Prognostic Staging of Extensively Pretreated Patients with Advanced HIV-1 Disease

Abstract Purpose: Determinants of therapeutic success are poorly characterized in patients with extensive HAART experience. Positive prognostic factors (PPFs) in the TORO trials could serve as the basis for a prognostically meaningful staging of treatment-experienced patients initiating a new antiretroviral regimen. Method: In TORO, triple-class-experienced patients with viral load (VL) ≥5,000 copies/mL received an optimized background regimen of 3-5 antiretrovirals (based on treatment history and baseline resistance testing) ± enfuvirtide (n = 995). Clinically relevant baseline PPFs that were predictive of 48-week virologic outcomes were identified via multiple regression analyses. Results: The likelihood of VL <400 copies/mL at 48 weeks (ITT analysis) was greater for those patients who had baseline CD4 count ≥100 cells/mm3 (odds ratio [OR] 2.1; 95% confidence intervals [CIs] 1.5, 3.1); baseline VL <5 log10 copies/mL (OR 1.8; 95% CIs 1.2, 2.6); received ≤10 prior antiretrovirals (OR 2.4; 95% CIs 1.6, 3.4); or received ≥2 active antiretrovirals in their background treatment regimen (OR 2.3; 95% CIs 1.6, 3.3). Overall, 67% of triple-class-experienced patients who met all four prognostic criteria and received enfuvirtide achieved VL <400 copies/mL at 48 weeks vs. 43% for non-enfuvirtide patients (p < .05). Similar results were obtained when the analysis was done separately in each of the randomization arms of the study. Conclusion: Our findings provide guidance for physicians on expected outcomes in treatment-experienced patients and should be of value in their clinical management, as well as in stratifying participants in clinical trials involving treatment-experienced patients.