Indinavir Nucleoside reverse transcriptase inhibitors

TC, lamivudine ABC, abacavir APV, amprenavir AST, aspartate aminotransferase ALT, alanine aminotransferase ATV, atazanavir CBC, complete blood cell count D/C, discontinue ddl, didano-sine d4T, stavudine EFV, efavirenz FTC, emtricitabine P1BV, hepatitis B virus F1CV, hepatitis C vims HIV, human immunodeficiency virus IDV, indinavir IV, intravenous LFT, liver function tests LPV/r, lopinavir + ritonavir NNRTI, nonnucleoside reverse transcriptase inhibitor NRTI, nucleoside reverse transcriptase inhibitor NVP, nevirapine PI, protease inhibitor PT, prothrombin time T.bili, total bilirubin TDF, tenofovir disoproxiI fumarate TPV, tipranavir ULN, upper limit of normal ZDV, zidovudine. 

Haas DW, Fessel WJ, Delapenha RA, Kessler H, Seekins D, Kaplan M, Ruiz NM, Ploughman LM, Labriola DF, Manion DJ. Therapy with efavirenz plus indinavir in patients with extensive prior nucleoside reverse-transcriptase inhibitor experience a randomized, double-bhnd, placebo-controlled trial. J Infect Dis 2001 183(3) 392-400. 

At the present time, there are at least 14 compounds that have been formally approved for the treatment of human immunodeficiency virus (HIV) infections. There are six nucleoside reverse transcriptase inhibitors (NRTIs) that, after their intracellular conversion to the 5 -triphosphate form, are able to interfere as competitive inhibitors of the normal substrates (dNTPs). These are zidovudine (AZT), didanosine (ddl), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), and abacavir (ABC). There are three nonnucleoside reverse transcriptase inhibitors (NNRTIs) — nevirapine, delavirdine, and efavirenz — that, as such, directly interact with the reverse transcriptase at a nonsubstrate binding, allosteric site. There are five HIV protease inhibitors (Pis saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir) that block the cleavage of precursor to mature HIV proteins, thus impairing the infectivity of the virus particles produced in the presence of these inhibitors. 

Efavirenz is a non-nucleoside reverse transcriptase inhibitor with excellent inhibitory activity against HTV-l. Its most frequent adverse effects involve the central nervous system and the skin (1). At the start of therapy, dizziness, insomnia, or fatigue is observed in most patients, and headache and even psychotic reactions have also been observed. A maculopapular rash is seen in about 10%. These adverse effects usually vanish within the first 2-4 weeks of therapy (2). About 1-2% of individuals stop taking efavirenz because of neurological or dermatological adverse events. Administration of efavirenz at bedtime reduces the incidence of severe adverse effects, and the rash can be managed by short-term antihistamines or topical corticosteroids (1). Nausea and vomiting are less often observed than in patients treated with zidovudine, lamivudine, or indinavir. 

Lichterfeld M, Nischalke HD, Bergmann F, Wiesel W, Rieke A, Theisen A, Fatkenheuer G, Oette M, Carls H, Fenske S, Nadler M, Knechten H, Wasmuth JC, Rockstroh JK. Long-term efficacy and safety of ritonavir/ indinavir at 400/400 mg twice a day in combination with two nucleoside reverse transcriptase inhibitors as first line antiretroviral therapy. HIV Med 2002 3(l) 37-43. 

Successful treatment of human immunodeficiency virus (HIV-1) infection has been achieved through successful implementation of highly active antiretroviral therapy, frequently referred to as HAART. This involves simultaneous administration of both nucleoside and nonnucleoside reverse transcriptase inhibitors and one or more protease inliibitors. The common nucleoside reverse transcriptase inhibitors are the thymidine analogs didanosine (ddl), lamivudine (3TC), and zalcitabine (ddC) and the non-thymidine analogs abacavir (Ziazen), stavudine (d4T), and zidovudine (AZT). The nonnucleoside reverse transcriptase inhibitors include delavirdine, efavirenz, and nevirapine. The protease inhibitors include indinavir, nelfinavir, ritonavir, and saquinavir. Response to therapy is monitored by quantification of HIV-RNA copies (viral load) and CD-4+ T-lymphocyte count. Successful therapy is indicated when viral load is reduced to <50 copies/mL and CD-4+ count >500 per mL. 

The FDA approves an HIV viral load test Nevirapine, the first anti-HIV drug of the non-nucleoside reverse transcriptase inhibitors (NNRTl) Ritonavir Pi Indinavir Pis... 

There is no cure for AIDS. Treatment seeks to suppress symptoms (e.g., antibiotics for the infections) and slow viral reproduction. Mortality rates have decreased since 1995 because of the introduction of a treatment protocol called highly active antiretroviral therapy (HAART) that consists of combinations of drugs from the following categories (1) nucleoside reverse transcriptase inhibitors (NRTIs) (e.g., azidothymidine, also called zidovudine or AZT), (2) non-nucleoside reverse transcriptase inhibitors (NNRTIs) (e.g., efavirenz) and protease inhibitors (e.g., indinavir). Both NRTIs and NNRTIs inhibit vDNA synthesis catalyzed by reverse transcriptase. Protease inhibitors are a class of drugs that prevent the processing of viral protein that is required for the assembly of new virions. 

Combination of 16 ARVs seven HIV protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfmavir, ritonavir, and saquinavir), seven nucleoside reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, and zidovudine), and two nonnucleoside reverse transcriptase inhibitors (efavirenz and nevirapine)... 

Marzolini, C. Telenti, A. Buclin, T. Biollaz, J. Decosterd, L.A. Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir, nel-finavir and the non-nucleoside reverse transcriptase inhibitor efavirenz by high-performance liquid chromatography after solid-phase extraction. J. Chromatogr. B, 2000, 740 (1), 43-58. 

DaiUy, E. Thomas, L. Kergueris, M.F. JolUet, P. Bourin, M. High-performance liquid chromatographic assay to determine the plasma levels of HIV-protease inhibitors (amprenavir, indinavir, nelflnavir, ritonavir and saquinavir) and the non-nucleoside reverse transcriptase inhibitor (nevirapine) after liquid-liquid extraction, J.Chromatogr.B, 2001, 758, 129-135. 

Faux, J. Venisse, N. Le Motil, G. Dupuis, A. Bouquet, S. Simultaneous determination of six HIV protease inhibitors, one metabolite, and two non-nucleoside reverse transcriptase inhibitors in human plasma by isocratic reversed-phase liquid chromatography after solid-phase extraction, Chromatographia 2003, 58, 421-426. [amprenavir indinavir lopinavir nelflnavir ritonavir saquinavir efavirenz nevirapine prazepsun]... 

Drugs currently used to treat AIDS l ]) act on the viral reverse transcriptase or the protease (see Fig. 14.22). The nonnucleoside drugs (e.g., efavirenz) bind to reverse transcriptase and inhibit its action. The nucleoside analogs (e.g., ZDV) add to the 3 end of the growing DNA transcript produced by reverse transcriptase and prevent further elongation. The protease inhibitors (e.g., indinavir) bind to the protease and prevent it from cleaving the polyprotein. 

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