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. 2021 Jul 28;8(10):ofab397.
doi: 10.1093/ofid/ofab397. eCollection 2021 Oct.

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

Newton Kalata  1 , Jayne Ellis  2 , Cecilia Kanyama  3 , Charles Kuoanfank  4 , Elvis Temfack  5 , Sayoki Mfinanga  6 , Sokoine Lesikari  6 , Duncan Chanda  7 , Shabir Lakhi  7 , Tinashe Nyazika  1 , Adrienne K Chan  8   9 , Joep J van Oosterhout  8 , Tao Chen  10 , Mina C Hosseinipour  3 , Olivier Lortholary  11 , Duolao Wang  10 , Shabbar Jaffar  10 , Angela Loyse  12 , Robert S Heyderman  2 , Thomas S Harrison  12   13 , Síle F Molloy  12
Affiliations

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

Newton Kalata et al. Open Forum Infect Dis. .

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.

Keywords: Antiretroviral therapy; Cryptococcal meningitis; HIV; Short-term mortality; Sub-Saharan Africa.

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Figures

Figure 1.
Figure 1.
Study cohort. Abbreviations: ACTA, Advancing Cryptococcal Meningitis Treatment for Africa; ART, antiretroviral therapy; CM, cryptococcal meningitis.
Figure 2.
Figure 2.
Kaplan-Meier survival plot by ART status. Abbreviation: ART, antiretroviral therapy.
See this image and copyright information in PMC

References

    1. Tenforde MW, Mokomane M, Leeme T, et al. . Advanced human immunodeficiency virus disease in botswana following successful antiretroviral therapy rollout: incidence of and temporal trends in cryptococcal meningitis. Clin Infect Dis 2017; 65:779–86. - PMC - PubMed
    1. Ellis J, Bangdiwala AS, Cresswell FV, et al. . The changing epidemiology of HIV-associated adult meningitis, Uganda 2015–2017. Open Forum Infect Dis 2019; 6:ofz419. - PMC - PubMed
    1. Boulware DR, Meya DB, Muzoora C, et al. ; COAT Trial Team. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med 2014; 370:2487–98. - PMC - PubMed
    1. Eshun-Wilson I, Okwen MP, Richardson M, Bicanic T. Early versus delayed antiretroviral treatment in HIV-positive people with cryptococcal meningitis. Cochrane Database Syst Rev 2018; 7:CD009012. - PMC - PubMed
    1. Alufandika M, Lawrence DS, Boyer-Chammard T, et al. ; the AMBITION-cm Study Group. A pragmatic approach to managing antiretroviral therapy-experienced patients diagnosed with HIV-associated cryptococcal meningitis: impact of antiretroviral therapy adherence and duration. AIDS 2020; 34:1425–8. - PMC - PubMed