CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

ETR, DRV/r and DTG was 92.1%, 82%, 98.6% and 95.7%, respectively. Number of AD was ≥3 in 85.6% of viremic subjects, while last ART regimen had a GSS ≥3 in 68.2% and a GSS=2 in 24%. The proportion of subjects with limited TO was 4.33% (n=9) of viremic subjects and 0.17% of the total study population. Among these 9 subjects, all had an AIDS history, with mean nadir CD4 of 53/ mm 3 , and 5/9 zenith HIV RNA >6 log 10 c/mL. If we extrapolate our results to all patients under care in France (2016 estimation: 112,877; 95% CI: 111,635- 114,053), we would obtain an estimate of 192 (95% CI: 190-194) HIV infected adults with limited TO. Conclusion: Few individuals on ART ≥6 months had persistent viremia; they very rarely harbored multi-resistant viruses for which it is not possible to construct a suppressive ARV regimen. In this context of poor adherence-related viremia without great loss of TO, interventions to improve compliance, rather than new ARV classes, are needed.

individual level and define factors predicting accumulation of resistance over time.

524 PRO 140 IN VITRO ACTIVITY IN HTE SUBJECTS WITH A 4-CLASS DRUG- RESISTANT HIV-1 VIRUS Stefano Rusconi 1 , Francesco Saladini 2 , Silvia Barbaliscia 3 , Andrea Poli 4 , Laura Galli 4 , Roberta Gagliardini 5 , Lidia Gazzola 6 , Daniela Francisci 7 , Francesca Vichi 8 , Emanuele Focà 9 , Maurizio Zazzi 2 , Maria M. Santoro 3 , Arianna Gabrieli 1 , Antonella Castagna 4 , for the PRESTIGIO Registry Study Group 1 University of Milan, Milan, Italy, 2 University of Siena, Siena, Italy, 3 University of Rome Tor Vergata, Rome, Italy, 4 San Raffaele Vita-Salute University, Milan, Italy, 5 Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, 6 Azienda Ospedaliera San Paolo, Milan, Italy, 7 University of Perugia, Perugia, Italy, 8 Santa Maria Annunziata Hospital, Florence, Italy, 9 University of Brescia, Brescia, Italy Background: PRO 140 is a novel humanized form of a mouse immunoglobulin G4 CCR5-directed monoclonal antibody with nanomolar potency in inhibiting HIV-1 cell entry through the CCR5 coreceptor. The aim of this study was to analyze HIV-1 tropism and in vitro susceptibility to PRO 140 according to MVC exposure in a cohort of heavily treatment-experienced (HTE) HIV-1-infected patients (pts) harboring a documented 4-class drug-resistance to NRTIs, NNRTIs, PIs, InSTIs, enrolled in the Italian PRESTIGIO Registry. Methods: Plasma RNA (viremic pts) or PBMC DNA (non-viremic pts) was used for Sanger sequencing and Next Generation Sequencing (NGS, Illumina platform) of the gp120-V3 region followed by geno2pheno [coreceptor] interpretation. Viral tropism and susceptibility to PRO 140 were assessed through a home-made phenotypic assay based on pseudotyped viruses expressing patient derived Env protein and luciferase as reporter gene. Pts demographics and laboratory data are described as median (Q1-Q3), mean (±SD) or frequency (%). Results: Among 25 pts, 20 (80%) were male, median age 50 years (44-53), time since HIV-1 diagnosis 23 years (19-26), time on ART 20 years (16-23), 14 (56%) with a previous AIDS diagnosis, 17 (68%) with maraviroc (MVC) exposure, a median CD4+ count 207 cells/µl (73-326) and a median viral load 4.58 log 10 copies/mL (4.02-5.11), with 2 pts with HIV-RNA<40 copies/mL. CCR5-tropic virus was observed in 36%, 43%, 36% accordingly to Sanger, NGS and the phenotypic assay; the overall concordance among the three methods was 65% while pairwise agreement ranged from 76% (NGS vs phenotypic assay) to 86% (Sanger vs phenotypic assay). All 9 viruses with CCR5-tropic phenotype were susceptible in vitro to PRO 140, with median IC 50 0.4 (0.3-0.7) nM, comparable to the IC 50 of the reference wild-type CCR5-tropic AD8 virus (mean IC 50 0.7±0.4 nM). There was a variation between MVC-naïve (n=3; median IC 50 =0.70, IQR=0.50- 1.2 nM) and MVC-exposed (n=6; median IC 50 =0.35, IQR=0.30-0.40 nM) pts (p=0.087 [Wilcoxon rank-sum test]) (Table 1). Current exposure to MVC was not associated with different PRO 140 activity (p=0.376). Conclusion: In this group of HTE pts with MDR virus, all CCR5-tropic strains were fully susceptible to PRO 140 and they were not significantly impacted by MVC exposure. PRO 140 can thus play a key role in subjects with very limited therapeutic options and CCR5-tropic virus.

