Mortality in first-episode HIV-associated cryptococcal meningitis in Peru

Abstract
Cryptococcal meningitis (CM) remains one of the leading causes of morbidity and mortality among people living with HIV, particularly in low and middle-income countries where access to standard antifungal therapy is limited. Despite global advances in HIV care, early diagnosis and effective treatment of cryptococcal disease continue to represent major challenges in resource-limited settings. We conducted a retrospective registry-based cohort study of HIV patients and a first episode of CM admitted to a Peruvian national referral hospital between 2005 and 2015. Cox proportional hazards models were used to identify independent variables related to 30- and 90-day mortality. A total of 83 patients were included, 87% were males with a median age (interquartile range) of 33.8 (28.7–45.1) years. At baseline, 27.7% of patients had received antiretroviral therapy. Mortality at 30 and 90 days was 26.5% and 31.3%, respectively. In multivariable Cox models, the limited sample availability (59 for baseline and 83 for treatment analyses), constrained the precision estimates; nevertheless, altered consciousness, hyponatremia, and headache as independent predictors of mortality [30-day Hazard Ratios (HR): 7.6 (2.2–26.0); 5.4 (1.6–18.2); 0.1 (0.02–0.4); and 90-day HR: 7.1 (2.0–26.0); 10.9 (2.8–41.8); 0.1 (0.02–0.4), respectively]. In treatment analyses, fluconazole monotherapy or the absence of antifungals were significantly associated with higher mortality [30-day HR: 2.7 (1.1–6.8); 21.1 (7.8–57.5) and 90-day HR: HR: 2.8 (1.1–7.3); 20.1 (7.4–54.5), respectively]. In resource-limited settings, mortality from HIV-associated CM remains unacceptably high. These findings underscore the urgent need to enhance early diagnostic strategies and ensure access to optimal antifungal therapy to improve survival outcomes.

Lay Summary
The study found high mortality among patients with first-episode HIV-associated cryptococcal meningitis in a middle-income setting lacking standard therapy. Fluconazole monotherapy increased deaths, while altered consciousness predicted poor outcomes; low serum sodium may also indicate death risk.