CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

was no difference observed in the frequency of PB and BMem between the time of AHI diagnosis and HIV- individuals (PB: 6.3% vs 8.2%, BMem: 58.0% vs 53.7%, respectively). However, 24 months post ART initiation a significant increase in the frequency of PB to 17.1%was observed compared to time of AHI diagnosis (6.3%, p≤0.01) and compared to HIV- (8.2%, p≤0.0001), which was similar to the frequency of PB in CHI (14.8%, p=0.24). The frequency of BMem decreased from 58.0% during AHI diagnosis to 50.1% at 24 months post ART initiation (p≤0.01). Following 24 months of ART the frequency of BMem (50.1%) was lower compared to HIV- (53.7%, p=0.03), but remained significantly higher compared to CHI (35.0%, p≤0.05). Interestingly, the expression of IgA, the most abundant isotype produced by mucosal PB, was higher in CHI compared to AHI following 24 months of ART (10.8% vs 4.7%, p=0.03), with no increase observed between AHI diagnosis and 24 months post ART initiation (6.1% vs 4.7%, p=0.43). Conclusion: HIV-related hyperactivation of mucosal B cells was observed despite early ART initiation. However, early ART appears to limit the loss of BMem compared to CHI as well as prevent increased IgA production by PB. These results provide further insights on mucosal B cell dynamics in HIV infection and another potential mechanism how early ART may limit immune system damage at the mucosal barrier. 299 IMPROVED CD4 T CELLS RESPONSES WITH EARLY TREATMENT DURING PRIMARY HIV INFECTION Camille Lecuroux 1 , Remonie Seng 1 , Asier Saez-Cirion 2 , Veronique Avettand- Fenoel 3 , Jean-Paul Viard 4 , Delphine Lebrasseur 1 , Claudine Duvivier 4 , Alain A. Venet 1 , Christine Rouzioux 3 , Cécile Goujard 4 , Laurence Meyer 1 , Antoine Chéret 3 1 INSERM, Le Kremlin-Bicetre, France, 2 Institut Pasteur, Paris, France, 3 Paris Descartes University, Paris, France, 4 Assistance Publique – Hôpitaux de Paris, Paris, France Background: Treatment as soon as possible, limiting viral replication, has been shown to reduce the expansion of the HIV reservoir (Laanani et al., CID, 2015). We investigated the impact of early control of HIV replication on CD4 and CD8 T cell functions. We studied the kinetics of CD4 and CD8 T cell responses during PHI and investigated the relationship between the control of viral load (VL) after 3 months of treatment (M03) and the quality of CD4 and CD8 T cell responses at month 24 of treatment (M24). Methods: In 50 subjects included in the ARNS-147 OPTIPRIM study, cytokine production (IL-2, MIP-1β and IFN-γ) was measured on peripheral blood mononuclear cells by flow cytometry after a 15-hour stimulation with relevant optimal peptide pools according to the subjects’ HLA-A and B alleles or p24 for CD8 and CD4 T cells, respectively at inclusion and at M24. In parallel, the capacity of CD8 T cells to suppress p24 production by autologous CD4 T cells in coculture was measured and expressed as Log10 of p24 decrease. Cytokine production at inclusion was explored according to the time after the estimated date of contamination by the Loess curve. Results: Analysis of cytokine production kinetics during PHI highlights the existence of a peak of CD8 T cells responses around 30 days after the estimated date of contamination. CD8+ T cell-mediated HIV suppression which was weak during PHI (median 0.092 Log10 of p24 decrease, IQR [0.019-0.305]) did not improve after 24 months of treatment (0.144 Log10 of p24 decrease [0.047-0.359], p=0.62). At M24, the proportion of CD4 T cells producing at least one cytokine in response to p24 stimulation tended to be higher in subjects with undetectable viral load at M03 compared with subjects that still had a detectable plasma viral load at M03 (threshold = 50 HIV-RNA copies/mL) (0.068% [0.035-0.340] vs 0.028% [0.008-0.044] of CD4 T cells, respectively; p=0.06). IFN-γ production contributed greatly to the difference, with 0.016% [0.008-0.096] of IFN-γ producing CD4 T cells in subjects with undetectable VL at M03 vs 0.003% [0.002-0.007] in subjects with detectable VL at M03, p<0.0001. Conclusion: Achieving a control of viral replication during the first 3 months of treatment initiated at PHI is crucial to protect the CD4 T cell function at long term. This is an additional argument for not delaying treatment initiation in PHI. 300 EFFECT OF TELMISARTAN GIVEN AT ART INITIATION IN AHI ON IMMUNE CELLS IN LYMPH NODES Supranee Buranapraditkun 1 , Hiroshi Takata 2 , Eugène Kroon 3 , Suthat Chottanapund 3 , Carlo Sacdalan 3 , Somporn Tipsuk 3 , Khunthalee Benjapornpong 3 , Bessara Nuntapinit 4 , Timothy Schacker 5 , Nicolas Chomont 6 , Merlin L. Robb 7 , Jintanat Ananworanich 7 , Serena S. Spudich 8 , Lydie Trautmann 2 , for the on behalf of the SEARCH018/RV408 Study group

