CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: Our results suggest that comprehensive Ab profiling coupled with systems analyses, can accurately define humoral immune profiles that track with distinct clinical outcomes following acute HIV infection. Specifically, the maintenance of gp120-specific and gp140-specific IgG3 may contribute to control of disease in spontaneous controllers. Thus, strategies to induce stable IgG3 responses may preserve control of the viral reservoir. Further analyses of fine epitope specificities on the viral envelope of IgG3 and IgG2 Abs during acute infection, along with additional effector functional measurements, may shed light on specific targets and mechanisms of antiviral control.

Conclusion: One year of ART reduced T cell activation and markers of immune exhaustion in HIV controllers, in some cases with further decreases after two years of ART. ART was well tolerated and did not adversely affect controller status when discontinued. These results provide additional support for ART in HIV controllers. 230 EFFICIENT ANTIBODY PROFILE IN HLA-B*57+ HIV CONTROLLERS Jéromine Klingler 1 , Angeline Rouers 2 , Géraldine Laumond 1 , Sylvie Schmidt 1 , Camille Ducloy 1 , Luzia Mayr 1 , Thomas Decoville 1 , Nathalie Salomé 1 , Assia Samri 2 , Veronique Avettand-Fenoel 3 , Faroudy Boufassa 4 , Christine Rouzioux 3 , Olivier Lambotte 4 , Arnaud Moris 2 , Christiane Moog 1 1 INSERM, Strasbourg, France, 2 INSERM, Paris, France, 3 AP–HP, Paris, France, 4 INSERM, Le Kremlin-Bicetre, France Background: Current HIV vaccination strategies strive to induce anti-HIV antibodies (Abs), several types of which are of interest. Among them, neutralizing Abs (NAbs) are able to protect macaques against experimental infection but are difficult to induce by vaccination. HIV Controllers (HIC; undetectable viral load without treatment) constitute an interesting cohort for the analysis of their Ab profile. Indeed, IgG1s and IgG3s polyfunctional activities and anti-gp41 IgG2s induction were associated with HIV control and slower disease progression. Recently, the frequency of HIV-Env-specific memory B cells has been correlated with the neutralization breadth in HIC patients positive for the HLA-B*57 protective allele. These data suggest that a specific Ab profile might have been induced in HIC patients, participating in the control of HIV. Methods: Our study aims to characterize the isotypes and functional responses of Abs induced in sera of 37 HIC (separated in 2 groups: HLA-B*57+ or HLA-B*57-), comparing to 21 chronic progressors (evolving to disease). We analyzed the distribution of isotypes in the different cohorts by ELISA and the neutralization activities by TZM-bl neutralization assays. The correlation between the detection of anti-HIV Abs and functional activities was analyzed by a Spearman rank correlation. Results: We found no differences in the induction of anti-HIV IgAs between HIC and chronic progressors, whilst chronic progressors induce more anti-HIV IgGs and anti-HIV-IgG2s than HIC. On the contrary, HIC patients induce higher proportions of anti-HIV IgG3s. Noteworthy, HIC patients display neutralizing activities against several HIV strains including transmitted/founder viruses, despite the presence of low antigen detection. Remarkably, these neutralizing activities positively correlate with IgG subtypes detection in the subgroup of HLA-B*57+ HIC, but not in HLA-B*57- HIC or chronic progressors. Conclusion: These results demonstrate that HIC patients display an unexpected Ab isotype profile. The detection of anti-HIV Abs is associated with neutralizing activity in HLA B*57+ HIC, suggesting that neutralization may contribute to HIV control in this subgroup of patients. Conversely, the absence of correlation between Ab profile and neutralization in HLA B*57- HIC further suggest that additional Ab functions may be involved. An in-depth characterization of the Ab profile will guide the design of new immunogens for a future vaccine. 231 THE CHAMP COHORT: POST-TREATMENT CONTROLLERS IDENTIFIED FROM 9 CLINICAL STUDIES Golnaz Namazi 1 , Jesse Fajnzylber 1 , Evgenia Aga 2 , Ronald Bosch 2 , Edward P. Acosta 3 , Jeffrey Jacobson 4 , Paul Volberding 5 , Daniel Skiest 6 , Ronald T. Mitsuyasu 7 , Robert T. Schooley 8 , Ann Collier 9 , Jean-Pierre Routy 10 , Bruce D. Walker 11 , Jonathan Z. Li 1 1 Brigham and Women’s Hospital, Boston, MA, USA, 2 Harvard University, Cambridge, MA, USA, 3 University of Alabama at Birmingham, Birmingham, AL, USA, 4 Temple University, Philadelphia, PA, USA, 5 University of California San Francisco, San Francisco, CA, USA, 6 Tufts University, Boston, MA, USA, 7 University of California Los Angeles, Los Angeles, CA, USA, 8 University of California San Diego, La Jolla, CA, USA, 9 University of Washington, Seattle, WA, USA, 10 McGill University, Montreal, QC, Canada, 11 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA Background: HIV post-treatment controllers (PTCs) are rare individuals who exhibit sustained HIV remission after treatment interruption (TI). A concerted international effort is needed to identify PTCs given their scarcity at any given research center or clinical trial. We describe PTCs identified from 9 clinical trials and cohorts as part of the Control of HIV after Antiretroviral Medication Pause (CHAMP) cohort. Understanding the incidence of PTC and their post-TI viral dynamics may provide mechanistic insights and has implications for the design of trials aimed at achieving HIV remission.

