Short-term measures of relative efficacy predict longer-term reductions in human immunodeficiency virus type 1 RNA levels following nelfinavir monotherapy

Abstract

We calculated the relative efficacy of treatment, defined as the rate of decline of virus levels in plasma during treatment relative to the rate of decline during highly potent combination therapy, in human immunodeficiency virus type 1 (HIV-1) patients treated for 56 days with different doses of the protease inhibitor nelfinavir. Relative efficacies based on the rate of decline of HIV-1 RNA levels in plasma over the first 14 to 21 days correlated with drug dose and viral load reduction by day 56. Calculation of relative treatment efficacies over the first 2 to 3 weeks of treatment can allow rapid assessment of new antiretroviral agents and dosing regimens, reducing the need to keep subjects in clinical trials on monotherapy for prolonged periods of time. Relative efficacy may also serve as a measure of treatment efficacy in patients in initiating established therapies.

FIG. 1

Mean reduction in HIV-1 RNA in plasma during the first 2 months for the five daily doses of nelfinavir.

FIG. 2

Correlation between reduction in HIV-1 RNA after 2 months of therapy, log(V₅₆/V₀), and two measures of relative efficacy, ɛ_4,14 and ɛ_4,21. For the five subjects in which monotherapy was modified at day 28 due to a failure to achieve a 10-fold reduction in viral load, we used log(V₂₈/V₀) in place of log(V₅₆/V₀). As described in the text, we believe this substitution is conservative, because virus will usually continue to increase following a viral load rebound in patients who remain on Pr inhibitor monotherapy. Symbols are defined as in Fig. 1.

FIG. 3

Mean drug concentration in plasma during the first 4 weeks for each of the six dosage regimens. Error bars indicate 95% confidence intervals.