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

Santos, André F.; Silveira, Jussara María; Muniz, Cláudia P.; Tornatore, Michele; Goes, Livia R; Mendoza-Sassi, Raúl Andrés; Martínez, Ana Maria Barral de; Tupinambás, Unaí; Greco, Dirceu Bartolomeu; Soares, Marcelo A.

doi:10.1016/j.jcv.2011.09.005

Cited by 10 publications

(12 citation statements)

References 34 publications

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“…Several studies have reported an increase in HIV-1C prevalence in that region. [8][9][10][11][12][13][14][15][16] In the city of Rio Grande, one of the foci of this study, such an increase is clearly evident: from 22% in 2002 to 56% in 2010. 16,17 The introduction of highly active antiretroviral therapy (HAART) in HIV-infected patients is associated with a marked reduction in morbidity and mortality.…”

Section: Introductionmentioning

confidence: 78%

“…The CN N348I and the RNH Q509L mutations, not seen in untreated subjects, 14 were found in patients under virological failure, sustaining the importance of these mutations in drug resistance. 40,41,[45][46][47] Interestingly, both viruses carrying Q509L were HIV-1C.…”

Section: Novel Hiv-1 Rt C-terminal Mutationsmentioning

confidence: 86%

“…Primers and PCR conditions for both reactions have been previously described. 14,16,28 Purified PCR products were sequenced with the Prism Ò BigDyeÔ Terminator Cycle Sequencing Ready Reaction Kit (Thermo Scientific, Carlsbad, USA) using the inner primers of each respective PCR reaction. DNA sequencing was carried out in an automated ABI 3130XL Genetic Analyzer (Thermo Scientific).…”

Section: Study Subjects and Sample Collectionmentioning

confidence: 99%

“…Global consensus was obtained from the Los Alamos database, whereas the Brazilian consensus was inferred using sequences obtained from this study and additional 91 HIV-1C sequences of CN and 115 of RNH recently described by our group. 14 The patients under treatment were divided in two groups: (1) Brazilian virologic control, in which the viral load was undetectable (<50 viral RNA copies/mL of blood) and (2) Brazilian RTI resistant.…”

Section: Sequence and Phylogenetic Analysesmentioning

confidence: 99%

“…23,24 Currently, CN and RNH are not included in resistance genotyping assays, but their clinical impact is controversial and remains poorly characterized. Limited studies have attempted to evaluate these mutations among drug-naive and treated subjects, 14,[25][26][27][28] and virtually all so far conducted have assessed them in HIV-1B, with very few reports in non-B subtypes. 14,28 Studies carried out with treatment-experienced patients have pinpointed differences in drug resistance occurring at the RT POL domain of distinct HIV-1 subtypes.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil

Barral

Sousa

Santos

et al. 2017

AIDS Research and Human Retroviruses

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Mutations in the connection and RNase H C-terminal reverse transcriptase (RT) domains of HIV-1 have been shown to impact drug resistance to RT inhibitors. However, their impact in the context of non-B subtypes has been poorly assessed. This study aimed to characterize resistance-related mutations in the C-terminal portions of RT in treatment-failing patients from southern Brazil, a region with endemic HIV-1 subtype C (HIV-1C). Viral RNA was isolated and reverse transcribed from 280 infected subjects, and genomic regions were analyzed by polymerase chain reaction, DNA sequencing, and phylogenetic analysis. Two novel mutations, M357R and E529D, were evidenced in Brazilian HIV-1C strains from treatment-failing patients. In global viral isolates of subjects on treatment, M357R was selected in HIV-1C and CRF01_AE and E529D was selected in HIV-1 subtype B (HIV-1B). While most C-terminal RT mutations described for HIV-1B also occur in HIV-1C, this work pinpointed novel mutations that display subtype-specific predominance or occurrence.

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Section: Introductionmentioning

confidence: 78%

Section: Novel Hiv-1 Rt C-terminal Mutationsmentioning

confidence: 86%

Section: Study Subjects and Sample Collectionmentioning

confidence: 99%

Section: Sequence and Phylogenetic Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil

Barral

Sousa

Santos

et al. 2017

AIDS Research and Human Retroviruses

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Role of RNase H Activity in NRTI/NNRTI Drug Resistance

Tachedjian

Sluis‐Cremer

2013

Human Immunodeficiency Virus Reverse Transcriptase

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Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance

et al. 2013

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Mutations in the connection subdomain (CN) and RNase H domain (RH) of HIV-1 reverse transcriptase (RT) from subtype B-infected patients enhance nucleoside and nonnucleoside RT inhibitor (NRTI and NNRTI) resistance by affecting the balance between polymerization and RNase H activity. To determine whether CN mutations in subtype C influence drug sensitivity, single genome sequencing was performed on Brazilian subtype C-infected patients failing RTI therapy. CN mutations identified were similar to subtype B, including A376S, A400T, Q334D, G335D, N348I, and A371V, and increased AZT resistance in the presence of thymidine analog mutations. CN mutations also enhanced NNRTI resistance in the presence of classical NNRTI mutations: etravirine resistance was enhanced 6- to 11-fold in the presence of L100I/K103N/Y181C. These results indicate that selection of CN mutations in treatment-experienced patients also occurs in subtype-C-infected patients and are likely to provide valuable information in predicting clinical RTI resistance.

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

Cited by 10 publications

References 34 publications

Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil

Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil

Role of RNase H Activity in NRTI/NNRTI Drug Resistance

Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance

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