Genotypic and Phenotypic Analyses of Human Immunodeficiency Virus Type 1 in Antiretroviral Drug-Naive Nigerian Patients
- 1 January 2006
- journal article
- Published by Mary Ann Liebert Inc in AIDS Research and Human Retroviruses
- Vol. 22 (1) , 22-26
- https://doi.org/10.1089/aid.2006.22.22
Abstract
We analyzed the subtypes and genotypic and phenotypic drug susceptibility profiles of 18 HIV-1 isolates from treatment-naive patients in Nigeria. A modified gp41-based heteroduplex mobility assay was used to determine the clade designation based on the envelope gene. The protease and most of the reverse transcriptase regions were cloned into a retroviral expression vector and sequenced. Samples were also analyzed phenotypically using a rapid phenotypic assay (PhenoSense HIV, ViroLogic, Inc.). According to the modified gp41-based heteroduplex mobility assay, the patients were infected with either clade G (17 specimens) or clade A (one specimen) isolates. From phylogenetic analyses of 1212 nucleotides of the polymerase gene, 14 of the 18 isolates were strongly grouped with subtype G reference strains. The remaining four isolates were grouped with the CRF_02_AG clade. Within the protease region, all 18 isolates had mutations/polymorphic substitutions at six locations compared to the HIV-1 NL4-3 reference sequence, two of which have been associated with resistance to protease inhibitors (K20I and M36I). At least half of the isolates had mutations/polymorphic substitutions at an additional five positions in the protease region. Within the reverse transcriptase (RT) region, all 18 isolates showed an E291D mutation/polymorphic substitution. Mutations/polymorphic substitutions were also found in at least half of the isolates at 21 positions. The phenotypic profiles of the viruses correlated well with the observed genotypes. Two isolates showed slightly reduced susceptibility to one or two of the five PIs assessed (ritonavir and ritonavir/nelfinavir) and all 18 viruses were susceptible to all NRTIs and NNRTIs analyzed.Keywords
This publication has 16 references indexed in Scilit:
- Impact of frequent natural polymorphisms at the protease gene on the in vitro susceptibility to protease inhibitors in HIV-1 non-B subtypesJournal of Clinical Virology, 2004
- Minor Mutations in HIV Protease at Baseline and Appearance of Primary Mutation 90M in Patients for Whom Their First Protease‐Inhibitor Antiretroviral Regimens FailedThe Journal of Infectious Diseases, 2004
- Measurement of HIV RNA in patients infected by subtype C by assays optimized for subtype B results in an underestimation of the viral loadJournal of Medical Virology, 2004
- Antiretroviral Drug Resistance in Non-Subtype B HIV-1, HIV-2 and SivAntiviral Therapy, 2004
- Failure to detect a non-B HIV-1 subtype by the HIV-1 Amplicor Monitor test, version 1.5AIDS, 2003
- Molecular surveillance of HIV-1 field strains in Nigeria in preparation for vaccine trials1Use of trade names is for identification only and does not constitute endorsement by the US Department of Health and Human Service, or the Centers for Disease Control and Prevention.1Vaccine, 2002
- Secondary Mutations in the Protease Region of Human Immunodeficiency Virus and Virologic Failure in Drug‐Naive Patients Treated with Protease Inhibitor–Based TherapyThe Journal of Infectious Diseases, 2001
- Development of an env gp41-Based Heteroduplex Mobility Assay for Rapid Human Immunodeficiency Virus Type 1 SubtypingJournal of Clinical Microbiology, 2001
- Erroneously Low or Undetectable Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid Load, Determined by Polymerase Chain Reaction, in West African and American Patients with Non-B Subtype HIV-1 InfectionClinical Infectious Diseases, 2001
- Protease sequences from HIV-1 group M subtypes A???H reveal distinct amino acid mutation patterns associated with protease resistance in protease inhibitor-naive individuals worldwideAIDS, 2000