Author:
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Letang, Emilio; Muller, Matthias C.; Ntamatungiro, Alex J.; Kimera, Namvua; Faini, Diana; Furrer, Hansjakob; Battegay, Manuel; Tanner, Marcel; Hatz, Christoph; Boulware, David R.; Glass, Tracy R.
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Abstract:
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Background. Cryptococcal meningitis is a leading cause of death
in people living with human immunodeficiency virus
(HIV)/acquired immune deficiency syndrome. The World Health
Organizations recommends pre-antiretroviral treatment (ART)
cryptococcal antigen (CRAG) screening in persons with CD4 below
100 cells/microL. We assessed the prevalence and outcome of
cryptococcal antigenemia in rural southern Tanzania. Methods. We
conducted a retrospective study including all ART-naive adults
with CD4 <150 cells/microL prospectively enrolled in the
Kilombero and Ulanga Antiretroviral Cohort between 2008 and
2012. Cryptococcal antigen was assessed in cryopreserved pre-ART
plasma. Cox regression estimated the composite outcome of death
or loss to follow-up (LFU) by CRAG status and fluconazole use.
Results. Of 750 ART-naive adults, 28 (3.7%) were CRAG-positive,
corresponding to a prevalence of 4.4% (23 of 520) in CD4 <100
and 2.2% (5 of 230) in CD4 100-150 cells/microL. Within 1 year,
75% (21 of 28) of CRAG-positive and 42% (302 of 722) of
CRAG-negative patients were dead or LFU (P<.001), with no
differences across CD4 strata. Cryptococcal antigen positivity
was an independent predictor of death or LFU after adjusting for
relevant confounders (hazard ratio [HR], 2.50; 95% confidence
interval [CI], 1.29-4.83; P = .006). Cryptococcal meningitis
occurred in 39% (11 of 28) of CRAG-positive patients, with
similar retention-in-care regardless of meningitis diagnosis (P
= .8). Cryptococcal antigen titer >1:160 was associated with
meningitis development (odds ratio, 4.83; 95% CI, 1.24-8.41; P =
.008). Fluconazole receipt decreased death or LFU in
CRAG-positive patients (HR, 0.18; 95% CI, .04-.78; P = .022).
Conclusions. Cryptococcal antigenemia predicted mortality or LFU
among ART-naive HIV-infected persons with CD4 <150
cells/microL, and fluconazole increased survival or
retention-in-care, suggesting that targeted pre-ART CRAG
screening may decrease early mortality or LFU. A CRAG screening
threshold of CD4 <100 cells/microL missed 18% of
CRAG-positive patients, suggesting guidelines should consider a
higher threshold. |