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

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dc.contributor.authorSzubert, Alexander J.
dc.contributor.authorPrendergast, Andrew J.
dc.contributor.authorMusiime, Victor
dc.contributor.authorMusoke, Philippa
dc.contributor.authorBwakura-Dangarembizi, Mutsa
dc.contributor.authorNahirya-Ntege, Patricia
dc.contributor.authorThomason, Margaret J.
dc.contributor.authorNkanya, Immaculate
dc.contributor.authorSenfuma, Oscar
dc.contributor.authorMudenge, Boniface
dc.contributor.authorWalker, A. Sarah
dc.date.accessioned2023-02-21T16:08:21Z
dc.date.available2023-02-21T16:08:21Z
dc.date.issued2017
dc.description.abstractAlthough 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. 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. 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.en_US
dc.identifier.citationSzubert, A. J., Prendergast, A. J., Spyer, M. J., Musiime, V., Musoke, P., Bwakura-Dangarembizi, M., ... & ARROW Trial Team. (2017). 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. PLoS medicine, 14(11), e1002432.https://doi.org/10.1371/journal.pmed.1002432en_US
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/7911
dc.language.isoenen_US
dc.publisherPLoS medicineen_US
dc.subjectVirologicalen_US
dc.subjectHIV-Infected Childrenen_US
dc.subjectAntiretroviral Therapyen_US
dc.titleVirological 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 Trialen_US
dc.typeArticleen_US
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