Liposomal Amphotericin B for the Treatment of Visceral Leishmaniasis

Table 2.patients.Findings of published studies of liposomal amphotericin B (LAmB) treatment in HIV-visceral leishmaniasis–coinfectedCountry Reference Study designSpain [35] Case series (relapseafter Sb V treatment)No. ofsubjectsTotal LAmBdose, mg/kg Regimen Initial response2 22.5 1.5 mg/kg per day for15 days21 1 mg/kg per day for 21daysGreece [36] Case series 2 40 1 mg/kg per day fordays 1–7 and 1.5mg/kg per day fordays 8–2920 0.75 mg/kg per day fordays 1–7 and 1.5mg/kg per day fordays 8–17Spain [37] Case series 5 40 4 mg/kg per day fordays 1–5, 10, 17, 31,and 38Europe b [23] Open-label, dose-finding 11 29–39 100 mg per day for 21daysItaly [38] Open-label, dose-finding 10 40 4 mg/kg per day fordays 1–5, 10, 17, 31,and 38France [39] Case series, secondaryprophylaxis5 60–86 by day 30 2.9–4.1 mg/kg per dayfor 5–24 days, followedby 2.7–3.8mg/kg every 15 daysto prevent relapseGood clinical response,parasite free at 3– 6months…Good clinical response;no relapse at 10–16months…Parasites cleared in80% of subjectsPartial clinical responsein 9 of 11 subjects;negative for parasitesat day 21Partial clinical responsein 7 of 8 subjects;negative for parasitesat day 453 of 5 subjects wererelapse free atmonths 13–22Relapserate, %0…0…40 a89 c88 d40 eNOTE. SB V , pentavalent antimonial drugs.a Relapses at 4 and 20 months.b Nine subjects from Italy, 1 from France, and 1 from Portugal.c Two deaths due to other causes, 8 relapses, and 1 cure.d Seven subjects experienced relapses at 2–7 months, 2 were lost to follow-up, and 1 was listed as “leishmanina positive.”e Two patients had relapse at 42 and 270 days and were re-treated with high-dose liposomal LAmB followed by prophylaxis, with good response in 1 of the2 patients.clusion of lower total doses in combination regimens. To filefor an extension of the preferential pricing scheme, figures detailingthe projected annual uptake will be compiled under theleadership of the WHO.RECOMMENDATIONSZoonotic VL (the Mediterranean Basin, the Middle East, andBrazil)• A total liposomal amphotericin B dose of 20 mg/kg is adequateto treat immunocompetent children and adults inthese regions.• The exact dosing schedule can be flexible (divided into dosesof 10 mg/kg on 2 consecutive days or in smaller divideddoses), but liposomal amphotericin B pharmacokineticssuggest that the initial dose will provide better tissue levelsif at least 5 mg/kg is given.• The schedule of 10 mg/kg/day on 2 consecutive days needsto be validated in adults with zoonotic VL.• Veterinary use of liposomal amphotericin B and other newantileishmanial drugs (e.g., miltefosine and paromomycin)should be avoided to prevent the development of resistance.Anthroponotic VL (South Asia and the Horn of Africa)• When unresponsiveness to antimonial drugs exceeds athreshold to be determined in each specific region, policymakers should strongly consider a shift to an alternativefirst-line regimen. An Indian expert committee has suggestedusing thresholds of 10%–20% unresponsiveness. Twopossible alternative regimens are an amphotericin B formulation(for example, liposomal amphotericin B at a totaldose of 20 mg/kg) or a combination regimen that does notinclude Sb V .922 • CID 2006:43 (1 October) • REVIEWS OF ANTI-INFECTIVE AGENTS