Clinical impact of double protease inhibitor boosting with lopinavir/ritonavir and amprenavir as part of salvage antiretroviral therapy.
OBJECTIVE
Double protease inhibitor (PI) boosting is being explored as a new strategy in salvage antiretroviral (ARV) therapy. However, if a negative drug interaction leads to decreased drug levels of either or both PIs, double PI boosting could lead to decreased virologic response. A negative drug interaction has been described between amprenavir (APV) and lopinavir/ritonavir (LPV/r). This observational cohort study assessed the virologic impact of the addition of APV to a salvage ARV regimen, which also contains LPV/r, compared to a regimen containing LPV/r alone.


METHODS
Patients initiated on a salvage ARV regimen that included LPV/r obtained from the expanded access program in Toronto, Canada, were evaluated. APV (600-1,200 mg bid) was added at the discretion of the treating physician.


RESULTS
Using multivariate Cox proportional hazards models, we found that the addition of APV to a LPV/r-containing salvage regimen was not significantly associated with time to virologic suppression (< 50 copies/mL; adjusted hazard ratio [HR] = 0.75, p =.12) or with time to virologic rebound (adjusted HR = 1.46, p =.34). Those patients who received higher doses of APV had an increased chance of virologic suppression (p =.03). In a subset of 27 patients, the median LPV C(trough) was significantly lower in patients receiving APV (p =.04), and the median APV C(trough) was reduced compared to reported controls.


CONCLUSIONS
Our data do not support an additional benefit in virologic reduction of double boosting with APV and LPV/r relative to LPV/r alone in salvage ARV therapy. Our study's limitations include its retrospective nature and the imbalance between the two groups potentially confounding the results. Although these factors were adjusted for in the multivariate analysis, a prospective randomized controlled trial is warranted to confirm our findings.
Immune Deficiency Treatment Centre, Montreal General Hospital, McGill University, Montreal, Quebec, Canada.
Mona
M
Loutfy
Janet
J
Raboud
Courtney
C
Thompson
Alice
A
Tseng
Zainab
Z
Abdurrahman
Colin
C
Kovacs
Anita
A
Rachlis
Elizabeth
E
Phillips
Gary
G
Rubin
Kevin
K
Gough
Sharon
S
Walmsley
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D002219:Carbamates; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009864:Ontario; D016016:Proportional Hazards Models; D011744:Pyrimidinones / Q000008:administration & dosage; D012189:Retrospective Studies; D019438:Ritonavir / Q000008:administration & dosage; D016879:Salvage Therapy; D013449:Sulfonamides / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D013449:Sulfonamides; D061466:Lopinavir; C095108:amprenavir; D019438:Ritonavir