CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Kaplan-Meier curve of time to death by culture status among 428 persons with known culture status. Conclusions: In this cohort, culture-negative TB was associated with a 61% increased risk of death compared to those with culture-confirmed TB. These findings raise the possibility that persons diagnosed with culture-negative TB may not have had TB, and died of other causes. This underscores the importance of accurate TB diagnosis in HIV+ persons.

THURSDAY, FEBRUARY 26, 2015 Session P-R5 Poster Session

Poster Hall

2:30 pm– 4:00 pm Cryptococcal Meningitis: Host Response, Treatment, and Outcomes 834 Local and Systemic Humoral Responses to Cryptococcal Meningitis in Patients With AIDS

Erin E. Finn 1 ; Jordan Janoff 1 ; Jeremy Rahkola 1 ; David B. Meya 2 ; Samuel Okurut 2 ; Andrew D. Kambugu 2 ; Paul Bohjanen 3 ; Kirsten Nielsen 3 ; David R. Boulware 3 ; Edward N. Janoff 1 1 Mucosal and Vaccine Research Colorado, Aurora, CO, US; 2 Makerere University College of Health Sciences, Kampala, Uganda; 3 University of Minnesota, Minneapolis, MN, US Background: Antibodies may support protection against meningitis caused by Cryptococcus neoformans (CM), a prominent cause of disease and death in persons with AIDS, among whom antibody defects are common. Methods: We measured total and Cryptococcus-specific IgG and IgM antibody levels by ELISA in serum and cerebrospinal fluid (CSF) from 41 antiretroviral therapy naïve adults with AIDS at the time of CM diagnosis in Kampala, Uganda. Cryptococcus-specific antibodies were directed against capsular glucuronoxylomannan (GXM) or unencapsulated organisms. Immune complexes (IC) were dissociated and neutralized with acid treatment and glycine. Results: The median CD4+ T cell count was 16/ m L and log 10 HIV RNA was 5.33 copies/mL. CSF-analysis showed median protein of 70 mg/dL, WBC of 30/mL [43% had <5 cells], cryptococcal antigen (CrAg) titer of 1:4,000 and cryptococcal colony forming units of log 10 5.4/mL. Total IgG in CSF exceeded IgM by over 20 fold (median 127 vs. 5.8 m g/mL). Levels of IgG and IgM specific to GXM were greater than levels specific to unencapsulated organisms. We detected GXM-specific IgG and IgM in CSF of 46% and 24% of subjects, respectively, and in 100% of sera. The antibodies detected in CSF were specific for GXM based on cross-adsorption with heterologous polysaccharides and proteins, but the specificity of IgM exceeded that of IgG. In the CSF, GXM-IgM was produced locally, whereas the GXM-IgG was likely transferred from serum based on the ratios of GXM-specific to total IgM and IgG in CSF and serum. The majority of GXM-IgG but not IgM in the CSF was bound by local capsular GXM as levels increased by 10-fold upon dissociation of IC. IC-bound antibodies had greater avidity than antibodies freely circulating in CSF. Levels of GXM-IgG or -IgM did not correlate with CSF WBC, protein, CrAg titer or mortality (11 of 41 died [26.8%] within 30 days). Conclusions: Specific antibodies that recognize the predominant capsular polysaccharide of C. neoformans (GXM) are present in the CSF of a subset of AIDS patients with CM. GXM-IgM, although present in fewer patients, was higher in concentration, specificity and avidity than GXM-IgG and was more likely produced locally at the site of infection. Enhancing levels of such antibodies may support opsonization of C. neoformans , promote cytokine production and cellular immune responses to the organism, and thereby faciliate protection against these common and often fatal infections. 835 Antiretroviral Therapy Alters the CSF Immune Response in Cryptococcal Meningitis James E. Scriven 1 ; Britta Urban 1 ; Lisa Graham 2 ; Charlotte Schutz 2 ; Robert J.Wilkinson 3 ; David R. Boulware 4 ; David Lalloo 1 ; Graeme Meintjes 2 1 Liverpool School of Tropical Medicine, Liverpool, United Kingdom; 2 University of Cape Town, Cape Town, South Africa; 3 Imperial College London, London, United Kingdom; 4 University of Minnesota, Minneapolis, MN, US Background: Cryptococcal meningitis (CM) is an important opportunistic infection in sub-Saharan Africa. Animal models suggest a M2 (alternatively activated) macrophage phenotype and Th2 response are detrimental during infection but studies in humans are limited. To address this we characterized the CSF immune response in HIV-associated CM, examined the effects of ART, and explored the relationship between CSF immune response, fungal burden and mortality. Methods: A prospective cohort study was conducted in South Africa. Persons with CM were enrolled and followed for 12 weeks. CSF immune response was examined using 11- colour flow cytometry and 17-plex luminex analysis. Fungal burden was measured using quantitative culture. Data were analysed using principal component analysis; p<0.05 with a false discovery rate (q) <0.1 were used to infer statistical significance.

Poster Abstracts

506

CROI 2015