Evolution of antiretroviral phenotypic and genotypic drug resistance in antiretroviral-naive HIV-1-infected children treated with abacavir/lamivudine, zidovudine/lamivudine or abacavir/zidovudine, with or without nelfinavir (the PENTA 5 trial).

Gibb, D; Walker, A; Kaye, S; De Rossi, A; Ait-Khaled, M; Pillay, D; Muñoz-Fernandez, M; Loveday, C; Compagnucci, A; Dunn, D; Babiker, A

Journal article

Evolution of antiretroviral phenotypic and genotypic drug resistance in antiretroviral-naive HIV-1-infected children treated with abacavir/lamivudine, zidovudine/lamivudine or abacavir/zidovudine, with or without nelfinavir (the PENTA 5 trial).

Abstract:: PURPOSE AND METHODS: To describe the evolution of resistance to zidovudine (ZDV), lamivudine (3TC), abacavir (ABC) and nelfinavir (NFV), 113 previously untreated children in the PENTA 5 trial had resistance assayed at baseline, rebound and/or 24, 48, 72 weeks (VIRCO: phenotyping and genotyping with 'Virtual Phenotype' interpretation). RESULTS: At baseline, few reverse transcriptase mutations and no primary protease inhibitor mutations were observed. Time to detectable HIV-1 RNA with reduced phenotypic susceptibility to any drug was shortest in the ZDV+3TC arm (overall logrank P=0.02). Through a median follow-up of 55 weeks, at their last assessment 11 (28%), 16 (40%) and 13 (32%) children with detectable HIV-1 RNA and a resistance test available had mutations conferring resistance to none, one, or two or more trial drugs, respectively, according to the virtual phenotype. Reduced phenotypic susceptibility to ABC only occurred in the 3TC+ABC arm and required K65R and/or L74V in addition to M184V. NFV-resistant virus was selected slowly through D30N or L90M pathways, and selection of ZDV-resistant virus was rare. CONCLUSIONS: Selection of 3TC-resistant virus was most frequent, followed by NFV and/or ABC; selection of ZDV-resistant virus was rare. Importantly, although in vitro, ABC selects for M184V as the first mutation, ABC did not select for M184V when combined with ZDV without 3TC. The most sustained HIV-1 RNA response was in the 3TC+ABC arm, but mutations conferring reduced susceptibility to 3TC and/or ABC evolved more frequently if virological failure occurred with 3TC+ABC than with ZDV+ABC.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Gibb, D., Walker, A., Kaye, S., De Rossi, A., Ait-Khaled, M., Pillay, D., Muñoz-Fernandez, M., Loveday, C., Compagnucci, A., Dunn, D., & Babiker, A. (2002). Evolution of antiretroviral phenotypic and genotypic drug resistance in antiretroviral-naive HIV-1-infected children treated with abacavir/lamivudine, zidovudine/lamivudine or abacavir/zidovudine, with or without nelfinavir (the PENTA 5 trial). Antiviral Therapy, 7(4), 293–303.

MLA Style

Gibb, D, et al. “Evolution of Antiretroviral Phenotypic and Genotypic Drug Resistance in Antiretroviral-Naive HIV-1-Infected Children Treated with Abacavir/Lamivudine, Zidovudine/Lamivudine or Abacavir/Zidovudine, with or without Nelfinavir (the PENTA 5 Trial).” Antiviral Therapy, vol. 7, no. 4, 2002, pp. 293–303.

Chicago Style

Gibb, D, A Walker, S Kaye, et al. 2002. “Evolution of Antiretroviral Phenotypic and Genotypic Drug Resistance in Antiretroviral-Naive HIV-1-Infected Children Treated with Abacavir/Lamivudine, Zidovudine/Lamivudine or Abacavir/Zidovudine, with or without Nelfinavir (the PENTA 5 Trial).” Antiviral Therapy 7 (4): 293–303.
Print