Long-term clinical outcomes in visceral leishmaniasis/human immunodeficiency virus-co-infected patients during and after pentamidine secondary prophylaxis in Ethiopia: a single-arm clinical trial

Background: We have conducted a single-arm trial evaluating monthly pentamidine secondary prophylaxis (PSP) to prevent visceral leishmaniasis (VL) relapse in Ethiopian HIV-patients. Outcomes at 12 months of PSP have been previously reported, supporting PSP effectiveness and safety. However, remaining relapse-free after PSP discontinuation is vital. We now report outcomes and associated factors for a period of upto 2.5 years after initiating PSP, including one year follow-up after PSP discontinuation.

Methods: The trial had three phases: 1) 12 months (M12) of PSP; 2) a 6-months PSP-extension period if CD4 count ≤200cells/μl at M12; 3) 12-months follow-up after stopping PSP. The probability of relapse and risk factors were calculated using Kaplan-Meier methods and Cox regression.

Results: For the 74 patients included, final study outcomes were: 39 (53%) relapse-free, 20 (27%) relapse, five (7%) deaths, ten (14%) lost. The two-year risk of relapse was 36.9% (95% CI 23.4%-55.0%), highest for those with a history of VL relapse and low baseline CD4 counts. 45 patients were relapse-free and in follow-up at M12 of PSP. This included 28 patients with M12 CD4 counts >200cells/µl, remaining relapse-free after PSP discontinuation. Amongst the 17 with M12 CD4 counts <200 cells/µl, one relapsed and three were lost during the PSP-extension period. During one year post-PSP follow-up, two patients relapsed and one was lost. No PSP-related serious adverse events were reported during the PSP-extension/post-PSP follow-up period.

Conclusions: M12 CD4 counts >200 cells/µL seem safe to discontinue PSP. The management of those failing to reach this remains to be defined.