CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

screening of subjects between the ages of 55-74 years as recommended in the general population may miss substantial numbers of cancers in HIV-infected smokers with a nadir CD4 cell count < 350/ m l. 728 CD4 Measures as Predictors of Lung Cancer Risk and Prognosis in HIV Infection Keith Sigel 1 ; Kristina Crothers 2 ; Kirsha Gordon 3 ; Sheldon Brown 4 ; David Rimland 5 ; Maria Rodriguez-Barradas 6 ; Cynthia Gibert 7 ; Matthew B. Goetz 8 ; Roger Bedimo 9 ; Robert Dubrow 10 1 Icahn School of Medicine at Mount Sinai, New York, NY, US; 2 University of Washington School of Medicine, Seattle, WA, US; 3 VA Connecticut Healthcare System and Yale University Schools of Medicine and Public Health, New Haven, CT, US; 4 James J. Peters VA Medical Center, Bronx, NY, US; 5 Atlanta VA Medical Center, Atlanta, GA, US; 6 Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, US; 7 Washington DC Veterans Affairs Medical Center, Washington, DC, US; 8 Los Angeles VA Medical Center, Los Angeles, CA, US; 9 Veterans Affairs North Texas Health Care System, Dallas, TX, US; 10 Yale University School of Public Health, New Haven, CT, US Background: Immunodeficiency may adversely affect both lung cancer risk and outcomes in the setting of HIV infection. Using data from a large HIV cohort, we investigated relationships between 1) recent and cumulative measures of CD4 and CD8 count and lung cancer incidence and 2) CD4 measures and lung cancer prognosis. Methods: We followed 26,065 HIV+ subjects from the Veterans Aging Cohort Study (VACS) for a minimum of 2 years, during 1999-2010. We linked VACS with the VA Central Cancer Registry to obtain incident, pathologically confirmed lung cancer cases. Our exposures of interest were longitudinal CD4 (<200 cells/mm 3 [c/mm 3 ], 200-500 c/mm 3 or >500 c/mm 3 ), CD4/CD8 (<0.4 or ≥ 0.4) and CD8 ( ≥ 850 c/mm 3 or <850 c/mm 3 ). We used Cox regression models to investigate the effect of time-updated CD4, CD4/CD8 ratio and CD8 measures on lung cancer risk, including values lagged 12 months, and 12- and 24-month simple moving averages. Models were adjusted for age, sex, race/ethnicity, smoking, and history of pneumonia and COPD. We then collected all non-small cell lung cancer cases from the full VACS (HIV+ and HIV- subjects from 1996-2010) and used conditional probability function regression (a competing risks method to account for higher risk of non-lung cancer death in HIV+) to compare lung cancer-specific survival in 3 groups: HIV- (n=679), HIV+ with CD4 ≥ 200 c/mm 3 at cancer diagnosis (n=299) and HIV+ with CD4<200 c/mm3 at cancer diagnosis (n=113). These analyses were adjusted for demographics, comorbidity score, cancer stage and histology, cancer diagnosis year, and cancer treatment. Results: We identified 325 (1.2%) cases of incident lung cancer in our cohort. In adjusted models (Table 1), a 12 month lagged CD4 count <200 c/mm 3 as well as moving averages of both CD4<200 c/mm 3 and CD4 200-500 c/mm 3 were significantly associated with increased lung cancer incidence. In similar adjusted models, 12-month moving averages of CD4/CD8 ratio <0.4 were also significantly associated with increased risk of lung cancer. Among lung cancer cases, lung cancer-specific survival did not differ between either of the HIV+ groups and the HIV- group (p>0.05) after adjustment.

Oral Abstracts

Table 1. Adjusted hazard ratios for lung cancer by CD4, CD4/CD8 ratio, and CD8 exposures. Conclusions: In our large HIV cohort, we found that several measures of recent and cumulative exposure to immunodeficiency were associated with increased lung cancer risk. CD4 count at time of cancer diagnosis was not associated with cancer-specific survival after accounting for competing risk of non-lung cancer death. 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.

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CROI 2015