CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Ambisome was priced at $72 per vial or less, this would be cost saving if efficacy is 85% or more. At a discounted price of $16.25 per vial and 85% efficacy, the health care systemwould save $2949 for every death averted from cryptococcal meningitis. Conclusion: Single dose Ambisome for asymptomatic cryptococcal infection given at 10mg/kg once in conjunction with fluconazole has potential to save lives and save costs, if proven effective.

1 University of Minnesota, Minneapolis, MN, USA, 2 Infectious Disease Institute, Kampala, Uganda, 3 Mbarara University of Science and Technology, Mbarara, Uganda, 4 University of Cape Town, Cape Town, South Africa Background: Cryptococcal meningitis and tuberculosis are both major causes of morbidity and mortality in persons with advanced HIV disease. Cytomegalovirus (CMV) viremia may be associated with increased mortality in HIV-infected persons with tuberculosis. It is not known if CMV viremia is associated with mortality in other AIDS-related opportunistic infections. Methods: We prospectively enrolled HIV-infected Ugandans with cryptococcal meningitis from 2010-2013 and cryopreserved plasma samples. Subsequently, we analyzed 121 randomly-selected, stored baseline samples for CMV DNA. We compared CMV viremia versus 10-week survival by time-to-event analysis. Results: Of 121 plasma samples tested, 63 (52%) had detectable CMV DNA (median viral load 298 copies/mL [IQR, 150 to 1630]). The median age was 36 years (IQR, 30 to 41), and the median CD4+ T cell count was 20 cells/µL (IQR, 9 to 72). A total of 43 deaths occurred. The mortality was 44% (28/63) in the CMV- positive group and 26% (15/58) in the CMV-negative group by 10-weeks (Hazard Ratio = 1.93; 95%CI, 1.02-3.61; P=0.04). Median CD4 counts did not differ between CMV-positive and CMV-negative groups (20 [IQR, 9 to 54] vs. 23 [IQR, 10 to 76] cells/µL, respectively; P=0.47). There was no association between the presence of CMV viremia and HIV RNA levels (P=0.71). Every 2-fold increase in IL-2 blood levels was associated with a lower probability of being CMV-positive (Odds Ratio = 0.74; 95%CI, 0.59-0.93; P=0.01). Conclusion: Half of persons with advanced AIDS and cryptococcal meningitis had CMV viremia. The presence of CMV viremia was significantly associated with mortality in persons with cryptococcal meningitis. It remains unclear if the relatively low level CMV viremia in the setting of high baseline mortality due to cryptococcal meningitis contributes to this mortality or may reflect underlying immune dysfunction (i.e. cause vs. effect). Further investigation is warranted. Ultimately, a randomized clinical trial of CMV treatment in advanced AIDS population would be needed to definitively answer if CMV viremia is a modifiable risk factor for mortality.

708 CRYPTOCOCCAL ANTIGENEMIA IN HIV PATIENTS WITH VIROLOGIC FAILURE IN UGANDA Edward Mpoza 1 , David Meya 1 , Maria S. Nabaggala 1 , Lillian Tugume 1 , Kenneth Ssebambulidde 1 , Joshua Rhein 2 , David R. Boulware 2 , Radha Rajasingham 2 1 Infectious Disease Institute, Kampala, Uganda, 2 University of Minnesota, Minneapolis, MN, USA Background: Cryptococcal antigen (CrAg) precedes fulminant cryptococcal meningitis, and preemptive treatment of those CrAg positive before development of meningitis is life-saving. The World Health Organization recommends screening and preemptive treatment for those with a CD4<100 cells/µL who are initiating ART. However, the proportion of patients presenting with fulminant cryptococcal meningitis is increasingly ART-experienced. It is not clear if there is a role for CrAg screening among ART-experienced persons with virologic failure. We evaluated CrAg prevalence among ART-experienced persons with suspected virologic failure in Uganda, and present 6-month survival and incidence of meningitis among CrAg-positive persons. Methods: We retrospectively performed CrAg testing on plasma samples of adults with virologic failure (HIV viral load >1000 copies/mL) between September 2017 and January 2018. For those CrAg-positive, ART history, incidence of cryptococcal meningitis, and 6-month survival were obtained from retrospective medical chart review. Results: We tested 1186 plasma samples of patients with viral loads >1000 copies/mL and found 35 CrAg-positive (prevalence of 2.95%). Of the 35 CrAg- positive persons, median ART duration was 42 months (IQR 14 to 78 months). We obtained 6-month outcome data on 21 CrAg-positive patients. Of these, 15 were alive, and 6 were dead. Five survivors were known to have received fluconazole. Two patients developed meningitis and survived with treatment. Thus, meningitis-free survival at 6-months was 13/21 (62%). Median viral load for CrAg negative was 11,650 copies/mL (IQR: 3,465 to 54,950), whereas median viral load for CrAg positives was 53,700 copies/mL (IQR: 17,513 to 163,500), (p<0.0001). Overall, 91% (32/35) of CrAg-positive persons had viral loads >5000 copies/mL compared with 64% (735/1149) of CrAg-negative (Odds Ratio = 6.0; 95%CI, 1.8 to 19.7, P=0.001). CrAg prevalence increased among higher viral loads with 4.2% (32/768) CrAg-positivity among those with >5000 copies/mL and 0.9% (5/553) CrAg-positivity among those with <5000 copies/mL Conclusion: CrAg prevalence was ~3% among ART-experienced persons with virologic failure, and median viral load was higher in CrAg positives compared to CrAg negatives. Meningitis-free survival was 62% at 6-months. Further studies to evaluate the potential benefit of CrAg screening in the ART-experienced population are warranted. 709 CYTOMEGALOVIRUS VIREMIA ASSOCIATED WITH MORTALITY IN CRYPTOCOCCAL MENINGITIS Caleb P. Skipper 1 , Mark R. Schleiss 1 , Jason C. Zabeli 1 , Nelmary Hernandez- Alvarado 1 , Sarah Lofgren 1 , Henry Nabeta 2 , Kabanda Taseera 3 , Abdu Musubire 2 , Charlotte Schutz 4 , Ananta Bangdiwala 1 , Katherine Huppler Hullsiek 1 , Conrad Muzoora 3 , David Meya 2 , Graeme Meintjes 4 , David R. Boulware 1 , for the COAT Trial Team

Poster Abstracts

710 ASYMPTOMATIC TALAROMYCES MARNEFFEI ANTIGENEMIA AND MORTALITY IN ADVANCED HIV DISEASE

Nguyen T. Thu 1 , Vu Quoc Dat 1 , Jasper F. Chan 2 , Hien T. Ha 1 , Dung T. Nguyen 3 , Anh T. Ho 4 , Patrick C. Woo 2 , Kwok-Yung Yuen 2 , Sheryl Lyss 5 , Moses Bateganya 5 , Kinh V. Nguyen 3 , Thuy Le 6 1 Oxford University Clinical Research Unit in Vietnam, Ho Chi Minh, Vietnam, 2 University of Hong Kong, Pok Fu Lam, Hong Kong, 3 National Hospital for Tropical Diseases, Hanoi, Vietnam, 4 CDC Hanoi, Hanoi, Vietnam, 5 CDC, Atlanta, GA, USA, 6 Duke University School of Medicine, Durham, NC, USA Background: Talaromyces marneffei (Tm) is a leading cause of HIV-associated infection with a mortality of 30% in SE Asia. Delay in culture diagnosis is associated with death. We have demonstrated in large cohorts that a novel Mp1p antigen detection assay is more sensitive than blood culture (90% vs. 70%) and is 98% specific in detecting Tm. We hypothesize that the test can

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