RESUMEN
HIV-1 genetic diversity information from a pediatric population is scarce. This study enrolled 128 children living with HIV/AIDS, 103 antiretroviral-treated and 25 naive, from the Sao Paulo metropolitan area. Gag, pol and env regions were amplified, and drug resistance mutations, V3 loop, tropism and viral clades were evaluated. Drug resistance mutations among naïve children infected by vertical transmission were uncommon (4.2%), whereas most ARV-experienced children showed extensive mutation patterns. Clade B predominated at the pol region, but the analysis of the three regions concatenated showed 28% with BF mosaic structures. The most common V3 motif was GPGR, followed by GWGR in clade B samples and GPGQ in clade F samples. A predicted X4 phenotype was observed in 27%, without correlation to HIV clade. These findings expand the limited information on molecular characteristics of HIV-1 among children living with HIV/AIDS in the area and may provide information useful for monitoring the epidemic.
Asunto(s)
Variación Genética , Genoma Viral , Infecciones por VIH/virología , VIH-1/genética , ARN Viral/genética , Adolescente , Secuencia de Aminoácidos , Brasil , Niño , Preescolar , Análisis por Conglomerados , Farmacorresistencia Viral , Femenino , Humanos , Lactante , Masculino , Datos de Secuencia Molecular , Mutación Missense , Filogenia , Análisis de Secuencia de ADN , Homología de Secuencia , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
Antiretroviral resistance mutations (ARM) are one of the major obstacles for pharmacological human immunodeficiency virus (HIV) suppression. Plasma HIV-1 RNA from 306 patients on antiretroviral therapy with virological failure was analyzed, most of them (60%) exposed to three or more regimens, and 28% of them have started therapy before 1997. The most common regimens in use at the time of genotype testing were AZT/3TC/nelfinavir, 3TC/D4T/nelfinavir and AZT/3TC/efavirenz. The majority of ARM occurred at protease (PR) gene at residue L90 (41%) and V82 (25%); at reverse transcriptase (RT) gene, mutations at residue M184 (V/I) were observed in 64%. One or more thymidine analogue mutations were detected in 73%. The number of ARM at PR gene increased from a mean of four mutations per patient who showed virological failure at the first ARV regimens to six mutations per patient exposed to six or more regimens; similar trend in RT was also observed. No differences in ARM at principal codon to the three drug classes for HIV-1 clades B or F were observed, but some polymorphisms in secondary codons showed significant differences. Strategies to improve the cost effectiveness of drug therapy and to optimize the sequencing and the rescue therapy are the major health priorities.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Farmacorresistencia Viral/genética , Infecciones por VIH/virología , VIH-1/genética , Mutación , Adolescente , Adulto , Brasil , Recuento de Linfocito CD4 , Niño , Protocolos Clínicos , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Proteasa del VIH/genética , Transcriptasa Inversa del VIH/genética , VIH-1/efectos de los fármacos , VIH-1/enzimología , Humanos , Masculino , Reacción en Cadena de la Polimerasa , ARN Viral/genéticaRESUMEN
Antiretroviral resistance mutations (ARM) are one of the major obstacles for pharmacological human immunodeficiency virus (HIV) suppression. Plasma HIV-1 RNA from 306 patients on antiretroviral therapy with virological failure was analyzed, most of them (60 percent) exposed to three or more regimens, and 28 percent of them have started therapy before 1997. The most common regimens in use at the time of genotype testing were AZT/3TC/nelfinavir, 3TC/D4T/nelfinavir and AZT/3TC/efavirenz. The majority of ARM occurred at protease (PR) gene at residue L90 (41 percent) and V82 (25 percent); at reverse transcriptase (RT) gene, mutations at residue M184 (V/I) were observed in 64 percent. One or more thymidine analogue mutations were detected in 73 percent. The number of ARM at PR gene increased from a mean of four mutations per patient who showed virological failure at the first ARV regimens to six mutations per patient exposed to six or more regimens; similar trend in RT was also observed. No differences in ARM at principal codon to the three drug classes for HIV-1 clades B or F were observed, but some polymorphisms in secondary codons showed significant differences. Strategies to improve the cost effectiveness of drug therapy and to optimize the sequencing and the rescue therapy are the major health priorities.
