Poor long-term outcomes despite improved hospital survival for patients with cryptococcal meningitis in rural, Northern Uganda.

BACKGROUND: Cryptococcal meningitis (CM) remains a major cause of death among people living with HIV in rural sub-Saharan Africa. We previously reported that a CM diagnosis and treatment program (CM-DTP) improved hospital survival for CM patients in rural, northern Uganda. This study aimed to evaluate the impact on long-term survival. METHODS: We conducted a retrospective study at Lira Regional Referral Hospital in Uganda evaluating long-term survival (≥1 year) of CM patients diagnosed after CM-DTP initiation (February 2017-September 2021). We compared with a baseline historical group of CM patients before CM-DTP implementation (January 2015-February 2017). Using Cox proportional hazards models, we assessed time-to-death in these groups, adjusting for confounders. RESULTS: We identified 318 CM patients, 105 in the Historical Group, and 213 in the CM-DTP Group. The Historical Group had a higher 30-day mortality of 78.5% compared to 42.2% in the CM-DTP Group. The overall survival rate for the CM-DTP group at three years was 25.6%. Attendance at follow-up visits (HR:0.13, 95% CI: [0.03-0.53], p <0.001), ART adherence (HR:0.27, 95% CI: [0.10-0.71], p = 0.008), and fluconazole adherence: (HR:0.03, 95% CI: [0.01-0.13], p <0.001), weight >50kg (HR:0.54, 95% CI: [0.35-0.84], p = 0.006), and performance of therapeutic lumbar punctures (HR:0.42, 95% CI: [0.24-0.71], p = 0.001), were associated with lower risk of death. Altered mentation was associated with increased death risk (HR: 1.63, 95% CI: 1.10-2.42, p = 0.016). CONCLUSION: Long-term survival of CM patients improved after the initiation of the CM-DTP. Despite this improved survival, long-term outcomes remained sub-optimal, suggesting that further work is needed to enhance long-term survival.

High Burden of Cryptococcal Meningitis Among Antiretroviral Therapy-Experienced Human Immunodeficiency Virus-Infected Patients in Northern Uganda in the Era of "Test and Treat": Implications for Cryptococcal Screening Programs.

BACKGROUND: The impact of the "test and treat" program for human immunodeficiency virus (HIV) treatment in rural areas of Uganda on cryptococcal antigen (CrAg) screening or cryptococcal meningitis (CM) is poorly understood. METHODS: We retrospectively evaluated clinical factors in 212 HIV-infected patients diagnosed with CM from February of 2017 to November of 2019 at Lira Regional Referral Hospital in northern Uganda. RESULTS: Among 212 patients diagnosed with CM, 58.5% were male. Median age was 35 years; CD4 count and HIV viral load (VL) were 86 cells/µL and 9463 copies/mL, respectively. Only 10% of patients had a previous history of CM. We found that 190 of 209 (90.9%) patients were ART experienced and 19 (9.1%) were ART naive. Overall, 90 of 212 (42.5%) patients died while hospitalized (median time to death, 14 days). Increased risk of death was associated with altered mental status (hazard ratio [HR], 6.6 [95% confidence interval {CI}, 2.411-18.219]; P ≤ .0001) and seizures (HR, 5.23 [95% CI, 1.245-21.991]; P = .024). CONCLUSIONS: Current guidelines recommend CrAg screening based on low CD4 counts for ART-naive patients and VL or clinical failure for ART-experienced patients. Using current guidelines for CrAg screening, some ART-experienced patients miss CrAg screening in resource-limited settings, when CD4 or VL tests are unavailable. We found that the majority of HIV-infected patients with CM were ART experienced (90.9%) at presentation. The high burden of CM in ART-experienced patients supports a need for improved CrAg screening of ART-exposed patients.