Switch of predicted HIV-1 tropism in treated subjects and its association with disease progression

Antonella Castagna, L. Monno, Stefania Carta, Laura Galli, Stefania Carrara, Valentina Fedele, G. Punzi, Iuri Fanti, P. Caramello, Alessandro C. Lepri, A. De Luca, F. Ceccherini-Silberstein, A. D'Arminio Monforte

Research output: Contribution to journalArticle

Abstract

Dynamics of human immunodeficiency virus type 1 (HIV-1) tropism after antiretroviral therapy (ART) initiation and their association with disease progression are poorly investigated. This was a cohort study on subjects from the ICONA cohort receiving ART with persistently detectable (PD) or persistently undetectable (PU) viral load (VL) and with stored plasma or peripheral blood mononuclear cell (PBMC) samples at 2 time-points (T1, T2) after ART initiation. HIV-1 co-receptor tropism was determined by V3-loop sequencing and the geno2pheno algorithm. A switch in viral tropism was defined if the tropism classification at T2 differed from that observed at T1. Time to disease progression, defined as the occurrence of a new acquired immune deficiency syndrome (AIDS)-defining event/death from T2, was also evaluated. One hundred ninety-five patients were analyzed (124 PD, 71 PU). Over a median follow-up of 22.6 (19.8-28.1) months, PD and PU patients showed similar rates (95% confidence interval) of switch to a non-R5 virus [PD: 6.9 (3.7-11.2)/100-person-years of follow-up (PYFU); PU: 8.0 (3.4-14.5)/100-PYFU; P=0.63] and of switch to a R5 virus [PD: 15.4 (7.3-26.4)/100-PYFU; PU: 8.1 (2.5-16.7)/100-PYFU; P=0.38]. Switch to non-R5 virus was predicted by nadir CD4+ before T1. Twenty-two (18%) PD and 4 (6%) PU subjects experienced disease progression (P=0.02). The risk of disease progression was independently associated with a switch in co-receptor tropism (adjusted hazard ratio=4.06, 95% CI: 1.20-13.80, P=0.03) as well as age, AIDS diagnosis, nadir CD4+ before T2, current CD4+, and VL. Switch of HIV-1 tropism under ART occurs in both directions, with similar rates in subjects with PD or PU VL and it might be predictive of future unfavorable clinical outcome.

Original languageEnglish
Article numbere5222
JournalMedicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries
Volume95
Issue number44
DOIs
Publication statusPublished - 2016

Fingerprint

Tropism
Disease Progression
HIV-1
Viral Load
Viruses
Acquired Immunodeficiency Syndrome
Viral Tropism
Therapeutics
Blood Cells
Cohort Studies
Confidence Intervals

Keywords

  • CCR5
  • Disease progression
  • FPR
  • HIV
  • Tropism switch

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Switch of predicted HIV-1 tropism in treated subjects and its association with disease progression. / Castagna, Antonella; Monno, L.; Carta, Stefania; Galli, Laura; Carrara, Stefania; Fedele, Valentina; Punzi, G.; Fanti, Iuri; Caramello, P.; Lepri, Alessandro C.; De Luca, A.; Ceccherini-Silberstein, F.; D'Arminio Monforte, A.

In: Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries, Vol. 95, No. 44, e5222, 2016.

Research output: Contribution to journalArticle

Castagna, Antonella ; Monno, L. ; Carta, Stefania ; Galli, Laura ; Carrara, Stefania ; Fedele, Valentina ; Punzi, G. ; Fanti, Iuri ; Caramello, P. ; Lepri, Alessandro C. ; De Luca, A. ; Ceccherini-Silberstein, F. ; D'Arminio Monforte, A. / Switch of predicted HIV-1 tropism in treated subjects and its association with disease progression. In: Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries. 2016 ; Vol. 95, No. 44.
@article{49d6314a06e64b6e84e41e209d7c2527,
title = "Switch of predicted HIV-1 tropism in treated subjects and its association with disease progression",
abstract = "Dynamics of human immunodeficiency virus type 1 (HIV-1) tropism after antiretroviral therapy (ART) initiation and their association with disease progression are poorly investigated. This was a cohort study on subjects from the ICONA cohort receiving ART with persistently detectable (PD) or persistently undetectable (PU) viral load (VL) and with stored plasma or peripheral blood mononuclear cell (PBMC) samples at 2 time-points (T1, T2) after ART initiation. HIV-1 co-receptor tropism was determined by V3-loop sequencing and the geno2pheno algorithm. A switch in viral tropism was defined if the tropism classification at T2 differed from that observed at T1. Time to disease progression, defined as the occurrence of a new acquired immune deficiency syndrome (AIDS)-defining event/death from T2, was also evaluated. One hundred ninety-five patients were analyzed (124 PD, 71 PU). Over a median follow-up of 22.6 (19.8-28.1) months, PD and PU patients showed similar rates (95{\%} confidence interval) of switch to a non-R5 virus [PD: 6.9 (3.7-11.2)/100-person-years of follow-up (PYFU); PU: 8.0 (3.4-14.5)/100-PYFU; P=0.63] and of switch to a R5 virus [PD: 15.4 (7.3-26.4)/100-PYFU; PU: 8.1 (2.5-16.7)/100-PYFU; P=0.38]. Switch to non-R5 virus was predicted by nadir CD4+ before T1. Twenty-two (18{\%}) PD and 4 (6{\%}) PU subjects experienced disease progression (P=0.02). The risk of disease progression was independently associated with a switch in co-receptor tropism (adjusted hazard ratio=4.06, 95{\%} CI: 1.20-13.80, P=0.03) as well as age, AIDS diagnosis, nadir CD4+ before T2, current CD4+, and VL. Switch of HIV-1 tropism under ART occurs in both directions, with similar rates in subjects with PD or PU VL and it might be predictive of future unfavorable clinical outcome.",
keywords = "CCR5, Disease progression, FPR, HIV, Tropism switch",
author = "Antonella Castagna and L. Monno and Stefania Carta and Laura Galli and Stefania Carrara and Valentina Fedele and G. Punzi and Iuri Fanti and P. Caramello and Lepri, {Alessandro C.} and {De Luca}, A. and F. Ceccherini-Silberstein and {D'Arminio Monforte}, A.",
year = "2016",
doi = "10.1097/MD.0000000000005222",
language = "English",
volume = "95",
journal = "Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries",
issn = "0025-7974",
publisher = "Lippincott Williams and Wilkins",
number = "44",

