CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

Methods: To gain insight into this cell biological process, we have used small hairpin RNA (shRNA) technology in primary monocyte-derived DCs (MDDCs) to suppress the expression of several hundred genes and analyze the impact on transfer of HIV-1 from DCs to T cells. Results: By combining flow cytometry with confocal and electron microscopy experiments, we have identified and validated the function of TSPAN7 and DNM2 in viral transfer. These proteins appear to be involved in the control of actin nucleation and stabilization, which are important in limiting HIV-1 endocytosis and maintenance of virus on dendritic processes for efficient transfer to T lymphocytes. The requirement for actin nucleation and dendrite formation in HIV-1 transfer is strongly supported by 28 additional genes identified in the shRNA screen. Conversely, knock down of 24 genes linked to different types of endocytosis resulted in increased HIV-1 transfer.

Conclusions: This genetic approach is a first step towards a better understanding of the molecular and cell biological aspects of HIV-1 transmission between DCs and T lymphocytes, which is needed to evaluate the importance of this process in infected individuals. This approach should provide new tools and new targets for the design of therapies that limit viral replication and boost innate immune responses to control HIV dissemination.

Oral Abstracts

Session O-4 Oral Abstracts

Room 6D

10:00 am– 12:15 pm New Discoveries in HIV Pathogenesis 47 Inflammation Persists Despite Early Initiation of ART in Acute HIV Infection

Netanya S. Utay 1 ; Jintanat Ananworanich 2 ; Suteera Pinyakorn 3 ; Adam Rupert 5 ; Duanghathai Sutthichom 3 ; Suwanna Puttamaswin 3 ; Bonnie M. Slike 2 ; Nelson L. Michael 2 ; Daniel C. Douek 4 ; Irini Sereti 4 1 University of Texas Medical Branch at Galveston, Galveston, TX, US; 2 US Military HIV Research Program, Silver Spring, MD, US; 3 South East Asia Research Collaboration with Hawaii, Bangkok, Thailand; 4 National Institutes of Health (NIH), Frederick, MD, US; 5 Leidos Biomedical Research, Inc, Frederick, MD, US Background: Biomarkers of microbial translocation, inflammation, coagulation and fibrosis predict morbidity and mortality in patients with chronic HIV infection. The effects of starting antiretroviral therapy (ART) in patients with acute HIV infection (AHI) on levels of these biomarkers in chronic treated infection are unknown and may illuminate the potential impact of early ART on clinical outcomes. Methods: Subjects were diagnosed with acute HIV infection and initiated ART within 0-5 days per RV254 protocol. Plasma levels of D-dimer, C-reactive protein (CRP), hyaluronic acid (HA), soluble CD14 (sCD14) and intestinal fatty acid binding protein (I-FABP, a marker of enterocyte turnover) were measured by ELFA (D-Dimer), Mesoscale (CRP) and ELISA (HA, sCD14, I-FABP) from 109 HIV-uninfected (HIV-) and 78 AHI Thai participants at diagnosis (week 0), weeks 2, 12, 24, 36, 48 and 96. Median values were compared between HIV+ and HIV- groups by Mann-Whitney test and longitudinal within-group comparisons by Wilcoxon matched-pairs signed rank test. Results: Median age was 28 years (range 24-33) for HIV+ subjects and 27 years (22-37) for HIV- subjects. 92.3% of HIV+ subjects and 77.1% of HIV- subjects were male. Median time since HIV acquisition was 16 days (12-22), CD4 T-cell count 384 (293-525) cells/mm 3 and HIV RNA 5.6 (5.1-6.3) log 10 copies/mL. Twenty subjects were diagnosed in 4th generation (4thG) stage 1 (median 12 days post-acquisition), 15 in stage 2 (16 days) and 43 in stage 3 (18 days). All week 0 biomarker levels were significantly higher in HIV+ than HIV- subjects (see table). I-FABP increased by week 2 and remained elevated regardless of 4thG stage. Other biomarkers did not decrease in individuals diagnosed in 4thG1 until week 12. sCD14, CRP and HA decreased by week 2 in individuals diagnosed in 4thG2, and sCD14, CRP, HA and D-dimer decreased by week 2 in individuals diagnosed in 4thG3. HIV+ subjects had significantly higher levels of all biomarkers except D-dimer after 48 and after 96 weeks of ART compared to HIV- subjects.

100

CROI 2015