Drug resistance in patients experiencing early virological failure under a triple combination including indinavir
AIDSPublished 1 September 2001
Óscar Gallego, Carmen de Mendoza, Maria Jesús Pérez‐Elías, Josep M. Guardiola, J. Pedreira, David Dalmau
Citations70
SJR quartileQ1
SJR score1.21
SNIP0.90
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Resistance to nucleoside analogues was more frequent than resistance to indinavir; treatment intensification in those patients without resistance, or a selective substitution of nucleosides in those with resistance limited to these compounds, might be justified.
Abstract
The overall rate of drug-resistant HIV genotypes was 38% (28/73) in patients with good adherence and who were experiencing a first virological failure under a triple combination regimen including indinavir; resistance to nucleoside analogues was more frequent than resistance to indinavir. Therefore, treatment intensification in those patients without resistance, or a selective substitution of nucleosides in those with resistance limited to these compounds, might be justified.
Keywords
Immunology and MicrobiologyMedicine
ScienceIdentification of a Reservoir for HIV-1 in Patients on Highly Active Antiretroviral Therapy
3,123 Citations1997Diana Finzi, Monika Hermankova +13 more
In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4+ T lymphocytes, and generally did not show mutations associated with resistance to the relevant antiretroviral drugs.
AIDS CareSelf-reported adherence to antiretroviral medications among participants in HIV clinical trials: The AACTG Adherence Instruments
1,442 Citations2000Margaret A. Chesney, Jeannette R. Ickovics +6 more
The AACTG Adherence Instruments, which are comprised of two self-report questionnaires for use in clinical trials conducted by the Adult AIDS Clinical Trials Group (AACTG), were administered to 75 patients in the USA.
Journal of Clinical InvestigationThe drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors.
1,063 Citations1998Richard B. Kim, Martin F. Fromm +5 more
It is demonstrated that P-glycoprotein limits the oral bioavailability and penetration of these agents into the brain and raises the possibility that higher HIV-1 protease inhibitor concentrations may be obtained by targeted pharmacologic inhibition of P- glycoprotein transport activity.
JAMAAntiretroviral Therapy in Adults
1,034 Citations2000Charles C. J. Carpenter, David A. Cooper +16 more
NatureIn vivo emergence of HIV-1 variants resistant to multiple protease inhibitors
979 Citations1995Jon H. Condra, William A. Schleif +14 more
Five resistant variants isolated from patients undergoing therapy with the protease inhibitor MK-639 exhibited cross-resistance to all members of a panel of six structurally diverse protease inhibitors, suggesting that com-bination therapy with multiple protease inhibition may not prevent loss of antiviral activity resulting from resistance selection.
Annals of Internal MedicineHighly Active Antiretroviral Therapy in a Large Urban Clinic: Risk Factors for Virologic Failure and Adverse Drug Reactions
853 Citations1999Gregory M. Lucas, Richard E. Chaisson +1 more
The hypothesis was that the virologic response to HAART would be substantially worse among unselected patients in an inner-city clinic than among patients enrolled in clinical trials, and this study analyzed data from a cohort of protease inhibitor-naive patients in whom HAART was initiated in the clinic between March 1996 and February 1998.
PubMedAntiretroviral drug resistance testing in adult HIV-1 infection: recommendations of an International AIDS Society-USA Panel.
783 Citations2000M S Hirsch, F Brun-Vézinet +12 more
New England Journal of MedicinePersistence of HIV-1 Transcription in Peripheral-Blood Mononuclear Cells in Patients Receiving Potent Antiretroviral Therapy
619 Citations1999Manohar R. Furtado, Duncan S. Callaway +6 more
Unless the quasi-steady state levels of HIV DNA and mRNA eventually disappear with longer periods of therapy, these findings suggest that HIV-1 infection cannot be eradicated with current treatments.
