Virological response and resistance among HIV-infected children receiving long-term antiretroviral therapy without virological monitoring in Uganda and Zimbabwe: Observational analyses within the randomised ARROW trial

Background: although who recommends viral load (vl) monitoring for those on antiretroviral therapy (art),availability in low-income countries remains limited. we investigated long-term vl and resistance in hiv-infected children managed without real-time vl monitoring. methods and findings: in the arrow factorial trial,1,206 children initiating art in uganda and zimbabwe between 15 march 2007 and 18 november 2008,aged a median 6 years old,with median cd4% of 12%,were randomised to monitoring with or without 12-weekly cd4 counts and to receive 2 nucleoside reverse transcriptase inhibitors (2nrti,mainly abacavir+lamivudine) with a non-nucleoside reverse transcriptase inhibitor (nnrti) or 3 nrtis as long-term art. all children had vl assayed retrospectively after a median of 4 years on art; those with >1,000 copies/ml were genotyped. three hundred and sixteen children had vl and genotypes assayed longitudinally (at least every 24 weeks). overall,67 (6%) switched to second-line art and 54 (4%) died. in children randomised to who-recommended 2nrti+nnrti long-term art,308/378 (81%) monitored with cd4 counts versus 297/375 (79%) without had vl <1,000 copies/ml at 4 years (difference = +2.3% [95% ci −3.4% to +8.0%]; p = 0.43),with no evidence of differences in intermediate/high-level resistance to 11 drugs. among children with longitudinal vls,only 5% of child-time post–week 24 was spent with persistent low-level viraemia (80–5,000 copies/ml) and 10% with vl rebound ≥5,000 copies/ml. no child resuppressed <80 copies/ml after confirmed vl rebound ≥5,000 copies/ml. a median of 1.0 (iqr 0.0,1.5) additional nrti mutation accumulated over 2 years’ rebound. nineteen out of 48 (40%) vls 1,000–5,000 copies/ml were immediately followed by resuppression <1,000 copies/ml,but only 17/155 (11%) vls ≥5,000 copies/ml resuppressed (p < 0.0001). main study limitations are that analyses were exploratory and treatment initiation used 2006 criteria,without pre-art genotypes. conclusions: in this study,children receiving first-line art in sub-saharan africa without real-time vl monitoring had good virological and resistance outcomes over 4 years,regardless of cd4 monitoring strategy. many children with detectable low-level viraemia spontaneously resuppressed,highlighting the importance of confirming virological failure before switching to second-line therapy. children experiencing rebound ≥5,000 copies/ml were much less likely to resuppress,but nrti resistance increased only slowly. these results are relevant to the increasing numbers of hiv-infected children receiving first-line art in sub-saharan africa with limited access to virological monitoring. © 2017 szubert et al.