Activity of a ritonavir plus saquinavir-containing regimen in patients with virologic evidence of indinavir or ritonavir failure.
OBJECTIVE
To evaluate the virologic activity of a ritonavir plus saquinavir-containing regimen in patients who have failed an indinavir or ritonavir-containing regimen.


METHODS
Patients were identified through a retrospective study evaluating the incidence of indinavir or ritonavir failure in our clinic.


METHODS
Eighteen patients failing indinavir or ritonavir therapy and who switched to a ritonavir-saquinavir-containing regimen were evaluated. Indinavir or ritonavir failure was defined as a plasma viral load > 1500 copies/ml (branched DNA) after 16 weeks of continuous therapy.


METHODS
All patients switched to ritonavir (400 mg twice daily) plus saquinavir (400 mg twice daily) and received concurrent therapy with two nucleoside reverse transcriptase inhibitors (NRTI). Twelve of the 18 patients modified their NRTI regimen at the time ritonavir-saquinavir was initiated.


METHODS
Plasma viral load was monitored using a branched DNA assay. Genotypic analysis was performed using a point mutation differential hybridization technique, and was confirmed with direct sequencing.


RESULTS
Fourteen out of 18 patients completed at least 24 weeks of therapy; the remaining four patients discontinued therapy after week 12 due to a lack of virologic response or intolerance. Plasma viral load decreased a median 1.4 log10 after 4 weeks of treatment with ritonavir-saquinavir. Only four patients had a greater than 0.5 log10 decrease in viral load after 24 weeks of therapy. In eight out of 10 patients evaluated, the V82A mutation was present at the time of the switch to ritonavir-saquinavir. Viral rebound on ritonavir-saquinavir was associated with the emergence of mutations at amino acids 46, 48, 54 and 90.


CONCLUSIONS
The combination of ritonavir, saquinavir and two NRTI resulted in a moderate but transient suppression of viral replication in patients who have failed indinavir or ritonavir therapy. Failure of ritonavir-saquinavir may be associated with the emergence of mutations associated with resistance to ritonavir/saquinavir monotherapy, particularly the L90M mutation.
University of California, San Francisco and San Francisco General Hospital, 94110, USA.
S G
SG
Deeks
R M
RM
Grant
G W
GW
Beatty
C
C
Horton
J
J
Detmer
S
S
Eastman
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006678:HIV / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D008297:Male; D009693:Nucleic Acid Hybridization; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use*; D019258:Saquinavir / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D019469:Indinavir; D019258:Saquinavir; D019438:Ritonavir