Incidence of HIV-1 drug resistance among antiretroviral treatment-naive individuals starting modern therapy combinations.
Détails
Etat: Public
Version: Final published version
Licence: Non spécifiée
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
ID Serval
serval:BIB_4B0819F08089
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Incidence of HIV-1 drug resistance among antiretroviral treatment-naive individuals starting modern therapy combinations.
Périodique
Clinical Infectious Diseases
Collaborateur⸱rice⸱s
Swiss HIV Cohort Study
Contributeur⸱rice⸱s
Barth J., Battegay M., Bernasconi E., Böni J., Bucher HC., Bürgisser P., Burton-Jeangros C., Calmy A., Cavassini M., Cellerai C., Egger M., Elzi L., Fehr J., Flepp M., Francioli P., Furrer H., Fux CA., Gorgievski M., Günthard H., Hasse B., Hirsch HH., Hirschel B., Hösli I., Kahlert C., Kaiser L., Keiser O., Kind C., Klimkait T., Kovari H., Ledergerber B., Martinetti G., Martinez de Tejada B., Müller N., Nadal D., Pantaleo C., Rauch A., Regenass S., Rickenbach M., Rudin C., Schmid P., Schultze D., Schöni-Affolter F., Schüpbach J., Speck R., Taffé P., Telenti A., Trkola A., Vernazza P., von Wyl V., Weber R., Yerly S.
ISSN
1537-6591 (Electronic)
ISSN-L
1058-4838
Statut éditorial
Publié
Date de publication
2012
Volume
54
Numéro
1
Pages
131-140
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
BACKGROUND: Estimates of drug resistance incidence to modern first-line combination antiretroviral therapies against human immunodeficiency virus (HIV) type 1 are complicated by limited availability of genotypic drug resistance tests (GRTs) and uncertain timing of resistance emergence.
METHODS: Five first-line combinations were studied (all paired with lamivudine or emtricitabine): efavirenz (EFV) plus zidovudine (AZT) (n = 524); EFV plus tenofovir (TDF) (n = 615); lopinavir (LPV) plus AZT (n = 573); LPV plus TDF (n = 301); and ritonavir-boosted atazanavir (ATZ/r) plus TDF (n = 250). Virological treatment outcomes were classified into 3 risk strata for emergence of resistance, based on whether undetectable HIV RNA levels were maintained during therapy and, if not, whether viral loads were >500 copies/mL during treatment. Probabilities for presence of resistance mutations were estimated from GRTs (n = 2876) according to risk stratum and therapy received at time of testing. On the basis of these data, events of resistance emergence were imputed for each individual and were assessed using survival analysis. Imputation was repeated 100 times, and results were summarized by median values (2.5th-97.5th percentile range).
RESULTS: Six years after treatment initiation, EFV plus AZT showed the highest cumulative resistance incidence (16%) of all regimens (<11%). Confounder-adjusted Cox regression confirmed that first-line EFV plus AZT (reference) was associated with a higher median hazard for resistance emergence, compared with other treatments: EFV plus TDF (hazard ratio [HR], 0.57; range, 0.42-0.76), LPV plus AZT (HR, 0.63; range, 0.45-0.89), LPV plus TDF (HR, 0.55; range, 0.33-0.83), ATZ/r plus TDF (HR, 0.43; range, 0.17-0.83). Two-thirds of resistance events were associated with detectable HIV RNA level ≤500 copies/mL during treatment, and only one-third with virological failure (HIV RNA level, >500 copies/mL).
CONCLUSIONS: The inclusion of TDF instead of AZT and ATZ/r was correlated with lower rates of resistance emergence, most likely because of improved tolerability and pharmacokinetics resulting from a once-daily dosage.
METHODS: Five first-line combinations were studied (all paired with lamivudine or emtricitabine): efavirenz (EFV) plus zidovudine (AZT) (n = 524); EFV plus tenofovir (TDF) (n = 615); lopinavir (LPV) plus AZT (n = 573); LPV plus TDF (n = 301); and ritonavir-boosted atazanavir (ATZ/r) plus TDF (n = 250). Virological treatment outcomes were classified into 3 risk strata for emergence of resistance, based on whether undetectable HIV RNA levels were maintained during therapy and, if not, whether viral loads were >500 copies/mL during treatment. Probabilities for presence of resistance mutations were estimated from GRTs (n = 2876) according to risk stratum and therapy received at time of testing. On the basis of these data, events of resistance emergence were imputed for each individual and were assessed using survival analysis. Imputation was repeated 100 times, and results were summarized by median values (2.5th-97.5th percentile range).
RESULTS: Six years after treatment initiation, EFV plus AZT showed the highest cumulative resistance incidence (16%) of all regimens (<11%). Confounder-adjusted Cox regression confirmed that first-line EFV plus AZT (reference) was associated with a higher median hazard for resistance emergence, compared with other treatments: EFV plus TDF (hazard ratio [HR], 0.57; range, 0.42-0.76), LPV plus AZT (HR, 0.63; range, 0.45-0.89), LPV plus TDF (HR, 0.55; range, 0.33-0.83), ATZ/r plus TDF (HR, 0.43; range, 0.17-0.83). Two-thirds of resistance events were associated with detectable HIV RNA level ≤500 copies/mL during treatment, and only one-third with virological failure (HIV RNA level, >500 copies/mL).
CONCLUSIONS: The inclusion of TDF instead of AZT and ATZ/r was correlated with lower rates of resistance emergence, most likely because of improved tolerability and pharmacokinetics resulting from a once-daily dosage.
Mots-clé
Adult, Anti-HIV Agents/administration & dosage, Anti-HIV Agents/pharmacology, Drug Resistance, Viral, Female, Genotype, HIV Infections/drug therapy, HIV Infections/virology, HIV-1/classification, HIV-1/drug effects, Humans, Incidence, Male, Middle Aged, Treatment Outcome, Viral Load
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/02/2013 17:22
Dernière modification de la notice
14/02/2022 8:54
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