2000The Journal of Infectious DiseasesOpen access

Effect of Zidovudine Resistance Mutations on Virologic Response to Treatment with Zidovudine‐Lamivudine‐Ritonavir: Genotypic Analysis of Human Immunodeficiency Virus Type 1 Isolates from AIDS Clinical Trials Group Protocol 315

Daniel R. Kuritzkes, Anne Sevin, Benjamin Young, Minoo Bakhtiari, Hulin Wu, Marty St. Clair, Elizabeth Connick, Alan Landay, John Spritzler, Harold A. Kessler, Michael M. Lederman

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Abstract

The effect of baseline drug resistance mutations on response to zidovudine, lamivudine, and ritonavir was evaluated in zidovudine-experienced persons infected with human immunodeficiency virus type 1 (HIV-1). Presence of the K70R mutation was associated with significantly higher plasma HIV-1 RNA levels at baseline. However, presence of resistance mutations did not affect the increase in plasma HIV-1 RNA during a 5-week drug washout, nor was there any effect on first-phase virus decay rates after initiation of therapy or on the probability of having plasma HIV-1 RNA levels <100 copies/mL at week 48. Polymorphisms at protease codons 10, 36, and 71 were associated with significantly faster second-phase decay rates. Suppression of plasma HIV-1 RNA despite presence of zidovudine resistance mutations implies that the presence of these mutations does not preclude a durable response to treatment with a potent 3-drug regimen.

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The effect of baseline drug resistance mutations on response to zidovudine, lamivudine, and ritonavir was evaluated in zidovudine-experienced persons infected with human immunodeficiency virus type 1 (HIV-1). Presence of the K70R mutation was associated with significantly higher plasma HIV-1 RNA levels at baseline. However, presence of resistance mutations did not affect the increase in plasma HIV-1 RNA during a 5-week drug washout, nor was there any effect on first-phase virus decay rates after initiation of therapy or on the probability of having plasma HIV-1 RNA levels <100 copies/mL at week 48. Polymorphisms at protease codons 10, 36, and 71 were associated with significantly faster second-phase decay rates. Suppression of plasma HIV-1 RNA despite presence of zidovudine resistance mutations implies that the presence of these mutations does not preclude a durable response to treatment with a potent 3-drug regimen.

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Available abstract

The effect of baseline drug resistance mutations on response to zidovudine, lamivudine, and ritonavir was evaluated in zidovudine-experienced persons infected with human immunodeficiency virus type 1 (HIV-1). Presence of the K70R mutation was associated with significantly higher plasma HIV-1 RNA levels at baseline. However, presence of resistance mutations did not affect the increase in plasma HIV-1 RNA during a 5-week drug washout, nor was there any effect on first-phase virus decay rates after initiation of therapy or on the probability of having plasma HIV-1 RNA levels <100 copies/mL at week 48. Polymorphisms at protease codons 10, 36, and 71 were associated with significantly faster second-phase decay rates. Suppression of plasma HIV-1 RNA despite presence of zidovudine resistance mutations implies that the presence of these mutations does not preclude a durable response to treatment with a potent 3-drug regimen.

Key concepts: Zidovudine, Ritonavir, Lamivudine, Virology, Resistance mutation, Drug resistance, Virus, Biology

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Effect of Zidovudine Resistance Mutations on Virologic Response to Treatment with Zidovudine‐Lamivudine‐Ritonavir: Genotypic Analysis of Human Immunodeficiency Virus Type 1 Isolates from AIDS Clinical Trials Group Protocol 315 — Research Paper | ScholarLens