SEATTLE, WASHINGTON

February 13–16, 2017

Conference Dates and Location: 
February 23-26, 2015 | Seattle, Washington
Abstract Number: 
111LB

Biomarkers to Predict Viral Rebound at Antiretroviral Therapy Interruption in SPARTAC

Author(s): 

Jacob Hurst1, James Williams1, John P. Thornhill2, Matthew Pace1, Chris Willberg1, Elizabeth Hamlyn3, Abdel Babiker4, Rodney Phillips1, Sarah Fidler2, John Frater1
1 University of Oxford, Oxford, United Kingdom. 2 St Mary's Hospital–Imperial College Healthcare NHS Trust, London, United Kingdom. 3 King's College London, London, United Kingdom. 4 Medical Research Council Clinical Trials Unit, London, United Kingdom.

Abstract Body: 

Background: Treatment of HIV-1 infection with antiretroviral therapy (ART) in the first few weeks or months following transmission may induce a state of virological remission or ‘post-treatment control' (PTC), in which viraemia remains suppressed when ART is stopped. We present an analysis of 18 immunological and virological biomarkers measured in primary HIV-1 infection (PHI) to determine if they may help predict PTC after treatment interruption (TI).

Methods: We retrospectively analysed a sub-group of samples from SPARTAC - a randomised controlled study of PHI incorporating a TI after 48 weeks of ART. We measured HIV-1 specific CD4 and CD8 T cell ELISpot responses, markers of T cell activation (HLA DR, CD38, CD25, CD69) and exhaustion (Tim-3, Lag-3, PD-1, TIGIT), soluble markers (Il-6, d-dimer), HIV-1 DNA (Total and Integrated), cell-associated unspliced RNA, CD4 count, plasma viral load and the CD4/CD8 ratio. Statistical analyses explored associations between biomarkers and Total HIV-1 DNA and time to viral rebound at TI, with measurements taken, where samples permitted, pre-therapy in all participants and at 48 weeks in those undertaking TI.

Results: We analysed 154 individuals prior to starting ART, a median of 73.8 days from the estimated date of seroconversion. 47 participants undertook a TI after 48 weeks of ART. In univariable regression models undertaken with samples from pre-therapy baseline, CD4/CD8 ratio, CD4 count, plasma viral load, CD8 CD38, CD8 PD-1, CD8 HLA DR, CD4 HLA DR, CD8 Lag-3 and d-dimer were significantly associated (all P<0.05) with HIV-1 DNA levels, but only CD4 count, viral load, CD8 CD38, CD8 Lag-3 and d-dimer survived in multivariable analyses.

When measured pre-therapy, and adjusting for levels of HIV-1 DNA, T cell exhaustion marker expression on CD4 (PD-1, Tim-3 and Lag-3) and CD8 (Tim-3 only) T cells predicted time to the return of viraemia (n=20; Table 1), but notably not when measured at TI. Apart from Total HIV-1 DNA, in this sub-group analysis we found no evidence for any other biomarkers associating with rebound when measured at baseline or at TI.

Conclusions: In the search for an algorithm of biomarkers to help stratify treated PHI patients according to likelihood of PTC, these data indicate that pre-therapy measurements may be informative and that markers of T cell exhaustion should be included alongside HIV-1 DNA levels. This may also open critical new avenues for understanding the mechanisms underlying PTC, which need to be explored in larger cohorts.

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Session Number: 
O-9
Session Title: 
New Insights Into HIV Persistence, Latency Reversal, and Viremia Rebound
Presenting Author: 
Frater, John
Presenter Institution: 
University of Oxford
Poster: 
Poster to be submitted.