February 6, 2001
This randomized, open, multi-center study was designed to evaluate the efficacy and safety of two HAART regimens in HIV-infected treatment naive patients. Specifically it compares a non-nucleoside-containing regimen (nevirapine 200mg BID NVP) to a protease-inhibitor-containing regimen (nelfinavir 750mg TID NFV) each given with the background nucleoside reverse transcriptase inhibitor Combivir (ZDV 300mg/3TC 150mg BID). The study enrolled 142 HIV-infected patients between November 1998 and August 1999 from hospitals in Spain and Argentina.
Baseline mean CD4 count was 359 (10-908) with mean HIV PCR RNA 5.15 (3.2-6.2) log10 copies/mL (median 4.78). One third of patients had HIV PCR RNA >100,000 copies/mL and 20% had CD4 <200µL (no difference between arms).
The interim 36-week data was presented. In an ITT analysis, 55.7% in the NFV arm versus 70.8% in the NVP arm had HIV PCR RNA <200 copies/mL (p=0.06). The on-treatment analysis showed 78% in NFV arm versus 83.7% in the NVP arm were <200 copies/mL (p=0.50).
By more stringent analysis measuring to <20 copies/mL, 38.6% in the NFV arm versus 66.7% in the NVP arm achieved this level of suppression in an ITT analysis (p<0.001). The OT analysis to <20 copies/mL showed 56.1% in the NFV arm versus 79.6% in the NVP arm (p=0.02).
A separate analysis excluding patients who were randomized but were never started on study drug, showed 62.9% in the NFV arm versus 72.9% in the NVP arm were <200 copies/mL. The viral load suppression to <20 copies/mL showed a significant difference between the arms, with 43.5% in the NFV arm versus 68.6% in the NVP arm achieved this level of suppression.
In addition to the 10 patients who did not return for follow-up after randomization (8 CBV/NFV and 2 CBV/NVP), there were significant number of discontinuations due to side effects (13/70 in NFV arm and 16/72 in NVP arm). These patients were allowed to switch to the other study drug, or to any other antiretroviral agent. Data was not available regarding the specific number of patients who switched to the other study drug or what other drug patients switched to.
This makes the ITT analysis very difficult to interpret in this case, given the large number of discontinuations, and the fact that this analysis attributes the success or failure of that arm to the initial randomized drug.
In this case the on-treatment analysis is more indicative of the activity of the drugs in each treatment arm, suggesting that a NVP BID with CBV BID regimen may be as effective as a NFV TID with CBV BID regimen. It should be noted, however, that CBV/NFV efficacy was lower than that seen in other studies. This may be accounted for in part by the lower adherence that was reported in the NFV arm of this study, even though the NFV trough levels all exceeded expected pre-dose levels.
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