CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Methods: A total of 64 participants, ages 40 and older, were recruited from the SCOPE cohort. There were 45 HIV-infected participants and 19 HIV-negative controls (who were matched by age, gender, and Framingham risk score to HIV patients). Thirty-four (76%) of the HIV-infected individuals were treated and virally suppressed, 7 (16%) were elite controllers, and 1 (2%) was treated and unsuppressed. NALT activation (NALT-A) was measured as average of maximum standardized uptake value (SUVmax) of FDG uptake within nasopharyngeal tissue. Immunophenotyping of T-cells and monocytes was performed by multiparameter flow cytometry on cryopreserved PBMCs. HIV reservoir was ascertained by measuring the frequency of CD4+ T-cells harboring integrated HIV DNA. Results: Average maximum standard uptake value of NALT was higher in HIV-infected individuals on ART vs matched HIV-negative controls (5.18 +/- 2.19 vs 3.40 +/- 1.04, p=0.023). SUVmax of NALT was positively correlated with nadir CD4 (r=0.507, p=0.002) and was inversely associated to markers of inflammation (IL-6: r=-0.429, p=0.014; sCD163: r=-0.380, p=0.032). A trend for an inverse association between NALT and the HIV reservoir was observed (r=-0.350, p=0.0563). However, among the elite controllers only, this finding was highly significant (NALT-A: N=5, r=-0.98, p=0.005). Conclusions: HIV-infected individuals had higher levels of NALT-A compared to matched HIV- negative controls. In HIV infection, activation of NALT tissue was associated with lower indices of inflammation, higher nadir CD4 count, and lower levels of the HIV reservoir. These novel observations suggest that an intact and active NALT may play a role in generating a response in the setting of HIV.

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HIV DNA Identified in Most Tissues of a Plasma-Negative HIV Autopsy Cohort Susanna L. Lamers 1 ; Rebecca Rose 1 ; David J. Nolan 2 ; Debra L. Garcia 3 ; Melissa Agsalda-Garcia 4 ; Bruce Shiramizu 4 ; Ekaterina Maidji 5 ; Cheryl Stoddart 5 ; Elyse Singer 6 ; Michael S. McGrath 5 1 Bioinfoexperts, LLC, Thibodaux, LA, USA; 2 Emerging Pathogens Inst, Univ of Florida, Gainesville, FL, USA; 3 AIDS and Cancer Specimen Resource, San Francisco, CA, USA; 4 Univ of Hawaii,

Honolulu, HI, USA; 5 Univ of California San Francisco, San Francisco, CA, USA; 6 Natl Neurological AIDS Bank, Los Angeles, CA, USA Background: While combined antiretroviral therapy (ART) can reduce plasma viral loads to undetectable levels, the degree to which virus is eliminated from other anatomical sites remains unclear. The high frequency of comorbidities in ART + HIV + patients suggests that persistence of virus may contribute to tissue pathologies. The goal of this study was to identify subjects with undetectable plasma and CSF viral load at death, assay a panel of their autopsy tissues for HIV, and assess tissue histopathology to discover the extent of residual anatomical HIV levels during cART and the potential relationship to tissue injury. Methods: The National Neurological AIDS Bank (NNAB) and AIDS and Cancer Specimen Resource (ACSR) autopsy cohort was screened to identify 20 HIV + /ART-treated participants who had undetectable plasma and CSF viral loads at autopsy. Extensive medical histories were compiled for each participant. Detailed histopathological findings were noted in multisite autopsy specimens (n=212, including up to 6 brain and 6 lymphoid tissues per subject). All tissues were assayed for the presence of HIV DNA using quantitative and digital drop PCR. A subset of tissues was evaluated for HIV RNA using RNAscope in situ hybridization assay. Results: The median patient age and length of HIV infection was 46.5 years and 12 years, respectively. Fifteen of the 20 patients developed cancer. Abnormal histological findings in the spleen, lung, lymph node and liver were identified in 90% of the participants. Aorta and kidney were abnormal in 50 and 60% of the participants, respectively. 75% of participants demonstrated a degree of atherosclerosis and all brain tissues analyzed demonstrated slight to severe pathology. Overall, 66% of the tissues studied contained HIV DNA copies >200/million cell equivalents. Selected RNAscope studies localized HIV to macrophages within cancer tissues ( See Figure ). In HIV RNA positive brain tissue, infiltrating macrophages surrounded HIV + cells.

Poster Abstracts

Conclusions: This study confirms the presence of HIV within diverse anatomical tissues in virally suppressed ART + patients. Persistent virus replication in tissues could promote inflammatory diseases, including cancer, atherosclerosis and other organ-associated diseases. These ACSR/NNAB cohorts, along with others of their kind, are highly valuable resources for future studies of HIV reservoirs and persistence.

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CROI 2016