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. 2018 May 24;5(8):ofy122.
doi: 10.1093/ofid/ofy122. eCollection 2018 Aug.

Detrimental Outcomes of Unmasking Cryptococcal Meningitis With Recent ART Initiation

Joshua Rhein  1   2 , Kathy H Hullsiek  1 , Emily E Evans  3 , Lillian Tugume  2 , Edwin Nuwagira  3 , Kenneth Ssebambulidde  2 , Reuben Kiggundu  2 , Edward Mpoza  2 , Abdu K Musubire  2 , Ananta S Bangdiwala  1 , Nathan C Bahr  1   2 , Darlisha A Williams  1   2 , Mahsa Abassi  1   2 , Conrad Muzoora  3 , David B Meya  2   4 , David R Boulware  1 ; ASTRO-CM study team
Collaborators, Affiliations

Detrimental Outcomes of Unmasking Cryptococcal Meningitis With Recent ART Initiation

Joshua Rhein et al. Open Forum Infect Dis. .

Abstract

Background: Increased antiretroviral therapy (ART) availability has been associated with more patients developing cryptococcosis after ART initiation. Despite this changing epidemiology, data regarding cryptococcal meningitis in those already receiving ART are limited. We compared clinical presentations and outcomes among ART-naïve and ART-experienced Ugandans.

Methods: We prospectively enrolled 605 HIV-infected persons with first-episode cryptococcal meningitis from August 2013 to May 2017 who received amphotericin-based combination therapy. We classified participants by ART status and ART duration and compared groups for 2-week survival.

Results: Overall, 46% (281/605) of participants were receiving ART at presentation. Compared with those not receiving ART, those receiving ART had higher CD4 counts (P < .001) and lower cerebrospinal fluid fungal burdens (P < .001). Of those receiving ART, 56% (156/281) initiated ART within 6 months, and 18% (51/281) initiated ART within 14 days. Two-week mortality did not differ by ART status (27% in both ART-naïve and ART-experienced%; P > .99). However, 47% (24/51) of those receiving ART for ≤14 days died within 2 weeks, compared with 19% (20/105) of those receiving ART for 15-182 days and 26% (32/125) of those receiving ART for >6 months (P < .001). Among persons receiving ART for >6 months, 87% had HIV viral loads >1000 copies/mL.

Conclusions: Cryptococcosis after ART initiation is common in Africa. Patients initiating ART who unmask cryptococcal meningitis are at a high risk of death. Immune recovery in the setting of central nervous system infection is detrimental, and management of this population requires further study. Implementing pre-ART cryptococcal antigen screening is urgently needed to prevent cryptococcal meningitis after ART initiation.

Keywords: HIV; antiretroviral therapy; cryptococcal meningitis; cryptococcus; immune reconstitution inflammatory syndrome.

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Figures

Figure 1.
Figure 1.
Study cohort. The cohort included persons with first-episode cryptococcal meningitis, of whom 46% were receiving antiretroviral therapy (ART) at presentation. More than half of the patients receiving ART at cryptococcal meningitis diagnosis had initiated ART within 6 months of diagnosis, 18% of whom initiated ART within 14 days of cryptococcal meningitis diagnosis. Abbreviations: ART, antiretroviral therapy; CM, cryptococcal meningitis.
Figure 2.
Figure 2.
Kaplan-Meier survival plot by antiretroviral therapy (ART) status and timing. Mortality was highest among 51 participants receiving ART for ≤14 days, compared with those receiving ART for a more extended period (n = 230) or those who were ART naïve (n = 324). The differences in mortality occurred over the initial ~3 weeks. Abbreviation: ART, antiretroviral therapy.
Figure 3.
Figure 3.
Hazard ratio for mortality within 30 days by duration from antiretroviral therapy (ART) initiation to development of cryptococcal meningitis. Among participants receiving ART, individuals developing cryptococcal meningitis within 28 days of initiating ART had increased mortality. The figure plots the hazard ratio for mortality within 2 weeks as a function of ART duration from ART initiation to development of cryptococcal meningitis. Abbreviations: ART, antiretroviral therapy; CI, confidence interval.
See this image and copyright information in PMC

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