Treatment of Visceral Leishmaniasis HIV-Related Dr. Fernando Laguna Hospital Carlos III Madrid

TREATMENT OF VISCERAL LEISHMANIASIS HIV-RELATED Which drug? Dose? Length?

PATIENTS and METHODS (I) Inclusion/Exclusion Randomization Treatment A Treatment B Parasitological cure Toxicity Relapses

PATIENTS and METHODS (II) HIV-infected patients with a first episode of VL >18 years old. Pancreatitis. Protrombin activity <40%. Aminotransferase >10 times. Creatinin >2 times. Miocardiopathy... Allergy... Pregnant woman... Study Population: Exclusion criteria: Setting: Tertiary Hospitals in Spain. Design : multicentre, open-label with blinded centralised randomisation, parallel, active-controlled clinical trial.

PATIENTS and METHODS (III) Endpoint: –Treatment was considered successful if no parasites were detected in a bone marrow aspirate performed 1 month after the end of therapy. Statistical analysis: –The primary analysis was performed following an intention-to-treat principle.

We unknewn the efficacy and safety of pentavalent antimonials. Amphotericin B was useful in immunocompetent patients with VL and it is very potent in vitro BACKGROUND

To compare the efficacy and safety of pentavalent antimonials with amphotericin B in HIV-infected patients with VL. AIM

Amphotericin B 0,7 mg/kg/d, 28 days Meglumine antimoniate 20 mg Sb v /kg/d, 28 days TREATMENT

RESULTS (I): Baseline data MA =19 AmB n=45 Gender (M, %) Age CD-4 T cells count18 ( ) 29 ( ) Risk practice for HIV (%) Previous AIDS (%) n= IVDU Homo/Bisexual men

RESULTS (II) : Outcome MA =19 AmB n=45 n=44 Uncompleted treatment Toxicity 5 5 Death 5 5 Abandoned Treatment 0 5 Completed Treatment Cured 29 (66%) 28 (62%) Not cured 4 2 Lost to follow-up 1 0

RESULTS (IV): Toxicity MA =19 AmB n=45 n=44 Pts. with at least one AE(%) 25(55) 27(60) Pts. With suspension of Treatment due to an AE 5(11) 5(11) Cardiotoxicity 6(14) 0 Hyperamylasemia 13(20) 0 Nephrotoxicity 2(5) 16(36)

Amphotericin B presents a similar efficacy than meglumine antimoniate administered for 28 days. Treatment-related adverse events leading to therapy discontinuation were similar in both groups. CONCLUSIONS

Amphotericin B lipid complex, an amphotericin B lipid formulation, is very effective in immunocompetent Indian patients with visceral leishmaniasis BACKGROUND

To compare the efficacy and safety of amphotericin B lipid complex (ABLC) versus meglumine antimoniate in HIV- infected patients with a first episode of VL. AIM

PATIENTS and METHODS (I) Treatment groups: –ABLC 3 mg/kg/d for 5 days (ABLC-5). –ABLC 3 mg/kg/d for 10 days (ABLC-10). –Meglumine antimoniate 20 mg Sb v /kg/d for 28 days (MA-28).

RESULTS (I): Baseline data MA-28 n=19 ABLC-5 n=18 ABLC-10 n=20 Gender (M/F) 15/316/3 17/3 Age34.1 ± ± ± 5.8 CD-4 T cells count75 ± 9076 ± ± 175 CD-4 T cells / 216 / 217 / 3 HIV stage (n): A B C Nº of patients under HAART theraphy 753

RESULTS (II): Outcome =19 Not confirmed VL No efficacy assessment Toxicity Death Lost follow-up Efficacy assessment Cured Not cured Major P. Violation MA ABLC-5 ABLC-10 n=19 n=18 n= (37%) (33%) * 2 1* (42%) 10

RESULTS (III): EFFICACY - ITT population

RESULTS (II): Adverse Events Treatment Related =19 Death Infusion-related AEs Phlebitis Vomiting Pancreatitis Hyperamilasemia Kidney failure Anemia worsening MA ABLC-5 ABLC

Amphotericin B lipid complex for 5 or 10 days presents a similar efficacy than meglumine antimoniate administered for 28 days, with a lower frequency of adverse events and a better tolerability. Treatment related adverse events leading to discontinuation were more frequent in antimonial group than in ABLC groups. CONCLUSION

Investigators (alphabetic order): Dr. J. AltésH. de l´Alt Penedés, Barcelona. Dr. J. Alvar y C. CañavateC. Nacional de Microbiología, Majadahonda. Dr. JR. Arribas y E. Torres H La Paz, Madrid. Dr. V.BoixH. General, Alicante. Dr. JM. Gatell y JM. Miró H. Clínic, Barcelona. Dr. J. Gómez Rodrigo H. Severo Ochoa, Leganés. Dr.M GórgolasF. Jiménez Díaz, Madrid. Dr. F. Laguna y P.MartínezH. Carlos III, Madrid. Dr. R. López-Vélez y JA. Pérez MolinaH. Ramón y Cajal, Madrid. Dr. M. MarquezH. Virgen de la Victoria, Málaga. Dr. FJ. Medrano y ME. Jiménez Mejías H. Virgen del Rocío, Sevilla. Dr. J. PasquauH. Virgen de las Nieves,Granada. Dr. F. Pulido y R. Rubio H. 12 de Octubre, Madrid. Dra. G. Picó H. Can Misses, Ibiza. Dr. E.Ribera y C. AzuajeH. Vall d´Hebron, Barcelona. Dra. A. SalasH. Son Dureta, Palma. Dr. J. Sanz H. de la Princesa, Madrid. Dr. G. Sirera y B.ClotetH. German Trias I Pujol, Badalona. Dr. J. Torre-Cisneros y JM. KindelánH. Reina Sofía, Córdoba. Dr. S.Videla y M.Sust L. Pensa-Esteve, Barcelona.