title: Mutational Heterogeneity in p6 Gag Late Assembly (L) Domains in HIV-1 Subtype C Viruses from South Africa.
abstract: Contradictory results have been reported on the impact of duplications/insertions in the HIV-1 gag-p6 late assembly domains [TSG101-binding P(T/S)APP motif and ALIX-binding LYPxnLxxL motif] heterogeneity following therapy failure. However, most studies are limited to small numbers of patients and do not include samples from South Africa, which has the largest number of HIV-1C-infected patients (HIV-1CZA). In this study we compared the gag-p6 variability among HIV-1CZA-infected patients from a South African clinical cohort who experienced antiretroviral therapy (ART) failure (n = 845) with ART-naive HIV-1CZA sequences (n = 706) downloaded from the Los Alamos database. Partial (PTA/PTV/APP) or complete P(T/S)APP duplications were less frequent in HIV-1CZA with ART failure compared to therapy-naive ones (14% vs. 30%; p < 0.001). In contrast, the tetrapeptide PYxE insertion, recently described by us, occurred more frequently (5-fold) in therapy-failure patients (p < 0.001) and was associated with a higher number of reverse transcriptase inhibitor (RTI) mutations (p = 0.04) among patients failing ART.
authors.affiliation: 1 Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Ujjwal
authors.initials: U
authors.lastname: Neogi
authors.affiliation: 2 Faculty of Medicine and Health Sciences, Division of Medical Virology, Stellenbosch University , Cape Town, South Africa .|3 National Health Laboratory Service (NHLS), Tygerberg Hospital , Tygerberg, South Africa .
authors.forename: Susan
authors.initials: S
authors.lastname: Engelbrecht
authors.affiliation: 3 National Health Laboratory Service (NHLS), Tygerberg Hospital , Tygerberg, South Africa .
authors.forename: Mathilda
authors.initials: M
authors.lastname: Claassen
authors.affiliation: 2 Faculty of Medicine and Health Sciences, Division of Medical Virology, Stellenbosch University , Cape Town, South Africa .
authors.forename: Graeme Brendon
authors.initials: GB
authors.lastname: Jacobs
authors.affiliation: 2 Faculty of Medicine and Health Sciences, Division of Medical Virology, Stellenbosch University , Cape Town, South Africa .|3 National Health Laboratory Service (NHLS), Tygerberg Hospital , Tygerberg, South Africa .
authors.forename: Gert
authors.initials: G
authors.lastname: van Zyl
authors.affiliation: 2 Faculty of Medicine and Health Sciences, Division of Medical Virology, Stellenbosch University , Cape Town, South Africa .|3 National Health Laboratory Service (NHLS), Tygerberg Hospital , Tygerberg, South Africa .
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Preiser
authors.affiliation: 1 Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet , Stockholm, Sweden .|4 Department of Medicine Huddinge, Unit of Infectious Diseases, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Anders
authors.initials: A
authors.lastname: Sonnerborg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D020816:Amino Acid Motifs; D023241:Antiretroviral Therapy, Highly Active; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009154:Mutation; D011110:Polymorphism, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013019:South Africa / Q000453:epidemiology; D017211:Treatment Failure; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054301:gag Gene Products, Human Immunodeficiency Virus