Statistical Methodology for Maximally HIV-RNA Suppressive Treatments in HIV-Infected Subjects

Statistical methods developed for survival analysis (time to event) were applied to treatments which are potent viral load suppressers in HIV-infected subjects. The methodology was applied to HIV-RNA levels obtained from the clinical study AG1343–511 (nelfinavir [NFV] in combination with zidovudine +lamivudine). Utilizing stringent treatment response definitions based on the limit of quantification (LOQ) of two assays, the analyses established that nelfinavir containing arms were significantly better than the control arm and the 750 mg NFV arm was superior to the 500 mg NFV arm. Analyses of durability (duration) of response revealed that subjects qualified as responders to more sensitive (lower LOQ) assay were associated with longer duration of response.

The statistical methodology utilized and the parameters defined in this article can be applied to the evaluation of anti-HIV treatments in general. For potent anti-HIV treatments, the method can be utilized with the definitions developed here; less potent treatments can be analyzed with proper modifications in definitions of response and relapse.