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Accumulation of Protease Mutations Among Patients on Non-Suppressive 2nd-Line ART in Nigeria

H. Rawizza, B. Chaplin, S. Meloni, P. Okonkwo, P. Kanki and the APIN PEPFAR Team

AIDS 2012 - Turning the Tide TogetherPEPFARAccumulation of Protease Mutations Among Patients on Non-Suppressive 2nd-Line ART in Nigeria

BackgroundIn 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 2nd-line (2L) failure.

Distribution of Harvard/APIN PEPFARART SitesMethodsSince 2004, the Harvard/APIN PEPFAR Program provided ART to >85,000 people in NigeriaApproximately 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 testingExamined accumulation of PR mutations by time on failing regimen

Table: Accumulation of Protease Mutations according to Time on Failing 2L ARTResults6,714 patients received PI-based ART661 (9.8%) met VF criteria53 genotypes performedPatients 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 6Median of 1.1 IAS PR mutations per 6 months on failing 2L therapyFor 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%

CharacteristicTime on Failing 2nd-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/mm3208 (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 mutations4 (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 Regimen2.7 (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 indicatedConclusionsNearly 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.

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