Poster Abstracts

523 FOUR-CLASS RESISTANCE IS RARE IN TREATMENT-EXPERIENCED PATIENTS ACROSS EUROPE Jurgen Vercauteren 1 , Anne-Mieke Vandamme 2 , Barbara Rossetti 3 , Massimiliano Fabbiani 3 , Francesca Incardona 4 , Kristof Theys 2 , Ana Abecasis 5 , Carole Devaux 6 , Rolf Kaiser 7 , Anders Sönnerborg 8 , Maurizio Zazzi 9 , for the EuResist Network Study Group 1 Rega Institute for Medical Research, Leuven, Belgium, 2 Katholieke University Leuven, Leuven, Belgium, 3 Siena University Hospital, Siena, Italy, 4 EuResist Network, Rome, Italy, 5 Instituto de Higiene e Medicina Tropical Universidade NOVA de Lisboa, Lisboa, Portugal, 6 Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg, 7 University of Cologne, Cologne, Germany, 8 Karolinska Institute, Stockholm, Sweden, 9 University of Siena, Siena, Italy Background: While most HIV-1 patients starting antiretroviral therapy (ART) in recent years achieve and maintain undetectable viral load, patients with a long ART history and failure of multiple therapy lines may have accumulated substantial drug resistance, challenging the possibility for virus control both at individual and population level. However, the prevalence of patients harboring virus with resistance to the four main drug classes (4CR) is largely unknown. Methods: From the EuResist database, we selected treated patients with protease, reverse transcriptase and integrase genotype information available at one or more time points. HIV-1 sequences were interpreted by the Stanford HIVdb 8.8 algorithm and cumulative scores were generated at each sequencing time point. 4CR was defined as high-level resistance to at least one drug in each of the four classes. The frequency of 4CR at each calendar year was estimated as the number of unique patients with 4CR divided by the number of unique patients with at least one sample, up to that year. Results: Complete four classes HIV-1 genotype information was available from 2643 distinct patients on ART contributing 3544 genotype data from Italy (49.9%), Germany (24.7%), Portugal (8.1%), Luxembourg (7.5%), Sweden (7.0%) and Belgium (2.7%). 66%were male and risk groups included 45.3%MSM, 18.6% drug users and 18.3% heterosexuals. Subtype B virus was harbored by 70.1% of patients and the most prevalent non-B subtypes were G (14.0%) and A1 (7.5%). Overall, 65 patients (2.5%) had 4CR. The prevalence of 4CR declined from 5.6% [95%CI: 1.6-13.8] in 2008 to 2.4% [95%CI: 1.8-3.1] in 2018 (P <0.001, chi-square test for trend; see figure). Patients with 4CR were older (49+/-12 vs. 46+/-11, P = 0.001) and harbored more often subtype B virus (85.3% vs. 69.7%, P = 0.013) with respect to patients without 4CR. No association was demonstrated between 4CR and gender or risk groups. Conclusion: In a large population of patients across Europe with complete HIV-1 genotype information, the prevalence of 4CR appears to be relatively low and possibly declining over recent years. Continuous surveillance of this challenging population is warranted to provide effective treatment at the

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