Trends in transmitted drug resistance to HIV-1 in the UK since 2010

Transcription

1 Trends in transmitted drug resistance to HIV-1 in the UK since 2010 Anna Tostevin, Ellen White, Sara Croxford, Valerie Delpech, Ian Williams, David Dunn on behalf of the UK HIV Drug Resistance Database

2 Introduction Transmitted drug resistance (TDR) occurs when an individual is infected with strain of HIV containing drug resistance mutations Newly diagnosed individuals with TDR start with potentially restricted treatment options. BHIVA recommends testing all individuals at HIV diagnosis to help selection of effective first line treatment Since 2001, UK HIV Drug Resistance Database central repository for resistance tests conducted by NHS labs as part of routine clinical care TDR in UK Rates of TDR declined from early 2000s Rates stabilised Aim What has happened to rates of TDR in the UK since 2009?

3 Methods Resistance tests successfully linked to demographic and clinical data from the UK Collaborative HIV Cohort Study (UKCHIC) and/or the HIV and AIDS Reporting System (HARS) held at Public Health England Patients aged 15 years and over with a first resistance test (protease and reverse transcriptase genes) between 2010 and 2013 prior to starting treatment TDR defined as presence of 1 or more mutations from the WHO 2009 surveillance list- modified to include E138K and all T215 revertants Subtyping REGA v3 Predicted drug susceptibility Stanford HIVDB algorithm v7.0 Integrase mutations- IAS 2013 major mutations

4 Results 16,425 patients with first resistance test Characteristics % Sex Male 74.1 Female 25.9 Exposure source MSM 45.9 Heterosexual Male 17.2 Heterosexual Female 22.1 IDU 1.8 Other/Unknown 12.9 Ethnicity White 49.7 Black African 23.9 Other/Unknown 26.3 Age at diagnosis Median age (yrs) 35.3 Region London 46.1 South England 13.4 North England 13.8 Midlands and East 19.8 Wales 2.7 Scotland 2.7 N Ireland 1.6 Characteristics % CD4 (within 3m test) < > Median CD4 count 342 Subtype A 5.8 B 49.2 C 21.7 G 2.7 CRF01_AE 3.4 CRF02_AG 7.0 Other 10.2

5 % TDR TDR Total MSM Heterosexual Male Heterosexual Female (n=756) 2003 (n=1111) 2004 (n=2281) 2005 (n=3858) 2006 (n=4948) 2007 (n=4962) 2008 (n=5561) 2009 (n=4795) 2010 (n=4467) 2011 (n=4387) 2012 (n=4044) 2013 (n=3527) Evidence of TDR in 7.5% Decline in MSM 9.8% % 2013 Stable in Heterosexual 6.7% % 2013

6 TDR by drug class % TDR % TDR MSM Any class (P=0.01) PI (P=0.13) NRTI (P=0.01) NNRTI (0.63) (n=1977) 2011 (n=2022) 2012 (n=2057) 2013 (n=1477) Het Any class (P=0.57) PI (P=0.83) NRTI (P=0.83) NNRTI (P=0.73) (n=1971) 2011 (n=1827) 2012 (n=1443) 2013 (n=1227)

7 TDR mutations and drug susceptibility Drug Mutation Class (n=4467) (n=4387) (n=4044) (n=3527) (n=16,425) PI L90M 41 (0.9) 23 (0.5) 21 (0.5) 26 (0.7) 111 (0.7) M46L 14 (0.3) 18 (0.4) 7 (0.2) 9 (0.3) 48 (0.3) NRTI T215 revertants 80 (1.8) 72 (1.6) 63 (1.6) 53 (1.5) 268 (1.6) M41L 46 (1) 30 (0.7) 38 (0.9) 27 (0.8) 141 (0.9) K219Q/N 35 (0.8) 30 (0.7) 15 (0.4) 14(0.4) 104 (0.6) M184V 22 (0.5) 26 (0.6) 15 (0.4) 13 (0.4) 76 (0.5) D67N 18 (0.4) 17 (0.4) 11 (0.3) 6 (0.2) 52 (0.3) T69D 15 (0.3) 8 (0.2) 14 (0.4) 6 (0.2) 43 (0.3) NNRTI K103N 109 (2.4) 86 (2) 94 (2.3) 65 (1.8) 354 (2.2) Y181C 25 (0.6) 21 (0.5) 14 (0.4) 6 (0.2) 66 (0.4) K101E 16 (0.4) 11 (0.3) 13 (0.3) 8 (0.2) 48 (0.3) PI NRTI NNRTI ATV FPV LPV DRV ABC TDF 3TC FTC RPV NVP EFV ETR low-level intermediate high-level % with resistance