}

TY - JOUR

T1 - Switch of predicted HIV-1 tropism in treated subjects and its association with disease progression

AU - Castagna, Antonella

AU - Monno, L.

AU - Carta, Stefania

AU - Galli, Laura

AU - Carrara, Stefania

AU - Fedele, Valentina

AU - Punzi, G.

AU - Fanti, Iuri

AU - Caramello, P.

AU - Lepri, Alessandro C.

AU - De Luca, A.

AU - Ceccherini-Silberstein, F.

AU - D'Arminio Monforte, A.

PY - 2016

Y1 - 2016

N2 - Dynamics of human immunodeficiency virus type 1 (HIV-1) tropism after antiretroviral therapy (ART) initiation and their association with disease progression are poorly investigated. This was a cohort study on subjects from the ICONA cohort receiving ART with persistently detectable (PD) or persistently undetectable (PU) viral load (VL) and with stored plasma or peripheral blood mononuclear cell (PBMC) samples at 2 time-points (T1, T2) after ART initiation. HIV-1 co-receptor tropism was determined by V3-loop sequencing and the geno2pheno algorithm. A switch in viral tropism was defined if the tropism classification at T2 differed from that observed at T1. Time to disease progression, defined as the occurrence of a new acquired immune deficiency syndrome (AIDS)-defining event/death from T2, was also evaluated. One hundred ninety-five patients were analyzed (124 PD, 71 PU). Over a median follow-up of 22.6 (19.8-28.1) months, PD and PU patients showed similar rates (95% confidence interval) of switch to a non-R5 virus [PD: 6.9 (3.7-11.2)/100-person-years of follow-up (PYFU); PU: 8.0 (3.4-14.5)/100-PYFU; P=0.63] and of switch to a R5 virus [PD: 15.4 (7.3-26.4)/100-PYFU; PU: 8.1 (2.5-16.7)/100-PYFU; P=0.38]. Switch to non-R5 virus was predicted by nadir CD4+ before T1. Twenty-two (18%) PD and 4 (6%) PU subjects experienced disease progression (P=0.02). The risk of disease progression was independently associated with a switch in co-receptor tropism (adjusted hazard ratio=4.06, 95% CI: 1.20-13.80, P=0.03) as well as age, AIDS diagnosis, nadir CD4+ before T2, current CD4+, and VL. Switch of HIV-1 tropism under ART occurs in both directions, with similar rates in subjects with PD or PU VL and it might be predictive of future unfavorable clinical outcome.

AB - Dynamics of human immunodeficiency virus type 1 (HIV-1) tropism after antiretroviral therapy (ART) initiation and their association with disease progression are poorly investigated. This was a cohort study on subjects from the ICONA cohort receiving ART with persistently detectable (PD) or persistently undetectable (PU) viral load (VL) and with stored plasma or peripheral blood mononuclear cell (PBMC) samples at 2 time-points (T1, T2) after ART initiation. HIV-1 co-receptor tropism was determined by V3-loop sequencing and the geno2pheno algorithm. A switch in viral tropism was defined if the tropism classification at T2 differed from that observed at T1. Time to disease progression, defined as the occurrence of a new acquired immune deficiency syndrome (AIDS)-defining event/death from T2, was also evaluated. One hundred ninety-five patients were analyzed (124 PD, 71 PU). Over a median follow-up of 22.6 (19.8-28.1) months, PD and PU patients showed similar rates (95% confidence interval) of switch to a non-R5 virus [PD: 6.9 (3.7-11.2)/100-person-years of follow-up (PYFU); PU: 8.0 (3.4-14.5)/100-PYFU; P=0.63] and of switch to a R5 virus [PD: 15.4 (7.3-26.4)/100-PYFU; PU: 8.1 (2.5-16.7)/100-PYFU; P=0.38]. Switch to non-R5 virus was predicted by nadir CD4+ before T1. Twenty-two (18%) PD and 4 (6%) PU subjects experienced disease progression (P=0.02). The risk of disease progression was independently associated with a switch in co-receptor tropism (adjusted hazard ratio=4.06, 95% CI: 1.20-13.80, P=0.03) as well as age, AIDS diagnosis, nadir CD4+ before T2, current CD4+, and VL. Switch of HIV-1 tropism under ART occurs in both directions, with similar rates in subjects with PD or PU VL and it might be predictive of future unfavorable clinical outcome.

KW - CCR5

KW - Disease progression

KW - FPR

KW - HIV

KW - Tropism switch

UR - http://www.scopus.com/inward/record.url?scp=84995946137&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84995946137&partnerID=8YFLogxK

U2 - 10.1097/MD.0000000000005222

DO - 10.1097/MD.0000000000005222

M3 - Article

VL - 95

JO - Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries

JF - Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries

SN - 0025-7974

IS - 44

M1 - e5222

ER -