Prevalence of mutations related to HIV-1 antiretroviral resistance in Brazilian patients failing HAART

Background: Current guidelines for antiretroviral (ARV) therapy recommend at least triple-drug combination, the so-called highly active antiretroviral therapy (HAART). Not all patients respond to HAART and the development of drug resistance remains one of the most serious obstacles to sustained suppression of HIV. Objective: in an attempt to correlate the HIV therapeutic failure with reverse transcriptase (RT) and protease resistance mutations, we describe the ARV resistance profile in patients failing HAART in Brazil. We studied 267 Brazilian HIV-1 infected patients failing HAART looking for mutations in RT and protease genes. the mutation profile of the viruses infecting these individuals were deduced and correlated to laboratorial parameters. Study Design: Two different HIV-1 genomic regions were targeted for PCR amplification, the protease (pro) and pal RT (palm finger region) genes. the mutations related to drug resistance in RT gene was analyzed using a line probe assay (LIPA(R)) and pro amino acids positions 82 and 90 were screened through RFLP using HincII restriction digestion. Results: There was strong correlation between the mutation in the pro and RT genes and therapeutic failure. the main mutation found in RT gene was the M184V (48%) followed by T69D/N (47%), T215Y/F (46%), M41L (39%), and L74V (7%). in the pro gene the main mutation found was L90M (26%) followed by dual substitution in L90M and V82A (6%). All mutations profiles matched very well with the patients drug regimen. Conclusions: This study has shown that 84.7% of HIV infected subjects failing HAART for more than 3 months presented viral genomic mutations associated with drug resistance. (C) 2002 Elsevier Science B.V. All rights reserved.Univ Fed Rio de Janeiro, CCS, Inst Biol, Dept Genet,Lab Virol Mol, BR-21944970 Rio de Janeiro, BrazilBrazilian Minist Hlth, Programa Brasileiro AIDS STD, Brasilia, DF, BrazilFiocruz MS, Inst Oswaldo Cruz, Lab Imunol, BR-21045900 Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Lab Petrobras, BR-21944970 Rio de Janeiro, BrazilUniv Fed Espirito Santos, Vitoria, ES, BrazilUniv Brasilia, Virol Lab, Brasilia, DF, BrazilLab Cent Saude Publ, Recife, PE, BrazilUniv Fed Estado São Paulo, Lab Retrovirol, São Paulo, BrazilUniv São Paulo, Dept Epidemiol, São Paulo, BrazilLab Cent Saude Publ, Florianopolis, SC, BrazilUniv Fed Santa Catarina, Florianopolis, SC, BrazilUniv Fed Estado São Paulo, Lab Retrovirol, São Paulo, BrazilWeb of Scienc

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events