CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Results: The median adjusted R² of the fitted curves is 0.94 (IQR: 0.79-1.00); 74.4% of fitted curves had an adjusted R² > 0.8. In the multivariate Cox regression model, older age (+5 years) and time to reach peak blood fungal load were independent predictors of death, HR=1.25, 95% CI: 1.07-1.47, p=0.005 and HR=1.23, 95% CI: 1.07-1.41, p = 0.002, respectively. The risk of death due to a delay in fungal clearance (of > 0 day)was statistically significant in patients who received Itraconazole, (HR=1.31, 95% CI: 1.12-1.53, p<0.001) but not in patients receiving Amphotericin B (HR=1.17, 95% CI: 0.86-1.58, p=0.313) (Figure). Conclusion: Time to initiation of blood fungal clearance is an independent predictor of 6-month mortality and can potentially be used as an outcome measure for early phase clinical trials to efficiently assess novel therapeutic strategies for HIV-associated talaromycosis.

detect pre-clinical disease in patients with advanced HIV disease, and Tm antigenemia (TmAg) is associated with higher mortality. Methods: We retrospectively tested for TmAg in stored baseline plasma samples from patients aged ≥18 years with CD4 count of ≤100 cells/µL who were newly enrolled in care at 22 HIV clinics across Vietnam and participated in the Vietnam Cryptococcal Retention in Care Study (CRICS), August 2015 to April 2017. We excluded 34 patients with a talaromycosis diagnosis at enrollment. We investigated the risk factors for TmAg using multiple logistic regression analysis and investigated the association between TmAg and time to death over 12 months with Cox regression analysis, adjusting for age (+10 years), baseline CD4 counts (≤ or> 50 cells/µL), and cryptococcal antigenemia (CrAg). Future analyses will take potential within-clinic correlation into account. Results: Baseline plasma samples were available for 1082/1174 patients: 74.2%were male; median age was 35 years (IQR: 31-41), and median CD4 count was 36 cells/ µL (IQR: 15-62). TmAg was detected in 45 (4.2%) patients (95% CI: 3.1%-5.6%) and was non-overlapping with CrAg (prevalence=2.9%). TmAg prevalence was higher in northern (33/497; 6.6%) than southern (12/585; 2.1%) Vietnam, Chi Square p<0.001. TmAg was independently associated with CD4 count ≤50 cells/µL (OR=3.5, 95% CI: 1.4-11.8, p=0.006) and residency in highland regions (OR=3.4, 95% CI: 1.8-6.3, p<0.001). Overall the probability of death was 12.7% (95% CI: 10.6-14.7), and was higher in TmAg-positive (30.0%; 95% CI: 14.0-43.1) than TmAg-negative (11.9%; 95% CI: 9.8-13.9) patients, Log-rank p=0.002. In multivariable survival analysis, TmAg was an independent predictor of death, hazard ratio =2.3, 95% CI: 1.3-4.2, p=0.006. Conclusion: CD4 count of less than 50 cells/µL and living in highland regions are independent risk factors for TmAg, and asymptomatic TmAg is an independent risk factor of death. The M1p1 antigen assay is therefore a useful tool to screen for asymptomatic talaromycosis for pre-emptive antifungal therapy. This has the potential to substantially reduce HIV mortality in Southeast Asia.

Poster Abstracts

712 WITHHOLDING PCP PROPHYLAXIS IN VIRALLY SUPPRESSED HIV PATIENTS FROM COHERE Andrew Atkinson , for the Opportunistic Infections Project Team of COHERE University Hospital of Bern, Bern, Switzerland Background: Analyses using COHERE data previously suggested (Clin Infect Dis 2010:51:611) that primary Pneumocystis Pneumonia (PcP) prophylaxis could be withdrawn in patients with CD4 counts of 100-200 cells/µL if HIV-RNA is suppressed, suggesting HIV replication as major risk factor for PcP. Given the wealth of new data available in COHERE we investigated whether prophylaxis might be withheld or stopped in all patients on antiretroviral therapy with suppressed plasma HIV RNA (<400c/mL) irrespective of CD4 count. Methods: We estimated the risk of primary PcP in COHERE patients on cART including time-updated CD4 counts, HIV-RNA and use of PcP prophylaxis. We emulated a hypothetical randomised trial using established causal inference methods in which inverse probability (IP) weighting adjusts for censoring selection bias. Eligibility criteria were plasma HIV RNA (<400c/mL) and CD4 counts ≤200 cells/µL. We emulated three trials comparing the effect of A.) continue PCP prophylaxis versus stop prophylaxis, B.) start and then continue PCP prophylaxis versus not starting prophylaxis, and C.) taking PCP prophylaxis versus not taking PCP prophylaxis, irrespective of PCP prophylaxis status at baseline. In each case, we estimated the hazard ratio (HR) fitting a pooled logistic model which included baseline characteristics (CD4, RNA, gender, age, transmission, geographical origin calendar year), used restricted cubic splines to capture CD4/RNA trajectories, and included polynomial time for modelling the baseline hazard. Results: There were 9,743 patients eligible for the emulated trials with a total of 18,550 person years followed-up during 1998-2015. The unadjusted incidence rate of PCP diagnosis was 1.5 per 1000py on PCP prophylaxis compared to 2.8 off PCP prophylaxis. The HR estimates for the PCP outcome from the 3 emulated trials were 2.0 ([0.61 6.4], p=0.3) for Trial A, 2.8 ([0.8 9.9], p=0.1) for Trial B, and 1.2 ([0.5, 3.2], p=0.8) for Trial C (see Figure). Conclusion: In virologically suppressed patients, irrespective of CD4 levels, the risk of PcP appears to be low, and similar for individuals on and off prophylaxis, although the precision of the results was limited due to the overall low incidence of PCP. This suggests that primary PcP prophylaxis might be withheld in this patient group.

711 PREDICTIVE MODELING OF MORTALITY IN INVASIVE TALAROMYCOSIS IN HIV PATIENTS Shengxin Tu 1 , Cliburn Chan 2 , Thuy Le 1 1 Duke University School of Medicine, Durham, NC, USA, 2 Duke University, Durham, NC, USA Background: Talaromycosis (formerly penicilliosis) is an invasive fungal infection endemic in Southeast Asia, and is a leading cause of death in patients with advanced HIV disease. We have demonstrated in the recent IVAP trial the superiority of Amphotericin B over Itraconazole with regard to mortality, clinical response, and blood fungal clearance. Here, we investigated if early fungicidal activity in blood is a useful surrogate endpoint for all-cause mortality for HIV- associated talaromycosis. Methods: IVAP trial enrolled 440 patients across 5 hospitals in Vietnam from October 2012 to December 2016. 391 (87%) patients who had at least 3 measurements of blood fungal load (in colony forming units [CFUs] per ml) during the first 2 weeks were included in the analysis. We used nonlinear regression to characterize individual fungal clearance dynamics with single and double exponential curves that were best fitted to the data. Individual parameters estimated from the model fit include: peak value of log fungal count (a), time to reach peak fungal load (c, days), and rate of fungal decline (br, log fungal count/ml/day). The parameters were used in a multivariate survival analysis to predict the risk of death over 6 months using Cox proportional hazard model, adjusting for age, antifungal treatment, antiretroviral status, intravenous drug use, baseline CD4 count, log fungal count at enrollment, and dyspnea requiring oxygen.

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