BiochemistryHIV-1 Protease Inhibitors Are Substrates for the<i>MDR</i>1 Multidrug Transporter
482 Citations1998Caroline Lee, Michael M. Gottesman +6 more
It is indicated that cells in patients that express the MDR1 transporter will be relatively resistant to the anti-viral effects of the HIV-1 protease inhibitors, and that absorption, excretion, and distribution of these inhibitors in the body may be affected by the multidrug transporter.
AIDSHIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy
424 Citations1999Steven G. Deeks, Frederick Hecht +5 more
Failure of potent protease inhibitor therapy to suppress HIV RNA levels below detectable levels is common in clinical practice, and can often be explained by their suboptimal use.
Journal of VirologyGenetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor
405 Citations1996Jon H. Condra, Daniel Holder +21 more
The evolution of this resistance to IDV was found to be cumulative, indicating the need for ongoing viral replication in this process and strongly suggest that therapy should be initiated with the most efficacious regimen available, both to suppress viral spread and to inhibit the replication that is required for the evolution of resistance.
Journal of VirologyReplicative Fitness of Protease Inhibitor-Resistant Mutants of Human Immunodeficiency Virus Type 1
402 Citations1999Javier Martínez‐Picado, Anu V. Savara +2 more
Results indicate that the mutations which are usually initially selected by nelfinavir and saquinavir, D30N and L90M, respectively, impair fitness, however, additional mutations may improve the replicative capacity of these and other drug-resistant mutants.
AIDSIncreased fitness of drug resistant HIV-1 protease as a result of acquisition of compensatory mutations during suboptimal therapy
376 Citations1999Monique Nijhuis, Rob Schuurman +7 more
The evolution and fitness of viral populations appearing in a patient who received protease monotherapy indicates that the viral population in the patient does not have to represent the fittest possible variants, and thus antiretroviral therapy may drive the viral populations first through a lower fitness level and then to a higher fitness level.
JAMAMechanisms of Virologic Failure in Previously Untreated HIV-Infected Patients From a Trial of Induction-Maintenance Therapy
372 Citations2000Diane Descamps
During the maintenance phase early and late virologic failures appeared to be related more to problems of adherence and antiretroviral treatment potency, respectively, than to selection of resistant mutant viruses.
Nucleic Acids ResearchA branched DNA signal amplification assay for quantification of nucleic acid targets below 100 molecules/ml
322 Citations1997Mark L. Collins
The branched DNA hybridization assay has been improved by the inclusion of the novel nucleotides, isoC and isoG, in the amplification sequences to prevent non-specific hybridization and permits increased signal amplification.
JAMADrug Susceptibility in HIV Infection After Viral Rebound in Patients Receiving Indinavir-Containing Regimens
307 Citations2000Diane V. Havlir
BiochemistryKinetic Characterization and Cross-Resistance Patterns Of HIV-1 Protease Mutants Selected under Drug Pressure
265 Citations1995Sergei Gulnik, Leonid I. Suvorov +5 more
The kinetic model along with the panel of mutants described here should be useful for evaluating and predicting patterns of resistance for HIV PR inhibitors and may aid in the selection of inhibitor combinations to combat drug resistance.
Archives of Internal MedicinePredictors of Virological Success and Ensuing Failure in HIV-Positive Patients Starting Highly Active Antiretroviral Therapy in Europe
239 Citations2000R Paredes
HAART is associated with a favorable virological response if started when the baseline HIV-1 RNA level is low, if at least 2 new nucleoside retrotranscriptase inhibitors are added, and if standard doses of saquinavir hard gel capsule are avoided as a single protease inhibitor.
AIDSPhenotypic and genotypic analysis of clinical HIV-1 isolates reveals extensive protease inhibitor cross-resistance: a survey of over 6000 samples
184 Citations2000Kurt Hertogs, Stuart Bloor +8 more
Extensive use of first-generation PIs leads to the emergence of HIV-1 isolates possessing cross-resistance to all members of this class, and identifying particular mutational profiles among these isolates may assist in the design of new generation inhibitors with specific activity against protease-mutant HIV strains.