8 Number % 1+ major resistance mutation Integrase testing and TDR Patients taking Int Inhibitors (UKCHIC only) Integrase resistance tests reported Resistance in treated patients Increasing use of Raltegravir and resistance testing of Integrase gene Majority of tests in experienced patients and stable resistance -15% Testing at baseline not common (120 tests )- no evidence yet of TDR to Integrase inhibitors 0

9 Conclusions , 92.5% had no detectable TDR at first resistance test Rates of TDR have decreased from 8.1% in 2010 to 6.6% in higher rates in MSM than heterosexual men and women Decline in MSM driven by reduction in NRTI resistance- loss of old TAMs Minimal resistance to recommended first line NRTIs and PIs. 3.5% of patients have resistance to Efavirenz (first line NNRTI)- testing for TDR may still help with selection of third agent Despite increasing use of Raltegravir, no TDR detected so far to Integrase inhibitors. Continue to monitor this as increasingly used and first line option

10 Acknowledgments Steering Committee: Celia Aitken (Gartnavel General Hospital, Glasgow); David Asboe, Anton Pozniak (Chelsea & Westminster Hospital, London); Patricia Cane (Public Health England, Porton Down); David Chadwick (South Tees Hospitals NHS Trust, Middlesbrough); Duncan Churchill (Brighton and Sussex University Hospitals NHS Trust); Duncan Clark (St Bartholomew's and The London NHS Trust); Simon Collins (HIV i-base, London); Valerie Delpech (Centre for Infections, Public Health England); Samuel Douthwaite (Guy s and St. Thomas NHS Foundation Trust, London); David Dunn, Esther Fearnhill, Kholoud Porter, Anna Tostevin, Ellen White (MRC Clinical Trials Unit at UCL, London); Christophe Fraser (Imperial College London); Anna Maria Geretti (Institute of Infection and Global Health, University of Liverpool); Antony Hale (Leeds Teaching Hospitals NHS Trust); Stéphane Hué (University College London); Steve Kaye (Imperial College, London); Paul Kellam (Wellcome Trust Sanger Institute & University College London Medical School); Linda Lazarus (Expert Advisory Group on AIDS Secretariat, Public Health England); Andrew Leigh-Brown (University of Edinburgh); Tamyo Mbisa (Virus Reference Department, Public Health England); Nicola Mackie (Imperial NHS Trust, London); Samuel Moses (King s College Hospital, London); Chloe Orkin (St. Bartholomew's Hospital, London); Eleni Nastouli, Deenan Pillay, Andrew Phillips, Caroline Sabin (University College London Medical School. London); Erasmus Smit (Public Health England, Birmingham Heartlands Hospital); Kate Templeton (Royal Infirmary of Edinburgh); Peter Tilston (Manchester Royal Infirmary); Ian Williams (Mortimer Market Centre, London); Hongyi Zhang (Addenbrooke s Hospital, Cambridge). Coordinating Centre: MRC Clinical Trials Unit at UCL (Hannah Castro, David Dunn, Keith Fairbrother, Esther Fearnhill, Kholoud Porter, Anna Tostevin, Ellen White) Centres contributing data: Clinical Microbiology and Public Health Laboratory, Addenbrooke s Hospital, Cambridge (Jane Greatorex); Guy s and St. Thomas NHS Foundation Trust, London (Siobhan O Shea, Jane Mullen); PHE Public Health Laboratory, Birmingham Heartlands Hospital, Birmingham (Erasmus Smit); PHE Virus Reference Department, London (Tamyo Mbisa); Imperial College Health NHS Trust, London (Alison Cox); King's College Hospital, London (Richard Tandy); Medical Microbiology Laboratory, Leeds Teaching Hospitals NHS Trust (Tracy Fawcett); Specialist Virology Centre, Liverpool (Mark Hopkins, Lynn Ashton); Department of Clinical Virology, Manchester Royal Infirmary, Manchester (Peter Tilston); Department of Virology, Royal Free Hospital, London (Claire Booth, Ana Garcia- Diaz); Edinburgh Specialist Virology Centre, Royal Infirmary of Edinburgh (Jill Shepherd); Department of Infection & Tropical Medicine, Royal Victoria Infirmary, Newcastle (Matthias L Schmid, Brendan Payne); South Tees Hospitals NHS Trust, Middlesbrough (David Chadwick); Department of Virology, St Bartholomew s and The London NHS Trust (Spiro Pereira, Jonathan Hubb); Molecular Diagnostic Unit, Imperial College, London (Steve Kaye); University College London Hospitals (Stuart Kirk); West of Scotland Specialist Virology Laboratory, Gartnavel, Glasgow (Rory Gunson, Amanda Bradley-Stewart, Celia Aitken). Funding: This work is currently supported by the UK Medical Research Council (Award Number ).