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Treatment with a regimen including efavirenz (EFV) and nevirapine (NVP) typically results in mutations L100I, Y181C/I, K103N, V106A/M, V108I, Y188C/H/L and G190A/S. [17] There are three main mechanisms of NNRTI resistance. In the first NRTI mutations disrupt specific contacts between the inhibitor and the NNRTI binding pocket.
Even though apricitabine is a little less potent in vitro compared to some other NRTIs, it maintains its activity against a broad spectrum of HIV-1 variants with NRTI resistance mutations. Apricitabine is in the final stage of clinical development for the treatment of NRTI-experienced patients.
Figure 3 Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) inhibit the reverse-transcriptase enzyme (RT) and therefore the replication of new viruses. The NNRTIs act by binding non-competitively to the RT enzyme (figure 3). The binding causes conformational change in the three-dimensional structure of the enzyme and creates the NNIBP.
Nucleoside reverse-transcriptase inhibitors (NRTI) and nucleotide reverse-transcriptase inhibitors (NtRTI) are nucleoside and nucleotide analogues which inhibit reverse transcription. HIV is an RNA virus, so it can not be integrated into the DNA in the nucleus of the human cell unless it is first "reverse" transcribed into DNA.
NRTIs / NtRTIs: NNRTI: INSTI: PI: PK enhancer: Combivir: lamivudine zidovudine: September 26, 1997 ViiV Healthcare: No Kaletra (developed countries) Aluvia (developing countries) lopinavir: ritonavir: September 15, 2000 Abbott Laboratories: No Trizivir: abacavir lamivudine zidovudine November 15, 2000 ViiV Healthcare Yes Epzicom Kivexa (EU, RU ...
Some nucleoside analogues, however, can function both as NRTIs and polymerase inhibitors for other viruses (e.g., hepatitis B). Less selective nucleoside analogues are used as chemotherapy agents to treat cancer, e.g. gemcitabine. They are also used as antiplatelet drugs to prevent the formation of blood clots, ticagrelor and cangrelor.
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 .
NNRTI 1998 Elvitegravir: HIV Gilead Sciences Integrase inhibitor 2012 (Fixed-dose combo Stribild) 2014 (single pill) 2015 ; Emtricitabine: HIV Gilead Sciences NRTI 2003 Enfuvirtide: HIV Entry inhibitor 2003 Ensitrelvir: COVID-19: Shionogi: 3C-like protease inhibitor Entecavir: HIV NRTI 2005 Etravirine (Intelence) [8] HIV NNRTI 2008 Famciclovir ...