Implementation of point-of-care testing and prevalence of cryptococcal antigenaemia among patients with advanced HIV disease in Mumbai, India

Abstract

Objectives: To describe the implementation of screening for cryptococcal antigenaemia by point-of-care (POC) serum cryptococcal antigen (CrAg) lateral flow assay, measure the prevalence and factors associated with serum cryptococcal antigenaemia in the routine programmatic setting.

Design: Cross-sectional study.

Setting: Seventeen publicly funded antiretroviral therapy (ART) centres in Mumbai, India.

Participants: Serum CrAg screening was offered to all adolescents (>10 years of age) and adults with advanced HIV disease (AHD) (CD4 <200 cells/mm³ or with WHO clinical stage III/IV) regardless of symptoms of cryptococcal meningitis.

Primary and secondary outcome measures: The primary outcome was to describe the implementation of serum CrAg screening and secondary outcome was to measure the prevalence of serum cryptococcal antigenaemia and its risk factors.

Results: A total of 2715 patients with AHD were tested for serum CrAg by POC assay. Of these, 25 (0.9%) had a CrAg positive result. Among CrAg-positive patients, only one had symptoms. Serum CrAg positivity was 3.6% (6/169) and 1.6% (6/520) among those presenting with CD4 <100 cells/mm³ in the treatment naïve and treatment experienced group, respectively. On multivariable analysis, CD4 count <100 cells/mm³ (OR: 2.3, 95% CI 1.01 to 5.3; p=0.05) and people living with HIV who were treatment naïve (OR: 2.5, 95% CI 1.04 to 6.0; p=0.04) were significantly associated with a positive serum CrAg result. Lumbar puncture was obtained in 20/25 patients within 4 days (range: 1-4 days) of positive serum CrAg result and one person was confirmed to have meningitis. All serum CrAg-positive patients who had a negative cerebrospinal fluid CrAg were offered pre-emptive therapy.

Conclusions: Implementation of a POC CrAg assay was possible with existing ART centre staff. Initiation of pre-emptive therapy and management of cryptococcal antigenaemia are operationally feasible at ART centres. The Indian National AIDS Control Programme may consider reflexive CrAg screening of all AHD patients with CD4 <100 cells/mm³.

Keywords: Epidemiology; HIV & AIDS; Public health.

Figure 1

Operational flow for screening and management of cryptococcal meningitis. AHD, advanced HIV disease; CrAg, cryptococcal antigen; CSF, cerebrospinal fluid; LP, lumbar puncture; PLHIV, people living with HIV; ADM, Advanced Disease Management.

Figure 2

Cascade of cryptococcal meningitis (CM) management and outcomes of patients screened positive for serum cryptococcal antigen. AHD, advanced HIV disease; CrAg, cryptococcal antigen; CSF, cerebrospinal fluid; LFU, lost to follow-up; LP, lumbar puncture.