Laboratory-Reflex Cryptococcal Antigen Screening Is Associated With a Survival Benefit in Tanzania

Abstract

Background: Cryptococcal antigen (CrAg) screening in persons with advanced HIV/AIDS is recommended to prevent death. Implementing CrAg screening only in outpatients may underestimate the true CrAg prevalence and decrease its potential impact. Our previous 12-month survival/retention in CrAg-positive persons not treated with fluconazole was 0%.

Methods: HIV testing was offered to all antiretroviral therapy-naive outpatients and hospitalized patients in Ifakara, Tanzania, followed by laboratory-reflex CrAg screening for CD4 <150 cells/μL. CrAg-positive individuals were offered lumbar punctures, and antifungals were tailored to the presence/absence of meningitis. We assessed the impact on survival and retention-in-care using multivariate Cox-regression models.

Results: We screened 560 individuals for CrAg. The median CD4 count was 61 cells/μL (interquartile range 26-103). CrAg prevalence was 6.1% (34/560) among individuals with CD4 ≤150 and 7.5% among ≤100 cells/μL. CrAg prevalence was 2.3-fold higher among hospitalized participants than in outpatients (12% vs 5.3%, P = 0.02). We performed lumbar punctures in 94% (32/34), and 31% (10/34) had cryptococcal meningitis. Mortality did not differ significantly between treated CrAg-positive without meningitis and CrAg-negative individuals (7.3 vs 5.4 deaths per 100 person-years, respectively, P = 0.25). Independent predictors of 6-month death/lost to follow-up were low CD4, cryptococcal meningitis (adjusted hazard ratio 2.76, 95% confidence interval: 1.31 to 5.82), and no antiretroviral therapy initiation (adjusted hazard ratio 3.12, 95% confidence interval: 2.16 to 4.50).

Conclusions: Implementing laboratory-reflex CrAg screening among outpatients and hospitalized individuals resulted in a rapid detection of cryptococcosis and a survival benefit. These results provide a model of a feasible, effective, and scalable CrAg screening and treatment strategy integrated into routine care in sub-Saharan Africa.

Figure 1:. Study profile of Cohort

Figure 2.. Timing from HIV testing through ART initiation

Timing from HIV diagnosis to ART initiation. P-values compare the median time between CrAg positive and CrAg negative individuals. Overall, the median time from entry into HIV care to CD4 testing, CrAg testing, and referral for lumbar puncture was 1 day in total with prioritization of addressing advanced HIV disease.

Figure 3.. Kaplan-Meier survival estimates of Death/ Lost to Follow-up by CrAg Status

3a (Top left): Kaplan-Meier survival estimates of death or loss to follow-up among CrAg negative versus Non-meningeal CrAg positive individuals. 3b (Top right): Kaplan-Meier survival estimates of death or loss to follow-up among CrAg negative versus Cryptococcal meningitis individuals. 3c (Bottom left): Kaplan-Meier survival estimates of death or loss to follow-up by CrAg status.3d (Bottom right): Kaplan-Meier survival estimates of death or loss to follow-up among CrAg negative versus CrAg positive by ART status.