title: In vivo HIV-1 hypermutation and viral loads among antiretroviral-naive Brazilian patients.
abstract: Hypermutation alludes to an excessive number of specific guanine-to-adenine (G- >A) substitutions in proviral DNA and this phenomenon is attributed to the catalytic activity of cellular APOBECs. Population studies relating hypermutation and the progression of infection by human immunodeficiency virus type 1 (HIV-1) have been performed to elucidate the effect of hypermutation on the natural course of HIV-1 infection. However, the many different approaches employed to assess hypermutation in nucleotide sequences render the comparison of results difficult. This study selected 157 treatment-naive patients and sought to correlate the hypermutation level of the proviral sequences in clinical samples with demographic variables, HIV-1 RNA viral load, and the level of CD4(+) T cells. Nested touchdown polymerase chain reaction (PCR) was performed with specific primers to detect hypermutation in the region of HIV-1 integrase, and the amplified sequences were run in agarose gels with HA-Yellow. The analysis of gel migration patterns using the k-means clustering method was validated by its agreement with the results obtained with the software Hypermut. Hypermutation was found in 31.2% of the investigated samples, and a correlation was observed between higher hypermutation levels and higher viral load levels. These findings suggest a high frequency of hypermutation detection in a Brazilian cohort, which can reflect a particular characteristic of this population, but also can result from the method approach by aiming at hypermutation-sensitive sites. Furthermore, we found that hypermutation events are pervasive during HIV-1 infection as a consequence of high viral replication, reflecting its role during disease progression.
authors: 1 Federal University of São Paulo , São Paulo, SP, Brazil .
authors: Mariana Leão
authors: ML
authors: de Lima-Stein
authors: Wagner Tadeu
authors: WT
authors: Alkmim
authors: Maria Clara de Souza
authors: MC
authors: Bizinoto
authors: Luis Fernandez
authors: LF
authors: Lopez
authors: Marcelo Nascimento
authors: MN
authors: Burattini
authors: Juliana Terzi
authors: JT
authors: Maricato
authors: Leila
authors: L
authors: Giron
authors: Maria Cecília Araripe
authors: MC
authors: Sucupira
authors: Ricardo Sobhie
authors: RS
authors: Diaz
authors: Luiz Mario
authors: LM
authors: Janini
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001483:Base Sequence; D001938:Brazil; D017931:DNA Primers; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017931:DNA Primers