CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

335 Enhanced Immune ReconstitutionWith Initiation of ART at HIV-1 Seroconversion (PHI) Sabine I. Kinloch 1 ; Colette Smith 1 ; KwongTsz-Shan 2 ; Jayne Ellis 2 ; Margaret Johnson 2 1 University College London, London, United Kingdom; 2 Royal Free London NHS Foundation Trust, London, United Kingdom Background: Early ART initiation has been shown recently to delay the time to AIDS, strengthening the case for early intervention. It is unclear whether immune reconstitution in particular, CD4/CD8 ratio, is enhanced with intervention at Primary HIV Infection (PHI). Methods: We undertook a retrospective study of a PHI cohort (ART initiation <3 months from PHI) from a single center (Royal Free Hospital, London, UK) who had received >5 years of continuous ART. The group were compared to a cohort of individuals who started ART at the same center during chronic infection (CI; ≥ 1 year after diagnosis) with a pre-ART CD4 count>350 cells/mm 3 and who also received >5 years(y) of continuous ART. Median CD4 count, CD4%, CD4/CD8 ratio and presence of optimal immune reconstitution (OIR) (CD4 ≥ 800 cells/mm 3 or CD4% ≥ 40% or CD4/CD8 ratio ≥ 1) were assessed and compared in the 2 cohorts at 1, 5 and 10y post-ART initiation by considering the measure that occurred closest to the time-point, provided it was <6 months. Time to normalization of CD4/CD8 ratio to ≥ 1 was also assessed using Kaplan-Meier methods. Results: 37 PHI and 115 CI individuals were included. Median age at time of HIV diagnosis was 34 vs 32 years in the PHI and CI cohorts, respectively. 35 (95%) vs 32 (87%) were male and 32 (87%) vs 84 (73%) were MSM. Median pre-ART nadir CD4 count, CD4% and CD4/CD8 ratios were: 417 vs 313 cells/mm 3 ; 18% vs 16%, and 0.30 vs 0.29, respectively. Median maximum pre-ART VL were 511,000 (range 3,400, >1.000,000 vs 278,022 (2593, >750,000) copies/mL, respectively. After 1, 5 and 10 y of ART, median CD4 count, CD4% and CD4/CD8 ratio were significantly higher in the PHI compared to the CI group across all time-points (Table). Similarly, OIR was more common in the PHI group at all time-points. The kinetics of CD4/CD8 ratio showed that the median time to achieving CD4/CD8 ratio ≥ 1 was 36 (95% CI 16-63) weeks in the PHI cohort and 187 (127-204) weeks in the CI cohort (p<0.0001; log rank test).

Conclusions: Immunological response to ART in this cohort was excellent, with high median CD4 counts after 10 y of ART. Despite this, ART initiation within 3 months of PHI shows improved immune reconstitution in terms of CD4 T cell count and CD4/CD8 ratio, when compared to a CI cohort initiating ART without severe immunosuppression,. These differences persisted even after 10 years of ART, suggesting damage to the immune system during the early stages of HIV infection can have long-term consequences. 336 cART-Driven Recovery of Immune Function Preferentially Targeting CXCR4-Tropic HIV-1 Joëlle Bader 1 ; Martin Däumer 2 ; Jürg Böni 4 ; Meri Gorgievski 3 ;Thomas Klimkait 1 The Swiss HIV Cohort Study 1 University of Basel, Basel, Switzerland; 2 Institute for Immunogenetics, Kaiserslautern, Germany; 3 University of Berne, Berne, Switzerland; 4 Swiss National Center for Retroviruses, Zürich, Switzerland Background: It has been shown that CXCR4-tropic HIV is better neutralized by the immune system than CCR5-tropic variants. Reasons therefore might be the less glycosylated envelope on CXCR4-tropic viruses and the antibody binding due to less steric hindrance. We hypothesize that CXCR4-tropic variants should be better eliminated by a competent immune system generated through efficient cART. Aim of this study was to monitor the frequency of CXCR4-tropic viruses through restoration of the immune system by cART. Methods: Seventeen patients in the Swiss HIV Cohort Study were followed yearly after virological suppression by tropism testing. All patients were fully suppressed throughout study time and showed good CD4 T cell restoration (>250 cell/mm 3 in 3 years) after cART initiation. For eight we included also three consecutive time points before cART. Frequency of CXCR4-tropic variants was analyzed by Illumina Miseq sequencing (FPR 3.5%, R5 < 2% X4). Results: Ten patients (59%) had only CCR5-tropic viruses after cART initiation, which stayed CCR5-tropic during follow-up. Of the seven remaining patients with CXCR4-tropic HIV, four (57%) showed decreasing frequencies of CXCR4-tropic variants during therapy. For 15 of the 17 patients we could perform proviral load testing on all time points, four (27%) showed increased proviral loads under therapy. Interestingly, all patients with increasing CXCR4-tropic frequencies had also increasing proviral loads. For four of the seven patients with CXCR4-tropism after therapy we could include tropism data before cART initiation, which showed that all of them had increasing frequencies of CXCR4-tropic viruses with time and without therapy. Two patients of them had even an R5 tropism three years before cART initiation. Conclusions: We identified a decrease in the frequency of CXCR4-tropic HIV variants under successful cART in the majority of patients in our study. An increase under therapy strictly correlated with increasing proviral loads. We suggest that CXCR4-tropic variants can be better eliminated by the recovering immune system under cART and similarly in early stages of the infection, when immune surveillance is still largely intact. On contrast, weakening of the immune system leads to an increase in CXCR4-tropic viruses. Therefore early therapy initiation and maintaining of an effective immune state might help to better control CXCR4-tropic HIV variants. 337 Repeated injections of r-hIL-7 in HIV Patients receiving ART in INSPIRE 2 & 3 trials Rodolphe Thiebaut 1 ; Ana Jarne 1 ; Jean-Pierre Routy 2 ; Irini Sereti 3 ; Margaret A. Fischl 4 ; Prudence Ive 5 ; Roberto Speck 6 ; GiuseppeTambussi 7 ;Yves Lévy 8 ; Michael M Lederman 9 on behalf of Inspire 2 and Inspire 3 study groups 1 Bordeaux University, Bordeaux, France; 2 McGill University, Montreal, Canada; 3 National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, US; 4 University of Miami, Miami, FL, US; 5 Wits Health consortium, Johannesburg, South Africa; 6 University Hospital Zurich, Zurich, Switzerland; 7 San Raffaele Scientific Institute, Milano, Italy; 8 INSERM, Paris, France; 9 Case Western Reserve University, Cleveland, OH, US Background: Phase I/II studies in HIV-infected patients receiving ART have shown that administration of 3 weekly subcutaneous (s/c) injections of Recombinant Human Interleukin 7 (r-hIL-7) is safe and increase numbers of both naive and memory CD4 and CD8 T cells. Here, we report the pooled data from two phase II trials evaluating the effect of repeated cycles of r-hIL-7 with the objective of restoring and maintaining CD4 T cell count over 500 cells/ m L.

Poster Abstracts

263

CROI 2015