Abstract
BackgroundHIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative. This study examined neurocognitive function among persons with asymptomatic cryptococcal antigenemia.MethodsParticipants from three prospective HIV cohorts underwent neurocognitive testing at the time of antiretroviral therapy (ART) initiation. Cohorts included persons with cryptococcal meningitis (N = 90), asymptomatic CrAg + (N = 87), and HIV-infected persons without central nervous system infection (N = 125). Z-scores for each neurocognitive test were calculated relative to an HIV-negative Ugandan population with a composite quantitative neurocognitive performance Z-score (QNPZ-8) created from eight tested domains. Neurocognitive function was measured pre-ART for all three cohorts and additionally after 4 weeks of ART (and 6 weeks of pre-emptive fluconazole) treatment among asymptomatic CrAg + participants.ResultsCryptococcal meningitis and asymptomatic CrAg + participants had lower median CD4 counts (17 and 26 cells/μL, respectively) than the HIV-infected control cohort (233 cells/μL) as well as lower Karnofsky performance status (60 and 70 vs. 90, respectively). The composite QNPZ-8 for asymptomatic CrAg + (−1.80 Z-score) fell between the cryptococcal meningitis cohort (−2.22 Z-score, P = 0.02) and HIV-infected controls (−1.36, P = 0.003). After four weeks of ART and six weeks of fluconazole, the asymptomatic CrAg + cohort neurocognitive performance improved (−1.0 Z-score, P < 0.001).ConclusionSignificant deficits in neurocognitive function were identified in asymptomatic CrAg + persons with advanced HIV/AIDS even without signs or sequelae of meningitis. Neurocognitive function in this group improves over time after initiation of pre-emptive fluconazole treatment and ART, but short term adherence support may be necessary.
Highlights
HIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative
Participants with asymptomatic cryptococcemia were slightly younger in age (median 31 years, interquartile range (IQR): 27–39 years) compared with participants with cryptococcal meningitis (36 years, Interquartile range (IQR): 30–40) and HIVinfected controls (37, IQR: 32–41) (Table 1)
At the other end of the spectrum, the HIV-infected controls had the lowest proportion with International HIV Dementia Scale (IHDS) < =10 (66%), the lowest depression scale scores (CES-D: 9, IQR: 5–17), highest Karnofsky performance score (90, IQR: 90–90), and significantly higher median CD4 counts (233 cells/μL, IQR: 183– 297) compared with the other two study populations
Summary
HIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative. Cryptococcal disease is potentially preventable as cryptococcal antigen (CrAg) is detectable in the peripheral blood weeks to months prior to the onset of symptomatic meningitis Many of these CrAg + persons exhibit no clinical signs or symptoms despite the presence of early disseminated infection, CrAg + persons have increased risk of developing meningitis or death compared to HIVinfected persons without cryptococcal antigenemia [6,7,8,9]. The World Health Organization (WHO) and U.S HIV guidelines recommend routine CrAg screening for HIVinfected persons with
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