Left main coronary artery spasm: medical versus surgical management.
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Publications and source records attributed to Charles Boucher.
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This report summarizes research advances that further our understanding of the evolution, mechanisms and clinical impact of HIV drug resistance presented at the XIVth International HIV Drug Resistance Workshop held in Quebec City, Canada from June 7-11, 2005. The topics that were discussed included the clinical implications of resistance in mother-to-child transmission, breakthroughs in technologies for studying resistance, resistance to new antiretroviral agents, mechanisms of HIV drug resistance, epidemiological trends, and HIV fitness and pathogenesis.
BACKGROUND: Mathematical modeling has suggested that alternating antiretroviral regimens while patients' viral load remains suppressed would minimize HIV resistance mutations. OBJECTIVE: To compare alternation of antiretroviral regimens with the current standard of switching regimens after viral load rebound. DESIGN: Randomized, multicenter, open-label, pilot trial. SETTING: 15 outpatient HIV clinics in Spain and Argentina. PATIENTS: 161 HIV-1-infected, antiretroviral-naive persons. INTERVENTION: Patients were assigned to continuously receive stavudine, didanosine, and efavirenz (standard of care, regimen A) or zidovudine, lamivudine, and nelfinavir (standard of care, regimen B) until virologic failure, or to alternate between those two regimens every 3 months while viral load was suppressed (regimen C). MEASUREMENTS: Time to virologic failure, percentage of patients with undetectable plasma viremia over 48 weeks, CD4 and CD8 cell counts, adverse events, emergence of drug resistance, drug adherence, and quality of life. RESULTS: Patients receiving standard-of-care regimens A and B did not differ. Virologic failure over 48 weeks was delayed in the alternating therapy group compared with the pooled standard-of-care group (incidence rate, 1.2 events/1000 person-weeks [95% CI, 0.3 to 3.6 events/1000 person-weeks] vs. 4.8 events/1000 person-weeks [CI, 2.9 to 7.4 events/1000 person-weeks]; P = 0.01). Genotypic drug resistance emerged in 79% of patients in the standard-of-care group who experienced on-therapy treatment failure. Patients in the standard-of-care and alternating therapy groups had similar CD4 cell counts, frequency of adverse events, reported drug adherence, and quality of life. CONCLUSIONS: Virologic outcome was better with alternating therapy than with the current standard of care, while adverse events and adherence were similar. The strategy of alternating therapy merits further investigation.
We compared 2 rules-based genotype interpretation systems and real or virtual phenotype through a retrospective analysis of a prospective trial. Genotypes were determined with VircoGEN II (VIRCO) and were interpreted with either RetroGram 1.4 or TRUGENE HIV-1 (guidelines 3.0) or original virtual phenotype (Virtual Phenotype; VIRCO), as available in the year 2000. Among 188 human immunodeficiency virus (HIV) type 1 isolates, overall concordance (kappa agreement) was observed for the 2 rules-based systems, whereas striking discordances were noted between them and real and virtual phenotype interpretations for stavudine, didanosine, zalcitabine, abacavir, and amprenavir (kappa<0.4). Clinical evaluation of a subset of 173 patients showed that both rules-based sensitivity scores were independently associated with HIV RNA loads <400 copies/mL at week 16 of during-treatment analysis (TRUGENE: odds ratio [OR], 2.90; 95% confidence interval [CI], 1.52-5.52; P=.001; RetroGram: OR, 2.34; 95% CI, 1.21-4.55; P=.012), whereas, in contrast to real or virtual phenotype, interpretations according to biological cut-offs were not (OR, 1.91; 95% CI, 0.77-4.76; P=.162).
OBJECTIVE: To determine the influence of age on the regeneration rate of naive and memory T cells in the blood of 45 adults on highly active antiretroviral therapy (HAART). METHODS: The age of the patients ranged from 25 to 57 years. Naive cells were defined as CD45RA+CD27+. Cells negative for CD45RA and/or CD27 were considered memory type cells. RESULTS: The recovery rates of naive CD4 and CD8 T cells were similar, were negatively correlated with age and were decreasing 5% and 3.6% per year, respectively. In a multivariate regression analysis, only age was significantly correlated with the naive T cell recovery rates. The recovery rate of memory T cells showed no relation to age. The average regeneration rate of naive CD4 T cells during HAART, i.e., 0.34 x 10(6) cells/l per day, is not lower than regeneration rates in HIV-negative adults following cytotoxic chemotherapy or CD4 monoclonal antibody therapy. CONCLUSION: These observations suggest that the thymus contributes considerably to the regeneration of naive T cells in adults on HAART, and that the impact of HIV infection on naive T cell production is small, or rapidly reversible.
OBJECTIVE: To determine whether HIV-1 genotyping and expert advice add additional short-term virologic benefit in guiding antiretroviral changes in HIV+ drug-experienced patients. DESIGN: A two factorial (genotyping and expert advice), randomized, open label, multi-center trial. The patients were stratified according to the number of treatment failures. PATIENTS AND METHODS: HIV-1 infected patients on stable antiretroviral therapy who presented virological failure were included into the study. Genotypic testing was performed by using TrueGene HIV Genotyping kit and the results were interpreted by a software package (RetroGram, version 1.0). An expert advisory committee suggested the new therapeutic approach based on clinical information alone or on clinical information plus HIV-1 genotyping results. Plasma HIV-1 RNA load, CD4+ cell count and adverse events were recorded at baseline and every 12 weeks. RESULTS: A total of 326 patients were included. The baseline CD4+ cell count and plasma HIV-1 RNA were 387 (+/- 224) x 10(6) cells/l and 4 (+/- 1) log(10) respectively. The proportion of patients with plasma HIV-1 RNA < 400 copies/ml at 24 weeks differed between genotyping and no genotyping arms (48.5 and 36.2%, P < 0.05). Factors associated with a higher probability of plasma HIV-1 RNA < 400 copies/ml were HIV-1 genotyping [odds ratio (OR), 1.7; 95% confidence interval (CI), 1.1-2.8; P = 0.016] and the expert advice in patients failing to a second-line antiretroviral therapy (OR, 3.2; 95% CI, 1.2-8.3; P = 0.016). CONCLUSIONS: HIV-1 genotyping interpreted by a software package improves the virological outcome when it is added to the clinical information as a basis for decisions on changing antiretroviral therapy. The expert advice also showed virologic benefit in the second failure group.