Olivier Epaulard1, Anne Signori-Schmuck2, Sylvie Larrat2, Om Kulkarni3, Michael G Blum3, Katia Fusillier4, Myriam Blanc5, Pascale Leclercq5, Olivier François3, Patrice Morand2. 1. Infectious Disease Unit, Centre Hospitalier Universitaire Grenoble Alpes, CS10217, 38043 Grenoble Cedex 9, France; Team "HIV and human persistent viruses", Institut de Biologie Structurale, UMR5075 CNRS-CEA-UGA, Grenoble, France; Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Université Grenoble Alpes, France. Electronic address: OEpaulard@chu-grenoble.fr. 2. Team "HIV and human persistent viruses", Institut de Biologie Structurale, UMR5075 CNRS-CEA-UGA, Grenoble, France; Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Université Grenoble Alpes, France; Virology Laboratory, Infectious Agents Department, Centre Hospitalier Universitaire Grenoble Alpes, CS10217, 38043 Grenoble Cedex 9, France. 3. Computational and Mathematical Biology, TIMC-IMAG UMR 5525 UJF-INPG-CNRS, Domaine de la Merci, 38706 La Tronche Cedex, France. 4. Virology Laboratory, Infectious Agents Department, Centre Hospitalier Universitaire Grenoble Alpes, CS10217, 38043 Grenoble Cedex 9, France. 5. Infectious Disease Unit, Centre Hospitalier Universitaire Grenoble Alpes, CS10217, 38043 Grenoble Cedex 9, France; Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Université Grenoble Alpes, France.
Abstract
BACKGROUND: Ultradeep pyrosequencing technologies permit an assessment of the genetic diversity and the presence and frequency of minority variants in a viral population. The effect of these parameters on the outcome of highly active antiretroviral therapy (HAART) in HIV-infected patients is poorly understood. OBJECTIVES: The present study used the pyrosequencing Roche 454 prototype assay to determine whether antiretroviral efficacy is correlated with viral diversity and minority drug resistance mutations in HIV-infected treatment-naive patients and to compare assay performance in B and non-B subtypes. STUDY DESIGN: The study included 30 HIV-1 infected naive patients (20 with subtype non-B and 10 with subtype B). Ultradeep pyrosequencing of protease and reverse transcriptase genes was performed at baseline and 1 month after HAART initiation. Plasma HIV VL was measured at 0 and after 1, 3, and 6 months of HAART. RESULTS: Pre-HAART minority drug resistance mutations were observed to NRTI in 4 patients, to NNRTI in 6 patients, and to PI in 1 patient; there was no difference in HAART-induced VL decay between patients. Pre-HAART diversity was significantly correlated with the time elapsed since HIV-1 infection diagnosis, but not with the subtype, VL, or CD4 count. Patients with an undetectable VL after 3 months of HAART had a higher pre-HAART diversity. Pre- and post-HAART diversities were not statistically different. There was no difference in assay performance between subtype B and non-B. CONCLUSIONS: A high pre-HAART viral diversity might have a positive effect on the outcome of HAART. Pre-therapeutic minority drug resistance mutations are uncommon in naive patients.
BACKGROUND: Ultradeep pyrosequencing technologies permit an assessment of the genetic diversity and the presence and frequency of minority variants in a viral population. The effect of these parameters on the outcome of highly active antiretroviral therapy (HAART) in HIV-infectedpatients is poorly understood. OBJECTIVES: The present study used the pyrosequencing Roche 454 prototype assay to determine whether antiretroviral efficacy is correlated with viral diversity and minority drug resistance mutations in HIV-infected treatment-naive patients and to compare assay performance in B and non-B subtypes. STUDY DESIGN: The study included 30 HIV-1 infected naivepatients (20 with subtype non-B and 10 with subtype B). Ultradeep pyrosequencing of protease and reverse transcriptase genes was performed at baseline and 1 month after HAART initiation. Plasma HIV VL was measured at 0 and after 1, 3, and 6 months of HAART. RESULTS: Pre-HAART minority drug resistance mutations were observed to NRTI in 4 patients, to NNRTI in 6 patients, and to PI in 1 patient; there was no difference in HAART-induced VL decay between patients. Pre-HAART diversity was significantly correlated with the time elapsed since HIV-1 infection diagnosis, but not with the subtype, VL, or CD4 count. Patients with an undetectable VL after 3 months of HAART had a higher pre-HAART diversity. Pre- and post-HAART diversities were not statistically different. There was no difference in assay performance between subtype B and non-B. CONCLUSIONS: A high pre-HAART viral diversity might have a positive effect on the outcome of HAART. Pre-therapeutic minority drug resistance mutations are uncommon in naive patients.
Authors: Herbert A Mbunkah; Silvia Bertagnolio; Raph L Hamers; Gillian Hunt; Seth Inzaule; Tobias F Rinke De Wit; Roger Paredes; Neil T Parkin; Michael R Jordan; Karin J Metzner Journal: J Infect Dis Date: 2020-04-27 Impact factor: 5.226