RESUMEN
The efficacy of sequential protease inhibitor therapy was studied in 16 human immunodeficiency virus (HIV) 1-infected persons in whom saquinavir with multiple nucleoside reverse transcriptase (RT) inhibitors (NRTI) had failed. Nelfinavir plus two NRTIs (new or continued) resulted in minimal (0.59 log RNA copies/mL) and transient (8 weeks) suppression of plasma HIV RNA levels. Rapid failure was surprisingly associated with baseline presence of protease gene mutation L90M (P=.04) in the absence of D30N and with RT mutations D67N (P<.01), K70R/S (P=.02), and K219Q/W/R/E (P<.01). Ten patients were subsequently switched to indinavir plus nevirapine and 2 NRTIs, resulting in a median 1.62 log reduction in plasma HIV RNA, with 3 patients maintaining 400 copies/mL for 24 weeks. These results suggest that nelfinavir may have limited utility after saquinavir failure, particularly without potent concomitant therapy. Combining an NRTI with a new protease inhibitor for rescue may improve response.
Asunto(s)
Inhibidores de la Proteasa del VIH/uso terapéutico , Seropositividad para VIH/tratamiento farmacológico , VIH-1 , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Resistencia a Medicamentos , Proteasa del VIH/genética , Transcriptasa Inversa del VIH/genética , Seropositividad para VIH/virología , VIH-1/genética , Humanos , Indinavir/uso terapéutico , Masculino , Persona de Mediana Edad , Nelfinavir/efectos adversos , Nelfinavir/uso terapéutico , Nevirapina/uso terapéutico , Polifarmacia , Pronóstico , ARN Viral/sangre , Saquinavir/uso terapéuticoRESUMEN
Herpesvirus papio (HVP) is a lymphotropic virus of baboons which is related to Epstein-Barr virus (EBV) and produces latent infection. The nucleotide sequence of the 5,775-base-pair (bp) EcoRI K fragment of HVP, which has previously been shown to confer the ability to replicate autonomously, has been determined. Within this DNA fragment is a region which bears structural and sequence similarity to the ori-P region of EBV. The HVP ori-P region has a 10- by 26-bp tandem array which is related to the 20- by 30-bp tandem array from the EBV ori-P region. In HVP there is an intervening region of 764 bp followed by five partial copies of the 26-bp monomer. Both the EBV and HVP 3' regions have the potential to form dyad structures which, however, differ in arrangement. We also demonstrate that a transcriptional enhancer which requires transactivation by a virus-encoded factor is present in the HVP ori-P.
Asunto(s)
Replicación del ADN , Herpesviridae/genética , Plásmidos , Animales , Secuencia de Bases , Línea Celular , Cloranfenicol O-Acetiltransferasa/genética , Desoxirribonucleasa EcoRI , Herpesvirus Humano 4/genética , Datos de Secuencia Molecular , Papio , Secuencias Repetitivas de Ácidos Nucleicos , Mapeo Restrictivo , Homología de Secuencia de Ácido NucleicoRESUMEN
Herpesvirus papio (HVP) and Epstein-Barr virus (EBV) are closely related biologically and biochemically; lymphoblastoid cells infected with either virus contain episomal viral DNA. The putative origin of replication for EBV plasmids (oriP) has been assigned to a 1,790-base-pair fragment (cis) in the short unique region of the genome which requires a viral function supplied in trans from elsewhere in the genome (J. Yates, N. Warren, D. Reisman, and B. Sugden, Proc. Natl. Acad. Sci. USA 81:3806-3810, 1984). We report here the identification of the putative origin of replication (cis) in HVP; we assigned it to the HVP EcoRI K fragment. The results indicate that the HVP replication process requires both a cis and a trans-acting function, analogous to that found in EBV.