1 Chulalongkorn University, Bangkok, Thailand, 2 Henry M Jackson Foundation, Silver Spring, MD, USA, 3 SEARCH, Bangkok, Thailand, 4 Armed Forces Research Institute of Medical Sciences in Bangkok, Bangkok, Thailand, 5 University of Minnesota, Minneapolis, MN, USA, 6 Université de Montréal, Montreal, QC, Canada, 7 Henry M Jackson Foundation, Bethesda, MD, USA, 8 Yale University, New Haven, CT, USA Background: HIV infection induces lymph node fibrosis and persistent inflammation even during successful ART. Telmisartan, an angiotensin II receptor blocker, could prevent fibrosis and inflammation in individuals with HIV when administered at time of ART initiation in acute HIV infection (AHI). We assessed telmisartan effect on preventing HIV-mediated damage and on HIV reservoirs in tissues in people randomized during AHI to telmisartan+ART (T+ART) versus ART alone. Methods: Cryopreserved LN cells at time of AHI and 48 weeks after were included from RV408 participants randomized to T+ART (n=7) versus ART alone (n=4). Additionally, LN samples from other RV254 participants at AHI (n=26) and post-ART at wk48 (n=13), to compare the RV408 randomized group to a larger group. Nine uninfected individuals were also included. B cells, CD4 and CD8 T cells were characterized by flow cytometry when sufficient cells permitted. Total HIV DNA levels in CD4 T cells were quantified by ultrasensitive PCR; collagen, TGFβ and TNFα were measured by immunohistochemistry. Results: In AHI, no differences were observed between the groups. At wk48, in LN, the frequencies of resting memory (RM) B cells (CD21+CD27+IgG+CD20+) were decreased in ART group in the RV408 and RV254 but maintained at similar levels as controls in the T+ART group (Fig.1a). Conversely, frequencies of tissue-like memory B cells and intermediate memory B cells were lower in LN in the T+ART group compared to the RV408 ART group (p=0.015 and p=0.039, respectively) as well as the RV254 group. In addition, in LN, frequencies of regulatory B cells (CD38hiCD24hiCD19+) were higher in the T+ART group compared to uninfected controls and trending to be higher compared to the ART groups (Fig.1b). No difference was observed between the two groups in activated CD4 and CD8 T cells (CD38+HLA-DR+ and Ki67+Bcl-2lo) in LN. The LN HIV DNA levels were not different between the T+ART and the ART groups (Fig.1c). No differences were observed in collagen deposition, TGFβ and TNFα between the two RV408 groups. Conclusion: Although the number of studied samples in the T+ART group in our study limits definitive conclusions, addition of telmisartan to ART during AHI did not reduce T cell activation, HIV reservoir or collagen deposition in LN. However, we observed higher RM B cells and Bregs in LN after T+ART versus ART alone. These data suggest that adjunctive therapy in AHI with telmisartan over 48 weeks may preserve immune cells in LN especially the B cell compartment.

Poster Abstracts

301 METFORMIN TREATMENT IN NONDIABETIC HIV-INFECTED INDIVIDUALS ON ART Delphine Planas 1 , Rosalie Ponte 2 , Amelie Pagliuzza 3 , Augustine Fert 1 , Laurence Raymond Marchand 3 , Annie Gosselin 3 , Franck P. Dupuy 2 , VikramMehraj 3 , Maged P. Ghali 4 , Sylvie Lesage 1 , Jonathan Angel 5 , Eric A. Cohen 1 , Nicolas Chomont 1 , Petronela Ancuta 1 , Jean-Pierre Routy 2 1 Université de Montréal, Montreal, QC, Canada, 2 McGill University Health Centre Research Institute, Montreal, QC, Canada, 3 Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada, 4 McGill University Health Centre, Glen site, Montreal, QC, Canada, 5 Ottawa Hospital Research Institute, Ottawa, OT, Canada Background: The mechanistic target of rapamycin (mTOR) promotes HIV transcription. In line, we demonstrated that HIV preferentially targets gut- homing CCR6+Th17 cells for replication/persistence via mTOR-dependent mechanisms. Thus, mTOR inhibitors may limit residual HIV transcription during ART and subsequently reduce immune activation/inflammation. Here, we

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