Long term outcomes and prognostics of visceral leishmaniasis in HIV infected patients with use of pentamidine as secondary prophylaxis based on CD4 level: a prospective cohort study in Ethiopia

Abstract

Background The long-term treatment outcome of visceral leishmaniasis (VL) patients with HIV co-infection is complicated by a high rate of relapse, especially when the CD4 count is low. Although use of secondary prophylaxis is recommended, it is not routinely practiced and data on its effectiveness and safety are limited. Methods A prospective cohort study was conducted in Northwest Ethiopia from August 2014 to August 2017 (NCT02011958). HIV-VL patients were followed for up to 12 months. Patients with CD4 cell counts below 200/μL at the end of VL treatment received pentamidine prophylaxis starting one month after parasitological cure, while those with CD4 count ≥200 cells/μL were followed without secondary prophylaxis. Compliance, safety and relapse-free survival, using Kaplan-Meier analysis methods to account for variable time at risk, were summarised. Risk factors for relapse or death were analysed. Results Fifty-four HIV patients were followed. The probability of relapse-free survival at one year was 50% (95% confidence interval [CI]: 35–63%): 53% (30–71%) in 22 patients with CD4 ≥200 cells/μL without pentamidine prophylaxis and 46% (26–63%) in 29 with CD4 <200 cells/μL who started pentamidine. Three patients with CD4 <200 cells/μL did not start pentamidine. Amongst those with CD4 ≥200 cells/μL, VL relapse was an independent risk factor for subsequent relapse or death (adjusted rate ratio: 5.42, 95% CI: 1.1–25.8). Except for one case of renal failure which was considered possibly related to pentamidine, there were no drug-related safety concerns. Conclusion The relapse-free survival rate for VL patients with HIV was low. Relapse-free survival of patients with CD4 count <200cells/μL given pentamidine secondary prophylaxis appeared to be comparable to patients with a CD4 count ≥200 cells/μL not given prophylaxis. Patients with relapsed VL are at higher risk for subsequent relapse and should be considered a priority for secondary prophylaxis, irrespective of their CD4 count.

Vulnerabilities to and the Socioeconomic and Psychosocial Impacts of the Leishmaniases: A Review

“…Malnutrition and HIV infection are the most significant comorbidities because they increase host susceptibility, are determinants for severity and clinical manifestations of the leishmaniases, and complicate accurate diagnosis and treatment. 25,85,[91][92][93] For instance, case-controlled research in Ethiopia has shown a three-fold increase in susceptibility to VL in malnourished individuals. 94,95 Additional research is needed to understand the impact of nutritional deficits on vector competence.…”

Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV

“…In Ethiopia, over 50% of VL/HIV co-infected patients will experience relapse of VL between 3 and 9 months post anti-leishmania treatment (12). The mechanisms accounting for the increased rate of VL relapse in VL/HIV co-infected patients are poorly characterised.…”

Diversity and within-host evolution of parasites from VL and VL/HIV patients in Northern Ethiopia

“…Little work has been done to investigate drug resistance markers in African visceral leishmaniasis, where drug resistance is not thought to be a significant clinical problem (Gidey et al 2019), and no genetic markers have -to our knowledge -been identified in the region. Identifying such resistance in recurrent VL/HIV would be complicated by the complex history of drug exposure for many of these patients, as clinicians frequently resort to second-line drugs or combinations in an attempt to improve treatment outcomes (Diro et al 2019;Monge-Maillo and López-Vélez 2016;Mohammed et al 2020).…”

“…In Ethiopia and elsewhere, HIV coinfection is known to increase the probability that L. donovani infections progress to symptomatic visceral leishmaniasis (Hurissa et al 2010;Albuquerque et al 2014). These co-infections are difficult to treat, with poor clinical outcomes for patients with very high mortality and high rates of relapse following treatment (Hurissa et al 2010;Diro et al 2019;Alemayehu, Wubshet, and Mesfin 2016;Diro et al 2014;Mohammed et al 2020). It is generally thought that cure of VL is not sterile, so that parasites continue to be present, but there is little direct evidence of this.…”