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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
St. Paul's Hospital, University of British Columbia, Vancouver, Canada. jmontaner@cfenet.ubc.ca
Julio
J
Montaner
Denise
D
Guimaraes
Jain
J
Chung
Zarina
Z
Gafoor
Miklos
M
Salgo
Ralph
R
DeMasi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D012367:RNA, Viral; D000077560:Enfuvirtide