Limited effectiveness of high-dose liposomal amphotericin B (AmBisome) for treatment of visceral leishmaniasis in an Ethiopian population with high HIV prevalence.
BACKGROUND
Due to unacceptably high mortality with pentavalent antimonials, Médecins Sans Frontières in 2006 began using liposomal amphotericin B (AmBisome) for visceral leishmaniasis (VL) patients in Ethiopia who were severely ill or positive for human immunodeficiency virus (HIV).


METHODS
We used clinical data obtained from January 2007 to January 2009 to compare outcomes by HIV status and VL episode (primary vs relapse) and to identify risk factors for treatment failure among patients treated with AmBisome monotherapy at a total dose of 30 mg/kg in 6 doses on alternate days, a higher dose than recommended by the World Health Organization (20 mg/kg).


RESULTS
Among 94 HIV-negative severely ill VL patients, 93% had initial cure and 6% died. Among 195 HIV-positive patients (116 primary, 79 relapse VL), 60% had initial cure, 7% died, and 32% were parasitological failures. AmBisome was less effective in the 79 HIV-positive VL relapse patients (38% initial cure, 5% mortality, 56% parasitological failure) than in the 116 HIV-positive primary VL patients (74% initial cure, 8% mortality, 16% parasitological failure). Sodium stibogluconate (SSG) rescue treatment increased the overall cure rate among all HIV-positive VL patients from 60% to 83%, but 16% (9 of 59) of rescue treatment patients died, mainly due to SSG toxicity.


CONCLUSIONS
High-dose AmBisome for VL is safe and effective in severely ill HIV-negative patients, and safe but less effective in HIV-positive patients. Combining AmBisome with another drug may enhance its effectiveness in HIV-positive VL patients. SSG should be avoided for treatment of VL in HIV-positive patients.
Public Health Department, Médecins Sans Frontières, Amsterdam, the Netherlands. koert.ritmeijer@amsterdam.msf.org
Koert
K
Ritmeijer
Rachel
R
ter Horst
Solomon
S
Chane
Endashaw Mengistu
EM
Aderie
Turid
T
Piening
Simon M
SM
Collin
Robert N
RN
Davidson
D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D005002:Ethiopia; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007223:Infant; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D012307:Risk Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
D000981:Antiprotozoal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B