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

Author:

Kalata Newton1,Ellis Jayne2ORCID,Kanyama Cecilia3ORCID,Kuoanfank Charles4,Temfack Elvis5ORCID,Mfinanga Sayoki6ORCID,Lesikari Sokoine6,Chanda Duncan7ORCID,Lakhi Shabir7ORCID,Nyazika Tinashe1ORCID,Chan Adrienne K89ORCID,van Oosterhout Joep J8ORCID,Chen Tao10,Hosseinipour Mina C3,Lortholary Olivier11ORCID,Wang Duolao10ORCID,Jaffar Shabbar10ORCID,Loyse Angela12ORCID,Heyderman Robert S2ORCID,Harrison Thomas S1213,Molloy Síle F12

Affiliation:

1. Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi

2. Division of Infection and Immunity, University College London, London, UK

3. University of North Carolina Project, Kamuzu Central Hospital, Lilongwe, Malawi

4. University of Dschang, Dschang, Cameroon

5. Douala General Hospital, Douala, Cameroon

6. Muhimbili Centre, National Institute for Medical Research, Dar Es Salaam, Tanzania

7. University Teaching Hospital, Lusaka, Zambia

8. Dignitas International, Zomba Central Hospital, Zomba, Malawi

9. Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada

10. Liverpool School of Tropical Medicine, Liverpool, UK

11. Necker Pasteur Center for Infectious Diseases and Tropical Medicine, IHU Imagine, Assistance Publique–Hôpitaux de Paris, Paris, France

12. Centre for Global Health, Institute of Infection and Immunity, St George University of London, London, UK

13. MRC Centre for Medical Mycology, University of Exeter, Exeter, UK

Abstract

Abstract Background An 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. Methods Six 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. Results Over 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. Conclusions In 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.

Funder

Medical Research Council, United Kingdom

French Agency for Research on AIDS and Viral Hepatitis

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Oncology

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