Abstract

ObjectivesThe aim of this study was to investigate associations between baseline characteristics and CD4 cell count response on first-line antiretroviral therapy and risk of virological failure (VF) with or without drug resistance. MethodsWe conducted an analysis of UK Collaborative HIV Cohort data linked to the UK HIV Drug Resistance Database. Inclusion criteria were viral sequence showing no resistance prior to initiation of first-line efavirenz + tenofovir disoproxil fumarate + emtricitabine and virological suppression within 6 months. Outcomes of VF (≥200 copies/mL) with or without drug resistance were assessed using a competing risks approach fitted jointly with a model for CD4 cell count recovery. Hazard ratios for each VF outcome were estimated for baseline CD4 cell count and viral load and characteristics of CD4 cell count response using latent variables on a standard normal scale. ResultsA total of 3640 people were included with 338 VF events; corresponding viral sequences were available in 134 with ≥1 resistance mutation in 36. VF with resistance was associated with lower baseline CD4 (0.30, 0.09–0.62), lower CD4 recovery (0.04, 0.00–0.17) and higher CD4 variability (4.40, 1.22–12.68). A different pattern of associations was observed for VF without resistance, but the strength of these results was less consistent across sensitivity analyses. Cumulative incidence of VF with resistance was estimated to be >2% at 3 years for baseline CD4 ≥350 cells/μL. ConclusionLower baseline CD4 cell count and suboptimal CD4 recovery are associated with VF with drug resistance. People with low CD4 cell count before ART or with suboptimal CD4 recovery on treatment should be a priority for regimens with high genetic barrier to resistance.

Highlights

  • Amongst people diagnosed with HIV in whom there is initial viral suppression, subsequent virological failure (VF) rates on modern antiretroviral therapy (ART) regimens are low [1]

  • We have found that for people living with HIV (PLHIV) who achieve initial viral suppression on EFV + TDF + FTC, the characteristics of CD4 cell count response to first-line ART are strongly associated with the risk of VF with emergence of drug resistance

  • Our results suggest that, in this cohort, there was a different set of factors associated with the event of VF without drug resistance

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Summary

Introduction

Amongst people diagnosed with HIV in whom there is initial viral suppression, subsequent virological failure (VF) rates on modern ART regimens are low [1]. It has been argued that routine monitoring of CD4 cell count observations could be reduced for PLHIV on suppressive ART [4,5], the CD4 cell count remains an important marker of immunological status [6], and so there is a motivation to further investigate associations between baseline and post-treatment CD4 cell counts and risk of VF and acquired drug resistance. The expected level of CD4 cell count recovery on virally suppressive ART is strongly dependent on the baseline observation at ART initiation [9,10,11,12], and so CD4 cell count recovery itself needs to be evaluated relative to that

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