Should cryptococcal antigen screening be considered as a routine procedure in antiretroviral therapy naïve severely immunocompromised HIV-seropositives – a prevalence study from Eastern India to support recent 2018 WHO guidelines

Abstract

Introduction: Cryptococcal meningitis, a leading opportunistic infection, causes significant morbidity and mortality in people with advanced human immunodeficiency virus (HIV). It accounts for an estimated 15% of acquired immune deficiency syndrome-related deaths globally. As recommended by the World Health Organization (WHO) 2018 guidelines, this invasive disease is preventable by routine cryptococcal antigen (CrAg) screening of all advanced HIV patients followed by pre-emptive antifungal therapy. An estimate of disease prevalence in antiretroviral treatment (ART)-naïve HIV-positive adult Indian population is essential to include this in routine screening strategy. We estimated CrAg prevalence as a guiding resource in a public health approach. Material and methods: The study design was longitudinal. ART naïve HIV-seropositive patients with CD4 count ≤ 100 cells/μl, attending ART center at the School of Tropical Medicine, Kolkata, India were screened for CrAg using both latex agglutination and lateral flow assay kits. A total of 390 subjects were enrolled into the study, and evaluated for association of CrAg with age, sex, CD4, presence of opportunistic infections, WHO HIV staging, and clinical symptoms. Results: Of 390 subjects tested, the median CD4 count was 42 cells/μl in CrAg-positive and 46 in CrAg-negative patients. Median (IQR) age of all participants was 40 (range, 34-46) years. CrAg positivity was 12.56%, comparatively higher in those with CD4 ≤ 50 cells/μl. Asymptomatic patients had CrAg positivity of 4.6%. Statistically significant association was noted with male sex ( p = 0.03), triad symptoms of fever, headache, vomiting ( p = 0.013), and altered mental status ( p = 0.033). Conclusions: This study aims to estimate CrAg prevalence in India to justify the need for routine screening and pre-emptive treatment in advanced HIV infection. Incorporating this screening would definitely reduce the risk of cryptococcus meningitis-induced mortality and morbidity, as recommended by the WHO guidelines.