High Prevalence of Secondary Resistance Mutations in Venezuelan HIV-1 Isolates

• Mariacarolina Dieudonne Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas
• Domingo Garzaro Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas
• Jaime Torres Sección de Infectología, Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela
• Laura Naranjo Sección de Infectología, Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela
• José Antonio Suárez Sección de Infectología, Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela
• Julio Castro Sección de Infectología, Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela
• Nahir Martínez Sección de Infectología, Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela
• Erika Castro Instituto de Inmunología, Universidad Central de Venezuela
• Lisbeth Berrueta Instituto de Inmunología Clínica, Facultad de Medicina, Universidad de Los Andes. Mérida
• Siham Salmen Instituto de Inmunología Clínica, Facultad de Medicina, Universidad de Los Andes. Mérida
• Marisol Devesa Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas
• Héctor R Rangel Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas
• Flor Helene Pujol Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas

Resumen

The genetic variability was studied in HIV-1 from Venezuelan patients with and without treatment, in order to evaluate the presence of polymorphisms and drug resistance mutations. Proviral DNA from peripheral blood mononuclear cells or viral RNA from plasma was extracted from the blood of 30 patients. Two regions from the polymerase gene, protease (Pr) and reverse transcriptase (RT) and one genomic fragment from the envelope (Env) gene were amplified and sequenced. All HIV-1 samples analyzed were classified as subtype B, without evidence of recombination. Although no primary protease mutations were detected, a high frequency of secondary mutations (86%, 19/22), associated to restoration of viral replicative fitness, was observed in strains circulating both in treated and non-treated patients. Resistance mutations to nucleoside RT inhibitors (NRTI) and non-nucleoside RT inhibitors (NNRTI) were detected in 35% (6/17) and 12% (2/17) of the viruses circulating in treated patients, respectively. Resistance mutations were also present in the virus infecting one antiretroviral na í¯ve individual (7.7%), suggesting that local screening for resistant mutation in na í¯ve patient might be important to minimize therapy failure. Future studies are warranted to assess the role of secondary mutation in the success of viral infection