CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: Our data showed that extracts of TwHF is helpful in CD4+ T cells recovery and also could dampen inflammation and immune activation for HIV INR individuals. The possible mechanisms of type I interferon signaling needs to be further explored. It could be a potential strategy combined with antiretroviral therapy to reduce immune activation and inflammation for HIV patients.

521 METABOLIC SHUT DOWN OF CD4 T CELL ACTIVITY AND FUNCTION INDUCED BY HAART Marek Korencak 1 , Enrico Richter 1 , Eva Eilers 1 , Bruce T. Schultz 1 , Patrick Juszczak 1 , Stefan Esser 2 , Hendrik Streeck 1 1 Institute for HIV Research, Essen, Germany, 2 University Hospital Essen, Essen, Germany Background: Metabolism plays a pivotal role in a cell’s ability to maintain their viability and fulfil their effector functions. It has been shown that cells in chronically HIV-infected individuals become exhausted and undergo a progressive loss of hierarchical functions, but the changes in their cellular metabolism remain unclear. In this study we evaluate the impact of HIV infection and individual HAART regimens on two major metabolic pathways – oxidative phosphorylation and glycolysis as well as on cellular function. Methods: Different cell types were isolated from PBMC of HIV-infected treatment-naïve and treated individuals as well as from healthy donors. Cells were stimulated in the presence of different ART regimens and their metabolic profiles were analysed by the extracellular flux analyser Seahorse XFp. We used multicolour flow cytometry to study the function and phenotype of PBMC of each individual and determined changes in ROS production as well as mtDNA content by qPCR. Results: NK cells, B cells, CD4 and CD8 T cells from HIV infected treatment- naïve individuals displayed significantly reduced basal and maximal respiration compared to healthy controls. The metabolic capacity strongly correlated with the expression of the inhibitory receptor PD-1 (p<0.0001) and immune activation level (defined as HLA-DR+ CD38+ expression; p<0.0001). Interestingly, while long-term HAART treatment robustly restored the bioenergetic profile of NK cells, B cells and CD8 T cells, it had a negative effect on CD4 T cells, particularly in Dolutegravir (DLG) containing regimens. We therefore assessed the impact of individual antiretrovirals on CD4 T cell metabolism. Strikingly, the integrase strand transfer inhibitors (INSTI) Elvitegravir (EVG) and DLG, but not Raltegravir (RAL), shut down the basal and maximal respiration of CD4 T cells. This significantly altered the functional profiles of the cells by driving them from a balanced polyfunctional response to a TNFα-dominated ‘stress’ immune response. Analysis of mitochondrial ROS and mtDNA quantities revealed increased mitochondrial toxicity, but not general cytotoxicity, in the presence of these drugs. Conclusion: Taken together, our data demonstrate a substantial disruption in the metabolic activity of lymphocytes during chronic HIV infection that is restored through antiretroviral therapy. However, two INSTI, DLG and EVG, diminish the metabolic activity in CD4 T cells, leading to a switch in functionality and impairment of overall function.

522 NATURAL CONTROL OF HIV INFECTION IN A COHORT OF YOUNG WOMEN IN SOUTH AFRICA: HPTN 068 Mariya V. Sivay 1 , Yinfeng Zhang 1 , Jing Wang 2 , Jessica M. Fogel 1 , Estelle Piwowar-Manning 1 , William Clarke 1 , Erica Hamilton 3 , Kathleen Kahn 4 , Amanda Selin 5 , Xavier Gomez-Olive 4 , Catherine MacPhail 6 , James P. Hughes 7 , Audrey Pettifor 5 , Susan H. Eshleman 1 1 The Johns Hopkins University, Baltimore, MD, USA, 2 Statistical Center for HIV/AIDS Research and Prevention, Seattle, WA, USA, 3 FHI 360, Durham, NC, USA, 4 University of the Witwatersrand, Johannesburg, South Africa, 5 University of North Carolina Chapel Hill, Chapel Hill, NC, USA, 6 University of Wollongong, Wollongong, Australia, 7 University of Washington, Seattle, WA, USA Background: HIV controllers are able to suppress viral replication to low levels without antiretroviral (ARV) therapy. The HIV Prevention Trials Network (HPTN) 068 trial was conducted in a rural area in South Africa and evaluated the impact on HIV incidence of a cash transfer conditional on high school attendance (study period: 2011-2015). The trial enrolled 81 HIV-infected and 2,448 HIV-uninfected women who were followed annually until their expected graduation date; some women had a post-graduation follow-up visit 1-2 years later. Overall, 164 women acquired HIV infection (seroconverters). We evaluated the frequency of HIV controllers in this cohort. Methods: HIV viral load (VL) testing was performed using the RealTime HIV-1 Viral Load assay (limit of quantification: 40 copies/mL). ARV drug testing was performed using a qualitative assay that detects 20 ARV drugs in 5 drug classes. HIV genotyping was performed for samples with VLs >400 copies/mL using the Viroseq HIV-1 Genotyping System, v2.8. Women were classified as viremic controllers if they had a VL ≤ 2,000 copies/mL at study enrollment or their first HIV-positive visit (for seroconverters), and maintained this level of viral suppression for at least 12 months in the absence of ARV drug use. Statistical analysis was performed using SAS software. Results: Thirty-four (13.9%) of the 245 HIV-infected women had VLs ≤2,000 copies/mL at the first visit tested with no ARV drugs detected at that visit (12 at enrollment; 22 at their first HIV-positive visit; three seroconverters had VLs <40 copies/mL at this visit). Fifteen of the 34 women were followed for ≥12 months. Twelve of the 15 women were classified as viremic controllers (seven who were HIV-infected at enrollment; five who seroconverted during the study; one woman had a single VL value ≥2,000 copies/mL during follow-up; median follow-up: 20 months, range 13-42 months). These women had sustained viral suppression with no ARV drugs detected during follow-up. Only one of 12 viremic controllers had HIV drug resistance. Conclusion: In this cohort of young women in rural South Africa, at least 5% were able to control viral replication to low levels in the absence of ARV drug use (8.6% of women who were HIV infected at enrollment and 3.1% of the seroconverters). These data may help inform future studies of HIV treatment and prevention in this high-incidence population.

Poster Abstracts

CROI 2018 190