Highly active antiretroviral therapy (HAART) has reduced the incidence of VL/HIV dramatically. However, HAART only partially prevents relapses, with one-year relapse rates ranging from 30 to 60%. Consequently, secondary prophylaxis is recommended for patients with <200 CD4+ cells/μL. In clinical practice, characterizing cellular immune response could help estimate the risk of relapse in VL/HIV coinfected patients. In this study, the lymphoproliferative response after stimulation with soluble Leishmania antigen was assessed in 2022 and 2023 in three cases of VL/HIV coinfection with long-term follow-up (17, 8 and 19 years). PCR and rK-39 results for Leishmania, HIV viral load, CD4 cell count, proliferation index, IFN-γ, IL-2, IP-10, IL-10 and TNF-α were determined. Heterogeneous results were obtained, with only one patient having developed specific cellular immunity against Leishmania. No cases of relapse were observed. The heterogeneity of lymphoproliferative test results in the three cases described highlights the need to identify surrogate markers of cure to guide maintenance or withdrawal of prophylaxis.