A Randomized Trial of Simplified Maintenance Therapy with Abacavir, Lamivudine, and Zidovudine in Human Immunodeficiency Virus Infection

This randomized study evaluated the efficacy and tolerability of continued treatment with protease inhibitor plus nucleoside-analogue combination regimens or a change to the simplified regimen of abacavir-lamivudine-zidovudine in patients with suppressed human immunodeficiency virus type 1 RNA for >6 months who did not have the reverse transcriptase 215 mutation

Milos Opravil

2002

Scholarcy highlights

  • This randomized study evaluated the efficacy and tolerability of continued treatment with protease inhibitor plus nucleoside-analogue combination regimens or a change to the simplified regimen of abacavir-lamivudine-zidovudine in patients with suppressed human immunodeficiency virus type 1 RNA for >6 months who did not have the reverse transcriptase 215 mutation
  • In this prospective, randomized trial, we tested the hypothesis that HIV-1–infected patients who have been virologically suppressed as a result of a protease inhibitor- and nucleoside-analogue reverse-transcriptase inhibitors-containing regimen may simplify their therapy by switching to the triple-NRTI combination of abacavir-lamivudine-zidovudine
  • Resistance mutations at codon 184 or 219 and history of prior zidovudine mono- or dual therapy were subsequently identified as significant predictors of virologic failure by multivariable Cox regression analysis
  • Baseline zidovudine resistance mutations have been previously reported to predict loss of virus suppression during maintenance therapy, and multiple zidovudine and lamivudine resistance mutations cause cross-resistance to abacavir. This stresses the importance of carefully assessing previous treatment history in potential candidates for treatment simplification, because the genotypic assay may not detect mutations expressed at low level in the archived virus
  • The impact of treatment history with other NRTIs could not be assessed in this study because zidovudine was the agent predominantly administered in mono- or dual therapy, our data indicate that archived virus resistant to NRTIs can quickly become the dominant circulating virus population if the new regimen is not fully suppressive
  • In a multivariable Cox regression analysis for all 150 patients with available results from baseline resistance testing, previous zidovudine mono- or dual therapy, resistance mutation in codon 184 or 219 of the reverse transcriptase at baseline, and higher CD8þ lymphocyte count at randomization were predictive of subsequent virologic failure
  • Cell-associated HIV-1 RNA in peripheral blood mononuclear cells, which correlates with virus load in lymph nodes, was determined for those patients who underwent tonsil biopsies and was similar between the groups, suggesting that the potency of this triple-NRTI regimen to suppress viral replication in cellular compartments is in the range of previously reported results from patients treated with PI-containing regimens
  • Cell-associated human immunodeficiency virus type 1 RNA in peripheral blood mononuclear cells, which correlates with virus load in lymph nodes , was determined for those patients who underwent tonsil biopsies and was similar between the groups, suggesting that the potency of this triple-nucleoside-analogue reverse-transcriptase inhibitors regimen to suppress viral replication in cellular compartments is in the range of previously reported results from patients treated with protease inhibitor-containing regimens

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