Reverse transcriptase inhibitors nucleoside/nucleotide

Dual nucleoside (nucleotide) reverse transcriptase inhibitor (NtRTI) backbones... 

Nucleoside (Nucleotide) reverse transcriptase inhibitors (NtRTIs) ... 

The current standard of care recommends the use of potent three-drug combinations, which typically involves two nucleoside/nucleotide reverse transcriptase inhibitors with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). By attacking HIV infection with three drugs at one time, practitioners seek to avoid the emergence of resistance strains within the patient. 

The purpose of this study is to determine whether once-daily dosing of the lopinavir/ritonavir (Kaletra) tablet in combination with investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors will reduce HIV viral load to very low levels in patients who have detectable viral loads with their current antiretroviral therapy. 

Study Design Treatment, randomized, open label, active control, parallel assignment, safety/efficacy study Official Title A Phase III, Randomized, Open-Label Study of Lopina-vir/Ritonavir Tablets 800/200mg Once-Daily Versus 400/100mg Twice-Daily When Co-administered With Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Antiretroviral-Experienced, HIV-1 Infected Subjects Primary Outcome Measures ... 

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors, including... 

NRTI nucleoside/nucleotide reverse transcriptase inhibitor... 

Le Saux T et al (2008) Quantification of seven nucleoside/nucleotide reverse transcriptase inhibitors in human plasma by high-performance liquid chromatography with tandem mass-spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 865 81-90... 

The 2, 3 -dideoxynucleoside (ddN) analogues (Fig. 3) encompass a vast group of compounds that have been found active against HIV and HBV, although they have been primarily pursued for the treatment of HIV infections (AIDS). They are targeted at the HIV-associated reverse transcriptase (RT) and therefore also referred to as nucleoside reverse transcriptase inhibitors (NRTIs). They have to be distinguished from the nucleotide reverse transcriptase inhibitors (NtRTIs) such as adefovir (PMEA) and tenofovir (PMPA) (see above) which, like the NRTIs, act as chain... 

Nucleoside reverse transcriptase inhibitor (NRTI)/nucleotide reverse transcriptase inhibitor (NtRI) A modified version of a naturally-occurring nucleoside or nucleotide that prevents human immunodeficiency virus (HIV) replication by interfering with the function of the viral reverse transcriptase enzyme. The nucleoside/nucleotide analog causes early termination of the proviral DNA chain. For activity, an NRTI requires three phosphorylation steps once inside the cell, whereas an NtRI has a phosphate group attached and needs only two phosphorylation steps inside the cell for activity. 

Zidovudine (ZDV or AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) and it was the first anti-HIV agent to be introduced. Other NRTIs include stavudine (d4T), lamivudine (3TC), didano-sine (ddl), abacavir (ABC) and zalcitabine (ddC). Recent additions to this class are emtricitabine (FTC) which has a molecular structure similar to 3TC and tenofovir (TDF) a nucleotide reverse transcriptase inhibitor. 

The replicative cycle of HIV presents many opportunities for the targeting of antiviral agents. The drugs in clinical use are classified as nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NTRTIs), and protease inhibitors (PI). 

The pharmacokinetics of lamivudine are described earlier in this chapter (see section, Nucleoside and Nucleotide Reverse Transcriptase Inhibitors). The more prolonged intracellular half-life in HBV cell lines (17-19 hours) than in HIV-infected cell lines (10.5-15.5 hours) allows for lower doses and less ffeguent administration. Lamivudine can be safely administered to patients with decompensated liver disease. 

Raltegravir, or Isentress (1), is the first FDA-approved inhibitor of HIV integrase. HIV/AIDS drugs are categorized according to their mode of action as nucleoside and nucleotide reverse transcriptase inhibitors [NRTIs, e.g., tenofovir (2)], nonnucleotide reverse transcriptase inhibitors [NNRTIs, e.g., efavirenz (3)] protease inhibitors [Pis, e.g., ritonavir (4)], fusion inhibitors [e.g., enfuvirtide (5)], entry inhibitors... 

Thumbnail Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Nucleotide Reverse Transcriptase Inhibitors (NtRTIs), NNRTI, Pis ... 

Kakuda TN. Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. Qin Ther 2000 22 ... 

Non-nucleoside RTIs that do not require metabolic activation (eg, delavirdine and nevirapine, efavirenz, which are not myelosuppressants) and a nucleotide reverse-transcriptase inhibitor (adefovir) have been introduced. Resistance emerges rapidly if these drugs are used as individual agents for management of HIV infection. However, they may provide additive or synergistic activity against HIV if used in combination regimens with NRTIs and/or Pis. 

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Nucleoside reverse transcriptase inhibitors (NRTIs) Nucleotide reverse transcriptase inhibitors Protease inhibitors... 

Boyd MA, Kumarasamy N, Moore CL, Nwizu C, Losso MH, Mohapi L, et al. Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen (SECOND-LINE) a randomised, open-label, non-inferiority study. Lancet... 

Nucleosides, nucleotides, peptidomimetics, and reverse transcriptase inhibitors in HIV infection therapy 98CCC449. 

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