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

1. 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

2. Accumulation of Protease Mutations Among Patients on Non-Suppressive 2nd-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 2nd-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% • Conclusions • Nearly two-thirdsof patients on failing 2L ART for >2 years accumulated significant PR resistance. • A significantresistance penalty isassociated with failing to switch non-suppressive 2L regimens, which highlights the importance of considering access to 3L ARVs.