Long-term Clinical Outcomes in Visceral Leishmaniasis/Human Immunodeficiency Virus-Coinfected Patients During and After Pentamidine Secondary Prophylaxis in Ethiopia: A Single-Arm Clinical Trial

Clin Infect Dis. 2018 Jan 18;66(3):444-451. doi: 10.1093/cid/cix807.

Abstract

Background: We have conducted a single-arm trial evaluating monthly pentamidine secondary prophylaxis (PSP) to prevent visceral leishmaniasis (VL) relapse in Ethiopian human immunodeficiency virus-infected 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 up to 2.5 years after initiating PSP, including 1-year follow-up after PSP discontinuation.

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

Results: For the 74 patients included, final study outcomes were as follows: 39 (53%) relapse-free, 20 (27%) relapsed, 5 (7%) deaths, 10 (14%) lost to follow-up. The 2-year risk of relapse was 36.9% (95% confidence interval, 23.4%-55.0%) and was highest for those with a history of VL relapse and low baseline CD4 count. Forty-five patients were relapse-free and in follow-up at month 12 of PSP. This included 28 patients with month 12 CD4 counts >200 cells/µL, remaining relapse-free after PSP discontinuation. Among the 17 with month 12 CD4 count <200 cells/µL, 1 relapsed and 3 were lost during the PSP extension period. During 1-year post-PSP follow-up, 2 patients relapsed and 1 was lost to follow-up. No PSP-related serious adverse events were reported during the PSP-extension/post-PSP follow-up period.

Conclusions: It seems safe to discontinue PSP at month 12 CD4 counts of >200 cells/µL. The management of those failing to reach this level remains to be defined.

Clinical trials registration: NCT01360762.

Keywords: Ethiopia; HIV; pentamidine; secondary prophylaxis; visceral leishmaniasis.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiprotozoal Agents / therapeutic use*
  • Coinfection / drug therapy*
  • Coinfection / parasitology
  • Coinfection / virology
  • Ethiopia
  • Female
  • HIV Infections / complications*
  • HIV Infections / parasitology
  • Humans
  • Leishmaniasis, Visceral / drug therapy*
  • Leishmaniasis, Visceral / virology
  • Male
  • Pentamidine / therapeutic use*
  • Recurrence
  • Risk Factors
  • Secondary Prevention
  • Time Factors
  • Treatment Outcome

Substances

  • Antiprotozoal Agents
  • Pentamidine

Associated data

  • ClinicalTrials.gov/NCT01360762