Short-term Mortality Outcomes of HIV-Associated Cryptococcal Meningitis in Antiretroviral Therapy-Naïve and -Experienced Patients in Sub-Saharan Africa.

Newton Kalata,Shabir Lakhi,Cecilia Kanyama,Charles Kuoanfank,Olivier Lortholary,Sayoki Mfinanga,Tao Chen,Duncan Chanda,Shabbar Jaffar,Sokoine Lesikari,Elvis Temfack,Duolao Wang,Jayne Ellis,Angela Loyse,Thomas S Harrison ,Robert S Heyderman ,Adrienne K Chan ,Joep J Van Oosterhout ,Mina C Hosseinipour ,Tinashe K Nyazika ,Síle F Molloy

doi:10.1093/ofid/ofab397

Abstract

BackgroundAn increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) before presentation. There is some evidence suggesting an increased 2-week mortality in those receiving ART for <14 days compared with those on ART for >14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or nonadherence, are not well described.MethodsSix hundred seventy-eight adults with a first episode of cryptococcal meningitis recruited into a randomized, noninferiority, multicenter phase 3 trial in 4 Sub-Saharan countries were analyzed to compare clinical presentation and 2- and 10-week mortality outcomes between ART-naïve and -experienced patients and between patients receiving ART for varying durations before presentation.ResultsOver half (56%; 381/678) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2 weeks (17% vs 20%; hazard ratio [HR], 0.85; 95% CI, 0.6–1.2; P = .35) and 10 weeks (38% vs 36%; HR, 1.03; 95% CI, 0.8–1.32; P = .82) for ART-experienced and ART-naïve patients. Among ART-experienced patients, using different cutoff points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART.ConclusionsIn this study, there were no significant differences in mortality at 2 and 10 weeks between ART-naïve and -experienced patients and between ART-experienced patients according to duration on ART.

Highlights

An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) prior to presentation
Cryptococcal meningitis (CM) continues to cause significant morbidity and mortality in people living with HIV (PLHIV) despite the scale-up of antiretroviral therapy (ART) in sub-Saharan Africa (SSA) and an increasing proportion of patients with HIV-associated cryptococcal meningitis are presenting on ART [1]
It is well recognised that early initiation of ART during induction treatment of CM results in t higher mortality [3, 4], data on outcomes for CM patients recently started on ART prior to ip presentation are few, and guidance on ART management r in this group is based largely on expert opinion [5]

Summary

Background

An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) prior to presentation. There is some evidence suggesting an increased two-week mortality in those receiving ART for less than 14 days compared with those on ART for more than 14 days. Presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or nonadherence are not well described. T Methods ip 678 adults with first episode of cryptococcal meningitis recruited into a randomized, nonr inferiority, multicentre phase 3 trial in 4 sub-Saharan countries were analysed to compare c clinical presentation and 2-and 10-week mortality outcomes between ART-naive and s experienced patients, and between patients receiving ART for varying durations prior to u presentation. P Conclusion ce In this study, there were no significant differences in mortality at 2-and 10-weeks between ART-.

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