Abstract
BackgroundAlthough 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 findingsIn 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.ConclusionsIn 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 registrationISRCTN Registry, ISRCTN24791884
Highlights
Children experiencing rebound !5,000 copies/ml were much less likely to resuppress, but nucleoside reverse transcriptase inhibitor (NRTI) resistance increased only slowly. These results are relevant to the increasing numbers of HIV-infected children receiving first-line antiretroviral therapy (ART) in sub-Saharan Africa with limited access to virological monitoring
The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set an ambitious target for 2020: that 90% of people living with HIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), and 90% receiving ART have viral load (VL) suppression [1]
Current guidelines recommend stopping routine CD4 monitoring, provided patients are clinically stable and virologically suppressed. Despite this push to increase VL monitoring and reduce reliance on immunological and clinical failure criteria, the availability of VL monitoring remains limited in low-income settings, and VL is less frequently measured in low-income settings than in well-resourced ones
Summary
The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set an ambitious target for 2020: that 90% of people living with HIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), and 90% receiving ART have viral load (VL) suppression [1]. Given their more limited access to antiretroviral drugs compared with adults; in 2015, only 49% of HIV-infected children globally were estimated to be receiving ART [2]. Current guidelines recommend stopping routine CD4 monitoring, provided patients are clinically stable and virologically suppressed. Despite this push to increase VL monitoring and reduce reliance on immunological and clinical failure criteria, the availability of VL monitoring remains limited in low-income settings (estimated at 25% of people living with HIV in 2014 [4]), and VL is less frequently measured in low-income settings than in well-resourced ones 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
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