ArticleAntiviral research2009
Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naïve patients.
Article in Antiviral research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2012Trial
- Characterisation of RT Connection and RNase H Polymorphisms in HIV-1 Subtype C in Botswana.Viruses · 2026Article
- Agreement between an in-house replication competent and a reference replication defective recombinant virus assay for measuring phenotypic resistance to HIV-1 protease, reverse transcriptase, and integrase inhibitors.Journal of clinical laboratory analysis · 2018Article
- Article
- Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil.AIDS research and human retroviruses · 2017Article
- FRET-based assay to screen inhibitors of HIV-1 reverse transcriptase and nucleocapsid protein.Nucleic acids research · 2016Article
- Inhibition of the DNA polymerase and RNase H activities of HIV-1 reverse transcriptase and HIV-1 replication by Brasenia schreberi (Junsai) and Petasites japonicus (Fuki) components.Journal of natural medicines · 2015Article
- Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation.The protein journal · 2014Article
- The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity.Journal of virology · 2014Article
- Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance.Virology · 2013Article
- Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant.Cellular and molecular biology (Noisy-le-Grand, France) · 2012Article
- Biochemical mechanism of HIV-1 resistance to rilpivirine.The Journal of biological chemistry · 2012Article
- Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity.Journal of acquired immune deficiency syndromes (1999) · 2012Article
- HIV-1 reverse transcriptase (RT) polymorphism 172K suppresses the effect of clinically relevant drug resistance mutations to both nucleoside and non-nucleoside RT inhibitors.The Journal of biological chemistry · 2012Article
- Anti-human immunodeficiency virus type 1 activity of novel 6-substituted 1-benzyl-3-(3,5-dimethylbenzyl)uracil derivatives.Antimicrobial agents and chemotherapy · 2012Article
- Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China.PloS one · 2012Article
- Connection domain mutations in HIV-1 reverse transcriptase do not impact etravirine susceptibility and virologic responses to etravirine-containing regimens.Antimicrobial agents and chemotherapy · 2011Article
- Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase.Journal of acquired immune deficiency syndromes (1999) · 2011Article
- Phenotypic characterization of drug resistance-associated mutations in HIV-1 RT connection and RNase H domains and their correlation with thymidine analogue mutations.The Journal of antimicrobial chemotherapy · 2011Article
- The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Some mutations in the connection subdomain of the polymerase domain and in the RNase H domain of HIV-1 reverse transcriptase (RT) have been shown to contribute to resistance to RT inhibitors. However, the clinical relevance of such mutations is not well understood. To address this point we determined the prevalence of such mutations in a cohort of antiretroviral treatment-naïve patients (n=123) and assessed whether these substitutions are associated with drug resistance in vitro and in vivo. We report here significant differences in the prevalence of substitutions among subtype B, and non-subtype B HIV isolates. Specifically, the E312Q, G333E, G335D, V365I, A371V and A376S substitutions were present in 2-6% of subtype B, whereas the G335D and A371V substitutions were commonly observed in 69% and 75% of non-B HIV-1 isolates. We observed a significant decline in the viral loads of patients that were infected with HIV-1 carrying these substitutions and were subsequently treated with triple drug regimens, even in the case where zidovudine (AZT) was included in such regimens. We show here that, generally, such single substitutions at the connection subdomain or RNase H domain have no influence on drug susceptibility in vitro by themselves. Instead, they generally enhance AZT resistance in the presence of excision-enhancing mutations (EEMs, also known as thymidine analogue-associated mutations, TAMs). However, N348I, A376S and Q509L did confer varying amounts of nevirapine resistance by themselves, even in the absence of EEMs. Our studies indicate that several connection subdomain and RNase H domain substitutions typically act as pre-therapy polymorphisms.
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