Visceral Leishmaniasis and HIV Co-infection in Bihar, India: Long-term Effectiveness and Treatment Outcomes with Liposomal Amphotericin B (AmBisome)

Abstract

BackgroundVisceral Leishmaniasis (VL; also known as kala-azar) is an ultimately fatal disease endemic in the Indian state of Bihar, while HIV/AIDS is an emerging disease in this region. A 2011 observational cohort study conducted in Bihar involving 55 VL/HIV co-infected patients treated with 20–25 mg/kg intravenous liposomal amphotericin B (AmBisome) estimated an 85.5% probability of survival and a 26.5% probability of VL relapse within 2 years. Here we report the long-term field outcomes of a larger cohort of co-infected patients treated with this regimen between 2007 and 2012.Methods and Principal FindingsIntravenous AmBisome (20–25 mg/kg) was administered to 159 VL/HIV co-infected patients (both primary infections and relapses) in four or five doses of 5 mg/kg over 4–10 days. Initial cure of VL at discharge was defined as improved symptoms, cessation of fever, improvement of appetite and recession of spleen enlargement. Test of cure was not routinely performed. Antiretroviral treatment (ART) was initiated in 23 (14.5%), 39 (24.5%) and 61 (38.4%) before, during and after admission respectively. Initial cure was achieved in all discharged patients. A total of 36 patients died during follow-up, including six who died shortly after admission. Death occurred at a median of 11 weeks (IQR 4–51) after starting VL treatment. Estimated mortality risk was 14.3% at six months, 22.4% at two years and 29.7% at four years after treatment. Among the 153 patients discharged from the hospital, 26 cases of VL relapse were diagnosed during follow-up, occurring at a median of 10 months (IQR 7–14) after discharge. After accounting for competing risks, the estimated risk of relapse was 16.1% at one year, 20.4% at two years and 25.9% at four years. Low hemoglobin level and concurrent infection with tuberculosis were independent risk factors for mortality, while ART initiated shortly after admission for VL treatment was associated with a 64–66% reduced risk of mortality and 75% reduced risk of relapse.SignificanceThis is the largest cohort of HIV-VL co-infected patients reported from the Indian subcontinent. Even after initial cure following treatment with AmBisome, these patients appear to have much higher rates of VL relapse and mortality than patients not known to be HIV-positive, although relapse rates appear to stabilize after 2 years. These results extend the earlier findings that co-infected patients are at increased risk of death and require a multidisciplinary approach for long-term management.

Protective Efficacy of Secondary Prophylaxis Against Visceral Leishmaniasis in Human Immunodeficiency Virus Coinfected Patients Over the Past 10 Years in Eastern India

“…Similar results were also seen in a recent study by Burza and others from Bihar, India. 10 These essentially demonstrate that the natural history of VL with HIV as a backdrop is significantly different from VL monoinfection despite good compliance with ART.…”

“…10 Another recent report from Bihar, India, identified failure to initiate ART and concurrent tuberculosis as independent risk factors for mortality and poor outcome but could not identify any factors associated with relapse. 32 However, none of these groups offered secondary prophylaxis against VL.…”

“…Relapse rates ranging from 25% to 61%, depending on varying definitions used, have been reported previously. 10,[20][21][22][23][24] A recent systematic review identified the following factors as predictors of relapse: failure of rise of CD4+ cells at follow-up, lack of secondary prophylaxis, and previous history of relapse of VL. 24 Secondary prophylaxis has previously been tried in HIV-VL especially in Europe and Africa.…”

“…7,8 The risk of developing VL is 100-2,300 times higher in HIV-infected patients than in HIV-negative individuals. 9,10 Though randomized controlled trials (RCTs) are yet to be available in the arena of HIV-VL, it is generally accepted that worse outcome, higher relapse rate, mortality, drug toxicity, and resistance are common in this group of patients. 10,11 Lack of RCT and high-quality evidence from well-designed studies in the field of HIV-VL coinfection makes treatment decisions and prognostications difficult.…”

Diagnosing Neglected Tropical Diseases in HIV Coinfection

“…Concerning VL-HIV coinfection, the typical form, characterized by fever, splenomegaly, and hepatomegaly, is more common. [80][81][82][83] However, atypical manifestations, including the involvement of the gastrointestinal tract and kidneys, have been reported, whereas diarrhea and cough are more prevalent in HIV-VL coinfected patients. 84,85 Regarding TL in HIV-infected patients, there are few reports in the literature.…”