Cryptococcal Antigen Screening Among Antiretroviral Therapy-Experienced People With HIV With Viral Load Nonsuppression in Rural Uganda

Background. The World Health Organization recommends screening for the cryptococcal antigen (CrAg), a predictor of cryptococcal meningitis, among antiretroviral therapy (ART)-naive people with HIV (PWH) with CD4 <100 cells/mm(3). CrAg positivity among ART-experienced PWH with viral load (VL) nonsuppression is not well established, yet high VLs are associated with cryptococcal meningitis independent of CD4 count. We compared the frequency and positivity yield of CrAg screening among ART-experienced PWH with VL nonsuppression and ART-naive PWH with CD4 <100 cells/mm(3) attending rural public health facilities in Uganda. Methods. We reviewed routinely generated programmatic reports on cryptococcal disease screening from 104 health facilities in 8 rural districts of Uganda from January 2018 to July 2019. A lateral flow assay (IMMY CrAg) was used to screen for cryptococcal disease. PWH were eligible for CrAg screening if they were ART-naive with CD4 <100 cell/mm(3) or ART-experienced with an HIV VL >1000 copies/mL after at least 6 months of ART. We used Pearson's chi-square test to compare the frequency and yield of CrAg screening. Results. Of 71860 ART-experienced PWH, 7210 (10.0%) were eligible for CrAg screening. Among 15417 ART-naive PWH, 5719 (37.1%) had a CD4 count measurement, of whom 937 (16.4%) were eligible for CrAg screening. The frequency of CrAg screening was 11.5% (830/7210) among eligible ART-experienced PWH compared with 95.1% (891/937) of eligible ART- naive PWH (P<.001). The CrAg positivity yield was 10.5% among eligible ART-experienced PWH compared with 13.8% among eligible ART-naive PWH (P=.035). Conclusions. The low frequency and high positivity yield of CrAg screening among ART-experienced PWH with VL nonsuppression suggest a need for VL- directed CrAg screening in this population. Studies are needed to evaluate the cost-effectiveness and impact of CrAg screening and fluconazole prophylaxis on the outcomes of ART-experienced PWH with VL nonsuppression.