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Original article

The association between detected drug resistance mutations and CD4+ T-cell decline in HIV-positive individuals maintained on a failing treatment regimen

Anna Schultze, Roger Paredes, Caroline Sabin, Andrew N Phillips, Deenan Pillay, Nicola Mackie, Antonella Castagna, David Chadwick, Karolin Falconer, Anna Maria Geretti, Frank A Post, Teresa Hill, Ole Kirk, Anton Pozniak, Mark Nelson, Anna Tostevin, David Dunn, Jens Lundgren, Alessandro Cozzi-Lepri

Corresponding author name: Anna Schultze
Corresponding author e-mail: anna.schultze@evidera.com

Citation: Antiviral Therapy 2018; 23:105-116
doi: 10.3851/IMP3178

Date accepted: 20 May 2017
Date published online: 19 June 2017

Abstract

Background: To analyse the effect of drug resistance mutations (DRM) on CD4+ T-cell (CD4) trends in HIV-positive people maintained on virologically failing antiretroviral therapy (ART).

Methods: Individuals from two large cohorts experiencing virological failure (VF) while maintained on ART with ≥1 CD4 count and ≥1 resistance test were included. CD4 slopes were estimated using linear mixed models. Principal component analysis (PCA) was used to assess the effect of clusters of mutations, defined using extracted component based scores from the PCA, on CD4 decline.

Results: 5,357 individuals contributing 7,661 VF episodes were included: any DRM were detected in 88.8% of episodes. After adjustment, CD4 counts declined less steeply during episodes where DRM were detected compared to episodes with no DRM (difference =28 cells/mm3/year, 95% CI =18, 39; P<0.001). Among individuals with at least one DRM, we found evidence that any nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance, the reverse transcriptase (RT) mutations M184V, D67N and T215Y as well as the protease mutations V82A and I54V were associated with reduced CD4 declines. The detection of any non-nucleoside reverse transcriptase inhibitor resistance, the RT mutations V179D and L74V were associated with steeper CD4 declines. The presence of some mutation patterns similar to the clusters identified by the PCA also affected the CD4 decline.

Conclusions: Detection of resistance and of certain DRM during VF of ART has a small but significant favourable effect on CD4 decline.

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