Prognostic staging of extensively pretreated patients with advanced HIV-1 disease

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.

In TORO, triple-class-experienced patients with viral load (VL) > or = 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.

The likelihood of VL < 400 copies/mL at 48 weeks (ITT analysis) was greater for those patients who had baseline CD4 count > or = 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 < or = 10 prior antiretrovirals (OR 2.4; 95% CIs 1.6, 3.4); or received > or = 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.

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.