Antiviral Therapy 8:163-171
Triple nucleoside combination zidovudine/ lamivudine/abacavir versus zidovudine/ lamivudine/nelfinavir as first-line therapy in HIV-1-infected adults: a randomized trial Sophie Matheron1*, Diane Descamps1, François Boué2, Jean-Michel Livrozet3, Alain Lafeuillade4, Christian Aquilina5, Didier Troisvallets6, Agnès Goetschel7, Françoise Brun-Vezinet1, Jean-Philippe Mamet7 & Cécile Thiaux7 on behalf of CNAF3007 study group 1
Hôpital Bichat Claude Bernard, Paris, France Hôpital Antoine Beclère, Paris, France 3 Hôpital Edouard Herriot, Lyon, France 4 Hôpital Chalucet, Toulon, France 5 Hôpital La Grave, Toulouse, France 6 Hôpital de Gonesse, Gonesse, France 7 GlaxoSmithKline, France 2
Corresponding author: Tel: + 33 1 40 25 78 83; Fax: +33 1 40 25 67 75; E-mail:
[email protected]
Objective: To compare the efficacy and safety of a triple nucleoside combination to a protease inhibitorcontaining triple regimen as first-line antiretroviral therapy (ART) in HIV-1-infected patients. Design: Open-label study in HIV-1-infected ART-naive adults, randomized to receive either Combivir (lamivudine 150 mg/zidovudine 300 mg twice daily) + abacavir (300 mg twice daily), or Combivir + nelfinavir (750 mg every 8 h) for 48 weeks. Plasma HIV-1 RNA, CD4 cell count and adverse events were assessed at baseline and weeks 4, 8, 16, 24, 32, 40 and 48. Results: 195 subjects (131 men, 64 women), median age 34 years, were randomized: 98 received combivir/abacavir and 97 combivir/nelfinavir. Baseline median plasma HIV-1 RNA was 4.2 log10 copies/ml [Interquartile range (IQR): 3.7–4.5.2] and 4.1 log10
copies/ml (IQR: 3.8–4.6), respectively. Baseline median CD4 cell count was 387 cells/mm3 (IQR: 194–501) and 449 cells/mm3 (IQR: 334–605), respectively. Nine patients (3 vs 6, respectively) did not start treatment or did not have any available efficacy data. At week 48, using the intent to treat analysis (switch/missing equals failure), plasma HIV-1 RNA was 6.4 mmol/l) or hypertriglyceridaemia (>4.5 mmol/l) were included only if these abnormalities were judged not clinically relevant by the investigator. All patients agreed to and signed a written informed consent form prior to initiation of any study-related procedures. This study received local Institutional Review board approval in October 1998. 164
Subjects with acute HIV infection, history of AIDSdefining event(s) (category C, 1993 CDC classification) or who had previously received any antiretroviral treatment, cytotoxic chemotherapeutic or immunomodulating agents, or radiation therapy, within 6 months before study drug administration, were not included in this trial. Pregnant or breast feeding women, and women without efficacious contraception were not eligible.
Study design This open-label randomized, multicentre study was initially planned to include 180 ART-naive subjects. Subjects were randomized by a centralized procedure to receive either Combivir one tablet twice daily plus abacavir (300 mg) one tablet twice daily, or Combivir one tablet twice daily plus nelfinavir (750 mg) three 250 mg capsules three times daily, for 48 weeks. The study was conducted between November 1998 and July 2000 in 61 sites in France. Virological failure was defined by either: a) a plasma HIV-1 RNA of at least 50 copies/ml at 6 months of follow-up and beyond, following at least one value
