For Nigerian children, access to new generation ARVs, viral load (VL) & drug resistance testing (DRT) are limited. Without DRT, second line failure is difficult to identify & treat. Knowledge of common drug resistance mutations (DRMs) may guide empiric salvage therapy. We evaluated for DRMs among a cohort of HIV+ children on second line ART.Methods:
This study was conducted at a large urban ART clinic. Registers identified children on second line ART who had failed NNRTI or ABC/3TC/AZT. Profile data were obtained from charts, & blood samples were processed for VL & DRT in a central lab. Failure was defined as VL ≥1000 copies per milliliter after ≥6 mos on ART. VL was performed with Roche Cobas AmpliPrep/TaqMan at a limit of 20 copies per milliliter. DRMs were defined using the 2013 IAS list.Results:
here were 973 children on ART at the clinic; 65/973 (6.7%) on second line; 15 had died, transferred, or lost to follow up. Blood samples were obtained from 47/50 children of which 62% were male. Median duration on first line and second line ART were 4.6 and 1.8 y respectively & 95% of children had received ART for ≥6 m. For 88% of children, first line ART was NVP-based. All children received LPV/r-based second line ART, with 41.5%, 34.2%, 14.6% receiving ABC+3T C, TDF+ + XTC, & AZT+3T C NRTI backbones respectively. Twelve of 47 samples had VL >1000 & received DRT. All 4 major PI DRMs detected (M46I, I50V, I54V, V82M) were found in 1 sample. Detections for NNRTI DRMs were in 4/12 samples for K103N & A98G, 3/12 for V179E & Y181C, & in 2 for V90I & G190A. For NRTI DRMs, M184V was found in 7/12 samples; M41L &T215 in 3, & K219Q, D67H, K70R, T69N in 2 samples.Discussion:
Given prior regimens, high frequency of M184V/M41L/T215 and K103N/A98G/Y181C were expected. No K65 DRMs were found, suggesting potential use of TDF or ABC in salvage, barring other key TAMs. Despite universal LPV/r use, only 1 sample had major PI DRMs. LPV/r & ABC or TDF use after >6 months shows low selection of key DRMs.Conclusions:
Including LPV/r+ABC or TDF in salvage may be helpful; however, new, suppressive, child-friendly drugs are needed.