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A prime example for this mechanism is the M184V mutation that confers resistance to lamivudine (3TC) and emtricitabine (FTC). [ 6 ] [ 7 ] Another well characterized set of mutations is the Q151M complex found in multi-drug resistant HIV which decreases reverse transcriptase's efficiency at incorporating NRTIs, but does not affect natural ...
The most frequent mutations observed in viruses isolated from patients who have been on a failing NNRTI containing chemotherapy are Lys-103N and Tyr-181C. NNRTI resistance has been linked to over 40 amino acid substitutions in vitro and in vivo. [7] Antiretroviral drugs are never used in monotherapy due to rapid resistance development.
Baseline resistance is the presence of resistance mutations in patients who have never been treated before for HIV. In countries with a high rate of baseline resistance, resistance testing is recommended before starting treatment; or, if the initiation of treatment is urgent, then a "best guess" treatment regimen should be started, which is ...
Currently, appearance of drug resistant viruses is an inevitable consequence of prolonged exposure of HIV-1 to antiretroviral therapy. Drug resistance is a serious clinical concern in treatment of viral infection, and it is a particularly difficult problem in treatment of HIV. [25] Resistance mutations are known for all approved NRTIs. [26]
Therefore, this NNRTI-binding pocket will inhibit reverse transcription in a way that is distinct to the NRTIs. [33] Nevirapine is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class. [34]
Etravirine is a human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor (NNRTI). [1] Unlike agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine. [4] Etravirine is marketed by Janssen, a subsidiary of Johnson & Johnson.
HIV drug resistance poses an issue because it reduces the possible HIV medications a person can take due to cross resistance. In cross resistance, an entire class of medication is considered ineffective in lowering a patient's HIV viral load because all the drugs in a given class share the same mechanism of action. [ 7 ]
Efavirenz is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class. [20] As most NNRTIs bind within the same pocket, viral strains which are resistant to efavirenz are usually also resistant to the other NNRTIs, nevirapine and delavirdine.