CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

760 Maximizing Detection and Improving Outcomes of Cryptococcosis in Rural Tanzania Diana Faini 1 ; AnethV. Kalinjuma 2 ; Julie Neborak 3 ; Alexa King 3 ; Dorcas Mnzava 2 ;Tracy Glass 4 ; Hansjakob Furrer 5 ; Christoph Hatz 4 ; David R. Boulware 3 ; Emilio Letang 4 1 Ifakara Hlth Inst, Dar es Salaam, Tanzania; 2 Ifakara Hlth Inst, Morogoro, Tanzania; 3 Univ of Minnesota, Minneapolis, MN, USA; 4 Swiss Trop Inst of PH, Basel, Switzerland; 5 Bern Univ Hosp and Univ of Bern, Bern, Switzerland Background: The WHO recommends pre-antiretroviral treatment (ART) CD4-targeted cryptococcal antigen (CRAG) screening in sub-Saharan Africa. Implementing this strategy only in outpatient settings may underestimate the true CRAG prevalence and decrease its impact. Methods: In October 2013, lab-reflex CRAG screening was implemented at the St. Francis Referral Hospital, Ifakara, Tanzania for all HIV+ hospitalized patients and outpatients with CD4 ≤150/μL. The impact on CRAG detection and outcome was assessed. Cox regression identified predictors of death/loss to follow-up (LFU) at 6 months. Results: Of 1976 persons registered from 10/2013 to 07/2015, 500 (25%) ART-naive had CD4 ≤150/μL and were CRAG screened, contributing 2965 persons-month follow-up. Median age was 39 years (IQR 33-46), median CD4 count was 58 cells/μL (IQR 23-100), and 12% (59/500) had tuberculosis. CRAG prevalence was 6.4% (32/500) and 7.7% (30/376) with CD4 counts ≤150 and ≤100 cells/μL respectively, 1.7-fold higher than the 2008-2012 outpatient prevalence in the same cohort (3.7%≤150cells/μL, p=0.021). Inpatients (n=82) had a CRAG prevalence of 12% vs. 5.3% in outpatients (p=0.02), and accounted for 31% of all CRAG+. Median time from HIV to CRAG testing was 1 day (IQR 0-6). A lumbar puncture was done on the same day of CRAG testing in 97% (31/32) CRAG+, and 39% (12/31) had cryptococcal meningitis (CM), 17% of whom (2/12) without neurologic symptoms. Fluconazole tailored for CM presence was started in 81% (26/32) of CRAG+ and ART in 72% CRAG+ (23/32) and 76% (382/500) overall. Known 6-month mortality for those recruited before 02/2015 (n=361) did not differ between CRAG-negative and CRAG+ without CM (9% vs.7%, p=0.9), yet was 86% (6/7) among CM patients (p<0.001). LFU was 31% (104/340), 29% (4/14), and 14% (1/7) respectively. Independent predictors of death/LFU at 6 months were CRAG+ (adjusted hazard ratio (aHR) 3.2, 95% CI 1.2-8.2), CM (aHR 5.5, 95% CI 1.7-18), no ART initiation (aHR 2.2, 95% CI 1.5-3.4), tuberculosis (aHR 1.8, 95% CI 1.03-3.2), and hemoglobin (aHR 1.2 per 1 g/dL decrease, 95% CI 1.1-1.3) (Fig.1). Conclusions: Implementation of lab-reflex CRAG screening resulted in an increased and rapid detection of CRAG and CM. Mortality was highest for CM patients but did not vary between CRAG+ without CM treated with pre-emptive fluconazole and CRAG-negative patients. These results support the urgent adoption of the WHO guidelines for CRAG screening in Africa and its implementation both in inpatient and outpatient settings.

761 Neurocognitive Function in HIV-Infected Persons With Cryptococcal Antigenemia Martha P. Montgomery 1 ; Noeline Nakasujja 2 ; Bozena M. Morawski 1 ; Radha Rajasingham 1 ; Elizabeth Nalintya 3 ; Renee Donahue Carlson 4 ; Jonathan E. Kaplan 5 ; Andrew Kambugu 3 ; David B. Meya 3 ; David R. Boulware 1 ; for the COAT and ORCASTrialTeams 1 Univ of Minnesota, Minneapolis, MN, USA; 2 Makerere Univ Coll of Hlth Scis, Kampala, Uganda; 3 Infectious Diseases Inst, Kampala, Uganda; 4 Emory Univ Sch of Med, Atlanta, GA, USA; 5 CDC, Atlanta, GA, USA Background: HIV-infected persons with detectable cryptococcal antigen (CRAG) in blood have increased mortality compared with HIV-infected persons who are CRAG-negative. This study examined neurocognitive function among persons with asymptomatic cryptococcal antigenemia. Methods: Participants from three prospective HIV cohorts underwent neurocognitive testing at 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(s) (n=125). Asymptomatic CRAG+ participants receiving preemptive fluconazole also had neurocognitive testing additionally performed 4 weeks after ART initiation. 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 4 weeks after ART initiation among asymptomatic CRAG+ participants. Results: Cryptococcal meningitis and asymptomatic CRAG+ participants had lower median CD4 counts (17 and 26 cells/mL, respectively) than the HIV-infected control cohort (233 cells/mL) 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). Overall neurocognitive function improved after four weeks of ART among the asymptomatic CRAG+ cohort (QNPZ-8 increased to -1.0, P<0.001) to be within one standard deviation of population norms and similar to other HIV-infected persons. Conclusions: Significant 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. 762 Immunologic Discrimination of Cryptococcal IRIS From Culture-Positive Relapse David R. Boulware 1 ; Joshua R. Rhein 1 ; Edward N. Janoff 2 ; Abdu Musubire 3 ; Andrew Kambugu 3 ; Paul Bohjanen 1 ; David B. Meya 3 ; for the COATTrialTeam 1 Univ of Minnesota, Minneapolis, MN, USA; 2 Univ of Colorado, Denver, CO, USA; 3 Infectious Diseases Inst, Kampala, Uganda Background: Immune Reconstitution Inflammatory Syndrome (IRIS) may complicate antiretroviral therapy (ART). Whereas ART promotes HIV viral suppression and CD4 + T cell increases on a population level, the utility of these measurements as objective diagnostic criteria for IRIS remains unclear for an individual. We determined whether CD4 and plasma HIV RNA measurements are diagnostically useful to help differentiate paradoxical IRIS from culture-positive relapse. Methods: In prospective cohorts with cryptococcal meningitis enrolled from 2006-2012, 70 HIV+ persons had 75 recurrent symptomatic meningitis episodes, due to paradoxical IRIS (n=62) or culture-positive relapse (n=13). IRIS was defined as per the INSHI consensus case definition, with CSF culture status being the primary determinant of the causative event. We compared CD4 count change, plasma HIV viral load change, and CSF cytokines (n=50) between IRIS vs relapse.

Poster Abstracts

317

CROI 2016