8th IAS Conference on HIV Pathogenesis, Treatment & Prevention 19â 22 July 2015, Vancouver, Canada

Abstract

IntroductionEarly initiation of longâ term antiretroviral therapy (ART) may lead to viral control after treatment discontinuation. Recent evidence indicates that ART initiated within seroconversion limits the HIVâ 1 reservoir size. Insight into the reservoir in patients with different timings of ART as well as those who can control HIVâ 1 without therapy should further inform new treatment strategies.MethodsA crossâ sectional study of HIVâ 1 reservoir size (total and integrated HIVâ 1 DNA) and dynamics (2â LTR circles and cellâ associated HIVâ 1 unspliced RNA (usRNA)) was performed in peripheral blood mononuclear cells (PBMCs) in 84 HIVâ 1 infected patients from four cohorts in two clinical centres (London, UK and Ghent, BE): longâ term treated patients with ART initiated during seroconversion (SRCV on ART; n=25) or chronic infection (Chronic ART; n=32), longâ term nonâ progressors (LTNP; n=17) and ARTâ naïve recent seroconverters (Recent SRCV; n=10). Total HIVâ 1 DNA, 2â LTR and usRNA were measured by ddPCR and integrated HIVâ 1 DNA by Aluâ HIV PCR. Clinical parameters including time on ART and aviremia, CD4 count and CD4/CD8 ratio were collected.ResultsMedian total HIVâ 1 DNA copies were: 92, 48, 137 and 1901 c/106 PBMCs in SRCV on ART, LTNP, Chronic ART and Recent SRCV, respectively. Significantly lower levels of total (p=0.041) and integrated HIVâ 1 DNA (p=0.003) were detected in early as compared to chronically treated patients, however these were higher than those found in LTNP (Figure 1a and 1b). Interestingly, similar levels of integrated HIVâ 1 DNA were found in Recent SRCV compared to the Chronic ART cohort (p=0.104), confirming very fast seeding of the reservoir (Figure 1b). Levels of usRNA were significantly lower in early compared to chronically treated cohort (p=0.007), indicating a lower transcriptional activity in early treated patients and similar to LTNP (p=0.615). Furthermore, early treated patients exhibited a higher CD4/CD8 ratio as compared to chronically treated patients (p=0.009), suggesting lower levels of residual immune activation.ConclusionsOur data demonstrate that longâ term early treated patients have smaller reservoir size as compared to patients treated during chronic infection, however not reaching levels found in LTNP. Interestingly, the reservoir dynamics in terms of 2â LTR and usRNA as well as the CD4/CD8 ratio in early treated patients are comparable to LTNP.Abstract WEAB0101â Figure 1. Total HIVâ 1 DNA (a) and integrated HIVâ 1 DNA (b) levels in four patient cohorts. Data is shown as log10 copies/million (c/M) PBMC and significant pâ values are indicated by *. Differences between the cohorts were determined by Wilcoxon Signed Rank test.10.7448/IAS.18.5.20398© 2015 Malatinkova E et al; licensee International AIDS SocietyPublished 22 July 2015Presenting author email: eva.malatinkova@ugent.be