RESUMEN
This report describes the detection of mutations in the pol gene of human immunodeficiency virus type 1 associated with resistance to zidovudine, didanosine, and lamivudine by genotyping by an oligonucleotide ligation assay specific codons in the pol gene amplified by PCR. Our studies demonstrate the sensitivity, simplicity, and specificity of this genotyping system.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Microbiana/genética , Genes pol , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Mutación , Codón , Didanosina/uso terapéutico , Infecciones por VIH/genética , VIH-1/efectos de los fármacos , Humanos , Lamivudine/uso terapéutico , Sondas de Oligonucleótidos/genética , Reacción en Cadena de la Polimerasa/métodos , ARN Viral/análisis , ARN Viral/genética , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Zidovudina/uso terapéuticoRESUMEN
To determine if the 32-bp deletion of the chemokine receptor CCR5 (delta32ccr5) protects against mother-to-infant transmission of HIV-1, specimens from all uninfected and infected children who were perinatally exposed to HIV-1 and observed since 1988 and whose mothers did not take zidovudine were assessed for delta32ccr5. The CCR5 genotype was determined using polymerase chain reaction (PCR) for 122 subjects, of whom 73 were HIV-1 infected and 49 were perinatally exposed but uninfected; 70% and 71%, respectively, were Caucasian. Eleven of 73 (15%) infected children and 4 of 49 (8%) exposed uninfected children were CCR5/delta32ccr5 heterozygotes (p = 0.40). Among subjects who had at least one Caucasian parent or grandparent, 11 of 51 (22%) HIV-1-infected persons and 4 of 35 (11%) uninfected persons were heterozygotes. None were homozygous for the delta32ccr5 allele. The estimated relative risk for mother-to-infant HIV-1 transmission in heterozygotes was 2.0. Furthermore, the 95% confidence interval (0.6, 7.3) suggested that it is unlikely that the true relative risk was <0.6. Thus, the infant CCR5/delta32ccr5 heterozygous genotype was not associated with a diminished risk of perinatally acquired HIV-1 infection.
Asunto(s)
Infecciones por VIH/genética , Infecciones por VIH/transmisión , VIH-1/genética , Heterocigoto , Transmisión Vertical de Enfermedad Infecciosa , Receptores CCR5/genética , Alelos , Niño , Femenino , Frecuencia de los Genes , Genotipo , Infecciones por VIH/epidemiología , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Oportunidad Relativa , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVE: To determine the effects of combination antiretroviral therapy including a protease inhibitor (PI combination therapy) in children with advanced HIV-1 disease. STUDY DESIGN: An observational study of HIV-1 plasma RNA, lymphocyte subsets, delayed type hypersensitivity and physical growth after initiation of PI combination therapy. RESULTS: In nine children the median HIV-1 plasma RNA decreased 1.7 log10 (mean, 1.57; range, 0.7 to 2.2) following PI combination therapy and CD4 cells increased a median of 499 (mean, 528; range, 9 to 1088) cells/microl. A rebound of RNA, associated with the development of resistance to the PI, occurred in three subjects. Three of six children were no longer anergic and all nine achieved normal weight-growth velocities. Ritonavir was well-tolerated, despite its bitter taste; however, four of five children treated with indinavir developed renal complications. CONCLUSIONS: PI combination therapy in children with advanced HIV-1 disease was associated with a decrease in HIV-1 RNA, improved immunologic measures and normal or better weight gain. Of concern was the rebound in plasma HIV-1 associated with resistance to the PI observed in one-third of patients. This emphasizes the need for larger studies to define optimal PI containing regimens with long term efficacy in children.