Efficacy of indinavir-ritonavir-based regimens in HIV-1-infected patients with prior protease inhibitor failures.
OBJECTIVE
To assess responses to indinavir (IDV)-ritonavir (RTV)-based regimens among HIV-1 infected patients with prior failure of protease inhibitors, and to assess the effects of adherence to therapy and pre-existing genotypic and phenotypic resistance on this response.


METHODS
Twenty-eight patients initiating salvage regimens with IDV-RTV (800 mg and 200 mg twice daily, respectively) plus one or more reverse transcriptase inhibitor (RTI) were identified retrospectively. Genotypic and phenotypic susceptibilities to multiple antiretroviral agents were determined on viral samples collected at initiation of the salvage regimens, and adherence to therapy was determined through patient self-reporting. Response to therapy (viral RNA </= 400 copies/ml) was assessed at the end of and beyond 6 months of follow-up.


RESULTS
Based on responses measured in the first 6 months of follow-up, 16 responders and 12 non-responders were identified without differences in baseline demographic factors, laboratory parameters, extent of prior antiretroviral therapy, or characteristics of the RTI components of the new IDV-RTV-based regimens. Adequate adherence was associated with virologic responses (P = 0.005). There were trends for genotypic and phenotypic resistance to be associated with adequate adherence, and, surprisingly, phenotypic resistance to IDV was associated with virologic response rather than with therapeutic failure (P = 0.02). Beyond 6 months of follow-up (mean follow-up 69 weeks), adequate adherence was still associated with virologic response (P = 0.001), but genotypic or phenotypic resistance to IDV were not associated with therapeutic failure.


CONCLUSIONS
These results suggest that IDV-RTV-based regimens may be able to overcome IDV resistance. This underscores the importance of drug adherence, potency, and exposure in determining virologic responses to antiretroviral therapy.
Campo
Rafael E
RE
Department of Pathology, University of Miami School of Medicine, Florida, USA.
Moreno
Jose N
JN
Suarez
German
G
Miller
Nancimae
N
Kolber
Michael A
MA
Holder
Daniel J
DJ
Shivaprakash
Malathi
M
DeAngelis
Dana M
DM
Wright
Jennifer L
JL
Schleif
William A
WA
Emini
Emilio A
EA
Condra
Jon H
JH
D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D008297:Male; D010349:Patient Compliance; D010641:Phenotype; D012189:Retrospective Studies; D019438:Ritonavir / Q000627:therapeutic use*; D016879:Salvage Therapy / Q000379:methods; D017211:Treatment Failure; D019562:Viral Load
D017320:HIV Protease Inhibitors; D019469:Indinavir; D016333:HIV Protease; D019438:Ritonavir