Risk factors for cryptococcal infection among people with HIV receiving care at a referral hospital in Uganda: a nested case–control study

Cryptococcal infection is a major cause of morbidity and mortality among people with HIV (PWH), particularly those with advanced immunosuppression. Cryptococcal infection, detected by a laboratory-confirmed positive serum cryptococcal antigen (CrAg) test (cryptococcal antigenemia), typically precedes cryptococcal meningitis and provides a critical window for prevention. However, recent data on its risk factors in Uganda are limited. We assessed the risk factors for cryptococcal infection among PWH with non-suppressed viral load and severe immunosuppression receiving care at a referral hospital in midwestern Uganda. We conducted a facility-based nested case-control study among PWH with non-suppressed viral load (viral load ≥ 1,000 copies/mL) and severe immunosuppression (CD4 < 200 cells/µL) at the Fort Portal Regional Referral Hospital in midwestern Uganda. Cases were PWH with a positive serum CrAg test, and controls were those with a negative serum CrAg test in a 1:2 case-to-control ratio, respectively. Socio-demographic and clinical data were retrospectively extracted from routine records. Multivariable binary logistic regression analysis was used to identify factors independently associated with cryptococcal infection. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were reported. We included 89 cases and 178 controls, with comparable mean age between the groups: 40.3 ± 12.4 years vs. 40.4 ± 11.7 years, respectively; p = 0.952. In the multivariable analysis, PWH with advanced World Health Organization (WHO) clinical stages III/IV compared to WHO clinical stages I/II (aOR 3.45, 95% CI 1.28–9.97), and those with missed clinic visits within three months before the serum CrAg testing compared to those without any missed clinic visits (aOR 2.39, 95% CI 1.14–5.02) had higher odds of cryptococcal infection. This study showed that among PWH with non-suppressed viral load and severe immunosuppression, cryptococcal infection is strongly associated with markers of advanced HIV disease and gaps in care engagement. Strengthening retention in care, improving clinic appointment tracking, and ensuring timely serum CrAg screening among PWH with non-suppressed viral load may reduce cryptococcal disease burden through early diagnosis and treatment. Not applicable.