The incidence of HIV drug resistance and its impact on progression of HIV disease among antiretroviral-naïve participants started on three different antiretroviral therapy strategies

Michael J. Kozal, Katherine Huppler Hullsiek, Rodger David MacArthur, Mary Van Der Berg-Wolf, Grace Peng, Ying Xiang, John D. Baxter, Jonathan Uy, Edward E. Telzak, Richard M. Novak

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background: Treatment-naïve participants were randomized to three antiretroviral strategies (all with nucleoside reverse transcriptase inhibitor [NRTI] background): protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or PI+NNRTI. The strategies were compared for drug resistance at first virologic failure (VF; HIV RNA >1000 copies/mL). The impact of resistance on AIDS or death was determined. Method: Drug resistance was determined by genotype. Cox models were used to compare the strategies for VF with resistance and to determine the impact of resistance on AIDS or death. Results: Of 1,360 participants, 866 experienced VF; 226 experienced AIDS or death (median follow-up 5 years). Rates (per 100 person-years) for VF with resistance were 14.9 (PI), 10.8 (NNRTI), and 11.5 (PI+NNRTI); hazard ratio (HR) was 0.78 (95% CI 0.61-0.99) for NNRTI versus PI. Compared to those with no VF, there was a significantly increased risk of AIDS or death for participants with solitary NNRTI resistance (HR 2.31, 95% CI 1.46-3.66) and for those failing with no known resistance (HR 1.78, 95% CI 1.18-2.68). Participants failing with solitary NNRTI resistance and with no resistance had the lowest percent of time on antiretroviral treatment (ART) and the lowest cumulative mean adherence scores. Conclusion: For treatment-naïve participants, the risk of AIDS or death is increased for those who failed virologically with solitary NNRTI resistance and those who failed with no known drug resistance compared to those with no virologic failure. Both the lack of ART exposure in nonadherent participants and the development of NNRTI resistance among those who take and fail their ART regimen predict poor clinical outcomes.

Original languageEnglish (US)
Pages (from-to)357-370
Number of pages14
JournalHIV Clinical Trials
Volume8
Issue number6
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Fingerprint

Reverse Transcriptase Inhibitors
Drug Resistance
Disease Progression
HIV
Incidence
Protease Inhibitors
Acquired Immunodeficiency Syndrome
Therapeutics
Nucleosides
Proportional Hazards Models
Genotype
RNA

Keywords

  • Antiretroviral therapy
  • Clinical trials
  • HIV drug resistance

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

The incidence of HIV drug resistance and its impact on progression of HIV disease among antiretroviral-naïve participants started on three different antiretroviral therapy strategies. / Kozal, Michael J.; Hullsiek, Katherine Huppler; MacArthur, Rodger David; Van Der Berg-Wolf, Mary; Peng, Grace; Xiang, Ying; Baxter, John D.; Uy, Jonathan; Telzak, Edward E.; Novak, Richard M.

In: HIV Clinical Trials, Vol. 8, No. 6, 01.11.2007, p. 357-370.

Research output: Contribution to journalArticle

Kozal, Michael J. ; Hullsiek, Katherine Huppler ; MacArthur, Rodger David ; Van Der Berg-Wolf, Mary ; Peng, Grace ; Xiang, Ying ; Baxter, John D. ; Uy, Jonathan ; Telzak, Edward E. ; Novak, Richard M. / The incidence of HIV drug resistance and its impact on progression of HIV disease among antiretroviral-naïve participants started on three different antiretroviral therapy strategies. In: HIV Clinical Trials. 2007 ; Vol. 8, No. 6. pp. 357-370.
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abstract = "Background: Treatment-na{\"i}ve participants were randomized to three antiretroviral strategies (all with nucleoside reverse transcriptase inhibitor [NRTI] background): protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or PI+NNRTI. The strategies were compared for drug resistance at first virologic failure (VF; HIV RNA >1000 copies/mL). The impact of resistance on AIDS or death was determined. Method: Drug resistance was determined by genotype. Cox models were used to compare the strategies for VF with resistance and to determine the impact of resistance on AIDS or death. Results: Of 1,360 participants, 866 experienced VF; 226 experienced AIDS or death (median follow-up 5 years). Rates (per 100 person-years) for VF with resistance were 14.9 (PI), 10.8 (NNRTI), and 11.5 (PI+NNRTI); hazard ratio (HR) was 0.78 (95{\%} CI 0.61-0.99) for NNRTI versus PI. Compared to those with no VF, there was a significantly increased risk of AIDS or death for participants with solitary NNRTI resistance (HR 2.31, 95{\%} CI 1.46-3.66) and for those failing with no known resistance (HR 1.78, 95{\%} CI 1.18-2.68). Participants failing with solitary NNRTI resistance and with no resistance had the lowest percent of time on antiretroviral treatment (ART) and the lowest cumulative mean adherence scores. Conclusion: For treatment-na{\"i}ve participants, the risk of AIDS or death is increased for those who failed virologically with solitary NNRTI resistance and those who failed with no known drug resistance compared to those with no virologic failure. Both the lack of ART exposure in nonadherent participants and the development of NNRTI resistance among those who take and fail their ART regimen predict poor clinical outcomes.",
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T1 - The incidence of HIV drug resistance and its impact on progression of HIV disease among antiretroviral-naïve participants started on three different antiretroviral therapy strategies

