CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Conclusion: Late presentation for HIV care was common, highlighting gaps in identifying people early and connecting them to effective treatment for optimal outcomes. CrAg prevalence was relatively low (2.9%) but other opportunistic infections such as tuberculosis, oral candidiasis and pneumocystis pneumonia were common. Longitudinal follow-up will help to evaluate the feasibility and cost of implementing CrAg screening and to assess survival among patients with advanced HIV infection in Vietnam. 742 CHANGES IN CRAG TITERS AMONG ASYMPTOMATIC HIV-POSITIVE PATIENTS Agnes Kiragga 1 , Francis Kakooza 1 , Bozena M. Morawski 2 , Elizabeth Nalintya 1 , Radha Rajasingham 2 , David Boulware 2 , David Meya 3 , Yukari C. Manabe 4 1 Infectious Diseases Inst, Kampala, Uganda, 2 Univ of Minnesota, Minneapolis, MN, USA, 3 Makerere Univ, Kampala, Uganda, 4 The Johns Hopkins Univ, Baltimore, MD, USA Background: In resource-limited settings, 5-9% of HIV-infected persons with <100 CD4 cells/µL have asymptomatic cryptococcal antigenemia. Cryptococcal antigen (CrAg) titers >=1:160 are associated with poor outcomes despite high-dose fluconazole. Delays while patients are waiting for CrAg results may impact CrAg titers and patient outcomes. We sought to understand the rate of change in titers and correlate these with patient outcomes. Methods: Asymptomatic, ART-naïve, HIV+ patients, >14 years, with CD4<100 cells/ µL received a lab-based reflexive plasma CrAg test with titers as part of an operational implementation study. Serum CrAg titers were repeated when positive participants returned for enrolment, receipt of fluconazole and ART initiation. We analyzed rate of change in log2 titers per day, and the correlation between CrAg titer change and outcomes. Results: Out of 152 CrAg positive patients, 120 with titers at screening and fluconazole initiation visits were included: 53(44.2%) men, median age 32(Interquartile range (IQR):27,40) years, median CD4 count 26 cells/uL (IQR: 9,56). Median time between screening and fluconazole initiation visits was 5 days (IQR: 2,8). At screening 59(49%) had a titer <1:160, of which 11(19%) experienced an increase to >=1:160 at enrolment. Similarly, 61(51%) had titer >=1:160 at screening, and of these 41 (64%) had titers remain >1:160. Among patients with screening titers <1:160, the mean (SD) rate of change in (log2) CrAg titers/day was 0.11(±0.54). Log2 titers performed at fluconazole initiation were more predictive and associated with higher risk of death than titers performed at fluconazole initiation adjusted Hazard Ratio (aHR) (1.36 (95% CI: 1.15,1.60) compared to screening titers aHR 0.94(95% CI: 0.83, 1.06), with adjusting for baseline CD4 counts. Compared to participants with titers persistently <1:160, higher risk of death occurred in those with screening titers <1:160 which increased to >=1:160 at fluconazole initiation (aHR 9.58 (95%CI 2.69, 34.14) or persistently high titers >=1:160 at both time points (aHR 3.55 (95%CI 1.13,11.15)) (Figure 1). Conclusion: Asymptomatic cryptococcal antigenemia with baseline titer >=1:160 or titers rising about that threshold is associated with increased risk of death at 6 months despite high dose fluconazole treatment and suggests that CrAg titers when starting preemptive antifungal therapy may guide the need for enhanced preemptive treatment.

Poster and Themed Discussion Abstracts

743 HIGH PREVALENCE OF CNS DISSEMINATION WITH ASYMPTOMATIC CRYPTOCOCCAL ANTIGENEMIA Azure T. Makadzange 1 , Admire Hlupeni 2 , Kathryn F. Boyd 3 , Takudzwa Chagumaira 2 , Christine Ross 4 , Snigdha Vallabhaneni 4 , Shirish Balachandra 4 , Moses Bateganya 4 , Chiratidzo E. Ndhlovu 2 1 Massachusetts General Hosp, Cambridge, MA, USA, 2 Univ of Zimbabwe, Harare, Zimbabwe, 3 Infectious Disease Rsr Lab, Harare, Zimbabwe, 5 CDC, Atlanta, GA, USA Background: Screening for serum cryptococcal antigenemia (sCrAg) in advanced HIV is WHO recommended but with limited evidence to guide management of asymptomatic sCrAg+ individuals. We implemented a sCrAg screening program and estimated the prevalence of sCrAg antigenemia, central nervous system (CNS) dissemination, and mortality. Methods: HIV-infected individuals with CD4 counts ≤100cells/μl were enrolled at 20 outpatient clinics in Harare from April 2015–June 2016 and screened for sCrAg using a lateral flow assay. Participants were excluded for symptoms of meningitis or recent diagnosis of cryptococcal meningitis (CM). Lumbar puncture (LP) was offered to sCrAg+ participants; those with CNS disease were hospitalized and received Amphotericin B with high dose fluconazole; sCrAg+ participants who declined LP and CSF CrAg- participants received high dose fluconazole. All sCrAg- and sCrAg+ participants were initiated on ART or switched from a failing regimen within a week or 4-weeks of enrollment respectively. Crude mortality rates were determined, cause of death was ascertained by review of medical records and/or family report. Hospitalization costs were obtained. All participants have completed 10-weeks of follow-up, follow-up to 12-months is ongoing. Results: We screened 1598 and enrolled 1334 asymptomatic participants; 132 were sCrAg+ (9.9%), 67 sCrAg+ (50.8%) participants agreed to an LP and CNS disease was confirmed in 13 (19.4%). All-cause mortality to date was 8.9% (n=119) and mortality among the sCrAg+ and sCrAg- groups was 17.4% and 8.0%, respectively (p=0.0003). Among those with LP, mortality in the CSF CrAg+ and CSF CrAg- was 30.8% and 13% respectively (p=0.12). Mortality was similar in those who accepted (16.4%) and those who declined LP (18.1%, p=0.79). Hospitalization costs for CSF CrAg+ participants ranged from US$650–950. Death occurred in a health care setting in 88 (74%) participants, cause of death was unknown in 53 (44.5%). A documented diagnosis or clinical suspicion of TB infection was present in 44 (35.3%) and CM in 9 (7.6%) participants who died. Conclusion: A positive sCrAg is associated with increased mortality. The prevalence of CNS dissemination among asymptomatic sCrAg+ individuals is high. However, due to the suggested comparable mortality and high management costs, the impact of LP in resource limited settings needs further study with risk stratification to determine patients most likely to benefit from evaluation for CNS disease and hospital-based management. 744 SERTRALINE AND HIGH-DOSE FLUCONAZOLE TREATMENT OF CRYPTOCOCCAL MENINGITIS IN TANZANIA Katende Andrew 1 , Gladys Mbwanji 1 , Diana Faini 1 , Aneth Kalinjuma 1 , Katherine Hullsiek 2 , Josh Rhein 2 , Maja Weisser 1 , David Meya 3 , David Boulware 2 , Emilio Letang 1

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