The Lancet1998 revision to the British HIV Association guidelines for antiretroviral treatment of HIV seropositive individuals
184 Citations1998Brian Gazzard, Graeme Graeme
The BHIVA guidelines are updated with a consensus drawn from a wide range of UK medical opinion, and data from two large clinical endpoint studies have been presented that show superior clinical benefit for the use of triple therapy compared with dual therapy.
AIDSAnalysis of HIV cross-resistance to protease inhibitors using a rapid single-cycle recombinant virus assay for patients failing on combination therapies
131 Citations1999Esther Race, Elizabeth M. Dam +3 more
The results suggest that, although the total number of protease mutations correlates with the degree of cross-resistance, the specific mechanisms accounting for primary resistance and for cross- Resistance may be different.
Antimicrobial Agents and ChemotherapyA Novel Human Immunodeficiency Virus Type 1 Reverse Transcriptase Mutational Pattern Confers Phenotypic Lamivudine Resistance in the Absence of Mutation 184V
119 Citations2000Kurt Hertogs, Stuart Bloor +10 more
The assumption that HIV-1 may have access to several different genetic pathways to escape drug pressure or that the increase in the frequency of particular mutations may affect susceptibility to drugs that have never been part of a particular regimen is supported.
AIDSIntroduction of HIV drug-resistance testing in clinical practice
74 Citations1999Rafael Rodrı́guez-Rosado, Carlos Briones +1 more
Journal of Virological MethodsIsolation of HIV-1 RNA from plasma: evaluation of eight different extraction methods
51 Citations1996C. Verhofstedea, Katrien Fransen +6 more
Of the single-step RNA purification methods, good results were obtained with the TRIzol method (Gibco Life Technologies, Paisley, UK) and with the extraction method offered by the NASBA kit (Organon Teknika, Turnhout, Belgium), and both are sensitive enough to detect low copy numbers of HIV-RNA in the plasma of asymptomatic patients.
Antimicrobial Agents and ChemotherapyLow Level of Cross-Resistance to Amprenavir (141W94) in Samples from Patients Pretreated with Other Protease Inhibitors
44 Citations2000Bárbara Schmidt, Klaus Korn +4 more
Amprenavir appears to be an interesting alternative for PI salvage therapy, as only 2 of 23 samples from nelfinavir-naive patients with resistance against indinavir, saquinavir, and ritonavir were still sensitive to nelfinvir.
Journal of Clinical MicrobiologyEarly Virological Failure in Naive Human Immunodeficiency Virus Patients Receiving Saquinavir (Soft Gel Capsule)-Stavudine-Zalcitabine (MIKADO Trial) Is Not Associated with Mutations Conferring Viral Resistance
29 Citations2000Mireille Mouroux, A. Yvon-Groussin +12 more
Results and the fact that the plasma SQV concentrations in the two groups prior to relapse were not significantly different strongly suggest that the early failure of this combination is not due to viral resistance but to a lack of compliance, pharmacological variability, and drug interactions or a combination of these factors.
Antiviral TherapyEfficiency of Drug Resistance Genotypic Tests in Specimens with Low HIV Viral Load
12 Citations1999M Gómez-Cano, Amalia Rubio +5 more
The results support that new, more sensitive, HIV RNA extraction methods need to be implemented for the rapid recognition of drug-resistant mutants in patients experiencing an early rebound in plasma viraemia.
AIDSHIV-1 resistance genotyping by sequencing produces inconsistent results for mixed viral populations
10 Citations2000John Frater, Cécile Claire Chaput +2 more
Aids ReviewsSecond Spanish Consensus on the Use of Drug Resistance Testing in Clinical Practice (Madrid, March 2000)
7 Citations2000Vincent Soriano, Emilio Ledesma +27 more