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Intensification of stable background therapy with abacavir in antiretroviral therapy experienced patients: 48‐week data from a randomized, double‐blind trial
Author(s) -
Katlama C,
Clotet B,
Plettenberg A,
Jost J,
Arasteh K,
Bernasconi E,
Jeantils V,
Cutrell A,
Stone C,
Purdon S
Publication year - 2001
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1046/j.1468-1293.2001.00043.x
Subject(s) - cart , medicine , abacavir , randomized controlled trial , antiretroviral therapy , human immunodeficiency virus (hiv) , placebo , viral load , pediatrics , immunology , pathology , mechanical engineering , alternative medicine , engineering
1Hôpital de la Pitie Salpetriere, Paris, France,2Hospital Germans Trias I Pujol, Barcelona, Spain,3Allgemeines Krankenhaus St Georg, Hamburg, Germany,4Universitatsspital, Zurich, Switzerland,5Auguste‐Viktoria‐Krankenhaus, Berlin, Germany,6Ospedale Civico, Lugano, Switzerland,7Hôpital Jean Verdier, Bondy, France,8Glaxo Wellcome Inc, Research Triangle Park, North Carolina, USA, and9HIV and Opportunistic Infections Development Group, Glaxo Wellcome R&D, Greenford Road, Middlesex UB6 0HE, UKObjectives 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 log 10 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 log 10 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 log 10 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.