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.

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Presentation transcript:

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 Turning the Tide Together

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

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) 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 ( )203 ( )114 (65-181)183 ( ) VL at 2L failure, copies/mL30,790 ( ,691) 27,808 (11, ,750) 29,510 ( ,328) 30,150 ( ,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 ( )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 ( )0.9 (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 ( )1.1 ( )1.8 ( ) ^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.