CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

528 DECLINE IN CLINICALLY RELEVANT RESISTANCE TO FIRST-LINE ARV REGIMENS IN SPAIN Marta Alvarez 1 , José Ángel Fernández-Caballero 1 , Ana B. Perez 1 , Nuria Espinosa 2 , Silvia García-Bujalance 3 , Maria Jesus Perez-Elias 4 , Rafael Delgado 5 , José A. Iribarren 6 , Isabel Viciana 7 , David Dalmau 8 , Antonio Aguilera 9 , Mar Masia 10 , Victoria Hernando 11 , Federico García 1 1 Hospital Universitario San Cecilio, Granada, Spain, 2 Hospital Universitario Virgen del Rocio, Sevilla, Spain, 3 La Paz University Hospital, Madrid, Spain, 4 Hospital Ramon y Cajal, Madrid, Spain, 5 Hospital Universitario 12 de Octubre, Madrid, Spain, 6 Hospital Donostia, San Sebastián, Spain, 7 Hospital Virgen de la Victoria, Málaga, Spain, 8 Hospital Universitari Mútua de Terrassa, Terrassa, Spain, 9 Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain, 10 Hospital General Universitario de Elche, Elche, Spain, 11 Institute de Salud Carlos III, Majadahonda, Spain Background: Transmitted drug resistance (TDR) is currently evaluated on single mutations. As initial regimens currently recommended by treatment guidelines include high genetic barrier antiretrovirals (ARVs), evaluating the clinically relevant resistance may be of interest. Here we present data on clinically relevant transmitted drug resistance to ARVs recommended for first line treatment in Spain during the period 2007-2017. Methods: We analysed 5484 RT & Pro Fasta sequences from CoRIS, the HIV ARV naïve cohort of the Spanish AIDS Research Network. As Integrase resistance is not part of routine testing in naïve patients in Spain, we run a surveillance programme (2012-2017) and tested 576 patients with samples available at the RIS Biobank. We evaluated the prevalence of TDR mutations using the WHO list 2009 update (Bennet et al) and the 2017 IAS list (Wensing et al) for Integrase mutations. Clinically relevant TDR was investigated using Stanford v 8.4 Algorithm. As recommended, potential low-level resistance was pooled into the susceptible category. First line regimens for each study period were those recommended by the Spanish treatment guidelines (GESIDA). Results: Overall, TDR mutations using the WHO list was 7.9% (3.6% NRTIs, 3.7% NNRTIs, 2.0% PIs), and 2,7 % INSTIs (IAS list), and no significant change during the study period was observed. Clinically Relevant resistance to recommended 1st line regimens showed a slow decline from 2007-2012, and peaked in 2013-2014 due to the inclusion of Rilpivirine for 1st line in the Spanish recommendations. Detailed results for 2007-2017 are shown in the table below: Conclusion: TDR remained stable in Spain through 2007-2017 when individual mutations were evaluated. However, clinically relevant TDR to approved first line regimens showed a slow decline from 2007 to 2017. Resistance to INSTIs remains at very low levels even in 2017 in Spain. These findings, together with the very low prevalence of resistance to first line NRTIs in 2015-2017 may question the need for baseline resistance prior to starting an INSTI based first line regimen in Spain.

