TY - JOUR
T1 - Detrimental outcomes of unmasking cryptococcal meningitis with recent ARt initiation
AU - ASTRO-CM Study Team
AU - Rhein, Joshua
AU - Hullsiek, Kathy H.
AU - Evans, Emily E.
AU - Tugume, Lillian
AU - Nuwagira, Edwin
AU - Ssebambulidde, Kenneth
AU - Kiggundu, Reuben
AU - Mpoza, Edward
AU - Musubire, Abdu K.
AU - Bangdiwala, Ananta S.
AU - Bahr, Nathan C.
AU - Williams, Darlisha A.
AU - Abassi, Mahsa
AU - Muzoora, Conrad
AU - Meya, David B.
AU - Boulware, David R.
AU - Nabeta, Henry W.
AU - Ndyetukira, Jane Francis
AU - Ahimbisibwe, Cynthia
AU - Kugonza, Florence
AU - Namuju, Carolyne
AU - Sadiq, Alisat
AU - Namudde, Alice
AU - Mwesigye, James
AU - Kandole, Tadeo Kiiza
AU - Kirumira, Paul
AU - Okirwoth, Michael
AU - Akampurira, Andrew
AU - Luggya, Tony
AU - Kaboggoza, Julian
AU - Laker, Eva
AU - Atwine, Leo
AU - Muganzi, Davis
AU - Velamakanni, Sruti S.
AU - Jawed, Bilal
AU - Pastick, Katelyn
AU - Merry, Matthew
AU - Stadelman, Anna
AU - Flynn, Andrew
AU - Wendy Fujita, A.
AU - Mukaremera, Liliane
AU - Lofgren, Sarah M.
AU - Morawski, Bozena M.
AU - Taseera, Kabanda
AU - Nielsen, Kirsten
AU - Bohjanen, Paul R.
AU - Kambugu, Andrew
N1 - Funding Information:
Financial support. This work was supported by the United States Fogarty International Center (K01TW010268, R25TW009345), National Institute of Neurologic Diseases and Stroke (R01NS086312), National Institute of Allergy and Infectious Diseases (T32AI055433), United Kingdom Medical Research Council/Wellcome Trust/Department for International Development (MRC MR/M007413/1), and Grand Challenges Canada (S4-0296-01). This work was also supported in part by the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at the University of Minnesota. Andrew Flynn and A. Wendy Fujita are Doris Duke International Clinical Research Fellows. David Meya was supported in part by a DELTAS Africa Initiative grant (DEL-15-011) to THRiVE-2.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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.
KW - Antiretroviral therapy
KW - Cryptococcal meningitis
KW - Cryptococcus
KW - HIV
KW - Immune reconstitution inflammatory syndrome
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U2 - 10.1093/ofid/ofy122
DO - 10.1093/ofid/ofy122
M3 - Article
C2 - 30094292
AN - SCOPUS:85062813939
SN - 2328-8957
VL - 5
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 8
ER -