AU - Kozal, Michael J.

AU - Hullsiek, Katherine Huppler

AU - MacArthur, Rodger David

AU - Van Der Berg-Wolf, Mary

AU - Peng, Grace

AU - Xiang, Ying

AU - Baxter, John D.

AU - Uy, Jonathan

AU - Telzak, Edward E.

AU - Novak, Richard M.

PY - 2007/11/1

Y1 - 2007/11/1

N2 - Background: Treatment-naïve participants were randomized to three antiretroviral strategies (all with nucleoside reverse transcriptase inhibitor [NRTI] background): protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or PI+NNRTI. The strategies were compared for drug resistance at first virologic failure (VF; HIV RNA >1000 copies/mL). The impact of resistance on AIDS or death was determined. Method: Drug resistance was determined by genotype. Cox models were used to compare the strategies for VF with resistance and to determine the impact of resistance on AIDS or death. Results: Of 1,360 participants, 866 experienced VF; 226 experienced AIDS or death (median follow-up 5 years). Rates (per 100 person-years) for VF with resistance were 14.9 (PI), 10.8 (NNRTI), and 11.5 (PI+NNRTI); hazard ratio (HR) was 0.78 (95% CI 0.61-0.99) for NNRTI versus PI. Compared to those with no VF, there was a significantly increased risk of AIDS or death for participants with solitary NNRTI resistance (HR 2.31, 95% CI 1.46-3.66) and for those failing with no known resistance (HR 1.78, 95% CI 1.18-2.68). Participants failing with solitary NNRTI resistance and with no resistance had the lowest percent of time on antiretroviral treatment (ART) and the lowest cumulative mean adherence scores. Conclusion: For treatment-naïve participants, the risk of AIDS or death is increased for those who failed virologically with solitary NNRTI resistance and those who failed with no known drug resistance compared to those with no virologic failure. Both the lack of ART exposure in nonadherent participants and the development of NNRTI resistance among those who take and fail their ART regimen predict poor clinical outcomes.

AB - Background: Treatment-naïve participants were randomized to three antiretroviral strategies (all with nucleoside reverse transcriptase inhibitor [NRTI] background): protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or PI+NNRTI. The strategies were compared for drug resistance at first virologic failure (VF; HIV RNA >1000 copies/mL). The impact of resistance on AIDS or death was determined. Method: Drug resistance was determined by genotype. Cox models were used to compare the strategies for VF with resistance and to determine the impact of resistance on AIDS or death. Results: Of 1,360 participants, 866 experienced VF; 226 experienced AIDS or death (median follow-up 5 years). Rates (per 100 person-years) for VF with resistance were 14.9 (PI), 10.8 (NNRTI), and 11.5 (PI+NNRTI); hazard ratio (HR) was 0.78 (95% CI 0.61-0.99) for NNRTI versus PI. Compared to those with no VF, there was a significantly increased risk of AIDS or death for participants with solitary NNRTI resistance (HR 2.31, 95% CI 1.46-3.66) and for those failing with no known resistance (HR 1.78, 95% CI 1.18-2.68). Participants failing with solitary NNRTI resistance and with no resistance had the lowest percent of time on antiretroviral treatment (ART) and the lowest cumulative mean adherence scores. Conclusion: For treatment-naïve participants, the risk of AIDS or death is increased for those who failed virologically with solitary NNRTI resistance and those who failed with no known drug resistance compared to those with no virologic failure. Both the lack of ART exposure in nonadherent participants and the development of NNRTI resistance among those who take and fail their ART regimen predict poor clinical outcomes.

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KW - Clinical trials

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