Genotype and phenotype at baseline and at failure in human immunodeficiency virus-infected antiretroviral-naive patients in a randomized trial comparing zidovudine and lamivudine plus nelfinavir or nevirapine.

For the 127 Spanish patients enrolled in the Combine Study, a resistance substudy was performed with 100 (79%) plasma samples obtained at baseline and with 18 samples obtained from 19 patients at the time they experienced treatment failure. At baseline, primary mutations to nonnucleoside reverse-transcriptase inhibitors and protease inhibitors were not detected, whereas mutations to nucleoside reverse-transcriptase inhibitors were observed in 10% of patients. At failure, mutations were detected in 7 of 16 patients. An agreement in the results of virtual and real phenotypes was observed in the 93 samples in which both tests were performed.

A randomized clinical trial comparing nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients (the Combine Study).

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.