BACKGROUND: Over recent years, treatment guidelines for human immunodeficiency virus (HIV) infection have evolved from monotherapy to combination regimens that include > or = 3 active drugs, resulting in a sharp decrease in morbidity and mortality. In the present article, we evaluated changes in HIV type 1 viral fitness associated with the sequential introduction of antiretroviral treatment strategies in 4 chronically infected patients with sustained CD4 cell count despite having a persistently detectable viral load. METHODS: Plasma samples were obtained before and during treatment to construct recombinant virus containing the 3'-end of gag, the protease and the reverse-transcriptase coding region. Drug susceptibility phenotype was evaluated with a panel of multiple reverse-transcriptase and protease inhibitors. Replicative capacity (RC) and infectivity were measured, and production of p24 was monitored after transfection. RESULTS: Multidrug-resistant (MDR) viruses selected during long-term antiretroviral therapy were less fit and infectious than their wild-type or monotherapy-selected counterparts, with the exception of viruses recovered from patient B. In 3 of 4 cases, p24 kinetics after transfection showed a delay in viral production of recombinant viruses containing MDR mutations. Data from the RC and infectivity assays showed good correlation (P < .03) and corroborated the p24 kinetics data. CONCLUSIONS: This study shows that accumulation of MDR mutations during long-term antiretroviral treatment results, albeit not in all cases, in reductions of viral fitness.
BACKGROUND: Over recent years, treatment guidelines for human immunodeficiency virus (HIV) infection have evolved from monotherapy to combination regimens that include > or = 3 active drugs, resulting in a sharp decrease in morbidity and mortality. In the present article, we evaluated changes in HIV type 1 viral fitness associated with the sequential introduction of antiretroviral treatment strategies in 4 chronically infected patients with sustained CD4 cell count despite having a persistently detectable viral load. METHODS: Plasma samples were obtained before and during treatment to construct recombinant virus containing the 3'-end of gag, the protease and the reverse-transcriptase coding region. Drug susceptibility phenotype was evaluated with a panel of multiple reverse-transcriptase and protease inhibitors. Replicative capacity (RC) and infectivity were measured, and production of p24 was monitored after transfection. RESULTS: Multidrug-resistant (MDR) viruses selected during long-term antiretroviral therapy were less fit and infectious than their wild-type or monotherapy-selected counterparts, with the exception of viruses recovered from patient B. In 3 of 4 cases, p24 kinetics after transfection showed a delay in viral production of recombinant viruses containing MDR mutations. Data from the RC and infectivity assays showed good correlation (P < .03) and corroborated the p24 kinetics data. CONCLUSIONS: This study shows that accumulation of MDR mutations during long-term antiretroviral treatment results, albeit not in all cases, in reductions of viral fitness.
Authors: Cristina Villena; Julia G Prado; Maria Carmen Puertas; Miguel Angel Martínez; Bonaventura Clotet; Lidia Ruiz; Neil T Parkin; Luis Menéndez-Arias; Javier Martinez-Picado Journal: J Virol Date: 2007-02-21 Impact factor: 5.103
Authors: Julia G Prado; Andrew Prendergast; Christina Thobakgale; Claudia Molina; Gareth Tudor-Williams; Thumbi Ndung'u; Bruce D Walker; Philip Goulder Journal: J Virol Date: 2010-01 Impact factor: 5.103
Authors: Ralph-Sydney Mboumba Bouassa; Helene Pere; Christian Diamant Mossoro-Kpinde; Pierre Roques; Jean Chrysostome Gody; Sandrine Moussa; David Veyer; Gerard Gresenguet; Charlotte Charpentier; Mohammad-Ali Jenabian; Joel Fleury Djoba Siawaya; Laurent Belec Journal: J Clin Med Res Date: 2020-06-04