1. Accumulation of Protease Mutations Among Patients on Non-Suppressive 2 nd -Line ART in Nigeria H. Rawizza, B. Chaplin, S. Meloni, P. Okonkwo, P. Kanki and the APIN PEPFAR Team AIDS 2012 - Turning the Tide Together

2. Accumulation of Protease Mutations Among Patients on Non-Suppressive 2 nd -Line ART in Nigeria Background In assessing the cost-effectiveness of CD4 versus viral load (VL) monitoring strategies, the “resistance cost” associated with delays in identifying non- suppression must be considered, and would likely favor a VL strategy. Here we examined the extent of protease (PR) mutation accumulation according to duration of 2 nd -line (2L) failure. Distribution of Harvard/APIN PEPFAR ART Sites Methods Since 2004, the Harvard/APIN PEPFAR Program provided ART to >85,000 people in Nigeria Approximately 8% of patients received protease inhibitor (PI)-based 2L therapy (mostly LPV/r) Subset of patients with VL failure (i.e., 2 consecutive VLs >1000 cpm after ≥6 months on 2L) underwent genotypic resistance testing Examined accumulation of PR mutations by time on failing regimen

3. Table: Accumulation of Protease Mutations according to Time on Failing 2L ART Results  6,714 patients received PI-based ART  661 (9.8%) met VF criteria  53 genotypes performed Patients with ≤12 months on non- suppressive 2L tx had a median of 3 IAS PR mutations, while those on for >24 mo. had a median of 6 Median of 1.1 IAS PR mutations per 6 months on failing 2L therapy For patients failing >24 months, high- or intermediate-level resistance to LPV/r and ATV/r was present in 64% and to DRV/r in 9% Characteristic Time on Failing 2 nd -Line Regimen^ 0-12 months (n=15) 13-24 months (n=27) >24 months (n=11) Total (n=53) Age (years), median (IQR)43 (34-47)*40 (34-43)42 (32-51)42 (33-46) % Female33%48%55%45% # ARVs previously used(range) 6 (4-7)6 (4-8)6 (5-9)6 (4-9) Duration on 1L, months23 (19-37)28 (16-37)16 (14-23)24 (15-35) Duration on 2L, months12 (8-20)20 ( 18-22)36 (34-50)20 (16-34) Time Failing on 2L, mo.8 (6-11)18 (16-20)34 (32-40)17 (12-22) 2L Avg. % Adherence89 (79-98)96 (87-100)91 (78-100)92 (84-100) CD4+ cell count at 2L failure, cells/mm 3 208 (124-255)203 (120-280)114 (65-181)183 (106-264) VL at 2L failure, copies/mL30,790 (7689- 114,691) 27,808 (11,398- 93,750) 29,510 (7621- 43,328) 30,150 (8238- 87,702) # Protease mutations, median (IQR) 3 (1-5)2 (0-5)6 (0-6.5)3 (0-5) Major PR mutations (IAS)0 (0-1.5)0 (0-3)3 (0-4)1 (0-3) Minor PR mutations2 (0.5-3.5)2 (0-2)2 (0-3)2 (0-2) # Patients (%) with no PR mutations 4 (27%)8 (30%)4 (36%)16 (30%) High- or Intermediate-level PI Resistance, # (%) Lopinavir (LPV/r)4 (27%)12 (44%)7 (64%)23 (43%) Atazanavir (ATV/r)4 (27%)12 (44%)7 (64%)23 (43%) Darunavir (DRV/r)0 (0%)4 (15%)1 (9%)5 (9%) # PR mutations / 6 months on Failing 2L Regimen 2.7 (0.5-3.7)0.9 (0-1.8)0.8 (0-1.1)1.1 (0-2.3) # PR mutations / 6 months 2L Failure (patients with no PR mutations excluded) 3.4 (2.6-4)1.4 (0.8-2.3)1.1 (0.9-1.2)1.8 (1.1-2.8) ^Time on failing 2L regimen to genotype *Numbers represent median (IQR), unless otherwise indicated Conclusions Nearly two-thirds of patients on failing 2L ART for >2 years accumulated significant PR resistance. A significant resistance penalty is associated with failing to switch non- suppressive 2L regimens, which highlights the importance of considering access to 3L ARVs.