The Journal of parasitology.

[17]  B. Das,et al.  DNA topoisomerases of Leishmania: the potential targets for anti-leishmanial therapy. , 2008, Advances in experimental medicine and biology.

[18]  M. Zucchetti,et al.  The pharmacokinetics of liposomal encapsulated daunorubicin are not modified by HAART in patients with HIV-associated Kaposi's sarcoma , 2000, Cancer Chemotherapy and Pharmacology.