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.

Details

Title
Detrimental Outcomes of Unmasking Cryptococcal Meningitis With Recent ART Initiation
Author
Rhein, Joshua 1 ; Hullsiek, Kathy H 2 ; Evans, Emily E 3 ; Tugume, Lillian 4 ; Nuwagira, Edwin 3 ; Ssebambulidde, Kenneth 4 ; Kiggundu, Reuben 4 ; Mpoza, Edward 4 ; Musubire, Abdu K 4 ; Bangdiwala, Ananta S 2 ; Bahr, Nathan C 1 ; Williams, Darlisha A 1 ; Abassi, Mahsa 1 ; Muzoora, Conrad 3 ; Meya, David B 5 ; Boulware, David R 2 ; Nabeta, Henry W; Ndyetukira, Jane Francis; Ahimbisibwe, Cynthia; Kugonza, Florence; Namuju, Carolyne; Sadiq, Alisat; Namudde, Alice; Mwesigye, James; Kandole, Tadeo Kiiza; Kirumira, Paul; Okirwoth, Michael; Akampurira, Andrew; Luggya, Tony; Kaboggoza, Julian; Laker, Eva; Atwine, Leo; Davis Muganzi; Velamakanni, Sruti S; Jawed, Bilal; Pastick, Katelyn; Merry, Matthew; Stadelman, Anna; Flynn, Andrew; Fujita, A Wendy; Mukaremera, Liliane; Lofgren, Sarah M; Morawski, Bozena M; Kabanda Taseera; Nielsen, Kirsten; Bohjanen, Paul R; Kambugu, Andrew

1  University of Minnesota, Minneapolis, Minneapolis; Infectious Diseases Institute, Makerere University, Kampala, Uganda 
2  University of Minnesota, Minneapolis, Minneapolis 
3  Mbarara University of Science and Technology, Mbarara, Uganda 
4  Infectious Diseases Institute, Makerere University, Kampala, Uganda 
5  Infectious Diseases Institute, Makerere University, Kampala, Uganda; School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda 
Publication year
2018
Publication date
Aug 2018
Publisher
Oxford University Press
e-ISSN
23288957
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1093/ofid/ofy122
ProQuest document ID
3171060983
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.