Risk of HIV-1 low level viremia to treatment failure in the - PowerPoint PPT Presentation

Risk of HIV-1 low level viremia to treatment failure in the AREVIR-RESINA cohort in Germany Nadine Lübke Düsseldorf AREVIR Meeting 2017

FDA Approval of antiretroviral drugs 1980-84 1985-89 1990-94 1995-99 2000-04 2005-09 2010-14 2015-16 1981 1987 1991 1995 2000 2005 2011 2015 First reported Zidovidine Didanosine Lamivudine Didanosine Tipranavir Eviplera Evotaz AIDS cases Saquinavir Trizivir Nevirapine XR Genvoya Kaletra Rilpivirine Prezcobix 1992 1996 2001 2006 2012 2016 Zalcitabine Indinavir Tenofovir Atripla Stribild Descovy Ritonavir Darunavir Odefsey Nevirapine 1994 1997 2003 2007 2013 Stavidine Combivir Emtricitabine Raltegravir Dolutegravir Delavirdine Atazanavir Maraviroc Nelfinavir Fosamprenavir Enfuvirtide 1998 2004 2008 2014 Abacavir Kivexa Etravirine Triumeq Efavirenz Truvada Elvitegravir Cobicistat 1999 2014 Amprenavir Triumeq Elvitegravir Cobicistat NRTI: Nucleoside Reverse Transcriptase Inhibitor; NNRTI: Non-Nucleoside Reverse Transcriptase Inhibitor; PI: Protease Inhibitor; INI: Integrase Inhibitor; EI: Enty Inhibitors; FDC: Fixed-Dose Combination 2 AREVIR Meeting 2017

Antiretroviral Therapy (ART) NNRTI Regimen PI Regimen INI Regimen NRTI NRTI NRTI + + NNRTI + PI INI NRTI NRTI NRTI AIM: Viral suppresion below the limit of detection NRTI – nucleoside reverse transcriptase inhibitor NNRT – non- nucleoside reverse transcriptase inhibitor PI – protease inhibitor INI – integrase inhibitor 3 AREVIR Meeting 2017

Low Level Viremia and Virological failure  2013: Persistent LLV between 50 and 999 cop/ml associated with increased risk of VF  2016: HIV-RNA >200 cop/ml was strongest predictor of VF  HIV-1 low level viremia (LLV) is predictive for virological failure (VF) 4 AREVIR Meeting 2017

Objectives Analysis of the association of LLV and virological failure to ART. 5 AREVIR Meeting 2017

Definitions  therapeutic success: reduction of the HIV-1 viral load (VL) below 50 copies/ml (German-Austrian guidelines for the treatment of HIV infection)  Low level viremia (LLV): repeated VL measurements between 50 and 200 copies/ml after initial therapeutic success  Virological failure (VF): confirmed viral load greater than 200 copies/ml following therapeutic success 6 AREVIR Meeting 2017

Material & Methods  AREVIR/RESINA database :  clinical and virological data of therapy-naïve (TN) and therapy-experienced (TE) HIV-1-infected patients in North Rhine-Westphalia, Germany  Query of the database:  therapies with VL measurements at least once every 24 weeks  patients who attained confirmed therapeutic success under ART and experienced confirmed LLV thereafter  2,485 first line and 3657 further-line therapies (6142 total) 7 AREVIR Meeting 2017

Frequency of Low Level Viremia  LLV occurred in 294/6142 documented therapies (4.8%)  Mean time to LLV: 27 months ( σ =20.7)  LLV rate increased in TE patients versus TN patients 8 AREVIR Meeting 2017

Virological failures subsequent to LLV  VF occurred in 56/294 (19%) cases subsequent to LLV  Median viral load at failure: 472 copies/ml (range 203-116590 cop/ml)  Mean LLV episode: 77.4 weeks ( σ =68.0)  VF rate increased in TE patients versus TN patients 9 AREVIR Meeting 2017

Risk of LLV and VF according to drug approval  Risk of LLV and subsequent virological failure is significantly increased with drugs approved ≤ 2004 10 AREVIR Meeting 2017

Risk of LLV and VF according to drug class  Most risk of LLV with PI regimens : 165/294 (56.1%) and NNRTI regimens : 76/294 (25.9%)  Comparable VF rates of NRTI-, NNRTI- and PI-based therapies (Ø=20%, range 17.1-22.2%) 11 AREVIR Meeting 2017

Risk of LLV and VF according to the drug * Approved ≤ 2004  VF after LLV was never related to integrase or entry inhibitors  Low risk of VF subsequent to LLV with drugs approved ≥ 2005 (p<0.001) 12 AREVIR Meeting 2017

Summary and Conclusion  low prevalence of LLV in patients on suppressive ART (4.8%)  VF subsequent to LLV observed in 19% of the cases  LLV and subsequent VF increased in therapy-experienced patients  Strongest predictor for VF subsequent to LLV was a treatment regimen containing drugs approved before 2005  Episodes of LLV in patients treated with drugs with high potency and a high barrier to resistance are not predictive for VF 13 AREVIR Meeting 2017

Thanks to… Institute of Virology, University of Cologne Institute of Virology, University of Düsseldorf Jörg Timm Rolf Kaiser Elena Knops Andreas Walker Jennifer Camdereli Veronica Di Cristanziano Iris Hermann Maria Neumann-Fraune Wiebke Moskorz Eugen Schülter Claudia Müller Robin Folgnandt Saleta Sierra-Aragon Eva Heger AREVIR- and RESINA-partners… Alejandro Pironti , Thomas Lengauer, MPI of Informatics, Saarbrücken Mark Oette, Dept. Gastroenterologie, Augustinerinnen Hospital, Cologne Stefan Esser, Dept. Dermatology, University Hospital Essen Björn Jensen, Dept. Gastroenterology, Hepatology and Infectious Diseases, UKD Norbert Bannert, Barbara Bartmeyer, Osama Hamouda, Klaus Jansen, Claudia Kücherer, Robert Koch Institut (RKI), Berlin Funding by MASTER-HIV/HEP (RKI) 14 AREVIR Meeting 2017

Questions? 15 AREVIR Meeting 2017