Predictors of Virological Failure and Time to Viral Suppression of First-Line Integrase Inhibitor-Based Antiretroviral Treatment.
HIV
drug resistance
integrase strand transfer inhibitors
minor drug resistance mutations
treatment outcome
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
05 10 2021
05 10 2021
Historique:
received:
23
06
2020
accepted:
19
10
2020
pubmed:
24
10
2020
medline:
21
10
2021
entrez:
23
10
2020
Statut:
ppublish
Résumé
Integrase strand transfer inhibitors (InSTIs) are recommended for first-line treatment of persons with human immunodeficiency virus (HIV). We identified risk factors, including baseline minor InSTI resistance mutations, for treatment failure of InSTI-based regimens. We studied time-to-treatment failure and time to viral suppression among 1419 drug-naive patients in the Swiss HIV Cohort Study. We performed Cox regression models adjusted for demographic factors, baseline HIV RNA/CD4 cell counts, AIDS-defining events, and the type of InSTI. In 646 patients with a baseline genotypic resistance test of the integrase, we studied the impact of minor integrase resistance mutations. We observed 121 virological failures during 18 447 person-years of follow-up. A baseline viral load ≥100 000 copies/mL (multivariable hazard ratio [mHR], 2.2; 95% confidence interval [CI], 1.3-3.6) and an AIDS-defining event (mHR, 1.8; 95% CI. 1.1-3.0) were associated with treatment failure. CD4 counts between 200 and 500 cells/µL (mHR, 0.5; 95% CI, .3-.8) and >500 cells/µL (mHR, 0.4; 95% CI, .2-.7) were protective. Time to suppression was shorter in lower viral load strata (mHR, 0.7; 95% CI, .6-.8) and in dolutegravir-based therapy (mHR, 1.2; 95% CI, 1.0-1.4). Minor resistance mutations were found at baseline in 104 of 646 (16%) patients with no effect on treatment outcome. Factors associated with treatment failure on InSTI-based first-line regimen remained similar to those of older treatments, in particular high viral load and low CD4 counts.
Sections du résumé
BACKGROUND
Integrase strand transfer inhibitors (InSTIs) are recommended for first-line treatment of persons with human immunodeficiency virus (HIV). We identified risk factors, including baseline minor InSTI resistance mutations, for treatment failure of InSTI-based regimens.
METHODS
We studied time-to-treatment failure and time to viral suppression among 1419 drug-naive patients in the Swiss HIV Cohort Study. We performed Cox regression models adjusted for demographic factors, baseline HIV RNA/CD4 cell counts, AIDS-defining events, and the type of InSTI. In 646 patients with a baseline genotypic resistance test of the integrase, we studied the impact of minor integrase resistance mutations.
RESULTS
We observed 121 virological failures during 18 447 person-years of follow-up. A baseline viral load ≥100 000 copies/mL (multivariable hazard ratio [mHR], 2.2; 95% confidence interval [CI], 1.3-3.6) and an AIDS-defining event (mHR, 1.8; 95% CI. 1.1-3.0) were associated with treatment failure. CD4 counts between 200 and 500 cells/µL (mHR, 0.5; 95% CI, .3-.8) and >500 cells/µL (mHR, 0.4; 95% CI, .2-.7) were protective. Time to suppression was shorter in lower viral load strata (mHR, 0.7; 95% CI, .6-.8) and in dolutegravir-based therapy (mHR, 1.2; 95% CI, 1.0-1.4). Minor resistance mutations were found at baseline in 104 of 646 (16%) patients with no effect on treatment outcome.
CONCLUSIONS
Factors associated with treatment failure on InSTI-based first-line regimen remained similar to those of older treatments, in particular high viral load and low CD4 counts.
Identifiants
pubmed: 33095848
pii: 5937176
doi: 10.1093/cid/ciaa1614
pmc: PMC8492202
doi:
Substances chimiques
Anti-Retroviral Agents
0
HIV Integrase Inhibitors
0
HIV Integrase
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2134-e2141Subventions
Organisme : Swiss National Science Foundation
ID : 177499
Pays : Switzerland
Organisme : SHCS Research Foundation
Organisme : Yvonne Jacob Foundation
Investigateurs
K Aebi-Popp
(K)
A Anagnostopoulos
(A)
M Battegay
(M)
E Bernasconi
(E)
J Böni
(J)
D L Braun
(DL)
H C Bucher
(HC)
A Calmy
(A)
M Cavassini
(M)
A Ciuffi
(A)
G Dollenmaier
(G)
M Egger
(M)
L Elzi
(L)
J Fehr
(J)
J Fellay
(J)
H Furrer
(H)
C A Fux
(CA)
H F Günthard
(HF)
D Haerry
(D)
B Hasse
(B)
H H Hirsch
(HH)
M Hoffmann
(M)
I Hösli
(I)
M Huber
(M)
C R Kahlert
(CR)
L Kaiser
(L)
O Keiser
(O)
T Klimkait
(T)
R D Kouyos
(RD)
H Kovari
(H)
B Ledergerber
(B)
G Martinetti
(G)
B Martinez de Tejada
(B)
C Marzolini
(C)
K J Metzner
(KJ)
N Müller
(N)
D Nicca
(D)
P Paioni
(P)
G Pantaleo
(G)
M Perreau
(M)
A Rauch
(A)
C Rudin
(C)
A U Scherrer
(AU)
P Schmid
(P)
R Speck
(R)
M Stöckle
(M)
P Tarr
(P)
A Trkola
(A)
P Vernazza
(P)
G Wandeler
(G)
R Weber
(R)
S Yerly
(S)
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
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