Adjunctive Single-Dose Liposomal Amphotericin to Prevent Cryptococcal Meningitis in People With Human Immunodeficiency Virus (HIV)-Associated Cryptococcal Antigenemia and Low Plasma Cryptococcal Antigen (CrAg) Titers.

BACKGROUND: Cryptococcal meningitis is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) predicts the development of meningitis. Historically, despite standard- of-care fluconazole, 25%-30% of asymptomatic CrAg-positive persons develop breakthrough meningitis or death. We evaluated whether adding single high-dose liposomal amphotericin B to standard pre-emptive fluconazole therapy could improve meningitis-free survival. METHODS: Participants with human immunodeficiency virus (HIV) and asymptomatic cryptococcal antigenemia in Uganda were randomized to liposomal amphotericin B (10 mg/kg once) with fluconazole or fluconazole alone through 24 weeks. We compared 24-week, meningitis-free survival time between treatment groups. After the second interim review, the Data Safety and Monitoring Board recommended no further enrollment of participants with low plasma CrAg lateral flow assay titers (≤1:80) due to futility. Herein, we present the results of participants with low plasma CrAg titers. RESULTS: 168 participants enrolled into the ACACIA trial had low plasma CrAg titers (≤1:80). During 24 weeks of follow-up, meningitis or death occurred in 14.5% (12/83) of participants randomized to liposomal amphotericin B with fluconazole versus 10.6% (9/85) assigned to fluconazole alone (hazard ratio, 1.42; 95% CI, .60-3.36; P = .431). Adverse events were more frequent in participants assigned to the intervention versus standard-of-care (28% vs 12%; P = .011). CONCLUSIONS: Among CrAg-positive persons with low titers (≤1:80), the addition of single-dose liposomal amphotericin B to fluconazole as pre-emptive therapy provided no additional clinical benefit. This trial provides supportive evidence that, in asymptomatic populations with low plasma CrAg titers, lumbar punctures are likely unnecessary as administration of meningitis treatment did not improve outcomes. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov (NCT03945448).

Effect of Coronavirus Disease 2019 Lockdowns on Identification of Advanced Human Immunodeficiency Virus Disease in Outpatient Clinics in Uganda.

Using data from 67 Ugandan human immunodeficiency virus (HIV) clinics (July 2019-January 2022), we report a 40% (1005/1662) reduction in the number of people with HIV presenting to care after August 2021 compared to prepandemic levels, with a greater proportion presenting with advanced HIV disease (20% vs 16% in the pre-coronavirus disease 2019 period).

Hyponatremia as a Predictor of Cryptococcal Meningitis and Death Among Asymptomatic Persons With HIV and Cryptococcal Antigenemia.

Among persons with human immunodeficiency virus-associated cryptococcal meningitis serum hyponatremia is a risk factor for mortality; however, the role of hyponatremia in persons with asymptomatic cryptococcal antigenemia is unknown. We found that serum hyponatremia ≤130 mmol/L is an independent risk factor for progression to meningitis and death in asymptomatic persons with cryptococcal antigenemia.