Primary HIV-1 drug resistance in the C-terminal domains of viral reverse transcriptase among drug-naïve patients from Southern Brazil

• Published in: Journal of clinical virology 2011-12, Vol.52 (4), p.373-376
• Main Authors: Santos, André F, Silveira, Jussara, Muniz, Cláudia P, Tornatore, Michele, Góes, Lívia R, Mendoza-Sassi, Raul A, Martinez, Ana M.B, Tupinambás, Unaí, Greco, Dirceu B, Soares, Marcelo A
• Format: Article
• Language: English
• Subjects: Adult; Allergy and Immunology; Biological and medical sciences; Brazil; Brazil - epidemiology; C-terminal; Connection; Drug resistance mutation; Drug Resistance, Viral; Female; Fundamental and applied biological sciences. Psychology; Genotype; HIV Infections - epidemiology; HIV Infections - virology; HIV Reverse Transcriptase - genetics; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious Disease; Infectious diseases; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Mutation, Missense; Polymerase Chain Reaction; Prevalence; Primary resistance; RNA, Viral - blood; RNA, Viral - genetics; RNA, Viral - isolation & purification; RNase H; Sequence Analysis, DNA; Viral diseases; Virology
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/j.jcv.2011.09.005

Abstract Background Major and accessory drug resistance mutations have been recently characterized in the C-terminal RT subdomains of HIV-1, connection and RNase H. However, their presence in treatment-naïve patients infected with HIV-1 non-B subtypes remains largely unknown. Objectives To characterize the patterns of primary resistance at the C-terminal RT subdomains of HIV-1 infecting subjects in the southern region of Brazil, where HIV-1 subtypes B and C co-circulate. Study design Plasma viral RNA was extracted from patients recently diagnosed for HIV infection (2005–2008). The protease and reverse transcriptase regions were PCR-amplified and sequenced. Infecting HIV subtypes were assigned by phylogenetic inference and drug resistance mutations were determined following the IAS consensus and recent reports on C-terminal RT mutations. Results The major mutation to NNRTI T369I/V was found in 1.8% of patients, while A376S was present in another 8.3%. In the RNase H domain, the compensatory mutation D488E was more frequently observed in subtype C than in subtype B ( p = 0.038), while the inverse was observed for mutation Q547K ( p < 0.001). The calculated codon genetic barrier showed that 22% of subtype B isolates, but no subtype C, carried T360, requiring two transitions to change into the resistance mutation 360V. Conclusions Major resistance-conferring mutations to NNRTI were detected in 10% of RT connection domain viral sequences from treatment-naïve subjects. We showed for the first time that the presence of specific polymorphisms can constrain the acquisition of definite resistance mutations in the connection and RNase H subdomains of HIV-1 RT.