Intensification of stable background therapy with abacavir in antiretroviral therapy experienced patients: 48‐week data from a randomized, double‐blind trial
Authors: Katlama C , Clotet B , Plettenberg A , Jost J , Arasteh K , Bernasconi E , Jeantils V , Cutrell A , Stone C , Purdon S ,   on behalf of the CNA3002 European Study Team
Published: March 2003

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Hôpital de la Pitie Salpetriere, Paris, France,

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Hospital Germans Trias I Pujol, Barcelona, Spain,

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Allgemeines Krankenhaus St Georg, Hamburg, Germany,

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Universitatsspital, Zurich, Switzerland,

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Auguste‐Viktoria‐Krankenhaus, Berlin, Germany,

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Ospedale Civico, Lugano, Switzerland,

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Hôpital Jean Verdier, Bondy, France,

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Glaxo Wellcome Inc, Research Triangle Park, North Carolina, USA, and

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HIV and Opportunistic Infections Development Group, Glaxo Wellcome R&D, Greenford Road, Middlesex UB6 0HE, UK
Objectives  To evaluate antiretroviral efficacy of abacavir (ABC) in antiretroviral‐experienced patients, by intensifying current antiretroviral therapy (CART) in patients with stable, detectable plasma HIV‐1 RNA.Methods  Thirty‐two European centres recruited HIV‐1 positive patients with ≤ 36 months of CART experience. Patients were randomized to receive either ABC (300 mg twice daily) plus CART (ABC + CART) or ABC placebo plus CART (CART). We assessed efficacy as measured by plasma HIV‐1 RNA and CD4+ cell counts and safety at baseline, weeks 2, 4 and every 4 weeks thereafter until week 48. Protocol‐defined criteria enabled patients to switch to open‐label ABC from week 8 onwards.Results  Ninety‐two patients with a median plasma of 3.66 log10 HIV‐1 RNA copies/mL and a median CD4+ cell count of 408 cells/μL were randomized to ABC + CART and 93 patients with a median plasma of 3.52 log10 HIV‐1 RNA copies/mL and a median CD4+ cell count of 411 cells/μL were randomized to CART. From weeks 8–48, 11 (12%) patients in the ABC + CART group and 34 (37%) patients in the CART group switched to open‐label ABC. At week 48, significantly more patients on ABC + CART (23/92, 25%) than on CART (5/93, 5%) had plasma ≤ 400 HIV‐1 RNA copies/mL (P < 0.001, intent‐to‐treat switch = failure population). Neither duration of previous nucleoside reverse transcriptase inhibitor treatment (up to 18 months) nor prior lamivudine therapy affected ABC efficacy. In the ABC + CART group, 16/25 (64%) patients with the M184V mutation at baseline had ≤ 400 copies/mL or a decrease ≥ 1 log10 copies/mL at week 16. More patients (19/46, 41%) with baseline viral load ≤ 5000 copies/mL had plasma < 400 HIV‐1 RNA copies/mL at 48 weeks than those > 5000 copies/mL (4/44, 9%). CD4+ cell counts increased by 102 cells/μL and 57 cells/μL at week 48 for the ABC + CART and CART groups, respectively (intent‐to‐treat, switch included). ABC addition had minimal impact on the CART safety profile.Conclusions  ABC intensification, in CART‐experienced patients with low viral loads and limited reverse transcriptase mutations, most of whom had previously been on double‐therapy, resulted in a significant and durable plasma HIV‐1 reduction and concomitant increase in CD4+ cell count. The presence of M184V at baseline had minimal impact on the efficacy of ABC.