Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338)

Susan A. Fiscus, Andrea Kovacs, Leslie A. Petch, Chengcheng Hu, Andrew A. Wiznia, Lynne M. Mofenson, Ram Yogev, Kenneth McIntosh, Stephen I. Pelton, Sonia Napravnik, Kenneth Stanley, Sharon A. Nachman

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: The association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI) resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI) resistant codons) for 92 clinically stable NRTI-experienced, PI-naive HIV-infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV) and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART) was studied. Results: There were few primary PI associated mutations in this PI-naive population, but 84% had NRTI mutations - codons 215 (66%), 41 (42%), 67 (37%), 210 (33%) and 70 (32%). None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006). Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017). Conclusion: No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen.

Original languageEnglish (US)
Article number2
JournalAIDS Research and Therapy
Volume4
DOIs
StatePublished - Mar 9 2007

Fingerprint

Reverse Transcriptase Inhibitors
Nucleosides
Mutation
Zidovudine
Highly Active Antiretroviral Therapy
Drug Resistance
Codon
Protease Inhibitors
Therapeutics
Stavudine
HIV Protease Inhibitors
Ritonavir
Lamivudine
Viral Load
HIV

ASJC Scopus subject areas

  • Molecular Medicine
  • Virology
  • Pharmacology (medical)

Cite this

Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338). / Fiscus, Susan A.; Kovacs, Andrea; Petch, Leslie A.; Hu, Chengcheng; Wiznia, Andrew A.; Mofenson, Lynne M.; Yogev, Ram; McIntosh, Kenneth; Pelton, Stephen I.; Napravnik, Sonia; Stanley, Kenneth; Nachman, Sharon A.

In: AIDS Research and Therapy, Vol. 4, 2, 09.03.2007.

Research output: Contribution to journalArticle

Fiscus, SA, Kovacs, A, Petch, LA, Hu, C, Wiznia, AA, Mofenson, LM, Yogev, R, McIntosh, K, Pelton, SI, Napravnik, S, Stanley, K & Nachman, SA 2007, 'Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338)', AIDS Research and Therapy, vol. 4, 2. https://doi.org/10.1186/1742-6405-4-2
Fiscus, Susan A. ; Kovacs, Andrea ; Petch, Leslie A. ; Hu, Chengcheng ; Wiznia, Andrew A. ; Mofenson, Lynne M. ; Yogev, Ram ; McIntosh, Kenneth ; Pelton, Stephen I. ; Napravnik, Sonia ; Stanley, Kenneth ; Nachman, Sharon A. / Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338). In: AIDS Research and Therapy. 2007 ; Vol. 4.
@article{11e948e9be5a4b8ba74d18c94cd776f3,
title = "Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338)",
abstract = "Background: The association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI) resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI) resistant codons) for 92 clinically stable NRTI-experienced, PI-naive HIV-infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV) and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART) was studied. Results: There were few primary PI associated mutations in this PI-naive population, but 84{\%} had NRTI mutations - codons 215 (66{\%}), 41 (42{\%}), 67 (37{\%}), 210 (33{\%}) and 70 (32{\%}). None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006). Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017). Conclusion: No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen.",
author = "Fiscus, {Susan A.} and Andrea Kovacs and Petch, {Leslie A.} and Chengcheng Hu and Wiznia, {Andrew A.} and Mofenson, {Lynne M.} and Ram Yogev and Kenneth McIntosh and Pelton, {Stephen I.} and Sonia Napravnik and Kenneth Stanley and Nachman, {Sharon A.}",
year = "2007",
month = "3",
day = "9",
doi = "10.1186/1742-6405-4-2",
language = "English (US)",
volume = "4",
journal = "AIDS Research and Therapy",
issn = "1742-6405",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338)

AU - Fiscus, Susan A.

AU - Kovacs, Andrea

AU - Petch, Leslie A.

AU - Hu, Chengcheng

AU - Wiznia, Andrew A.

AU - Mofenson, Lynne M.

AU - Yogev, Ram

AU - McIntosh, Kenneth

AU - Pelton, Stephen I.

AU - Napravnik, Sonia

AU - Stanley, Kenneth

AU - Nachman, Sharon A.

PY - 2007/3/9

Y1 - 2007/3/9

N2 - Background: The association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI) resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI) resistant codons) for 92 clinically stable NRTI-experienced, PI-naive HIV-infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV) and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART) was studied. Results: There were few primary PI associated mutations in this PI-naive population, but 84% had NRTI mutations - codons 215 (66%), 41 (42%), 67 (37%), 210 (33%) and 70 (32%). None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006). Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017). Conclusion: No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen.

AB - Background: The association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI) resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI) resistant codons) for 92 clinically stable NRTI-experienced, PI-naive HIV-infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV) and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART) was studied. Results: There were few primary PI associated mutations in this PI-naive population, but 84% had NRTI mutations - codons 215 (66%), 41 (42%), 67 (37%), 210 (33%) and 70 (32%). None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006). Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017). Conclusion: No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen.

UR - http://www.scopus.com/inward/record.url?scp=33847674401&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847674401&partnerID=8YFLogxK

U2 - 10.1186/1742-6405-4-2

DO - 10.1186/1742-6405-4-2

M3 - Article

AN - SCOPUS:33847674401

VL - 4

JO - AIDS Research and Therapy

JF - AIDS Research and Therapy

SN - 1742-6405

M1 - 2

ER -