CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Background: The disseminated talaromycosis (Tm) has emerged as a leading cause of opportunistic infections and mortality in patients with advanced HIV disease in Southeast Asia but remains largely neglected. Here, we presented the estimates of the global Tm burden and modeled Tm projection to inform treatment and prevention strategies. Methods: First, we conducted a systematic review of all laboratory-confirmed, non-duplicating Tm cases published in the English and Chinese literature from the first case in 1964 to December 2017. We characterized the Tm global epidemiology, mapped Tm distribution, and used Maxent modeling to investigate ecological and meterorolgical drivers of Tm incidence. Second, we used numbers of known and unknown AIDS and treatment failure and treatment default from UNAIDS and national estimates to estimate the number of people at risk for Tm, and we estimated the cumulative and annual Tm cases and mortality based on reported regional Tm prevalence. Third, we used Bayesian regression modeling to predict the Tm epidemic to 2025 based on regional HIV/AIDS projection. Results: 686 of 1086 screened studies were included after excluding duplicated reports. A total of 22, 537 Tm cases were reported in 33 countries to end of 2017. 89.9% of patients were infected with HIV; 74.4%were male; 0.5%were children; 99.7%were autochthonous cases from Asia. China (60.3%), Thailand (30.4%), and Vietnam (8.4%) were the highest burden countries. The AIDS incidence, distribution of the Rhizomys bamboo rat, precipitation of wettest month, mean temperature of warmest quarter, and mean temperature of driest quarter were independent predictors of Tm incidence. We estimated a mean Tm prevalence of 4.7% (95% CI 4.7–4.8) among individuals with AIDS in Southeast Asia, with a total of 181,900 (95% CI 107,900–251,600) accumulative Tm cases and 29,700 (95% CI: 16,600–45,700) Tm death globally. We estimated that 12,700 (95% CI: 7,900–14,400) Tm cases and 2,200 (95 CI: 1,200-2,800) Tm deaths occurred in 2015. Figure 1A showed the geographical distribution and travel routes of reported cases, and Figure 1B showed the Tm epidemic projection to 2025. Conclusion: Despite substantial progress in HIV field, Tm remains a major neglected cause of HIV-associated morbidity and mortality in Southeast Asia. Our study highlights the need for improved Tm surveillance, diagnosis and treatment, and the need to improve HIV testing and treatment in this region.

