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

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

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Risk of HIV-1 low level viremia to treatment failure in the AREVIR-RESINA cohort in Germany Nadine Lbke Dsseldorf 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

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AREVIR Meeting 2017

Risk of HIV-1 low level viremia to treatment failure in the AREVIR-RESINA cohort in Germany

Nadine Lübke Düsseldorf

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FDA Approval of antiretroviral drugs

NRTI: Nucleoside Reverse Transcriptase Inhibitor; NNRTI: Non-Nucleoside Reverse Transcriptase Inhibitor; PI: Protease Inhibitor; INI: Integrase Inhibitor; EI: Enty Inhibitors; FDC: Fixed-Dose Combination

1980-84 1985-89 1990-94 1995-99 2000-04 2005-09 2010-14 2015-16 1981 First reported AIDS cases 1987 Zidovidine 1991 Didanosine 1995 Lamivudine Saquinavir 2000 Didanosine Trizivir Kaletra 2005 Tipranavir 2011 Eviplera Nevirapine XR Rilpivirine 2015 Evotaz Genvoya Prezcobix 1992 Zalcitabine 1996 Indinavir Ritonavir Nevirapine 2001 Tenofovir 2006 Atripla Darunavir 2012 Stribild 2016 Descovy Odefsey 1994 Stavidine 1997 Combivir Delavirdine Nelfinavir 2003 Emtricitabine Atazanavir Fosamprenavir Enfuvirtide 2007 Raltegravir Maraviroc 2013 Dolutegravir 1998 Abacavir Efavirenz 2004 Kivexa Truvada 2008 Etravirine 2014 Triumeq Elvitegravir Cobicistat 1999 Amprenavir 2014 Triumeq Elvitegravir Cobicistat 2

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Antiretroviral Therapy (ART)

NNRTI Regimen PI Regimen INI Regimen

NRTI NRTI NRTI NRTI NRTI NRTI + + + NNRTI PI INI NRTI – nucleoside reverse transcriptase inhibitor NNRT – non- nucleoside reverse transcriptase inhibitor PI – protease inhibitor INI – integrase inhibitor

AIM: Viral suppresion below the limit of detection

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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)

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Objectives

Analysis of the association of LLV and virological failure to ART.

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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

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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)

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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

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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

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Risk of LLV and VF according to drug approval

  • Risk of LLV and subsequent virological failure is

significantly increased with drugs approved ≤ 2004

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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%)

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Risk of LLV and VF according to the drug

  • 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)

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* Approved ≤ 2004

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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

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Thanks to…

Institute of Virology, University of Cologne Rolf Kaiser Elena Knops Veronica Di Cristanziano Maria Neumann-Fraune Eugen Schülter Claudia Müller Saleta Sierra-Aragon Eva Heger Institute of Virology, University of Düsseldorf Jörg Timm Andreas Walker Jennifer Camdereli Iris Hermann Wiebke Moskorz Robin Folgnandt 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

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Funding by MASTER-HIV/HEP (RKI)

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Questions?

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