Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors.
Result: E312Q, G335C/D, N348I, A360I/V, V365I and A376S) have been identified that significantly contribute to AZT resistance by reducing RNase H activity.
Connection subdomain mutations in HIV-1 subtype-C treatment-experienced patients enhance NRTI and NNRTI drug resistance.
Introduction: Eight novel mutations, E312Q, G335C/D, N348I, A360I/V, V365I, and A376S, were identified within the CN of RT that significantly contributed to AZT resistance, and these mutations were further found to decrease RNase H activity, leading to decreased susceptibility to AZT.
Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase.
Introduction: For example, the G333D/E, G335C, N348I, A360V/I, T369V and A371V mutations have all be shown to augment AZT resistance alone or in combination with TAMs.
Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity.
PMID: 22828721
2012
Journal of acquired immune deficiency syndromes (1999)
Method: The CD mutations considered were E312Q, Y318F, G333D/E, G335C/D, N348I, A360I, A360V, V365I, A371V, A376S, and E399G.
Discussion: In subtype B, CD mutations that have been associated with resistance include E312Q, G333E/D, G335D, N3481, A360I/V, V365I, T369I, A371V and A376S [6-9], but these a
Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy.
Introduction: Examples are E312Q, G335C/D, N348I, A360I/V, V365I and A376S in the HIV-1 RT connection subdomain, and Q509L, H539N and D549N in the RNase H domain.
Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China.
Discussion: Nikolenko et al reported in 2007 that such mutations as E312Q, G335C/D, N348I, A360I/V, V365I and A376S at the connection domain could confer resistance to AZT to a certain extent.
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.
PMID: 21350368
2011
Journal of acquired immune deficiency syndromes (1999)
Introduction: Other connection domain mutations, including G333D/E, G335C/D, A360I/V, A365I and
Discussion: These studies have identified a number of mutations in the C-terminus of RT that are more frequent in ART-experienced patients compared to ART-naive including E312Q, G333D/E, G335C/D, N348I, R356K, R358K, A360I/V, A365I, T369I, A371V, A376S and K451R.
Connection domain mutations in HIV-1 reverse transcriptase do not impact etravirine susceptibility and virologic responses to etravirine-containing regimens.
PMID: 21464253
2011
Antimicrobial agents and chemotherapy
Connection domain mutations in treatment-experienced patients in the OPTIMA trial.
PMID: 20130473
2010
Journal of acquired immune deficiency syndromes (1999)
Abstract: Frequencies of E312Q, Y318F, G333D, G333E, G335C, G335D, N348I, A360I, A360V, V365I, A371V, A376S, and E399G were compared with a treatment-naive population.
Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients.
Result: None of the clinical isolates of our cohort had the G333D, G335C, N348I, A360I/V
Discussion: Furthermore, the G333D, G335C, N348I, A360I/V and Q509L substitutions were not observed in our cohort, and were also rarely observed among treatment-naive patients (less than 1%) in the Stanford HIV Drug Resistance Database.
Discussion: However, site directed mutagenesis studies showed that G333D, G335C, A360I/V and Q509L did not confer significant AZT resistance in the absence of other AZT resistance mutations.
HIV mutation literature information.
PMID: 
2016
Nucleic acids research
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