Asymptomatic Cryptococcal Antigenemia in People Living with HIV (PLHIV) with Severe Immunosuppression: Is Routine CrAg Screening Indicated in India?

Background: Cryptococcal meningitis (CM) is a common, life-threatening opportunistic infection (OI) among people living with HIV (PLHIV) in India. Serum Cryptococcal antigen (CrAg) positivity is predictive of future occurrence of CM and pre-emptive treatment reduces its mortality. Routine CrAg screening among PLHIV is not adopted by India's national programme. This study evaluated the prevalence of CrAg and assessed CrAg positivity in predicting all-cause mortality among PLHIV.
Methods: This prospective study was conducted in a tertiary care, public health facility in New Delhi, India. Prevalence of CrAg was assessed in 128 ART naive adult PLHIV with CD4 < 100 cells/mm3 using a latex agglutination test. Age, gender, weight, body mass index (BMI), CD4 count, haemoglobin, serum albumin, and presence of other OI were evaluated as determinants of CrAg positivity. Subjects were followed up for occurrence of CM and mortality (all-cause) at 12 weeks and 6 months.
Results: The mean age of the subjects was 36.2±9.48 years, 73.4% were men, 21.09% women and 5.46% were transgender. The mean BMI was 18.4±2.53 kg/m2 and 64% of subjects belonged to the lower socio-economic strata. Mean CD4 counts of the subjects was 54.9±26.58 cells/mm3 and 42.97% had CD4 < 50 cells/mm3. The prevalence of CrAg in the subjects was 3.125 % (4/128). None of the factors assessed showed statistically significant difference between the 2 groups, though CD4 count <50 cells/mm3, low serum albumin and presence of oral candidiasis had a stronger association with CrAg positivity. None of the subjects developed CM during follow up. At 12 weeks, 3/4 (75%) CrAg positive patients were alive compared to 118/124 (95.16%) of CrAg negative subjects. At 6 months, 50% (2/4) CrAg positive patients had died compared to 10.48% (13/124) CrAg negative (p<0.01).
Conclusions: Though CrAg prevalence in PLHIV with CD4<100 cells/mm3 is moderate, asymptomatic CrAg positivity among PLHIV with CD4 < 100cells/mm3 is significantly associated with higher all-cause mortality. CrAg testing is very cost effective and India's National AIDS Control Programme should seriously consider routine screening among the severely immunosuppressed PLHIV.