Institutional development in the Nile equatorial lakes sub-basin: learning from the experience of the Kagera Basin Organisation

River basinsOrganizationsInstitutional development

Institutional development in the Nile equatorial lakes sub-basin: learning from the experience of the Kagera Basin Organization

River basinsInstitutional development

Institutional development in the Nile equatorial lakes sub-basin learning from the experience of the Kagera Basin Organisation

River basinsInstitutional development

Mapping the medical outcomes study HIV health survey (MOS-HIV) to the EuroQoL 5 Dimension (EQ-5D-3L) utility index

10.1186/s12955-019-1135-8Health and Quality of Life Outcomes1718

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. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN24791884.The ARROW trial was jointly funded by the UK Medical Research Council (MRC, mrc.ac.uk) grant numbers G0300400 (AJP, VM, PM, MB-D, NK, DMG, ASW) and G1001190 (AJP, VM, PM, MB-D, NK, DMG, ASW) and the UK Department for International Development (DFID, gov.uk/dfid) (DMG) under the MRC/DFID Concordat agreement. It was also part of the EDCTP2 programme supported by the European Union; drugs were donated and viral load and genotyping assays were funded by ViiV Healthcare/GlaxoSmithKline. The MRC Clinical Trials Unit at UCL (AJS, MJS, MJT, DMG, ASW) is supported by funding from the MRC (MC_UU_12023/26). AJP is a Wellcome Trust Fellow (grant number 108065/Z/15/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript