RESUMEN
Genotypic surveys suggest that human immunodeficiency virus type 1 (HIV-1) and HIV-2 evolve different sets of mutations in response to nucleoside reverse-transcriptase inhibitors (NRTIs). We used site-directed mutagenesis, culture-based phenotyping, and cell-free assays to determine the resistance profiles conferred by specific amino acid replacements in HIV-2 reverse transcriptase. Although thymidine analogue mutations had no effect on zidovudine sensitivity, the addition of Q151M together with K65R or M184V was sufficient for high-level resistance to both lamivudine and zidovudine in HIV-2, and the combination of K65R, Q151M, and M184V conferred classwide NRTI resistance. These data suggest that current NRTI-based regimens are suboptimal for treating HIV-2 infection.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Antivirales/farmacología , Infecciones por VIH/tratamiento farmacológico , VIH-2/genética , ADN Polimerasa Dirigida por ARN/genética , Inhibidores de la Transcriptasa Inversa/uso terapéutico , África Occidental/epidemiología , Sustitución de Aminoácidos , Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral/efectos de los fármacos , Predisposición Genética a la Enfermedad , VIH-1/efectos de los fármacos , VIH-1/genética , VIH-2/efectos de los fármacos , VIH-2/enzimología , Humanos , Mutagénesis Sitio-Dirigida , Fenotipo , ADN Polimerasa Dirigida por ARN/efectos de los fármacos , Zidovudina/farmacologíaRESUMEN
Using an indicator cell assay that directly quantifies viral replication, we show that human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2, respectively) exhibit similar sensitivities to 3'-azido-3'-deoxythymidine (zidovudine) as well as other nucleoside analog inhibitors of reverse transcriptase. These data support the use of nucleoside analogs for antiviral therapy of HIV-2 infection.