Abstract
BACKGROUND: Cryptococcal meningitis (CM) remains a leading cause of mortality among people with advanced HIV disease (AHD) in sub-Saharan Africa. Current guidelines recommend induction therapy with amphotericin B and flucytosine, typically administered in an inpatient setting due to concerns over severe clinical presentation and drug-related toxicities. This requirement poses a significant burden on resource-limited health systems. We evaluated the real-world outcomes of a fully outpatient model for CM therapy in Maputo, Mozambique. METHODS: A longitudinal retrospective cohort study was conducted at the Centro de Referência de Alto-Maé (CRAM), a specialized AHD outpatient clinic. We included 83 PLWH with laboratory-confirmed CM treated between October 2020 and December 2024. The primary outcome was hospitalization-free survival (HFS) within the first 10 weeks of treatment. Secondary outcomes included the frequency and severity of adverse drug reactions (ADRs), analysed by tracking haemoglobin (Hgb), potassium (K+), and creatinine (Creat) levels on days 1, 3, and 7 of induction therapy, and retention in care (RIC) at 6, 12, and 24 months. Statistical analyses included Kaplan-Meier survival estimates and paired t-tests. RESULTS: The median age was 37 years (IQR: 27-42), 63.9% were male, and the median CD4 count was 62 cells/µL (IQR: 27-105). Most patients (95.2%) were symptomatic at presentation, and 56.6% had concurrent tuberculosis. For the 52 patients who completed the full induction protocol at CRAM, the HFS rate at 10 weeks was 84.6% (44/52), with an overall survival of 90.4% (47/52). ADR analysis (n = 52) showed a predictable pattern of mild, manageable toxicity: a significant decline in Hgb (11.2 ± 1.8 to 10.6 ± 2.0 g/dL, p < 0.001) and K+ (4.27 ± 0.66 to 3.86 ± 0.78 mmol/L, p = 0.008), and a transient increase in Creat (0.83 ± 0.42 to 1.13 ± 0.64 mg/dL, p = 0.001) from day 1 to day 3, with stabilization or a trend toward recovery by day 7. No significant differences in ADRs were found between single-dose (47%) and multiple-dose (53%) L-AmB regimens. RIC for the entire cohort (n = 83) was high at 81.9% at 6 months, declining to 74.0% at 12 months and 70.4% at 24 months. CONCLUSIONS: An ambulatory model for CM therapy is feasible and effective in a resource-limited setting, demonstrating high hospitalization-free survival, manageable and reversible adverse drug reactions, and excellent medium-term retention in care. These findings suggest potential benefits and provide support for re-evaluating the standard of inpatient care. They indicate that integrating outpatient CM management into advanced HIV disease (AHD) care packages could help alleviate health system burdens and may contribute to improved patient outcomes.