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Drug resistance profile at failure of integrase inhibitors containing regimens Antiretroviral Resistance Cohort Analysis www.hivarca.net April 20, 2016 Drug resistance profile at failure of integrase inhibitors containing regimens • The driver criterium for the selection of the patients was the availability of a genotypic drug resistance test on integrase region after the start of an antiretroviral regimen containing a INI, according to the viral load; the tests have been performed on RNA from plasma/serum samples, excluding whole blood, PBMC and liquor matrix in order to depict the drug resistance profile to INIs at virological failure. • Since 2008 a total of 294 genotypic drug resistance tests on integrase region at potential virological failure from patients administered with an INI-based antiretroviral regimen has been selected for the analysis. Test INI 2008 - 2016 50 45 40 35 30 25 20 15 10 5 0 2008 2009 2010 2011 2012 2013 2014 2015 2016 INI genotypic resistance test since 2008 Feature Value Age, median (IQR) 47 (41-52) Male gender, % 198 (67.3) Ethnicity, Caucasian 202 (68.7) Log viral load, median (IQR) at baseline 3.8 (3.1-4.8) CD4 cell counts, median (IQR) at baseline 246 (95-406) %CD4 cell counts, median (IQR) at baseline 15.0 (7.6-23.0) Nadir CD4 cell counts, median (IQR) .… Zenith viral load, median (IQR) …. Log viral load, median (IQR) at failure 3.4 (2.7-4.4) CD4 cell counts, median (IQR) at failure 296 (176-477) %CD4 cell counts, median (IQR) at failure 17.0 (9.0-24.0) Years since HIV diagnosis, median (IQR) …. Total weeks of treatment, median (IQR) 103 (61-139) Past treatment lines, median (IQR) Subtype B, % RAL/EVG/DTG 10 (5-14) 206 (70) 269/1/24 Test Stratification performed at different VL Total: 184 (known viral load) 33.7% 59 41 28 18 VL<200 200≤VL<500 22 16 500≤VL<1000 1000 ≤VL<10000 10000<VL<100000 ≥100000 Reasons for INI-based regimen discontinuation Reason for INI interruption Not reported N % 143 48.6 Virological failure 97 32.9 Adherence issues 12 4.1 Immunological failure 4 1.4 Intensification 3 1.0 Other 5 1.7 Supervised interruption 3 1.0 Toxicity 7 2.4 Simplification 9 3.1 11 3.7 Obsolete therapy INI major drug resistance mutations according to VL rank (all INI interruption reasons n=184) Major: 155 or 148 or 143 Other: other than 155, 148 or 143 16 None 13 16 11 11 6 VL < 200 7 8 4 6 200 ≤ VL < 500 30 8 3 18 2 6 500 ≤ VL < 1000 major 1000 ≤ VL < 10000 10000 ≤ VL < 100000 other 7 12 >100000 none p=0.01 INI major drug resistance mutations according to VL rank (only virological/immunological failure n=79) Major: 155 or 148 or 143 6 Other: other than 155, 148 or 143 4 None 3 1 1 1 18 0 4 2 VL < 200 3 2 2 200 ≤ VL < 500 4 0 5 14 9 500 ≤ VL < 1000 major 1000 ≤ VL < 10000 10000 ≤ VL < 100000 other >100000 none p=0.02 Preliminary results •The GRT at LLV is performed as a routine test, according to the current Guidelines (33.7% for INI tests) •The prevalence of drug-resistance mutations is higher if VL>1000 cp/mL than if VL<1000 cp/mL (both for all patients and for patients presenting virological/immunological failures) •The rate of viral rebound in presence of at least 1 INI major drug resistance mutations (via 155 and/or 148 and/or 143 pathway) is 42.4% and 63.3% for all patients and for only virological/immunological failures, respectively. In progress analysis •Impact of viral subtype and gender •Evaluation of background regimen •Presence of 155 vs 148 vs 143 according to VL rank •Co-presence of 155 and/or 148 and/or 143 mutations according to VL rank •Impact of other INI mutation (other than 155, 148 and 143) on susceptibility to INI •Impact of other INI mutation on virological rebound without INI major mutations •Most of the patients have been treated with RAL: evaluation of susceptibility to Elvitegravir and Dolutegravir