14th International HIV Drug Resistance Workshop 7-11 June 2005, Québec City, Canada

TWENTY-FOUR-WEEK EFFICACY AND RESISTANCE PROFILE OF A ZIDOVUDINE/LAMIVUDINE/TENOFOVIR DF COMBINATION THERAPY IN ANTIRETROVIRAL-NAÏVE PATIENTS

Antivir Ther. 10, Suppl 1:S22 (abstract no. 20)

B Masquelier¹, D Neau¹, S Boucher¹, V Lavignolle-Aurillac², MH Schrive¹, P Recordon-Pinson¹, JM Ragnaud¹, H Fleury^1
1 Bordeaux University Hospital, Bordeaux, France ² INSERM U593, Bordeaux, France

BACKGROUND: Previous studies suggested the existence of antagonistic interactions between the reverse transcriptase (RT) mutations K65R and T215Y/F and that the addition of zidovudine (ZDV) to tenofovir DF (TDF)-containing regimens could prevent the selection of K65R and maintain antiviral efficacy. In this context we decided to test the antiviral efficacy of a triple therapy with ZDV/lamivudine (3TC)+TDF.

METHODS: Antiretroviral-naïve patients were proposed to receive 300 mg ZDV/150 mg 3TC twice a day+300 mg TDF once a day in an open pilot study. Clinical, virological and immunological follow-up was assessed at baseline therapy (M0), at months 1, 3 and every three months. RT genotype was determined from plasma RNA at baseline and at virological failure, and from proviral DNA at M0 and at M6.

RESULTS: Twenty-four patients were included; three patients had an acute HIV-1 infection, and 21 patients were chronically infected. At baseline, the median CD4 cell count was 443/µl (interquartile range (IQR): 351–559) and the median plasma viral load (VL) was 4.38 log₁₀ copies/ml (IQR: 3.95–4.89). Transmitted resistance mutations were observed at M0 in five patients, including T215D/C (four patients) and M41L (three patients). After one month on therapy, the median decrease in VL was –2.26 log₁₀ copies/ml (IQR: - 2.52;-1.86). Three patients stopped therapy between M0 and M6. At M6, 63% of the patients had a VL<50 copies/ml and 75% a VL<500 copies/ml with an intend-to-treat analysis and 83% of the patients had a VL<50 copies/ml and 100% a VL<500 copies/ml (on-treatment analysis). The median increase in CD4 cells at M6 was +129 cells/µl. Three patients had a virological rebound on therapy. Two rebounds were with wild-type viruses, the latter showed the selection of TAMs and M184V on a background of baseline M41L+T215D. No additional NRTI resistance mutation was observed in proviral DNA at M6 compared to baseline.

CONCLUSION: The virological response in our study demonstrates the antiviral efficacy of the ZDV/3TC/TDF combination therapy. The presence of ZDV in the combination could have prevented the selection of K65R. This combination therapy could be of interest when other antiretroviral classes cannot be prescribed.

PRESENTING AUTHOR: B Masquelier

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2005-06-07
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