Methods: TDRAMs were sought in plasma samples from 373 patients in 2014, 388 in 2015 and 375 in 2016 (n=1136), from 46 clinical centers. Protease and reverse-transcriptase TDRAMs were identified from the 2009 Stanford Resistance Surveillance list; etravirine, rilpivirine and integrase mutations from the IAS and ANRS lists. Doravirine-associated mutations identified in vitro and defining DOR resistance in this study were: V106A, V106M, V108I, H221Y, F227L, F227C, F227V, M230I, L234I, P236L. The HIV envelope gene was sequenced and tropismwas determined using the Geno2Pheno algorithm (FPR 10%). HIV-1 subtype was determined from the RT sequence. Results: Patients were mainly men (90%), having sex with men (73%), living in the Paris area (41%). At inclusion, the median CD4 cell count and plasma HIV-1 RNA were 480/µL (IQR: 330–637) and 5.5 log 10 cp/mL (IQR: 4.7–6.4), respectively. By the Stanford list, the prevalence of virus with PR or RT RAMs was 10.6% (CI95% [8.92;12.59]). Prevalence of PI and NRTI resistance was 2.8% (CI95% [1.93;3.95]) and 5.1% [3.90;6.55]; prevalence of NNRTI resistance was 4.0% [2.90;5.26] or 10.2% [8.51;12.12] including etravirine and rilpivirine RAMs. INI RAMs were observed in 5.3% of samples [3.96;6.97]: L74M n=9, E92Q/G n=2, T97A n=14, E138K n=3, E157Q n=18, S230R n=2, R263K n=2. The double mutant E92Q+T97A was observed in 1 patient. The overall prevalence of sequences with at least 1 DOR associated mutation was 0.9% [0.42; 1.61]. The frequency of TDRAMs to NRTI, NNRTI, PI and INI was stable over time (Figure). At enrolment, 81/523 (15.5%) of samples harbored a X4/DM tropic virus. In a multivariate analysis, age (>30 years) was the only factor significantly associated with TDRAMs while baseline characteristics such as gender, transmission route, CD4 count, viral load, subtype and year of inclusion were not. The prevalence of non-B subtype increased from 37.1% in 2014 to 50.2% in 2016 (p<0.0027). Conclusion: In France in the 2014/2016 period, the overall prevalence of TDRAMs was 10.6%, similarly to the previous surveys (going back to 1996 for PI and NRTI.) However, we describe a high level of NNRTI resistance (10.2%) including ETR and RPV (only 0.9% of resistance to doravirine) and a high prevalence of INI RAMs.

Poster Abstracts

530 HIV DRUG RESISTANCE AS A SIGNIFICANT DRIVER OF FIRST-LINE TREATMENT FAILURE IN UGANDA

Suzanne McCluskey 1 , Nicholas Musinguzi 2 , Kimia Kamelian 3 , Guinevere Q. Lee 1 , Yap Boum 4 , Bosco M. Bwana 2 , Conrad Muzoora 2 , Jeffrey N. Martin 5 , Peter W. Hunt 5 , Vincent C. Marconi 6 , David R. Bangsberg 7 , Jessica E. Haberer 1 , P. Richard Harrigan 3 , Mark J. Siedner 1 1 Massachusetts General Hospital, Boston, MA, USA, 2 Mbarara University of Science and Technology, Mbarara, Uganda, 3 British Columbia Centre for Excellence in HIV/ AIDS, Vancouver, BC, Canada, 4 Epicentre, Mbarara, Uganda, 5 University of California San Francisco, San Francisco, CA, USA, 6 Emory University, Atlanta, GA, USA, 7 Oregon Health and Sciences University, Portland, OR, USA Background: The World Health Organization recommends a change to second line antiretroviral therapy (ART) after two HIV RNA results >1,000 copies/mL with interval adherence support. We have previously shown that adherence does not predict resuppression following failure with HIV RNA >1,000 copies/ mL. Herein, we seek to evaluate the effect of HIV drug resistance (HIVDR) at first line failure on rates of resuppression. Methods: We analyzed data from the Uganda AIDS Rural Treatment Outcomes study, which followed adults with HIV initiating ART with objective adherence monitoring (2005-2015). Participants underwent quarterly HIV RNA tests

529 HIGH PREVALENCE OF NNRTI AND INI-RESISTANT POLYMORPHIC VIRUS IN PRIMARY HIV INFECTION Marie-Laure Chaix Baudier 1 , Maxime Grudé 2 , Heloise M. Delagreverie 1 , Catherine Roussel 3 , Helene Pere 4 , Helene Le Guillou-Guillemette 5 , Julia Dina 6 , Anne Signori-Schmuck 7 , Marie-Josee Carles 8 , Laurence Morand-Joubert 9 , Jacques Izopet 10 , Laurence Meyer 11 , Lambert Assoumou 2 , Diane Descamps 12 1 Hôpital Saint-Louis, Paris, France, 2 INSERM, Paris, France, 3 CHU de Amiens, Amiens, France, 4 Georges Pompidou European Hospital, Paris, France, 5 CHU de Angers, Angers, France, 6 CHU de Caen, Caen, France, 7 CHU de Grenoble, Grenoble, France, 8 CHU de Nimes, Nimes, France, 9 Saint-Antoine Hospital, Paris, France, 10 Toulouse University Hospital, Toulouse, France, 11 INSERM, Le Kremlin-Bicetre, France, 12 Bichat– Claude Bernard Hospital, Paris, France Background: According to the French ANRS program for HIV-1 resistance surveillance, we estimated the prevalence of transmitted drug resistance associated mutations (TDRAMs) in primary infected patients (PHI) diagnosed in France in 2014-2016.

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