Virologic and immunologic response to a boosted double-protease inhibitor-based therapy in highly pretreated HIV-1-infected patients.
OBJECTIVE
To assess the virologic and immunologic response to a boosted double-protease inhibitor (PI) regimen of highly pretreated patients infected with HIV-1 and to examine the role of PI resistance and concentration of serum saquinavir.


METHODS
In an open-label prospective study, lopinavir/ritonavir, saquinavir-sgc, lamivudine, and other nucleoside analogues were offered to highly pretreated patients who had advanced HIV-1 infection and who had failed at least 2 previous highly active antiretroviral therapy regimens including at least 1 nonnucleoside reverse transcriptase inhibitor. The relationship between baseline drug resistance and steady-state saquinavir serum levels and early (week 4) and sustained (week 48) virologic response was documented.


RESULTS
35 advanced HIV-1 patients were enrolled. The boosted double-PI regimen was well tolerated. Twenty-two (63%) of the 35 patients had a > 0.8 log(10) decrease in HIV viral load at week 4. After 48 weeks of follow-up, the 22 patients who remained on the study therapy had an average decrease in viral load of 1 log(10) and had a median increase in CD4 cells of 60 cell/microL. Multiple logistic regression analysis indicated that genotypic resistance to both PIs and the week-3 trough concentrations of saquinavir were associated with virologic outcome at week 4. The presence of > or = 6 lopinavir mutations [odds ratio (OR) 0.03; 95% CI 0.01 to 0.79] and the 48V mutation (OR 0.01; 95%CI <0.01 to 0.88) was independently associated with lower odds of achieving an early response, whereas a higher saquinavir concentration at week 3 (OR 8.36; 95% CI 1.28 to 54.70) was associated with greater odds of an early response.


CONCLUSIONS
These findings suggest that baseline PI resistance and saquinavir concentration were associated with virologic response and should be considered when planning salvage therapy.
Immunodeficiency Service, Montreal Chest Institute, McGill University Health Centre, 3650 rue St-Urbain, Montreal, Quebec, H2X 2P4 Canada.
Graham H R
GH
Smith
Mohamed-Rachid
MR
Boulassel
Marina
M
Klien
Nobert
N
Gilmore
Jean
J
MacLeod
Roger
R
LeBlanc
Pierre
P
René
Jean-Pierre
JP
Routy
Richard G
RG
Lalonde
D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D048588:Benzoxazines; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000008:administration & dosage; D011744:Pyrimidinones / Q000008:administration & dosage; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage; D016879:Salvage Therapy; D019258:Saquinavir / Q000008:administration & dosage / Q000097:blood; D019562:Viral Load
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D010078:Oxazines; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019259:Lamivudine; C098320:efavirenz; D019258:Saquinavir; D019438:Ritonavir