A Study of Clearance of Infection in HIV-Associated Cryptococcal Meningitis after Amphotericin-Based Induction and Fluconazole-Based Consolidation Therapy

Abstract

Introduction\u2003India has third largest human immunodeficiency virus (HIV) population in the world. Average HIV prevalence was 0.22% (range, 0.16–0.30%) in 2017, and Manipur is one of the five states with the highest prevalence of HIV. Cryptococcal meningitis being one of the acquired immunodeficiency syndrome (AIDS)-defining illnesses is the second most common cause of opportunistic neuro-infection and usually occurs in advanced HIV disease when the cluster of differentiation 4 glycoprotein (CD4+) count is usually less than 100 cells/µL. Treatment includes amphotericin-B induction therapy for 2 weeks followed by fluconazole consolidation therapy for 8 weeks as per National AIDS Control Organisation guidelines. There is not much data on how much infection is cleared off after induction and consolidation treatment. So, this study was conducted to know the clearance of Cryptococci in cerebrospinal fluid (CSF) after induction and consolidation treatment in people living with HIV (PLHIV)-associated cryptococcal meningitis. Objective\u2003This work aimed to study the persistence of cryptococcal meningitis after amphotericin-based 2 weeks of induction therapy and 8 weeks of consolidation therapy with fluconazole and to evaluate the association between CD4 count and clearance rate of cryptococcal infection. Materials and Methods\u2003The study was conducted in Department of Medicine, Regional Institute of Medical Sciences, Imphal, from 2016 to 2018. Fifty-one patients above 18 years of age diagnosed as cryptococcal meningitis with HIV were included and treated with amphotericin for 2 weeks and fluconazole for 10 weeks. CSF analysis was done at 2nd and 10th weeks to study the clearance of infection. Results\u2003At 2nd week of induction therapy, out of 51 patients, 28 (54.9%) got cleared of infection, 18 (35.3%) had persistent infection, and 5 (9.2%) patients had either died or discontinued treatment. At 10th week of consolidation therapy, 36 (70.5%) patients got cleared of cryptococcal infection, 2 (4%) patients were having persistent infection, and 5 (9.8%) patients died, while 8 (15.7%) patients were lost in follow-up. However, after excluding mortality and lost in follow-up cases, from analysis in final outcome, 94% (34 out of 36) patients showed response to this regimen. Conclusion\u2003The present study showed that cryptococcal meningitis in PLHIV responded to amphotericin-based induction therapy with 60% clearance of infection followed by fluconazole-based consolidation therapy with 94% of clearance of infection. However, there is still need for good antifungal regimen that could clear infection in induction phase with less side effects.