RESUMEN
Objectives: The present study investigated the relationship between genomic variability and resistance of HIV-1 sequences in protease (PR) and reverse transcriptase (RT) regions of the pol gene. In addition, we analysed the resistance among 651 individuals presenting antiretroviral virological failure, from 2009 to 2011, in the state of São Paulo, Brazil. Methods: The genomic variability was quantified by using informational entropy methods and the relationship between resistance and replicative fitness, as inferred by the residual viral load and CD4+ T cell count. Results: The number of antiretroviral schemes is related to the number of resistance mutations in the HIV-1 PR (α = 0.2511, P = 0.0003, R2 = 0.8672) and the RT (α = 0.7892, P = 0.0001, R2 = 0.9141). Increased informational entropy rate is related to lower levels of HIV-1 viral loads (α = -0.0121, P = 0.0471, R2 = 0.7923), lower levels of CD4+ T cell counts (α = -0.0120, P = 0.0335, R2 = 0.8221) and a higher number of antiretroviral resistance-related mutations. Conclusions: Less organized HIV genomes as inferred by higher levels of informational entropy relate to less competent host immune systems, lower levels of HIV replication and HIV genetic evolution as a consequence of antiretroviral resistance.
Asunto(s)
Antirretrovirales/farmacología , Farmacorresistencia Viral , Infecciones por VIH/virología , Integrasa de VIH/genética , Proteasa del VIH/genética , VIH-1/efectos de los fármacos , Mutación , Antirretrovirales/administración & dosificación , Brasil , Recuento de Linfocito CD4 , Aptitud Genética , Infecciones por VIH/tratamiento farmacológico , VIH-1/enzimología , VIH-1/genética , Humanos , Insuficiencia del Tratamiento , Carga ViralRESUMEN
Malignant melanoma is an aggressive skin cancer with limited therapeutic options. Cancer is the second largest cause of death in society and one of the most difficult diseases to treat. Advances in biotechnology have enabled the current use of nanotechnology via the application of nanomaterials, especially as drug delivery systems for the transportation of very small particles. In this context, carbon nanotubes, with a potential role in the diagnosis and treatment of melanoma, are still an emerging research field. Their properties have been extensively studied for the use of antineoplastics drugs, as well as for DNA and RNA interference for the treatment of cancer. However, the most important challenge in nanomedicine is to decrease the toxicity and increase the biocompatibility of the nanomaterials used to transport therapeutic molecules. In this sense, this article addresses the recent advances in the use of carbon nanotubes in melanoma therapy and highlights the opportunities and challenges in this area. The advances and challenges involving these topics are essential to the success of nanoconjugate systems, and studies improving the comprehension of these nanosystems contribute to the development of specific antitumor therapies.
RESUMEN
Malignant melanoma is an aggressive skin cancer with limited therapeutic options. Cancer is the second largest cause of death in society and one of the most difficult diseases to treat. Advances in biotechnology have enabled the current use of nanotechnology via the application of nanomaterials, especially as drug delivery systems for the transportation of very small particles. In this context, carbon nanotubes, with a potential role in the diagnosis and treatment of melanoma, are still an emerging research field. Their properties have been extensively studied for the use of antineoplastics drugs, as well as for DNA and RNA interference for the treatment of cancer. However, the most important challenge in nanomedicine is to decrease the toxicity and increase the biocompatibility of the nanomaterials used to transport therapeutic molecules. In this sense, this article addresses the recent advances in the use of carbon nanotubes in melanoma therapy and highlights the opportunities and challenges in this area. The advances and challenges involving these topics are essential to the success of nanoconjugate systems, and studies improving the comprehension of these nanosystems contribute to the development of specific antitumor therapies.