CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: IL-18, a highly pro-inflammatory cytokine linked to organ damage, was associated with clinical failure in persons who were virologically suppressed in diverse settings, suggesting that persistent inflammation in HIV-infected persons on ARV may contribute to further disease progression. Unexpectedly, IFN γ levels were inversely related to the risk of clinical failure, suggesting a link with immune restoration. 314 Impact of Partner HIV Status on Immune Activation and Inflammation During Chronic HIV Shameem Z. Jaumdally 1 ; Pamela Gumbi 1 ; Hoyam Gamieldien 1 ; Anabela Picton 2 ; CarolineTiemessen 2 ; Lindi Masson 1 ; Lenine Liebenberg 3 ; David Coetzee 1 ; Anna-LiseWilliamson 1 ; Jo-Ann Passmore 1 1 University of Cape Town, Cape Town, South Africa; 2 National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa; 3 Centre for AIDS Programme Research in South Africa, Durban, South Africa; 4 University of Cape Town, Cape Town, South Africa Background: The role of immune activation and inflammation on the rate of HIV disease progression has been proposed as a critical determinant of pathogenesis, but the mechanism is not fully understood. HIV+ individuals with HIV- partners (discordant relationship) versus HIV+ partners (concordant relationship) provide valuable insight to the role of continued HIV exposure on the clinical course of HIV infection. This study compared the impact of systemic viral load, T cell activation and inflammatory cytokine profiles on rate of disease progression in HIV+ concordant and discordant couples. Methods: The impact of sexual partner status on systemic immune activation and inflammatory cytokine production in HIV+ individuals in HIV concordant (n=195) or discordant (n=142) long-term relationships was determined by flow cytometric analysis and luminex assays. Sequencing and qPCR were performed to determine CCR5 haplotypes. Results: HIV+ concordant individuals had 0.5 Log 10 higher plasma viral loads than HIV+ discordant ones (p<0.0001), and this was maintained over 24 months. However, this did not predict worse disease outcome (measured by absolute blood CD4 counts at later time points). HIV+ concordant individuals had higher frequencies of activated T-cells (CD3+CD38+CCR5+) in blood than HIV+ discordant counterparts. Individuals with plasma HIV loads >1500 copies/ml had higher frequencies of CD4+CCR5+ (p=0.007), CD8+CD38+ (p=0.01) and CD8+HLA-DR+CD38+ (p=0.01) T-cells compared to individuals with plasma viral loads <1500 cps/ml. CCR5 promoter haplotypes were not found to be a determinant in the CCR5 expression levels by T-cells. HIV+ concordant individuals had significantly higher concentrations of IL-1 β (p=0.04) and TNF- α (p=0.03) in plasma than HIV+ discordant individuals. In women, plasma viral loads predicted genital tract viral loads (Rho=0.65; p<0.0001), with HIV+ concordant women having higher genital viral loads than HIV+ discordant women (p=0.001). HIV+ women with detectable HIV in genital secretions had higher genital concentrations of IP-10 (p=0.002), IL-1 α (p=0.007), IL-1 β (p=0.004), IL-6 (p=0.005), IL-8 (p=0.008), MCP-1 (p=0.03), MIP-1 β (p=0.01), IL-10 (p=0.01), and G-CSF (p=0.002) than those with no detectable genital HIV. Conclusions: This study suggests that partner’s HIV status influences systemic viral loads, immune activation and inflammation, and is potentially a key factor ensuring continued HIV replication, but did not influence disease outcome. 315 Pretherapy Inflammation and Long-Term CD4 Response to Antiretroviral Therapy Amit C. Achhra 1 ; Andrew N. Phillips 2 ; Sean Emery 1 ; Rodger D. MacArthur 3 ; Hansjakob Furrer 4 ; Stéphane DeWit 5 ; Marcelo H. Losso 6 ; Matthew G. Law 1 On behalf of the INSIGHT SMART and FIRST Study groups 1 Kirby Institute, University of New South Wales, Sydney, Australia; 2 University College London, London, United Kingdom; 3 Wayne State University, Detroit, MI, US; 4 University Hospital Bern, Bern, Switzerland; 5 Saint- Pierre University Hospital, Brussels, Belgium; 6 Hospital J.M. Ramos Mejía, Buenos Aires, Argentina Background: Pre-antiretroviral therapy (ART) inflammation/ coagulation activation predict clinical outcomes. However, it is unknown whether these processes result in blunted CD4+ count (CD4) responses to ART, thereby resulting in clinical outcomes. The objective of this analysis was to perform exploratory analyses assessing whether pre-ART inflammatory marker levels predicted the CD4 response to ART. Methods: Analyses were based on data from the SMART and FIRST trials. The SMART study was an international trial evaluating continuous (viral suppression (VS) versus interrupted (drug conversation (DC)) ART and the FIRST trial evaluated 3 first-line ART regimens with ≥ 2 classes. For this analysis, participants had to be ART-naïve or off ART at randomisation and (re)starting ART and have C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer measured (available at randomisation for the majority of SMART participants and a selected group from FIRST who participated in previous biomarker studies). Using random effects linear models, we assessed the association between each of the biomarker levels, categorised as quartiles, and change in CD4 from ART-start to 24 months post-ART. Analyses adjusted for pre-ART CD4, study arm, follow-up time and other known confounders. Sensitivity analyses included separate analyses by trials (given it was a selected sub-sample in FIRST) and excluding the DC arm in SMART. Results: Overall, 1084 individuals (659 from SMART (26% ART naïve) and 425 from FIRST) met the eligibility criteria, providing 8264 CD4 measurements. 75%were male with the mean age of 42 years, 37% and 47%were white and black respectively, and 10% and 33%, respectively, were hepatitis B and C positive. The median (inter-quartile range) baseline CD4 (cells/mm 3 ) were 360 (265-473) overall and 416 (350-530) and 100 (22-300) in SMART and FIRST, respectively. All of the biomarkers were inversely associated with baseline CD4 in FIRST but not in SMART. The figure shows the mean change in CD4 post-ART by quartiles of CRP, IL-6 and D-dimer. In adjusted models, there did not appear to be any clear relationship between changing biomarker levels and mean change in CD4 (P for trend: CRP: 0.97; IL-6: 0.25 and D-dimer: 0.29). Sensitivity analyses yielded similar results.

Poster Abstracts

Figure: Change in CD4 count since (re)initiation of ART by pre-ART quartiles of CRP, IL-6 and D-dimer. Q=quartile (e.g. Q1= 1st quartile etc.).

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CROI 2015