14-day mortality in either Q1 or Q4, but participants with Q1 (low) levels of cytokines involved in Th2 cell function IL-13 (p=0.004) and IL-33 (p=0.039) had increased risk of 14-day mortality. Conclusion: These findings demonstrate a crucial role for cytotoxic cell populations and naive T-cell stimulation in human cryptococcal outcomes. Further research efforts should include characterizing the role and activating stimuli of cytotoxic cells in the clearance of Cryptococcus as well as T-cell function in activation of the adaptive immune response in humans with cryptococcosis. 748 TUBERCULOSIS IN HIV-ASSOCIATED CRYPTOCOCCAL MENINGITIS AND ITS IMPACT ON MORTALITY Morris K. Rutakingirwa 1 , Fiona V. Cresswell 2 , Enock Kagimu 1 , Edwin Nuwagira 3 , Kenneth Ssebambulidde 1 , Lillian Tugume 1 , Edward Mpoza 1 , Joanna Dobbin 1 , Richard Kwizera 1 , Darlisha Williams 1 , Conrad Muzoora 3 , David B. Meya 1 , David R. Boulware 4 , Katherine Huppler Hullsiek 4 , Joshua Rhein 4 1 Infectious Disease Institute, Kampala, Uganda, 2 London School of Hygiene & Tropical Medicine, London, UK, 3 Mbarara University of Science and Technology, Mbarara, Uganda, 4 University of Minnesota, Minneapolis, MN, USA Background: Tuberculosis (TB) and cryptococcal meningitis are leading causes of morbidity and mortality in advanced HIV. Data on TB co-infection amongst people with cryptococcosis is scarce. We described the occurrence of TB in Ugandan adults with cryptococcal meningitis and determined the impact of co-infection on survival. Methods: We performed a retrospective analysis of patients diagnosed with cryptococcal meningitis during 2010-2017. Baseline TB status was classified as: 1) ‘prevalent TB’ if TB diagnosed >14 days prior to cryptococcal diagnosis, 2) ‘concurrent TB’ if diagnosed with TB +/-14 days from cryptococcal diagnosis, or 3) ‘No baseline TB’. Baseline demographics were compared. Among those with no baseline TB, ‘TB incident’ was defined as occurrence of TB >14 days after cryptococcal diagnosis. Time-updated proportional hazards regression models were used to assess TB diagnosis as a risk factor for death. Models were adjusted for age, antiretroviral therapy status, Glasgow Coma Scale <15, and initial CSF quantitative cryptococcal culture. Results: Of 870 with cryptococcosis, 50 (6%) had prevalent TB, 67 (8%) had concurrent TB, and 753 (86%) had no baseline TB. Baseline demographics were similar between groups with exception of weight, duration on ART and CSF opening pressure. The 18-week mortality was 50% in prevalent TB, 46% in concurrent TB, and 45% in the no TB group. Among 753 participants without baseline TB, 67 (9%) were diagnosed with incident TB, with a median time to TB incidence of 41 [IQR, 22-69] days. TB diagnosis was associated with an increased risk of death (Hazard Ratio (HR)=1.62; 95%CI, 1.23, 2.14; p<0.01), which increased in models adjusted for age, ART use, GCS < 15 and CSF quantitative culture (HR=1.75; 95%CI, 1.33, 2.32; p<0.001) (table). Conclusion: Nearly a quarter of adults with cryptococcosis received treatment for TB, giving rise to potential drug-drug interactions and overlapping toxicities. There is an increased risk of death in patients who begin TB treatment after cryptococcal diagnosis. Further studies are needed to better characterize the increased risk of mortality with Cryptococcus and TB co-infection, and to determine the benefit of systematic TB screening in patients with cryptococcal meningitis.

Poster Abstracts

750 SUPERIOR ACCURACY OF THE Mp1p ANTIGEN ASSAY OVER CULTURES IN DIAGNOSING TALAROMYCOSIS Ly T. Vo 1 , Thu T. Nguyen 2 , Thanh T. Nguyen 3 , Nguyen Le Nhu Tung 4 , Jasper F. Chan 5 , Patrick C. Woo 5 , Chau V. Nguyen 4 , Nga N. Cao 1 , Kwok-Yung Yuen 5 , Thuy Le 2 1 University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam, 2 Duke University School of Medicine, Durham, NC, USA, 3 Oxford University Clinical Research Unit in Vietnam, Ho Chi Minh, Vietnam, 4 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, 5 University of Hong Kong, Pok Fu Lam, Hong Kong Background: Talaromyces marneffei infection (Tm) is a leading cause of HIV-associated morbidity and mortality in SE Asia. Diagnostic delays due to protracted culture methods is the most challenging clinical problem. We have demonstrated that the Mp1p antigen enzyme immunoassay (EIA) is more sensitive than blood culture in detecting Tm in a retrospective cohort. Here we

749 THE GLOBAL DISTRIBUTION, DRIVERS, AND BURDEN OF TALAROMYCOSIS, 1964-2017

Chuanyi Ning 1 , Wudi Wei 1 , Bo Xu 2 , Thanh T. Nguyen 3 , Li Ye1, Hao Liang 1 , Thuy Le 4 1 Guangxi Medical University, Nanning, China, 2 Tsinghua University, Beijing, China, 3 Oxford University Clinical Research Unit in Vietnam, Ho Chi Minh, Vietnam, 4 Duke University, Durham, NC, USA

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