Poster Abstracts

229 ART REDUCES T CELL ACTIVATION AND IMMUNE EXHAUSTION MARKERS IN HIV CONTROLLERS Jonathan Z. Li 1 , Florencia P. Segal 1 , Ronald Bosch 2 , Christina Lalama 2 , Randall Tressler 3 , Cornelius N. Van Dam 4 , Michael Keefer 5 , Mary Carrington 6 , Mathias Lichterfeld 1 , Daniel R. Kuritzkes 1 , Xu G. Yu 7 , Alan Landay 8 , Paul E. Sax 1 1 Brigham and Women’s Hospital, Boston, MA, USA, 2 Harvard University, Boston, MA, USA, 3 NIAID, Bethesda, MD, USA, 4 University of North Carolina Greensboro, Greensboro, NC, USA, 5 University of Rochester, Rochester, NY, USA, 6 NIH, Frederick, MD, USA, 7 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA, 8 Rush University Medical Center, Chicago, IL, USA Background: Despite low or undetectable plasma HIV RNA, many HIV controllers (HCs) have detectable viral replication and elevated systemic inflammation. We assessed the effect of ART on HIV suppression, viral reservoir, immune activation, markers of inflammation, and quality of life in HCs. Methods: A5308 is a prospective, open-label study of RPV/FTC/TDF in ART- naive HCs with viral loads (VLs) <500 cp/mL for ≥12 months. After 48 weeks of ART, HCs had the option to be followed for an additional 48 weeks with optional ART. The primary outcome was the change in %CD38+HLA-DR+ CD8+ T cells after 24-48 weeks of ART. Outcomes were evaluated by repeated measures GEE models. Immune phenotyping was performed by flow cytometry. Soluble inflammatory markers were measured by ELISA. Residual viremia (RV) was measured by the integrase single-copy assay (iSCA); reservoir size by levels of total HIV DNA in CD4+ cells. Quality of life (QoL) was measured by the EQ-5D questionnaire. Results: Thirty-five HCs completed ≥24 weeks of ART and were analyzed. Before ART, HCs with undetectable VL by the iSCA had higher CD4+ counts than those with detectable VL (median 1128 vs. 659 cells/mm 3 , P=0.03) and lower levels of both CD8+ (median 19.4% vs. 26.5%, P=0.04) and CD4+ cell activation (2.3% vs. 2.9%, P=0.04). RPV/FTC/TDF was well tolerated, resulting in a modest, but significant improvement in self-reported QoL; two-thirds of HCs elected to continue ART through 96 weeks. ART was effective in further reducing RV: 81% of HCs had detectable RV pre-ART vs. 6% after 24-48 weeks of ART (P<0.001). ART use resulted in a significant decline in the %CD38+HLA-DR+CD8+ cells at 24-48 (-4.0%, P=0.001) and 72-96 (-7.2%, P<0.001) weeks after ART initiation. After ART initiation, several markers of immune exhaustion (%PD1+, %TIGIT+, %CD160+ on CD8+ cells and %CD160 on CD4+ cells) declined. ART use decreased IP-10 levels, but increased levels of sCD163. There were no significant changes in the CD4+ counts or levels of total HIV DNA. Four HCs discontinued ART with ≥10 weeks of subsequent follow-up. All 4 HCs maintained VL<40 copies/mL at the last study time point, a median of 26 weeks after stopping ART.

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CROI 2018