Predictors of Visceral Leishmaniasis Relapse in HIV-Infected Patients: A Systematic Review

Background and Objectives: Visceral leishmaniasis (VL) is a common complication in AIDS patients living in Leishmania-endemic areas. Although antiretroviral therapy has changed the clinical course of HIV infection and its associated illnesses, the prevention of VL relapses remains a challenge for the care of HIV and Leishmania co-infected patients. This work is a systematic review of previous studies that have described predictors of VL relapse in HIV-infected patients. Review Methods: We searched the electronic databases of MEDLINE, LILACS, and the Cochrane Central Register of Controlled Trials. Studies were selected if they included HIV-infected individuals with a VL diagnosis and patient follow-up after the leishmaniasis treatment with an analysis of the clearly defined outcome of prediction of relapse. Results: Eighteen out 178 studies satisfied the specified inclusion criteria. Most patients were males between 30 and 40 years of age, and HIV transmission was primarily via intravenous drug use. Previous VL episodes were identified as risk factors for relapse in 3 studies. Two studies found that baseline CD4+ T cell count above 100 cells/mL was associated with a decreased relapse rate. The observation of an increase in CD4+ T cells at patient follow-up was associated with protection from relapse in 5 of 7 studies. Meta-analysis of all studies assessing secondary prophylaxis showed significant reduction of VL relapse rate following prophylaxis. None of the five observational studies evaluating the impact of highly active antiretroviral therapy use found a reduction in the risk of VL relapse upon patient follow-up. Conclusion: Some predictors of VL relapse could be identified: a) the absence of an increase in CD4+ cells at follow-up; b) lack of secondary prophylaxis; and c) previous history of VL relapse. CD4+ counts below 100 cells/mL at the time of primary VL diagnosis may also be a predictive factor for VL relapse. Author Summary: Visceral leishmaniasis (VL) is the most serious form of an insect-transmitted parasitic disease prevalent in 70 countries. The disease is caused by species of the L. donovani complex found in different geographical regions. These parasites have substantially different clinical, drug susceptibility and epidemiological characteristics. According to data from the World Health Organization, the areas where HIV-Leishmania co-infection is distributed are extensive. HIV infection increases the risk of developing VL, reduces the likelihood of a therapeutic response, and greatly increases the probability of relapse. A better understanding of the factors promoting relapses is essential; therefore we performed a systematic review of articles involving all articles assessing the predictors of VL relapse in HIV-infected individuals older than 14 years of age. Out of 178 relevant articles, 18 met the inclusion criteria and in total, data from 1017 patients were analyzed. We identified previous episodes of VL relapse, CD4+ lymphocyte count fewer than 100 cells/mL at VL diagnosis, and the absence of an increase in CD4+ counts at follow-up as major factors associated with VL relapse. Knowledge of relapse predictors can help to identify patients with different degrees of risk, facilitate and direct prophylaxis choices, and aid in patient counseling.