A Randomized Clinical Trial Comparing Nelfinavir Or Nevirapine Associated to Zidovudine/Lamivudine in HIV-Infected Naive Patients (The Combine Study)

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Abstract
Background: Non-nucleoside reverse transcriptase inhibitor-containing regimens may be a valid alternative to protease inhibitor-containing regimens for initial antiretroviral therapy, but to date few studies comparing these two strategies have been performed. Objective: To evaluate the efficacy and safety of nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients. Design: Randomized, open-label, multicentre trial. Setting: Twelve centres in Spain (9) and Argentina (3). Patients: One hundred and forty-two HIV-infected naive patients without AIDS. Interventions: Patients received combivir (zidovudine 300 mg/lamivudine 150 mg, twice-daily) plus either nelfinavir (1250 mg) twice-daily (zidovudine/lamivudine/nelfinavir, n=70) or nevirapine (200 mg) twice-daily (zidovudine/lamivudine/nevirapine, n=72), and were followed for 12 months. The primary endpoint was the proportion of patients with a plasma HIV-1 RNA (pVL) of less than 200 copies/ml by PCR at 12 months. pVL of less than 20 copies/ml (PCR), changes in CD4 counts, clinical progression and adverse events were also evaluated. Efficacy was assessed using intent-to-treat (ITT) (missing=failure) and on-treatment analysis. Results: At 12 months in the ITT analysis the proportion of patients with pVL below 200 copies/ml was 60% (95% CI 48.5–71.5) in the zidovudine/lamivudine/nelfinavir arm and 75% (95% CI 65–85) in the zidovudine/lamivudine/nevirapine arm ( P=0.06), and the proportion below 20 copies/ml was 50% (95% CI 38.3–61.7) and 65% (95% CI 54.2–76.2), respectively ( P=0.06). No differences were found when comparing the subgroup of patients with baseline pVL of more than 100 000 copies/ml. A gain of +173 and +162 CD4 cells/mm3, respectively, was observed. Zidovudine/lamivudine/nelfinavir was discontinued in 21% of patients, and zidovudine/lamivudine/ nevirapine in 25%, due to toxicity ( P>0.2). Conclusions: Our results suggest that zidovudine/ lamivudine/nevirapine is at least as effective as zidovudine/lamivudine/nelfinavir as first-line therapy for HIV disease.

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