CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

frequencies ranged from 23%-69% for kits using viral lysate (AVQ, SRD), and 23-77% for kit using Env and Gag (GSC, BIO) as AG. Increased HIV seronegative frequencies (62%) pre-ATI was observed with test kits employing HIV Env (gp41) as the detecting AG (ARC, DET). Similar HIV seropositive frequencies following ATI were detected with all tests (85%-92%). Conclusion: HIV serology may remain negative following early ART initiation, particularly in Fiebig I, with frequencies differing by tests. However, the majority of participants who underwent short ATI became HIV seropositive on almost all tests.

344 REEVALUATING SIGNALS OF VIRAL REPLICATION & EVOLUTION IN LYMPHOID TISSUE DURING ART Daniel S. Rosenbloom 1 , Alison L. Hill 2 , Sarah B. Laskey 3 , Robert Siliciano 3 1 Columbia University Medical Center, New York, NY, USA, 2 Harvard University, Cambridge, MA, USA, 3 Johns Hopkins University, Baltimore, MD, USA Background: Mechanisms for long-term HIV persistence despite antiretroviral therapy (ART) continue to be debated. Many studies have offered evidence that ART halts self-sustaining viral replication in most patients and that long-lived resting memory CD4+ T-cells support a stable latent reservoir (LR) of integrated virus. However, Lorenzo-Redondo et al. [Nature, 2016] deep-sequenced lymph node and blood samples from three participants during the first six months of ART, finding viral genetic signals of persistent replication and evolution. We show that these signals are expected outcomes of the known multi-phasic decay of infected cells during ART and do not provide evidence of ongoing replication. Methods: We designed a simulation of HIV infection before and after ART, including changes in viral population size, multiple infected cell types with different lifespans, and mutation/selection within and outside sequenced regions. To test the hypothesis that the observed genetic signals could arise without replication, ART was assumed to block all new infection. To estimate infected cell lifespans, we fit a multi-phase decay model to longitudinal LR measurements from early-treated individuals. Roughly 12,000 simulations were run with a range of plausible parameter values; those with realistic levels of genetic diversity and divergence were included in analyses. To reduce reliance on assumed parameter values, we repeated our analysis using actual sequence data from acute infection to seed a hypothetical LR. Results: At zero, three, and six months following ART initiation, short-lived viral populations comprise >99%, 96%, and 76% of infected resting cells, masking the persistent reservoir. Applying the same population genetic and phylogenetic methods previously used to support claims of ongoing replication in lymphoid tissue, we found that up to 57% of simulations generated a false signal of ongoing replication in all tests. Time-structured phylogenies can also yield a misleading appearance of evolution (Figure). Analysis of acute infection data suggests that individuals with major sequence changes before treatment (CTL escape) produce a false signal of ongoing replication 92% of the time. Conclusion: Investigation of ongoing replication during ART must wait >1 year following the start of ART; earlier analysis is unreliable. Where possible, population genetic studies of viral evolution should be conducted with reference to specific models of viral dynamics and literature on growth/decay of subpopulations.

Poster Abstracts

343 HIV SEROLOGY FOLLOWING TREATMENT INTERRUPTION IN VERY EARLY TREATED PEOPLE Rapee Trichavaroj 1 , Supanit Pattanachaiwit 2 , Sasiwimol Ubolyam 3 , Panadda Sawangsinth 4 , Jintana Intasan 4 , Eugène Kroon 4 , Donn Colby 4 , Robert J. O’Connell 1 , Sandhya Vasan 1 , Praphan Phanuphak 2 , Nittaya Phanuphak 2 , Jintanat Ananworanich 5 , Mark de Souza 4 , Siriwat Akapirat 1 1 Armed Forces Research Institute of Medical Sciences in Bangkok, Bangkok, Thailand, 2 Thai Red Cross AIDS Research Center, Bangkok, Thailand, 3 HIV–NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 4 SEARCH, Bangkok, Thailand, 5 Walter Reed Army Institute of Research, Silver Spring, MD, USA Background: Antiretroviral therapy (ART) initiated during acute HIV infection (AHI) may result in HIV seronegativity. Little is known about the serologic profile following ART treatment interruption (ATI) in such individuals. Knowledge gained could inform recommendations for HIV diagnostic testing following pre- and post-exposure prophylaxis. Methods: Participants initiating ART and virally suppressed during Fiebig (F)-I or F-III stage of AHI were enrolled in two ATI studies and resumed ART with VL > 1000 copies/ml (median duration of ATI was 4.5 weeks). HIV serostatus was determined pre- (median [range]:122.6 wks [5.0-285.1]) and post-ATI; median:5.3 wks [0.4-53.9]), using Avioq HIV Microelisa (AVQ, 2ndG IA), Genscreen HIV-1/2 (GSC, 3rdG IA), Architect HIV Ag/Ab Combo (ARC, 4thG IA), Determine HIV-1/2 (DET, RDT), SD Bioline HIV-1/2 3.0 (BIO, RDT) and Serodia HIV (SRD, RDT), all of which are widely used in Thailand: ARC 35%, DET 62%, BIO 32% and SRD 14% of laboratories (N=264) surveyed. Results: Participants (N=8) initiating ART during F-I AHI were frequently HIV seronegative pre-ATI by AVQ (88%), followed by ARC, BIO, DET (75%), and GSC and SRD (38%). The frequency of seropositivity following ATI varied for participants (75%-88%) depending on the test (Table 1). One participant was HIV seronegative throughout the study by ARC only while another showed non- reactivity to all tests throughout the study. Eighty % of participants initiating ART during F-III AHI (N=5) were HIV seronegative pre-ATI by BIO and 40% by ARC, AVQ and DET. All participants were seropositive pre-ATI by GSC and SRD. All participants were seropositive post ATI for all tests. Pre-ATI HIV seronegative

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