Incidence and predictors of virologic failure of antiretroviral triple-drug therapy in a community-based cohort.
Highly active antiretroviral therapy fails to reach its recommended goal of sustained suppression of viral replication in a substantial proportion of patients. We analyzed incidence and predictors of virologic failure of the first regimen of a triple-drug combination therapy, including a protease inhibitor and two nucleoside analog reverse transcriptase inhibitors (NRTIs), in 274 HIV-infected patients. Long-term virologic response to combination therapy including salvage regimens was assessed 2.5 years after treatment initiation. During an initial observation period of up to 1.8 years (median, 0.8 years) 152 patients (55%) experienced sustained suppression of HIV-1 RNA to <500 copies/ml. Failure to reduce viral load to <500 copies/ml within 6 months (initial failure) was observed in 51 patients (19%). Independent risk factors for initial failure included higher baseline viral load; addition of a protease inhibitor to an unchanged NRTI regimen; use of saquinavir hard-gel capsules; and longer duration of prior NRTI treatment. Within a median of 7 months viral load rebound above 500 copies/ml occurred in 71 of 223 patients (32%) whose viral load had initially decreased below this threshold. In proportional hazard analysis none of the potential risk factors was significantly associated with viral load rebound. However, in 40 patients (56%) with viral load rebound, incomplete adherence to therapy or treatment interruptions preceded the rebound. Virologic outcome after 2.5 years correlated with initial response to the first regimen: viral load was <500 copies/ml in 88, 55, and 21% of patients with sustained suppression, viral load rebound, and initial failure, respectively.
Paris
D
D
Department of Medicine, University Hospital, Zurich, Switzerland.
Ledergerber
B
B
Weber
R
R
Jost
J
J
Flepp
M
M
Opravil
M
M
Ruef
C
C
Zimmerli
S
S
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D016049:Didanosine / Q000008:administration & dosage / Q000627:therapeutic use; D018450:Disease Progression; D004334:Drug Administration Schedule; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D019469:Indinavir / Q000008:administration & dosage / Q000627:therapeutic use; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D016879:Salvage Therapy; D019258:Saquinavir / Q000008:administration & dosage / Q000627:therapeutic use; D018119:Stavudine / Q000008:administration & dosage / Q000627:therapeutic use; D013557:Switzerland; D017211:Treatment Failure; D019562:Viral Load; D016047:Zalcitabine / Q000008:administration & dosage / Q000627:therapeutic use; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D016047:Zalcitabine; D018119:Stavudine; D016049:Didanosine; D019258:Saquinavir; D019438:Ritonavir