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J Antimicrob Chemother. 2018 Apr 1;73(4):1039-1044. doi: 10.1093/jac/dkx511.

Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen.

Author information

1
IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Laboratoire de Virologie, Hôpital Bichat, AP-HP, Paris, France.
2
Sorbonne University, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris, France.
3
AP-HP, Laboratoire de Virologie, Hôpital La Pitié Salpêtrière, Paris, France.
4
CHU Nantes, Laboratoire de Virologie, Nantes, France.
5
CHRU Lille, Laboratoire de Virologie, Lille, France.
6
Hôpital Tenon, Laboratoire de Virologie, Paris, France.
7
Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013, Paris, France; AP-HP, Centre Hospitalo-Universitaire Saint-Antoine, Laboratoire de Virologie, F-75012, Paris, France.
8
CHU Bordeaux, Laboratoire de Virologie, Bordeaux, France.
9
CHU Rennes, Laboratoire de Virologie, Rennes, France.
10
CHU Rouen, Laboratoire de Virologie, Rouen, France.
11
CHU Montpellier, Laboratoire de Virologie, Montpellier, France.
12
CHU Caen, Laboratoire de Virologie, Caen, France.
13
Hôpital Paul Brousse, Laboratoire de Virologie, Villejuif, France.
14
CHU Clermont-Ferrand, Laboratoire de Virologie, Clermont-Ferrand, France.
15
CHU Amiens, Laboratoire de Virologie, Amiens, France.
16
CHU Grenoble, Laboratoire de Virologie, Grenoble, France.
17
CHU Toulouse, Laboratoire de Virologie, Toulouse, France.
18
Hôpital St Louis, Laboratoire de Virologie, Paris, France.

Abstract

Objectives:

To assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen.

Methods:

This was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay.

Results:

Prevalence of the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B subtypes, respectively. Thirty-nine INI-naive patients with E157Q-mutated virus initiated an INI-based regimen. Among them, 15 had a viral load (VL) <50 copies/mL at initiation and virological suppression was maintained during the first year of follow-up in all but two exhibiting a viral blip. Twenty-four patients had a VL > 50 copies/mL at the time of INI-based regimen initiation. Among them eight were receiving a first-line regimen and the only two patients who did not reach VL < 50 copies/mL at week 24 were receiving elvitegravir. The 16 remaining patients were ART experienced in virological failure with drug-resistant viruses displaying several virological outcomes independently of the genotypic susceptibility score. Phenotypic analyses showed a fold change in EC50 of 0.6, 0.9 and 1.9 for raltegravir, dolutegravir and elvitegravir, respectively, in a subtype B context, and 1.1, 1.9 and 2.4 for raltegravir, dolutegravir and elvitegravir, respectively, in a CRF02_AG context.

Conclusions:

Assessment of virological response in 39 patients initiating an INI-based regimen with E157Q-mutated virus, in combination with phenotypic analysis, suggests that particular attention should be paid to antiretroviral-naive patients and dolutegravir should be preferentially used in these patients.

PMID:
29342281
DOI:
10.1093/jac/dkx511

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